Interpretable machine learning-based prediction of 28-day mortality in ICU patients with sepsis: a multicenter retrospective study.

Background: Sepsis is a major cause of mortality in intensive care units (ICUs) and continues to pose a significant global health challenge, with sepsis-related deaths contributing substantially to the overall burden on healthcare systems worldwide. The primary objective was to construct and evaluate a machine learning (ML) model for forecasting 28-day all-cause mortality among ICU sepsis patients.

Methods: Data for the study was sourced from the eICU Collaborative Research Database (eICU-CRD) (version 2.

The nuclear factor-κ B inhibitor SN50 enhances the efficacy of B-cell maturation antigen-targeted chimeric antigen receptor T-cell therapy.

Not available.

The left amygdala is genetically sexually-dimorphic: multi-omics analysis of structural MRI volumes.

Brain anatomy plays a key role in complex behaviors and mental disorders that are sexually divergent. While our understanding of the sex differences in the brain anatomy remains relatively limited, particularly of the underlying genetic and molecular mechanisms that contribute to these differences. We performed the largest study of sex differences in brain volumes (N = 33,208) by examining sex differences both in the raw brain volumes and after controlling the whole brain volumes.

Isolation of proteins on chromatin (iPOC) reveals signaling pathway-dependent alterations in the DNA-bound proteome.

Signaling pathways often convergence on transcription factors (TFs) and other DNA-binding proteins (DBPs) that regulate chromatin structure and gene expression, thereby governing a broad range of essential cellular functions. However, the repertoire of DBPs is incompletely understood even for the best-characterized pathways. Here, we optimized a strategy for the isolation of Proteins on Chromatin (iPOC) exploiting tagged nucleoside analogues to label the DNA and capture associated proteins, thus enabling the comprehensive, sensitive, and unbiased characterization of the DNA-bound proteome.

Phosphoproteomic analysis of X-ray-irradiated planarians provides novel insights into the DNA damage response.

Phosphorylation plays a crucial role in the cellular response to radiation and cancer therapies, yet phosphoproteomics studies in planarians remain underexplored despite the organism's remarkable regenerative capacities. This study utilized advanced ion mobility mass spectrometry for 4D-label-free quantitative proteomics to identify phosphorylation sites associated with irradiation in planarians. A total of 33,284 phosphorylation sites from 15,505 phosphorylated peptides and 4710 unique phosphoproteins were identified.

Innovative approaches for enzyme immobilization in milk processing: advancements and industrial applications.

The dairy industry is progressively integrating advanced enzyme technologies to optimize processing efficiency and elevate product quality. Among these technologies, enzyme immobilization has emerged as a pivotal innovation, offering considerable benefits in terms of enzyme reusability, stability, and overall process sustainability. This review paper explores the latest improvements in enzyme immobilization techniques and their industrial applications within milk processing.

Deciphering the complex molecular architecture of the genetically modified soybean FG72 through paired-end whole genome sequencing.

The clear molecular characterization of genetically modified (GM) plants and animals is a prerequisite for obtaining regulatory approval and safety certification for commercial cultivation. This characterization includes the identification of the transferred DNA (T-DNA) insertion site, its flanking sequences, the copy number of inserted genes, and the detection of any unintended genomic alterations accompanying the transformation process. In this study, we performed a comprehensive molecular characterization of the well-known GM soybean event FG72 using paired-end whole-genome sequencing (PE-WGS).

Oncogenic mutant KRAS inhibition through oxidation at cysteine 118.

Specific reactive oxygen species activate the GTPase Kirsten rat sarcoma virus (KRAS) by reacting with cysteine 118 (C118), leading to an electron transfer between C118 and nucleoside guanosine diphosphate (GDP), which causes the release of GDP. Here, we have mimicked permanent oxidation of human KRAS at C118 by replacing C118 with aspartic acid (C118D) in KRAS to show that oncogenic mutant KRAS is selectively inhibited via oxidation at C118, both in vitro and in vivo. Moreover, the combined treatment of hydrogen-peroxide-producing pro-oxidant paraquat and nitric-oxide-producing inhibitor N(ω)-nitro-l-arginine methyl ester selectively inhibits human mutant KRAS activity by inducing oxidization at C118.

