Genes最新文献

{"title":"Single-Cell RNA Sequencing of Uterine Tissue from a 70-Day-Old Female Rabbit: Cellular Composition and Fibroblast-Associated Networks.","authors":"Tianyou Du, Kerui Xie, Wenli Zhang, Xun Xie, Xinzhong Fan, Dan Wang, Qin Zhang","doi":"10.3390/genes17091131","DOIUrl":"10.3390/genes17091131","url":null,"abstract":"<p><p><b>Background/Objectives:</b> The cellular composition and molecular features of the rabbit uterus remain incompletely understood. This study aimed to provide an initial single-cell characterization of the cell populations, transcriptional features, and predicted communication networks identified in one rabbit uterine-body specimen. <b>Methods:</b> Single-cell RNA sequencing was performed on uterine-body tissue from one 70-day-old female Kangda V-line rabbit. Following quality control, cells were clustered and annotated using canonical markers. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, descriptive functional module scoring, CellChat, and high-dimensional weighted gene co-expression network analysis were used to characterize cell-associated expression patterns, predicted intercellular communication, and fibroblast co-expression modules. <b>Results:</b> A total of 9251 cells from this single specimen were retained and resolved into 16 preliminary clusters; 15 clusters were assigned to nine major cell types, whereas one small cluster remained unclassified. Fibroblasts were the predominant cell population among the analyzed cells (76.6%), followed by smooth muscle cells (10.9%). Functional analyses highlighted expression programs related to extracellular matrix organization, contractility, vascular function, epithelial barrier maintenance, and immune responses. CellChat analysis using an unadjusted empirical permutation <i>p</i> value < 0.05 predicted prominent COLLAGEN, LAMININ, CD99, MIF, and PTN signaling. Integration with fibroblast co-expression modules identified 21 candidate genes, including <i>COL1A1</i>, <i>COL1A2</i>, <i>COL6A2</i>, <i>LAMC1</i>, <i>PTN</i>, <i>BMP2</i>, and <i>PDGFRA</i>, linking fibroblast-associated expression programs with predicted extracellular-matrix, adhesion, vascular, and developmental relationships. <b>Conclusions:</b> This single-specimen study provides a preliminary cell-level reference for rabbit uterine tissue. The relatively high proportion of fibroblasts and the predicted communication patterns generate testable hypotheses for future studies using independent animals and functional validation.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149059968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-Wide Identification, Evolutionary Characterization, and Salt-Stress Expression Profiling of Antimicrobial Peptide Gene Families in the Xerophytic Recretohalophyte <i>Reaumuria soongarica</i>.","authors":"Youwu Wang, Shuihong Chen, Amjad Hussain, Xiufeng Han","doi":"10.3390/genes17091126","DOIUrl":"10.3390/genes17091126","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Antimicrobial peptides (AMPs) contribute to plant innate immunity and abiotic-stress adaptation, but their repertoires remain poorly characterized in extremophytic plants. We aimed to define AMP gene families and their expression under Na₂SO₄ treatment in the xerophytic recretohalophyte <i>Reaumuria soongarica</i>. <b>Methods:</b> Six canonical AMP families were screened using hidden Markov model and homology searches, domain verification, gene-model and transcript-support assessment, nsLTP boundary curation, phylogenetic and synteny analyses, and reanalysis of public RNA-sequencing data from 0, 200, and 400 mM Na₂SO₄ treatments. <b>Results:</b> We identified 73 candidates: 15 defensins, 18 Snakin/GASA genes and 40 nsLTPs, including seven previously unannotated, transcript-supported models. <i>RsLTP20</i> was reported separately as a reference-dependent C4-like candidate. Four sequence and alignment strategies supported two defensin, one Snakin/GASA and three nsLTP local groups. No tested promoter pattern was significantly enriched after multiple-testing correction. At 400 mM Na₂SO₄ relative to the control, 18 of the 66 catalogue members represented in the quantification reference were differentially expressed (12 upregulated and six downregulated; BH-adjusted <i>p</i> < 0.05 and |log₂ fold change| > 1). Comparison with 38 <i>Tamarix austromongolica</i> candidates identified 27 reciprocal-best-hit pairs; genomic collinearity supported 25 direct candidate pairs. A separate Arabidopsis comparison recovered 26 candidate-anchored pairs. <b>Conclusions:</b> This curated catalogue defines conservative phylogenetic groups and provides candidates for experimental analysis of stress adaptation and peptide function.