Genes基因
Genes(英文缩写 GENES-BASEL),ISSN 2073-4425,eISSN 2073-4425,中文译名:基因 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-09-27 至 2026-09-27，按本站收录文献的发表日期统计。
期刊介绍
Genes 最新收录文献
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1. 4-Phenylbutyrate Plus Wildtype GAT-1 Augmentation: A Dual Therapy to Rescue SLC6A1 Variant-Associated Developmental and Epileptic Encephalopathy.
PMID:日期:2026-08-21Pathogenic variants in SLC6A1, which encodes the γ-aminobutyric acid (GABA) transporter GAT-1, cause developmental and epileptic encephalopathies (DEEs) through reduced GABA uptake, impaired transporter trafficking, and functional haploinsufficiency. 4-phenylbutyrate (PBA) is a clinically available small molecule with chemical-chaperone and histone-deacetylase-inhibitor activities that can rescue misfolded GABAergic proteins, but variant-level rescue data are needed to guide precision treatment. We report a novel de novo missense mutation p.Ala305Val in GAT-1 encoding SLC6A1, in a patient with myoclonic-atonic epilepsy and a developmental and epileptic encephalopathy phenotype. Ala305Val was compared with the residue-matched comparator p.Ala305Thr (Ala305Thr). Variant effects were evaluated by (i) protein-structure prediction across nine stability-prediction algorithms using the cryo-EM-derived human GAT-1 template (PDB 7Y7W); (ii) 3H-GABA uptake assays in HEK293T cells and in human iPSC-derived astrocytes and cortical neurons; (iii) live-cell confocal microscopy of ER colocalization; (iv) pharmacologic rescue with PBA, TUDCA and salubrinal (v) and GAT-1 cDNA gene-augmentation, alone and in combination with PBA. AI-based stability predictors uniformly indicated destabilization of GAT-1 p.Ala305Val and GAT-1 p.Ala305Thr. GAT-1 p.Ala305Val reduced 3H GABA uptake across HEK293Ts, astrocytes, and neurons. The mutant transporter accumulated within the endoplasmic reticulum (ER), with ER colocalization rising from approximately 30% in wildtype to ~80% in GAT-1 p.Ala305Val; PBA reduced ER retention to approximately ~40% and restored total GAT-1 fluorescence toward wildtype levels. Pharmacochaperones (PBA, TUDCA) restored GABA uptake for the mutant transporters. Wildtype GAT-1 gene augmentation improved GABA uptake in the heterozygous condition but combined PBA plus wildtype allele augmentation produced rescue greater than either intervention alone in the available dose-response ranges. GAT-1 p.Ala305Val is a trafficking-impaired, loss-of-function variant whose dysfunction is amenable to two convergent therapeutic axes: pharmacologic correction of folding and trafficking, and augmentation of functional transporter expression. These findings support a two-pronged precision-medicine framework for SLC6A1-related DEEs in which PBA increased the transporter function augmented by genetic approaches.
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2. {"_":"Single-Cell and Bulk Transcriptomics Reveal an Epithelial - Signaling Axis Associated with Severe COVID-19 Susceptibility.","i":["LTF","LRP11"]}
PMID:日期:2026-08-21The molecular mechanisms underlying susceptibility to severe COVID-19 remain incompletely understood. We aimed to identify the signaling pathways associated with disease severity by integrating transcriptomic data and characterizing ligand-receptor interactions involved in the host response to SARS-CoV-2 infection. We integrated publicly available bulk RNA-sequencing data from nasopharyngeal (NP) swabs (GSE152075) and single-cell RNA-sequencing data from bronchoalveolar lavage fluid samples (GSE145926). Analyses focused on secreted ligands and their cognate receptors and were performed in relation to demographic and clinical characteristics associated with susceptibility to severe COVID-19, including sex, age, and viral load. Patients with characteristics associated with increased susceptibility to severe disease, including male sex, advanced age, and high viral load, exhibited transcriptional programs enriched for inflammatory and immune-response pathways. In contrast, individuals with lower susceptibility displayed reduced expression of 43 ligand genes compared with matched negative controls, suggesting distinct secretory programs associated with the host response to infection. We identified an association between the expression of lactoferrin () and its receptor, LDL receptor-related protein 11 (), and susceptibility to severe COVID-19. was predominantly expressed in human pulmonary epithelial cells, and its expression increased during SARS-CoV-2 infection in monkeys. Our findings provide insight into the molecular mechanisms associated with susceptibility to severe COVID-19 through the analysis of ligand and receptor expression in nasopharyngeal swabs and bronchoalveolar lavage fluid samples. The association between and highlights a potentially relevant signaling axis in disease pathogenesis and provides a rationale for future functional studies aimed at clarifying its role in COVID-19 severity.
