In metabolic dysfunction-associated fatty liver disease (MAFLD) research, reference genes for qPCR are crucial but often unvalidated.

This study identifies two pedigrees with autosomal dominant polycystic kidney disease (ADPKD) caused by de novo PKD1 variants. Proband A carried a heterozygous splicing variant (c.9202-16G > A), presenting with bilateral renal cysts. The miniGENE assay confirmed this variant causes aberrant splicing with a 60-base excision, leading to a frameshift and a predicted truncated protein. Proband B carried a missense variant (c.2180 T > C; p.Leu727Pro), presenting with polycystic kidney and liver disease. Structural modeling revealed this variant severely disrupts local secondary structure and a critical spatial interaction, compromising protein stability. Functional analyses demonstrate that both de novo variants are pathogenic through distinct mechanisms, implicating aberrant splicing and structural disruption in ADPKD etiology.

To conduct a case-control study (pilot study) in Africa (Mali) in comparing the gut microbiota of patients with stage III colorectal cancer (CRC) using next-generation sequencing.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that can lead to progressive disability. TNF inhibitors (TNFi) have shown promise in improving disease progression and prognosis; however, only 60% to 70% of patients respond well. Genetic variations have been linked to this therapeutic failure. Genetic variants in the IL17 gene are associated with TNFi therapy responses and RA susceptibility, but few studies have explored this in the Brazilian population. This study assesses variants in the IL-17 pathway (rs763780, rs2275913, rs3819024) in RA patients undergoing TNFi treatment in Salvador, BA.

Pediatric brain tumors (PBTs) are the leading type of solid tumors in children, profoundly affecting both survival rates and quality of life. Methotrexate (MTX) is an essential chemotherapy drug for treating these tumors; however, its efficacy and toxicity vary among patients due to genetic factors.

Advances in genetics and genomics have transformed our understanding of personality. The observation that personality traits run in families has prompted extensive study into their heritability and underlying genetic architecture. However, there is a significant discrepancy between psychiatric classifications of personality disorders and genomic findings, suggesting a need to reorient these classifications toward a more dimensional, biologically informed perspective. This article reviews key genetic and genomic findings in personality, focusing on the "Big Five" model, which has proven consistency with genomic research. Twin studies estimate heritability accounts for about 40-50% of personality, while the rest of phenotypic variation is explained by the non-shared environment, which influence personality through epigenetic changes. Genome-wide association studies (GWAS) have identified numerous genetic variants on nearly all chromosomes that influence personality traits, particularly neuroticism. These variants are involved in biological pathways such as neurogenesis and neuronal differentiation. GWAS have also revealed significant genetic correlations between personality traits and major psychiatric disorders, supporting a biological continuum between them. This supports the hypothesis which states that a typical behavioral trait is associated with many genetic variants, each contributing a very small effect. Future research should incorporate epigenetic evidence, study genetic interactions, and expand the diversity of study populations beyond European ancestry to improve the generalizability of findings.

Bladder cancer (BCa) remains one of the most challenging malignancies in oncology, driven by deep molecular heterogeneity, dynamic tumor evolution and complex tumor-microenvironment interactions. Despite advances in molecular characterization and the introduction of new treatments, translating biological knowledge into meaningful clinical benefits remains a major bottleneck. In recent years, next-generation 3D preclinical models have emerged as essential tools to recapitulate BCa complexity, offering new opportunities to investigate tumor biology and support the development of personalized treatment strategies. This review provides an overview of available 3D models for BCa, discusses their application and highlights their growing integration into clinical trials to guide real-time therapeutic decisions.

