Search Results (422)

The uplift of the Qinghai–Tibet Plateau has shaped a unique extreme environment, fostering distinct endemic aquatic organisms. Schizopygopsis pylzovi, a vulnerable endemic fish in the upper Yellow River, is a key model for studying the biogeographic patterns of plateau fish. To assess its genetic characteristics and evolutionary dynamics, we comprehensively evaluated 11 geographic populations of S. pylzovi using two complementary mitochondrial markers, the conserved COI gene and the fast-evolving D-loop region. A total of 142 COI and 143 D-loop sequences were analyzed, and sequences alignment, haplotype network construction, AMOVA, and neutrality tests were performed. AMOVA revealed that genetic variation was mainly distributed within populations, indicating weak population differentiation. Neutrality tests and mismatch distribution analysis suggested historical and recent population expansion events. Our findings highlight the value of joint analysis using COI and D-loop markers in revealing the genetic structure of S. pylzovi, provide new insights into the impact of plateau uplift on fish evolution, and establish a scientific basis for the conservation of this vulnerable species. Full article

The rapid evolution of metabolic resistance to chemical insecticides and the adaptation to plant allelochemicals in insect pests have become major challenges in global pest management. While the overexpression of cytochrome P450 monooxygenases (P450s) is a well-recognized classic detoxification mechanism, the upstream epigenetic and post-transcriptional regulatory networks governing this process have only recently been elucidated. In this narrative review, the latest research progress on microRNAs (miRNAs) as crucial “fine-tuners” in insect detoxification networks is systematically summarized. The classic regulatory model is highlighted: the induced or constitutive downregulation of specific miRNAs relieves the translational repression of their target P450 genes, thereby contributing to metabolic resistance to major insecticide classes, including neonicotinoids, diamides, and pro-insecticides. Furthermore, the evolutionary recruitment mechanisms of conserved miRNAs in host plant adaptation are explored, and how endocrine signals, such as juvenile hormone (JH) and 20-hydroxyecdysone (20E), synergistically regulate the miRNA–P450 axis is analyzed. The “sponge effect”, wherein highly expressed P450 mRNAs act as competitive endogenous RNAs (ceRNAs) to sequester miRNAs, and the consequent physiological trade-offs (fitness costs) resulting from the prioritization of metabolic resources toward the detoxification system are comprehensively discussed. Finally, the current core methodologies for miRNA functional validation are critically evaluated, and the application potential and ecological safety prerequisites of miRNA-based nanobiopesticides for targeted and sustainable pest management are discussed. By integrating mechanistic insights with translational perspectives, this review highlights miRNA–P450 regulatory networks as key determinants of insecticide resistance evolution and as promising targets for developing more precise, environmentally compatible pest-management strategies. Full article

Antimicrobial resistance (AMR) is a leading global cause of death, with recent World Health Organization (WHO) data revealing that one in six laboratory-confirmed bacterial infections shows resistance to at least one antibiotic treatment. This review comprehensively analyzes the AMR landscape in 2026, detailing its evolution, mechanisms, and the innovative strategies being deployed to combat it. Driven by Darwinian selection and accelerated by factors like antibiotic overuse during the Coronavirus Disease 2019 (COVID-19) pandemic (predominantly in hospitalized patients with suspected bacterial co-infection), AMR is propelled by a diverse molecular arsenal in bacteria. Key mechanisms include enzymatic drug inactivation (e.g., the diversifying β-lactamase superfamily), target site modification (e.g., mcr genes conferring colistin resistance), efflux pumps, and biofilm formation. The rapid global spread of these traits is facilitated by a dynamic “mobilome”, a network of plasmids and transposons that shuttle resistance genes between species. This crisis has sparked a major scientific mobilization. Advances include the discovery of novel antibiotic scaffolds like lariocidin and the regulatory approval of critical new antibiotic/inhibitor combinations such as sulbactam/durlobactam and aztreonam/avibactam, which target highly resistant Gram-negative bacteria. Moreover, the first-in-class antibiotic gepotidacin offers a new option for urinary tract infections. Beyond traditional drugs, the pipeline is diversifying to include phage therapy, antivirulence strategies, and artificial intelligence-guided drug discovery. This diversification is critical as it helps preserve the effectiveness of existing Medically Important Antimicrobials (MIAs), those deemed essential for human medicine, by providing alternative or adjunctive treatment options. However, scientific innovation alone is insufficient. This review argues that lasting success requires parallel progress in global policy and infrastructure. Strategic priorities beyond 2026 must include finalizing and funding updated global action plans, strengthening real-time surveillance and diagnostic capacity, especially in low-resource settings, and implementing new economic models to de-risk antibiotic development. Embedding effective antimicrobial stewardship within universal health coverage and pandemic preparedness plans is crucial. Ultimately, defeating AMR demands an unprecedented, coordinated global effort that outpaces the relentless adaptability of bacterial pathogens. Full article

