@article{%a1.%Y_296,

title = {Assessing mechanisms and evidence of a causal role for cellular senescence and somatic mutations in aging},

author = {Trastus LA and {d'Adda di Fagagna F}},

url = {https://www.aging-us.com/article/206414/text},

doi = {10.18632/aging.206414},

year  = {2026},

date = {2026-10-05},

journal = {Aging},

volume = {18},

issue = {1},

pages = {1066-1076},

abstract = {Understanding the primary molecular and cellular drivers of aging and how they trigger systemic functional decline remains a fundamental challenge. This review focuses on two proposed drivers of aging, cellular senescence and somatic DNA mutations, critically discusses the evidence for their association with organismal aging, and appraises their causal contribution to it. Several studies support the notion that cellular senescence can cause aging, acting through cell-intrinsic and, likely more significantly, cell-extrinsic mechanisms such as the senescence-associated secretory phenotype. Differently, the mutational burden is strongly correlated with aging, but we argue that the causal contribution of altered DNA sequences to age-related functional decline remains difficult to untangle from its originating genotoxic events.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_295,

title = {Tracking micro- and nanoplastics in Aedes albopictus: From ingestion to metabolic disruption},

author = {Soldano S and Bonanomi M and Aramini T and Moyano A and Garbelli A and Croce AC and Weththimuni ML and Vaghi P and Puggioli A and Gomulski LM and Gaglio D and Scolari F},

url = {https://www.sciencedirect.com/science/article/pii/S004896972502087X?via%3Dihub},

doi = {10.1016/j.scitotenv.2025.180447},

year  = {2026},

date = {2026-10-05},

journal = {Science of the total environment},

abstract = {Urban aquatic environments are increasingly contaminated with micro- and nanoplastics (MNLPs), posing risks to biodiversity and human health. These environments are ideal breeding sites for larvae of the Asian tiger mosquito Aedes albopictus, a key arbovirus vector. While plastic pollution is a global concern, physiological and metabolic consequences of MNPL-exposure in mosquitoes remain poorly understood. Combining epifluorescence and confocal imaging, mosquito life-history parameter assessment, and high-throughput metabolomic profiling, we investigated the effects of polystyrene MNPLs on Ae. albopictus. We demonstrated that ingested MNPLs cross the larval gut barrier, persist in various tissues, and are retained through development. Exposure did not significantly affect pre-imaginal survival or development time, but reduced larval body weight and caused profound metabolic alterations. Metabolomic analyses revealed downregulation of central carbon metabolism, particularly glycolysis and pentose phosphate pathway, alongside amino acid alterations linked to stress responses. Notably, MNPL-exposure also affected juvenile hormone biosynthesis, suggesting endocrine disruption. This trend was observed in both NP- and MP-exposed larvae, with a greater number of differentially regulated metabolites following MP-treatment. Interestingly, TCA cycle dysregulation was more pronounced in NP-exposed larvae, whereas perturbations in glutathione metabolism, amino sugar metabolism and nitrogen excretion were associated with MP-exposure. These findings highlight the metabolic and physiological consequences of MNPL-exposure, with potential implications for mosquito ecology, vector capacity, and environmental dissemination of plastic contaminants. Given the role of Ae. albopictus in disease transmission and its adaptation to urban habitats, further research is needed to explore the long-term ecological and epidemiological consequences of plastic pollution on mosquito populations.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{%a1.%Y_294,

title = {The telomeric DNA damage response as a therapeutic target in idiopathic pulmonary fibrosis},

author = {Rossiello F and Cicio G and Sepe S and Mancheno-Ferris A and Cancila V and Castellini A and Rey F and Bertolazzi G and Oppezzo A and Marinelli E and Cabrini M and di Lillo A and Tavella S and Rosso I and Buffa FM and Tripodo C and {d'Adda di Fagagna F}},

url = {https://link.springer.com/article/10.1038/s44321-026-00500-x},

doi = {10.1038/s44321-026-00500-x},

year  = {2026},

date = {2026-10-05},

urldate = {2026-10-05},

journal = {EMBO molecular medicine},

volume = {18},

issue = {9},

pages = {3704-3744},

abstract = {Telomere dysfunction and the telomeric DNA damage response (tDDR) activation correlate with aging and age-related diseases, including idiopathic pulmonary fibrosis (IPF). However, a causal role for tDDR in IPF pathogenesis has not been determined. IPF patients frequently bear germline mutations in telomerase genes, critically short telomeres, and markers of tDDR and cellular senescence. We previously demonstrated that telomeric antisense-oligonucleotides (tASOs) targeting telomeric non-coding RNAs are selective tDDR inhibitors. Here, we employed late-generation telomerase knockout mice as a genetic model of IPF. Systemic tASOs treatment reduces DDR-including in stem/progenitor cells-inflammation, and lung fibrosis in young, adult, and old mice. Markers of DDR correlate with lung pathology, and tDDR inhibition normalizes molecular and pathological phenotypes, uncoupling telomere lengths from their deleterious consequences. Transcriptomic changes in telomerase knockout mice recapitulate those observed in normal aged mice and in IPF patients, and they are reversed upon tDDR inhibition. These results highlight the pathogenic causative relevance of tDDR activation in IPF pathogenesis and support tASOs as a promising therapeutic strategy for IPF and for telomere biology diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_293,

title = {Cancer of unknown primary genomic profiling from cell-free DNA provides insights into CUP biology and vulnerabilities},

author = {Roncarati R and Fontana B and Pace I and Durante G and Conci N and Soru A and Gallerani G and Riefolo M and Salamon I and Laprovitera N and Broseghini E and Naddeo M and Espis A and Sales G and Diciotti S and D'Errico A and Rihawi K and Ardizzoni A and Ferracin M},

url = {https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2026.1777582/full},

doi = {1777582},

year  = {2026},

date = {2026-10-05},

journal = {Frontiers in medicine},

volume = {13},

pages = {1777582},

abstract = {Introduction: Cancer of unknown primary (CUP) is a metastatic malignancy with no identifiable site of origin, accounting for 2-5% of cancer diagnoses. Its marked heterogeneity and the limited availability of tumor tissue pose major challenges to genomic profiling. Methods: In this retrospective observational study, we applied a 92-gene CUP-specific targeted sequencing panel to liquid biopsy samples from 39 CUP patients, analyzing circulating cell-free DNA (ccfDNA) together with paired germline DNA (gDNA), when available. Somatic, germline, and CHIP-related variants were classified using predefined variant allele frequency (VAF) thresholds and paired ccfDNA/gDNA comparison. Results: We identified somatic mutations in 78 of 92 genes and 44 clinically relevant variants (Tier I-III), most frequently affecting NF1, KRAS, ARID1A, and PIK3CA. Mutated genes were primarily involved in cell-cycle regulation, receptor tyrosine kinase signaling, and NOTCH pathways. Recurrent genetic alterations were detected in 15 genes, including canonical hotspot mutations in TP53, KRAS, and PIK3CA, 10 of which were shared by three or more patients. Actionable mutations, as defined by current clinical annotation guidelines, were identified in 13 genes, supporting the potential role of molecularly guided therapies in CUP. Likely CHIP-associated variants, defined as mutations in CHIP-associated genes with VAF ≥ 2% in PBMC-derived genomic DNA, were detected in 17 patients. In addition, pathogenic germline variants in MITF, NTRK1, and BAP1 were identified in three patients; notably, the NTRK1 germline variant was accompanied by an independent somatic mutation in the same gene. Discussion: Overall, these findings support liquid biopsy as a valuable approach for molecular profiling of CUP and highlight the critical importance of paired ccfDNA/gDNA analysis, including CHIP assessment, to accurately distinguish somatic, germline, and hematopoiesis-related variants.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_292,

title = {Spiroplasma in Glossina fuscipes fuscipes: a potential manipulator of male reproduction},

author = {Piccinno R and Fiorenza G and Lescai F and Carpanzano S and Gstöttenmayer F and Dera K-sM and Croce AC and de Beer CJ and Weiss BL and Santorsola M and Pinnola A and Gasperi G and Forneris F and Aksoy S and Abd-Alla AMM and Malacrida AR},

url = {https://journals.asm.org/doi/10.1128/msystems.00526-26?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed},

doi = {10.1128/msystems.00526-26},

year  = {2026},

date = {2026-10-05},

journal = {mSystems},

abstract = {Glossina fuscipes fuscipes (Gff) is a riverine species of the Glossina genus (tsetse flies). It is one of the principal vector species responsible for transmitting human African trypanosomiasis across a broad swath of sub-Saharan Africa. Consequently, it remains a primary target for vector-control interventions in endemic regions. As with other Glossina species, G. fuscipes houses a highly streamlined microbiota, composed of maternally transmitted endosymbionts mandatory for survival, which also significantly impacts the vectorial capacity. Among them, the obligate Wigglesworthia provides essential nutrients and stimulates maturation of the fly's immune system, providing a refractory effect against Trypanosoma. It also harbors the commensal Sodalis and parasitic Wolbachia, the latter of which induces cytoplasmic incompatibility. In addition, Gff hosts a Spiroplasma strain that enhances host refractoriness to trypanosome infection but disrupts female metabolic and reproductive homeostasis. We used high-throughput RNA sequencing to examine the impact of Spiroplasma on male testes and accessory glands to reveal how this microbe exerts its influence on male reproductive physiology. We found that Spiroplasma substantially alters testes physiology, downregulating genes involved in energy metabolism and sperm function, suggesting reduced male reproductive fitness. In contrast, accessory gland gene expression was not significantly affected despite the critical role of these organs in semen production and reproductive success, considering also that the bacterium exploits the ejaculate to further increase its population prevalence. Spiroplasma infection also correlated with increased abundance of other symbionts, including Wigglesworthia.IMPORTANCEA complex host-symbiont interplay makes the Spiroplasma harbored in tsetse fly intriguing. The unexpected male-specific energetic costs of Spiroplasma infection keep open the biological question of why this bacterium is maintained in this species. On the other hand, Spiroplasma infection correlates with increased abundance of Wigglesworthia, promoting trypanosome refractoriness. The present work adds a valuable layer to further interpret the ecological and evolutionary narrative of Spiroplasma interactions, and lays the preliminary groundwork to explore the potential of using Spiroplasma as a biocontrol agent. While acknowledging that our findings were derived from a long-established laboratory colony, the data on the modulation of fly reproductive fitness and on the possible contribution to trypanosome refractoriness found make Spiroplasma intriguing for strategic integration into environmentally sustainable vector management programs, potentially in concert with the Sterile Insect Technique. The results provide significant advances in symbiont-host interactions, bringing new insight into understanding the role of symbionts in viviparous tsetse flies. We also provide a community forum for discussion on the possible use of bacteria as species-specific biocontrol.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{%a1.%Y_291,