Ascorbate peroxidase (APX) enzymes are pivotal in scavenging reactive oxygen species (ROS) and maintaining redox homeostasis in plants, a function critical for survival under abiotic stress conditions. To investigate this key enzyme system in the rubber-producing dandelion Taraxacum kok-saghyz (Tk)-an emerging model for sustainable rubber production-we conducted a genome-wide analysis of its APX genes. We identified seven TkAPX genes, whose predicted subcellular localizations include the cytoplasm, plasma membrane, and chloroplasts. Promoter analysis revealed an abundance of stress-responsive motifs, supporting their potential role in stress adaptation. By integrating time-course qPCR of the TkAPX family under heat stress with transcriptome-wide expression profiling across tissues, we identified TkAPX250a as a pivotal candidate. This gene showed a remarkable ∼ 20-fold increase in transcript levels in subsequent transgenic lines compared to wild-type controls, confirming highly efficient transgene expression without silencing. Under thermal stress, these transgenic lines exhibited reduced ROS accumulation and membrane lipid peroxidation while maintaining higher chlorophyll content and biomass, demonstrating that TkAPX250a coordinately enhances thermotolerance and photosynthetic stability. Mechanistically, TkAPX250a overexpression not only enhanced APX activity and lowered HO accumulation but also synergistically upregulated the activities of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD). Time-resolved assays under heat stress further delineated a stratified antioxidant hierarchy within this coordinated response, with SOD and CAT acting as core responders. These findings establish TkAPX250a as a central genetic regulator in abiotic stress adaptation and provide a molecular basis for breeding stressresilient rubber crops, addressing a critical need in agriculture under changing climate conditions.

Rescuing stalled ribosomes from the truncated mRNA is identified as a crucial process for the survival of a bacterial cell. A small RNA named tmRNA (transfer messenger RNA), and protein SmpB (Small protein B), together constitute a ribosome rescue apparatus which is ubiquitous among most of the eubacteria and archaea. tmRNA mediated ribosome rescue process (also called trans-translation) has been found to be the major pathway of clearance of stalled ribosome complexes. In the process, tmRNA-SmpB complex recycles stalled ribosomes by making them undergo normal translation and termination. Apart from rescuing stalled ribosomes, trans-translation modulates other cellular pathways (such as cell cycle, oxidative stress, nutritional stress, DNA damage response and so on) by regulating the intracellular level of various proteins. It becomes more and more obvious that the function of trans-translation apparatus is diverse and plays a role in bacterial pathogenesis also. This review will focus on the key findings on the involvement of tmRNA and its partner SmpB in regulation of pathogenesis and virulence in different pathogenic bacteria.

PURA syndrome is a rare genetic disorder characterized by obvious hypotonia, feeding difficulties, apnea, and drowsiness, which is caused by variants in the Purine Rich Element Binding Protein A (PURA) on chromosome 5q31.2-q31.3, and is inherited in an autosomal dominant manner. This condition presents challenges for early diagnosis and effective treatment. This study investigates its pathogenic mechanisms and potential therapeutic strategies.

Malaria caused by Plasmodium vivax remains a significant public health challenge, with vaccine development hindered by factors such as antigenic diversity and immune evasion. The Cysteine-Rich Protective Antigen (CyRPA), a key protein involved in erythrocyte invasion, has emerged as a promising vaccine candidate. However, its genetic diversity and immunological properties have not been fully explored. This study aimed to analyze the genetic diversity, selective pressures, and antigenic potential of the pvcyrpa locus using 950 sequences, including 42 newly obtained isolates from Colombia. The pvcyrpa gene displayed high nucleotide diversity shaped by both natural selection and recombination. In-silico predictions identified B- and T-cell epitopes, encompassing mainly polymorphic regions, with strong binding affinities predicted for multiple HLA alleles. Notably, these epitopes overlapped with regions previously shown to elicit immune responses in natural infections, as reported in a recent study. Moreover, immune simulation of a multiepitope C-terminal construct predicted a robust humoral memory profile. Collectively, these genetic, epitope-mapping, and immune-simulation findings highlight the conserved C-terminal region of PvCyRPA as a strong, broadly reactive vaccine candidate, providing a rational basis for subsequent in-vitro and in-vivo validation.