Persistently high levels of abiotic stress define extreme environments. Even for adapted extremophiles, we argue this stress remains a continuous physiological challenge, necessitating energetically costly homeostasis. Crucially, this persistent pressure drives a self-reinforcing feedback loop across biological scales: it accelerates genomic evolution and concurrently reshapes ecological network architecture. Genomic innovations provide new traits for network reconfiguration, while the restructured network acts as a selective filter guiding subsequent evolution. This loop underpins extreme ecosystem resilience—the capacity for stress-induced adaptive restructuring. We synthesize mechanisms of this stress-adaptation interplay, propose testable hypotheses and outline experimental evolution approaches to validate this predictive framework for microbial responses to global change. Full article

Plant diseases remain a major constraint to crop productivity and global food security. Conventional breeding has long been used to develop resistant cultivars through the introgression of resistance traits from wild relatives and the selection of favorable phenotypes. However, this process is often slow and limited by linkage drag, known genetic diversity, intrinsic genetic limitations, and the rapid evolution of pathogen populations. Molecular breeding strategies, including marker-assisted selection and genomic selection, have improved the precision of resistance breeding but still rely on existing genetic variation. Recent advances in genome editing technologies are transforming plant breeding by enabling precise modification of gene targets. CRISPR-based systems allow targeted gene knockouts, promoter editing, allelic replacement, and multiplex editing to rapidly generate resistance traits. Many studies have demonstrated that editing susceptibility genes or regulatory regions can enhance resistance to diverse pathogens. Recent research shows that resistance can also be improved by targeting non-classical genes involved in plant immunity, including transcription factors, membrane transporters, heat shock proteins, cell wall-related genes, metabolic enzymes, and epigenetic regulators. Emerging tools such as base editing, prime editing, regulatory tools, and transposon-associated genome engineering systems are further expanding the precision and versatility of plant genome editing. Despite these advances, challenges related to delivery systems, editing efficiency, regulatory frameworks, and field validation remain. Continued technological progress and improved knowledge of plant immune networks will be essential to fully integrate genome editing into crop improvement programs. Full article

The rapid evolution of transcriptome sequencing technologies has driven significant breakthroughs across the life sciences. The advent of single-cell RNA-sequencing (scRNA-seq) has enabled gene expression profiling at single-cell resolution, whereas spatial transcriptomics further contextualizes these transcriptional profiles within preserved tissue morphology. Concurrently, advancements in artificial intelligence have introduced unprecedented opportunities in bioinformatics. As a core component of artificial intelligence, machine learning (ML) substantially outperforms traditional computational methods in deciphering complex, high-dimensional biological data. This review systematically summarizes the significant advantages of integrating ML algorithms into transcriptomic workflows. By leveraging these advanced computational tools, researchers can efficiently extract comprehensive biological insights, elucidate intricate Gene Regulatory Networks, and generate intuitive visualizations. Ultimately, ML-driven transcriptomics provides a robust technical foundation for disease diagnosis, drug discovery, and precision medicine. These advancements underscore the pivotal role of ML in transforming transcriptomic data analysis into an intelligent, highly precise, and multidimensional discipline, thereby accelerating future biological discoveries. Full article

