Horsegram (Macrotyloma uniflorum), a member of the Fabaceae family, is a nutritious and low-cost legume used for both grain and fodder. This study employed a genome-wide association approach to identify loci linked to key agronomic traits in horsegram. Plant height, seed size, and shoot fresh weight were evaluated in a panel of 96 diverse genotypes. GBS was performed using the Illumina HiSeq platform, yielding 20,241 high-quality SNPs after filtering at a 5
Cyclin genes are plant cell cycle regulators that play essential roles in growth, development, and reproduction. However, the evolutionary dynamics and genomic organization of cyclin genes across the Brassicaceae family remain poorly understood, particularly in the context of allotetraploid genome evolution. Here, we investigated the diversity, expansion mechanisms, and potential functional diversification of cyclin genes across ten Brassicaceae genomes, including four Arabidopsis and six Brassica species. A total of 1087 cyclin genes representing 23 cyclin types were identified. Comparative genomic analyses revealed that cyclin gene expansion was strongly influenced by polyploidization in Brassica species, with 1845 duplication events involving 1063 genes. Whole-genome duplication was the predominant mechanism driving expansion, while both inter- and intra-genomic duplications contributed to gene retention in tetraploid Brassica species, with the highest duplication frequency observed in Brassica juncea. Across genomes, 120 physical gene clusters were identified, including homogeneous and heterogeneous types. Ortholog analysis between progenitor and allotetraploid species identified 852 orthologous pairs involving 366 genes, indicating extensive conservation following allotetraploid formation. Phylogenetic analysis resolved cyclins into three major clades, while expression-based clustering in Brassica napus grouped genes into four major clusters, suggesting functional diversification. Integration of pan-genomic and flowering-time QTL analyses further identified two cyclin genes, Bna21cycA2 and Bna113cycD4, which contain amino acid polymorphisms and represent putative candidate variations potentially associated with flowering-time variation across multiple genomes. These findings provide new insights into the evolutionary expansion, retention, and potential functional divergence of cyclin genes in Brassicaceae and highlight candidate loci for future functional studies and crop improvement.
Urease is a nickel-dependent, multi-gene bacterial system that contributes to nitrogen acquisition, pH homeostasis, and ecological adaptation, yet most comparative studies rely on single-gene markers such as ureC. Here, we analyzed 237 complete genomes from a stratified bacterial panel integrating ecological and genome-level metadata, annotation-guided screening, profile-HMM detection, locus reconstruction, and species-tree comparison. Within this panel, 149 genomes encoded at least one complete urease locus, 11 contained candidate but incomplete neighborhoods, and 77 lacked any supported urease locus. At the locus level, we recovered 173 urease-associated neighborhoods, including 150 canonical ureABC loci, 7 Helicobacter AB fusion loci, and 16 partial or split loci. The canonical three-subunit architecture therefore dominated the dataset, whereas the Helicobacter-type configuration persisted as a small but stable lineage-restricted alternative. Eight genomes encoded duplicated complete canonical systems, and in each case, both loci mapped to the same top-level assembly sequence record. Their paired loci differed in gene order and typically shared only about 62–63
Uterine leiomyomas (ULMs) are the most common benign gynecological tumors affecting women in reproductive age. Symptoms such as abnormal uterine bleeding, pelvic pain, and infertility may occur, leading to a significant decline in patients’ quality of life. In addition, ULMs represent the second leading indication for gynecological surgery in Brazil, imposing a substantial economic burden on the public healthcare system. However, despite their high prevalence and clinical impact, there is still no curative clinical treatment for these tumors, and the molecular mechanisms underlying their development and clinical behavior remain poorly understood. Recent studies have demonstrated the involvement of the Sonic Hedgehog (SHH) signaling pathway in uterine mesenchymal tumors. Therefore, the aim of this study was to investigate the expression profile and regulation of the SHH and Wnt signaling pathways in ULMs, as well as to evaluate their potential role in tumor progression through integrative analyses of promoter methylation, mRNA expression, and microRNA-mediated regulation. Initially, 106 genes related to SHH, Wnt signaling pathways were examined in ULM, compared to normal myometrium (MM) by real-time PCR. Interactions among SHH pathway genes were assessed through multivariate analysis. In addition, methylation profiles of nine key SHH-related genes were evaluated using methylation-specific assays, and the expression of 84 microRNAs (miRNAs) was analyzed in association with differentially expressed genes potentially involved in tumorigenesis. Differential expression analysis identified 23 dysregulated genes, including 13 upregulated and 10 downregulated genes. Multivariate analysis suggested that SHH pathway activation in ULMs occurs independently of SHH–PTCH1 binding and may involve GLI1, CCND1, and BCL-2. Significant DNA methylation alterations were detected in PTCH1, SMO, GLI1, GLI3, GREM1, and WNT1. Furthermore, 16 miRNAs were differentially expressed, eight of which showed significant correlations with their predicted target genes. Collectively, these findings suggest that ULM pathogenesis involves a complex regulatory network integrating SHH and Wnt signaling pathways, epigenetic modifications, and microRNA-mediated post-transcriptional regulation. These results provide novel insights into the molecular mechanisms underlying ULM development and identify candidate regulatory elements that may serve as potential biomarkers or therapeutic targets in future functional studies on uterine fibroids.
