Search Results (24,073)

Driven by increasing demand in the health and wellness industry, Traditional Chinese Medicine (TCM) agriculture currently faces significant challenges related to supply–demand imbalances and continuous cropping obstacles (CCOs). Intercropping and crop rotation can mitigate yield decline and environmental stress by improving microclimates and rhizosphere ecology. However, there is still a lack of bibliometric synthesis within this research area. To analyze research hotspots and evolutionary trends, 192 articles on the intercropping and crop rotation of medicinal plants were collected from the Web of Science Core Collection (1998–2025), including databases such as the Science Citation Index Expanded (SCIE), the Social Science Citation Index (SSCI) and the Conference Proceedings Citation Index (CPCI). The results revealed a steady increase in publication volume over time. China emerged as the most prolific contributor (93 articles), while the United States occupied a pivotal position in the global collaborative network, achieving a high centrality of 0.90. Research hotspots in this field have evolved from an early emphasis on plant yield and quality toward the mechanisms for alleviating CCOs, interspecific interactions within the rhizosphere microbiome, and the ecological management of soil health. Keyword bursts indicate that “microbial community” and “carbon” have emerged as the current research frontiers. To clarify the micro-mechanisms by which intercropping and crop rotation patterns mitigate or prevent CCOs, future research should prioritize the integration of multi-omics approaches to resolve molecular interactions within the “microbe–plant–soil” nexus. Key priorities include the development of functional Synthetic Microbial Communities (SynComs) and the establishment of comprehensive evaluation systems for ecological cultivation. Furthermore, aligning these models with global climate neutrality strategies would facilitate the balance between high-quality medicinal production and ecosystem stability. Full article

Chemotaxis enables eukaryotic cells to detect and migrate along extracellular chemoattractant gradients spanning several orders of magnitude. This remarkable dynamic range relies on adaptation, a process that allows cells to reset their signaling machinery while preserving sensitivity to incremental changes in stimulus intensity. Although numerous actin-dependent feedback mechanisms have been characterized, the molecular basis of adaptation within an actin-independent core gradient-sensing module remains poorly understood. Here, we identify the Ras GTPase-activating protein, C2GAP1, as a critical F-actin-independent effector of the heterotrimeric G protein, Gα2, in Dictyostelium discoideum. Using cytoskeleton-free gradient-sensing cells, quantitative imaging, biochemical assays, FRET-based G-protein activation measurements, and structural modeling, we demonstrate that C2GAP1 controls concentration-dependent adaptation during gradient sensing. Mechanistically, C2GAP1 directly associates with Gα2 in both GDP- and GTP-bound states, with preferential binding to activated Gα2, thereby sustaining membrane recruitment and locally attenuating Ras and downstream signaling. Loss of C2GAP1 enhances G-protein activation, disrupts local inhibition, and impairs rapid reorientation in dynamic gradients. These findings define a direct coupling between heterotrimeric G proteins and the RasGAP, C2GAP1, as a core adaptive module that enables gradient sensing across a wide concentration range. Full article

Background/Objectives: Phillygenin (PHI), a natural lignan derived from Forsythia suspensa, has garnered attention for its potential to alleviate chronic diseases, including chronic colitis, pulmonary fibrosis, and diabetes. Chronic kidney disease (CKD) poses a global health challenge, characterized by high morbidity and mortality rates and associated with a spectrum of secondary complications. In this study, we aim to investigate the therapeutic effectiveness of PHI on CKD and also identify molecular signals by using a unilateral ureteral obstruction (UUO) mouse model and in vitro experiments. Methods: C57BL/6 mice were administered PHI at 50 mg/kg/day to assess its therapeutic effectiveness. In vitro, lipopolysaccharide (LPS) and adenosine triphosphate (ATP) were used to induce pyroptosis, also known as pyroptosis, in renal proximal tubular cells (NRK52E). Results: After PHI treatment for 14 consecutive days, the collagen deposition and extracellular matrix (ECM) accumulation, the expression of oxidative stress response proteins (catalase, superoxide dismutase 2, NADPH oxidase 4, and thioredoxin reductase 1), pro-inflammatory markers (TNF-α and Cyclooxygenase-2(COX-2), and infiltration of neutrophils and macrophages were significantly ameliorated in the UUO mice. Interestingly, the pyroptosis-related proteins (NLRP3/Caspase-1/GSDMD/IL-1β) and cell apoptotic death were also conspicuously relieved after treatment with PHI. Furthermore, PHI administration significantly attenuated the ATP/LPS-induced NF-κB/NLRP3/Caspase-1/GSDMD pyroptosis signal pathway in NRK52E cells. Conclusions: These results demonstrate, for the first time, that PHI treatment ameliorates inflammation and the related pyroptosis via inhibitory regulation of the NF-κB/NLRP3/Caspase-1/GSDMD axis, leading to attenuated renal fibrosis and progressive CKD in UUO mice and in vitro. Our findings suggest that PHI could be a nutraceutical candidate for attenuating CKD progression. Full article