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Compound-Heterozygous Variants in PYCR1 Expand the Variant Spectrum of Autosomal Recessive Cutis Laxa.","authors":"Xin Wang, Zhuran Zhao, Weike Cheng, Jing Liu, Shimin Zhang, Yanhui Dong, Shuai Xu","doi":"10.3390/genes17091129","DOIUrl":"10.3390/genes17091129","url":null,"abstract":"<p><strong>Background and objectives: </strong>Autosomal recessive cutis laxa (ARCL) is a genetically heterogeneous group of connective-tissue disorders characterized by loose, inelastic skin and variable systemic involvement. Biallelic variants in PYCR1 are associated with PYCR1-related ARCL, including ARCL type IIB (OMIM #612940) and type IIIB (OMIM #614438). We aimed to characterize the clinical and molecular findings in one affected family and provide segregation and variant-specific functional evidence for two previously unreported PYCR1 variants.</p><p><strong>Methods: </strong>The proband and family underwent whole-exome sequencing with copy-number analysis and Sanger confirmation. The splice-site variant was evaluated by qualitative RT-PCR and Sanger sequencing of endogenous peripheral-blood PYCR1 transcripts, whereas the frameshift variant was studied in a heterologous expression system by qPCR and Western blotting. Neuroimaging, exploratory EEG spectral analysis, and public developmental transcriptomic/single-cell resources were used for complementary phenotypic context.</p><p><strong>Results: </strong>The 16-year-old proband had thin lax skin with prominent superficial veins, generalized joint hypermobility, facial dysmorphism, reduced muscle bulk, and motor developmental delay. Chinese WAIS-IV showed a markedly uneven profile (VCI 52; PRI 94; FSIQ 75). Two previously unreported PYCR1 variants were identified in trans: maternally inherited NM_006907.4:c.139-1G>A and paternally inherited NM_006907.4:c.724_725del, p.(Leu242AlafsTer31). Endogenous RNA analysis identified exon 3 skipping associated with c.139-1G>A (r.139_318del), predicting p.(Met48_Lys107del). The c.724_725del construct showed consistently reduced steady-state abundance of the truncated PYCR1 protein relative to WT across three independent experiments. Both variants were classified as likely pathogenic using the ACMG/AMP framework with relevant ClinGen refinements. Brain MRI revealed irregular morphology of the anterior corpus callosum.</p><p><strong>Discussion: </strong>These two previously unreported variants extend the PYCR1 variant spectrum and are supported by complementary segregation, RNA-level, and protein-level evidence. The neurodevelopmental observations provide additional phenotypic context and are interpreted descriptively.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Donor-Type-Dependent Heterogeneity of Ischemia-Reperfusion Injury in Lung Transplantation: A Multi-Cohort Transcriptomic Interaction Analysis of DCD Versus DBD Lungs.","authors":"Zezhao Ji, Yanbin Peng, Lixin Wang","doi":"10.3390/genes17091127","DOIUrl":"10.3390/genes17091127","url":null,"abstract":"<p><strong>Background: </strong>Donation after circulatory death (DCD) and donation after brain death (DBD) donor lungs are widely used in lung transplantation yet managed as equivalent with respect to ischemia-reperfusion injury (IRI), despite fundamentally different ischemic backgrounds: warm ischemia in DCD versus neurogenic-inflammatory priming in DBD donors.</p><p><strong>Methods: </strong>Using GSE18995 (n = 35) as the core discovery interaction cohort for a 2 × 2 factorial limma model (donor type × reperfusion time), we integrated GSEA of metabolic and programmed cell death pathways, CIBERSORTx immune deconvolution, WGCNA, donor-stratified machine learning prediction of primary graft dysfunction (PGD), and CMap drug repurposing, validated externally in two independent cohorts (n = 153) and two PGD outcome sets (n = 55).</p><p><strong>Results: </strong>We identified 623 DCD-specific, 487 DBD-specific, and 1845 shared IRI genes. DCD grafts exhibited suppressed oxidative phosphorylation with compensatory glycolysis, dominant necroptosis and ferroptosis, and robust neutrophil influx, whereas DBD lungs showed mild metabolic disturbance, predominant pyroptosis and apoptosis, and M1 macrophage infiltration. Stratified PGD models (DCD AUC = 0.85; DBD AUC = 0.83) outperformed a universal model (AUC = 0.76).</p><p><strong>Conclusions: </strong>Molecularly distinct IRI signatures support donor-type-aware ex vivo lung perfusion protocols for precision lung transplantation.