title = {Hair Follicle Microenvironment Changes in Collagen VI-Myopathy Patients with Alopecia},

author = {Pampaloni F and Piraccini BM and Bruni F and Quadrelli F and Misciali C and Merlini L and Di Martino A and Schena E and Cenni V and Starace M and Sabatelli P},

url = {https://www.mdpi.com/2073-4409/15/15/1351},

doi = {10.3390/cells15151351},

year  = {2026},

date = {2026-10-05},

journal = {Cells},

volume = {15},

issue = {15},

pages = {1351},

abstract = {Collagen VI-related myopathies (COL6-RM) are rare hereditary disorders characterized by skeletal muscle dysfunction and skin manifestations, including keratosis pilaris, hypertrophic scars, and keloids. We recently found that alopecia is a novel and previously unrecognized scalp phenotype in COL6-RM; however, the precise pathogenetic mechanisms underlying hair follicle dysfunction in these patients remain incompletely understood. We performed a comprehensive immunohistochemical, ultrastructural, and proteomic characterization of scalp biopsies from six COL6-RM patients presenting with hair loss and scalp itching. We found structural alterations in the hair follicle extracellular matrix architecture, particularly in the inner fibrous sheath surrounding the hair follicle. In addition, the analysis of the perifollicular adipose tissue and derived cell cultures showed changes in lipid droplet size consistent with a tendency toward cell hypertrophy. Strikingly, proteomic profiling of adipokines revealed a pro-inflammatory and extracellular matrix-remodeling signature. Consistent with inflammation and extracellular matrix remodeling, CD68 macrophages and MMP2 expression were increased in the dermis of COL6-RM patients, particularly around the perifollicular adipocytes. Overall, these data indicate a complex pathological signature involving ECM and adipose tissue remodeling. In this context, collagen VI emerges as a potential regulator of the hair follicle microenvironment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_290,

title = {Therapeutic inhibition of telomeric DNA damage response rescues hematopoietic dysfunction driven by telomere shortening and aging},

author = {Oppezzo A and Sepe S and Cicio G and Cancila V and Sasso E and Conti A and Marinelli E and Cabrini M and Pallavi R and Iacomino N and Simoni M and Malyshev D and Boggio S and di Lillo A and Rosso I and Tavella S and Trastus LA and Rossiello F and Roscia G and Cantaloni P and Manenti A and Cavalcante P and Pelicci PG and Di Micco R and Nicosia A and Tripodo C and {d'Adda di Fagagna F}},

url = {https://www.nature.com/articles/s43587-026-01136-9},

doi = {10.1038/s43587-026-01136-9},

year  = {2026},

date = {2026-10-05},

journal = {Nature aging},

volume = {6},

issue = {7},

pages = {1377-1394},

abstract = {Telomeres progressively shorten and accumulate damage with aging, and this contributes to cellular senescence and hematopoietic dysfunction. We previously showed that telomere dysfunction induces synthesis of telomeric noncoding RNAs required for activation of the telomeric DNA damage response (tDDR), a driver of senescence and inflammation. However, whether the tDDR causally impairs hematopoiesis remained unclear. Here we show in telomerase-deficient Terc-/- mice, which recapitulate telomere-driven hematopoietic dysfunction and aging, that targeting telomeric noncoding RNAs with telomeric antisense oligonucleotides (tASO) suppresses tDDR in hematopoietic organs, reduces senescence and inflammation, alleviates hematopoietic dysfunction, and enhances hematopoietic stem cell fitness and repopulating potential in vivo. Similar observations were recapitulated in aged wild-type mice, and ex vivo treatment with tASO improved the function of human hematopoietic stem cells from aged donors. Taken together, our results identify tDDR as a pathogenic driver of hematopoietic decline and support tASO-mediated tDDR inhibition as a potential therapeutic strategy for telomere biology disorders and age-associated hematopoietic aging.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_289,

title = {Comprehensive genomic profiling of mucosal melanoma reveals novel fusion transcripts and dysregulation of cell-cycle, MAPK, and PI3K pathways},

author = {Monti M and Romanello MB and Agnelli L and Orlandi M and Bertoli L and Picinoli S and Pezzali I and Mandelli GE and Medicina D and Ribaudo G and Busico A and Conca E and Pellegrini V and Balzarini P and Gallucci D and {Di Matteo A} and Lombardi D and Ghigna C and Pruneri G and Gianoncelli A and Rossato M and Vermi W},

url = {https://pathsocjournals.onlinelibrary.wiley.com/doi/10.1002/path.70108},

doi = {10.1002/path.70108},

year  = {2026},

date = {2026-10-05},

journal = {Journal of pathology},

abstract = {Mucosal melanomas (MMs) are rare, aggressive cancers with poor outcomes and limited response to standard therapies. A significant knowledge gap exists regarding their genomic landscape and corresponding druggable targets. This study explores this issue through a multi-omic analysis, including whole exome-, RNA-, and targeted sequencing, of unique sinonasal mucosal melanoma (SN-MM) cell lines. SN-MM cell lines showed a low tumour mutational burden and low genomic instability, suggesting that their DNA repair mechanisms are largely intact. However, they exhibited a high prevalence of structural variants, likely from catastrophic genomic events. We also found novel, clinically actionable variants, including oncogenic fusion transcripts. Key findings, such as fusion transcripts and single-nucleotide variants, were validated on diagnostic biopsies. Moreover, using a break-apart FISH assay, we identified BRAF rearrangements as recurrent events in MM, supporting their biological relevance. The MAPK pathway was found to have a significant functional role, sustained by variants such as BRAF p.Asn581Ser, NRAS p.Gly12Asp, and the MKRN1::BRAF fusion. This pathway activation was effectively inhibited by the MEK inhibitor trametinib. This genomic and functional profiling unveiled novel molecular hubs in MM. The findings propose that MEK inhibitors may represent a relevant therapeutic option for BRAF fusions and non-V600 BRAF mutant tumours, providing a novel strategy for this challenging disease. Further molecular and functional validation of novel variants, and particularly of BRAF rearrangements, may reveal additional clinically relevant therapeutic targets. © 2026 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{%a1.%Y_288,

title = {Nucleoporin TPR integrates MAPK signaling with mitogen-induced transcriptional programs},

author = {Liu J and Zheng Y and Xiong Y and Ma R and Lin Z and Lin H and Andújar-Sánchez M and Bartkova J and Liu J and Foiani M and Bartek J and Kosar M},

url = {https://www.nature.com/articles/s41419-026-08760-8},

doi = {10.1038/s41419-026-08760-8},

year  = {2026},

date = {2026-10-05},

journal = {Cell death and disease},

volume = {17},

issue = {1},

pages = {400},

abstract = {The nuclear pore complex (NPC) component TPR has emerged as a multifunctional scaffold implicated in mitosis, chromatin organization, mRNA export, and genome stability. However, TPR's role in mitogenic signal transduction remains largely unexplored. Here, we investigate whether nucleoporin TPR functions as a MAPK-regulated nuclear component that modulates mitogenic signals initiated at the plasma membrane-including EGFR activation-and their transcriptional output. Transcriptomic profiling reveals that TPR depletion reshapes EGF-induced, MAPK-responsive gene expression, including altered expression of MAPK pathway components and enhanced induction of the immediate-early gene FOS. Functionally, TPR-depleted cells exhibit increased FOS induction upon EGF stimulation and altered EGF-driven cell-cycle progression. Using a novel phospho-specific monoclonal antibody, we show that TPR is phosphorylated at Ser2155 following EGFR activation via the canonical RAS-RAF-MEK-ERK MAPK cascade, placing TPR downstream of MAPK pathway activation. This phosphorylation is suppressed by clinically used EGFR and BRAF inhibitors and, conversely, is constitutively induced by oncogenic RAS and BRAF, indicating that Ser2155 phosphorylation reflects MAPK pathway activity. In vivo, CRISPR/Cas9-engineered Tpr haploinsufficient mice show changes in MAPK pathway regulatory gene expression in bulk spleen RNA-seq, consistent with findings in human cells, and enhanced Fos induction in splenocytes upon CD3/CD28 stimulation, together suggesting a conserved association between TPR levels and altered MAPK-related transcriptomic profiles. Finally, immunohistochemical analysis reveals elevated TPR phosphorylation in serous ovarian carcinoma and heterogeneous phosphorylation patterns in triple-negative breast cancer, two tumor types frequently characterized by MAPK pathway hyperactivation. Together, these findings uncover a previously unappreciated role for TPR as a MAPK-responsive nuclear factor and support a model in which NPC-associated components fine-tune mitogen-induced transcriptional responses.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_287,

title = {Systematic Structure-Activity Relationship Investigation on Novel 5‑Alkyl-6-benzyl-2-{[(methylthio/phenylthio)alkyl]thio}-pyrimidin-4(3 H)‑ones Endowed with Potent Anti-HIV‑1 Activity},