Metabolically dysfunction-associated steatotic liver disease (MASLD), a globally prevalent metabolic condition, is increasingly linked to impaired mitophagy. However, its regulatory mechanisms in MASLD are not fully elucidated. This study investigated the role of Zinc finger protein 143 (ZNF143) in regulating hepatocyte mitophagy during MASLD development and the mechanisms involved. We employed two complementary MASLD models: (1) C57BL/6J mice fed a high-fat diet (HFD) for 16 weeks and (2) Huh-7 cells exposed to free fatty acid (FFA). Pathological changes were detected by H E Staining. Cellular lipid deposition and mitochondrial damage were assessed using Oil Red O, JC-1 staining and transmission electron microscope (TEM), respectively. The intermolecular interaction was identified by dual-luciferase reporter assay, ChIP, and Co-IP. ZNF143 was upregulated in MASLD models, and its knockdown mitigated lipid accumulation and liver injury by activating hepatocyte mitophagy. ZNF143 promoted SMAD-specific E3 ubiquitin-protein ligase 1 (SMURF1) transcription by binding to its promoter region. Moreover, SMURF1 mediated transient receptor potential vanilloid type 1 (TRPV1) ubiquitination and degradation. Finally, knockdown of TRPV1 or overexpression of SMURF1 reversed the promoting effect of ZNF143 knockdown on mitophagy in FFA-treated Huh-7 cells. In short, ZNF143 upregulation exacerbated MASLD progression by mediating TRPV1 ubiquitination and degradation through transcriptionally activating SMURF1.
Cervical cancer remains a leading cause of cancer-related morbidity and mortality among women worldwide. Although genomic alterations in oncogenic signaling pathways have been implicated in cervical carcinogenesis, the functional impact of recurrent driver mutations remains incompletely understood. Whole-exome sequencing was performed on paired tumor and matched non-tumor tissues from 61 patients to identify recurrent somatic alterations. Functional significance was subsequently evaluated using cervical cancer cell models through proliferation, invasion, apoptosis, and signaling pathway analyses. Tumorigenic potential was further assessed using a xenograft mouse model. Genomic profiling identified PIK3CA as one of the most frequently mutated genes in cervical cancer. Functional analyses demonstrated that PIK3CA E545K mutation (PIK3CA-E545K-MUT) significantly enhanced tumor cell proliferation and invasive capacity while suppressing apoptosis. Mechanistically, these effects were associated with sustained activation of the AKT/mTOR signaling pathway, as evidenced by increased phosphorylation of key downstream effectors. Consistently, in vivo xenograft experiments confirmed that PIK3CA-E545K-MUT-driven signaling activation promoted tumor growth. Our findings establish a functional and mechanistic link between recurrent PIK3CA-E545K-MUT and aggressive tumor behavior in cervical cancer via AKT/mTOR pathway activation. These results provide experimental support for targeting the PI3K/AKT/mTOR axis as a potential therapeutic strategy in cervical cancer.
Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer, characterized by high invasiveness, poor prognosis, and limited therapeutic options. Cancer-associated fibroblasts (CAFs), as a core component of the tumor microenvironment (TME), have been shown to promote the malignant progression of NSCLC, but the specific regulatory mechanisms remain incompletely understood. This study aims to investigate the role of CAFs and their metabolic products, particularly lactate, in the progression of NSCLC. CAFs and normal fibroblasts (NFs) were cultured, and the conditioned media (CM) were collected and used to treat NSCLC cells. Cell proliferation was assessed using CCK-8 and EdU assays, while cell migration was evaluated through transwell assays. The expression of E-cadherin and N-cadherin was detected by immunofluorescence (IF). Additionally, lactate levels, gene expression, and lactylation levels were assessed using a lactate detection kit, RT-qPCR, Western blot (WB), and chromatin immunoprecipitation (ChIP). The CM from CAFs enhanced the proliferation, migration, and epithelial-mesenchymal transition (EMT) of NSCLC cells. Our experiments revealed that the metabolites from CAFs, particularly lactate, had a promoting effect on NSCLC. In lactate-treated NSCLC cells, the expression levels of stemness genes were significantly upregulated, accompanied by increased lactylation levels of H3K18. In in vivo experiments, tumors from the lactate treatment group exhibited higher growth rates and increased expression of stemness genes. Furthermore, human NSCLC tumor tissues showed significant upregulation of stemness genes. This study demonstrates that lactate derived from CAFs promotes the expression of stemness genes by mediating H3K18 lactylation in the promoters of these genes in NSCLC cells, thereby accelerating the malignant phenotype formation of NSCLC cells. These findings provide new insights into the role of CAFs in the TME and identify potential therapeutic targets for NSCLC.
Microsatellites, or simple sequence repeats (SSRs), are abundant genomic features, but their evolutionary interpretation is often limited by detector-dependent discovery and single-reference surveys that count repeats without resolving homologous repeat states. We characterized pan-SSR architecture in the cyprinid Acrossocheilus fasciatus by integrating four genome assemblies within the AF_xajfe coordinate system. Synthetic ground-truth calibration identified Tandem Repeats Finder as the most accurate and parameter-stable algorithm, and coordinate-anchored merging resolved 499,190 pan-SSR entries comprising 39,150 core, 235,720 dispensable, and 224,320 private components. In homologous shared components, repeat-unit count variation dominated polymorphism (26.2
Tethered cord syndrome (TCS) is a neurodevelopmental disorder associated with neural tube defects (NTD), yet its genetic underpinnings remain poorly characterized. To elucidate its molecular basis, we conducted whole-exome sequencing (WES) on 81 TCS patients. Our analysis revealed that MNX1 variants, including two microdeletions and a deleterious missense variant, accounted for 3.7
Blood proteins may play causal roles in cardiovascular diseases (CVDs) such as heart failure (HF) and peripheral artery disease (PAD). Proteome-wide Mendelian randomization (MR) has been widely used to prioritize drug targets for CVD in European populations, but its application to non-European populations remains limited. We conducted a proteome-wide MR analysis to evaluate the potential causal effects of 2,922 plasma proteins on five CVDs—atrial fibrillation (AF), coronary artery disease (CAD), HF, ischemic heart disease (IHD), and PAD. Analyses were performed across African (n = 931), East Asian (n = 262), and European (n = 10,840) populations using genetic instrument data from the UK Biobank cohort. Significant associations were further examined with genetic colocalization to strengthen causal inference. Using MR and colocalization analyses, we identified 53 significant protein–CVD associations across multi-populations, including 16 in African, six in East Asian, and 31 in European populations, respectively. Cross-population comparisons revealed four protein–CVD associations unique to African population and another four specific to East Asian population. Integration with clinical trial data prioritized 14 protein–disease pairs as promising candidates for therapeutic development or drug repurposing. Our findings highlight the value of proteome-wide MR in evaluating drug target applicability across populations. Several protein–disease associations were population-specific, emphasizing the need for inclusive genetic research to inform precision medicine in CVD prevention and treatment.
