Search Results (4,562)

Cadmium (Cd) is an environmental toxicant that poses significant risks to food safety and public health through its bioaccumulation in the food chain. The liver is a primary target for chronic Cd toxicity, yet the system-level mechanisms, particularly in physiologically relevant swine models, remain incompletely understood. This study employed an integrated multi-omics approach to elucidate the mechanisms of Cd-exposed hepatotoxicity in weaned piglets. We combined histopathological examination, transmission electron microscopy, and transcriptome sequencing. Our results revealed severe hepatic damage, characterized by disorganized architecture, vacuolar degeneration, mitochondrial dysfunction, and autophagic activation. Network toxicology predicted 3727 potential targets of Cd-exposed liver injury, while transcriptomics identified 1092 differentially expressed genes (DEGs). Crucially, the convergent analysis of both datasets demonstrated that the PI3K-Akt signaling pathway was the central hub, pinpointing it as a pivotal mechanism in Cd-driven hepatotoxicity. Functional enrichment analyses further highlighted dysregulation in immune-inflammatory responses, lipid metabolism, and oxidative stress. Our findings provide a comprehensive systems-level perspective on chronic Cd hepatotoxicity in a translational swine model. We propose the PI3K-Akt pathway and other identified core targets (EGFR, histones, ribosomal proteins) as critical biomarkers for monitoring Cd contamination in swine production chains, offering valuable insights for environmental risk assessment and agricultural product safety. Full article

Background: Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality. The prognostic significance and functional role of sodium overload-induced necrosis (a novel form of regulated cell death driven by disrupted sodium homeostasis, hereafter abbreviated as NECSO) in LUAD are largely unexplored. Methods: A prognostic model was constructed utilizing the NECSO key gene TRPM4 and analyzed through Cox, LASSO, and multivariate Cox regression analyses. LUAD patients were stratified into high- and low-risk groups. The model’s predictive performance was evaluated using time-dependent ROC curves and nomograms. Functional enrichment analysis elucidated underlying biological disparities. The tumor immune microenvironment was characterized using ESTIMATE, ssGSEA, CIBERSORTx, and TIDE algorithms, with results corrected for multiple testing. Drug sensitivity to chemotherapeutic and targeted agents was predicted. The functional role of a key gene, DENND1C, was validated in vitro. Its association with immunotherapy survival outcomes was assessed in a real-world cohort. Results: The NECSO-based prognostic signature demonstrated robust performance in risk stratification across training and independent validation cohorts. Patients in the high-risk group exhibited significantly shorter overall survival. Functional enrichment revealed associations with processes related to plasma membrane integrity, cell death, metabolism, and immune response. Multi-algorithm immunogenomic analyses consistently identified an immunosuppressive microenvironment in high-risk patients. The risk score was predictive of differential sensitivity to therapeutics, including taxanes and EGFR inhibitors. In vitro experiments confirmed DENND1C as a tumor suppressor, inhibiting LUAD cell proliferation, invasion, and migration. Furthermore, high DENND1C expression was associated with improved survival in patients receiving immunotherapy. Conclusions: This study establishes and validates a novel NECSO-based prognostic model for LUAD. DENND1C is identified as a key tumor suppressor and a potential biomarker for immunotherapy, offering insights for personalized treatment strategies in LUAD. Full article

