Search Results (3,657)

Real-valued inter-residue distance maps provide essential spatial information for understanding protein folding mechanisms and guiding downstream applications such as function annotation, drug discovery, and structural modeling. However, existing prediction methods often struggle to capture long-range dependencies and to maintain topological consistency across different structural scales. To address these challenges, we propose a novel prediction framework that integrates a Mamba architecture, based on a selective state space model, to effectively model global interactions, and incorporates the Kolmogorov–Arnold Network (KAN) to enhance nonlinear structural representation. Extensive experiments on standard benchmark datasets, including CASP13, CASP14, and CASP15, demonstrate prediction accuracies of 86.53%, 85.44%, and 82.77%, respectively, outperforming state-of-the-art approaches. These results indicate that the proposed framework substantially improves the fidelity of real-valued distance prediction and offers a promising tool for downstream structural and functional studies. Full article

Soybean (Glycine max) is a globally important crop, as it has high protein and lipid content and plays a central role in sustainable agriculture. Recent advances in rhizosphere biology have highlighted the critical role of soybean root exudates, particularly isoflavones and other secondary metabolites, in shaping microbial community structure and function. These exudates mediate complex, bidirectional signalling with rhizosphere microorganisms, influencing nutrient acquisition, stress resilience, and disease suppression. This review describes current knowledge on soybean–microbe interactions, with a focus on the emerging concept of the rhizosphere as a dynamic communication network. Particular attention is given to Bacillus velezensis S141, a plant growth-promoting rhizobacterium (PGPR) with distinctive traits, including β-glucosidase-mediated isoflavone hydrolysis, phytohormone production, and drought resilience. Coinoculation studies with Bradyrhizobium spp. demonstrate enhanced nodulation, nitrogen fixation, and yield, supported by transcriptomic and ultrastructural evidence. Comparative genomic analyses further underscore host-adaptive features of S141, distinguishing it from other Bacillus strains. Despite promising findings, mechanistic gaps remain regarding metabolite-mediated signalling and environmental robustness. Future research integrating metabolomics, synthetic ecology, and microbial consortia design will be essential to harness rhizosphere signalling for climate-resilient, low-input soybean cultivation. Full article

Drug resistance is an important challenge in medical research and clinical practice, posing a serious threat to the effectiveness of current therapeutic strategies. Transcriptomics has played a crucial role in analyzing resistance-related genes and pathways, while the application of machine learning in high-throughput data analysis and prediction has also opened up new avenues in this field. However, existing studies mostly focus on a single drug or specific categories, and their conclusions are limited in applicability across drug categories, while studies on drugs beyond antibacterial and antitumor categories remain limited. In this study, we systematically analyzed the transcriptomic data of resistant cell lines treated with 1738 drugs spanning 82 categories and identified core genes through an integrated analysis of three classical machine learning methods. Using the antibacterial drug salinomycin as an example, we established a resistance prediction model that demonstrated high predictive accuracy, indicating the significant value of the selected core genes in prediction. Meanwhile, some of the core genes identified through the protein–protein interaction (PPI) network overlapped with those derived from machine learning analysis, further supporting the reliability of these core genes. Pathway enrichment analysis of differential genes revealed potential resistance mechanisms. This study provides a new perspective for exploring resistance mechanisms across drug categories and highlights potential directions for resistance intervention strategies and novel drug development. Full article

Plant immunity research is being reshaped by integrative multi-omics approaches that connect transcriptomic, proteomic, and interactomic data to build systems-level views of plant–pathogen interactions. This review outlines the scope and methodological landscape of these approaches, with particular emphasis on how transcriptomic and proteomic insights converge through network-based analyses to elucidate defense regulation. Transcriptomics captures infection-induced transcriptional reprogramming, while proteomics reveals protein abundance changes, post-translational modifications, and signaling dynamics essential for immune activation. Network-driven computational frameworks including iOmicsPASS, WGCNA, and DIABLO enable the identification of regulatory modules, hub genes, and concordant or discordant molecular patterns that structure plant defense responses. Interactomic techniques such as yeast two-hybrid screening and affinity purification–mass spectrometry further map host–pathogen protein–protein interactions, highlighting key immune nodes such as receptor-like kinases, R proteins, and effector-targeted complexes. Recent advances in machine learning and gene regulatory network modeling enhance the predictive interpretation of transcription–translation relationships, especially under combined or fluctuating stress conditions. By synthesizing these developments, this review clarifies how integrative multi-omics and network-based frameworks deepen understanding of the architecture and coordination of plant immune networks and support the identification of molecular targets for engineering durable pathogen resistance. Full article