Gamma-glutamyl transferase (GGT) regarded as a biomarker of liver dysfunction or excessive alcohol consumption; however, existing genome-wide association studies (GWAS) have been conducted predominantly in European populations and East Asian populations from Japan and the Taiwan region, with limited investigation in ethnic minorities from Guizhou Province. Previous genetic studies have demonstrated that Guizhou ethnic minorities share an East Asian genetic background while exhibiting specific genetic structures, a pattern that is also confirmed by our principal component analysis (PCA) results. We therefore performed a GWAS in this population and identified a genome-wide significant signal at 8q12.3 in female ethnic minorities from Guizhou. Fine-mapping and functional annotation analyses suggest that a regulatory pathway involving Runt-related transcription factor 1 (Runx1)–Cytochrome P450 family 7 subfamily B member 1 (CYP7B1)–cholesterol–reactive oxygen species (ROS)–glutathione (GSH) may contribute to the regulation of GGT levels. Mendelian randomization (MR) analyses further supported a causal relationship between GGT levels and autoimmune hepatitis (AIH). These findings uncover a genetic mechanism underlying GGT variation at 8q12.3 in female ethnic minorities from Guizhou, implicating a pathway linked to cholesterol metabolism and oxidative stress, and providing potential targets and insights for precision prevention and treatment of related diseases.
Artificial intelligence (AI) is rapidly becoming a core methodological pillar of molecular biology and precision medicine, and Africa is a uniquely consequential setting for this transition because the continent combines the world’s greatest human genomic diversity with the most severe underrepresentation of that diversity in the datasets and reference resources on which AI models are built and benchmarked. This narrative review examines, for a genetics and genomics readership, where AI-driven methods are already strengthening African molecular biology, where the supporting evidence remains preliminary, and what is required to translate technical capability into scientifically robust and equitable benefit. The central argument is that AI is especially consequential in African molecular biology, not simply because it automates analysis, but because it can help unlock insight from African genomic diversity, pathogen biology, and clinically relevant multi-omics data that remain underrepresented in global models. Across core molecular domains, AI is accelerating protein structure prediction, high-throughput variant calling and pan-genomic reference construction, genome-wide association analysis, transcriptomic interpretation, drug discovery, and CRISPR guide design. African initiatives such as H3Africa, the African Genome Variation Project, H3ABioNet, and the H3D Centre show that locally generated datasets and African-led computational pipelines can already support meaningful discovery, from improved variant interpretation to structure-guided therapeutic prioritization. At the same time, persistent barriers remain, including underrepresentation of African genomes in training data and reference genomes, uneven computational infrastructure, limited interdisciplinary training, fragmented governance, and the risk that AI-derived benefits will remain inaccessible to the populations whose data enable them. We conclude that the future impact of AI in African molecular biology will depend less on adopting global tools in the abstract and more on building African-led datasets, validation pipelines, governance frameworks, and translational pathways that make molecular discovery both scientifically robust and equitably useful. Looking ahead, the central perspective offered by this review is that Africa’s exceptional genomic diversity should be treated as a scientific asset rather than an analytical liability: realising this will require population-representative pan-genome references, sustained computational capacity, and governance structures that ensure African populations are not only the source of the underlying data but also the principal beneficiaries of the discoveries it enables.
Hair yield is the main economic value of Zhexi Angora rabbit, and it is an important index to measure its productive traits. The TRPV3 gene has been found to be associated with wool yield. This study aims to investigate the correlation between TRPV3 and wool production traits in rabbits, with the goal of improving wool yield. In the current study, flow cytometry and CCK-8 assays were used to investigate the effect of the TRPV3 gene on the proliferation and apoptosis of dermal papilla cells (DPCs) in rabbit hair follicles (HFs). Results showed that the TRPV3 gene regulates the mRNA expression of genes involved in HF development (BMP4, SFRP2, TGF-β1, WNT5a, and STAT1), as detected by qRT-PCR analysis. The core promoter region of TRPV3 was identified through dual luciferase activity tests, and Sanger sequencing was used to detect polymorphisms in both the exonic and promoter regions of TRPV3. The analysis showed a single SNP in the exon region, which had no significant association with wool production. However, five SNPs were detected in the promoter region, with the g.48897415G> A site showing a significant association with wool production in Zhexi Angora rabbits. Moreover, rabbits carrying the AA genotype also showed higher transcriptional activity. The mutation at g.48897415G> A in the promoter region introduced seven extra transcription factors (TFs) (RFX4, RFX3, RFX2, ZNF45, RFX1, Zfp668, and ZNF655). In conclusion, the g.48897415G > A mutation in TRPV3 is significantly associated with wool yield, and the TRPV3 gene inhibits the proliferation of DPCs. This locus can be used as a molecular marker for wool traits in rabbits, allowing early selection and precise breeding of high-wool-yield strains to shorten the breeding cycle and improve efficiency to enhance both the yield and quality of rabbit wool.
