Search Results (1,933)

Medical artificial intelligence (AI) systems depend heavily on high-quality data representations to support accurate prediction, diagnosis, and clinical decision-making. However, the availability of large, well-annotated medical datasets is often constrained by cost, privacy concerns, and the need for expert labeling, motivating growing interest in self-supervised representation learning. Among these approaches, contrastive learning has emerged as one of the most influential paradigms, driving major advances in representation learning across computer vision and natural language processing. This paper presents a comprehensive review of contrastive learning in medical AI, highlighting its theoretical foundations, methodological developments, and practical applications in medical imaging, electronic health records, physiological signal analysis, and genomics. Furthermore, we identify recurring challenges, including pair construction, sensitivity to data augmentations, and inconsistencies in evaluation protocols, while discussing emerging trends such as multimodal alignment, federated learning, and privacy-preserving frameworks. Through a synthesis of current developments and open research directions, this review provides insights to advance data-efficient, reliable, and generalizable medical AI systems. Full article

Objectives: To characterize the prenatal phenotypic spectrum, genetic findings, and pregnancy outcomes of fetal renal agenesis (RA), and to clarify the complementary roles of chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in phenotype-stratified prenatal evaluation. Methods: This retrospective study included 203 RA fetuses between March 2017 and November 2025. All cases underwent genome-wide copy number variant (CNV) analysis, and selected cases underwent WES. Detection rates were compared across subgroups by laterality, isolated vs. non-isolated phenotype, fetal sex, and presence of extrarenal anomalies. Pregnancy outcomes and postnatal imaging follow-up were collected when available. A systematic literature review of prenatal genetic testing in RA fetuses was performed. Results: Among 203 fetuses, unilateral RA accounted for 92.6% of cases, and 65.0% were isolated. Chromosomal abnormalities were identified in 15 fetuses (7.4%), including aneuploidies and pathogenic or likely pathogenic (P/LP) CNVs. WES identified P/LP single nucleotide variants in 8 of 127 cases (6.3%), increasing to 8.7% when variants with potential clinical relevance were included. Diagnostic yield of WES was significantly higher in bilateral RA, non-isolated cases, and fetuses with extrarenal anomalies. Postnatal follow-up confirmed RA in most liveborn cases, although additional phenotypes emerged in some children. Literature synthesis identified recurrent CNVs at 16p11.2 and 22q11.21 and frequent involvement of FRAS1, FREM2, GFRA1, and GREB1L. Conclusions: RA shows marked phenotypic and genetic heterogeneity. CMA remains a first-tier prenatal test, while WES provides substantial incremental yield in bilateral, non-isolated, or extrarenal-associated RA. Integrated, phenotype-driven testing with longitudinal follow-up supports improved prognostication and genetic counseling. Full article

Type 1 diabetes mellitus (T1D) is a common autoimmune disease during childhood with a substantial genetic component. Individual genome-wide association studies (GWAS) often have limited power and are predominantly based on European-ancestry populations. To provide a more robust synthesis of genetic associations, we conducted a meta-analysis using summary-level GWAS data from three independent pediatric T1D studies obtained from the NHGRI-EBI GWAS Catalog. Harmonized single-nucleotide polymorphisms (SNPs) shared across all datasets were analyzed using inverse-variance weighted fixed-effects and random-effects models, with between-study heterogeneity assessed using Cochran’s Q test and the $I^2$ statistic. Of the 4,297,702 million common SNPs analyzed, 3524 reached genome-wide significance ($p<5\times {10}^{-8}$), demonstrating strong and consistent associations with T1D risk. The most prominent signals clustered on chromosome 6, consistent with known immune-related loci, and included both risk-increasing and protective variants, in agreement with prior biological findings. Heterogeneity across studies was minimal, with $I^2$ values near $0\%$ for nearly all SNPs. These findings highlight robust and reproducible SNP-level associations with pediatric T1D, providing an updated foundation for functional follow-up and translational studies. Full article

