Genes最新文献

{"title":"Transcriptome Analysis of Deltamethrin Resistance Mechanisms in <i>Aedes aegypti</i> Populations from Metro Manila, Philippines.","authors":"Marc Ralph M Solomon, Ma Anita M Bautista","doi":"10.3390/genes17091093","DOIUrl":"10.3390/genes17091093","url":null,"abstract":"<p><p><b>Background</b>: Arboviral transmission by <i>Aedes aegypti</i> is exacerbated by insecticide resistance, which undermines effective vector control strategies. In the Philippines, deltamethrin resistance in several <i>Ae. aegypti</i> populations has been reported and prompts an investigation into the possible molecular mechanisms involved. <b>Methods</b>: Two <i>Ae. aegypti</i> populations were subjected to susceptibility assays to deltamethrin and were RNA-sequenced for transcriptome analysis. <b>Results</b>: The two (2) <i>Ae. aegypti</i> populations were resistant to deltamethrin and had LC₅₀ values of 1.26 and 2.15 μg/mL at the zeroth generation (G0) that shifted to 2.21 and 2.08 μg/mL at the second generation (G2) after sublethal deltamethrin exposure, although not statistically significant. Relative to a control population unexposed to any insecticide, DGE analysis of the RNA-Seq data revealed significant upregulation of cytochrome P450, glutathione S-transferase, and carboxyl/cholinesterase genes in resistant populations. Moreover, GO and KEGG analyses revealed enrichment of cytochrome P450-related terms and xenobiotic metabolism pathways. <b>Conclusions</b>: RNA-Seq analysis results of selected genes show concordance with their respective gene expression measured via qPCR (R = 0.89; <i>p</i> = 0.00049). This study provides insights into the possible molecular mechanisms of deltamethrin resistance in Philippine <i>Ae. aegypti</i> populations, providing informed decision-making in vector management.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060473","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":"Complete Mitochondrial Genome of the Endemic Loach <i>Leptobotia tchangi</i> and Its Phylogenetic Placement Within Botiidae.","authors":"Yuting Hu, Guoqing Duan, Huaxing Zhou, Amei Liu, Huan Wang","doi":"10.3390/genes17091087","DOIUrl":"10.3390/genes17091087","url":null,"abstract":"<p><strong>Background: </strong><i>Leptobotia tchangi</i> is a loach species endemic to South China, but its mitochondrial genome has not yet been characterized, limiting understanding of its evolutionary relationships and conservation genetics.</p><p><strong>Methods: </strong>Here, we report the first complete mitochondrial genome of <i>L. tchangi</i>, using next-generation sequencing, assembly and bioinformatics analyses.</p><p><strong>Results: </strong>The double-stranded circular mitogenome has 16,590 bp and contains: 13 protein-coding genes (PCGs), 2 ribosomal RNA genes, 22 transfer RNA genes, and a non-coding control region (D-loop) containing conserved ETAS and CSB motifs. The overall base composition is 25.0% thymine (T), 27.9% cytosine (C), 31.1% adenine (A), and 16.0% guanine (G), showing a clear A + T bias (56.1%) which is consistent with other Botiidae mitogenomes. To infer the phylogenetic placement of <i>L. tchangi</i> within Botiidae, we conducted both Bayesian inference and maximum-likelihood phylogenetic analyses based on the concatenated PCG sequences. Our results strongly support (1) the monophyly of the subfamilies Leptobotiinae and Botiinae, as well as the monophyly of each genus within the family Botiidae; (2) three sister-group relationships within Botiinae: (<i>Botia</i> + <i>Chromobotia</i>), (<i>Ambastaia</i> + <i>Sinibotia</i>), and (<i>Syncrossus</i> + <i>Yasuhikotakia</i>), with the latter two species groups also being sister groups; (3) <i>L. tchangi</i> being most closely related to <i>Leptobotia taeniops</i>.</p><p><strong>Conclusions: </strong>These findings not only provide essential molecular markers for the species identification and conservation genetics of <i>L. tchangi</i>, but also clarify the taxonomic status of <i>L. tchangi</i> within Botiidae.