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3. BMAL1-Mediated Circadian Regulation of Oocyte Quality and IVF Outcomes.
PMID:日期:2026-08-21[中文摘要] 成功的胚胎发育早在受精之前就已在卵巢卵泡精密调控的微环境中展开。越来越多的数据表明，昼夜节律调控系统影响多个决定卵母细胞能力的进程，包括线粒体活性、氧化平衡、减数分裂发育和细胞代谢。脑和肌肉ARNT样蛋白1（BMAL1）作为昼夜节律调控中的关键转录因子，因其在卵巢生理和生殖功能中的重要作用而受到广泛关注。BMAL1信号失调与卵泡发育受损、类固醇生成减少、线粒体功能障碍、氧化应激升高以及减数分裂纺锤体组织异常有关，这些都可能对卵母细胞质量和早期胚胎发育产生负面影响。近期实验和临床研究结果表明，辅助生殖的结果可能受到昼夜节律紊乱、睡眠问题、肥胖、衰老和代谢功能障碍的影响。
[英文摘要] Successful embryo development transpires far before fertilization inside the meticulously regulated microenvironment of the ovarian follicle. Increasing data indicates that circadian regulatory systems influence several processes that define oocyte competence, including mitochondrial activity, oxidative balance, meiotic development, and cellular metabolism. Brain and muscle ARNT-like protein 1 (BMAL1), an essential transcription factor in circadian regulation, has garnered significant interest due to its crucial involvement in ovarian physiology and reproductive function. Dysregulated BMAL1 signaling has been linked to compromised folliculogenesis, diminished steroidogenesis, mitochondrial dysfunction, elevated oxidative stress, and irregularities in meiotic spindle organization, all of which may negatively impact oocyte quality and early embryo development. Recent experimental and clinical findings indicate that results of assisted reproduction may be influenced by circadian disruption, sleep problems, obesity, ageing, and metabolic dysfunction.
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4. Functional Characterization of Patient-Derived Myotubes Carrying ANO5 and ORAI3 Variants in RYR1-Negative Malignant Hyperthermia Susceptibility.
PMID:日期:2026-08-20Malignant hyperthermia (MH) is a life-threatening pharmacogenetic disorder of skeletal muscle primarily associated with pathogenic variants in ; however, a substantial proportion of MH-susceptible individuals lack identifiable variants in known genes. This study aimed to identify novel genetic contributors in Ca-induced Ca release (CICR)-positive patients without variants and to evaluate their functional relevance. Among 29 CICR-positive individuals without pathogenic variants identified by gene panel testing, five patients underwent whole-exome sequencing (WES). In one family, heterozygous variants in (p.Arg547Gln) and (p.Arg287Cys) were identified. To evaluate their functional significance, intracellular Ca dynamics were analyzed in primary myotubes derived from Case 165, an affected individual carrying both variants, and compared with those from CICR-negative controls and CICR-positive patients harboring variants. Myotubes derived from Case 165 demonstrated enhanced sensitivity to caffeine and 4-chloro-m-cresol, elevated resting intracellular Ca levels, and greater Ca reduction under Ca-free conditions compared with CICR-negative controls, resembling the phenotype observed in the RYR1 variant group. In contrast, dantrolene-induced Ca reduction was significantly greater only in the RYR1 variant group. These findings suggest that and variants may contribute to abnormal Ca regulation in MH-susceptible individuals without mutations and highlight the importance of combining genomic analysis with functional validation to identify novel genetic contributors to MH susceptibility.
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5. Dissecting Missing Heritability in Rare Inherited Macular Dystrophies.
PMID:日期:2026-08-20To describe the genetic resolution rate, molecular findings, and genotype-phenotype correlations of non- and non- inherited macular dystrophies (IMDs) within an Irish inherited retinal disease (IRD) registry. Retrospective review of individuals with a clinical diagnosis of macular or cone dystrophy. Comprehensive phenotyping (dilated ocular biomicroscopy, multimodal retinal imaging, visual electrophysiology) and genetic testing (panel-based next-generation sequencing, single-gene testing, whole exome/genome sequencing, WES/WGS). Variants were interpreted using ACMG AMP criteria, and genotype-phenotype match was confirmed through multidisciplinary review. 232 patients with macular/cone dystrophies were identified. and accounted for most molecular diagnoses (47.4%). Removing and , 59.0% of IMDs were genetically unresolved, higher than the rate in general IRD cohorts. Deep phenotyping enabled diagnostic reclassification in 13/72 (18.1%), namely achromatopsia, congenital stationary night blindness, and oculocutaneous albinism. Further genetic testing resolved 35/72 (48.6%) of those unresolved on first-line testing, with being most prevalent (n = 12), followed by , , , and . Characteristic phenotypic signatures-such as -associated retinal thickening and retinoschisis or -associated Stargardt-like changes-supported known genotype-phenotype correlations. Genetic resolution rates for rare IMDs remain lower than pan-retinal IRD phenotypes. Beyond and , IMDs exhibit substantial genetic and phenotypic heterogeneity (24 genotypes in this cohort), with low molecular diagnostic rates despite comprehensive sequencing approaches. Detailed multimodal phenotyping (i.e., structural, functional and extra-ocular) is essential to refine diagnosis, guide genetic testing and interpret candidate variants. Genetic testing is challenging when the retinal phenotype is advanced (i.e., atrophy) or lacks pathognomonic features. Meticulous phenotyping (functional, structural and systemic) and broader genomic strategies (e.g., WES/WGS) may further increase diagnostic yield, though gene panel content is constantly improving. Consistently improving molecular diagnostic rates will ensure equitable access to emerging gene-specific therapies.