Prader–Willi (PWS) and Angelman (AS) syndromes were the first examples in humans with errors in genomic imprinting, usually from de novo 15q11-q13 deletions of different parent origin (paternal in PWS and maternal in AS). Dozens of genes and transcripts are found in the 15q11-q13 region, and may play a role in PWS, specifically paternally expressed SNURF-SNRPN and MAGEL2 genes, while AS is due to the maternally expressed UBE3A gene. These three causative genes, including their encoding proteins, were targeted. This review article summarizes and illustrates the current understanding and cause of both PWS and AS using strategies to include the literature sources of key words and searchable web-based programs with databases for integrated gene and protein interactions, biological processes, and molecular mechanisms available for the two imprinting disorders. The SNURF-SNRPN gene is key in developing complex spliceosomal snRNP assemblies required for mRNA processing, cellular events, splicing, and binding required for detailed protein production and variation, neurodevelopment, immunodeficiency, and cell migration. The MAGEL2 gene is involved with the regulation of retrograde transport and promotion of endosomal assembly, oxytocin and reproduction, as well as circadian rhythm, transcriptional activity control, and appetite. The UBE3A gene encodes a key enzyme for the ubiquitin protein degradation system, apoptosis, tumor suppression, cell adhesion, and targeting proteins for degradation, autophagy, signaling pathways, and circadian rhythm. PWS is characterized early with infantile hypotonia, a poor suck, and failure to thrive with hypogenitalism/hypogonadism. Later, growth and other hormone deficiencies, developmental delays, and behavioral problems are noted with hyperphagia and morbid obesity, if not externally controlled. AS is characterized by seizures, lack of speech, severe learning disabilities, inappropriate laughter, and ataxia. This review captures the clinical presentation, natural history, causes with genetics, mechanisms, and description of established laboratory testing for genetic confirmation of each disorder. Three separate searchable web-based programs and databases that included information from the updated literature and other sources were used to identify and examine integrated genetic findings with predicted gene and protein interactions, molecular mechanisms and functions, biological processes, pathways, and gene-disease associations for candidate or causative genes per disorder. The natural history, review of pathophysiology, clinical presentation, genetics, and genetic-phenotypic findings were described along with computational biology, molecular mechanisms, genetic testing approaches, and status for each disorder, management and treatment options, clinical trial experiences, and future strategies. Conclusions and limitations were discussed to improve understanding, clinical care, genetics, diagnostic protocols, therapeutic agents, and genetic counseling for those with these genomic imprinting disorders. Full article

This study presents the complete sequencing and comparative genomic analysis of Leimania (Viannia) naiffi and Leishmania (Viannia) shawi, species of epidemiological relevance in the Brazilian Amazon. Genome assemblies yielded sizes of 32.13 Mb and 32.51 Mb, with 8170 and 7767 annotated genes, respectively. Predicted gene functions were primarily related to catalytic, binding, and ATP-dependent activities. Pangenome analysis revealed a core genome of 6256 genes alongside notable species-specific differences, including 46 and 25 unique genes in L. naiffi and L. shawi. Functional screening identified pharmacologically promising proteins such as calpains, ABC transporters, and notably, GSK-3. Ploidy analysis indicated tetraploidy on chromosome 8 in L. naiffi and chromosome 2 in L. shawi. Genetic variability assessment detected 34,480 SNPs in L. naiffi and 26,562 in L. shawi, indicating greater genomic diversity in the former. Phylogenetic inference based on the polA1 gene confirmed the placement of both species within the Leishmania (Viannia) subgenus. These findings advance Leishmania genomics knowledge by highlighting unique genetic signatures, regions of high variability, and potential therapeutic targets. This work establishes a foundation for future research on evolution, pathogenicity, and drug development for leishmaniasis. Full article

