Search Results (284)

Encapsulation is a major cellular defense reaction in lepidopterans. However, in the oriental armyworm (Mythimna separata), the molecular regulators that coordinate hemocyte adhesion and multilayer capsule assembly remain poorly defined. In this study, we identified Mythimna separata encapsulation related gene 1 (MysERG1) as a novel cellular immune regulatory gene. MysERG1 transcripts were most abundant in hemocytes and were notably upregulated in adherent hemocytes as well as in samples of capsules, indicating an association with adhesion-dependent hemocyte activation. Following separation of granulocytes and plasmatocytes, MysERG1 expression was observed to be higher in adherent plasmatocytes than in adherent granulocytes. However, recombinant MysERG1 selectively increased granulocyte adhesion but did not significantly affect plasmatocyte adhesion and was specifically localized on granulocytes. Additionally, recombinant MysERG1 enhanced hemocyte aggregation on foreign surfaces, highlighting its functional role in facilitating encapsulation. Functional knockdown using double-stranded RNA significantly reduced the size of the capsules, indicating that MysERG1 is required for robust capsule formation. This study identifies MysERG1 as a novel factor involved in hemocyte cooperation during encapsulation in M. separata and presents a conceptual framework for inter-hemocyte communication mechanisms in lepidopteran cellular immunity. Full article

Bioconversion of lignocellulosic biomass into edible, nutrient-rich products using low-cost forestry waste offers substantial ecological and economic benefits. Composting forestry waste as a substrate for oyster mushroom (Pleurotus ostreatus) cultivation is an effective recovery strategy. However, the specific microbial-driven mechanisms by which nitrogen sources regulate lignocellulose degradation and compost quality during forestry waste composting for Pleurotus ostreatus substrate preparation remain to be elucidated. We evaluated three organic nitrogen sources (bran, soybean meal, and chicken manure) and one inorganic source (diammonium phosphate, DAP) during composting of forest-waste-based substrates. Composting performance and cultivation outcomes were assessed using physicochemical analyses, lignocellulose degradation measurements, high-throughput sequencing of bacterial 16S rRNA and fungal ITS, and biological efficiency. Organic nitrogen sources enhanced compost temperature and lignocellulose degradation by providing sustained nitrogen release, promoting stable colonization of core microbial communities and cooperative bacteria–fungi networks. In contrast, inorganic nitrogen resulted in slower heating, minimal lignocellulose degradation (0.75%), and unstable, competition-dominated microbial networks. Nitrogen sources indirectly shaped microbial communities by regulating the C/N ratio, pH, and electrical conductivity. Lignocellulose degradation and bacterial diversity significantly influenced mushroom biological efficiency, with bacterial diversity strongly regulating degradation rates. The forest waste–bran treatment achieved the highest biological efficiency (78.35%). These findings offer a practical strategy for optimizing forestry waste bioconversion into fungal protein. Full article

Mediator is a central transcriptional coactivator that connects sequence-specific transcription factors with RNA polymerase II to control inducible gene expression in plants. MED16 is a Mediator tail module subunit that functions as a context-dependent integrator, helping coordinate developmental programs with environmental adaptation. This review summarizes current evidence for MED16 function from structural and evolutionary perspectives to physiological outputs, with emphasis on how MED16 interacts with transcription factors and other Mediator subunits to shape RNA polymerase II engagement at target loci. In terms of development, MED16 contributes to organ growth and root system architecture, and comparative studies have revealed that it plays conserved roles in lineage-specific wiring. Under abiotic stress, MED16 supports the efficient activation of stress-inducible transcription, including cold acclimation and nutrient stress responses such as phosphate starvation-dependent root remodeling. In immunity, MED16 modulates salicylic acid- and jasmonate/ethylene-associated defence outputs and can be targeted by plant viruses, which is consistent with its role in antiviral transcriptional responses. Mechanistically, MED16 participates in cooperative and competitive interactions within the Mediator complex that tune hormone-responsive outputs, exemplified by MED25-related competition in abscisic acid signalling. We highlight key limitations and future directions, including the need for mechanistic validation beyond Arabidopsis, clearer models of dosage control in crops, improved understanding of context-dependent tail configurations, and high-resolution mapping of MED16 interaction interfaces. Full article