Background/Objectives: SHP2 (PTPN11) is a key regulator of RAS/MAPK signaling and a well-validated target in cancer and developmental disorders. Designing ligands for its catalytic site is challenging due to the pocket’s intrinsic flexibility and the presence of conserved structural water molecules critical for ligand recognition, which limits traditional discovery approaches. This study aimed to systematically identify and prioritize novel SHP2-binding candidates using a computational strategy that accounts for these challenges. Methods: An integrative computational workflow was applied, combining water-aware docking, large-scale virtual screening of 714,409 compounds, MM/GBSA binding free-energy analysis, AI-driven chemical space modeling using ChemBERTa, and microsecond-scale molecular dynamics (MD) simulations. The high-resolution catalytic PTP domain of SHP2 structure was analyzed to identify conserved water molecules (W711, W716, W726, W776) essential for reproducing the crystallographic binding mode of the reference ligand 3LU. Candidates were prioritized based on docking scores, physicochemical criteria, structural inspection, MM/GBSA energetic profiles, and occupancy of distinct chemical space regions. Results: Seven compounds were selected. SwissADME analysis confirmed favorable drug-likeness and GI absorption, with no BBB permeation. ChemBERTa embeddings revealed substantial structural novelty relative to known SHP2 inhibitors. 1 μs molecular dynamics simulations suggested stable binding of compound 4 (2-(3-methyl-2,6-dioxopurin-7-yl)acetate) and persistent interactions with the conserved water network. MM/GBSA evaluation subsequently highlighted its energetically coherent profile. Conclusions: The workflow prioritizes compound 4 as a promising and structurally innovative SHP2-binding candidate. This integrative strategy provides a generalizable approach for targeting proteins with flexible pockets, critical water networks, and limited scaffold diversity, offering a roadmap for challenging computational ligand-prioritization projects. Full article

The antimicrobial resistance of Acinetobacter baumannii necessitates the development of novel therapeutic strategies targeting essential enzymes such as Undecaprenyl Pyrophosphate Phosphatase (UppP). This study explored spider venom peptides in silico as potential allosteric inhibitors of A. baumannii UppP. A systematic literature review was conducted to select eight α-helical peptides with reported anti-A. baumannii activity, followed by their computational physicochemical characterization. Three-dimensional models of A. baumannii UppP and the candidate peptides were generated, and a putative allosteric binding site was validated through molecular docking of a known inhibitor of the BacA homolog. The eight peptides were subsequently docked to this validated site using HADDOCK. Results revealed variable binding affinities; peptides LC-AMP-I1, Lycosin-II, and GK37 exhibited the most favorable HADDOCK scores and extensive interaction networks, consistent with their reported high antimicrobial potency. Other candidates, notably Lt-MAP2, showed low binding affinity but high predicted synergistic potential. These findings identify promising spider venom peptide candidates, suggesting dual (membrane disruption/UppP inhibition) or synergistic mechanisms of action, and validate UppP as a viable pharmacological target for peptide-based inhibitors. Full article

The increasing demand for sustainable agriculture has intensified interest in beneficial microbes as eco-friendly alternatives to chemical pesticides for plant disease control. Among these, plant growth-promoting rhizobacteria (PGPR) have attracted great interest because they can suppress plant pathogens and strengthen plant health through molecular mechanisms. Recent studies suggest that PGPR protect plants from disease not only by directly attacking pathogens but also by changing how plant immune genes are expressed through epigenetic processes. This review brings together current knowledge on epigenetic regulation in plant–PGPR interactions, focusing on DNA methylation, histone modifications, and non-coding RNA pathways. PGPR colonization activates plant immune signaling through pattern recognition receptors, MAPK cascades, reactive oxygen species, and plant hormones. The review also covers the range of bacterial signals—including lipopolysaccharides, flagellin, cyclic lipopeptides, and volatile organic compounds—that prepare plant defenses, and explains how the recognition of these signals reshapes chromatin structure at defense genes. In addition, the review discusses how these changes may influence induced systemic resistance and examines emerging, though still limited, evidence on whether they could potentially be transmitted to subsequent generations. A better understanding of how microbial signals regulate host epigenetics may reveal new ways to improve plant immunity and balance growth with defense. Overall, available evidence indicates that PGPR-induced epigenetic changes represent a promising and environmentally friendly approach to crop protection; however, field-level validation and mechanistic confirmation in non-model crop species remain necessary before this strategy can be considered practically applicable. Full article

