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In China, Codonopsis Radix (CR) is frequently consumed both as food and medicine. Here, a comprehensive strategy based on fingerprinting and chemometric approaches was created to explore the influence of origins, storage time and kneading processing on the quality of CR. Firstly, high-performance liquid chromatography with diode array detection was used to obtain the fingerprints of 35 batches of CR from six different origins and 33 batches of CR from varying storage times or kneading procedures. Secondly, chemometric methods including similarity analysis (SA), principal component analysis (PCA), hierarchical clustering analysis (HCA), and two-way orthogonal partial least square with discriminant analysis (O2PLS—DA) were used to evaluate the differences of chemical components in CR so as to identify its source and reflect its quality. Moreover, 13 and 16 major compounds were identified as marker compounds for the discrimination of CR from different origins, storage time and kneading processing, respectively. Furthermore, the relative content of the marker components and the exact content of Lobetyolin were measured, indicating that the contents of these components vary significantly between various CR samples. Meanwhile, the chemical components of CR were identified using Mass spectrometry. According to the findings of our investigation, the quality of CR from Gansu was the best, followed by Shanxi and then Sichuan. The quality of CR from Chongqing and Guizhou was poor. At the same time, the quality of CR was the best when it was kneaded and stored for 0 years, indicating that the traditional kneading process of CR is of great significance. Conclusively, HPLC fingerprint in conjunction with chemical pattern recognition and component content determination can be employed to differentiate the raw materials of different CR samples. Additionally, it is also a reliable, comprehensive and prospective method for quality control and evaluation of CR.

During meiosis, chromosomes exhibit dramatic changes in morphology and intranuclear positioning. How these changes influence homolog pairing, alignment, and recombination remain elusive. Using Hi-C, we systematically mapped 3D genome architecture throughout all meiotic prophase substages during mouse spermatogenesis. Our data uncover two major chromosome organizational features varying along the chromosome axis during early meiotic prophase, when homolog alignment occurs. First, transcriptionally active and inactive genomic regions form alternating domains consisting of shorter and longer chromatin loops, respectively. Second, the force-transmitting LINC complex promotes the alignment of ends of different chromosomes over a range of up to 20% of chromosome length. Both features correlate with the pattern of homolog interactions and the distribution of recombination events. Collectively, our data reveal the influences of transcription and force on meiotic chromosome structure and suggest chromosome organization may provide an infrastructure for the modulation of meiotic recombination in higher eukaryotes. During meiosis, chromosomes undergo dramatic changes in morphology and intranuclear positioning. Here the authors mapped the 3D genome architecture throughout mouse spermatogenesis by Hi-C of sorted cells to reveal the contributions of transcriptional activity and mechanical force in modulating homolog alignment and recombination.

Stimulator of interferon genes (STING) is critical for cytosolic DNA-triggered innate immunity. STING is modified by several types of polyubiquitin chains. Here, we report that the deubiquitinase CYLD sustains STING signaling by stabilizing the STING protein. CYLD deficiency promoted the K48-linked polyubiquitination and degradation of STING, attenuating the induction of IRF3-responsive genes after HSV-1 infection or the transfection of DNA ligands. Additionally, CYLD knockout mice were more susceptible to HSV-1 infection than their wild-type (WT) littermates. Mechanistically, STING translocated from the ER to the Golgi upon HSV-1 stimulation; CYLD partially accumulated with STING and interacted selectively with K48-linked polyubiquitin chains on STING, specifically removing the K48-linked polyubiquitin chains from STING and ultimately boosting the innate antiviral response. Our study reveals that CYLD is a novel checkpoint in the cGAS-STING signaling pathway and sheds new light on the dynamic regulation of STING activity by ubiquitination.

Hypochlorous acid (HOCl) is a reactive substance that reacts with most biomolecules and is essential in physiological and pathological processes. Abnormally elevated HOCl levels may cause inflammation and other disease responses. To further understand its key role in inflammation, HOCl must be detected in situ. Here, we designed a hydroxytricyanopyrrole-based small-molecule fluorescent probe (HTCP-NTC) to monitor and identify trace amounts of HOCl in biological systems. In the presence of HOCl, HTCP-NTC released hydroxyl groups that emit strong fluorescence covering a wide wavelength range from the visible to near-infrared region owing to the resumption of the intramolecular charge transfer process. Additionally, HTCP-NTC demonstrated a 202-fold fluorescence enhancement accompanied by a large Stokes shift and a low detection limit (21.7 nM). Furthermore, HTCP-NTC provided a rapid response to HOCl within 18 s, allowing real-time monitoring of intracellular HOCl. HTCP-NTC exhibited rapid kinetics and biocompatibility, allowing effective monitoring of the exogenous and endogenous HOCl fluctuations in living cells. Finally, based on fluorescence imaging, HTCP-NTC is a potential method for understanding the relationship between inflammation and HOCl.