Soil salinization remains a major global challenge, and rice cultivation has been widely practiced in saline–alkali soils of the black soil region in Northeast China as an effective strategy for soil improvement. However, this practice is often slow to produce benefits and is prone to secondary salinization, limiting rapid gains in soil fertility and crop productivity. To address these limitations, this study evaluated the effects of four soil amendment strategies (microbial inoculant, organic fertilizer, biochar, and their combined application) on bacterial and fungal communities, as assessed by high-throughput sequencing of the 16S rRNA gene and the ITS region, respectively. The application of microbial inoculants significantly increased bacterial diversity and richness, while all amendment treatments promoted the enrichment of key microbial groups. Organic inputs strongly influenced microbial community assembly, with microbial inoculant and combined treatments shifting assembly toward more deterministic processes. In addition, the amendments altered microbial interaction networks, leading to widespread cooperative relationships dominated by positive associations and strong interactions across taxonomic groups. Notably, the combined treatment reshaped bacterial functional profiles and reduced the predicted abundance of pathogenic fungi. Overall, these results demonstrate that organic amelioration strategies can improve the ecological functioning of saline–alkali soils by regulating microbial community assembly and interactions. This study provides a robust theoretical framework and scalable practical solutions for the integrated management and sustainable development of saline–alkali agriculture. Full article

Biological soil crusts (BSCs) are critical ecological components in arid lands. Their formation and stability hinge on the assembly and interactive networks of cyanobacteria-led bacterial communities. Yet, how different functional cyanobacteria shape the underlying microbial structure and assembly rules is poorly understood. Here, we cultivated artificial algal crusts using two representative cyanobacteria: the nitrogen-fixing Leptolyngbya sp. and the non-nitrogen-fixing Microcoleus vaginatus (M. vaginatus CM01). A total of six treatments were established based on the presence or absence of spraying with in situ BSCs leachate: a control group without inoculation of algae or bacteria (soil, S); a treatment group sprayed only with bacterial suspension (soil + bacteria, SB); a treatment group sprayed only with M. vaginatus CM01 (soil + M. vaginatus CM01, SM); a treatment group co-inoculated with both BSCs leachate and M. vaginatus CM01 (soil + M. vaginatus CM01 + bacteria, SMB); a treatment group inoculated only with Leptolyngbya sp. CT01 (soil + Leptolyngbya sp. CT01, SL); and a treatment group co-inoculated with Leptolyngbya sp. CT01 and biocrust leachate (soil + Leptolyngbya sp. CT01 + bacteria, SLB). By integrating 16S rRNA gene sequencing, neutral community modeling (NCM), and structural equation modeling (SEM), we dissected differences in Cyano-BSCs development, bacterial community composition, co-occurrence networks, and assembly mechanisms. Inoculation with M. vaginatus CM01 (SM, SMB) superiorly promoted Cyano-BSCs development: the SM group achieved the highest coverage (23.33%), while the SMB group showed marked increases in organic matter (OM, 4.10 g·kg⁻¹) and chlorophyll a (Chla, 13.40 μg·g⁻¹), alongside a >5-fold rise in bacterial, cyanobacterial, and nitrogen-fixation gene abundances versus controls. The mechanism centers on extracellular polymeric substances (EPS) secreted by M. vaginatus, which homogenized the microenvironment, suppressed stochastic bacterial dispersal (NCM, SM: R² = 0.698), and enhanced deterministic selection. This process forged a highly cooperative network (89.74% positive links, average degree 34.71) that directionally enriched Cyanobacteria (relative abundance 40.40%). The Shannon index of Cyano-BSCs from the group (SMB) reached 7.72 ± 0.09, reflecting high microbial community diversity. SEM confirmed M. vaginatus directly regulated bacterial assembly (path coefficient = 0.59, p < 0.05) and indirectly improved the soil environment (path coefficient = 0.64, p < 0.05), establishing a “cyanobacteria-community-environment” feedback loop. Conversely, the Leptolyngbya sp. groups (SL, SLB), despite enriching nitrogen-fixing bacteria and fungi, exhibited low carbon fixation efficiency (notably 1.26 g·kg⁻¹ OM in SL) and lack of EPS; communities remained stochastic (NCM, SL: R² = 0.751) with no effective regulatory pathway—a pattern mirrored in S and SB groups. Our findings demonstrate that M. vaginatus acts as a core engineer of biological soil Cyano-BSCs formation via an “EPS-mediated habitat filtering—functional group enrichment—cooperative network assembly” cascade, enforcing deterministic community construction. Leptolyngbya sp., with limited niche-constructing ability, fails to exert comparable control. This work provides a targeted framework for the artificial restoration of Cyano-BSCs in arid zones. Full article