Background/Objectives: In severe peripheral artery disease (PAD) with limb ischemia, hypercholesterolemia (HC) is associated with impaired neovascularization. Extracellular vesicles (EVs) are present within ischemic muscles, and they contain microRNAs (miRs) involved in several biological functions, including angiogenesis and neovascularization. Methods: We used a mouse model of PAD and compared the response to hindlimb ischemia in hypercholesterolemic ApoE^−/− vs. normocholesterolemic mice. Next-generation sequencing (NGS) was used to perform full miR expression profiling in ischemic skeletal muscles and in EVs of varying sizes—large EVs (lEVs) and small EVs (sEVs)—within these muscles. Results: We identified several miRs with potential pro-angiogenic effects (angiomiRs) that are reduced by HC in lEVs (Let-7b-5p, miR-151-3p, Let-7c-5p) or sEVs (miR-21a-5p, miR-196b-5p, miR-340-5p). As proof of principle, we showed that the overexpression of Let-7b-5p in lEVs, or miR-21a-5p in sEVs, can significantly increase the angiogenic capacity of these EVs in vitro. HC also impaired the enrichment of specific angiomiRs in lEVs (miR-100-5p), sEVs (miR-142a-3p), or in both lEVs and sEVs (miR-146b-5p). In silico approaches, including the prediction of miR targets, pathway unions, and gene unions, identified the resulting predictive effects of HC-modulated miRs in EVs on processes with key roles in the modulation of angiogenesis and neovascularization, such as the regulation of the actin cytoskeleton and focal adhesion and the HIF-1, MAPK, AMPK, and PI3K-Akt signaling pathways. Conclusions: Our results constitute an important first step towards the identification of specific miRs that could be targeted to improve EV angiogenic function in hypercholesterolemic conditions and reduce tissue ischemia in patients with severe PAD. Full article

As a critically important global food crop, wheat has been increasingly threatened by the frequent occurrence of extreme high-temperature events, which impairs its growth and development, resulting in reduced seed-setting rate, compromised grain quality and diminished yield. Therefore, identifying heat-tolerant genes and enhancing thermotolerance through molecular breeding are essential strategies for wheat improvement. In this study, we retrieved spatial transcriptomic data from the public database PRJNA427246, which captured gene expression profiles in flag leaves and grains of the heat-sensitive wheat cultivar Chinese Spring (CS) under 37 °C heat stress at time points of 0 min, 5 min, 10 min, 30 min, 1 h, and 4 h. Weighted Gene Co-expression Network Analysis (WGCNA) was used to construct co-expression networks for flag leaf and grain transcriptomes. One highly significant module was identified in each tissue, along with 35 hub genes that showed a strong temporal association with heat stress progression. Notably, both modules contained the previously characterized thermotolerance gene TaMBF1c, suggesting that additional heat-responsive genes may be present within these modules. Simultaneous analysis of the expression data from four groups (encompassing different tissues and high-temperature treatments) for the 35 core genes revealed that genes from the TaHSP20 family, TaMBF1c family, and other related genes exhibit coordinated expression patterns in terms of the temporal dynamics and tissue distribution of stress responses. Additionally, 27 genes of the small heat shock protein (HSP20) family are predicted to be involved in the endoplasmic reticulum-associated degradation (ERAD) pathway. They assist in clearing misfolded proteins induced by stress, thereby helping to maintain endoplasmic reticulum homeostasis and cellular functions under stress conditions. Finally, the expression levels of three core genes, TaHSP20-1, TaPCDP4, and TaMBF1c-D, were validated by qRT-PCR in two wheat cultivars with distinct thermotolerance: S116 (Zhehuamai 2008) and S128 (Yangmai 33). These findings provide new insights into the molecular mechanisms underlying heat tolerance in wheat and offer valuable genetic resources for breeding thermotolerant varieties. Full article

Background: In plants, members of the MADS-box gene family encode transcription factors that regulate a wide range of developmental processes, including cell differentiation, organ identity, floral induction, and responses to environmental stimuli. Moreover, MADS-box genes play central roles in the well-known ABCDE model of floral development. Teak (Tectona grandis), a woody species belonging to the Lamiaceae family, is recognized for its medicinal and agricultural significance. The recent availability of a chromosome-level genome assembly for T. grandis has enabled the genome-wide identification of 87 MADS-box genes, which are distributed across 18 pseudo-chromosomes. Methods: The amino acid sequences of these genes were compared with orthologous proteins from Arabidopsis thaliana, Sesamum indicum, and Amborella trichopoda to infer the phylogenetic relationships. The structures of key floral quartets in the MADS-box proteins were predicted, and the stability of these predicted tetramers were analyzed via molecular dynamics simulations. Results: The phylogenetic analysis classified the genes into 33 Type I and 54 Type II MADS-box members, forming four major clades (MIKC^C, MIKC*, Mα, and Mγ), while the Mβ-type clade was absent. A conserved motif analysis revealed that the Type II genes exhibited greater motif diversity than the Type I, suggesting that T. grandis Type II MADS-box genes possess more complex structures and potentially broader functions. The transcriptomic data from different tissues showed that the MIKC-type genes were particularly active during flower development. Although stable over the simulation time, the T. grandis AP3 ortholog had shorter I and K domains and had an odd mode of protein–protein interaction. Conclusion: Overall, the presented genome-wide analysis provides a comprehensive base for understanding the evolutionary diversification of the MADS-box gene family in T. grandis and identifies candidate genes for future structural and functional characterization. Full article