author = {Hailu GS and Degtyarenko E and Fabbrizi E and Golovina A and Voronkov A and Mancini A and Nawrozkij MB and Chernyshov V and Bavagnoli L and Bianchi E and Astolfi R and Ragno R and Esté JA and Crespan E and Fiorentino F and Ivanov R and Mai A and Rotili D},

url = {https://pubs.acs.org/acsodf/article/11/38/58141/5431420/Systematic-Structure-Activity-Relationship},

doi = {58141},

year  = {2026},

date = {2026-10-05},

journal = {ACS omega},

volume = {10},

issue = {38},

pages = {58141},

abstract = {Four series of 5-alkyl-6-benzyl-2-[(methylthio/phenylthio)-alkyl]-thiopyrimidin-4-(3H)-ones were systematically diversified at C2, C5, and C6 and evaluated as anti-HIV-1 agents. In MT-4 cells, these compounds displayed low-to-moderate cytotoxicity and subnanomolar-to-submicromolar inhibition of WT HIV-1, with potency governed by a balanced SAR. Ortho-dihalogenated C6-benzyl groups, particularly 2,6-F2 and 2,6-Cl2, were generally favored. In the 2,6-dihalobenzyl series, optimal activity required C5 methyl combined with para-substituted phenylthiomethyl groups at C2, whereas 3,5-Me2-benzyl analogues benefited from C5 isopropyl paired with methylthioethyl (24l) or unsubstituted phenylthiomethyl (24m) C2 side chains. The p-methoxyphenyl-thiomethyl thiothymine derivatives 21e (2,6-F2) and 23e (2,6-Cl2) emerged as lead inhibitors, showing high selectivity, potent activity against WT and clinically relevant HIV-1 variants, superior efficacy compared with nevirapine and efavirenz, dapivirine-like potency, and improved resistance tolerance relative to phenethyl-S-DABO bioisosteres. Together, biological and QSAR and docking data contribute to defining optimization strategies aimed at achieving durable anti-HIV-1 activity within the investigated chemotype and support further development of next-generation NNRTIs with improved efficacy against clinically relevant HIV-1 strains.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_286,

title = {Synergistic role of TFEB/TFE3 and mTORC1 in kidney cystogenesis and tumorigenesis},

author = {Ferniani M and Sambri I and Huynh T and Pennella R and Tufano G and Herz NJ and Rossi B and Iannaccone A and Trepiccione F and Calcagnì A and Ballabio A},

url = {https://www.nature.com/articles/s41418-026-01881-9},

doi = {10.1038/s41418-026-01881-9},

year  = {2026},

date = {2026-10-05},

journal = {Cell death and differentiation},

abstract = {Birt-Hogg-Dubé (BHD) and Tuberous Sclerosis (TSC) are inherited cancer syndromes associated with kidney cystogenesis and tumorigenesis and caused by mutations of the folliculin (FLCN) and TSC1/2 genes, respectively. We and others previously showed that Transcription Factors EB (TFEB) and E3 (TFE3) are the main drivers of the kidney phenotypes observed in mouse models of these conditions. These transcription factors are also responsible for the feedback hyperactivation of the mechanistic Target of Rapamycin Complex 1 (mTORC1), a known tumorigenic factor. This raises the question of whether TFEB/TFE3 exert their oncogenic activity by inducing mTORC1 or by mTORC1-independent pathways. To address this question, we generated kidney-specific mouse models in which we knocked out factors that differentially control mTORC1 and TFEB/TFE3, thus uncoupling their activities. Specifically, we generated three kidney-specific conditional knockout lines: (1) Depdc5-KO mice in which loss of GATOR1 activity leads to mTORC1 hyperactivation and TFEB/TFE3 inhibition, (2) RagC-KO mice in which TFEB/TFE3 are constitutively active and mTORC1 activity is partially inhibited due to impaired Rag heterodimer formation, and (3) Flcn/RagC double KO mice to test whether mTORC1 inhibition induced by RagC loss ameliorates the aggressive kidney phenotype of FLCN KO mice. Comparison between these models revealed that mTORC1 hyperactivation is a key driver of cystogenesis and tumorigenesis, while TFEB/TFE3 constitutive activation further enhances and accelerates pathology by establishing a transcriptional program that integrates metabolic and stress-response pathways. Together, our findings define an oncogenic mechanism by which both mTORC1 and TFEB/TFE3 hyperactivation cooperate in kidney tumorigenesis.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{%a1.%Y_285,

title = {miRNA-mediated cell-to-cell communications boost DNA repair during the radioadaptive response},

author = {Domínguez-Perez MDC and Fernandez-Avila MJ and Gonzalez-Vinceiro L and Zannini L and Peinado H and GonzAlez-Prieto R and García-Rodríguez N and Huertas P},

url = {https://academic.oup.com/nar/article/54/14/gkag764/8751565?login=true},

doi = {10.1093/nar/gkag764},

year  = {2026},

date = {2026-10-05},

journal = {Nucleic acids research},

volume = {54},

issue = {14},

abstract = {The radioadaptive response (RAR) is a phenomenon in which a low, or priming, dose of ionizing radiation enhances cellular resistance to subsequent higher doses. We investigated whether RAR involves alterations in homologous recombination (HR), a high-fidelity DNA repair pathway. Using fibroblast models, we found that primed cells exhibit accelerated DNA end resection, an initial and essential HR step. This effect is mostly mediated by a bystander mechanism involving small extracellular vesicles (sEVs), as conditioned media fully replicated it. RNA profiling of sEVs identified miR-126-3p and miR-451a as key regulators of this response. Significantly, inhibiting miR-451a induced RAR in normally unresponsive cells. We further identified a miR-451a-p38-CCAR2 axis that promotes HR through suppression of CCAR2. Our findings delineate a novel microRNA-mediated, sEV-driven mechanism that regulates HR during RAR, with potential therapeutic implications.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{E2026,

title = {Exploring the role of conformational restriction in 5-alkyl-6-benzyl-2-{[(methylthio)methyl]thio}pyrimidin-4(3H)-ones: Effects in HIV-1 infected cells and reverse transcriptase enzymes},

author = {Degtyarenko E and Hailu GS and Fabbrizi E and Golovina A and Voronkov A and Astolfi R and Giuliani L and Mancini A and Nawrozkij MB and Chernyshov V and Pupillo C and Cirilli R and Bavagnoli L and Ragno R and Esté JA and Crespan E and Fiorentino F and Ivanov R and Mai A and Rotili D},

url = {https://www.sciencedirect.com/science/article/pii/S022352342600749X?via%3Dihub},

doi = {10.1016/j.ejmech.2026.119304},

year  = {2026},

date = {2026-10-05},

urldate = {2026-10-05},

journal = {European journal of medicinal chemistry},

volume = {320},

pages = {119304},

abstract = {Conformational restriction is a powerful strategy previously used to optimize several HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTI) series, including 3,4-dihydro-2-alkoxy-6-benzyl-4-oxopyrimidines (DABOs). Herein, we report the design, synthesis, and biological evaluation of a focused series of conformationally restricted 5-alkyl-2-{[(methylthio)methyl]thio}-6-(1-phenylethyl)-DABO (MTM-S-DABOs) compounds (16d-f, 17d-f, 18d-f, and 19d-f) comparing them with the corresponding unconstrained 6-phenylmethyl analogues (16a-c, 17a-c, 18a-c, and 19a-c). The introduction of a methyl group at the C6 α-benzylic position of the pyrimidinone core of MTM-S-DABOs markedly enhanced the antiviral potency and reverse transcriptase inhibition when combined with less bulky C5 substituents, whereas it generally reduced activity if combined with C5 isopropyl substitution. Among the investigated analogues, the 2,6-difluorophenyl (16e) and the 2-chloro-6-fluorophenyl (17d) derivatives emerged as the most promising racemic compounds, showing subnanomolar activity against wt HIV-1, low nanomolar potency against the mutant K103 N and the multidrug-resistant clinical isolate IRLL98, and (sub)micromolar activity against Y181C, Y188L, and K103N + Y181C strains. Enzymatic assays confirmed HIV-1 reverse transcriptase (RT) as the primary target and supported the cellular SAR trends. Enantioseparation of 16e and 17d combined with CD studies and the evaluation of the antiviral activity both in cells and with recombinant RTs revealed a pronounced enantioselectivity, with the R enantiomers displaying superior antiviral profiles compared with the corresponding S enantiomers and racemates. Notably, (R)-16e and (R)-17d combined subnanomolar activity against wt HIV-1 and IRLL98 with high selectivity and potent inhibition of resistant RT variants. These findings identify conformationally restricted MTM-S-DABOs, particularly their R enantiomers, as highly potent second-generation NNRTI leads for further optimization.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y,

title = {Early-onset cancer and modifiable risk: quantifying the combined impact of excess body weight and alcohol on breast and colorectal cancer in Italy (18-34 years)},

author = {Bolpagni F and Lanati S and Biino G and Labrini L and Madini N and Vincenti A and Manuelli M and Sottotetti F and Locati LD and Cena H},