Background: Sheep (Ovis aries) tail fat serves as a crucial energy reserve for adapting to harsh environments. However, excessive deposition can reduce farming efficiency and product quality. Elucidating the regulatory mechanisms of tail fat deposition is of great significance for genetic improvement in sheep. Methods: In this study, transcriptome sequencing was conducted on tail fat tissues from fat-tailed Kazakh sheep (KAZ), thin-tailed Suffolk sheep (SFK), and their F2 hybrid sheep (CSH) (3 individuals per group). Subsequently, qRT-PCR validation, Enrichr, and KEGG database analyses were performed to investigate the molecular pathways involved in tail fat deposition. Results: High-quality clean reads were obtained from sequencing, with a genome alignment rate ranging from 76.15% to 79.43% and good data reproducibility. Differential expression analysis revealed multiple differentially expressed genes (DEGs) between KAZ and CSH groups, KAZ and SFK groups, as well as SFK and CSH groups. Five core candidate genes (BDH1, EPHX1, BCAT2, FASN, ACACA) were identified, all enriched in the fatty acid synthesis pathway and highly expressed in fat-tailed sheep, which was confirmed by qRT-PCR. Additionally, 189 lncRNAs were identified to collectively regulate target genes (e.g., FABP family, AGPAT2), along with three common differentially expressed miRNAs (novel_120, novel_171, novel_440) targeting genes enriched in lipid transport and lipid droplet formation pathways. Conclusions: This study confirms that the lncRNA-mRNA-miRNA regulatory axis is a key pathway in tail fat formation, providing important theoretical support and molecular targets for genetic improvement of ovine tail fat deposition traits. Full article

Fetal hemoglobin (HbF) plays a central role in mitigating the pathophysiological effects of sickle cell disease (SCD). Understanding the genetic determinants influencing HbF expression is essential for identifying the factors contributing to its modulation. This review provides an updated synthesis of evidence on HbF modulation, focusing on β^s haplotypes and their molecular characterization through Sanger sequencing, polymorphisms consistently associated with HbF levels in genome-wide association studies (GWAS), and recent advances in gene editing targeting HbF expression. An integrative review (2016–2025) was conducted using PubMed/MEDLINE, Scopus, and Web of Science, encompassing original research, experimental studies, systematic reviews, and genomic analyses. Key regulatory loci such as BCL11A, HBS1L-MYB (HMIP), and the HBB cluster explain a significant proportion of HbF variability across populations. Furthermore, additional variants in KLF1, NFIX, BACH2, and ZBTB7A have emerged as potential modulators in specific cohorts. Regarding advances in γ-globin editing, “prime editing”, although still in the experimental phase, has recently emerged as an innovative approach capable of introducing multiple HPFH-like mutations within γ-globin promoters, expanding future therapeutic possibilities in SCD. This review also provides a comparative overview of prime editing and other gene-editing strategies for HbF modulation, such as CRISPR-Cas9 and Base editing. Collectively, this work outlines the current landscape of HbF modulation and provides an informative basis for future research aimed at advancing precision-oriented therapeutic strategies in sickle cell disease. Full article

The rise in antimicrobial resistance (AMR) among the most clinically significant bacteria presents a global threat. The coexistence of resistance mechanisms to both carbapenems and colistin is particularly concerning, as these are last-line treatments, specifically reserved for the most challenging infections caused by clinically multidrug-resistant Enterobacterales. Natural aquatic environments have become environmental reservoirs for the transmission of AMR, particularly concerning mechanisms against these two types of critically important drugs. The crucial role of environmental settings as a driving force for the spread and evolution of AMR associated with these drugs is underestimated, and scientific knowledge on this topic is limited. This review aims to fill an important gap in the scientific literature and comprehensively consolidate the available data on carbapenem- and colistin-associated AMR in the aquatic environment. This study provides a comprehensive synthesis of the current knowledge by integrating bibliographic data with a detailed genomic analysis of 278 bacterial genomes sourced from natural waters. It explores the distribution of carbapenemase and mobile colistin resistance (mcr) genes, identifying their hosts, geographical spread, and complex gene–plasmid–host associations. This review distinguishes two critical host groups for genes that provide resistance to last-resort drugs, Enterobacterales and autochthonous aquatic microbiota, highlighting both confirmed and potential interactions between them. Crucially, genomic analysis highlights the alarming co-occurrence of carbapenem and colistin resistance in single cells and on single plasmids, contributing to the spread of multidrug resistance phenotypes. These findings clearly indicate that aquatic environments are not merely passive recipients but active, evolving hubs for high-risk AMR determinants. Future research should focus on the interplay between allochthonous vectors and autochthonous microbiota to better understand the long-term stabilization of carbapenemase and mcr genes. Such efforts, combined with advanced sequencing technologies, are essential to ensure that carbapenems and colistin remain viable treatment options in clinical settings. Full article