This study investigates whether fecal microbiota transplantation (FMT) can alleviate gut microbiota dysbiosis induced by a high-fat diet (HFD) through modulation of fatty acid metabolism, competition for nutrients, production of short-chain fatty acids (SCFAs), and restoration of mucus layer integrity. To elucidate the mechanisms by which FMT regulates colonic microbial function and host metabolic responses, 80 male Bal b/c mice were randomly assigned to four experimental groups (n = 20 per group): Normal Diet Group (NDG), High-Fat Diet Group (HDG), Restrictive Diet Group (RDG), and HDG recipients of NDG-derived fecal microbiota (FMT group). The intervention lasted for 12 weeks, during which body weight was monitored biweekly. At the end of the experiment, tissue and fecal samples were collected to assess digestive enzyme activities, intestinal histomorphology, gene expression related to gut barrier function, and gut microbiota composition via 16S rRNA gene sequencing. Results showed that mice in the HDG exhibited significantly higher final body weight and greater weight gain compared to those in the NDG and RDG (p < 0.05). Notably, FMT treatment markedly attenuated HFD-induced weight gain (p < 0.05), reducing it to levels comparable with the NDG (p > 0.05). While HFD significantly elevated the activities of α-amylase and trypsin (p < 0.05), FMT supplementation effectively suppressed these enzymatic activities (p < 0.05). Moreover, FMT ameliorated HFD-induced intestinal architectural damage, as evidenced by significant increases in villus height and the villus height-to-crypt depth ratio (V/C) (p < 0.05). At the molecular level, FMT significantly downregulated the expression of pro-inflammatory cytokines (IL-1β, IL-1α, TNF-α) and upregulated key tight junction proteins (Occludin, Claudin-1, ZO-1) and mucin-2 (MUC2) relative to the HDG (p < 0.05). 16S rRNA analysis demonstrated that FMT substantially increased the abundance of beneficial genera such as Lactobacillus and Bifidobacterium while reducing opportunistic pathogens including Romboutsia (p < 0.05). Furthermore, alpha diversity indices (Chao1 and ACE) were significantly higher in the FMT group than in all other groups (p < 0.05), indicating enhanced microbial richness and community stability. Functional prediction using PICRUSt2 revealed that FMT-enriched metabolic pathways (particularly those associated with SCFA production) and enhanced gut barrier-related functions. Collectively, this study deepens our understanding of host–microbe interactions under HFD-induced metabolic stress and provides mechanistic insights into how FMT restores gut homeostasis, highlighting its potential as a therapeutic strategy for diet-induced dysbiosis and associated metabolic disorders. Full article

