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Deciphering how plant-microbiota interactions achieve beneficial outcomes for crops will provide innovative strategies for sustainable agriculture. Here, we dissected rice-microbiota dynamics using a tailored gnotobiotic cultivation system that models the semiaquatic environment in a paddy field. Inoculation with native soil microbiota resulted in root-growth-promotion (RGP) and root-growth-inhibition (RGI) phenomena in different cultivars. This preference persisted in a simplified synthetic community and individual bacterial strains, indicating that cultivar-specific growth promotion is an intrinsic property of microbial inocula. Though stochastic process dominated the assembly of root microbiome in gnotobiotic cultivation, absolute quantification revealed that imbalance of detrimental and beneficial bacterial loads in roots correlated with RGP or RGI outcomes in different rice cultivars. From the host perspective, genetic screening identified that receptor-like kinase mutants, including OsFLS2 (FLAGELLIN-SENSITIVE 2), inverted microbiota functionality, converting RGP to RGI. In particular, over 4534 rice genes responded to microbiota inoculation and 46.1% of them were reprogrammed in osfls2 mutants, demonstrating the prominent regulatory role of OsFLS2 in rice-microbiota signaling. On the basis of these results, we propose that the rice-microbiota relationships are gated by cultivar-specific preferences of the bacterial microbiota and host immune receptor kinase, which provides a useful framework for crop microbiome engineering in the future.

A clinical study reported that Abelmoschus manihot (L.) Medic (A. manihot), in the form of Huangkui capsule (HKC), combined with irbesartan (IRB) is an effective therapy for patients with diabetic kidney disease (DKD). The bioactive components of HKC are total flavones extracted from A. manihot (TFA). To explore the pharmaceutical molecular mechanisms underlying the efficacy of A. manihot in the treatment of DKD, we have combined SpaTial Enhanced REsolution Omics-sequencing (at 0.25 μm resolution) with single-cell full-length RNA sequencing. We employed the db/db mouse model of type 2 diabetes and DKD. These experimental methods generated the first single-cell resolution pharmacopathological spatial atlas in kidneys of db/db mice that were treated with TFA or IRB. TFA exhibited therapeutic effects on DKD comparable to those of TFA combined with IRB. Following genome-wide gene screening and molecular docking simulation, we have identified the key renal receptors (Itga3, Itga5, Tgfbr1, etc.) and regulators (Jun, Junb, Stat1, etc.) underlying the therapeutic action of TFA in DKD. This study provides novel insights into the pharmaceutical mechanisms of A. manihot in the treatment of DKD.

Bone growth and regeneration remain major clinical challenges. Deer antlers, the fastest-growing mammalian bone, regenerate via endochondral ossification and elongate up to 2 cm per day, far surpassing the ~2 cm annual growth of human growth plates. Here, we systematically mapped the cellular landscape of the antler growth center (AGC) using single-nucleus RNA sequencing, chromatin accessibility profiling, and spatial transcriptomics. The AGC harbors a large stem-progenitor pool that drives rapid elongation through vigorous proliferation supported by paracrine signaling. These proliferative cells exhibit a transcriptional program with intrinsically low tumorigenic potential, associated with apoptotic regulation. The AGC also establishes a vascularized niche that supports robust angiogenesis, sustains accelerated cartilage growth, and enables efficient recruitment of osteogenic cells. Notably, antlers employ a hybrid ossification strategy, combining endochondral ossification with direct hypertrophic chondrocyte-to-osteoblast transdifferentiation, likely via PHEX⁺ intermediates. Collectively, these findings refine fundamental concepts of endochondral ossification and offer insights for regenerative bone therapies.

Cancer immune evasion is orchestrated by tumor-intrinsic molecular constraints that remain incompletely defined. Here, we performed an in vivo genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) loss-of-function screen to catalogue gene regulatory determinants of immune evasion in cancer cells. We identify C9ORF50 as a novel splicing regulator whose inhibition profoundly sensitizes cancer to immune surveillance. Integrated multi-omics profiling reveals this intrinsically disordered protein exhibits liquid-liquid phase separation properties and forms nuclear condensates that colocalize with spliceosome components. Genetic ablation correlates with intron retention in multiple spliceosome components and cytoplasmic accumulation of double-stranded RNA, which is associated with type I interferon activation and enhances chemokine-mediated T cell recruitment. As a result, C9ORF50 inhibition amplifies tumor cell immunogenicity, enhancing T cell infiltration in poorly infiltrated tumors. Clinically, elevated C9ORF50 expression correlates with poor survival and diminished lymphoid infiltration across malignancies. Therapeutic targeting of C9ORF50 using RNA interference enhances T cell infiltration and suppresses tumor growth. Our work identifies C9ORF50 as a candidate therapeutic target that modulates RNA splicing and tumor immunity, suggesting splicing regulation as a potential strategy to enhance immunotherapy responses.

