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PubMed2026

Ramu stunt virus genome reveals previously unreported segments and nucleocapsid domain duplication in Mechlorovirus.

Ramu stunt virus (RmSV), a member of the genus Mechlorovirus within the family Phenuiviridae, was previously described as a six-segmented RNA virus infecting sugarcane. In this study, we re-examined type material and additional isolates using high-throughput sequencing and RT-PCR validation, revealing that RmSV possesses a nine-segmented genome, making it the largest reported in the Phenuiviridae. This expanded architecture includes duplicated RNA segments (RNA 2a and RNA 2b) encoding nucleocapsid-like proteins and two novel segments (RNA 7 and RNA 8). Comparative analysis showed that RNA 2a and 2b share about 84% amino acid identity, while RNA 5 encodes a third nucleocapsid homolog, indicating unprecedented domain redundancy. Structural modeling confirmed that all three nucleocapsid proteins maintain a conserved fold despite low sequence identity, with electrostatic mapping suggesting differential RNA-binding potential. Additionally, RNA 6 encodes a hypothetical protein structurally similar to the rice stripe virus disease-specific S-protein, implicating a role in symptom development. Transcript abundance analysis revealed RNA 6 as the most highly expressed segment across isolates. These findings revise the genomic composition of RmSV, highlight mechanisms of genome plasticity and adaptive evolution in plant-infecting bunyaviruses, and underscore practical implications for diagnostic assay design, resistance breeding, and biosecurity surveillance.

Genome, Viral↗

PubMed2026

The Thyroid-Brain Network: Exploring Inflammation, Immune Mechanisms and Common Triggers in Thyroid-Related Neurological Dysfunction.

Autoimmune thyroid diseases (AITD), including Hashimoto's thyroiditis and Graves' disease, represent the most prevalent endocrine disorders worldwide, affecting hundreds of millions with profound but often under recognized neurological consequences. There are emerging lines of evidence establishing inflammation and immunity as the critical missing link connecting peripheral thyroid dysfunction to central nervous system manifestations. Thyroid hormones function as essential neuromodulators governing neurodevelopment, synaptic plasticity, and cognitive processing through integrated genomic and non-genomic mechanisms, with region-specific cerebral metabolic disturbances correlating with distinct neuropsychiatric symptoms. The immunological perspective reveals that AITD propagates neuroinflammation through convergent pathways: molecular mimicry enabling cross-reactivity between thyroid and neural antigens, cytokine-mediated disruption of neurotransmitter metabolism, HMGB1-driven glial activation, and blood-brain barrier compromise facilitating immune cell infiltration. The thyroid-gut-microbiota axis emerges as a critical mediator wherein dysbiosis perpetuates both thyroid autoimmunity and neuroinflammation through impaired serotonin precursor availability and increased intestinal permeability. Mitochondrial dysfunction represents an energetic common denominator, as thyroid hormone dysregulation directly impairs oxidative phosphorylation, producing region-specific cerebral metabolic disturbances. Simultaneous compromise of monoamine systems, cholinergic signaling abnormalities, and glutamate excitotoxicity creates a particularly toxic neurochemical state in untreated thyroid dysfunction. Common triggers such as psychological stress, gut dysbiosis, and mitochondrial impairment may activate interconnected pathways that simultaneously compromise thyroid and brain function, revealing that these disorders share fundamental mechanistic origins. These insights have been discussed in the current review to enhance the understanding of thyroid-brain function, the core mechanisms and consequences of functional deficits.

Journal Article↗

PubMed2026

Genome-wide scans reveal candidate genes associated with wing morph differentiation in Tetrix japonica.