To determine the gene content of an organism, the reads generated by the sequencing process must be assembled using an assembly strategy, either by reference or de novo. However, this process often results in multiple sequences called contigs, which, after the sorting steps, are grouped into scaffolds. The completion stage aims to obtain a single genomic sequence, called a complete genome, which is not a trivial task. Various analytical strategies have been developed to help in this process, many of which have been implemented in computer tools to obtain complete genomes or as close to this as possible, the so-called drafts. The manuscript presents ContigPolishing, a computational tool with a simple and intuitive graphical interface, developed to improve the assembly of prokaryotic genomes, such as bacteria and metagenomes. Despite existing software, there is a gap for solutions that combine simplicity and robustness. ContigPolishing addresses this need, featuring an integrated database that allows processing to be resumed at any time. The tool was validated with 90 NCBI datasets from genera such as Escherichia coli, Corynebacterium, and Nocardia, as well as raw reads from the SRA database to simulate real-world situations. The results showed improvement in the contiguity of the assemblies, with an increase in N50 and improvement in L50, and a reduction in the number of contigs, by extending the contigs using the similarity between their flanks. In some cases, the software was able to elevate the status of genomes from draft to complete, proving its efficiency. ContigPolishing is available at: https://github.com/allanverasce/contigpolishing.

Laryngeal leukoplakia represents the most frequent precancerous lesion in laryngeal carcinogenesis, yet its transformation mechanisms remain elusive. By performing scRNA-seq on ten clinical specimens (five leukoplakia lesions across pathological stages, four early carcinomas, and one control), we established the first single-cell atlas of this malignant progression. Computational analysis revealed dynamic microenvironmental shifts dominated by epithelial cells, fibroblasts, and mononuclear phagocytes. We identified two critical epithelial subpopulations: Epi_4 (tumor-like cells), a high-grade dysplasia-specific subpopulation with high malignant potential, and Epi_5 (tumor cells) in carcinoma, which carries a favorable prognostic gene signature (Module 3). Furthermore, Epi_4 showed preferential communication with cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) via the JAG1-NOTCH4 and CXCL5-CXCR1 axes, suggesting actionable therapeutic targets. We also observed the progressive activation of genes involved in redox processes (NQO1, GSTM3, UCHL1, NTRK2) via the KEAP1-NRF2 pathway. This work systematically characterizes the cellular and molecular landscape during laryngeal leukoplakia malignant transformation, providing a framework for future mechanistic studies and early detection strategies.

Sepsis-induced cardiomyopathy (SICM) significantly contributes to sepsis-related mortality, yet its molecular mechanisms remain incompletely understood. Here, we identify cuproptosis-a copper-dependent mitochondrial cell death pathway-as a critical driver of SICM pathogenesis. In a murine SICM model induced by lipopolysaccharide (LPS), cardiac dysfunction was accompanied by myocardial copper accumulation and dysregulation of cuproptosis regulators. RNA sequencing (RNA-seq) analysis revealed cuproptosis as one of the top enriched pathways. Crucially, we demonstrate that the m7G methyltransferase Mettl1 functions as a cardioprotective factor. Mettl1 expression was upregulated in septic hearts and positively correlated with copper levels. In vitro, Mettl1 knockdown exacerbated LPS-induced cytotoxicity in cardiomyocytes and amplified intracellular copper overload. Mechanistically, Mettl1 deficiency potentiated LPS-triggered upregulation of FDX1-a key executor of cuproptosis-and suppressed PDHA1 expression. Our findings establish Mettl1 as a novel suppressor of cuproptosis that confers protection against sepsis-induced cardiotoxicity by restraining FDX1-mediated copper-dependent cell death. Targeting the Mettl1-FDX1 axis may offer a promising therapeutic strategy for SICM.