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wired to Survive: How AML Cytogenetics Shape Apoptotic Dependence and Venetoclax Resistance.","authors":"Arnold Rojas, Sahil Jethi, Tulin Budak-Alpdogan, Manoj K Pandey","doi":"10.3390/genes17091122","DOIUrl":"10.3390/genes17091122","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is cytogenetically and phenotypically heterogeneous, and this diversity contributes to differences in how patients respond to therapies that target apoptosis. Venetoclax, a selective BCL-2 inhibitor, has been demonstrated to improve outcomes when combined with hypomethylating drugs (HMAs) such as azacitidine or decitabine; nonetheless, clinical trials have indicated that resistance and recurrence are prevalent. This review examines the current evidence linking chromosomal abnormalities and cellular differentiation state to mitochondrial apoptotic pathways, with an emphasis on how these factors influence dependence on certain anti-apoptotic BCL-2 family proteins. We summarize how specific cytogenetic subtypes and high-risk groups (including monosomy 7/del(7q) and complex karyotype/TP53-altered AML) frequently show stress-adaptive signaling and reliance on multiple anti-apoptotic pathways, which can limit the durability of response to BCL-2 inhibition. Lineage-associated dependencies are also examined, such as monocytic differentiation (which leads to increased MCL-1 reliance) and erythroid/megakaryocytic differentiation, which has been associated with increased BCL-XL dependence and venetoclax resistance. Finally, we discuss the therapeutic implications of dependence mapping, including venetoclax combinations and direct MCL-1/BCL-XL targeting, and propose promising biomarker strategies that can detect dependence shifts early and guide appropriate treatment selection.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>H. pylori</i> Outer Membrane Protein Antibody Response, MHC/HLA-DMA Methylation, and Gastric Cancer Risk: A Multi-Layer Evidence Integration Study Using Mendelian Randomization.","authors":"Yangxi Fu, Zheng Wang, Shan Liu, Lin Liu, Xudong Tang","doi":"10.3390/genes17091125","DOIUrl":"10.3390/genes17091125","url":null,"abstract":"<p><p><b>Background:</b><i>Helicobacter pylori</i> (<i>H. pylori</i>) infection is a well-established risk factor for gastric cancer; however, evidence on the associations between antigen-specific antibody traits, host methylation, and gastric cancer risk remains limited. <b>Methods:</b> Using a forward two-sample Mendelian randomization (MR) design, we integrated methylation quantitative trait loci (mQTLs), external cohorts, The Cancer Genome Atlas-Stomach Adenocarcinoma (TCGA-STAD), and functional annotations through a three-stage framework (antibody trait screening, CpG prioritization, and external replication) to evaluate a two-step pathway from host antibody response to gastric cancer via DNA methylation. <b>Results:</b> Among six <i>H. pylori</i> antigens, antibody response to outer membrane protein (OMP) showed the strongest positive association with gastric cancer risk (OR = 1.186, 95% CI: 1.079-1.304, raw <i>p</i> = 4.08 × 10^-4). CpG-level prioritization identified cg24290947 (annotated to HLA-DMA) as a methylation site linked to gastric cancer susceptibility, with an inverse MR association (beta = -0.2347, 95% CI: -0.3980 to -0.0713, raw <i>p</i> = 0.00487). External exploration showed that cg24290947 methylation was elevated in <i>H. pylori</i>-positive gastric mucosa; however, its direct tumor-normal difference in a 12-pair cohort was not significant, although regional methylation perturbations were observed. HLA-DMA and MHC-II expression were consistently higher in tumor versus normal tissues across three cohorts, whereas TCGA-STAD did not support a stable linear relationship between cg24290947 methylation and HLA-DMA/MHC-II expression; three of six composition-adjusted models showed nominal significance but were model-dependent. These signals were enriched in antigen processing and presentation pathways. <b>Conclusions:</b> cg24290947/HLA-DMA represents a hypothesis-generating regional methylation candidate for further investigation rather than a confirmed linear transcriptional regulator. The MR evidence is based on European-ancestry summary data; its generalizability and any clinical predictive value warrant independent evaluation.