url = {https://link.springer.com/article/10.1186/s12889-026-28219-x},

doi = {10.1186/s12889-026-28219-x},

year  = {2026},

date = {2026-10-05},

urldate = {2026-10-05},

journal = {BMC public health},

volume = {26},

issue = {1},

pages = {2350},

abstract = {Background: Rising rates of cancers diagnosed before the age of 50 have been reported worldwide, including in Italy. Among modifiable risk factors, excess body weight (overweight and obesity) and alcohol consumption independently and synergistically increase the risk of breast and colorectal cancers, including early-onset disease. However, the population-level burden attributable to these exposures among adolescents and young adults (AYA) remains poorly quantified. Methods: We combined a targeted overview of the literature with a quantitative Population Attributable Fraction (PAF) analysis to estimate the proportion of early-onset breast and colorectal cancers attributable to overweight/obesity, high-risk alcohol consumption, and their combined exposure in the Italian population aged 18-34 years. Sex- and age-specific prevalence data were derived from the national surveillance system ""PASSI"", while relative risks were obtained from meta-analyses and large cohort studies, prioritizing estimates from early-onset populations when available. PAFs were estimated using the Bruzzi et al. method, while combined PAFs were calculated assuming independence between exposures. Uncertainty was assessed through Monte Carlo simulations and sensitivity analyses on prevalence and relative risk assumptions. Results: Among Italian young adults aged 18-34 years, overweight and obesity together accounted for a substantial proportion of early-onset colorectal cancer cases, while high-risk alcohol consumption showed the largest individual attributable fraction. The combined contribution of excess body weight and high-risk alcohol consumption reached 16.6% of early-onset colorectal cancer cases. For early-onset breast cancer in young women, high-risk alcohol consumption was associated with PAFs of 4.6%. Sensitivity analyses confirmed the robustness of the estimates and indicated that uncertainty in relative risk assumptions represented the main source of variability. Conclusions: Obesity and alcohol consumption contribute meaningfully to the burden of early-onset breast and colorectal cancers in Italy. Integrating weight management and alcohol risk assessment into clinical practice and public health strategies targeting young adults could prevent a measurable proportion of these cancers and help counteract the rising incidence of malignancies at young ages.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_284,

title = {From Tissue Specificity to Systemic Cues: Shaping MYC‑Driven Tumor Metabolism},

author = {Alamoudi AA and Mao Y and Zadra G and Labbe' DP},

url = {https://aacrjournals.org/cancerres/article-abstract/doi/10.1158/0008-5472.CAN-26-0142/787226/From-Tissue-Specificity-to-Systemic-Cues-Shaping?redirectedFrom=fulltext},

doi = {10.1158/0008-5472.CAN-26-0142},

year  = {2026},

date = {2026-10-05},

journal = {Cancer research},

volume = {88},

issue = {19},

pages = {4744-4754},

abstract = {The proto-oncogene MYC acts as a master regulator of diverse metabolic programs that fuel tumor initiation and progression, but the exact programs it activates depend heavily on context, tissue type, accompanying mutations, and the tumor microenvironment (TME). Furthermore, extrinsic influences, including diet and systemic metabolism, interact with MYC to reshape tumor and stromal cell metabolism, revealing a multifaceted metabolic landscape governed by MYC. This review focuses on MYC-driven in vivo metabolic addictions and discusses tissue-specific programs, TME interactions, and systemic influences to illustrate how MYC-driven metabolic reprogramming creates context-dependent vulnerabilities. These insights may uncover actionable targets and guide precision therapeutic strategies for MYC-driven cancers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_283,

title = {Nucleoporin TPR integrates MAPK signaling with mitogen-induced transcriptional programs},

author = {Liu J and Zheng Y and Xiong Y and Ma R and Lin Z and Lin H and Anduar-Sanchez M and Bartkova J and Liu J and Foiani M and Bartek J and Kosar M},

url = {https://www.nature.com/articles/s41419-026-08760-8},

doi = {10.1038/s41419-026-08760-8},

year  = {2026},

date = {2026-06-16},

journal = {Cell death and disease},

volume = {17},

issue = {1},

pages = {400},

abstract = {The nuclear pore complex (NPC) component TPR has emerged as a multifunctional scaffold implicated in mitosis, chromatin organization, mRNA export, and genome stability. However, TPR's role in mitogenic signal transduction remains largely unexplored. Here, we investigate whether nucleoporin TPR functions as a MAPK-regulated nuclear component that modulates mitogenic signals initiated at the plasma membrane-including EGFR activation-and their transcriptional output. Transcriptomic profiling reveals that TPR depletion reshapes EGF-induced, MAPK-responsive gene expression, including altered expression of MAPK pathway components and enhanced induction of the immediate-early gene FOS. Functionally, TPR-depleted cells exhibit increased FOS induction upon EGF stimulation and altered EGF-driven cell-cycle progression. Using a novel phospho-specific monoclonal antibody, we show that TPR is phosphorylated at Ser2155 following EGFR activation via the canonical RAS-RAF-MEK-ERK MAPK cascade, placing TPR downstream of MAPK pathway activation. This phosphorylation is suppressed by clinically used EGFR and BRAF inhibitors and, conversely, is constitutively induced by oncogenic RAS and BRAF, indicating that Ser2155 phosphorylation reflects MAPK pathway activity. In vivo, CRISPR/Cas9-engineered Tpr haploinsufficient mice show changes in MAPK pathway regulatory gene expression in bulk spleen RNA-seq, consistent with findings in human cells, and enhanced Fos induction in splenocytes upon CD3/CD28 stimulation, together suggesting a conserved association between TPR levels and altered MAPK-related transcriptomic profiles. Finally, immunohistochemical analysis reveals elevated TPR phosphorylation in serous ovarian carcinoma and heterogeneous phosphorylation patterns in triple-negative breast cancer, two tumor types frequently characterized by MAPK pathway hyperactivation. Together, these findings uncover a previously unappreciated role for TPR as a MAPK-responsive nuclear factor and support a model in which NPC-associated components fine-tune mitogen-induced transcriptional responses.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_282,

title = {Site-specific DNA double-strand break induces local transcription in cis and protein expression},

author = {di Lillo A and Tavella S and Iannelli F and Crisafulli G and Gioia U and Trastus LA and Cabrini M and {d'Adda di Fagagna F} },

url = {https://www.nature.com/articles/s42003-026-10230-y},

doi = {10.1038/s42003-026-10230-y},

year  = {2026},

date = {2026-06-16},

urldate = {2026-06-16},

journal = {Communications biology},

volume = {9},

issue = {1},

pages = {1000},

abstract = {The DNA damage response is a complex network of pathways that cells activate to safeguard genome integrity following DNA damage, including DNA double-strand breaks. We and others previously reported that RNA polymerase II, together with components of the preinitiation complex, is recruited to exposed DNA ends. This results in the assembly of a fully competent transcriptional apparatus and the synthesis of damage-induced long non-coding RNAs, which are necessary for full DNA damage response activation. Thus, DNA double-strand breaks could act as transcriptional promoters. Whether such DNA breaks, generated upstream of an open reading frame lacking a transcriptional promoter and followed by a polyadenylation signal, can induce the transcription of a coding RNA that is subsequently translated into a protein product remains unknown. Here, taking advantage of the CRISPR/Cas9 technology, we generate a sequence-specific double-strand break upstream of a promoter-less, and therefore silent, reporter gene in two distinct cellular systems. In both cell models, a DNA double-strand break is sufficient to trigger the expression of polyadenylated transcripts and a protein product. Collectively, our results demonstrate that DNA double-strand breaks can act as functional promoters capable of driving protein synthesis, revealing an additional mechanism through which DNA damage can regulate gene expression.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{%a1.%Y_281,

title = {Integrated RNA sequencing and in vivo biosensor imaging define the early pathogenic cascade of Duchenne muscular dystrophy},

author = {Cannone E and La Spina M and Gnutti B and Tesoriero C and Castagnaro S and Tobia C and La Via L and Sabatelli P and Faldini C and Fiume G and Vettori A and Finazzi D and Gennarelli M and Magri C and Schiavone M},

url = {https://www.sciencedirect.com/science/article/pii/S1931524426001192?via%3Dihub},

doi = {10.1016/j.trsl.2026.06.007},

year  = {2026},

date = {2026-06-16},

urldate = {2026-06-16},

journal = {Translational research},

volume = {295},

pages = {31-49},

abstract = {Duchenne muscular dystrophy (DMD) is a lethal muscle disease caused by loss of dystrophin, and characterized by progressive muscle wasting, with massive replacement of muscle fibers with adipose tissue. Yet, the early molecular events that initiate pathology remain poorly defined. Here, we combined longitudinal RNA sequencing of sapje dystrophic zebrafish (a single-mutation vertebrate model of human DMD characterized by a severe phenotype), transcriptomic profiling of human DMD myoblasts and myotubes, and functional in vivo imaging using pathway-specific zebrafish biosensors to reconstruct the cascade of events triggered by dystrophin deficiency. We observed that the earliest stages of disease are characterized by marked downregulation of genes controlling cytosolic Ca2+ homeostasis, mitochondrial function and organization, and Pax3/Mef2a/Srf-mediated transcriptional programs essential for satellite cell maintenance and muscle differentiation. These early deficits precede robust but ineffective regenerative and metabolic compensatory responses, accompanied by extracellular matrix remodeling and TGFβ activation. At advanced stages, both sapje zebrafish and human DMD myotubes converge on profound mitochondrial dysfunction, impaired cell-cycle control, and chronic inflammation signaling. Live imaging of sapje zebrafish biosensors validated these transcriptomic signatures, revealing reduced Notch, Bmp, Shh, Hif-1a and Wnt signaling, along with aberrant TGFβ activity and disrupted mitochondrial dynamics in vivo. Together, these findings identify a conserved temporal sequence linking early Ca2+ dysregulation to mitochondrial failure, satellite cell hyperactivation, and fibrotic remodeling, providing mechanistic insights and therapeutic targets for early intervention in DMD patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_280,

title = {Role of hypertrophic adipocytes, collagen VI, and CD38 in adipose tissue fibrosis in obesity},