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6. {"_":"Genetic Structure of the Perennial Flax Trifecta: , , .","i":["Linum austriacum","L. lewisii","L. perenne"]}
PMID:日期:2026-08-20. Annual flaxseed () is the most cultivated species. Perennial species (, , ) show potential as alternative oilseed and fiber sources. It is critical to determine genetic variation in any collection to understand relationships and utilization within a breeding program. The research objectives were to analyze the genetic structure of the trifecta perennial flax using single-nucleotide polymorphic (SNP) markers for species differentiation and to discover potential Centers of Origin and/or diversity. . We tested 70 USDA-GRIN-global wild populations (19 , 32 , 19 ; N = 850 seedling genotypes) to generate 9804 DArTseqLD SNPs (Group 1). . After filtering, within 1199 SNPs (261 genotypes; Group 2) remained; in , there were 90 unique SNPs (273 genotypes; Group 3); in there were 2716 SNPs (309 genotypes; Group 4). Four genetic clusters were detected using STRUCTURE, consistent with principal coordinate analysis and SplitsTrees. Clear distinctions within and among each perennial species' populations were found, separating into two distinct pure taxon groupings, along with peripheral populations or outliers. Both and potentially had two putative Centers of Origin, although had one. . The occurrence of sympatric species in the wild could explain the occurrence of peripheral population groups within each taxon, although other explanations are also possible. This may be consistent with the potential for genetic exchange between the perennial species and the greater genetic variability available. Future research will evaluate additional to further delineate the genetic structure and variation within the genus .
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7. Integrated Analysis of Multiple Databases Identifies Tissue Inhibitor of Metalloproteinase 1 Expression and Its Association with the Immune Microenvironment in Colorectal Cancer.
PMID:日期:2026-08-20In recent decades, the incidence of colorectal cancer (CRC) has been rising worldwide. CRC ranks second in cancer-related mortality. The identification of reliable biomarkers for early diagnosis and prognosis prediction, along with a deeper understanding of the underlying molecular events, holds substantial promise for improving patient outcomes. The tissue inhibitor of the metalloproteinase 1 () gene is overexpressed in various gastrointestinal malignancies and contributes to tumor progression. However, its role in regulating the CRC tumor immune microenvironment (TIME) and its potential as a clinically actionable prognostic biomarker remain unclear. To probe how acts as a prognosis-related candidate biomarker in colorectal carcinoma, TCGA-derived datasets were adopted to conduct Kaplan-Meier survival assessment. We also investigated the connection between the expression abundance of and the infiltration of immune populations and intratumoral lymphocytes; furthermore, immune checkpoint-related genes were systematically assessed across multiple tumor types via the TISIDB and TIMER2.0 platforms, with particular emphasis on CRC. We adopted the ESTIMATE scoring system to figure out how gene expression correlates with the phenotypic properties of the colorectal-cancer TIME. We relied on the limma toolkit for the screening of differential transcripts from high- and low- cohorts. Enrichment assessments covering Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes entries were then carried out to predict the potential biological pathways associated with . We constructed the protein-protein interaction map for -interacting partners via the STRING repository. To further explore -correlated genes, we performed Venn diagram intersection analysis combined with Spearman's correlation test. Finally, quantitative reverse-transcription PCR was then implemented to detect messenger-RNA abundance inside the RKO colorectal carcinoma cell line as well as normal colonic epithelial CCD-18Co cells, which offered in vitro experimental verification for our bioinformatic outcomes. According to outcome data, transcripts were markedly up-regulated in CRC specimens and cell lines relative to normal samples. Elevated expression served as a poor-prognosis indicator for overall survival (hazard ratio [HR] = 0.43, 95% confidence interval [CI] = 0.29-0.64, < 0.001) and disease-specific survival (HR = 0.39, 95% CI = 0.22-0.68, = 0.001) among colorectal-carcinoma patients. -high and -low groups exhibited notable differences in immune cell infiltration (CD8 T, macrophage, mast, neutrophil, B, monocyte, dendritic, and CD4 T cells). expression was also significantly correlated with tumor-infiltrating lymphocytes, key immune checkpoint genes (e.g., [] and ), and immunomodulatory chemokines (e.g., and ). Twelve -interacting DEGs were selected: , , , and a cluster of nine (////////), all of which showed significant positive correlations with (r = 0.31-0.63, all < 0.001). expression correlates with features of the tumor immune microenvironment and extracellular matrix remodeling in CRC, suggesting that shows potential as a candidate biomarker. However, its potential as a therapeutic target warrants further experimental investigation.