Wing dimorphism is an important dispersal-related trait in insects, but its genomic basis remains poorly understood in pygmy grasshoppers. Here, we integrated genome-wide single-nucleotide polymorphism (SNP) analyses, population structure inference, selection scans, and functional annotation to investigate genomic differentiation between long- and short-winged Tetrix japonica. Principal component analysis (PCA), ADMIXTURE, and phylogenetic analyses revealed weak genome-wide separation between morphs, indicating differentiation on a largely shared genetic background. Genome-wide scans based on the fixation index (FST), nucleotide diversity ratios, and Tajima's D, using 50-kb non-overlapping windows and empirical top-5% outlier thresholds, identified multiple candidate regions across seven chromosomes. The broader long- and short-winged candidate sets spanned 9.35 Mb and 9.37 Mb and directly overlapped 82 and 77 genes, respectively. Candidate genes were associated with signaling/hormone regulation, membrane transport, metabolism, cytoskeletal organization, extracellular matrix structure, and development. Short-winged candidate genes were significantly enriched for ABC-type transporter activity and ATP hydrolysis activity. Because all individuals originated from a single laboratory-maintained population with weak genome-wide structure, these regions should be regarded as candidate loci from a screening-stage analysis that require validation in independent populations and by functional assays, rather than as confirmed targets of selection.

Animals↗

PubMed2026

Fructophilic lactic acid bacteria as a window into multi-scale convergent evolution.

Fructophilic lactic acid bacteria (FLAB) are a group of lactic acid bacteria with unique growth characteristics, that is, poor growth on glucose. Their growth is enhanced in the presence of fructose or external electron acceptors. These organisms inhabit fructose-rich environments such as flowers, fruits, and pollinating insects, particularly honey bees. Apilactobacillus spp. and Fructobacillus spp. are representatives of FLAB, although they belong to phylogenetically distant clades. These organisms commonly possess markedly small genomes with a low number of coding DNA sequences. Furthermore, their genomes are characterized by a markedly reduced number of genes involved in carbohydrate transport and metabolism. Genome reduction in FLAB reflects convergent adaptation to fructose-rich environments rather than general genome streamlining. The two distinct FLAB genera, Fructobacillus and Apilactobacillus, independently lost more than 100 genes in statistically similar orders. In contrast, genes involved in carbohydrate and amino acid metabolism exhibited reversed orders of loss between the two genera. Furthermore, FLAB genomes lack an intact bifunctional alcohol/aldehyde dehydrogenase gene (adhE), which causes their poor growth on glucose. A comparative genomic study suggested the evolutionary process underlying adhE gene decay during adaptation to the fructose-rich environments, including pollinating insects. In conclusion, FLAB represent a unique example of habitat-driven convergent reductive evolution that can be investigated across multiple biological scales - from individual genes to whole genomes - in the diverse LAB group with a wide range of habitats, and partially share the fructophilic evolution with eukaryotic yeasts found in fructose-rich habitats.

Fructose↗

PubMed2026

Maternal age as a driver of genome instability: mechanisms linking aneuploidy, mutagenesis and mitochondrial dysfunction.

Advanced maternal age is a well-established risk factor for adverse reproductive outcomes due to increased rates of aneuploidy. However, emerging evidence indicates that the genetic consequences of maternal aging extend well beyond chromosome mis-segregation. Aging oocytes acquire a broad spectrum of genetic abnormalities, including maternally derived nuclear de novo mutations (DNMs) and mitochondrial DNA mutations, together with epigenetic dysregulation of DNA methylation and post-translational modification levels. These changes reflect the unique biology of the female germline in which oocytes remain arrested in meiotic prophase I for decades. Age-related deterioration of key processes, such as erosion of cohesion complexes, altered meiotic recombination, and weakened spindle assembly checkpoint surveillance collectively destabilize meiotic chromosome architecture, directly driving chromosome mis-segregation. At the same time, accumulation of endogenous DNA damage and declining DNA damage and repair processes increase the chances of transmitting lesions that can be converted into sequence-level mutations during the earliest embryonic divisions, when genome maintenance relies exclusively on maternal factors. High-resolution sequencing studies further demonstrate that maternal aging is associated with increased DNMs burden in both nuclear and mitochondrial DNA. Together, these findings support a model in which maternal aging is a driver of genome-wide instability that links aneuploidy and mutagenesis through shared defects in meiotic surveillance, declining DNA repair efficiency, and mitochondrial function. This framework positions delayed childbearing as a multifaceted genetic risk factor that extend beyond aneuploidy to include mutations and other genomic alterations that can impact intergenerational genetic risk.

Aneuploidy↗

PubMed2026

A systematic literature review of cultural concepts taught by pharmacist preceptors during pharmacy student experiential placements.