Background: Hydroxycinnamoyl-CoA quinate hydroxycinnamoyl-transferase (HQT) is an essential enzyme for chlorogenic acid (CGA) biosynthesis in plants. Multiple HQT-encoding genes potentially involved in CGA synthesis in sweet potato (Ipomoea batatas) have been predicted. However, the functions of these genes have not been verified. Methods: In this study, the gene IbHQT1 was isolated from the sweet potato cultivar ‘Nanshu-88’ and functionally characterized using transgenic technology. Results: IbHQT1 encodes a protein comprising 431 amino acids, with conserved HXXXD and DFGWG motifs characteristic of BAHD acyltransferase family members. A phylogenetic analysis indicated that IbHQT1 has a close evolutionary relationship with StHQT in Solanum tuberosum. According to qPCR data, IbHQT1 is highly expressed in young leaves, and its expression is affected by exogenous MeJA (100 µM), ABA (100 µM), GA₃ (50 µM), and SA (100 µM). Analyses of cis-acting regulatory elements indicated that the IbHQT1 promoter contains multiple elements responsive to MeJA, ABA, SA, GA₃, and light. In plants overexpressing IbHQT1, CGA contents in mature leaves and storage roots increased 1.30- to 1.44-fold and 1.28- to 1.43-fold, respectively. Conversely, in IbHQT1-RNAi lines, CGA contents in mature leaves and storage roots decreased by 16–38% and 18–40%, respectively. Conclusions: These findings indicate that IbHQT1 positively regulates CGA biosynthesis in sweet potato plants. Full article

Background: Triple-negative breast cancers (TNBCs) are among the most aggressive breast tumors, due not only to the absence of clinically functional biomarkers used in other molecular subtypes, but also their marked heterogeneity and pronounced migratory and invasive behavior. The search for new molecules of interest for risk prediction, diagnosis and therapy stems from the class of long non-coding RNAs (lncRNAs), which often display context-dependent (“dual”) functions and tissue specificity. Among them, lncRNA LINC01133 stands out for its dysregulation across cancer, although its molecular role in TNBC remains unclear. Methods: In the present study, we used the human TNBC cell line Hs578T to generate a cell panel comprising the parental line (Hs578T_wt), the control line (Hs578T_ctr), and the LINC01133 knockout line (Hs578T_ko). Subsequently, we performed bulk RNA-Seq to identify KO-associated Differentially Expressed Genes (DEGs) using ko_vs_ctr as the primary contrast. Functional interpretation was achieved by Over-Representation Analysis (ORA) using Gene Ontology. We then conducted a comparative patient-cohort analysis using TCGA-BRCA Basal-like/TNBC cases (TCGA/BRCA n = 1098; Basal-like/TNBC n = 199), classified with the AIMS algorithm, and evaluated concordance between KO-associated signatures and patient tumor expression patterns via trend-based analyses across the LINC01133 expression levels and associated genes. Results: A total of 265 KO-dominant DEGs were identified in Hs578T_ko, reflecting transcriptional changes consistent with tumor progression, with enrichment of pathways associated with LINC01133 knockout including cell adhesion, cell–cell interactions, epithelial–mesenchymal transition (EMT), and extracellular matrix (ECM) remodeling. The main DEGs included ITIH5, GLUL, CACNB2, PDX1, ASPN, PTGER3, MFAP4, PI15, EPHB6, and CPA3 with additional candidates, such as KAZN and the lncRNA gene SSC4D, which have been implicated in migration/invasion, ECM remodeling, or signaling across multiple tumor contexts. Translational analyses in TCGA-BRCA basal-like tumors suggested a descriptive association in which lower LINC01133 levels were accompanied by shifts in the expression trends of genes linked to ECM/EMT programs and modulation of genes related to cell adhesion and protease inhibition. Conclusions: These results suggest a transcriptional model in which LINC01133 is associated with TNBC-related gene expression programs in a concentration-dependent manner, with loss of LINC01133 being associated with a transcriptomic shift toward pro-migratory/ECM remodeling signatures. While functional validation is required to establish causality, these data support LINC01133 as a molecule of interest in breast cancer research. Full article