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060323","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":"Serum Urate and Renal Dysfunction: Bidirectional Genetic Associations, External Validation, and Exploratory Multi-Omics Characterization of Antithrombin (SERPINC1) in Hyperuricemic Nephropathy.","authors":"Lei Jin, Feng Wang","doi":"10.3390/genes17091084","DOIUrl":"10.3390/genes17091084","url":null,"abstract":"<p><p><b>Background:</b> Hyperuricemic nephropathy (UAN) involves a systemic thromboinflammatory axis, yet the role of antithrombin (AT, SERPINC1) remains incompletely defined. While AT has anticoagulant and anti-inflammatory properties, whether it contributes to UAN as a disease-responsive molecular node remains uncertain. <b>Methods:</b> We integrated two-sample MR of serum urate and renal traits with complementary sensitivity analyses, cis-eQTL and pQTL analyses of SERPINC1, and exploratory transcriptomic, proteomic, metabolomic, and coexpression analyses. The available data were used to assess genetic associations and to distinguish genetic evidence from cross-dataset molecular patterns. <b>Results:</b> Genetically predicted serum urate showed positive or negative associations with BUN and eGFR, respectively, but the primary analyses showed substantial heterogeneity. Reverse-direction estimates were also associated with serum urate, representing reciprocal genetic relationships between related renal traits and urate rather than proof of a temporal feedback cycle. Available data did not demonstrate mediation through genetically predicted whole-blood SERPINC1 expression. Three deCODE cis-pQTL instruments gave inconsistent renal estimates: nominally lower BUN (β = -0.0290, <i>p</i> = 0.047), null eGFR (β = -0.0036, <i>p</i> = 0.472), and higher CKD risk (β = +0.3361, <i>p</i> = 0.020) with directional pleiotropy evidence. Exploratory multi-omics analyses showed higher PBMC SERPINC1 expression during acute gout and a nominal urinary proteomic difference that did not survive multiple-testing correction (FDR = 0.998). <b>Conclusions:</b> SERPINC1 is best interpreted as a responsive molecular feature requiring further validation, rather than as a demonstrated genetic mediator or renal-protective therapeutic target. The transcriptomic and urinary findings represent cross-dataset, stage-associated observations and should not be interpreted as proven sequential phases.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060460","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":"Allelic Variants of the <i>DPYD</i> Gene in Russian Patients with Cancer: The Results of Exome Sequencing.","authors":"Denis Fedorinov, Vladimir Lyadov, Marina Lyadova, Sherzod Abdullaev, Ivan Sychev, Anna Filatova, Lavrentii Danilov, Oleg Glotov, Iuliia Budagova, Karin Mirzaev, Dmitry Sychev","doi":"10.3390/genes17091082","DOIUrl":"10.3390/genes17091082","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Background/Objectives&lt;/b&gt;: Pharmacogenetic testing of the dihydropyrimidine dehydrogenase gene (&lt;i&gt;DPYD&lt;/i&gt;) is increasingly incorporated into clinical practice to identify patients at increased risk of fluoropyrimidine-related toxicity. However, most routine assays target a limited number of well-established variants, whereas the &lt;i&gt;DPYD&lt;/i&gt; gene demonstrates substantial population variability and may harbor rare potentially functional alleles that are not detected by conventional targeted testing. Data describing coding and splice-region &lt;i&gt;DPYD&lt;/i&gt; variants detectable by whole-exome sequencing in Russian oncology populations remain limited. This study aimed to characterize the frequency and distribution of common, clinically relevant, and rare &lt;i&gt;DPYD&lt;/i&gt; variants in a Russian cohort of patients receiving fluoropyrimidine-containing chemotherapy and to compare the observed allele frequencies with European and East Asian reference populations. &lt;b&gt;Methods&lt;/b&gt;: Descriptive pharmacogenetic analysis was performed in 339 patients with malignant tumors treated with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT), folinic acid, fluorouracil, and oxaliplatin (FOLFOX), or folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) regimens. Whole-exome sequencing was performed using Illumina technology with exome enrichment by KAPA HyperExome and a sequencing depth of at least 100×. Sequence reads were aligned to the Genome Reference Consortium Human