Search Results (23,800)

Multilingual learning is key in natural language processing, but is challenged by the transfer–interference trade-off, where positive transfer benefits certain languages, while negative interference affects others. Prior methods, including linguistic-based and embedding-based language clustering, have attempted to address this; yet, they remain constrained by their static design and lack of task-specific feedback. In this study, we propose a novel computational strategy inspired by molecular design that constructs molecules with targeted properties. Languages are modeled as nodes in an undirected graph, with edges representing the transfer strength. This language molecule is optimized via Reinforcement Learning to adjust edge connections and weights to enhance positive transfer and minimize interference, where graph clustering is applied, and clusters are then evaluated on the Named Entity Recognition and POS tagging tasks using 25 languages from the WikiANN dataset and 12 typologically diverse languages from the UDPOS dataset. Compared to linguistic and embedding-based language clustering baselines, our method yields substantial improvements, especially for low-resource languages, with some showing over 35% increase in F1 score, while high-resource languages benefit moderately, confirming reduced transfer–interference trade-off. Our atom–language model offers a novel path for multilingual learning, inspired by molecular principles from physical sciences. Full article

Background/Objectives: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline and chronic neuroinflammation. Increasing evidence suggests that the imbalance between pro-inflammatory Th17 cells and anti-inflammatory regulatory T (Treg) cells plays a critical role in AD pathogenesis. However, a comprehensive synthesis of how natural compounds modulate Th17/Treg balance in AD remains lacking. This review aims to summarize current preclinical evidence on Th17/Treg dysregulation and evaluate the immunomodulatory potential of natural compounds in AD. Methods: This review focuses on preclinical evidence derived from experimental AD models and related inflammatory models to evaluate how natural compounds modulate Th17/Treg balance, neuroinflammation, and cognitive function, with an emphasis on underlying molecular and immunometabolic mechanisms. Results: Th17/Treg imbalance contributes significantly to AD-associated neuroinflammation and disease progression. Representative natural compounds, including paeoniflorin, quercetin, and ganoderic acid A, have demonstrated the ability to rebalance Th17/Treg responses, suppress neuroinflammation, and improve neuronal survival in experimental models. These compounds are highlighted due to their relatively stronger evidence in AD-related models and more clearly defined immunomodulatory mechanisms. These effects are partially mediated through modulation of key signaling pathways and immunometabolic reprogramming. Conclusions: Targeting Th17/Treg balance with natural compounds represents a promising multi-target immunomodulatory strategy for AD. However, most current evidence is derived from preclinical or non-AD models, and clinical validation remains limited. Future studies should prioritize AD-specific models and translational research to evaluate therapeutic potential in humans. Full article

Background: Methylthioadenosine phosphorylase (MTAP) deficiency caused by homozygous deletion is prevalent in solid tumors and contributes to malignant progression, thereby rendering cancer cells vulnerable to dysfunction of protein arginine methyltransferase 5 (PRMT5). This study aimed to investigate whether Poly (ADP-ribose) polymerase (PARP) inhibitors could exploit this vulnerability through PRMT5 inactivation in MTAP-deficient tumors. Methods: PRMT5 activity was assessed in vitro and in vivo following PARP inhibitor treatment. The antitumor effects of PARP inhibitors alone or in combination with either the MTAP inhibitor MTDIA or the PRMT5 inhibitor EPZ015666 were evaluated in solid tumor models, including MTAP-deficient tumor models in vivo. Results: PARP inhibitors effectively inactivated PRMT5 in vitro and in vivo and exacerbated DNA double-strand breaks induced by PARP inhibition. Moreover, PARP inhibitors showed significant synergistic effects when combined with either MTDIA or EPZ015666 in solid tumor models. MTAP-deficient tumors exhibited increased vulnerability to olaparib in vivo, and combined treatment with olaparib plus MTDIA or EPZ015666 produced improved therapeutic outcomes compared with olaparib alone. Conclusions: These findings identify PARP inhibitors as a potential therapeutic strategy for MTAP-deficient tumors through targeted inactivation of PRMT5 and support further evaluation of PARP inhibitor-based combination therapies in this molecular context. Full article