The survival of complex multicellular organisms depends on continuous inter-organ communication networks that coordinate organism-wide responses across physiological conditions and stress states, including adaptation to environmental challenges, infection, and injury. Rather than operating as isolated units, organ systems are integrated through interconnected signaling networks that transmit biological information across tissues. Building on prior work examining individual physiological pathways, this review introduces a unified systems-level framework that integrates inter-organ communication into a coherent model of organism-wide regulation. This review proposes a systems-level framework in which homeostasis is maintained through eight principal communication systems: neural, endocrine, immune-inflammatory, vascular, lymphatic, metabolic, microbiome–gut, and mechanical-structural. Epithelial barriers function as dynamic signaling interfaces within multiple systems, while extracellular vesicles act as cross-system mediators of information transfer rather than as independent communication networks. These systems operate across distinct temporal scales to coordinate host defense, metabolic adaptation, vascular regulation, and tissue repair. The framework further introduces a temporal hierarchy of signaling dynamics that links communication systems to phase-specific responses during physiological stress. Within this integrated network, glucocorticoid receptor α (GRα) is proposed to function as a systems-level regulator of inter-organ communication, supported by converging mechanistic, experimental, and clinical evidence, with variability in the strength of evidence across domains. In contrast to prior reviews, which addressed GRα function within individual systems, this work conceptualizes GRα as a central rheostat coordinating cross-system signaling and temporal transitions in homeostatic correction. Evidence was identified through hypothesis-driven searches using the Consensus AI platform and verified through manual review of primary biomedical literature. GRα, a ligand-activated transcription factor expressed in most nucleated cells, enables hormonal stress signals to coordinate gene-expression programs across tissues, modulating neuroendocrine responses, endothelial function, inflammatory signaling, metabolic regulation, microbiome–host interactions, and tissue remodeling. Systemic responses to stress progress through three phases of homeostatic correction—Priming, Modulatory, and Restorative—within which GRα supports integrated organism-wide adaptation. This integrative framework provides a mechanistic basis for understanding the emergence and temporal evolution of biological responses in health and critical illness. Full article

Animal manure represents a critical reservoir that facilitates the dissemination of antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs). However, the current understanding of ARG evolution during extensive composting remains insufficient. This study systematically investigated two common aerobic composting techniques: push-flow trough composting (FC) and membrane-covered composting (FM). Results indicated that both processes demonstrated substantial antibiotic removal capacities, achieving total removal rates of 88.89% (FC) and 79.20% (FM). Nevertheless, their effectiveness in removing ARGs varied considerably. During the 31 days of composting, the total removal rates of ARGs were 59.97% (FC) and 76.11% (FM), while the removal rates for class 1 integron (intI1) were 2.31% (FC) and 69.13% (FM). With the exception of tetX, tetG, and tetW, all other ARGs exhibited a rebound during the later stage of the FC process. In contrast, the FM process effectively reduced the risk of ARG rebound during this phase, which can be attributed to its extended thermophilic period and the physical barrier effect of the semi-permeable membrane. Network analysis indicated that ARGs were primarily associated with Bacillota and Pseudomonadota. The Partial Least Squares Path Model (PLS-PM) revealed that the bacterial community was the main factor influencing ARG dynamics in FC, while in FM, both the bacterial community and intI1 were the primary drivers. This study provides critical insights for optimizing composting strategies to prevent the dissemination of antibiotic resistance. Full article

Senecavirus A (SVA) has rapidly emerged as a globally distributed swine pathogen, with clinical signs mimicking vesicular diseases such as Foot-and-Mouth Disease, posing challenges for timely detection and control. Here, we analyzed 329 complete SVA genomes spanning multiple continents to provide a comprehensive view of its evolutionary dynamics, recombination patterns, haplotype diversity, and global dissemination. Phylogenetic analyses revealed two major lineages: Lineage 1, consisting mainly of early strains from the United States before 2007, and Lineage 2, which emerged post-2007 and subsequently spread across the Americas and East Asia. Recombination was confined to Lineage 2 and concentrated in nonstructural regions, particularly 2C, highlighting intra-lineage genetic exchange as a driver of recent diversification. Haplotype analysis of the 3AB gene identified 170 distinct haplotypes, revealing a star-like network structure consistent with rapid population expansion from a central ancestral variant, while secondary branches reflect ongoing regional diversification. Despite this high genetic variation, genome-wide dN/dS ratios remained below one, and purifying selection was strongest in the N-terminal domains of structural and nonstructural proteins, indicating functional constraints that maintain viral fitness. Time-scaled phylogenetic reconstruction and Bayesian Skyline analysis revealed rapid lineage diversification and a marked increase in effective population size in the early 2010s. Phylogeographic inference further identified repeated introductions from the Americas into East Asia, likely facilitated by swine trade and other anthropogenic factors. Collectively, SVA evolution is driven by frequent mutation and intra-lineage recombination yet constrained by pervasive purifying selection, generating extensive genetic diversity while maintaining functional integrity, with implications for genomic surveillance and targeted control. Full article