Build 38 (GRCh38) reference genome, germline variants were called using Genome Analysis Toolkit (GATK), HaplotypeCaller, and functional annotation was performed with Ensembl Variant Effect Predictor. &lt;i&gt;DPYD&lt;/i&gt; variants were classified according to their population frequency, predicted functional effect, ClinVar annotations, and current pharmacogenetic recommendations. Allele and genotype frequencies were calculated and descriptively compared with Genome Aggregation Database (gnomAD) v4.1.1 Non-Finnish European and East Asian populations. &lt;b&gt;Results&lt;/b&gt;: Seventeen &lt;i&gt;DPYD&lt;/i&gt; variants were identified. The most frequent alternative alleles were rs1801265 (24.93%), rs1801159 (17.70%), rs2297595 (11.06%), rs1801160 (7.08%), and rs17376848 (5.16%). Their distribution was generally closer to that observed in the Non-Finnish European population than in East Asian populations. The established reduced-function variant rs67376798 (c.2846A&gt;T, p.Asp949Val) was detected in one heterozygous patient, corresponding to a carrier frequency of 0.29% and an allele frequency of 0.15%. The HapB3 proxy variant rs56038477 (c.1236G&gt;A) was identified in 13 heterozygous patients, with a carrier frequency of 3.83% and an allele frequency of 1.92%; confirmation of the functional intronic variant rs75017182 would be required for definitive HapB3 assignment. Overall, rs67376798 or rs56038477 was detected in 14 patients (4.13%). In addition, rare variants with a cohort allele frequency below 1% were identif","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060246","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":"Analysis of the Mechanisms of Rice <i>oszfp30</i> Mutant in Improving Forage-Quality-Related Traits Based on Transcriptome and Metabolome Analyses.","authors":"Chenfei Dong, Ruijie Zhao, Pengtao Shang, Yichen Jiang, Yue He, Yanhong Yan, Chao Chen","doi":"10.3390/genes17091086","DOIUrl":"10.3390/genes17091086","url":null,"abstract":"<p><strong>Background/objectives: </strong>Using straw as feed is crucial for addressing resource scarcity and waste-based environmental pollution and alleviating the contradiction between forage production and food security. However, rice straw has disadvantages such as a high lignin, cellulose, and hemicellulose content, as well as a dense cell wall structure, which greatly limit its utilization as feed. Improving the forage quality of rice straw through genetic breeding is an important means of enhancing its utilization rate.</p><p><strong>Methods: </strong>To explore the molecular basis underlying the improved nutritional and cell wall compositional traits of the rice lines (<i>oszfp30-1</i> and <i>oszfp30-2</i>) obtained in previous studies, we conducted phenotypic, physiological, transcriptomic, and metabolomic analyses on <i>oszfp30-1</i>, <i>oszfp30-2</i> and the wild type (WT) after 50 days of pot cultivation.</p><p><strong>Results: </strong><i>oszfp30-1</i> and <i>oszfp30-2</i> exhibited higher plant height, above-ground biomass, crude protein, and crude fat content, while their hemicellulose, cellulose, and lignin contents were significantly lower than those of the wild type. Transcriptomics was used to identify 737 common differentially expressed genes (DEGs), and metabolomics was used to identify 189 common differentially expressed metabolites (DEMs). KEGG analysis revealed that these DEGs and DEMs were significantly enriched in terpene biosynthesis, starch and sucrose metabolism, phenylpropanoid biosynthesis, and amino sugar and nucleotide sugar metabolism.</p><p><strong>Conclusions: </strong>Our research reveals that the improvement in forage-quality-related traits is closely related to key genes involved in gibberellin synthesis, including <i>GA20ox</i>, <i>GA2ox</i>, and <i>GA3ox</i>; key genes involved in cellulose synthesis, including <i>OsSUS</i> and <i>UGPase</i>; key genes involved in hemicellulose synthesis, including <i>UXS</i> and <i>IRX10</i>; and key genes involved in lignin synthesis, including <i>CCR</i>, <i>CAD</i>, <i>CCoAOMT</i>, and <i>COMT</i>. These identified DEGs and DEMs are associated with the <i>OsZFP30</i> mutation and may be downstream targets of this transcription factor, providing a foundation for further research on the <i>OsZFP30</i> regulatory network.