MCMCtree and r8s are among the most popular molecular dating tools in the current genomic era, but their utility is hampered by steep learning curves, particularly concerning input file formatting, the complexity of fossil calibration setup, tree visualization, and model selection. To enhance their usability and improve research efficiency, we developed three new tools: MDGUI (for molecular dating analysis), TimeTreeAnno (for timetree visualization), and MCMCTracer (for convergence assessment). We integrated these into the PhyloSuite v2 platform, along with MCMCtree and r8s plugins, to create a comprehensive molecular dating suite. Compared to existing solutions that we benchmarked, our toolkit offers a more intuitive interface and streamlined workflow, featuring visual calibration point configuration, support for multiple alignment formats, automated model selection and implementation for downstream analyses, one-click pause/resume functionality, multithreading acceleration, and on-demand MCMC convergence assessment and plotting. Furthermore, PhyloSuite v2 introduces other advanced features, including gene duplicate resolution during the extraction step, significantly accelerated data handling capabilities (specifically, format conversion and concatenation), deeper integration of the latest IQ-TREE models and functions, and further streamlining of the entire phylogenetic analysis workflow. The update also includes adaptation to high-resolution screens and numerous bug fixes. The source code for the new version of PhyloSuite is available at https://github.com/dongzhang0725/PhyloSuite.

Antimicrobial resistance (AMR) disseminates throughout the soil-plant continuum via complex microbial interactions. Plants shape root- and leaf-associated microbiomes that sustain plant health; however, soil-borne legacies-enriched with antibiotic-producing microbes and resistance genes-govern AMR dynamics across agroecosystems. Using 16S rRNA gene sequencing, shotgun metagenomics, and high-throughput quantitative PCR, we profiled antibiotic resistance genes (ARGs), mobile genetic elements, and virulence factor genes across bulk soil, rhizosphere, phyllosphere, and root endosphere within soil-tomato and soil-strawberry continua. Recurrent bacterial wilt amplified the resistome, particularly polypeptide resistance genes, thereby establishing the rhizosphere as a major hotspot of ARG accumulation. Multidrug-resistant Ralstonia solanacearum (R. solanacearum) strains acted as major ARG reservoirs, harboring resistance determinants on both chromosomes and megaplasmids. Collectively, these findings demonstrate that pathogen-driven restructuring of the plant microbiome accelerates ARG dissemination, establishing soil-borne diseases as critical amplifiers of AMR across agricultural ecosystems.

We used snRNA-seq to construct a high-resolution atlas of pectoral muscle development in broiler chickens from neonatal to adult stages. This analysis revealed pronounced molecular heterogeneity among satellite cells across developmental phases and uncovered a previously uncharacterized Runx1 ⁺ satellite cell subpopulation. By integrating pseudotime trajectory reconstruction, gene set enrichment analysis, dynamic expression profiling and loss-of-function assays, we established a critical regulatory role for RUNX1 in muscle hypertrophy. Mechanistically, RUNX1 promotes myotube hypertrophy by transcriptionally repressing Pik3r1, thereby reducing PI3K p85α levels, destabilizing PTEN, and activating the PI3K/AKT/mTOR signaling cascade, which enhances protein synthesis and drives myotube growth.

[This corrects the article DOI: 10.1002/imt2.272.].

This study introduces whole microbiota transplantation (WMT), a synergistic therapeutic approach that concurrently transplants small intestinal and fecal microbiota. In germ-free mice, WMT outperforms conventional fecal microbiota transplantation (FMT) in restoring gut microbiota diversity and abundance. Moreover, in a chemotherapy-induced intestinal mucositis model, WMT alleviates intestinal inflammation and reverses microbiota dysbiosis. Encapsulation in layer-by-layer self-assembled nanocapsules further boosts microbial survival and colonization, amplifying WMT's anti-inflammatory effects and microbiota restoration in a mouse model of pan-intestinal infection. Overall, WMT represents a precise strategy for reshaping microbial homeostasis across the entire gastrointestinal tract, with therapeutic promise for inflammatory bowel diseases and small-intestinal disorders.

The intratumoral microbiome is an emerging hallmark of cancer, yet its multi-kingdom host-microbiome ecosystem in colorectal cancer (CRC) remains poorly characterized. Here, we conducted an integrated analysis using deep shotgun metagenomics and proteomics on 185 tissue samples, including adenoma (A), paired tumor (T), and para-tumor (P). We identified 4057 bacterial, 61 fungal, 108 archaeal, and 374 viral species in tissues and revealed distinct intratumor microbiota dysbiosis, indicating a CRC-specific multi-kingdom microbial ecosystem. Proteomic profiling uncovered four CRC subtypes (C1-C4), each with unique clinical prognoses and molecular signatures. We further discovered that host-microbiome interactions are dynamically reorganized during carcinogenesis, where different microbial taxa converge on common host pathways through distinct proteins. Leveraging this interplay, we identified 14 multi-kingdom microbial and 8 protein markers that strongly distinguished A from T samples (area under the receiver operating characteristic curve (AUROC) = 0.962), with external validation in two independent datasets (AUROC = 0.920 and 0.735). Moreover, we constructed an early- versus advanced-stage classifier using 8 microbial and 4 protein markers, which demonstrated high diagnostic accuracy (AUROC = 0.926) and was validated externally (AUROC = 0.659-0.744). Functional validation in patient-derived organoids and murine allograft models confirmed that enterotoxigenic Bacteroides fragilis and Fusobacterium nucleatum promoted tumor growth by activating Wnt/β-catenin and NF-κB signaling pathways, corroborating the functional potential of these biomarkers. Together, these findings reveal dynamic host-microbiome interactions at the protein level, tracing the transition from adenoma to carcinoma and offering potential diagnostic and therapeutic targets for CRC.