BACKGROUND: Cultural concepts such as cultural intelligence, awareness, competency and safety are essential in guiding culturally responsive care in health professional practice. Pharmacist preceptors play a pivotal role in sharing both clinical and cultural safe practice with pharmacy students. Culturally responsive care can contribute to achieving health equity, which is especially important for Indigenous communities. AIM: To review literature on cultural concepts in pharmacist preceptorship practices, and how these concepts are taught and communicated to pharmacy students during experiential learning. METHOD: The systematic review followed the PRISMA 2020 guideline. Scopus, PubMed, and Google Scholar were used to identify articles specific to pharmacist preceptors and pharmacy students published between 2015 and 2025, and available in English. RESULTS: Three full-text articles met the inclusion criteria. Major themes and subthemes were identified; pharmacist preceptors lacked preparedness to teach cultural concepts, resulting in variability in preceptors' understanding of cultural concepts and confidence in fulfilling preceptor responsibilities, underutilised structured frameworks to guide students' learning, challenges with preceptorship due to limited resources and support, and the influence of preceptorship on student learning, which impacted students' learning and competency. CONCLUSION: Pharmacy students had minimal exposure to culturally informed pharmacist preceptorship. It is likely that pharmacist preceptors require country-specific educational resources to support culturally safe preceptorship. Future research is required to substantiate these findings, and to guide culturally responsive practice and promote equitable health outcomes in diverse populations.

Humans↗

PubMed2026

Pcgf5 controls the exit from totipotency in mouse embryonic stem cells.

Mouse embryonic stem cell (ESC) cultures contain a rare subpopulation of two-cell-like cells (2CLCs) that transiently reactivate a two-cell embryo-like transcriptional program characteristic of zygotic genome activation (ZGA), including the endogenous retrovirus MERVL and Zscan4, and thereby regain a totipotent-like state. Polycomb repressive complex 1 (PRC1)-mediated H2AK119ub1 has been implicated in restraining entry into the 2C-like state through Pcgf6, yet the factors governing exit from this state and loss of totipotency remain poorly defined. Here, we show that among the six Pcgf paralogs, Pcgf5, which is most prominently upregulated in 2CLCs and forms an MERVL-driven chimeric transcript (Pcgf5MT2C_Mm) during ZGA in 2-cell embryos, controls exit from the 2C-like state in mouse ESCs. Using a reporter ESC line carrying MERVL-tdTomato and Zscan4c-EGFP (MtZG), we manipulated Pcgf5 dosage bidirectionally. Doxycycline (Dox)-inducible overexpression (OE) of Pcgf5 reduced the double-positive (DP) 2C-like population. Conversely, CRISPR-mediated knockout (KO) of Pcgf5 by targeting a common exon shared by all Pcgf5 variants (hereafter, total Pcgf5) increased the DP population. Time-lapse imaging directly confirmed that these changes reflected genuine differences in duration of the 2C-like state: OE shortened, whereas KO prolonged, the time cells spent in this state. These findings reveal that a Polycomb group factor controls not only entry into but also exit from the 2C-like state.

Animals↗

PubMed2026

Age- and sex-adjusted genomic differences between Korean and Beat AML cohorts.

Genomic profiling plays a central role in risk stratification and therapeutic decision-making in acute myeloid leukemia (AML), yet the clinical implications of population-specific genomic architectures remain incompletely defined. We conducted a prospective, multicenter study of 603 adults with newly diagnosed AML in Korea, integrating targeted sequencing of 83 recurrently mutated genes with comprehensive clinical annotation across treatment intensities, including allogeneic hematopoietic stem cell transplantation (allo-HSCT). For contextual comparison, genomic profiles were evaluated against the Beat AML cohort. The overall genomic landscape was broadly conserved, supporting shared core disease biology across populations. However, RUNX1::RUNX1T1, CEBPA, GATA2, KIT, and DDX41 mutations were more frequent in the Korean cohort, whereas FLT3 and NPM1 mutations were less common. These differences translated into a distinct distribution of European LeukemiaNet (ELN) 2022 risk categories, with implications for therapeutic stratification. Notably, most DDX41 alterations were germline (3.2%), highlighting the need for systematic germline evaluation with implications for genetic counseling and donor selection. Although unadjusted overall survival appeared longer in the Korean cohort, this difference was not significant after adjustment for key clinical variables. These findings indicate that population-specific genomic distributions reshape the clinical application of risk stratification and support population-aware precision medicine strategies in AML.