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060199","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":"Two Separable Aging Domains in Blood DNA Methylation Scores Developed for Cancer Research: Mitotic Replication and Early-Life Systemic Dysregulation.","authors":"Katelyn N Austin, Man-Kit Lei","doi":"10.3390/genes17091083","DOIUrl":"10.3390/genes17091083","url":null,"abstract":"<p><p><b>Background/Objectives</b>: DNA methylation (DNAm)-based aging measures are increasingly being used in biological aging, disease vulnerability, and cancer-related risk. However, it remains unclear whether these measures capture a single generalized aging process or separable biological domains relevant to cancer-relevant biological vulnerability. <b>Methods</b>: Using data from the Family and Community Health Study (FACHS), we examine whether blood-based DNAm scores capture two distinct biological domains relevant to cancer susceptibility: a replication/mitotic domain, indexed by CellDRIFT, EpiTOC2, and MiAge, and an early-life systemic dysregulation domain, indexed by DunedinPACE, GrimAgeV2, and PhenoAge. <b>Results</b>: Regression results showed clear domain specificity. CRP, BMI, alcohol methylation, and AHRR/cg05575921 were positively associated with the early-life systemic dysregulation domain but showed weak or null associations with the replication/mitotic domain. Cross-domain tests confirmed significantly stronger associations for the early-life systemic dysregulation domain for CRP, BMI, and alcohol methylation, with a marginal difference for AHRR/cg05575921. In contrast, telomere-related methylation and immune-cell composition showed a different pattern. DNAmTL was inversely associated with both domains and did not differ significantly across domains. <b>Conclusions</b>: These findings suggest that blood-based DNAm aging measures do not reflect a single aging process. Instead, they distinguish at least two cancer-relevant methylation domains: one reflecting replication-driven mitotic aging and hematopoietic cell-turnover biology, and another reflecting early-life systemic dysregulation vulnerability linked to inflammation, metabolic risk, smoking methylation, and alcohol-related methylation. This two-domain framework may help clarify how blood DNAm profiles capture complementary biological processes relevant to cancer susceptibility and guide future studies of methylation-based cancer risk.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060541","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":"TMO-Net+: An Enhanced Tumor Multi-Omics Pre-Trained Network for Multi-Task Learning in Oncology.","authors":"Wei Liu, Xuan Liu, Shuyu Zhou, Kaiyang Li, Xiangzhi Wang, Ke Chen, Lilu Guo, Rui Zhang, Qingzhi Su","doi":"10.3390/genes17091085","DOIUrl":"10.3390/genes17091085","url":null,"abstract":"<p><strong>Background: </strong>Tumor heterogeneity arises from complex interactions among diverse biological factors, posing a major challenge for the development of robust multi-omics data integration methods. While the existing Tumor Multi-Omics pre-trained Network (TMO-Net) enables the fusion of multi-omics features into unified representations, its practical utility is constrained by issues such as missing modalities, incomplete within-omics data, and high-dimensional noise. To overcome these limitations, we propose TMO-Net+, an enhanced architecture specifically designed to improve the robustness and reliability of multi-omics modeling.</p><p><strong>Methods: </strong>TMO-Net+ introduces several coordinated architectural enhancements. First, a feature attention encoder is applied to each omics data type to reduce the influence of modality-dependent input variation. Second, we combine a gated Mixture-of-Experts (MoE) module with a Product-of Experts (PoE) mechanism to capture sample-specific contributions and enable robust inference even when partial omics data are available. Additionally, a supervised deep classification head with a tailored loss function is incorporated to enhance the separability of learned embeddings in the latent space.