Pugionium cornutum is a biennial herb belonging to the Brassicaceae family and is an endemic species of the Mongolian Plateau, exhibiting strong stress tolerance and notable medicinal value. In this study, the PcHARBI1-5 gene was cloned from P. cornutum and functionally characterized through heterologous transformation in Arabidopsis thaliana. Transgenic overexpression lines (OE) and homologous knockout mutants (KO-1) were generated, and their phenotypic differences were systematically evaluated under controlled conditions. Overexpression of PcHARBI1-5 significantly promoted early flowering in Arabidopsis, with transgenic plants flowering approximately four days earlier than wild-type controls, whereas the KO-1 mutant exhibited a delay of about three days. Furthermore, transgenic lines displayed enhanced agronomic performance, including longer roots, increased plant height, greater lateral branching, elongated siliques, and higher seed yield per plant. Gene expression analysis revealed that PcHARBI1-5 modulates flowering time by down-regulating the floral repressor FLC and up-regulating key floral integrators FT and SOC1. Taken together, this study reports the successful cloning and functional validation of PcHARBI1-5 from P. cornutum, demonstrating its pivotal role in accelerating flowering and improving multiple agronomic traits. These findings highlight PcHARBI1-5 as a promising candidate gene for molecular breeding strategies aimed at developing early-maturing and high-yielding crop varieties.

China harbors rich indigenous goat resources. However, factors such as the introduction of exotic breeds and crossbreeding have led to a decline in local populations and obscured genetic structures. Consequently, it is imperative to conduct genetic diversity and population structure assessments of key indigenous goat populations. This study employed Super-GBS sequencing technology to evaluate genetic diversity and population structure in eight goat breeds (n = 211), and further identified candidate genes associated with production traits and environmental adaptation through selection signature analysis. Ziwuling black goat (ZWL) exhibited the highest diversity, whereas Dazu black goat (DZH) showed the lowest. Pairwise F revealed strong differentiation between DZH and Liaoning cashmere / Inner Mongolia cashmere goat (NMC) (0.1221) due to geographic isolation, but negligible divergence between Ziwuling cashmere (ZWLH) and Hexi cashmere (HXC) (0.0066), indicating gene flow. Population structure resolved three clades: DZH as an independent lineage, Yimeng black goat (YMH) clustering with ZWL, and multiple cashmere subgroups. Runs of homozygosity (ROH) revealed elevated inbreeding in DZH (F = 0.178) versus lower levels in cashmere breeds (0.071-0.098). Selective sweeps identified 252 genes linked to cashmere traits, including DCN, SEMA3D, FGF5, enriched in TGF-β, MAPK, and circadian rhythm pathways regulating hair follicle cycling. Comparative scans between arid-adapted NMC and subtropical DZH identified 372 genes (e.g., MTOR, ROBO2, PPP3CA) involved in thermogenesis, water reabsorption, and hypoxia response. Together, these findings highlight how artificial selection and environmental adaptation jointly shape goat genomic architecture. Conservation should prioritize populations with declining diversity (e.g., ZWLH, SXC) and implement controlled breeding to reduce inbreeding, thereby safeguarding agro-biodiversity and sustainable utilization.

Tooth agenesis (TA), one of the most common craniofacial developmental anomalies, is characterized by the congenital absence of one or more teeth. While numerous genes have been implicated in non-syndromic tooth agenesis (NSTA), its genetic architecture often remains complex. In this study, we investigated the genetic basis of NSTA in a two-generation Chinese family utilizing whole-exome sequencing (WES) complemented by Sanger sequencing. Our analysis revealed a complex segregation pattern of multiple variants. After systematic filtering based on pathogenicity predictions and minor allele frequency (MAF), we identified eight potential contributory variants. These include homozygous missense variants in EDAR (c.1109 T > C), GHR (c.1630A > C), and COL17A1 (c.629C > T), a heterozygous missense variant in CEP152 (c.161C > T), and DSP (c.5213G > A) and three rare heterozygous missense variants in CCDC154 (c.925C > T), FRAS1 (c.9628G > A), and NBAS (c.5095G > A). Notably, the variants in GHR, CCDC154, FRAS1, and NBAS represent potential novel candidate genes for NSTA, thereby expanding the variant spectrum associated with this condition. The co-segregation of these multi-locus variants suggests that inheritancemightbe complex, perhaps involving oligogenic mechanisms. Thispoints to the possibilityof intricate genetic interactions in tooth development, offering new clues about the molecular basis of familial NSTA.