Cognitive frailty (CF), characterized by concurrent cognitive and motor decline, is a major challenge to healthy aging, yet effective interventions remain limited. Klotho, an anti-aging protein that declines with age, has been implicated in both hippocampal function and skeletal muscle homeostasis. In this study, we investigated whether aerobic exercise combined with multisensory stimulation training (CT) ameliorates age-related CF through systemic Klotho signaling. A 16-month-old mouse model of age-related CF was assigned to aerobic training, multisensory stimulation, or combined training, and behavioral, electrophysiological, histological, and molecular assessments were performed. To examine the mechanistic role of Klotho, dual-route shRNA delivery was used to inhibit systemic Klotho expression. CT significantly improved cognitive and motor performance compared with either intervention alone. CT also increased hippocampal dendritic spine density and long-term potentiation, reduced collagen deposition in gastrocnemius muscle, and upregulated Klotho, FGF19, and FGFR1 expression in both hippocampus and muscle, accompanied by elevated serum Klotho levels. Klotho knockdown attenuated these beneficial effects, reduced PSD95 and GluN2B expression, and increased MuRF3 and TNF-α levels. These findings suggest that CT alleviates cognitive frailty and that systemic Klotho is a key mediator linking hippocampal synaptic function and skeletal muscle homeostasis. Full article

Tau is a protein associated with microtubules principally expressed in neuronal cells, where it plays a fundamental role in cytoskeleton stabilization and axonal transport. Several diseases collectively named tauopathies, such as Alzheimer’s disease, have been associated with an imbalance in the expression of alternative spliced Tau transcripts and the accumulation of hyperphosphorylated Tau, causing dysfunction and death of neuronal cells. Therefore, understanding the Tau exon splicing mechanisms may contribute to elucidating molecular factors that could underlie the development of neurodegenerative disorders. The aim of this study was to define the role of selected splicing factors in regulating Tau exon expression in cell lines and neuronal organoids. We demonstrated the role of the RNA-binding motif protein 20 (RBM20) splicing factor in regulating Tau exon 6 and exon 10, applying RNA-binding assay and qPCR analyses. Furthermore, we demonstrated that Tau expression was regulated during cerebral organoid differentiation, recapitulating in vivo Tau expression. These results suggest the feasibility of using brain organoid technology to study Tau alternative splicing during neural development, confirming that 3D cellular models could be used to study and characterize pathological processes taking place in Tau-related pathologies. Full article

Tick-borne viruses (TBVs) are a diverse group of arthropod-borne pathogens maintained in complex transmission cycles involving both tick vectors and vertebrate hosts. Among the known TBV transmission routes, co-feeding transmission, in which virus is transferred from an infected tick to an uninfected tick feeding on the same vertebrate host even in the absence of a detectable viremia, represents an important route that contributes to viral maintenance in nature. Although co-feeding transmission has been demonstrated across multiple vector, host, and virus combinations, the mechanisms governing this transmission route remain poorly defined. This review synthesizes current understanding of co-feeding transmission and highlights the importance of ecological and immunological factors that shape this process in nature. Specifically, we emphasize the role of the cutaneous microenvironment at the tick co-feeding site, where localized viral replication and tick salivary factors create conditions favorable for virus transfer between co-feeding ticks. We also highlight the requirements for co-feeding transmission to occur in nature and across seasons. Together, these insights support a model in which localized skin infection is a central feature of co-feeding transmission while underscoring key gaps in our understanding of the cellular and molecular mechanisms that govern this process. Full article