author = {Di Vincenzo A and Luca T and Perugini J and Lezoche G and Barresi V and De Geronimo V and Donati A and Casarotta E and Tomasello M and Pezzino S and Scuderi C and Di Cristoforo A and Pieroni A and Petrelli M and Napoli MV and Figueiredo N and Corgosinho FC and Sbarbati A and Merlini L and Sabatelli P and Graciotti L and Spadoni T and Dani C and Mattioli-Belmonte M and Condorelli DF and Gabrielli A and Malavasi F and Giordano A and Castorina S and Cinti S},

url = {https://www.nature.com/articles/s41598-026-49848-7},

doi = {10.1038/s41598-026-49848-7},

year  = {2026},

date = {2026-05-18},

urldate = {2026-05-18},

journal = {Scientific reports},

volume = {16},

issue = {1},

pages = {19503},

abstract = {not available},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_279,

title = {Pharmacological Restoration of Mitochondrial Permeability Transition Pore Flickering by High-Content Drug Repurposing},

author = {Franchini E and Bulloni M and Sorgente A and Paulikova K and Cassina L and Marafelli I and Sambri I and Pattini L and Casari G},

doi = {10.1016/j.phrs.2026.108234},

year  = {2026},

date = {2026-05-18},

urldate = {2026-05-18},

journal = {Pharmacological research},

volume = {229},

pages = {108234},

abstract = {The mitochondrial permeability transition pore (mPTP) is a voltage‑ and calcium‑regulated channel located in the inner mitochondrial membrane whose activity critically influences cellular fate. While prolonged pore opening leads to mitochondrial depolarization, matrix swelling, and cell death, brief and reversible opening events, referred to as flickering, enable controlled release of calcium and reactive oxygen species and serve essential physiological functions. Emerging evidence indicates that restoring physiological mPTP flickering, rather than suppressing pore activity, may be beneficial in disorders characterized by impaired pore dynamics, including hereditary spastic paraplegia type 7 (SPG7). However, no approved therapies are currently available to promote controlled mPTP pore opening. To identify pharmacological modulators of flickering, we performed a high-content screening of 2,000 FDA and EMA-approved compounds using a validated fluorescence-based assay coupled with automated image analysis. Thirteen compounds increased both the frequency and the area of flickering events while preserving cellular and mitochondrial integrity. Validation in fibroblasts derived from SPG7 patient cells and healthy control confirmed reproducible activity across distinct genetic backgrounds. Among the prioritized candidates, berberine emerged as the most robust modulator, consistently enhancing mPTP flickering independently of SPG7 mutation status. Notably, berberine selectively increased the proportion of small-size flickering events, indicative of physiological pore activity. These findings identify berberine as a promising modulator of mPTP dynamics and support pharmacological restoration of physiological flickering as a potential therapeutic strategy for SPG7 and other disorders associated with impaired mitochondrial permeability transition pore regulation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_278,

title = {Degrees of H2AX phosphorylation correlate with unique features of the intratumoral immune microenvironment in colorectal carcinomas},

author = {Berrino E and Bellomo SE and Aquilano MC and Falcinelli M and Chesta A and Valtorta E and Zampieri D and Mauri G and Sala G and Marsoni S and Bardelli A and Sartore-Bianchi A and Siena S and Sapino A and Bonoldi E and {d'Adda di Fagagna F} and Marchiò C},

url = {https://pmc.ncbi.nlm.nih.gov/articles/PMC13071407/},

doi = {Oncologist},

year  = {2026},

date = {2026-05-18},

journal = {Oncologist},

volume = {31},

issue = {5},

abstract = {Background: The phosphorylated form of the histone H2AX (γH2AX), a sensor of DNA double-strand breaks (DSB), can serve as a biomarker of DNA damage and therapy response. This study aimed to evaluate the association between γH2AX expression and pathological, molecular, and immune features in colorectal cancer (CRC). Patients and methods: Levels of γH2AX were assessed by immunohistochemistry in a cohort of 198 CRCs, alongside immune-related markers (CD3 and CD8). A sub-cohort of 65 CRCs (26 γH2AX- and 39 γH2AX+) underwent RNA extraction and gene expression profiling using the IO360 Nanostring Panel to infer immune cell composition. Overall survival data were analyzed for exploratory correlations. Results: γH2AX+ CRCs (155/198, 78%) were significantly associated with higher stage and tumor grade (P < .01). A lower γH2AX prevalence was found in MMR-deficient tumors (64%) compared to MMR-proficient cases (81%, P = .05). γH2AX+ tumors showed increased CD3+ cell infiltration in the overall population (P = .038) and in MMR-proficient CRCs (P = .028). Gene expression analysis revealed higher T-cell counts (P < .01) and reduced B-cell abundance (P < .01) in γH2AX+ CRCs. Unsupervised clustering identified 3 immune subgroups with differential γH2AX accumulation. Cluster #3, enriched in γH2AX+ tumors, displayed increased CD8+ T-cells and conferred the best survival outcome. Conclusion: Elevated γH2AX expression correlates with MMR proficiency, aggressive histopathologic features, and a distinctive immune-active microenvironment in CRC. These findings may support γH2AX as a marker of immune-modulated CRC subgroups with potential prognostic and therapeutic relevance.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_277,

title = {Mechano-metabolic feedback connects tissue fluidity to mitochondrial DNA-dependent immunity in breast cancer},

author = {Palamidessi A and Frittoli E and Corada M and Martini E and Barzaghi L and Milanese C and Beznoussenko GV and Lazzarin A and Bellini EN and Mironov AA and Lavagnino Z and Magni S and Barozzi S and Parazzoli D and Tizzoni L and Dall'Olio V and Cancila V and Romani P and Di Bona M and Zobalova R and Boukalova S and Rediti M and Mastroberardino PG and Neuzil J and Foiani M and Dupont S and Tripodo C and Scita G},

url = {https://www.nature.com/articles/s41467-026-71795-0},

doi = {10.1038/s41467-026-71795-0},

year  = {2026},

date = {2026-05-18},

urldate = {2026-05-18},

journal = {Nature communications},

volume = {17},

issue = {1},

pages = {6374},

abstract = {Why some tumors respond to immunotherapy ("hot" tumors) while others remain resistant ("cold" tumors) is a central challenge in oncology. Elevated RAB5A-dependent endocytosis drives tissue fluidization during the transition to invasive breast carcinoma, but its immunological consequences are unclear. Here we show that RAB5A-driven fluidization induces a mechano-metabolic stress response that disrupts the AMPK-AKAP1-DRP1 mitochondrial fission pathway, causing mitochondrial elongation. RAB5A vesicles interact with hyperfused mitochondria and promote BAX/BAK-dependent pore formation, leading to limited mitochondrial outer membrane permeabilization. This sub-lethal event is amplified by palmitoylated GASDERMIN A oligomerization on mitochondria, establishing a positive feedback loop. The resulting release of mitochondrial DNA activates the cGAS-STING innate immune pathway and drives a hyperinflammatory state. Consequently, RAB5A-expressing tumors in immunocompetent mice grow more slowly, show increased immune infiltration, and display enhanced sensitivity to immune-checkpoint blockade in a BAX/BAK-, cGAS/STING-, and mtDNA-dependent manner. These findings connect mechanical stress, mitochondrial dynamics, and innate immunity, revealing strategies to potentiate antitumor immunotherapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_276,

title = {PDS5 proteins control genome architecture by limiting the lifetime of cohesin-NIPBL complexes},

author = {Wutz G and Davidson IF and Banigan EJ and Stocsits RR and Kawasumi R and Tang W and Nagasaka K and Costantino L and Jansen R and Hirota K and Branzei D and Mirny LA and Peters JM},

url = {https://www.sciencedirect.com/science/article/pii/S1097276526002017?via%3Dihub},

doi = {10.1016/j.molcel.2026.03.025},

year  = {2026},

date = {2026-05-18},

journal = {Molecular cell},

volume = {86},

issue = {9},

pages = {1614-1634},

abstract = {Cohesin-NIPBL complexes extrude genomic DNA into loops that are constrained by CTCF boundaries. This process has important regulatory functions and weakens the separation between euchromatic and heterochromatic compartments. Cohesin can also bind PDS5 proteins, which do not support loop extrusion but are required for the formation of CTCF boundaries. How PDS5 proteins perform this function is unknown. Here we show, by in vitro single-molecule imaging, that human PDS5 proteins stop loop extrusion by facilitating the dissociation of NIPBL from cohesin. Hi-C experiments suggest that this function is required for the establishment of CTCF boundaries in cells. In silico modeling indicates that PDS5 proteins enable the separation between compartments by limiting cohesin's velocity and chromatin residence time. The degree of this compartmentalization depends on the frequency with which chromatin is extruded relative to the time it takes for compartments to form. These results identify PDS5 proteins as key regulators of genome organization.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_275,

title = {Stability of c-Myc Protein in Early S Phase Is Regulated by the Interaction with PCNA},

author = {Cardano M and Cazzalini O and Maraventano G and Stivala LA and Zannini L and Prosperi E},

url = {https://www.mdpi.com/1422-0067/27/6/2745},

doi = {10.3390/ijms27062745},

year  = {2026},

date = {2026-05-18},

journal = {International journal of molecular sciences},

volume = {27},

issue = {6},

abstract = {The transcription factor c-Myc is known to regulate DNA replication via a non-transcriptional mechanism by interacting with proteins of the pre-replicative complex. In addition, c-Myc localizes to DNA replication foci, similarly to Proliferating Cell Nuclear Antigen (PCNA); however, the significance of this localization remains unclear. Here, we investigated whether c-Myc interacts with PCNA and analyzed the possible function of this association. We found a conserved interaction motif, the PCNA-interacting protein (PIP) box, in the N-terminal region of c-Myc. Confocal microscopy analysis showed co-localization with PCNA in early S-phase, but not in late S-phase cells. Co-immunoprecipitation from cell extracts and pull-down of recombinant proteins indicated a direct physical association between c-Myc and PCNA, which was confirmed in situ by the Proximity Ligation Assay (PLA). Further experiments demonstrated that c-Myc interacts with CUL4A and DDB1, components of the Cullin Ring E3 ubiquitin ligase 4 (CRL4) complex, in which PCNA functions as a cofactor. Mutations in the PIP box of c-Myc, as well as depletion of CUL4A by RNA interference, resulted in an increased stability of c-Myc protein. These results suggest that the interaction with PCNA functionally contributes to the regulation of c-Myc stability in early S phase via the CRL4 complex.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_274,