The emergence of membrane boundaries represents a decisive transition in the origin of life, yet the molecular nature of the earliest abiotic membranes remains uncertain. Existing models based on simple fatty acids, while experimentally tractable, often lack the environmental robustness required under fluctuating prebiotic conditions. Furthermore, the absence of clear pathways linking primitive amphiphiles to later phospholipid systems highlights the need for chemically continuous intermediate frameworks. Here, we explore borate-bridged amphiphile–carbohydrate conjugates as plausible intermediates between simple prebiotic surfactants and modern lipid bilayers. These conjugates arise from low-molecular-weight polyols—including glycerol, butane-1,2,3,4-tetraol, pentane-1,2,3,4,5-pentaol, and hexane-1,2,3,4,5,6-hexitol—reacting with long-chain alkyl ethers and borate species under alkaline conditions, enabling reversible coupling to ribose and other vicinal diol-containing sugars. This chemistry integrates three essential properties for early compartmentalization: hydrolytically robust ether-linked hydrophobic domains, multivalent and highly hydrated headgroups, and environmentally responsive borate coordination. Comparative physicochemical analysis suggests that single-tail alkylglycerol derivatives preferentially form micelles and interfacial films, while di- and tri-tail tetritol and pentitol conjugates favor lamellar assemblies and vesicle formation across realistic prebiotic pH and salinity ranges. Hexitol-based systems, particularly those bearing three hydrophobic chains, may act as membrane-stabilizing components that enhance rigidity and reduce permeability under extreme conditions. We propose that heterogeneous mixtures dominated by two-tail polyol diethers, supplemented by tri-tail stabilizers and surface-active alkylglycerols, could provide mechanically robust, pH-tunable, and sugar-decorated abiotic membranes. Such borate-mediated amphiphiles offer a chemically coherent framework linking carbohydrate stabilization, ether lipid persistence, and dynamic self-assembly, potentially representing a transitional stage in the evolutionary pathway from primitive amphiphilic films to biologically encoded membranes. Full article

Background: Cellular senescence is a key regulatory mechanism in tumor initiation and progression, influencing cancer development through modulation of the cell cycle, the immune microenvironment, and inflammatory responses. However, the molecular characteristics and potential clinical value of senescence-related genes in lung adenocarcinoma (LUAD) have not been systematically elucidated. This study aimed to comprehensively characterize the expression patterns, molecular subtypes, and prognostic significance of cellular senescence-related genes in LUAD, and to identify key regulatory determinants. Methods: Transcriptomic data of cellular senescence-related genes were obtained from The Cancer Genome Atlas (TCGA) cohort, and integrated analyses were performed to characterize their mutational landscape, copy number variations, and differential expression profiles. Senescence-related molecular subtypes were established using consensus clustering, followed by gene set variation analysis (GSVA) for pathway enrichment and immune infiltration analyses. A prognostic risk model was subsequently constructed using LASSO-penalized Cox regression, and its predictive performance was systematically evaluated. Candidate key regulators were further prioritized through bioinformatic screening, identifying FOLR1 as a hub gene. The biological function of FOLR1 was validated by qRT–PCR, Western blotting, assessment in clinical specimens, and a subcutaneous xenograft tumor model in mice. Results: Cellular senescence-related genes in LUAD exhibited a high frequency of somatic mutations and copy number alterations, accompanied by marked transcriptional dysregulation. Based on the expression profiles of these genes, LUAD patients could be stratified into three distinct molecular subtypes with significantly different clinical outcomes. These subtypes displayed pronounced heterogeneity in pathway enrichment patterns and immune cell infiltration. The subsequently developed prognostic signature demonstrated robust predictive performance in both the training and validation cohorts. Functional assays showed that FOLR1 was significantly downregulated in LUAD tissues and cell lines; FOLR1 knockdown promoted tumor cell proliferation, whereas restoration of its expression or pharmacological intervention markedly suppressed tumor progression. Consistently, in vivo xenograft experiments further corroborated the tumor-suppressive role of FOLR1 in lung adenocarcinoma. Conclusions: This study systematically delineated the molecular landscape of cellular senescence-related genes in LUAD and elucidated their associations with the tumor immune microenvironment and patient prognosis. Moreover, FOLR1 was identified as a potential tumor suppressor and therapeutic target. These findings provide a theoretical basis for senescence-informed molecular stratification and the development of precision treatment strategies in lung adenocarcinoma. Full article