Prostate cancer is one of the most common malignant tumors of the male genitourinary system. The impaired activity of natural killer (NK) cells observed in prostate cancer may contribute to immune evasion. This study aimed to develop robust NK cell-related diagnostic signatures. Based on NK related genes identified by scRNA-seq analysis, weighted gene co-expression network analysis, least absolute shrinkage and selection operator regression analysis, and machine learning algorithms were used to develop a novel diagnostic model. The expression of diagnostic genes was validated using tumor and adjacent normal tissues collected from prostate cancer patients. The biological functions of KIT as an NK cell related gene were further evaluated in prostate cancer cells. A nine-gene NK cell-related diagnostic signature was developed, including , , , , , , , , and . These genes were validated in independent datasets and showed strong predictive ability for prostate cancer diagnosis (AUC >0.8). Based on the expression profiles of these genes, nine compounds were identified that may influence drug sensitivity in prostate cancer. Furthermore, the expressions of , , and were successfully validated in collected prostate cancer tissue samples. Functional experiments demonstrated that KIT overexpression enhanced the cytotoxicity of NK-92 cells against prostate cancer PC-3 cells, inhibited cancer cell viability, cell migration and invasion, and increased the secretion of cytokines such as IFN-γ, Gzms-A, Gzms-B, and Perforin, as well as the degranulation marker CD107a. This study provides a new understanding of NK cell related gene signatures in prostate cancer diagnosis and highlights KIT as a promising candidate for future therapeutic investigation. Further research is needed to explore the mechanisms underlying the expression of these genes and their roles in the tumor microenvironment.

To integrate multi-cohort transcriptomic, single-cell, and experimental data to identify diagnostic signature genes for septic shock, establish a peripheral blood molecular diagnostic model, and elucidate the m6A regulatory mechanisms of key genes. Candidate genes were identified from five GEO peripheral blood cohorts through batch effect-corrected differential expression analysis and WGCNA, followed by parallel GO/DO enrichment analysis. Feature genes were selected using PPI networks combined with LASSO, SVM-RFE, and random forest algorithms. A 5-gene artificial neural network (ANN) diagnostic model was constructed and validated using ROC and logistic regression in GSE95233, GSE131761, and clinical cohorts. Immune cell composition and expression of characteristic genes in neutrophils were analyzed using CIBERSORT and GSE167363 single-cell data. The METTL14/YTHDF1-S100A12 m6A axis was elucidated via qRT-PCR, Western blot, MeRIP-qPCR, RIP-qPCR, and Actinomycin D experiments. In CLP mice, siMETTL14 was administered for intervention and assessment of lung injury. A total of 76 sepsis-shock-associated candidate genes were identified, enriched in the bacterial defense pathway. Five robust candidate genes (S100A12, MMP8, PGLYRP1, CEACAM8, MMP9) were selected by integrating PPI and three machine learning algorithms. The constructed ANN achieved high AUC across multiple cohorts, and all five genes showed significantly elevated mRNA and protein levels in peripheral blood from clinical sepsis patients. CIBERSORT and single-cell results indicated significant neutrophil expansion, with the five genes predominantly enriched in neutrophils and progressively elevated with worsening outcomes. m6A-related experiments demonstrated that METTL14 mediates m6A modification and stabilizes S100A12 mRNA through YTHDF1 recognition; knocking down either METTL14 or YTHDF1 accelerated its degradation. silencing of METTL14 in CLP mice reduced lung tissue injury and lipid peroxidation/ferroptosis levels. In this study, a diagnostic signature was established for septic shock comprising five neutrophil-associated genes and an ANN model, revealing the regulatory role of the METTL14/YTHDF1-mediated m6A-S100A12 axis in neutrophils. This suggests the METTL14/m6A pathway as a potential diagnostic and therapeutic target.

Using biomass-derived solvents in various organic reactions is challenging for the fine chemicals industry. We herein report a Pd/C catalyzed Suzuki–Miyaura reaction in water extract of suaeda salsa (WES) without using external phosphine ligand, base, and organic solvent. The cross-coupling reactions were carried out in a basic WES medium with a broad substrate scope and wide functional group tolerance. Furthermore, the high purity of solid biaryl products can be obtained by column chromatography or filtration.