GDSL esterase/lipase (GELP) proteins constitute an evolutionarily conserved yet functionally diversified hydrolase family in land plants. They participate in cuticle and secondary cell wall biosynthesis, seed lipid remobilization, reproductive development, and hormone-mediated responses to biotic and abiotic stresses. Despite extensive genome-wide and comparative genomic studies that have categorized large GELPs across numerous crops and model species, only a fraction of members have been functionally characterized in plants, and their catalytic mechanisms and regulatory architectures remain poorly understood. Recent population genomics and cross-species orthogroup analyses in 46 angiosperms have uncovered substantial natural variation within GELP coding sequences and regulatory regions, providing a powerful framework to link allelic diversity to evolutionary trajectories and physiological functions. This review synthesizes current knowledge on GELP evolution, biochemical properties, and roles in development and stress adaptation, and critically evaluates how these insights can be translated into biotechnology and molecular breeding strategies. It highlights emerging resources and concepts from orthogroup-based classification and multi-species datasets that enable systematic discovery of GELP alleles affecting agronomic traits. It further outlines research exploiting GELPs in crop improvement, emphasizing the integration of reverse and forward genetics with multi-omics profiling, biochemical and structural characterization, and gene regulatory network reconstruction. Systematic assessment of the phenotypic impacts of single and combinatorial GELP perturbations on yield, quality, and stress resilience is proposed as a key step toward translating basic insights into breeding and engineering strategies. Full article

Triplophysa yarkandensis (Cypriniformes: Nemacheilidae), a rare endemic fish in the Tarim River Basin, Xinjiang, China, plays a pivotal role in maintaining the stability of plateau saline–alkaline aquatic ecosystems, yet its survival is increasingly threatened by habitat salinization. However, the multi-dimensional synergistic adaptation mechanisms linking its phenotypic variation, intestinal structure, and associated microbial communities to extreme saline–alkaline stress remain poorly understood. In this study, we innovatively integrated morphological/intestinal histological characterization, 16S rRNA gene sequencing, and microbial ecological analyses (co-occurrence networks and assembly processes) to systematically decode its adaptive strategies. Results revealed that T. yarkandensis exhibits a streamlined body shape, morphological variability, and elongated intestinal villi that may support locomotion and nutrient/ion uptake under osmotic stress. Its gut exerts a stringent selective filter, driving distinct differentiation between water and gut microbial communities—with gut-enriched core taxa (Aurantimicrobium and Aestuariivirga) and functional pathways (unsaturated fatty acid biosynthesis and ABC transporters) specialized for osmoregulation. Notably, the water microbial assembly is dominated by stochastic processes, while the gut assembly relies on host-driven deterministic selection, forming a habitat-specific adaptive pattern. These findings uncover the synergistic adaptation system of host phenotype and gut microbiota for survival in extreme saline–alkaline habitats, advancing our understanding of fish–microbe co-evolution in extreme ecosystems and providing critical theoretical support for the conservation of rare plateau fish, as well as guidance for the utilization of saline–alkaline water resources in aquaculture. Full article

This study conducted a genome-wide identification and functional analysis of the glutathione S-transferase (GST) gene family in the xerophytic desert shrub Reaumuria soongorica. A total of 67 GST genes were identified, classified into seven subfamilies, including Phi and Tau, with family expansion primarily attributed to small-scale duplication events. The findings revealed that ResoGST52, a member of the Tau subfamily, serves as a core gene in drought response, exhibiting significant upregulation of 2.40-fold in leaves and 9.01-fold in roots under drought stress. Mechanistic investigations indicated that the expression of ResoGST52 is likely directly regulated by the transcription factor ResoDof17, with specific hydrogen bonding interactions identified between the two. Co-expression network analysis further demonstrated that ResoGST52 cooperates with key pathways such as plant hormone signaling, MAPK cascades, and glutathione metabolism to collectively respond to drought stress. Notably, evolutionary analysis revealed that ResoGST52 has undergone positive selection, with three positively selected sites identified. Among these, the p.Ala115Ser mutation increases the volume of the protein’s active site pocket, while the remaining mutations enhance surface hydrophobicity, thereby improving protein stability and catalytic efficiency under extreme drought conditions. In summary, this study not only systematically identifies the GST gene family in R. soongorica but also elucidates the central role of ResoGST52 in drought adaptation through multiple layers—from transcriptional regulation and co-expression networks to protein structural adaptive evolution—providing valuable candidate genes and theoretical insights for genetic improvement of drought tolerance in crops. Full article