This study investigates shared molecular mechanisms between pyoderma gangrenosum (PG) and inflammatory bowel disease (IBD) and systematically evaluates the therapeutic potential of JAK inhibitors targeting this pathway. Despite the clear clinical comorbidity, the core inflammatory pathways driving cross-tissue associations between the two diseases remain unclear. Furthermore, systematic mechanistic evidence is lacking regarding whether JAK inhibitors act by regulating shared pathological pathways in patients with comorbidities. To address this, this study integrated PG skin and IBD intestinal transcriptome data, single-cell transcriptomic data, and genome-wide association study (GWAS) meta-data from public databases. It employed a multi-level computational biology approach combining Mendelian randomization, weighted gene co-expression network analysis, protein interaction network construction, molecular docking simulations, and system dynamics modeling. The results revealed that genetic analysis confirmed IBD as a causal risk factor for PG, precisely identifying six shared genetic loci. Transcriptomic analysis identified a cross-tissue conserved inflammatory module centered on the JAK-STAT pathway, with JAK2 and STAT3 identified as network hubs. Molecular docking predicted high affinity of baricitinib for both JAK1 and JAK2, while system dynamics modeling demonstrated that its intervention effectively suppresses signaling in the shared inflammatory network. This study reveals the molecular basis of the “gut–skin axis” comorbidity between PG and IBD from a multi-omics integration perspective. It provides predictive computational evidence for the use of JAK inhibitors in targeted comorbidity therapy. Baricitinib is identified as a particularly promising candidate. These findings advance the transition from empirical drug use to mechanism-guided precision treatment strategies. Although this study provides multiscale computational simulation evidence, the lack of direct experimental validation of these predicted results necessitates further confirmation through in vitro and in vivo experiments. Full article

The rapid accumulation of genome-scale data has transformed plant biology from descriptive genetics to predictive and increasingly mechanistic genomics. Longan (Dimocarpus longan Lour.) is an economically important subtropical fruit tree in China and Southeast Asia, but compared with model plants and major temperate fruit crops, its genomic resources and functional studies have developed relatively late. Here, we review recent progress in longan genomics with emphasis on three interrelated areas: genome assembly and annotation, transcriptomic resources, and representative gene family studies associated with flowering, somatic embryogenesis, and transporter-mediated stress tolerance. The progression from the first draft genome of ‘Honghezi’ to the chromosome-scale assemblies of ‘Jidanben’ and ‘Shixia’ has substantially improved contiguity and gene annotation, thereby enabling population-genomic analysis, genome-wide gene family identification, and candidate-gene discovery. Available transcriptomic datasets further support studies of reproductive development, stress responses, and embryogenic competence, although cross-study integration remains limited. We also summarize how gene family analyses have advanced the current understanding of floral induction, continuous flowering, somatic embryogenesis, mineral transport, and sugar transport in longan. Importantly, the field is still dominated by cataloguing and expression-based inference, whereas causal validation, pan-genomic analysis, and multi-omics integration remain insufficient. We therefore argue that future progress in longan molecular breeding will depend on integrating high-quality genomic resources with functional validation, standardized comparative annotation, and improved transformation or regeneration systems. Full article

Peri-implant marginal bone stability remains a major determinant of long-term implant success, yet clinical studies report early marginal bone changes ranging from near-stable conditions in some protocols to approximately 1–2 mm during the first year in more traditional series, underscoring considerable biological variability. In the present review, a remodeling-dominant state refers to turnover-led peri-implant adaptation with limited net cortical gain, whereas modeling-driven apposition refers to uncoupled surface bone addition and cortical reinforcement. We conducted a structured narrative review of PubMed/MEDLINE, Scopus, and Web of Science for literature published between 2000 and February 2026 and qualitatively synthesized direct peri-implant evidence, craniofacial/oral non-implant evidence, and extrapolative mechanobiology from long-bone and systemic models. The available literature supports osteocyte-centered SOST/Wnt regulation as biologically plausible for peri-implant cortical adaptation; however, direct human peri-implant molecular validation remains limited. Based on this synthesis, we propose a hypothesis-generating framework in which mechanical signal profile, microenvironmental stability, and host-related factors influence the probability of transition from a remodeling-dominant to a modeling-dominant peri-implant state. This framework should therefore be interpreted as a testable conceptual model rather than a validated peri-implant mechanism. Its main value lies in organizing current evidence and defining priorities for translational studies that integrate molecular, imaging, and biomechanical endpoints. Full article