Journal Article↗

PubMed2026

Assessment of Genetic Correlations Between Tobacco or Alcohol Use and Neurodegenerative Diseases Using East Asian Genetic Ancestry Genome-Wide Association Study Results.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most prevalent late-onset neurodegenerative diseases worldwide. Both are influenced in part by genetic factors and are currently incurable. Tobacco and alcohol, the two most common substances used among the general adult population, are potential AD/PD risk factors and are also heritable. Although important progress has been made, most existing research on the genetics of AD and PD has been carried out in individuals of European genetic ancestry. Investigations in a broad range of groups are crucial to understand disease mechanisms. Given the current availability of ancestry-specific tobacco and alcohol use as well as AD and PD genome-wide association study summary statistics, we performed global and local genetic correlation analyses using East Asian datasets. Genes within the correlated genetic regions were subsequently used to identify potentially enriched biological pathways between substance use and neurodegenerative diseases. We identified a global genetic correlation between smoking cessation and PD, which we confirmed in complementary European genetic ancestry data. Gene set enrichment analyses highlighted potentially shared genetic mechanisms between breast cancer and AD, which warrants further exploration. This work aims to promote further analyses across genetic ancestry groups.

Female↗

PubMed2026

Divergent trajectories of genome architecture and chromosome evolution in ferns and angiosperms.

Ferns and angiosperms represent the two largest vascular plant lineages but exhibit striking genomic and ecological contrasts. We investigated whether differences in genome size, chromosome architecture, GC content, and stomatal traits reveal divergent evolutionary trajectories between these lineages. We assembled the most comprehensive dataset to date, integrating genome size, chromosome number and size, GC content, and stomatal traits for over 1100 fern species and compared it with an extensive angiosperm dataset. Ferns exhibited markedly lower variability and c. 16-fold slower rates of chromosome size evolution than angiosperms. A persistent positive relationship between genome size and chromosome number in ferns suggests limited cytological post-polyploid diploidization. While ferns generally possess larger stomata, this difference disappears after accounting for genome size, indicating that nucleotypic constraints, rather than lineage-specific physiology, dictate stomatal dimensions. Both groups share a unimodal GC-genome size relationship peaking at c. 14 Gbp. Larger fern chromosomes imply lower genome-wide recombination rates, potentially limiting genetic reshuffling and adaptive potential. Our results highlight fundamentally divergent evolutionary trajectories, likely shaped by meiotic symmetry in ferns and meiotic asymmetry, possibly centromere drive, and post-polyploid diploidization in angiosperms, defining the functional and genomic landscapes of these lineages across deep evolutionary timescales.

Genome, Plant↗

PubMed2026

A multi-model genome-wide association study identifies genetic variants underlying resistance to Largemouth Bass Ranavirus (LMBV) in Micropterus salmoides.

Largemouth bass (Micropterus salmoides) is an economically important freshwater aquaculture species, yet recurrent outbreaks of Largemouth Bass Ranavirus (LMBV) continue to impair production and cause substantial losses. The genetic basis of host variation in LMBV resistance remains insufficiently characterized. Here, we applied a multi-model genome-wide association study (GWAS) to identify loci associated with resistance following a controlled challenge with the LMBV-23PY strain. Whole-genome resequencing was performed for 146 phenotyped fish, including 72 susceptible and 74 resistant individuals. After stringent quality control, 877,262 high-quality variants were retained and tested using six GWAS models. Across binary survival status and survival time phenotypes, 32 shared suggestive variants were consistently detected across models, representing suggestive loci for LMBV-23PY resistance. Genes within ±50 kb of these loci were annotated, and functional enrichment highlighted immune- and redox-related biological processes. Three prioritized candidates-GSTT3L (glutathione S-transferase theta-3-like), CGRP2 (calcitonin gene-related peptide 2), and NPPC (natriuretic peptide C)-were associated with pathways involved in oxidative stress responses and immune regulation. Collectively, these results provide insight into the genetic architecture of LMBV-23PY resistance in largemouth bass and identify suggestive variants and associated candidate genes for downstream validation, functional interrogation, and the development of marker-assisted and genome-enabled breeding strategies.