</p><p><strong>Results: </strong>Extensive experiments on pan-cancer datasets demonstrate that TMO-Net+ consistently outperforms the original TMO-Net, as measured by LogME scores. Furthermore, in various downstream tasks (e.g., pan-cancer classification, primary/metastatic site prediction, and prognostic modeling), TMO-Net+ achieves superior performance under partial-omics settings, which proves that it enhances the robustness and cross-cancer transferability of the multi-omics representations.</p><p><strong>Conclusions: </strong>The proposed TMO-Net+ improves the robustness and cross-cancer transferability of multi-omics representations within the evaluated TCGA cohorts. Biological interpretability analyses further show that TMO-Net+ prioritizes established cancer-driver genes, preserves cancer-dependent molecular-state information, and adaptively redistributes relative modality contributions across molecular states. By addressing modality-level missingness and modality-dependent input variation, it offers a reliable framework for integrative tumor analysis within the evaluated TCGA cohorts.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060434","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":"Integrating Next-Generation Reproductive Organoids with Genomics, Multi-Omics and Bioengineering to Understand Human Infertility.","authors":"Paul Barreau, Cyril Djari, John De Vos, Nino-Guy Cassuto, Said Assou","doi":"10.3390/genes17091080","DOIUrl":"10.3390/genes17091080","url":null,"abstract":"<p><p>Infertility affects approximately one in six individuals worldwide and is a highly heterogeneous disorder resulting from the complex interplay of genetic, epigenetic, endocrine, environmental and lifestyle factors. Although numerous genes and molecular pathways involved in female and male infertility have been identified, elucidating the functional consequences of disease-associated variants remains challenging due to the lack of relevant human experimental models. In recent years, reproductive organoids have emerged as powerful three-dimensional systems that recapitulate key structural, cellular and functional characteristics of the ovary, fallopian tube, endometrium, testis and early embryo. Here, we review the current landscape of reproductive organoid models based on a focused analysis of the literature, with particular emphasis on original studies describing their generation, characterization and applications. Beyond modeling tissue development and reproductive physiology, these models provide unique opportunities to investigate infertility-associated mechanisms, gene regulatory networks, cell-cell communication and tissue-specific responses to environmental and pharmacological stimuli. Single-cell and spatial transcriptomics, multi-omics, CRISPR/Cas9 genome editing, artificial intelligence and bioengineering technologies, including organ-on-chip systems, are expanding their potential as next-generation platforms for functional genomics, disease modeling, biomarker discovery and therapeutic screening. However, current reproductive organoids remain simplified representations of native tissues, with limitations in physiological maturity, reproducibility and standardization, while their clinical predictive value remains to be established. Overall, by linking genomic variation with molecular regulation, cellular phenotypes and tissue organization, reproductive organoids represent promising preclinical platforms for understanding human infertility and may ultimately contribute to the development of precision reproductive medicine.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060281","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":"Identification and Validation of the Nrf2/Slc2a1 Axis in Alzheimer's Disease.","authors":"Yantong Luo, Jingjing Deng, Yuanzhan Loh, Hongduo Lu, Nanbu Wang, Chunzhi Tang, Bin Zhang","doi":"10.3390/genes17091081","DOIUrl":"10.3390/genes17091081","url":null,"abstract":"<p><p>Background/Objects: Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by progressive cognitive decline. Although Nrf2 is a key regulator of oxidative stress in AD, the molecular factors associated with Nrf2 signaling and their potential regulatory relationships remain incompletely understood. This study aimed to systematically identify and validate a novel Nrf2-associated