The opioid system plays a crucial role in maintaining gastrointestinal homeostasis. Endogenous opioid peptide enkephalins have anti-inflammatory effect and participate in the treatment of inflammatory bowel diseases (IBDs). Here, we investigated the effect of natural enkephalinase inhibitor human opiorphin (HO) on dextran sodium sulfate (DSS)-induced colitis in mice. Our results showed that central administration of HO attenuated DSS-induced colitis, as indicated by the reduction of disease activity index (DAI) scores, macroscopic scores, histological scores, and the myeloperoxidase (MPO) activity. Moreover, HO alleviated DSS-induced inflammation by decreasing inflammatory cytokines TNF-α, IL-6, and IL-1β, and increasing anti-inflammatory cytokine IL-10 in both serum and colon tissues in DSS-treated mice. The potential anti-inflammatory effect of HO at a dose of 40 μg/kg was observed as evidenced by a decrease in nuclear factor κB (NF-κB) p65, toll-like receptor-4 (TLR-4), iNOS, and COX-2. HO also improved intestinal barrier function by enhancing the expression of tight junction proteins. Furthermore, HO treatment significantly inhibited activities of neutral endopeptidase (NEP) and aminopeptidase N (APN), elevated serum enkephalins concentrations, and increased expressions of mu and delta opioid receptors. In addition, pretreatment with opioid receptor antagonist naloxone hydrochloride (NH) compromised the protective effect of HO and aggravated colitis symptoms, as indicated by inhibited anti-inflammatory effects, disrupted intestinal barrier function, and decreased opioid receptor activity. In conclusion, these data indicate that HO protects against DSS-induced colitis by inhibiting TLR4/NF-κB pathway activation and improving intestinal barrier function through activation of the endogenous opioid system. Therefore, targeting the opioid system with peptidase inhibitors intervention would be a novel strategy in the therapy of IBD.

Zn–CO2 batteries are excellent candidates for both electrical energy output and CO2 utilization, whereas the main challenge is to design electrocatalysts for electrocatalytic CO2 reduction reactions with high selectivity and low cost. Herein, the three‐phase heterojunction Cu‐based electrocatalyst (Cu/Cu2O‐Sb2O3‐15) is synthesized and evaluated for highly selective CO2 reduction to CO, which shows the highest faradaic efficiency of 96.3% at −1.3 V versus reversible hydrogen electrode, exceeding the previously reported best values for Cu‐based materials. In situ spectroscopy and theoretical analysis indicate that the Sb incorporation into the three‐phase heterojunction Cu/Cu2O‐Sb2O3‐15 nanomaterial promotes the formation of key *COOH intermediates compared with the normal Cu/Cu2O composites. Furthermore, the rechargeable aqueous Zn–CO2 battery assembled with Cu/Cu2O‐Sb2O3‐15 as the cathode harvests a peak power density of 3.01 mW cm−2 as well as outstanding cycling stability of 417 cycles. This research provides fresh perspectives for designing advanced cathodic electrocatalysts for rechargeable Zn–CO2 batteries with high‐efficient electricity output together with CO2 utilization. This work proposes an advanced cathodic electrocatalyst of three‐phase heterojunction Cu‐based catalyst (Cu/Cu2O‐Sb2O3‐15) for rechargeable Zn–CO2 batteries with high‐efficient electricity output together with CO2 utilization.

seedlings are grown in alpine uncultivated meadow soil with rainfed agroecosystems to ensure the quality of after seedling transplantation. The aim was to investigate the rhizosphere bacterial and fungal communities during the growth stages of seedlings. The bacterial and fungal communities were investigated by HiSeq sequencing of 16S and 18S rDNA, respectively. Proteobacteria and Bacteroidetes were bacterial dominant phyla throughout growth stages. Fungal dominant phyla varied with growth stages, dominant phyla Ascomycota and Chytridiomycota in AM5, dominant phyla Basidiomycota, Ascomycota and Zygomycota in BM5, and dominant phyla Basidiomycota and Ascomycota in CM5. There was no significant variation in the alpha-diversity of the bacterial and fungal communities, but significant variation was in the beta-diversity. We found that the variation of microbial community composition was accompanied by the changes in community function. The relative abundance of fungal pathogens increased with plant growth. We also identified the core microbes, significant-changing microbes, stage-specific microbes, and host-specific microbes. Plant weight, root length, root diameter, soil pH, rainfall, and climate temperature were the key divers to microbial community composition. Our findings reported the variation and environmental drivers of rhizosphere bacterial and fungal communities during the growth of seedlings, which enhance the understanding of the rhizosphere microbial community in this habitat.