title = {Pre-treatment circulating microRNA signatures predict outcomes of anti-CD19 CAR T-cell therapy},

author = {Naddeo M and Roncarati R and De Felice F and Zuin E and Pace I and Iannotta F and Laprovitera N and Fontana B and Durante G and Salamon I and Storci G and De Matteis S and Ricci F and Bertuccio SN and Messelodi D and Ursi M and Roberto M and Barbato F and Ardizzoia F and Tomassini E and Sinigaglia B and Zazzeroni L and Dan E and Duardo RC and Vaglio F and Tassoni M and Pellegrini C and Gentilini M and Maffini E and Casadei B and Sales G and Zinzani PL and Bonafe’ M and Ferracin M and Bonifazi F},

url = {https://haematologica.org/article/view/14143},

doi = {10.3324/haematol.2025.300294},

year  = {2026},

date = {2026-05-18},

journal = {Haematologica},

abstract = {not available},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{%a1.%Y_273,

title = {Validation of an enhanced pediatric vitamin D deficiency score incorporating sun exposure timing and BMI z-score: analysis in a combined cohort of children},

author = {Calcaterra V and Cena H and Biino G and Scavone IAM and Vincenti A and Zuccotti G},

url = {https://link.springer.com/article/10.1007/s00431-026-06890-x},

doi = {10.1007/s00431-026-06890-x},

year  = {2026},

date = {2026-05-18},

journal = {European journal of pediatrics},

volume = {185},

issue = {4},

pages = {226},

abstract = {Early identification of vitamin D (VitD) deficiency in childhood is essential to support timely prevention and intervention strategies. Building on the previously validated pediatric EVIDENCe-Q questionnaire, this study aimed to refine the tool by integrating two patient-specific weighted variables, sun exposure during peak UVB hours, and BMI z-score categories, both recognized determinants of circulating 25-hydroxyvitamin D (25-OH-D) levels. A total of 354 children (190F/164 M) completed a 20-item pediatric VitD risk questionnaire. Serum 25-OH-D concentrations were available for 280 participants. Three scoring algorithms were evaluated: the unweighted standard model, the sun-weighted model, and the sun + BMI-weighted model. Statistical analyses included ANOVA, Pearson correlations, and receiver operating characteristic (ROC) analyses across biochemical thresholds of vitamin D deficiency and insufficiency (< 10, < 20, and < 30 ng/mL). Vitamin D deficiency (< 10 ng/mL) was observed in 6.8% of participants, while insufficiency affected 38.1% (< 20 ng/mL) and 74.7% (< 30 ng/mL). The unweighted standard model did not discriminate among vitamin D categories (p = 0.622). In contrast, both weighted models showed significant discrimination (sun-weighted: p = 0.036; sun + BMI-weighted: p = 0.030). Only the sun + BMI-weighted model was significantly correlated with serum 25-OH-D levels (r = - 0.13; p = 0.023). ROC analyses demonstrated limited accuracy for the unweighted model, whereas the weighted models showed moderate discriminatory ability, with the Sun + BMI-Weighted Model providing the strongest overall performance.

 Conclusions: Incorporating weighted patient-specific variables improves the discriminatory capacity of the pediatric EVIDENCe-Q. Despite moderate accuracy, particularly at lower thresholds, the refined questionnaire, especially the sun + BMI-weighted version, represents a practical, noninvasive screening tool to identify children at risk of hypovitaminosis D.

 What is known: • Vitamin D deficiency is highly prevalent in children worldwide, even in sun-rich regions, and is influenced by factors such as sun exposure and adiposity. • Serum 25-OH-D measurement is the diagnostic gold standard, while questionnaire-based tools offer a non-invasive but currently less accurate alternative in pediatrics.

 What is new: • Incorporating weighted factors for peak UVB sun exposure and BMI z-score signifi cantly improves the predictive performance of the pediatric EVIDENCe-Q. • The Sun + BMI-weighted model shows a significant correlation with serum 25-OH-D and enhances identification of children at risk of hypovitaminosis D (30 ng/mL).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y,

title = {Editorial Overview: Integrating behaviour, ecology, and technology in contemporary insect science},

author = {Scolari F and Perez-Staples D},

url = {https://www.sciencedirect.com/science/article/pii/S2214574526000532?via%3Dihub},

doi = {10.1016/j.cois.2026.101537},

year  = {2026},

date = {2026-05-18},

urldate = {2026-05-18},

journal = {Current opinion in insect science},

pages = {101537},

abstract = {not available},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_271,

title = {Emerin is necessary for microtubule-organizing center translocation to the nuclear envelope of muscle cells},

author = {Mattioli E and Cenni V and Sabatelli P and Schena E and Santi S and Fiorillo C and Bruno C and Pini A and Giannotta M and Cavallo M and Errani C and Cattin E and Benati D and Recchia A and Lattanzi G},

url = {https://www.nature.com/articles/s41419-026-08819-6},

doi = {10.1038/s41419-026-08819-6},

year  = {2026},

date = {2026-05-18},

urldate = {2026-05-18},

journal = {Cell death and disease},

volume = {17},

issue = {1},

pages = {615},

abstract = {During myogenic differentiation, the Microtubule-Organizing Center (MTOC) is relocated to the nuclear envelope by a molecular platform including Linker of Nucleoskeleton and Cytoskeleton (LINC) complex proteins, A Kinase Anchoring Proteins (AKAP9 and AKAP6) and Pericentriolar Material 1 (PCM-1). Here, we show that emerin is required for centrosomal protein recruitment to the nuclear periphery of myonuclei and microtubule dynamics. In fact, in type 1 Emery-Dreifuss Muscular Dystrophy (EDMD1), loss of emerin was associated with altered pericentrin recruitment to the nuclear envelope, LINC protein impairment at the nuclear poles of myonuclei and microtubule organization defects. As a consequence, dynein, mitochondrial distribution and nuclear alignment along the longitudinal axis of the myotubes were altered in EDMD1 myotubes. Moreover, reduced levels of AKAP6 and PKA were detected at the nuclear periphery of EDMD1 myotubes, possibly contributing to an aberrant nuclear localization of the mechanosensing factor YAP. Upon rescue of emerin expression by CRISPR correction of mutated EMD gene: SUN1/2, pericentrin, AKAP6 and PKA were restored at the nuclear envelope and a correct YAP localization was observed in EDMD1 muscle cells. These results show that emerin is required for Nuclear Envelope-MTOC (NE-MTOC) organization in differentiating skeletal muscle cells and suggest that disruption of such complex is a key pathogenetic event in Emery-Dreifuss Muscular Dystrophy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_270,

title = {Targeting the FNIP2-SERCA2b axis improves metabolic and mitochondrial defects in Ataxia Telangiectasia},

author = {Vinciguerra M and El Kharef C and Bruhn C and Falbo L and Milanese C and Audano M and Beznoussenko GV and Mironov AA and Delia D and Foiani M and Mastroberardino PG and Mitro N and Costanzo V},

url = {https://pmc.ncbi.nlm.nih.gov/articles/PMC13031930/},

doi = {10.1038/s41419-026-08507-5},

year  = {2026},

date = {2026-05-18},

journal = {Cell death & disease},

volume = {17},

issue = {1},

pages = {290},

abstract = {Ataxia telangiectasia (AT) is a rare multisystem disorder caused by the loss of functional ATM protein, leading to immunodeficiency, cancer predisposition, neurodegeneration, diabetes, heart failure, and premature aging. Although ATM's role as a sensor of DNA double-strand breaks (DSBs) is well established, the mechanisms underlying the diverse AT phenotypes remain incompletely understood, with evidence suggesting they extend beyond DSB sensing. Here, we uncover widespread glycogen accumulation as a key feature of AT cells and tissues, driven by dysregulated glucose metabolism and impaired mitochondrial respiration assessed with a multidimensional approach including metabolomics, flux analysis, histopathology, bioenergetic measurements, and electron tomography. These metabolic defects contribute to reduced cellular viability and premature senescence observed in AT patient-derived cells. Strikingly, inactivation of FNIP2, which controls mitochondrial respiration, partially rescues these defects in AT cellular models. We show that FNIP2 interacts with the SERCA2b calcium channel, and its inactivation enhances cytoplasmic calcium availability, stimulating mitochondrial respiration and increasing glucose consumption. This metabolic reprogramming prevents glycogen accumulation and improves survival in AT primary cells. Our findings provide novel insights into AT pathophysiology and indicate the FNIP2-SERCA2b axis as a novel potential target for mitigating the systemic effects of AT and improving outcomes in this complex disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_269,

title = {Proteasomal-dependent CHK1 degradation leads to DNA damage accumulation in ALS cellular model systems},

author = {Modafferi S and Silenzi V and Garbelli A and Lazoi G and Scarian E and D'Uva S and Santini T and Riccardi A and Cozzolino M and Pansarasa O and D'Ambrosi N and Sabbioneda S and Morlando M and Francia S},