The single von Willebrand factor C (SVWC) domain-containing protein family represents a crucial class of immune molecules recently identified in insects and crustaceans. Initially regarded as functional analogs of vertebrate interferons (IFNs) due to their virus-induced expression and activation of the Janus kinase-signal transducer and activator of the transcription (JAK-STAT) pathway, recent studies have revealed that SVWC proteins possess far more complex functions. Many SVWC members are themselves a novel class of pattern recognition receptors (PRRs) that can directly bind to viruses and bacteria. Importantly, SVWCs are not a single entity but a highly diverse family—multiple subtypes exist in Drosophila, Bombyx mori, and shrimp—a gene expansion that implies functional differentiation. This review systematically examines the multifunctionality of SVWC proteins in insects and crustaceans, with a particular focus on the functional specialization driven by subtype diversity. We delve into the complex regulatory networks governing SVWC expression, including the differential activation by nuclear factor kappa B (NF-κB) pathways (Dorsal, Rel-2, Relish) and interferon regulatory factor (IRF) pathways. We detail the unique signaling mechanism by which SVWCs activate the JAK-STAT pathway via integrins, rather than the canonical Domeless receptor. Furthermore, we extend the discussion to the emerging roles of SVWCs as PRRs in humoral immunity (activating Toll/IMD pathways to induce antimicrobial peptides) and cellular immunity (mediating hemocyte phagocytosis). Based on current evidence, We propose that diverse SVWC subtypes may recognize distinct pathogens, bind to different integrin receptors, and activate specific STAT variants via disparate upstream induction pathways, thereby establishing a systematic and hierarchical immunoregulatory network. This understanding positions the SVWC protein family as a central hub in the insect immune network and offers a novel perspective on the complexity and evolution of invertebrate immunity. Full article

Citrus genomes as storehouses of genetic information of immense commercial utility remain untapped for the improvement of fruit quality traits and other production-related stresses. With the rapid expansion of transcriptomic datasets, integrative meta-analysis has further aided in uncovering interspecies molecular mechanisms associated with fruit quality development. In this study, we performed a cross-project RNA-Seq meta-analysis, integrating multiple publicly available BioProjects encompassing diverse citrus species, viz., Citrus sinensis, C. reticulata, C. maxima, C. clementina, C. japonica, and C. papeda, known to dominate the morphogenetic evolution of the citrus industry. High-throughput RNA-Seq data were processed using various bioinformatics tools. A total of 15 interspecies comparisons identified 676 unique DEGs, enriched in pathways related to secondary juice yield and processing quality traits. We also established that domestication aided in metabolism, oxidative stress responses, phenylpropanoid and flavonoid biosynthesis, and hormone-mediated signaling. Multivariate analyses (PCA and heatmap visualization) highlighted distinct yet overlapping expression patterns across these citrus species. By combining differential expression, co-expression network analysis and QTL-GWAS integration, we identified 19 high-confidence candidate genes responsible for transcriptomic variation associated with measurable fruit quality traits. Genes such as LOC102612823 and LOC102607495, which co-localized with seed number QTLs on chromosome 1, represented strong candidates regulating reproductive development and seed formation, the traits that directly influence fruit texture and market acceptability. Genes linked to juice content QTLs, including LOC102611137 and LOC102612553 on chromosome 5, suggested their roles in metabolic regulations behind juice accumulation. These loci provided definitive breeding clues for enhancing the reshaping of citrus fruit transcriptomes while retaining key ancestral regulatory components. Full article

Targeted therapies are reshaping oncology by enabling treatment selection based on actionable molecular alterations, improving precision, and reducing unnecessary toxicity. This review provides an up-to-date overview of current targeted treatment modalities and the medicinal chemistry principles that support their discovery and optimization. We synthesize evidence on small-molecule and biologic strategies spanning receptor and non-receptor kinases and their major signaling axes (PI3K-AKT-mTOR and RAS-RAF-MEK-ERK), apoptosis regulation (BCL-2 family), DNA repair via poly(ADP-ribose) polymerase (PARP) inhibition, and epigenetic or metabolic targets including histone deacetylases (HDACs), bromodomain and extra-terminal proteins (BET), and mutant isocitrate dehydrogenases (IDH1/2). Across these areas, we summarize recurrent resistance mechanisms and the rationale for combination or sequential approaches. Biologic targeted therapy is discussed in parallel, including immune checkpoint blockade, antibody–drug conjugates, bispecific antibodies (BsAb), and cell therapies such as chimeric antigen receptor T cells, with emphasis on biomarker-guided patient stratification. Finally, we outline emerging directions beyond canonical nodes, including modulation of the p53-MDM2/MDM4 axis, ferroptosis control through AIFM2/FSP1, and innate immune pathways such as CD47-SIRPa and the stimulator of interferon genes (STING). Overall, the field is shifting from single-target inhibition toward integrated strategies that combine precise molecular targeting with an understanding of signaling network dynamics, resistance evolution, and therapeutic vulnerabilities. Full article