Microplastics (MPs) are pervasive environmental pollutants, widely distributed from aquatic ecosystems to the terrestrial food chain, and represent a potential route of human exposure. Although several reviews have addressed MP contamination, a critical synthesis focusing on pathways through which consumer goods directly enter food and beverages, along with corresponding industry and regulatory responses, is lacking. This review fills this gap by proposing the direct release of MPs from common sources such as food packaging, kitchen utensils, and household appliances, linking the release mechanisms to human health risks. The release mechanisms of MPs under thermal stress, mechanical abrasion, chemical leaching, and environmental factors, as well as a risk-driven framework for MP release, are summarized. Human exposure through ingestion is the predominant route, while inhalation and dermal contact are additional pathways. In vitro and animal studies have associated MP exposure to inflammatory responses and oxidative stress, neurotoxicity, and genomic instability as endpoints, though direct causal evidence in humans remains lacking, and extrapolation from model systems necessitates caution. This review revealed that dietary intake from kitchen sources is the primary pathway for MP exposure, higher than the inhalation pathway. Most importantly, this review critically sheds light on the initiatives that should be taken by industries with respect to global strategies and new policies to alleviate these challenges. However, while there has been an upsurge in research commenced in this area, there are still research gaps that need to be addressed to explore food matrices such as dairy products, meat, and wine in the context of the supply chain. In conclusion, we pointed out the challenges that limit this research with the aim of improving standardization; research approaches and a risk assessment framework to protect health; and the key differences between MP and nanoplastic (NP) detection, toxicity, and regulatory strategies, underscoring the need for size-resolved risk assessments. Full article

Alkane is a predominant wax component, whose production requires the aids of CER1 and CER3. In rice, OsCER1 and OsCER3 are present in multiple copies. Until now, the roles of these genes have been studied individually; however, a systematic comparison of their relative contributions to cuticular wax biosynthesis has not yet been carried out. Phylogenetic tree analysis revealed that CER1s and CER3s from different plants are classified into two subgroups. RT-qPCR analysis showed that these genes display distinct expression patterns, revealing their specific roles in wax production. Promoter prediction analysis showed that cis-elements responding to light, phytohormones and stress are enriched in the promoter region of OsCER1s and OsCER3s. These proteins are all localized in the endoplasmic reticulum. Further study showed that OsCER1s and OsCER3s are inclined to form a complex during the wax synthesis. Finally, the wax analysis of single mutants showed that among the examined genes, OsCER3a mutation greatly reduced the total wax amounts to 19.6% of wild-type plant with a decrease in most of wax components, whereas mutation of other genes including OsCER3b, OsCER3c, OsCER1a and OsCER1c slightly or barely affect wax production, suggesting that OsCER3a plays major roles in rice wax production whereas other proteins redundantly participate in the wax synthesis. Additionally, the wax increasing rates of Arabidopsis expressing OSCER1 are lower than those of overexpressing AtCER1. Taken together, our study identified the predominant genes involved in wax production, which will be useful for genetically engineering rice with enhanced stress tolerance. Full article

Ergot alkaloids derived from lysergic acid have impacted humankind significantly as toxins in agriculture and as the foundations of several pharmaceuticals. Few fungi capable of producing lysergic acid derivatives have been found outside the family Clavicipitaceae. Based on its phylogenetic placement, we hypothesized the recently described fungus Aspergillus aspearensis (Aspergillaceae) would synthesize lysergic acid amides. Cultures of A. aspearensis produced abundant lysergic acid α-hydroxyethylamide (LAH) and lesser amounts of other lysergic acid derivatives. Conidia contained high concentrations of ergot alkaloids, whereas sclerotia contained significantly less. Approximately half of the ergot alkaloids produced were secreted into the culture medium. When spores of A. aspearensis were injected into larvae of the model insect Galleria mellonella, larvae died at a significantly faster rate than control larvae. The fungus produced ergot alkaloids during insect pathogenesis and later produced conidia and sclerotia on cadavers, indicating it can complete its life cycle in an insect. The genome of A. aspearensis contained two complete ergot alkaloid synthesis gene clusters, similar to those of A. leporis; however, unlike its sister species, none of the ergot cluster genes were pseudogenized. Aspergillus aspearensis is a newly discovered source of ergot alkaloids and may be useful for studying and producing these important chemicals. Full article