url = {https://www.nature.com/articles/s41419-026-08603-6},

doi = {10.1038/s41419-026-08603-6},

year  = {2026},

date = {2026-05-18},

urldate = {2026-05-18},

journal = {Cell death & disease},

volume = {17},

issue = {1},

pages = {599},

abstract = {Amyotrophic lateral sclerosis (ALS) is characterised by the aggregation of TDP-43 and mutant FUS in the cytoplasm of affected motor neurons. Accumulation of DNA damage is emerging as a novel correlative trait of ALS. We recently showed that formation of TDP-43 and FUS cytoplasmic inclusions (CIs) lead to DNA damage accumulation through dysregulation of the DNA damage response (DDR). However, the multiple molecular mechanisms contributing to DNA damage accumulation in affected motor neurons in ALS have not been fully elucidated. In recent years, chemical inhibition of the serine/threonine kinase CHK1 was shown to lead to accumulation of DNA breaks as well as increased apoptosis, in differentiated cortical neurons. Notably, CHK1 has been involved in DNA double-strand break repair in non-dividing cells, by acting through the histone chaperone ASF1A. In this article, we show that cells bearing FUS and TDP-43 CIs show downregulation of the protein levels of CHK1 and ASF1A. We observe CHK1 protein downregulation in neuronal cell lines, as well as in patient-derived motor neurons progenitors and in the spinal cord of a FUS-ALS mouse model. Restoration of the nuclear levels of CHK1 and ASF1A via transient overexpression, is sufficient to reduce DNA damage signal accumulation and rescues DDR defects. Importantly, we show that the ubiquitin-proteasome pathway is responsible for CHK1 degradation in cells bearing FUS CI, since its inhibition restores CHK1 and ASF1A protein levels. Our study demonstrates that proteasomal-dependent CHK1 and ASF1A downregulation contributes to accumulation of DNA damage in cells affected by ALS-linked protein aggregates.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_268,

title = {TSPY-like 2, Beyond the Histone Chaperone Role},

author = {Bonenti E and Cardano M and Buscemi G and Zannini L},

url = {https://www.mdpi.com/2218-273X/16/3/378},

doi = {10.3390/biom16030378},

year  = {2026},

date = {2026-05-18},

journal = {Biomolecules},

volume = {16},

issue = {3},

pages = {378},

abstract = {Chromatin is a dynamic cellular structure basically constituted by nucleosomes, which consist of a DNA sequence wrapped around an octameric histones core. Histone synthesis and transport, nucleosome formation and proper chromatin assembly is an ordered and stepwise process guided by histone chaperones. Several families of histone chaperones have been identified and one of them is the nucleosome assembly protein (NAP) superfamily. Members of this family have been involved not only in chromatin constitution and regulation but also in several other cellular processes, such as nucleocytoplasmic shuttling, DNA replication, transcription and cell-cycle regulation. Testis specific protein Y-like 2 (TSPYL2) is a peculiar member of the NAP superfamily of histone chaperone. This protein has been initially isolated as a nuclear antigen in patients affected by discoid lupus erythematosus and as a TGF-β target. Its ability to bind histones has been demonstrated. In addition, TSPYL2 has been reported to regulate transcription, cell-cycle progression and the DNA-damage response, independently of its role in chromatin organization. In accordance with its multiple functions, defects in TSPYL2 have been associated with different diseases, mainly cancer and neurodevelopmental abnormalities. In this review we summarize and discuss the multiple cellular functions of TSPYL2, pointing out new and unexpected aspects like a sex-related activity and their relationship with different diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_267,

title = {Bi-allelic variants in FSD1L cause a neurodevelopmental disorder overlapping with L1 syndrome},

author = {Serpieri V and Vezain-Mouchard M and Orsi A and Lecointre M and Mazzotta C and Marguet F and Garbelli A and Marcorelles P and Celli L and Goldenberg A and De Mori R and Drouot N and Petrizzelli F and Janin F and Nicolas G and Smal N and Condoluci C and Marini C and Tran-Mau-Them F and Ruault V and Micalizzi A and Bione S and Mazza T and Pichiecchio A and Ginevrino M and Weckhuysen S and Bedois A and Desnous B and Hermitte L and Rabie G and Kanaan M and Gonzalez BJ and Sabbioneda S and Laquerrière A and Saugier-Veber P and Valente EM},

url = {https://www.sciencedirect.com/science/article/pii/S0002929726000364?via%3Dihub},

doi = {10.1016/j.ajhg.2026.01.014},

year  = {2026},

date = {2026-03-16},

journal = {American journal of human genetics},

volume = {113},

issue = {3},

pages = {600-615},

abstract = {Disruption of the complex processes underlying central nervous system development leads to a broad spectrum of brain malformations and neurodevelopmental disorders, often with a genetic cause. Here, we report bi-allelic pathogenic variants in fibronectin type III and SPRY domain-containing 1-like (FSD1L), encoding a protein of unknown function, in eleven individuals, including five fetuses from six unrelated families. The phenotype ranges from severe hydrocephalus, corpus callosum agenesis, and absent pyramid decussation to a neurodevelopmental syndrome characterized by severe intellectual disability, spastic tetraparesis, reduced vision, and epilepsy, associated with corpus callosum agenesis/hypoplasia, mild ventricular dilation, optic nerve hypoplasia, and white matter reduction. This phenotype closely resembles that observed in L1 syndrome, caused by pathogenic variants in L1CAM, encoding a neural adhesion molecule. The knockdown of Fsd1l in mouse embryos recapitulated the ventricular dilation observed in affected fetuses. Immunohistochemical studies in human control fetuses revealed that FSD1L localized to neurons with commissural fate and projection neurons during human development. Induced pluripotent stem cell (iPSC)-derived neural progenitor cells from affected individuals failed to differentiate into premature neurons and to properly form neurospheres while undergoing increased cell death. In neural progenitors, FSD1L localized with microtubules of the mitotic spindle during M phase and to the transition zone and along the axoneme of the primary cilium during interphase. In line with this, fibroblasts from affected individuals exhibited marked alterations of the mitotic spindle and reduced ciliogenesis and ciliary length compared to control cells. Our findings define FSD1L as a microtubule-associated protein implicated in neuronal differentiation, axon guidance, and fasciculation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_266,

title = {Identification of 3-cyanoquinolines as broad-spectrum inhibitors of Monkeypox virus and other sexually transmitted pathogens},

author = {Martina MG and Mathez G and Rubini D and Valenti ME and Lachat P and Cristinelli S and Kebbi Beghdadi C and Carlen V and Crespan E and Bianchi E and Opota O and Greub G and Ciuffi A and Gouttenoire J and Radi M and Cagno V},

url = {https://www.sciencedirect.com/science/article/pii/S0753332226001125?via%3Dihub},

doi = {10.1016/j.biopha.2026.119080},

year  = {2026},

date = {2026-03-16},

journal = {Biomedecine & pharmacotherapie},

volume = {196},

pages = {119080},

abstract = {Sexually transmitted infections (STIs) remain a major global health concern, contributing significantly to morbidity and facilitating the co-transmission of other pathogens. Recent outbreaks of Monkeypox virus (MPXV) have further underscored the urgent need for broad-spectrum antiviral agents effective against emerging and re-emerging sexually transmissible viruses. We report here the design and synthesis of a series of 3-cyanoquinoline-based Src inhibitors to evaluate their antimicrobial efficacy against sexually transmitted pathogens. Among them, compound 7d demonstrated potent inhibitory activity against MPXV, Herpes simplex virus types 1 and 2, Hepatitis C virus, Human immunodeficiency virus, and Chlamydia trachomatis at non-toxic concentrations. Owing to its broad-spectrum profile and favorable cytotoxicity profile, compound 7d represents a promising candidate for development as a topical microbicide for the prevention and treatment of STIs. Interestingly, the screening also identified compound 7g, which, despite lacking Src inhibitory activity, exhibited selective antiviral activity against members of the Poxviridae family, suggesting the involvement of alternative host-dependent mechanisms that can be further exploited. Both compounds were non-toxic in relevant epithelial and mucosal tissue models. Collectively, these findings highlight the therapeutic potential of 3-cyanoquinoline derivatives as scaffolds for the development of novel broad-spectrum microbicides targeting a range of sexually transmitted pathogens.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_265,

title = {α-ketoglutarate/succinate ratio imbalance impairs thymine DNA glycosylase function and base excision repair process increasing susceptibility to pancreatic cancer},

author = {Malatesta S and Vigiano Benedetti V and Salviati E and Illi B and Manni I and Middonti E and Rampioni Vinciguerra GL and Licursi V and Troilo F and Colotti G and Cipolla L and Sabbioneda S and Perfetto L and Piaggio G and Bussolino F and Di Nicolantonio F and Campiglia P and Sommella EM and Mori M and Cencioni C and Spallotta F},

url = {https://www.nature.com/articles/s41419-026-08475-w},

doi = {10.1038/s41419-026-08475-w},

year  = {2026},

date = {2026-03-16},

journal = {Cell death and disease},

volume = {17},

issue = {1},

pages = {242},

abstract = {Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, with chronic metabolic disorders increasing risk and severity. Prolonged exposure to altered metabolism changes specific metabolite levels, impacting epigenetic landscape contributing neoplastic lesion acquisition. This study examines the interplay between metabolism and epigenetics in dysmetabolic-driven PDAC tumorigenesis, exploiting LSL-KrasG12D;PDX-1-Cre mice (KC mice) exposed to high-fat diet (HFD) and KRAS-mutated human pancreatic ductal epithelial (HPDE) cells. Untargeted metabolomics of HFD-fed KC pancreata reveals altered free fatty acid and elevated S-adenosyl methionine levels during tumorigenesis. Targeted metabolomics shows increased succinate alongside reduced α-ketoglutarate levels. This imbalance suggests an epigenetic derangement, targeting DNA methylation. In KRAS-mutated HPDE cells exposed to altered metabolism, the DNA demethylation complex of ten-to-eleven-translocation methylcytosine 1 and thymine DNA glycosylase (TDG) is disrupted, leading to iterative cytosine modification and apurinic/apyrimidinic (AP) site accumulation. Succinate directly binds TDG at arginine 275, hyperactivating it and increasing AP site formation. This alteration combined with the methylation-prone metabolic environment, impairs the base excision repair pathway by hypermethylating and downmodulating DNA ligases LIG1 and LIG3. This predisposes to genomic instability and pancreatic preneoplastic lesion development. These findings uncover a metabolic-epigenetic axis in dysmetabolic PDAC, highlighting how metabolite-driven epigenetic changes compromise DNA repair and drive tumorigenesis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_264,