Microplastics (MPs) can serve as bearers of microorganisms and additional contaminants. However, the functional composition and assembly processes of plastisphere bacteria in co-contaminated soil–plant systems are not yet well understood. Using a pot experiment, we examined the effects of both individual and combined cadmium (Cd) and polypropylene (PP) MP contamination on the development of the bioenergy plant sorghum. The bacterial community, co-occurrence networks, and assembly processes in the rhizosphere soil and PP plastisphere were investigated using high-throughput sequencing. Compared with contamination by a single compound, combined contamination with Cd and PP had a more potent inhibitory effect on the development of sorghum. PCoA and diversity indices indicate that the bacterial community on PP plastics is structurally simpler than that in rhizosphere soil. The PP plastisphere could recruit bacteria from the genera Sphingomonas, Rhizobium, and Bacillus. The bacterial communities in the soil and the PP plastisphere were mostly formed by stochastic processes, with diffusion limitation playing a greater role in the bacterial community in the PP plastisphere. Co-occurrence network analysis revealed differences between the bacterial communities in the soil and in the PP plastisphere, with the network in the PP plastisphere showing lower complexity and connectivity. Functional prediction revealed that the prevalence of nitrogen cycling genes was greater in the PP plastisphere than in the dirt and that the PP plastisphere presented greater metabolic activity. The relative prevalence of metabolic pathways associated with human diseases was markedly elevated in the PP plastisphere, which may be correlated with the dissemination of pathogenic microorganisms. These findings indicate that the PP plastisphere, as a distinct microbial niche, might attract certain bacteria, consequently affecting the functional characteristics of cocontaminated soil–plant systems. Full article

Dentathalia scutellariae (Hymenoptera: Athaliidae) is a major pest of Scutellaria baicalensis, a plant of significant economic and medicinal value. To date, no genomic resources have been available for this species, limiting research into its biology and control. Here, we reported a genome assembly of D. scutellariae with high accuracy and contiguity, sequenced by PacBio HiFi long-read and MGI-Seq short-read methods. The genome assembly is 157.00 Mb in length with a contig N50 of 4.04 Mb. The complete BUSCO score was 98.8%. The genome contained 14.73 Mb of repetitive elements, representing 9.38% of the total genome size. We predicted 14,904 protein-coding genes, of which 12,327 genes were annotated functionally. Gene family analysis of D. scutellariae revealed 422 expanded and 113 contracted gene families. Notably, genes within expanded families were significantly enriched in retinol metabolism and drug metabolism–cytochrome P450 pathways. We present the first high-quality genome assembly of D. scutellariae, which serves as a foundational genomic resource. This dataset will facilitate future studies on the molecular basis of D. scutellariae’s pest status, host adaptation, and the development of targeted control strategies. Full article

Non-AIDS-defining cancers (NADCs) have emerged as an increasingly prominent cause of non-AIDS-related morbidity and mortality among people living with HIV (PLWH). However, the scarcity of NADC clinical samples, compounded by privacy and security constraints, continues to present formidable obstacles to advancing pathological and clinical investigations. In this study, we adopted a joint analysis strategy and deeply integrated and analyzed transcriptomic data from 12,486 PLWH and cancer patients to systematically identify potential key regulators for 23 NADCs. This effort culminated in NADCdb—a database specifically engineered for NADC pathological exploration, structured around three mechanistic frameworks rooted in the interplay of immunosuppression, chronic inflammation, carcinogenic viral infections, and HIV-derived oncogenic pathways. The “rNADC” module performed risk assessment by prioritizing genes with aberrant expression trajectories, deploying bidirectional stepwise regression coupled with logistic modeling to stratify the risks for 21 NADCs. The “dNADC” module, synergized patients’ dysregulated genes with their regulatory networks, using Random Forest (RF) and Conditional Inference Trees (CITs) to identify pathogenic drivers of NADCs, with an accuracy exceeding 75% (in the external validation cohort, the prediction accuracy of the HIV-associated clear cell renal cell carcinoma model exceeded 90%). Meanwhile, “iPredict” identified 1905 key immune biomarkers for 16 NADCs based on the distinct immune statuses of patients. Importantly, we conducted multi-dimensional profiling of these key determinants, including in-depth functional annotations, phenotype correlations, protein–protein interaction (PPI) networks, TF-miRNA-target regulatory networks, and drug prediction, to deeply dissect their mechanistic roles in NADC pathogenesis. In summary, NADCdb serves as a novel, centralized resource that integrates data and provides analytical frameworks, offering fresh perspectives and a valuable platform for the scientific exploration of NADCs. Full article