Heavy metal (HM) contamination threatens plant health and poses significant challenges to agriculture and ecosystem functioning. Plant-associated microorganisms from HM-contaminated environments play a vital role in enhancing host stress tolerance and are promising candidates for sustainable, microbe-based strategies to support plant fitness. Non-legume-associated rhizobia, however, remain poorly described in this context. In this study, we characterized Rhizobium metallidurans strain NS41, an endophyte of goldenrod (Solidago canadensis) growing at a highly metal-contaminated site. To our knowledge, this is the first report of this species associated with a non-leguminous host, thereby expanding current knowledge about R. metallidurans. Genome analysis revealed determinants of HM resistance, oxidative and osmotic stress mitigation, and metabolism of plant-derived compounds, but no canonical nodulation genes, indicating a facultative endophytic, rather than nodulation-dependent, lifestyle adapted to metalliferous environments. In vitro, NS41 demonstrated tolerance to high Zn, Cd, and As(III) concentrations (MIC 20 mM, 2.5 mM, 5 mM, respectively), produced indole-3-acetic acid and ammonia, and solubilized phosphates. In a maize pot experiment in HM-contaminated soil, seed inoculation with NS41 resulted in lower hydrogen peroxide and anthocyanin levels and higher chlorophyll content, without significantly altering biomass or Cd accumulation. This identifies NS41 as a stress-mitigating endophyte rather than a strong direct growth promoter under the tested conditions. Together, these genomic features and stress-mitigating phenotype support further investigation of NS41 as a plant-protective bioinoculant for improving plant performance on HM-contaminated soils.
Long non-coding RNA (lncRNA) antisense RNA 1 (LOXL1-AS1), reportedly, exerts carcinogenic effects in cancers including non-small cell lung cancer (NSCLC) via competitive endogenous RNA (ceRNA) mechanism. Additionally, previous studies have implied that microRNA-122-5p (miR-122-5p) and E2F transcription factor 3 (E2F3) have cancer-promoting properties and tumor-suppressive properties, respectively. Here we aim to further explore the function and mechanism of LOXL1-AS1 in NSCLC. In this experimental study, we found that LOXL1-AS1 was high expression in NSCLC tissues and cell lines. High LOXL1-AS1 expression was significantly relevant to the advanced tumor node metastasis (TNM) stage and positive lymph node metastasis of NSCLC patients. LOXL1-AS1 overexpression promoted proliferation, migration and invasion of NSCLC cells, while LOXL1-AS1 knockdown had the opposite effect. LOXL1-AS1 could sponge miR-122-5p. E2F3 was a downstream target of miR-122-5p. LOXL1-AS1 increased E2F3 expression through repressing miR-122-5p. In addition, miR-122-5p up-regulation or E2F3 knockdown could offset the promoting effect of LOXL1-AS1 overexpression on proliferation, migration and invasion of NSCLC cells. Overall, this study demonstrates that LOXL1-AS1 promotes NSCLC cell proliferation and migration in vitro, and correlates with poor clinical outcomes, partially via modulating miR-122-5p/E2F3 axis.