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8. Chronic Urticaria-Associated Syndromes: Is Andersen-Tawil Syndrome One of Them?
8. 慢性荨麻疹相关综合征：Andersen-Tawil综合征是其中之一吗？PMID:日期:2026-08-19The spectrum of syndromes associated with chronic urticaria (CU) is broad, ranging from monogenic autoinflammatory diseases (a single gene defect drives disease through dysregulated innate immunity) to multifactorial and acquired conditions (urticaria arises as part of a broader, polygenic or immune-mediated systemic process). Monogenic autoinflammatory conditions presenting with urticaria include cryopyrin-associated periodic syndromes (CAPS)-encompassing familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease (NOMID/CINCA) and the broader group of familial cold urticarias. Monogenic conditions with well-characterized gain-of-function NLR family pyrin domain containing 3 () variants present with recurrent hives, a cardinal feature associated with recurrent fevers. Multifactorial and acquired autoinflammatory or immune-mediated conditions include Schnitzler syndrome, adult-onset Still's disease, hypereosinophilic syndrome, Gleich syndrome, Wells syndrome, and Sjögren syndrome. Multifactorial conditions, including Schnitzler syndrome and Still's disease, manifest similarly, with CU as an initial sign and a shared pathogenic mechanism of innate immune dysregulation, with interleukin-1β playing a central, pro-inflammatory role as a major pyrogen. Here, we also present a female patient with clinically established Andersen-Tawil syndrome (ATS) who developed recurrent hives on her extremities within minutes after vigorous exercise. To our knowledge, this is the first report of a co-occurrence of CU and ATS. The hives were successfully attenuated by oral intake of effervescent potassium chloride during physical activity. This observation raises the possibility that chronic inducible urticaria may represent a previously unrecognized cutaneous ATS manifestation and suggests a potential pathophysiological link between potassium-channel dysfunction and mast cell activation. Distinguishing whether hives are an isolated symptom or part of a broader syndrome is critically important, as it might be crucial for the patient outcome.
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9. {"_":"H3K27me3 Dynamic Turnover as a Gate Keeper of Defence Gene Expression in .","i":["Arabidopsis"]}
PMID:日期:2026-08-19Histone 3 lysine 27 tri-methylation (H3K27me3) is a chromatin mark typically associated with transcriptional repression. Histone demethylation, and particularly the removal of H3K27me3, has been linked to abiotic stress tolerance in plants. However, less is known about its role in biotic stress responses. We exploited immunity-related transcriptomics data combined with chromatin-state data to identify an association between chromatin modifications and plant immunity in . We also measured the expression and H3K27me3 levels at immune-responsive loci, at and at histone deacetylase mutants. We identified H3K27me3 as a mark correlated with the silencing of defence gene loci. Moreover, we showed that the expression of a subset of flg22-induced genes is repressed by H3K27me3 prior to elicitation, and that expression negatively correlates with the mark upon activation of immunity. Notably, our studies also revealed a role for the H3K27 demethylase REF6 in plant defence. Loss of REF6 allows ectopic H3K27me3 deposition at target genes, revealing that these loci are actively regulated by the demethylase. Our data provide insight into the regulation of plant immune responses through chromatin dynamics.
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10. RNA Modifications Modulate Biomolecular Condensates in Stress and Disease.
PMID:日期:2026-08-19Biomolecular condensates are dynamic membraneless organelles composed of proteins and RNAs that assemble through multivalent interactions and provide cells with powerful means to regulate gene expression in space and time. Different epitranscriptomic marks such as mA, mA, and mC can reshape RNA structure-binding interfaces and multivalency and, in this manner, tuning which transcripts nucleate or partition into specific condensates and influencing their material state. This review summarizes how individual RNA modifications and their associated proteins regulate the formation and function of BMCs such as stress granules, P-bodies, nuclear bodies and disease-linked condensates in cancer and neurodegeneration. It highlights emerging concepts of combinatorial "epitranscriptomic codes" and bidirectional feedback between condensates and RNA-modifying enzymes and discusses the current experimental and technical gaps that still limit our understanding of modification crosstalk and condensate topology.