Extrusion processing can induce gel-like network formation in plant proteins, enabling the advancement of structured meat alternatives with tailored textural properties. In this study, extrusion-induced gelation behavior of isolated mung bean protein (IMBP) was systematically investigated during the manufacture of low-moisture meat analogs (LMMA). The effects of key processing variables, rotational speed of the screw, moisture level, and processing temperature on gel network development, hydration behavior, and textural responses were evaluated using response surface methodology as an analytical framework. Increasing moisture content promoted protein hydration and facilitated the formation of continuous gel-like interactions, resulting in enhanced pore development and water-holding capacity. Variations in screw speed and processing temperature further modulated the extent of protein denaturation and network consolidation, influencing nitrogen solubility and mechanical properties. While the integrity index remained relatively insensitive to processing conditions, structural and functional responses exhibited clear dependencies on extrusion-induced gelation dynamics. The extrusion conditions of 39% moisture, 216 rpm, and 159 °C promoted the development of a well-defined protein network, leading to improved functional properties. These findings provide mechanistic insight into extrusion-driven gelation of IMBP and highlight its potential as a protein matrix for gel-based meat analog applications. Full article

Within the canonical auxin signaling pathway, Auxin Response Factors (ARFs) are transcriptionally repressed by AUX/IAA proteins under low auxin conditions, and this repression is alleviated as auxin concentrations increase. By contrast, ARF3 functions as a central regulator of gynoecium morphogenesis in Arabidopsis via a non-canonical auxin-sensing mechanism that relies on dose-dependent modulation of its protein–protein interaction network. To investigate whether an analogous regulatory mechanism operates in tomato (Solanum lycopersicum), we identified the tomato ARF3 homolog (SlARF3) and utilized it as bait in a yeast two-hybrid (Y2H) screen. This screening approach yielded 137 positive clones, corresponding to 118 putative interacting proteins. Notably, all of these interactions were abolished in the presence of 3-indoleacetic acid (IAA), indicating that SlARF3 engages in auxin-sensitive protein–protein interactions and thereby mediates auxin-dependent signal transduction. Among these, we identified an auxin-sensitive interaction between SlARF3 and TM29, a central regulator of parthenocarpy, underscoring its critical role in this developmental pathway. Functional analyses further demonstrated that silencing SlARF3 induces parthenocarpic fruit formation. Taken together, these findings define a previously uncharacterized SlARF3-centered interaction network and provide a conceptual framework for elucidating non-canonical auxin signaling pathways underlying tomato development. Full article

Background: Mycoplasma pneumoniae pneumonia (MPP) is a common community-acquired pneumonia in children. Increasing drug resistance highlights the need for more effective treatments with fewer side effects. The Qingfei Tongluo Jiedu formula (QTJD) has demonstrated clinical efficacy against MPP; however, its underlying mechanisms remain unclear. This study aimed to explore the mechanism of QTJD on MPP using network pharmacology and in vitro experiments. Methods: Network pharmacology was used to identify the active compounds and signaling pathways of QTJD in MPP. QTJD-containing serum was prepared, and primary mouse lung and bone marrow cells were isolated to examine the effects of QTJD on macrophage polarization through butyric acid. Cell viability assays, flow cytometry, and quantitative reverse transcription-polymerase chain reaction were performed. GPR109^−/− cells were used to confirm the receptor mediating butyric acid’s action, and Western blotting was employed to assess the MAPK signaling pathway. Results: QTJD promoted macrophage polarization and alleviated the inflammatory response caused by Mycoplasma pneumoniae. High-performance liquid chromatography-electrospray ionization mass spectrometry combined with network pharmacology identified 20 active compounds. Protein-protein interaction analysis revealed 10 core target, including JUN and Tumor Necrosis Factor (TNF), while enrichment analysis highlighted pathways such as Mitogen-Activated Protein Kinase (MAPK) and Phosphoinositide 3-Kinase-Protein Kinase B. Experimental validation demonstrated that QTJD reduced M1 markers (CD86, CXCL10) by increasing butyrate levels (p < 0.01) and enhanced M2 markers (CD206, Arg-1, MRC-1), promoting M2 polarization. QTJD inhibited ERK1/2, p38, and JNK1/2 (p < 0.01). In GPR109A^−/− mice macrophages, QTJD suppressed p38 and JNK1/2 (p < 0.01) but showed no effect on ERK1/2 (p > 0.05), confirming involvement of the butyrate-GPR109A-MAPK pathway. Conclusions: QTJD effectively alleviates MPP by regulating macrophage polarization through the butyrate-GPR109A-MAPK pathway. Future studies should explore how QTJD modulates pulmonary immunity through gut microbiota and butyrate production and elucidate its immunoregulatory mechanisms along the gut-lung axis using multi-omics approaches. Full article