Liver fibrosis induced by Schistosoma japonicum Katsurada, 1904 (S. japonicum) infection lacks effective diagnostic markers and specific anti-fibrotic therapies. Although dysregulated iron homeostasis and ferroptosis pathways may contribute to its pathogenesis, the core regulatory mechanisms remain elusive. To unravel the ferroptosis-related molecular features, this study integrated transcriptomic datasets (GSE25713 and GSE59276) from S. japonicum-infected mouse livers. Following batch effect correction and normalization, ferroptosis-related differentially expressed genes (FRDEGs) were identified. Subsequently, core hub genes were screened through the construction of a protein–protein interaction (PPI) network, functional enrichment analysis, immune infiltration evaluation, and receiver operating characteristic (ROC) analysis. The expression patterns of these hub genes were further validated in an S. japonicum-infected mouse model using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The study identified 7 hub genes (Lcn2, Timp1, Cth, Cp, Hmox1, Cbs, and Gclc) as key regulatory molecules. Functional enrichment analysis revealed that these hub genes are closely associated with sulfur amino acid metabolism and oxidative stress responses. Specifically, key enzymes involved in cysteine and glutathione (GSH) synthesis (Cth, Cbs, Gclc) were consistently downregulated, suggesting a severe impairment of the host antioxidant defense capacity. Conversely, pro-fibrotic and pro-inflammatory markers (Timp1, Lcn2, Hmox1) were upregulated. This molecular pattern was significantly associated with a remodeled immune microenvironment, characterized by increased infiltration of neutrophils and eosinophils. In vivo validation confirmed the expression trends of 6 hub genes, corroborating the bioinformatics predictions, while the discrepancy in Cp expression highlighted the complexity of post-transcriptional regulation in vivo. The identified hub genes demonstrated excellent diagnostic potential, with Timp1 achieving an area under the curve (AUC) of 1.000. This study elucidates the molecular link between S. japonicum infection and the ferroptosis pathway, suggesting that these hub genes may drive liver fibrosis progression by regulating sulfur metabolism and the immune microenvironment. These findings offer potential diagnostic biomarkers and novel therapeutic targets for schistosomal liver fibrosis. Full article

The placenta is often described as the “window to the brain” due to its crucial role in fetal neurological development. In this study, we investigated a family where the older male offspring exhibited severe neurodevelopmental and mild motor coordination disorders. His brother displayed emotional and behavioral dysregulation along with mild motor coordination disorders. The father was asymptomatic, while the mother and daughter showed mild learning disabilities. Whole exome sequencing (WES) identified a disruptive X-linked pathogenic variant, c.1088_1089del p.Asp363GlyfsTer2, within the calpain-6 (CAPN6) gene. We have submitted this variant to the ClinVar database (RCV005234146.2). The variant was found in hemizygous condition in the affected male offspring and in heterozygous condition in both the mother and daughter. As predicted, the variant undergoes nonsense-mediated mRNA decay (NMD), preventing the translation of the CAPN6 gene into a functional protein. CAPN6 is a critical gene predominantly expressed in placental and trophoblast tissues. Although its function is not well characterized, CAPN6 is also expressed in several regions of the developing brain. Recent studies have shown that genetic variants in CAPN6 significantly influence vascular endothelial growth factor (VEGF) activity, thereby affecting angiogenesis and the blood supply essential for fetal growth and development. Although CAPN6 lacks an MIM phenotype code, we hypothesize that it might be enumerated as a novel candidate gene contributing to neurodevelopmental disorders. Functional studies are imperative to elucidate the role of CAPN6 in placental function and its potential implications for neurodevelopmental processes. This work aims to inspire further research into the role of CAPN6 in placental biology and its relevance to neurodevelopmental disorders. Full article