This study explored the flavor profiling of baked potatoes, with a focus on how maturity affects the volatile flavor. By using HS-SPME-GC-MS, sensory evaluation, multivariate statistical analysis and computational modeling, a total of 99 volatile compounds were finally identified. Multivariate statistical analysis yielded 36 different important compounds (VIP > 1, p < 0.05). Subsequently, combined with relative odor activity value (ROAV), four key compounds including 2-ethyl-3,5-dimethylpyrazine, 2,6-diethylpyrazine, ethyl acetate and benzeneacetaldehyde were identified as potential indicators of baked potatoes with different maturities. Further, molecular docking analysis revealed the interactions between key pyrazine compounds and human olfactory receptors OR5K1 through hydrogen bonds and other interactions. These findings provide new insights into the relationship between potato maturity and flavor differences, and also lays a foundation for in-depth exploration into flavor identification and perception. Full article

Background: Colorectal intraepithelial neoplasia (CR-EN) is a precursor lesion of colitis-associated colorectal cancer (CAC). This study investigated the interventional effects and molecular mechanisms of Rhapontici Radix extract on CR-EN. Methods: An azoxymethane/dextran sulfate sodium (AOM/DSS)-induced mouse model of colonic intraepithelial neoplasia, bioinformatics analysis, organoid models, and HCT116 cell experiments were employed, coupled with histopathological examination, inflammatory cytokine detection, Western blot, immunofluorescence, and HPLC-MS/MS. Results: The results showed that the YAP/AKT-PI3K signaling pathway is aberrantly activated in CRC. Rhapontici Radix extract ameliorated colonic pathology, suppressed inflammatory responses, and remodeled gut microbiota composition in model mice. The extract selectively inhibited the proliferation of CR-EN organoids by downregulating Ki67 and β-catenin while upregulating p53, and suppressed the proliferation, colony formation, and migration of HCT116 cells. Mechanistically, the extract modulated the YAP/PI3K/AKT pathway by upregulating phosphorylated YAP (p-YAP) and downregulating phosphorylated AKT (p-AKT), phosphorylated PI3K (p-PI3K), and their downstream targets p-SRC and c-MYC. Conclusions: This study suggests that Rhapontici Radix extract intervenes in inflammation-associated carcinogenesis through a multi-pathway, multi-target strategy, offering potential therapeutic targets for CAC prevention and treatment. Full article

Background/Objectives: Understanding the genetic basis of food consumption is a key step toward precision nutrition, viewed as a long-term future perspective. This study aimed to investigate genetic variants associated with grapefruit (Citrus paradisi) intake and to evaluate their potential relationship with obesity risk. Methods: A genome-wide association study (GWAS) was conducted on 19,653 European-ancestry participants from two prospective cohorts, the Nurses’ Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS). We employed a functional annotation strategy to select a suggestive locus for follow-up analysis, and computationally derived molecular docking simulations explored a plausible functional link between grapefruit’s bioactive compounds and the candidate gene product. Results: Although falling short of the conventional threshold for genome-wide significance, a suggestive locus was prioritized on chromosome 14, with the lead single nucleotide polymorphism (SNP), rs2124 (p < 5 × 10⁻⁶), located within the metabolic gene ADCK1 (aarF domain containing kinase 1). Molecular docking simulations supported a plausible mechanistic hypothesis, indicating that key bioactive compounds in grapefruit could bind with high affinity to the ADCK1 protein. Consistent with the GWAS finding, individuals with the CC genotype reported lower mean grapefruit intake. This genotype was also associated with other lifestyle factors, notably, lower physical activity in women. In age- and multivariate-adjusted models, the CC genotype was associated with a modestly increased risk of incident obesity in females, but not in males. Conclusions: Our exploratory findings suggest a prioritized candidate locus associated with grapefruit intake, and its link to obesity risk may be mediated by the metabolic gene ADCK1. However, given the lack of genome-wide significance and independent replication, these findings should be considered preliminary and exploratory. These hypothesis-generating results support the integration of genetics and dietary habits, warranting further mechanistic validation. Full article