Mutations in TP53 inhibit p53 protective behaviors including cell cycle arrest, DNA damage repair protein recruitment, and apoptosis. The ubiquity of p53 in genome-stabilizing functions leads to an aberrant tumor microenvironment in TP53-mutated myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Profound immunosuppression mediated by myeloid-derived suppressor cells, the upregulation of cytokines and cell-surface receptors on leukemic cells, the suppression of native immune regulator cells, and metabolic aberrations in the bone marrow are features of the TP53-mutated AML/MDS marrow microenvironment. These localized changes in the bone marrow microenvironment (BMME) explain why traditional therapies for MDS/AML, including chemotherapeutics and hypomethylating agents, are not as effective in TP53-mutated myeloid neoplasms and demonstrate the dire need for new treatments in this patient population. The unique pathophysiology of TP53-mutated disease also provides new therapeutic approaches which are being studied, including intracellular targets (MDM2, p53), cell-surface protein biologics (immune checkpoint inhibitors, BiTE therapy, and antibody–drug conjugates), cell therapies (CAR-T, NK-cell), signal transduction pathways (Hedgehog, Wnt, NF-κB, CCRL2, and HIF-1α), and co-opted biologic pathways (cholesterol synthesis and glycolysis). In this review, we will discuss the pathophysiologic anomalies of the tumor microenvironment in TP53-mutant MDS/AML, the hypothesized mechanisms of chemoresistance it imparts, and how novel therapies are leveraging diverse therapeutic targets to address this critical area of need. Full article

Leaves are the primary photosynthetic organs, and alterations in leaf color can affect photosynthesis and plant biomass. In an EMS-mutagenized SN9816 population, we identified two white-striped mutants, ws21-1 and ws21-2. Both mutants showed severely reduced pigment content, defective chloroplasts, and elevated reactive oxygen species. The ws21-2 allele caused a near-complete albino phenotype, while ws21-1 resulted in milder striping. Genetic mapping and cloning identified causal mutations in OsRNRS1, encoding the small subunit of ribonucleotide reductase. The G583R (ws21-1) and Y365F (ws21-2) mutations likely impair enzyme activity, disrupting the dNTP pool for plastid genome replication and causing aberrant chloroplast development. Correspondingly, the expression of genes for chlorophyll synthesis, photosynthesis, and ROS metabolism was altered. Our findings directly link nuclear-encoded nucleotide metabolism to chloroplast biogenesis and demonstrate that dNTP homeostasis is critical for maintaining photosynthetic capacity and redox balance in plants. Full article

Currently, the differences in the responses of the organic acid metabolism in rapeseed (Brassica napus L.) roots to saline and alkaline stresses are still unknown. To clarify the differences, different saline (100 (LS) and 200 (HS) mmol/L NaCl) and alkaline (20 (LA) and 40 (HA) mmol/L Na₂CO₃) treatments were applied to rapeseed. Then, targeted metabolomics was used to quantitatively analyze the changes in organic acid metabolism in the root system. The results showed that compared with the control group without stress (CK), 21, 18, 27, and 20 differentially accumulated organic acid metabolites were detected in the rapeseed roots under LS, HS, LA, and HA, respectively. In addition, 26, 6, 34, and 14 differentially accumulated organic acids were detected in the rapeseed root exudates under LS, HS, LA, and HA, respectively. Based on the activities of key enzymes related to the tricarboxylic acid cycle (TCA), antioxidant enzyme activities, organic acid metabolism, and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis in rapeseed roots, rapeseed mainly resisted saline and alkaline stresses by increasing organic acid synthesis and scavenging reactive oxygen species. Specifically, rapeseed resisted saline stress mainly by increasing the secretion of TCA cycle-related organic acids such as succinic acid, L-malic acid, fumaric acid, and cis-aconitic acid. In addition to secreting organic acids, rapeseed also resisted alkaline stress by increasing the secretion of phenolic acids such as 4-hydroxybenzoic acid, ferulic acid, and 4-coumaric acid. Notably, the number of secreted organic acid types and the increase in organic acid content under alkaline stress were higher than those under saline stress. The results of this study provide an important basis for the breeding of saline and alkaline stress-tolerant rapeseed varieties. Full article