Animals↗

PubMed2026

Feasibility, Satisfaction, and Preliminary Efficacy Trial of text4FATHER for Engaging Expectant Fathers in Infant Care from Pregnancy to Early Infancy.

Engaging fathers perinatally improves infant outcomes and parent well-being, yet few strategies share evidence with fathers. We explored the feasibility, acceptability, and preliminary efficacy of text4FATHER-a texting intervention designed to improve fathers' infant care beliefs, self-efficacy, behaviors, and partner support from mid-pregnancy to 2 months post-birth. In this exploratory pilot randomized controlled trial, 97 adult expectant fathers with less than a college degree were randomized to receive text4FATHER or not. Self-reported outcomes by fathers and mothers were assessed at baseline (mid-pregnancy) and 2 months post-birth. We analyzed intent-to-treat effects using random coefficient regression models. We found recruiting expectant fathers feasible; of eligible father-mother dyads, 123/163 consented (recruitment feasibility = 68%). All intervention fathers (100%) reported being satisfied with text4FATHER; 100% of mothers of intervention fathers also reported satisfaction with the father getting texts. First-time fathers' antenatal attachment beliefs and coparenting support were higher in text4FATHER condition vs. control from baseline to 7-month follow-up; increases in first-time fathers' confidence in fathering and infant care were also observed-the latter finding was corroborated by partners of first-time fathers. text4FATHER is a promising intervention, particularly for first-time expectant fathers with lower educational levels who have no natural clinical or public health touchpoints. Its efficacy and effectiveness should be confirmed using larger and more diverse samples.

Confidence↗

PubMed2026

Protein isolation markedly enhances in vitro digestibility, nutritional quality, and bioactivity of fungal mycelial proteins.

Fungal mycelial proteins are promising sustainable protein sources, yet their nutritional utilization is often limited by structural constraints. This study systematically evaluated the effects of protein isolation on the proteomic composition, gastrointestinal digestion behavior, amino acid utilization, and bioactivity of Pleurotus citrinopileatus mycelial proteins. Quantitative proteomics identified 3591 proteins, of which 3374 were shared between mycelial flour (PCMF) and protein isolate (PCMPI), indicating that PCMPI primarily represents the soluble proteome fraction. In vitro digestion revealed that PCMPI exhibited significantly higher digestibility (93.98%) than PCMF (42.98%) (p < 0.05), reaching levels comparable to whey protein isolate. Enhanced enzymatic accessibility in PCMPI promoted rapid peptide generation during the gastric phase and efficient amino acid release during the intestinal phase, resulting in higher peptide (634.76 mg/g) and free amino acid levels (341.69 mg/g) at the digestion endpoint. Consequently, PCMPI achieved a balanced amino acid profile with a PDCAAS of 1.0. Moreover, its digestion products exhibited stronger antioxidant activity (IC₅₀ = 8.36 mg/mL) and ACE inhibitory activity (IC₅₀ = 15.65 mg/mL) compared with PCMF. Mechanistically, protein isolation disrupted the cell wall matrix, shifting digestion from a structure-limited to an accessibility-driven regime. Collectively, these findings demonstrate that protein isolation markedly enhances the digestibility, nutritional quality, and functional potential of mycelial proteins, supporting their application as high-value sustainable protein ingredients.

Digestion↗

PubMed2026

Artificial Intelligence for Diagnosis, Risk Stratification, and Prognosis of Neuroblastoma - A Systematic Review and Meta-Analysis.