signaling axis in AD. Results: Slc2a1 was identified as a key Nrf2-associated candidate gene. In the SCOP-induced AD model, reduced Nrf2 expression was accompanied by decreased Slc2a1 expression, cognitive impairment, hippocampal neuronal injury, excessive ROS accumulation, and mitochondrial abnormalities. Pharmacological modulation of Nrf2 was associated with corresponding changes in Slc2a1 expression, while Nrf2 activation was accompanied by improvements in oxidative stress and neuronal injury. Conclusions: This study identifies a potential functional relationship between Nrf2 signaling and Slc2a1 expression in AD-related pathology and proposes the Nrf2/Slc2a1 pathway as a potential mechanistic framework linking oxidative stress to mitochondrial abnormalities.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060196","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":"Precision Oncology in Non-Small Cell Lung Cancer: Integrating Molecular Diagnostics, Targeted Therapies, and Resistance Mechanisms.","authors":"Aleksandra Litkowska, Jan Wojtas, Kaja Nadulska, Grzegorz Kurec, Oliwia Burdan, Paweł Adam Krawczyk","doi":"10.3390/genes17091076","DOIUrl":"10.3390/genes17091076","url":null,"abstract":"<p><strong>Background: </strong>Precision oncology has significantly transformed the management of non-small cell lung cancer (NSCLC) through the integration of molecular diagnostics, targeted therapies, and biomarker-driven treatment selection. Advances in next-generation sequencing (NGS) and liquid biopsy have improved the identification of actionable molecular alterations and enabled dynamic monitoring of tumor evolution.</p><p><strong>Objective: </strong>To provide a structured narrative review of current evidence regarding actionable molecular biomarkers, diagnostic methodologies, targeted therapies, and future directions in NSCLC precision oncology, with a specific focus on conceptualizing acquired resistance mechanisms.</p><p><strong>Methods: </strong>A structured narrative literature review was conducted by searching PubMed and Google Scholar for English-language studies published between 2015 and 2026. Eligible publications included clinical trials, cohort studies, translational research, reviews, and clinical guidelines addressing molecular profiling, targeted treatments, diagnostic approaches, and resistance mechanisms in NSCLC.</p><p><strong>Results: </strong>A total of 99 foundational studies and clinical documents were analyzed. Key actionable biomarkers included <i>EGFR</i> (Epidermal Growth Factor Receptor), <i>ALK</i> (Anaplastic Lymphoma Kinase), <i>ROS1</i> (ROS Proto-Oncogene 1, Receptor Tyrosine Kinase), <i>KRAS</i> (Kirsten Rat Sarcoma Viral Oncogene Homolog), <i>RET</i> (Rearranged during Transfection), <i>MET</i> (Mesenchymal-Epithelial Transition Factor), <i>HER2</i> (Human Epidermal Growth Factor Receptor 2) and <i>NTRK</i> (Neurotrophic Tyrosine Receptor Kinase) alterations, along with emerging targets such as <i>NRG1</i> (Neuregulin 1) fusions. NGS emerged as the cornerstone of comprehensive molecular profiling, while liquid biopsy enabled longitudinal monitoring of tumor dynamics and resistance development. To organize the biological complexity of treatment failure, acquired resistance mechanisms were categorized into a three-tiered conceptual framework: target-centric genetic evolution (Tier 1), cellular plasticity and intratumoral heterogeneity (Tier 2), and non-genetic/microenvironmental adaptation (Tier 3). Targeted therapies significantly improved clinical outcomes compared with conventional chemotherapy; however, acquired resistance remained a major challenge across all tiers.</p><p><strong>Conclusions: </strong>Precision oncology in NSCLC is evolving from a biomarker-focused approach toward a dynamic framework integrating molecular diagnostics, targeted therapies, and continuous resistance monitoring. The proposed three-tiered resistance framework provides a structured basis for understanding treatment failure, guiding molecular reassessment at progression, and informing future adaptive therapeutic strategies to improve long-term patient outcomes.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060301","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}