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-Wide Identification and Characterization of the CBL Gene Family in <i>Ziziphus jujuba</i> var. <i>spinosa</i>.","authors":"Yilong Lu, Yong Fan, Kun Liu, Jian Wen, Jialin Sun, Wensong Sun","doi":"10.3390/genes17091121","DOIUrl":"10.3390/genes17091121","url":null,"abstract":"<p><strong>Background: </strong>Calcineurin B-like (CBL) protein-mediated calcium signaling represents a core regulatory pathway underlying plant abiotic stress adaptation. <i>Ziziphus jujuba</i> var. <i>spinosa</i> (sour jujube) is a perennial woody species with remarkable saline-alkali and drought tolerance, yet the <i>CBL</i> gene family in this species has not been systematically characterized.</p><p><strong>Methods: </strong>We performed genome-wide identification and characterization of the <i>CBL</i> gene family in sour jujube through integrated bioinformatic analyses, transcriptomic profiling, qRT-PCR, and yeast two-hybrid (Y2H) assays, with the annotation of one gene manually corrected based on molecular cloning and transcriptome validation.</p><p><strong>Results: </strong>Ten non-redundant <i>ZjCBL</i> genes were identified and grouped into three phylogenetic clades. Synteny and selection pressure analyses identified two collinear gene pairs that have undergone strong purifying selection. All ZjCBL proteins contain canonical EF-hand motifs and are predicted to be mainly localized to the plasma membrane, with ZjCBL4 and ZjCBL9 harboring additional N-terminal transmembrane helices. The promoter regions of <i>ZjCBL</i> genes are enriched in hormone- and stress-responsive cis-acting elements. <i>ZjCBL1</i>, <i>ZjCBL2</i>, <i>ZjCBL3</i>, and <i>ZjCBL5</i> were highly expressed across multiple tissues, and <i>ZjCBL1</i> exhibited sustained upregulation under long-term saline-alkali stress, concurrent with the accumulation of osmoprotectants. Y2H assays confirmed that ZjCBL1 interacts with two ZjCIPK proteins, exhibiting a stronger interaction signal with ZjCIPK13.</p><p><strong>Conclusions: </strong>This study provides the first systematic characterization of the <i>CBL</i> gene family in sour jujube and revises the annotation of <i>ZjCBL1</i>, establishing <i>ZjCBL1</i> as an important component of the ZjCBL-ZjCIPK signaling network and offering candidate gene resources for molecular breeding to enhance stress tolerance in fruit crops.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rare Cancer-Associated Mutations May Affect the AF1 Phosphoregulatory Domain of RARγ.","authors":"Eliezer Kopf","doi":"10.3390/genes17091119","DOIUrl":"10.3390/genes17091119","url":null,"abstract":"<p><strong>Background/objectives: </strong>Retinoic acid receptor γ (RARγ), encoded by RARG, is increasingly recognized as a cancer-associated regulator through aberrant expression in multiple solid tumors and recurrent gene rearrangements in acute myeloid leukemia. While the oncogenic relevance of RARγ is well established, the potential involvement of its N-terminal activation function-1 (AF1) domain in human cancer remains poorly characterized. Previous biochemical studies demonstrated that phosphorylation of Ser66 and Ser68 in RARγ2, corresponding to Ser77 and Ser79 in canonical RARγ1, is required for ligand-dependent receptor activation, ubiquitination, and proteasome-mediated degradation.</p><p><strong>Methods: </strong>To determine whether this experimentally validated phosphoregulatory region is altered in human cancer, we interrogated the Catalogue of Somatic Mutations in Cancer (COSMIC v104, GRCh38) at single-residue resolution. Mutation data were integrated with clinical and pathological information obtained from the corresponding primary publications and public annotation resources.</p><p><strong>Results: </strong>Rare somatic mutations affecting the AF1 phosphoregulatory region were identified, including the missense variants p.S77L and p.S79L, the nonsense variant p.S79*, and the in-frame insertion p.S77_P78insLQ. These alterations occurred in independent epithelial malignancies, including cervical neuroendocrine carcinoma, head and neck squamous cell carcinoma, lung adenocarcinoma, bladder carcinoma, and gastric neuroendocrine carcinoma. Notably, the truncating p.S79* mutation was detected in five spatially distinct regions of a single EGFR-mutant lung adenocarcinoma, consistent with an early clonal event during tumor evolution. Rare cancer-associated mutations affect a previously characterized AF1 phosphoregulatory module of RARγ. These findings extend established RARγ regulatory biology into the context of human malignancy and broaden the spectrum of reported cancer-associated RARG alterations. While the functional consequences of these rare variants remain unknown, their occurrence within residues known to regulate receptor activation and turnover highlights the AF1 phosphoregulatory region as a candidate for future mechanistic investigation.