Composition and the predicted functions of fungal communities and the key drivers in acidic soils of Jiaodong Peninsula, China.

Introduction: Soil acidification imperils soil health and hinders the agricultural sustainability. As being more tolerant than bacteria to soil acidification, so it would be more meaningful for agricultural management and crop yield to characterize fungal community in acidic soils and manifest its key drivers.

Method: This study investigated the composition and diversity of fungal communities and its key driving factors by collecting 90 soil samples from the acidic region of Jiaodong Peninsula China, spanning 3 × 10 km.

Pupylation-based proximity labeling reveals regulatory factors in cellulose biosynthesis in Arabidopsis.

Knowledge about how and where proteins interact provides a pillar for cell biology. Protein proximity-labeling has emerged as an important tool to detect protein interactions. Biotin-related proximity labeling approaches are by far the most commonly used but may have labeling-related drawbacks.

AlphaFold-Based AI Docking Reveals AMPK/SIRT1-TFEB Pathway Modulation by Traditional Chinese Medicine in Metabolic-Associated Fatty Liver Disease.

Metabolic-associated fatty liver disease (MAFLD) is a chronic, progressive disorder characterized by hepatic steatosis and excessive lipid accumulation. Its high global adult prevalence (approximately 50.7%), however, FDA-approved therapeutic drugs remains lacking.

Antigenicity evaluation of the synthetic trisaccharides related to Plesiomonas shigelloides serotype O51 O-antigen containing an acetamidino group.

Bacterial surface polysaccharides are widely decorated with diverse rare functional groups. An understanding of the role of these functional groups in immunological activity of the glycans is required for the development of carbohydrate-based treatment against bacterial infectious diseases. Here, the antigenicity evaluation of synthetic trisaccharide 1 related to Plesiomonas shigelloides serotype O51 lipopolysaccharide (LPS) O-antigen and its acetamido derivative 2 was achieved to elucidate the immunological importance of O-antigen structure.

Chinese yam (Dioscorea opposita Thunb.) starch-ferulic acid complexes: Preparation, characterization, and physicochemical properties.

Polyphenols are known to interact with starch to form the V-type inclusion complex or the noninclusive complex. It is hypothesized that the addition of polyphenols could improve the properties of Chinese yam (Dioscorea opposita Thunb.) starch, and the properties of the complexes could be regulated by controlling the additive amount of polyphenols.

Inhibition of cap-dependent endonuclease in influenza virus with ADC189: a pre-clinical analysis and phase I trial.

ADC189 is a novel drug of cap-dependent endonuclease inhibitor. In our study, its antiviral efficacy was evaluated in vitro and in vivo, and compared with baloxavir marboxil and oseltamivir. A first-in-human phase I study in healthy volunteers included single ascending dose (SAD) and food effect (FE) parts.

Mapping Dynamic Protein Clustering with AIEgen-Active Chemigenetic Probe.

Protein clustering/disassembling is a fundamental process in biomolecular condensates, playing crucial roles in cell fate decision and cellular homeostasis. However, the inherent features of protein clustering, especially for its reversible behavior and subtle microenvironment variation, present significant hurdles in probe chemistry for tracking protein clustering dynamics. Herein, we report a bilateral-tailored chemigenetic probe, in which an "amphiphilic" AIEgen QMSO3Cl is covalently conjugated to a protein tag that is genetically fused to protein-of-interest (POI).

Comparative analysis of the genomic and expression profiles of ANLN and KDR as prognostic markers in breast Cancer.