The Mediator complex is a central regulator of eukaryotic transcription, functioning as a dynamic molecular interface between gene-specific transcription factors and RNA polymerase II (Pol II). Although its overall architecture and general role in transcription have been extensively reviewed, accumulating genetic, genomic, and clinical evidence indicates that individual Mediator subunits make distinct and non-redundant contributions to human physiology and disease. In this review, we move beyond a generic description of Mediator function and present a subunit-resolved synthesis of Mediator biology with an emphasis on disease pathogenesis. A key feature of this review is a comprehensive table integrating disease associations and molecular functions of individual human Mediator subunits, enabling rapid assessment of functional specialization across the complex. We further discuss chromatin-based mechanisms of Mediator action, including cooperation with cohesin and architectural factors to regulate enhancer-promoter communication and higher-order genome organization. By organizing recent structural, mechanistic, and pathological findings into a unified framework, this review highlights how disruption of specific Mediator subunits contributes to cancer, developmental disorders, and metabolic disease, and outlines emerging opportunities for therapeutic intervention. Full article

Background: DNMT3B is frequently overexpressed in molecular subsets of acute myeloid leukemia (AML) and is associated with poor prognosis. Unlike DNMT3A, DNMT3B is rarely mutated, suggesting dysregulation through epigenetic mechanisms. The regulatory basis and downstream consequences of DNMT3B overexpression in AML remain incompletely defined. Methods: We integrated analyses of BeatAML, TCGA, and BLUEPRINT cohorts with multi-omic profiling (RNA-seq, DNA methylation, ATAC-seq, and proteomics) in DNMT3B-high AML models. Nanaomycin A (NanA) was used as a DNMT3B-directed functional probe to interrogate cis-regulatory remodeling, transcriptional circuitry, and apoptotic dependencies. Results: DNMT3B overexpression was linked to enhancer-associated chromatin activation rather than recurrent genetic mutation, particularly in CEBPA- and NPM1-mutant AML. NanA exposure produced focal epigenomic remodeling, including 6900 differentially methylated CpGs, with 268 CpGs located within regions of altered chromatin accessibility. These changes were accompanied by coordinated transcriptomic and proteomic reprogramming enriched for cell-cycle, checkpoint, and stress-response pathways. Functionally, DNMT3B perturbation induced redistribution of cell-cycle phases with increased S-phase fraction and progressive apoptosis. Transcriptional profiling demonstrated induction of BH3-only sensitizers (NOXA, PUMA), repression of BCL2, and compensatory upregulation of MCL1 and BCL-XL, collectively reshaping apoptotic dependency. Combined DNMT3B perturbation and BCL2 inhibition produced cooperative cytotoxicity in DNMT3B-high AML models. Conclusion: DNMT3B functions as a context-dependent epigenetic regulator linking enhancer-associated chromatin organization with proliferative control and apoptotic resistance in AML. DNMT3B-directed epigenetic perturbation remodels cis-regulatory circuitry and is associated with increased venetoclax responsiveness, supporting DNMT3B-governed networks as a candidate co-targeting axis in high-risk AML. Full article