title = {The glycine-arginine-rich motif of 53BP1 modulates RNA interactions necessary for its liquid-liquid phase separation during DNA Damage Response},

author = {Terraneo F and Ceccon M and Sapkota O and Zheng T and Brizioli M and Dello Stritto A and Cummings S and Codispoti S and Ossolengo G and Orsenigo F and Magni S and Gottinger A and Mattevi A and Fuxreiter M and Fawzi NL and Lottersberger F and Giavazzi F and {d'Adda di Fagagna F}},

url = {https://www.biorxiv.org/content/10.64898/2026.01.30.702603v1},

doi = {10.64898/2026.01.30.702603},

year  = {2026},

date = {2026-03-16},

journal = {bioRxiv},

abstract = {The DNA damage response relies on the rapid assembly of repair factors into foci with properties of liquid-liquid phase separation, driven by de novo transcription of damage-induced RNAs. 53BP1 is a key component of these condensates, yet the molecular determinants driving this process remain unknown. Here, through computational, structural and in vitro approaches, we identify the oligomerization domain of 53BP1 and its glycine-arginine-rich (GAR) motif as crucial for RNA interactions and phase separation. Biophysical characterization reveals that 53BP1-RNA condensates can progressively mature into a more stable state, and that GAR mutants display aberrant material properties. Using a cellular model of telomere fusion events, we demonstrate that the GAR motif is essential for 53BP1-mediated DNA repair, which depends on the combined contributions of RNA binding and appropriate condensate biophysical properties. Therefore, RNA-driven 53BP1 condensation is functionally required to maintain genome integrity.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{%a1.%Y_263,

title = {Autofluorescence and Fourier transform infrared analyses trace dietary fluorophores and reveal plastic contamination in the gut of mosquito larvae},

author = {Soldano S and Weththimuni ML and Oldani A and Girella A and Moyano A and Croce AC and Licchelli M and Gomulski LM and Scolari F},

url = {https://www.nature.com/articles/s41598-026-38938-1},

doi = {10.1038/s41598-026-38938-1},

year  = {2026},

date = {2026-03-16},

urldate = {2026-03-16},

journal = {Scientific reports},

volume = {16},

issue = {1},

pages = {7841},

abstract = {No abstract available},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_262,

title = {Molecular evolution of animal aging},

author = {Nussey DH and {d'Adda di Fagagna F} and Bardin AJ and Blau H and Brunet A and Bulavin DV and Guo L and Hara E and Junker JP and Gorbunova V and Mittelbrunn M and Rera M and Reznick J and Seluanov A and Schumacher B and Teeling EC and Valenzano DR and Ye J and Yun MH and Garinis GA and Gilson E},

url = {https://link.springer.com/article/10.1038/s44318-026-00725-z},

doi = {10.1038/s44318-026-00725-z},

year  = {2026},

date = {2026-03-16},

urldate = {2026-03-16},

journal = {EMBO journal},

volume = {45},

issue = {7},

pages = {2095-2111},

abstract = {Comparative biology plays a crucial role in uncovering fundamental biological mechanisms and providing evolutionary models for their variation. This approach is particularly valuable for studying aging, given the remarkable diversity in aging trajectories across the tree of life. Many evolutionary theories of aging were proposed well before the discovery of the molecular mechanisms involved, and they remain largely theoretical. Moreover, the growing number of model organisms and the expanding array of experimental and theoretical approaches used to study aging have often remained compartmentalized. As a result, integrating these diverse insights into a unified framework has become increasingly important. As a step toward this goal, this field perspective outlines general biological mechanisms that help explain the variability in aging patterns and longevity across the animal kingdom.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_261,

title = {DNA double-strand break response at a glance},

author = {Esposito F and Francia S},

url = {https://journals.biologists.com/jcs/article-abstract/139/4/jcs263423/370955/DNA-double-strand-break-response-at-a-glance?redirectedFrom=fulltext},

doi = {10.1242/jcs.263423},

year  = {2026},

date = {2026-03-16},

urldate = {2026-03-16},

journal = {Journal of cell science},

volume = {139},

issue = {4},

pages = {jcs263423},

abstract = {DNA double-strand breaks (DSBs) are among the most cytotoxic and most frequent lesions that arise in the mammalian genome; they occur as a result of both external insults and internal metabolic activities. Failures in damage signalling and repair of DSBs can result in permanent cell cycle arrest, cellular senescence, cell death or the accumulation of mutations and genomic instability - events that ultimately disrupt tissue homeostasis. To reduce these detrimental outcomes, cells have evolved a sophisticated and tightly coordinated network of mechanisms for detecting, signalling and repairing DNA lesions, collectively known as the DNA damage response (DDR). Repair occurs within the chromatin landscape, with DDR sensors, mediators, signalling kinases and ubiquitin ligases rapidly recruited to the site of damage. Simultaneously, local chromatin modifications and remodelling take place, which also modulate local transcriptional activity. More complex chromatin dynamics are subsequently orchestrated within the three-dimensional nuclear space - persistent DSBs are actively relocated to specialized nuclear domains and chromatin compartments undergo spatial reorganization to facilitate efficient repair. In this Cell Science at a Glance article and the accompanying poster, we explore the interplay between local and global chromatin dynamics that coordinate DSB repair and preserve genome integrity within the context of a highly dynamic epigenome.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_260,

title = {Complex I Modulator BI4500 Reduces MASH by Limiting Oxidative Stress and Reprogramming Lipid Metabolism via AMPK in MCD Rats},

author = {Di Pasqua LG and Lotti S and Trucchi M and Palladini G and Croce AC and Protopapa F and Feletti F and Kauschke SG and Sun P and Vairetti M and Ferrigno A},

url = {https://www.mdpi.com/2076-3921/15/1/82},

doi = {10.3390/antiox15010082},

year  = {2026},

date = {2026-02-04},

journal = {Antioxidants},

volume = {15},

issue = {1},

abstract = {Background: Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a multifactorial liver disease in which mitochondrial dysfunction, oxidative stress, and inflammation play key roles in driving the progression toward metabolic dysfunction-associated steatohepatitis (MASH) and hepatocellular carcinoma (HCC). Dysfunctional mitochondria generate excess reactive oxygen species (ROS), impair antioxidant defenses, activate pro-inflammatory pathways and hepatic stellate cells, and perpetuate liver injury. Mitochondrial Complex I is a major ROS source, particularly under conditions of dysregulated energy metabolism. Since Complex I inhibition by metformin was shown to reduce ROS and activate the adenosine monophosphate-activated protein kinase (AMPK), this study aimed to evaluate whether a novel Complex I Modulator (CIM, BI4500) could attenuate oxidative stress, inflammation, and consequently reduce lipid accumulation and fibrosis in a methionine- and choline-deficient diet (MCD)-fed rat model of MASH. Methods: Rats were fed an MCD or an isocaloric control diet for six weeks. From week four, animals received daily oral treatment with CIM (10 mg/kg) or vehicle (Natrosol). At the endpoint, liver tissue was collected for histological, biochemical, and molecular analyses. Lipid droplet area, inflammatory infiltration, and collagen deposition were evaluated on tissue sections; total lipid content and oxidative stress markers were assessed in homogenates and isolated mitochondria. Molecular pathways related to oxidative stress, lipid metabolism, and fibrosis were assessed at protein and mRNA levels. Results: CIM treatment significantly reduced oxidative stress (ROS, lipid peroxidation, nitrogen species), promoting AMPK activation and metabolic reprogramming. This included increased expression of peroxisome proliferator-activated receptor alpha (PPAR-α) and its target genes, and decreased sterol regulatory element binding protein-1c (SREBP-1c)-driven lipogenesis. These changes halted fibrosis progression, as confirmed by Picro-Sirius Red staining and fibrosis markers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_259,

title = {Dissecting the Interaction Domains of SARS-CoV-2 Nucleocapsid Protein and Human RNA Helicase DDX3X and Search for Potential Inhibitors},

author = {Lodola C and Pallotta MM and Manetti F and Governa P and Crespan E and Maga G and Secchi M},

url = {https://www.mdpi.com/1422-0067/27/2/672},

doi = {10.3390/ijms27020672},

year  = {2026},

date = {2026-02-04},

urldate = {2026-02-04},

journal = {International journal of molecular sciences},

volume = {27},

issue = {2},

pages = {672},

abstract = {The SARS-CoV-2 nucleocapsid protein (Np) plays multifunctional roles in the viral life cycle. By interacting with host cellular proteins, Np regulates viral RNA transcription, replication, and immune evasion. It controls genome packaging and counteracts host RNA interference mediated antiviral responses through its RNA binding activity. Previous studies revealed a physical interaction between Np and DDX3X, a human DEAD-box RNA helicase that facilitates the replication of several viruses. This interaction enhances Np affinity for double-stranded RNA and inhibits DDX3X helicase activity. Since Np-RNA binding activity promotes ribonucleoprotein complex formation, targeting this interaction is a promising antiviral strategy. We generated truncated protein variants to define interaction regions between Np and DDX3X. Using AlphaFold modelling, we identified RecA2 as the key DDX3X domain involved in Np binding. Finally, to disrupt Np-RNA complex formation, we screened a small molecule library of putative binders of Np N-terminal region and identified two candidate inhibitors for further development.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}