PURPOSE: To synthesizes evidence on artificial intelligence (AI) performance in neuroblastoma (NB) diagnosis, risk stratification, prognosis, and genomic characterization. MATERIALS AND METHODS: A systematic review and meta-analysis was conducted following PRISMA 2020 guidelines (PROSPERO: CRD42024539475) across five databases. Meta-analyses used random-effects models with logit-transformed Area Under the Curve (AUCs) and cluster-robust standard errors. AI models were classified as Machine Learning Models (MLM) or Hybrid Nomograms (HN) based on their construction methodology. RESULTS: Of 3,742 articles identified, 53 were included. MLMs demonstrated higher point estimates than radiologists in differential diagnosis (AUC: 0.87 vs. 0.83), though this difference was not statistically significant and carried substantial uncertainty. HNs achieved stronger performance in risk stratification (AUC: 0.87). AI-derived nomograms (AUC: 0.9) and gene signatures (AUC: 0.8) outperformed conventional prognostic markers descriptively. Chemotherapy response prediction remained below clinical utility thresholds across all model types. Only 33.9% of models reported calibration and 24.5% underwent external validation. CONCLUSIONS: AI demonstrates proof-of-concept across multiple NB clinical domains. However, clinical adoption remains premature given persistent gaps in external validation, calibration, dataset size, and pediatric-specific model development. Future studies should test these models prospectively in multicenter pediatric cohorts, ideally through COG or SIOPEN, using shared definitions for diagnosis, risk group, treatment response, and survival outcomes.

Humans↗

PubMed2026

Distinct cell morphotypes of Aureobasidium melanogenum ZN exhibit differential functional profiles in promoting maize growth.

Black yeast-like fungi of the genus Aureobasidium exhibit morphological plasticity, but whether distinct cellular states within the same genetic background are associated with different plant growth-promoting functions remains unclear. Here, yeast-like cells (YL), swollen cells (SC), and chlamydospores (CH) of Aureobasidium melanogenum ZN were characterized. YL was associated mainly with siderophore production and laccase activity, SC with extracellular polysaccharide accumulation, and CH with phosphate mobilization and higher ammonia and IAA production. Whole-genome and comparative genomic analyses revealed a shared repertoire related to nutrient acquisition, auxin-associated metabolism, extracellular oxidation, and carbohydrate remodeling, with expansions in nutrient- and cell-surface-related gene families. Transcriptomic and metabolomic analyses showed distinct deployment of these capacities, with CH exhibiting broad reprogramming of tryptophan-associated, nitrogen, phosphate, central-carbon, and amino-acid metabolism. In maize, CH at the optimal inoculation concentration of 105 CFU·mL-1 produced the strongest growth promotion, increasing plant height, dry biomass, root length, root surface area, and root volume by 58.6%, 365.1%, 191.0%, 194.3%, and 222.4%, respectively. Consistent with this pronounced growth phenotype, maize root transcriptomics showed coordinated CH-induced responses involving root development, nutrient transport, redox regulation, and root-interface remodeling. Root-zone tracking showed greater short-term stability and persistence of CH. These findings identify cellular state as an important functional dimension of Aureobasidium-plant interactions and provide a basis for developing fungal inoculants with defined beneficial cellular states.

Zea mays↗

PubMed2026

Comparative transcriptomic analysis of the gills and hepatopancreas of freshwater-cultured Litopenaeus vannamei under chronic nitrite stress.

To investigate the differences in molecular responses between the gills and hepatopancreas of freshwater-cultured Litopenaeus vannamei under chronic nitrite stress, a 30-day chronic stress experiment was conducted with a control group and a stress group. Transcriptomic analysis of the gills and hepatopancreas was performed using Illumina sequencing; differentially expressed genes (DEGs) were identified, and GO, KEGG, GSEA, PPI, and RT-qPCR validation were carried out. The results showed that 196 DEGs (161 up-regulated and 35 down-regulated) were identified in the gills, and 287 DEGs (199 up-regulated and 88 down-regulated) in the hepatopancreas, with only 18 DEGs shared between the two tissues. DEGs in the gills were enriched in oxidoreductase activity, glycerophospholipid metabolism, and tyrosine metabolism; DEGs in the hepatopancreas were enriched in lipid transporter activity, phagosome, ECM-receptor interaction, and riboflavin metabolism. GSEA revealed significant suppression of the mTOR pathway in the gills and the Polycomb complex pathway in the hepatopancreas. PPI network analysis identified hub genes P5CS and eEF2 in the gills, and PER, TUBB1, SHMT, and TUBB4B in the hepatopancreas. RT-qPCR validation was consistent with the RNA-seq results (R2 = 0.764). This study indicates that, under chronic nitrite stress, the gill response is centered on redox regulation and inhibition of growth metabolism, whereas the hepatopancreas response primarily involves lipid transport, cytoskeletal remodeling, and phagosome activation. The two tissues synergistically adapt through fundamental biosynthetic and motor protein pathways. This research provides molecular evidence for deciphering the nitrite tolerance mechanisms in freshwater-cultured shrimp.