Cadmium (Cd) contamination of agricultural soils threatens crop productivity and food safety by disrupting physiological and molecular processes in plants. Increasing evidence indicates that epigenetic regulation, including DNA methylation, histone modifications, and emerging epitranscriptomic marks such as RNA methylation, plays a crucial role in coordinating plant responses to Cd stress. In parallel, plant-associated microbiomes have emerged as influential modulators of metal uptake, antioxidant capacity, hormone signaling, and stress resilience. Yet the mechanisms by which microbiome-derived signals intersect with host chromatin and transcriptome regulation under Cd exposure remain poorly understood. This review synthesizes current knowledge on plant epigenetic responses to Cd stress and critically examines how microbial metabolites, phytohormones, and redox-active compounds shape plant regulatory networks. Network-based ecological studies reveal that increased microbial community complexity and cooperative interactions are consistently associated with reduced Cd accumulation and enhanced plant performance, suggesting that microbial organization itself may represent an additional regulatory layer influencing plant responses. Despite compelling conceptual links, direct experimental evidence connecting microbiome signals to stable epigenetic or epitranscriptomic reprogramming under Cd stress remains limited. To date, only limited experimental studies have demonstrated causal relationships between microbial cues and host DNA or RNA methylation dynamics in Cd-exposed plants, highlighting clear mechanistic potential while also underscoring remaining knowledge gaps. By integrating physiological, ecological, and chromatin-level perspectives, this review identifies key unanswered questions and outlines future research directions to establish causal links between microbial community dynamics, epigenetic regulation, and long-term Cd stress adaptation in plants. Full article

Intracerebral hemorrhage (ICH) is the deadliest subtype of stroke, and its primary harm to the human body arises from the formation of brain hematomas. Promoting microglial-mediated endogenous hematoma clearance has become a key focus in current ICH treatment strategies. Semaphorin 3s (Sema3s) are molecular signals involved in the regulation of the central nervous system, angiogenesis, and microenvironment homeostasis, and they are closely associated with various central nervous system diseases. Hematoma clearance and inflammation regulation are crucial to the role of microglia, yet the mechanisms by which Sema3s regulate microglia after ICH remain unclear. Here, using high-throughput RNA sequencing of a mouse ICH model, we identified that neuron-derived Sema3B is downregulated after ICH. Further mechanistic studies revealed that Sema3B can bind to PlexinA1 on microglia, activating NRF2 to promote the expression of the phagocytic receptor TREM2 and the key hematoma clearance molecule HO-1. Furthermore, Sema3B enhances the interaction between PlexinA1 and TREM2, cooperatively boosting microglial phagocytosis of the hematoma after ICH. Furthermore, Sema3B regulates the M2 polarization of microglia, exerting an anti-inflammatory effect. Our findings suggest that manipulating microglial phagocytosis of hematoma and inflammation suppression via regulation of Sema3B may be a potential strategy for treating patients with ICH. Full article

Traditionally, scientists tend to approach cancer research in a reductionistic way: aiming at uncovering underlying, separate components in malignant processes. And indeed, great progress has been made by reducing the development of a tumor to single, specific genes and mutations. For instance, familial adenomatous polyposis (FAP) could be reduced to a germline mutation in the Adenomatous Polyposis Coli (APC) gene. The escape of tumor cells from immune surveillance could be reduced to the tumor expression of immune checkpoints, resulting in new approaches in tumor therapy by applying immune checkpoint inhibitors. However, a germline mutation in APC is not 1:1 related to colorectal cancer (CRC), and only some patients respond to immune checkpoint inhibitors. The point here is that biological systems, also comprising cancer, have properties that cannot be reduced to single components. The cooperation of the single components results in new, emergent properties. The outcome of an interaction in a complex network, like the immune system, depends on the many cell types involved and the numerous molecules that interact and activate or inhibit pathways. The way the composing elements are organized is a causal factor in itself for any emergent property. The rise of genomic analysis at the end of the previous century, enabling us to sequence a full genome at the DNA and RNA levels, has initiated an awareness of the need for ‘systems biology’: to consider a full system and how it is organized, in all of its aspects, to understand biological pathways and their outcomes. In this review, we outline the prospects and limitations of systems biology in cancer research and propose a causal framework that integrates upward and downward causation and multiple realizability to understand the emergent properties of tumors that determine the dynamics of tumor development. Full article