Background/objectives: Metabolomics has emerged as a powerful systems-biology tool for deciphering dynamic metabolic alterations occurring during infectious diseases and following vaccination. While genomics and proteomics provide extensive molecular and regulatory information, metabolomics uniquely reflects the biochemical phenotype associated with infection, immune activation, and immunometabolic reprogramming. The objective of this review is to provide an integrated analysis of metabolomics applications across both neglected tropical diseases (NTDs) and non-NTD pathogens, highlighting its dual role in biomarker discovery and vaccine response evaluation. Methods: A comprehensive literature-based synthesis was conducted to examine metabolomic studies in infectious diseases and vaccinology. Metabolic perturbations associated with specific pathogens, as well as vaccine-induced metabolic changes and correlates of immune responses, were systematically analyzed and compared across NTD and non-NTD contexts. Results: Distinct pathogen- and vaccine-associated metabolic signatures were identified, reflecting alterations in glycolysis, amino acid metabolism, lipid remodeling, and immunoregulatory pathways. Comparative analysis revealed both shared and disease-specific metabolic biomarkers across NTDs and non-NTD infections. Importantly, vaccine-related metabolic correlates were shown to mirror immune activation states and, in some cases, predict immunogenicity and response durability. Conclusions: This review bridges metabolomics research in infectious disease pathogenesis and vaccine immunology across the NTD and non-NTD spectrum. By integrating these domains, it introduces the concept of “metabolic immuno-signatures” as predictive and translational tools for evaluating vaccine efficacy and immune response outcomes. Full article

Antibiotic resistance is an escalating global health problem that calls for new types of treatments beyond standard antibiotics. This review examines how targeting bacterial metalloproteins, especially those involved in siderophore-driven iron uptake and manganese-based oxidative defense, could lead to more selective antibacterial drugs that are less toxic to humans. Recent research shows that metals and metal-containing compounds can act as antimicrobials, but many of their biological roles are still not well understood. By synthesizing current evidence, this article critically evaluates translational strategies targeting bacterial metalloproteins. These include siderophore–antibiotic conjugates, metal trafficking inhibitors, and catalytic metallodrugs. The review suggests that therapies using receptor-mediated uptake and guided by genomic data deserve priority in clinical development. The review also highlights unresolved challenges in selectivity, toxicity, and resistance mechanisms, offering a roadmap for future research. This review integrates evidence from multiple databases to provide a comprehensive framework for targeting bacterial metalloproteins, combining narrative synthesis with systematic methodology. Full article

The phage-resistant mutant (PRM) strains of Escherichia coli (E. coli) exhibited abundant genetic and phenotypic diversity. IS elements played a vital role in creating various genetic divergences and regulating gene functions under phage infection stress. Genetic variations of PRM strains derived from E. coli MG1655 and mutation frequencies of coevolved E. coli populations with phages were explored by high-throughput sequencing and resequencing. Infrequent-restriction-site PCR (IRS-PCR) and carbon utilization test revealed the genetic and phenotypic diversity of the PRM strains. Numerous and discrepant mutation sites (MSs) were observed in the PRM strains and the coevolved populations, and many MSs were related to the synthesis of flagella and LPS, which often serve as receptors in a phage invasion. The insertions of various IS elements in key gene locations were also frequently found in the PRM strains, which indicate for the first time that IS elements played a vital role in generating genetic divergence and regulating gene functions under phage infection stress. Resequencing revealed that the coevolved populations at three evolving stages had discrepant profiles of MSs, and nearly all detected MSs occurred in the coevolved populations, which led to coexisting phages that increased the mutation rates and expedited the occurrence of the defective MSs in E. coli populations. In summary, our results reveal that the widespread and abundant presence of phages may provide one important force driving bacterial genomic evolution and prompt bacterial genetic divergence via accelerated mutation and increased mutation rates in the E. coli genome. Full article