Background: Adenoid cystic carcinoma (ACC) demonstrates marked clinical heterogeneity that is inadequately explained by conventional histopathologic and staging systems alone. Recent studies have identified two molecular subtypes based on transcriptomic profiling and MYC/TP63 expression (ACC I: MYC-high/TP63-low; ACC II: MYC-low/TP63-high) with potential prognostic significance. However, the magnitude and consistency of their survival impact remain uncertain. Methods: A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. PubMed, Embase, and PubMed Central were searched through January 2026 for studies reporting overall survival in ACC stratified by MYC/TP63 molecular subtype. Hazard ratios (HRs) were pooled using random-effects models. Heterogeneity, subgroup analyses by classification method, sensitivity analyses, cumulative meta-analysis, influence diagnostics, and publication bias assessment were performed. Results: Five independent cohorts from two publications comprising 247 patients (90 ACC I, 157 ACC II) were included. ACC I was associated with significantly worse overall survival compared with ACC II, with a pooled HR of 3.88 (95% CI: 2.55–5.90; p < 0.001). No statistical heterogeneity was observed (I² = 0%). Prognostic separation was consistent across RNA sequencing and immunohistochemistry-based classification methods. Conclusions: Transcriptomic and MYC/TP63-based molecular subtyping provides strong and reproducible prognostic stratification in ACC. ACC I tumors confer an approximately four-fold higher mortality risk compared with ACC II tumors. Incorporation of molecular subtype into routine diagnostic and clinical decision-making may improve risk stratification, surveillance strategies, and future trial design in ACC. Full article

Body measurement traits are key indicators for evaluating growth performance, production potential, and breeding value in Yili horses. However, studies investigating the association between body measurement traits and mutation loci in Yili horses remain limited. In this study, 255 adult Yili mares were used as the study population, including 152 speed-type and 103 meat-type individuals. Whole-genome resequencing was performed, and four phenotypic traits and body weight were measured. A mixed linear model (MLM)-based genome-wide association study (GWAS) was conducted using GEMMA (v 0.98.5), incorporating age, farm effects, and top three principal components as covariates. In parallel, a machine learning-based GWAS (ML-GWAS) framework integrating Lasso regression for feature selection and Random Forest (RF) with five-fold cross-validation was applied to improve the detection of complex genetic signals. Using both conventional GWAS methods and machine learning-based GWAS approaches, a total of 238 mutation loci significantly associated with body measurement traits were identified, and 277 candidate genes were annotated. These genes may play a role in several biological processes, including skeletal development, muscle formation, cell growth, energy metabolism, and protein synthesis. The findings suggest that genetic variations have already manifested among the studied groups. The results indicate that genetic differences have already emerged among different Yili horse populations at the genomic level. Furthermore, this study demonstrates that integrating machine learning with conventional GWAS effectively improves the detection efficiency of loci associated with complex traits, while also providing new molecular evidence for understanding the genetic mechanisms underlying differences in body measurement traits among Yili horse groups. Full article

Background/Objective: Sesame (Sesamum indicum L.) is a nutritionally and economically important oilseed crop that is grown predominantly by smallholder farmers in Mozambique. However, its breeding process is constrained by a limited understanding of the genetic diversity in sesame germplasm. Therefore, this study determined the genetic diversity and population structure of a panel of 109 sesame accessions from Instituto de Investigação Agrária de Mocambique (IIAM) using DArTseq SNPs. Methods: The generated 14,763 SNPs were filtered, retaining 11,502 high-quality SNPs for this study. Results: Overall genetic diversity was moderate (mean He = 0.30, Ho = 0.30, MAF = 0.21, PIC = 0.25). Population structure analysis using sparse non-negative matrix factorization identified eight subpopulations, consistent with principal component analysis implemented via the Latent factor mixed model. Discriminant analysis of principal components (DAPC) and Ward’s hierarchical clustering based on Nei’s distance resolved the same eight clusters, although DAPC revealed overlap among clusters, consistent with extensive admixture. Analysis of molecular variance showed that 85.85% of total molecular variation was within subpopulations and 14.15% among the subpopulations. Pairwise fixation indices (ranging from 0.02 to 0.10) identified divergent subpopulations 7 and 1 as suitable candidates for hybridization. Within subpopulations, observed heterozygosity exceeded expected heterozygosity, likely reflecting residual heterozygosity in sesame landraces, admixture, reverse Wahlund effect and scoring of paralogs as heterozygous SNPs. Conclusions: Overall, this study provided insights into sesame’s genetic diversity in Mozambique, contributing to germplasm conservation and informed parental selection. Full article