The oral cavity acts as the anatomical gateway to the respiratory tract, sharing both microbiological and pathophysiological links with the lower airways. Although radiotherapy is a cornerstone treatment for lung cancer, reliable oral microbiome biomarkers for predicting patient outcomes remain lacking. We analyzed the oral microbiome of 136 lung cancer patients and 199 healthy controls across discovery and two validation cohorts via 16S rRNA sequencing. Healthy controls exhibited a significantly higher abundance of Streptococcus compared to patients (p = 0.049, p < 0.001, p < 0.001, respectively). The structure of the microbial community exhibited substantial dynamic changes during treatment. Responders showed enrichment of Rothia aeria (p = 0.027) and Prevotella salivae (p = 0.043), associated with prolonged overall survival (OS) and progression-free survival (PFS), whereas non-responders exhibited elevated Porphyromonas endodontalis (p = 0.037) correlating with shorter OS and PFS. According to Analysis of Compositions of Microbiomes with Bias Correction 2 (ANCOM-BC2) analysis, Akkermansia and Alistipes were nearly absent in non-responders, while Desulfovibrio and Moraxella were virtually absent in responders. A diagnostic model based on Streptococcus achieved area under the curve (AUC) values of 0.85 (95% CI: 0.78–0.91) and 0.99 (95% CI: 0.98–1) in the validation cohorts, and a response prediction model incorporating Prevotella salivae and Neisseria oralis yielded an AUC of 0.74 (95% CI: 0.58–0.90). Furthermore, in small cell lung cancer, microbiota richness and diversity were inversely correlated with Eastern Cooperative Oncology Group (ECOG) performance status (p = 0.008, p < 0.001, respectively) and pro-gastrin-releasing peptide (ProGRP) levels (p = 0.065, p = 0.084, respectively). These results demonstrate that lung cancer-associated oral microbiota signatures dynamically reflect therapeutic response and survival outcomes, supporting their potential role as non-invasive biomarkers for diagnosis and prognosis. Full article

The tumor microenvironment (TME) orchestrates tumor growth, immune evasion, and therapeutic response in head and neck squamous cell carcinoma (HNSCC). Current immune checkpoint inhibitors (ICIs) target the programmed death receptor-1/programmed death-ligand 1 (PD-1/PD-L1) axis and improve survival in recurrent, metastatic, and locally advanced HNSCC. Tumor cells produced exosomes directly suppress cytotoxic T-lymphocytes activity by modulating immune checkpoint pathways and disrupting T-cell receptor signaling. Cancer-associated fibroblast-derived exosomes (CAF-Exos) function indirectly by conditioning immune escape and tumor growth. Together, these exosomal populations cooperate to create an immunosuppressive niche that hinders the efficacy of immunotherapies. CAF-Exos induce TME changes that exclude CD8⁺ T-cells, promote regulatory T-cells (Tregs), and upregulate PD-L1 expression in tumor cells. The bidirectional transfer of microRNAs (miRNAs) between tumor cells and CAFs enhances epithelial–mesenchymal transition (EMT), suppresses cytotoxic lymphocytes, and undermines ICI efficacy. This review article summarizes recent publications about plasma-derived exosomes from HNSCC patients. These exosomes carry tumor and immune checkpoint markers, reflect tumor burden and treatment response, and strongly modulate immune cells by suppressing T- and B-cell activity and promoting immunosuppressive macrophages. We encourage functional and biomechanistic future studies in the field of HNSCC that examine how CAF subtypes exosomes achieve an immunoresistant TME. Full article

High temperatures induce oxidative stress and the production of a large amount of malondialdehyde (MDA) in the Pacific oyster Crassostrea gigas, and they can even lead to mass mortality. Aldehyde dehydrogenase (ALDH) degrades MDA and is attracting increasing attention for its role in enhancing antioxidant defense capacity. This study identified 14 ALDH family members in the oyster genome. Among them, CgALDH6A1 harbored a conserved ALDH_F6_MMSDH domain (known to catalyze the oxidation of aliphatic and aromatic aldehydes) and was likely involved in the high-temperature stress response through the detoxification of accumulated toxic aldehydes. In the gills, CgALDH6A1 had significantly higher mRNA expression than other tissues, with a significant increase at 12 h under 28 °C high-temperature stress. During the outdoor aquaculture period, the mRNA transcripts of CgALDH6A1 in the gills exhibited a significant increase from June to October. After the expression of CgALDH6A1 was inhibited by RNAi, the MDA content in the gills increased significantly (1.31-fold, p < 0.01), while the activities of superoxide dismutase (SOD) (0.93-fold, p < 0.05) and catalase (CAT) (0.45-fold, p < 0.001) and total antioxidant capacity (T-AOC) (0.54-fold, p < 0.01) decreased significantly under high-temperature stress. Meanwhile, the gill tissue was observed to be disorganized with obvious filament swelling. After the oysters were treated with CgALDH6A1 agonist (Alda-1), the MDA content (0.59-fold, p < 0.001) in the gills decreased significantly, while the activities of SOD (1.33-fold, p < 0.001), CAT (1.81-fold, p < 0.001), and T-AOC (1.79-fold, p < 0.01) all increased significantly 48 h after high-temperature stress. However, no obvious morphological changes were observed in the gills. These results demonstrate that CgALDH6A1 plays a key role in regulating the oxidative stress response by degrading MDA under high-temperature stress and plays a cooperative role with the antioxidant system in alleviating oxidative stress under high-temperature stress. Full article