Ferroptosis of mesenchymal stem cells (MSCs) is a critical bottleneck restricting the efficiency of ruminant biological breeding. Phloretin, a natural bioactive polyphenol, exhibits potential ferroptosis-inhibitory activity. However, the regulatory effects and underlying mechanisms of phloretin on ruminant MSCs remain poorly understood. This study aimed to investigate the effects of phloretin on ferroptosis and elucidate its underlying molecular mechanisms. Herein, we isolated and cultured adipose-derived mesenchymal stem cells (AD-MSCs) from adipose tissue of a 9-day-old Leizhou goat and established a ferroptosis model in these cells using RSL3. We detected cell viability, proliferation, migration, ferroptosis-related indexes and key protein expression. The results showed that phloretin (25 and 50 μM) dose-dependently inhibited ferroptosis in goat AD-MSCs, reducing intracellular ferrous ion (Fe²⁺), reactive oxygen species (ROS) and lipid peroxidation levels, restoring glutathione content, and ameliorating mitochondrial structural damage. Mechanistically, phloretin exerted its anti-ferroptosis effects through direct antioxidant activity, activation of the Nrf2/HO-1/GPX4 signaling pathway and Fe²⁺ chelation. Nrf2 and GPX4 were key targets in this process. These results provide preliminary in vitro evidence and a theoretical basis for the potential application of phloretin in future research related to meat goat production and ruminant breeding. Full article

Glucosinolates (GSLs) are unique sulfur-containing secondary metabolites in Brassica crops that critically influence stress resistance, nutritional quality, and economic value. This review systematically summarizes the chemical classification, tissue-specific distribution, and conserved three-phase biosynthetic pathway of GSLs in Brassica species. We dissect the core MYB–MYC–WRKY transcriptional regulatory network, elucidate how whole-genome duplication-driven gene functional diversification shapes species-specific GSL accumulation patterns, and outline the multi-layered regulatory system integrating endogenous and exogenous signals. Furthermore, we consolidate recent advances in the genetic dissection of GSL traits and molecular breeding strategies for targeted trait improvement. Finally, we propose a three-tiered regulatory cascade model for GSL metabolism and highlight future research priorities to address current breeding bottlenecks. This work provides a systematic theoretical framework for functional research and precision breeding of GSL metabolism in Brassica crops. Full article

Mechanical stress has been implicated in retinal pigment epithelium (RPE) dysfunction and angiogenic signaling in retinal disorders; however, its direct in vivo effects on the RPE–choroid complex remain incompletely understood. Here, we established a mouse model of localized mechanical stress by subconjunctival implantation of glass beads (0.8–1.2 mm in diameter) in eight-week-old C57BL/6J mice to induce transscleral stretching of the RPE. Ocular tissues were analyzed two days after implantation using histological, immunohistochemical, and molecular approaches, and inflammatory mediators were quantified by multiplex cytokine assays. Mechanical stress induced focal serous retinal detachment, elongation of photoreceptor outer segments, and disruption of the RPE tight junction protein ZO-1. VEGF expression in the RPE–choroid complex was significantly upregulated and accompanied by increased levels of inflammatory mediators, including MCP-1. Intravitreal administration of anti-VEGF agents effectively suppressed stress-induced VEGF expression. These findings indicate that mechanical stress is sufficient to induce structural disruption and angiogenic signaling in the RPE in vivo, providing a useful experimental platform for investigating stress-related retinal responses and therapeutic modulation of VEGF signaling. Full article

Genotyping is a key step in molecular breeding. Due to its cost-effectiveness, accuracy, and flexibility, genotyping by target sequencing (GBTS) has become a preferred technology for medium-density genotyping. In this study, a new GBTS array for fresh edible maize was developed using resequencing data from 477 lines. The array contains 5759 SNPs evenly distributed across the maize genome, with average minor allele frequency (MAF) and polymorphism information content (PIC) values of 0.40 and 0.36, respectively. These SNPs are closely associated with 1566 functional genes. Cluster analysis of 198 maize lines based on the GBTS array was consistent with their pedigree relationships. Furthermore, 277 fresh waxy maize lines were genotyped and used for genomic selection analyses of hundred-kernel weight, kernel length, and kernel width. Comparative evaluation of different models indicated that Ridge Regression Best Linear Unbiased Prediction (rrBLUP) was the optimal model, with prediction accuracies of 0.33, 0.64, and 0.36, respectively. Additional analyses using different marker densities based on the rrBLUP model showed that prediction accuracy did not increase when the number of markers exceeded 2000, indicating that this array provides sufficient marker density for genetic analysis and genomic selection. Overall, this array provides a useful tool for genetic studies of fresh edible maize and facilitates the application of genomic selection in breeding programs. Full article