Kutta is an indigenous sheep breed found in the mountainous region of Swat, Pakistan. In this study we evaluated the performance of Kutta sheep within their natural habitat and identified genomic regions associated with environmental adaptability using whole genome sequencing. Flocks are mostly managed under a transhumant production system with year-round breeding. Kutta sheep demonstrated higher lambing efficiency under the available resources. Although the body size of rams and ewes was comparable, significant variation was observed among different age groups. Whole genome sequencing identified 15.46 million variants relative to Oar_v1.0 reference genome assembly. Exonic variants accounted for 2.3
ALPK3, a gene associated with pediatric cardiomyopathy, plays a pivotal role in cardiac development, yet the regulatory mechanisms governing its involvement in cardiomyocyte apoptosis are still not well understood. Detect the expression changes of ALPK3 in embryonic and neonatal mouse heart tissues at various developmental stages (E11.5, E12.5, E14.5, and P3). Establish ALPK3 knockdown cell lines to evaluate phenotypic changes in cardiomyocyte apoptosis. At the cellular level, validate the mechanism by which ALPK3 regulates cardiomyocyte apoptosis through the Notch1 signaling pathway. Transcriptional analysis of ALPK3 in embryonic mouse hearts revealed a progressive increase in expression during development, peaking in the perinatal period. In vitro experiments using ALPK3-knockdown AC16 cardiomyocytes demonstrated a 50% reduction in ALPK3 mRNA and protein levels, accompanied by significant apoptosis induction. RNA sequencing indicates that Notch1 signaling is significantly inhibited. ALPK3 deficiency suppressed Notch1 signaling, as evidenced by reduced levels of Hes-1 and NICD proteins; however, treatment with the Notch1 ligand Jagged1 reversed these effects. Furthermore, ALPK3 knockdown elevated pro-apoptotic BAX and decreased anti-apoptotic BCL-2 expression, whereas Jagged1 restored their levels. The findings indicate that ALPK3 regulates cardiomyocyte apoptosis and viability via the Notch1 pathway, offering mechanistic insights into ALPK3-associated cardiomyopathy and highlighting potential therapeutic targets for heart failure.
Neutrophil extracellular traps (NETs) facilitate inflammation and epithelial-mesenchymal transition (EMT), promoting the progression of pulmonary fibrosis. Various machine learning methods were used to screen for prognostic genes. Based on prognostic genes, a risk model was constructed to assess their ability for prognosis prediction of idiopathic pulmonary fibrosis (IPF). Mendelian Randomization (MR) analysis evaluated causal associations between IPF and prognostic genes, while GSE122960 examined cell-type-specific expression. A bleomycin-induced pulmonary fibrosis mouse was established, collagen deposition was assessed by Masson and Picrosirius Red staining, the expression of prognostic genes were validated by Reverse Transcription quantitative Polymerase Chain Reaction (RT-qPCR) and Western blot (WB), and NETs-related protein ( Cith3 and MPO ) were evaluated by immunofluorescence. A comprehensive analysis resulted in the identification of 3 prognostic genes (MMP1, CXCR7, and TPST1), followed by the development of a NET-inflammation-associated prognostic model, which well predicted the prognosis of IPF. Moreover, exploratory MR analysis suggested possible positive associations between genetically predicted MMP1 and TPST1 expression and IPF risk. Single-cell analysis revealed the expression of MMP1 and TPST1 differed significantly in monocytes between IPF patients and controls. Furthermore, significant differences were identified in functional pathways and immune cell infiltration between risk groups. Masson and Picrosirius Red staining confirmed collagen deposition in the bleomycin-induced pulmonary fibrosis mouse model. RT-qPCR and WB showed higher expression of MMP1, CXCR7, and TPST1 in pulmonary fibrosis mice than in controls. Cith3 + MPO double immunofluorescence staining showed increased NETs-related signals in the model group than the control. These findings provide potential prognostic markers for IPF patients and may enhance comprehension of the disease’s underlying inflammatory and fibrotic processes.
Epilepsy and psychosis are dysfunctions of the nervous system that may occasionally co-occur. The current study was designed to investigate the causes of psychosis with or without epilepsy in Pakistani families. We identified two consanguineous families in which all affected members had treatment-resistant psychosis while three patients also had epilepsy. Every participant was examined by psychiatrists and a psychologist, while epilepsy was diagnosed by neurologists. The doctors confirmed the presence of severe psychosis with or without epilepsy in the patients and their absence in other participants. Exome sequencing identified a biallelic variant c.570G > T; p.Trp190Cys in CLN8 that segregated with the phenotype of epilepsy with psychosis in one family whereas the results for the other family were negative. CLN8 variant affects an amino acid which is conserved in diverse vertebrate orthologues. In-silico analysis indicated that substitution of tryptophan with cysteine resulted in the loss of an intramolecular interaction, which may affect protein folding. This study emphasizes that CLN8-related phenotype can include severe treatment-resistant psychosis and also provides a genotypic extension.