Current research on glial cells has primarily focused on central nervous system glial cells (CNS glia), with relatively fewer studies on EGCs. Given the critical role of EGCs in maintaining intestinal homeostasis and neural function, this study aimed to investigate their immunomodulatory effects under inflammatory conditions. Primary EGCs were isolated and an inflammatory model was established by treatment with lipopolysaccharide (LPS). Following LPS induction, cellular samples were collected for transcriptomic analysis to identify differentially expressed genes. The analysis revealed that 88 genes were significantly altered, with 60 upregulated and 28 downregulated. Through Gene Ontology (GO) classification, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway mapping, and protein–protein interaction (PPI) network analysis, several key regulatory genes were identified: chemokine-related genes (IL8L2, IL8L1, CCL4, CCL5, and CX3CL1); negative feedback regulation-related genes (TNFAIP3 and ZC3H12A); homeostasis-maintaining genes (C1QB and LY86); and arachidonic acid metabolism-related genes (PTGS2 and GGT2). Under LPS stimulation without impairing EGC viability, EGCs may recruit immune cells by regulating the aforementioned genes. Additionally, arachidonic acid and its metabolites likely play important regulatory roles in EGC-mediated immunomodulation. These findings provide new theoretical insights and potential targets for further elucidating the pathogenesis of intestinal inflammation and developing targeted therapies. Full article

Bt Cry toxins remain the cornerstone of transgenic crop protection against Lepidopteran pests, yet field-evolved resistance, particularly in invasive species such as Spodoptera frugiperda and Helicoverpa armigera, can threaten their long-term efficacy. This review presents a comprehensive and unified mechanistic framework that synthesizes current understanding of Bt Cry toxin modes of action and the complex, multilayered regulatory mechanisms of field-evolved resistance. Beyond the classical pore-formation model, emerging evidence highlights signal transduction cascades, immune evasion via suppression of Toll/IMD pathways, and tripartite toxin–host–microbiota interactions that can dynamically modulate protoxin activation and receptor accessibility. Resistance arises from target-site alterations (e.g., ABCC2/ABCC3, Cadherin mutations), altered midgut protease profiles, enhanced immune regeneration, and microbiota-mediated detoxification, orchestrated by transcription factor networks (GATA, FoxA, FTZ-F1), constitutive MAPK hyperactivation (especially MAP4K4-driven cascades), along with preliminary emerging findings on non-coding RNA involvement. Countermeasures now integrate synergistic Cry/Vip pyramiding, CRISPR/Cas9-validated receptor knockouts revealing functional redundancy, Domain III chimerization (e.g., Cry1A.105), phage-assisted continuous evolution (PACE), and the emerging application of AlphaFold3 for structure-guided rational redesign of resistance-breaking variants. Future sustainability hinges on system-level integration of single-cell transcriptomics, midgut-specific CRISPR screens, microbiome engineering, and AI-accelerated protein design to preempt resistance trajectories and secure Bt biotechnology within integrated resistance and pest management frameworks. Full article

Background: Esophageal squamous cell carcinoma (ESCC) remains a highly lethal malignancy with limited effective treatments. Broadleaf Vetch (Vicia amoena, BV) is a traditional medicinal herb with potential anticancer properties, but its mechanisms in ESCC are not fully understood. Methods: Network pharmacology was used to identify BV-related therapeutic targets and pathways. Molecular docking validated interactions between BV components and core proteins. In vitro assays evaluated proliferation, colony formation, migration, invasion, epithelial–mesenchymal transition (EMT) markers, and ferroptosis-related indices. An ESCC xenograft model was used to assess antitumor efficacy in vivo. Results: Five major BV components and 363 ESCC-related targets were identified, highlighting the PI3K–AKT pathway and key nodes such as EGFR, AKT1, SRC, TP53, and GPX4. BV significantly inhibited ESCC cell proliferation, migration, and invasion, and reversed EMT marker expression. Ferroptosis induction was evidenced by significant Fe²⁺ accumulation, elevated reactive oxygen species (ROS) and malondialdehyde levels, alongside glutathione depletion. BV treatment also precipitated mitochondrial dysfunction. In parallel, BV downregulated GPX4 and SLC7A11. Notably, these changes were largely reversed by the ferroptosis inhibitor Ferrostatin-1. In vivo, BV suppressed tumor growth and regulated EMT- and ferroptosis-associated proteins in xenograft tissues. Conclusions: BV exerts dual antitumor effects in ESCC by suppressing EMT and inducing ferroptosis. These findings suggest BV may represent a potential multi-target phytotherapeutic candidate for ESCC. Full article