Background/Objectives: Fall armyworm (FAW) (Spodoptera frugiperda) is a major constraint to maize production in Sub-Saharan Africa, including Mozambique. This study aimed to evaluate maize genotypes for resistance to FAW under greenhouse and field conditions and to assess the association between phenotypic resistance and genomic variation based on single nucleotide polymorphisms (SNPs). Methods: A total of 20 maize genotypes from the Agricultural Research Institute of Mozambique (IIAM) and the International Maize and Wheat Improvement Center (CIMMYT) were evaluated. FAW damage was quantified using the area under the damage progress curve (AUDPC). Phenotypic data were analyzed using ANOVA and mixed models, while molecular analysis was conducted using 10,603 SNP markers located on chromosomes previously associated with FAW resistance. Results: Significant genotypic differences were observed under greenhouse conditions (F = 1.94, p = 0.012) and in the field (p = 0.021), although environmental factors reduced variation in the field. Genotypes such as CML67, CML338, and Kenya amarelo (Acc3550) exhibited consistently lower AUDPC values across environments, indicating stable resistance. However, SNP allele proportion was not significantly associated with phenotypic resistance (r = 0.34, p = 0.147), and regression and ANOVA analyses confirmed the absence of a significant relationship (p > 0.05). Conclusions: FAW resistance in maize is quantitatively inherited and not explained by general genomic variation across candidate regions. Phenotypic screening remains essential, and further studies are required to identify specific loci for effective marker-assisted selection. The identified stable genotypes represent valuable resources for breeding FAW-resistant maize adapted to Mozambique. Full article

Amyloid-β (Aβ) protein, a cleavage product of the amyloid precursor protein (APP), is the main component of neuritic plaques in Alzheimer’s disease (AD), and its accumulation has been considered as the molecular driver of Alzheimer’s pathogenesis. Aβ has been a primary target for therapy since the amyloid cascade theory was put forth, with methods designed to prevent the generation of Aβ. The APP 5′-untranslated region (UTR) mRNA encodes a functional structured iron-responsive element (IRE) that represents a potential target for small molecule inhibitors as an anti-amyloid therapy for AD. Here, we offer a comprehensive strategy that uses RNA-targeted binding to inhibit APP translation. The IRE family is among the few 3-D mRNA regulatory elements with a known 3-D structure. Accordingly, we exploit these structural and functional characteristics as our strategy to target APP IRE structured mRNA to identify anti-amyloid drugs. The mRNA encoding proteins involved in iron metabolism are regulated by this family of similar nucleotide sequences. Post-transcriptional control of cytoplasmic mRNA is a rapidly developing area of biomedicine. Across animals, evolutionarily conserved IRE mRNAs serve as a model system for 3-D mRNAs. IRE mRNAs have shown great promise for chemical manipulation of mRNA and protein expression in biological systems by yielding “proof of principle” data for small molecules targeting mRNA structures. A novel approach to identifying RNA-directed therapeutics to regulate APP expression and Aβ-peptide generation for AD treatments is exemplified by APP 5′-UTR-directed small molecule inhibitors. Full article

Ferroptosis is an iron-dependent form of regulated cell death characterized by lipid peroxidation and failure of cellular antioxidant defenses. Increasing evidence indicates that ferroptosis contributes to the biological effects of radiotherapy and influences both tumor radiosensitivity and normal tissue injury. Because radiotherapy is a central treatment modality for many head and neck cancers, understanding how ferroptosis interacts with radiation responses has important translational implications. Ionizing radiation can induce ferroptosis through reactive oxygen species generation, disruption of glutathione metabolism, suppression of the SLC7A11–GSH–GPX4 antioxidant axis, and remodeling of membrane lipid composition. Conversely, tumor cells frequently develop radioresistance by reinforcing ferroptosis-suppressive pathways, including enhanced cystine transport, lipid desaturation, and metabolic adaptation. In head and neck cancers such as head and neck squamous cell carcinoma, nasopharyngeal carcinoma, oral squamous cell carcinoma, and thyroid malignancies, experimental studies show that modulation of ferroptosis significantly alters radiation response. Strategies that promote ferroptosis—including inhibition of antioxidant defenses, targeting of lipid metabolism, and modulation of iron homeostasis—have demonstrated radiosensitizing effects in preclinical models. However, ferroptosis may also contribute to radiation-induced normal tissue injury, particularly in oxidative stress-sensitive organs such as the salivary glands. This review summarizes the molecular basis of ferroptosis in radiotherapy, examines its role in radiosensitivity and radioresistance in head and neck cancers, and discusses therapeutic strategies to exploit ferroptosis while minimizing normal tissue toxicity. Full article