Animals↗

PubMed2026

Clonal haematopoiesis of indeterminate potential and epigenetic age acceleration: Systematic review and meta-analysis.

Clonal haematopoiesis of indeterminate potential (CHIP) represents somatic mutations in haematopoietic stem cells that drive clonal expansion. Epigenetic age acceleration (EAA), estimated from DNA methylation (DNAm) clocks, may capture age-related changes in haematopoiesis. This systematic review and meta-analysis was conducted to synthesise evidence on associations between CHIP and EAA and explore shared biological mechanisms that may underlie this relationship. Six databases were searched from January 1, 2011, to June 6, 2025, adhering to PRISMA 2020. Random-effects meta-analyses were performed. Five studies comprising 7483 individuals (ages 55-79, 67.1% female) assessing associations between CHIP and DNAm clocks were included. Across studies, CHIP individuals had higher EAA than no-CHIP individuals, and larger clones were associated with higher EAA. Meta-analysis of three cross-sectional studies (n = 6946) showed that CHIP had higher EAA versus no-CHIP for Horvath1Age IEAA (mean difference, MD=2.84 years, 95% confidence interval, CI: 1.49-4.19), HannumAge EEAA (MD=2.31 years, 95% CI: 1.14-3.49), PhenoAge (MD=1.84 years, 95% CI: 0.96-2.71), and GrimAge (MD=1.20 years, 95% CI: 0.80-1.61). Both DNMT3A- and TET2-mutated CHIP were associated with higher EAA with TET2-mutated CHIP showing larger effect sizes and more consistent associations than DNMT3A-mutated CHIP across DNAm clocks tested. Higher EAA may also act as an effect modifier for morbidity and mortality in CHIP. Larger longitudinal studies are needed to verify a temporal relationship and determine whether EAA provides incremental prognostic value for morbidity and mortality in CHIP.

Humans↗

PubMed2026

A conserved distal-tail helical extension defines a tailspike attachment architecture in Gram-negative siphophages.

Rapid growth of bacteriophage genome collections has outpaced functional annotation of tail-tip proteins, limiting comparative analysis of host-recognition structures. Starting from a shared distal-tail gene organization in the Salmonella phages 9NA and Jersey, I developed a morphogenetic bioinformatic framework integrating gene synteny, sequence comparison, profile hidden Markov model (HMM) screening, structural evidence, structure-aware searching, and AlphaFold modeling. Comparison with the experimentally characterized lambda and Sf11 tail assemblies identified a predominantly alpha-helical C-terminal extension of the distal-tail (DT) protein associated with tailspike attachment, termed the distal-tail helical extension (DT-helix). Screening 541,986 proteins from 5167 complete NCBI RefSeq tailed-phage genomes, followed by evidence-based evaluation of sequence, genomic context, and structural architecture, identified 165 curated DT-helical-extension-associated phages. Their DT proteins segregated into six sequence groups. In the four principal multi-member groups, cognate tailspikes showed group-specific conservation in proximal N-terminal regions but substantially greater downstream diversity, consistent with sequence constraint at the DT-tailspike attachment boundary. A complementary ProstT5/Foldseek search supported the established groups but revealed no convincing additional highly divergent family. Together with the experimentally characterized Sf11 attachment interface, these findings define a recurrent morphogenetic architecture linking conserved distal-tail scaffolds to more variable receptor-binding proteins across siphophages infecting Gram-negative bacteria. Although universal exchangeability is not established, the identified scaffold-receptor-binding boundaries provide a framework for molecular characterization and rational phage engineering. Accession-level information for the 165 curated phages is available through PhageTailDB.

Viral Tail Proteins↗