Background: The present study set out to identify key miRNAs, TFs and signaling pathways associated with bladder cancer, with a view to elucidating the networks of miRNA-TF-gene interactions that may serve as potential molecular biomarkers for disease diagnosis. Methods: An integrative analysis was conducted using the publicly available microarray dataset GSE130598. Expression profanalyzede analyzed from 42 muscle-invasive bladder cancer (MIBC) tissues and 42 matched adjacent normal bladder tissues. After data preprocessing and normalization, differentially expressed genes (DEGs) were identified. To identify the associated biological processes and signaling pathways, functional enrichment analyses were conducted using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Protein–protein interaction (PPI) network analysis was then employed to identify hub genes and key molecular interaction modules associated with bladder cancer. Results: MYC, TP53, SP1, E2F1, E2F3, NFKB1, and TWIST1 were identified as central transcriptional regulators, indicating their roles in controlling genes involved in cell cycle regulation, DNA damage response, and tumor progression. Several miRNA families, including miR-200, miR-17, miR-29, miR-141, and miR-548, have been identified as key post-transcriptional regulators, suggesting their involvement in oncogenic signaling and cellular differentiation. PPI network analysis revealed MAPK3, AKT1, CHEK1, CDK1, AURKA, and AURKB as hub genes associated with cell proliferation, mitotic control, and intracellular signaling. Conclusions: Fundamental molecular processes underlying bladder cancer pathogenesis include cell cycle control, signal transduction, and genomic stability. These findings provide insight into the molecular regulatory landscape of MIBC and highlight potential targets for diagnostic and prognostic applications. Full article

Asparagine synthetase (AS) is a key enzyme in plant nitrogen metabolic network. Beyond its canonical role as a major nitrogen transport and storage molecule, asparagine also serves critical functions in plant immunity and tolerance to environmental stresses. This review systematically summarizes the characteristics of the core AS-mediated asparagine biosynthesis pathway and two other minor pathways in plants. It details the distribution of the AS gene family, protein structure, and evolutionary classification. The mechanisms governing AS expression are analyzed, revealing tissue-specific patterns and precise regulation by nitrogen availability, abiotic stresses, and exogenous hormones, mediated through an interactive network of cis-acting elements and transcription factors. Furthermore, the biological functions of AS are multifaceted: it influences plant biomass and nitrogen use efficiency by regulating nitrogen uptake, transport, and recycling during growth and development; it contributes to abiotic stress tolerance by synthesizing asparagine to maintain cellular osmotic balance and scavenge reactive oxygen species; and it indirectly enhances antibacterial and antiviral capacity by activating the SA signaling pathway and modulating programmed cell death. Current knowledge gaps remain regarding the crosstalk between AS-mediated signaling pathways, the upstream transcriptional regulatory network, and the balance between nitrogen utilization and disease resistance in crop breeding. Future research aimed at addressing these questions will provide a theoretical foundation and molecular targets for improving crop nitrogen use efficiency and breeding resistant cultivars. 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

Long-chain non-coding RNAs (lncRNAs) play important regulatory roles in the growth and development of skeletal muscle, but systematic identification and functional studies of lncRNAs related to porcine skeletal muscle development remain limited. Based on a previously constructed panoramic map of porcine skeletal muscle lncRNAs, lncRNA-ssc.37456 was identified as differentially expressed in porcine skeletal muscle before and after birth. Its function and potential mechanisms were investigated using a porcine skeletal muscle regeneration model, a primary skeletal muscle cell differentiation model, and knockdown and overexpression experiments in vitro. lncRNA-ssc.37456 was upregulated on day 7 of regeneration, with expression positively correlated with the muscle differentiation marker MYHC and negatively correlated with the proliferation marker PAX7. During differentiation of porcine primary myoblasts, expression continuously increased, peaking on day 4. Knockdown of lncRNA-ssc.37456 by small interfering RNA (siRNA) significantly increased cell proliferation, upregulated mRNA and protein levels of proliferation-related genes KI67 and PCNA, and increased the proportion of EdU-positive cells. Conversely, expression of differentiation-related genes MYOG and MYHC decreased, and immunofluorescence analysis revealed reduced myotube formation and differentiation index. Overexpression of lncRNA-ssc.37456 promoted differentiation and inhibited proliferation, showing effects opposite to those observed in knockdown experiments. Nucleocytoplasmic fractionation indicated predominant cytoplasmic localization, suggesting potential function through a ceRNA mechanism. An interaction network with miRNAs was constructed based on the miRDB database, indicating a potential miRNA “sponge” regulatory mechanism. These results indicate that lncRNA-ssc.37456 participates in porcine skeletal muscle development by regulating the transition of muscle cells from proliferation to differentiation, providing molecular insights and potential targets for muscle biology research and the molecular breeding of growth traits. 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