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect-Allele Frequencies at Cardiometabolic Risk Loci in an Uzbek Cohort from Tashkent: A Central Asian Reference and Priorities for Polygenic Score Validation.","authors":"Alisher A Abdullaev, Darya V Zakirova, Sergei A Kosushkin, Fazliddin Z Xonboev, Guzal J Abdullaeva, Rano B Alieva, Shahlo U Turdikulova","doi":"10.3390/genes17091117","DOIUrl":"10.3390/genes17091117","url":null,"abstract":"<p><strong>Background/objectives: </strong>Central Asian populations are almost entirely absent from genomic reference resources, yet Uzbekistan has one of the fastest rates of growth in age-standardised type 2 diabetes (T2D) incidence. Allele frequencies at cardiometabolic risk loci are unknown, limiting the interpretation of polygenic risk scores (PRS) derived elsewhere. We aimed to characterise effect-allele frequencies in an Uzbek cohort from Tashkent and quantify divergence from 1000 Genomes panels to guide future PRS evaluation.</p><p><strong>Methods: </strong>We genotyped 171 adults from Tashkent (131 with T2D, 40 without) on a custom Agilent SureSelect panel of cardiometabolic candidate SNPs. After quality control, 1939 variants were analysed. Effect-allele frequencies were compared with 1000 Genomes Phase 3 superpopulations (EUR, SAS, EAS, AFR) using Hudson FST and Nei's genetic distance with bootstrap 95% CIs (1000 replicates). Case-control association was assessed descriptively using both unadjusted and age- and sex-adjusted additive logistic regression, with the adjusted model as primary.</p><p><strong>Results: </strong>Reference frequencies were available for 1533 of 1939 variants (1363 at MAF ≥ 0.05). Frequencies clustered with South Asian (FST = 0.077, 95% CI 0.065-0.089) and European panels (FST = 0.086, 95% CI 0.072-0.099), which were indistinguishable (ΔFST = -0.010, 95% CI -0.022 to 0.003) and more divergent from East Asian and African panels. Divergence from the European and South Asian panels was unrelated to nominal association status (Mann-Whitney <i>p</i> = 0.99 and 0.57). In the primary age- and sex-adjusted analysis, no variant survived multiple-testing correction (minimum Bonferroni-adjusted and false-discovery-rate q = 0.28), consistent with the unadjusted sensitivity analysis.</p><p><strong>Conclusions: </strong>This study provides the first systematic allele-frequency reference for cardiometabolic risk loci in an Uzbek cohort from Tashkent. The profile is closest to South Asian and European panels and identifies PRS from these ancestries as priority candidates for future local validation in Central Asian settings. The case-control analysis was underpowered and is reported descriptively.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Architects of Aggression: The Molecular Blueprint of Glioma Progression.","authors":"David Aebisher, Jakub Tylutki, Angelika Myśliwiec, Nazarii Kozak, Dorota Bartusik-Aebisher","doi":"10.3390/genes17091120","DOIUrl":"10.3390/genes17091120","url":null,"abstract":"<p><p>Despite decades of clinical validation, glioblastoma (GBM) treatment remains tethered to a dismal 15-to-16-month survival plateau, heavily thwarted by the ys blood-brain barrier (BBB) and profound cellular heterogeneity. While the 2021 World Health Organization Classification of Tumors of the Central Nervous System (WHO CNS5) fundamentally reoriented diagnosis around definitive molecular signatures, such as isocitrate dehydrogenase (IDH)-wildtype status, epidermal growth factor receptor (EGFR) amplification, and +7/-10 chromosomal alterations, the ultimate obstacle to clinical efficacy is the tumor's intense non-genetic plasticity. Malignant cells reject rigid hierarchies; single-nucleus insights reveal a fluid transcriptomic continuum spanning neurodevelopmental lineages, novel glia-like or neuronal-like states, and highly resilient proneural-mesenchymal (PM) hybrid populations. This intrinsic dynamism is reinforced by functional neuro-gliomal integration into the host brain via electrochemical TM synapses, an immunologically cold niche dominated by secreted phosphoprotein 1 (SPP1+) myeloid cells, and a self-reinforcing hypoxic-angiogenic loop. Under cytotoxic therapy, these networks execute rapid adaptive remodeling, selecting for hypermutator phenotypes and specialized senescence-associated secretory phenotypes (SASP) that dictate aggressive recurrence.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}