Pseudogymnoascus destructans (Pd) invades the skin tissue of bats, leading to severe population declines. The skin microbiome plays a crucial role in protecting hosts from fungal infection and exhibits pronounced spatiotemporal dynamics in its structure and function. Meanwhile, metabolites derived from microbial communities reflect the host physiological state and participate in microbe–pathogen interactions. In this study, we investigated the spatiotemporal dynamics of skin bacterial communities and metabolites during hibernation in Rhinolophus ferrumequinum by integrating 16S rRNA sequencing with untargeted metabolomics and experimentally verified the antifungal effects of microbially derived potential metabolites against Pd. Our results revealed that the structure of the skin bacterial community varied significantly across sampling contexts, with its assembly primarily governed by stochastic processes. Bacterial diversity reached its lowest level during middle hibernation, accompanied by a simplified co-occurrence network dominated by cooperative or mutualistic interactions. Additionally, metabolomic analyses demonstrated systematic metabolic remodeling of bat skin across hibernation stages, marked by significant enrichment of multiple pathways closely involved in host antimicrobial defense. Furthermore, metabolite profiles differed across locations, and the abundance patterns of several metabolites were strongly correlated with Pd infection levels. Integrated analyses identified multiple metabolites that showed significant correlations with bacterial genera capable of synthesizing the corresponding compounds. In vitro validation confirmed that nine metabolites effectively inhibited the growth of Pd, among which melatonin exhibited the strongest antifungal activity. Collectively, this study reveals the dynamics of the skin microbiome and metabolites of R. ferrumequinum during hibernation, providing novel insights into the defensive role of skin-associated microbes and metabolites in maintaining population health and resilience against fungal pathogens. Full article

Background: Epithelial–mesenchymal transition (EMT) is a fundamental process that drives invasion and metastasis in patients with diffuse-type gastric cancer (DGC). The role of SMARCD3, a subunit of the SWI/SNF chromatin remodeling complex, in this process is largely unknown. The aim of this study is to elucidate the molecular mechanism through which SMARCD3 integrates with the PI3K-AKT and WNT/β-catenin signaling pathways to promote EMT and gastric cancer progression. Methods: Stable SMARCD3-overexpressing MKN45 and MKN74 cell lines were established. RNA sequencing (RNA-seq) was performed to investigate signaling alterations. Western blot analysis confirmed the expression of EMT markers (Snail and Slug) and the phosphorylation of AKT (Ser473) and GSK3β (Ser9). PI3K dependency was tested using the inhibitor LY294002. Cooperative effects were examined by activating the WNT pathway with WNT3A. Results: SMARCD3 overexpression upregulated PI3K-AKT and WNT signaling, which correlated with increased Snail/Slug expression and increased AKT/GSK3β phosphorylation. GSK3β inactivation (pSer9) stabilizes Snail, driving EMT. LY294002 treatment suppressed Snail/Slug expression, attenuated AKT activation, and reversed the mesenchymal phenotype. Furthermore, WNT3A treatment synergistically increased nuclear Snail accumulation. Conclusions: SMARCD3 acts as a critical epigenetic regulator that promotes EMT in patients with gastric cancer through the integration of the PI3K-AKT and WNT/β-catenin pathways. Targeting this SMARCD3-mediated mechanism offers a promising therapeutic strategy to inhibit metastasis and improve outcomes for patients with gastric cancer. Full article