Unlabelled: Breast cancer (BC) remains a highly heterogeneous disease, complicating diagnosis and treatment. This study investigates the prognostic significance of Anillin () and Kinase Insert Domain Receptor () genes, focusing on their mutational and expression landscapes in BC using data from The Cancer Genome Atlas (TCGA). We found that high expression is strongly associated with poor overall survival, highlighting its potential as a robust prognostic marker.

Metabolic engineering of for high-level production of pneumocandin B.

Pneumocandin B (PB) is a lipohexapeptide synthesized by and serves as the precursor for the widely used antifungal drug caspofungin acetate (Cancidas®). However, the low titer of PB results in fermentation and purification costs during caspofungin production, limiting its widespread clinical application. Here, we engineered an efficient PB-producing strain of by systems metabolic engineering strategies, including multi-omics analysis and multilevel metabolic engineering.

Inhibition of Hepatitis B Virus Replication by a Novel GalNAc-siRNA In Vivo and In Vitro.

Current antiviral therapy for the chronic hepatitis B virus (HBV) has a low clinical cure rate, high administration frequency, and limited efficacy in reducing HBsAg levels, leading to poor patient compliance. Novel agents are required to achieve HBV functional cure, and reduction of HBV antigenemia may enhance the activation of effective and long-lasting host immune control. HT-101 is a siRNA currently in phase I clinical trials with promising prospects for future applications.

LDHAα, a lactate dehydrogenase A isoform, promotes glycolysis and tumor progression.

Lactate dehydrogenase A (LDHA) is upregulated in multiple cancer types and contributes to the Warburg effect. Several studies have found that many tumor-related genes have subtypes and play important roles in promoting cancer development. Here, we identified a novel LDHA transcript, which produced a new protein 3 kDa larger than LDHA, which we named LDHAα.

Dual targeting PD-L1 and 4-1BB to overcome dendritic cell-mediated lenalidomide resistance in follicular lymphoma.

Immunomodulatory agent lenalidomide is effective in treating follicular lymphoma (FL). We conducted the first trial of immunotherapy rituximab plus lenalidomide in newly diagnosed FL in China (NCT03715309). One-hundred and fifteen patients were enrolled and treated with rituximab 375 mg/m intravenously on day 0 and lenalidomide 25 mg orally on day 1-10 for 6 cycles of induction treatment, as well as lenalidomide for 6 cycles and rituximab for 8 cycles of maintenance treatment.

Purification, crystal structural characterization of porcine kidney dipeptidyl peptidase IV (PkDPP-IV) and its interaction with oyster derived inhibitory peptide ILAPPER.

Dipeptidyl peptidase IV (DPP-IV) is an important target enzyme for the treatment of type 2 diabetes mellitus (T2DM). Increasing researchers try to screen DPP-IV inhibitory peptides while the cost of DPP-IV is high. In this study, PkDPP-IV was efficiently purified by acid precipitation, ammonium sulfate salting out and gel filtration chromatography with a purification of 283.

Deciphering the mechanisms of long non-coding RNAs in ferroptosis: insights into its clinical significance in cancer progression and immunology.

A new type of nonapoptotic, iron-dependent cell death induced by lipid peroxidation is known as ferroptosis. Numerous pathological processes, including inflammation and cancer, have been demonstrated to be influenced by changes in the ferroptosis-regulating network. Long non-coding RNAs (LncRNAs) are a group of functional RNA molecules that are not translated into proteins, which can regulate gene expression in various manners.

Discovery of 1,2,4-benzotriazine derivatives as new hematopoietic progenitor kinase 1 (HPK1) inhibitors.

Hematopoietic progenitor kinase 1 (HPK1), which negatively regulates immune signaling, has emerged as an attractive small-molecule drug target for tumor immunotherapy. Herein, we report the discovery of the 1,2,4-benzotriazine derivatives as new potent HPK1 inhibitors. Notably, compound A29 exhibited improved HPK1 inhibitory activity relative to compound 1 in the ADP-Glo kinase assay (IC = 2.