The effect of blood glucose levels on serum triglyceride clearance in patients with hyperlipidemic acute pancreatitis.

Preventing moderately severe and severe acute pancreatitis (MSAP & SAP) is the primary goal of the management of hyperlipidemic acute pancreatitis (HLAP). The main aim of this study was to investigate the factors affecting serum triglyceride (TG) clearance, particularly blood glucose (GLU) levels, which could potentially help to prevent the development of MSAP & SAP. The clinical data from 177 patients with MSAP & SAP and 195 patients with mild acute pancreatitis (MAP) on days 1-6 after the onset were collected and analyzed by multivariate logistic regression to identify the factors that have an impact on the severity of HLAP, especially TG.

Development of an AI model for predicting hypoxia status and prognosis in non-small cell lung cancer using multi-modal data.

Background: Prognosis prediction is crucial for non-small cell lung cancer (NSCLC) treatment planning. While tumor hypoxia significantly impacts patient outcomes, identifying hypoxic genomic markers remains challenging. This study sought to identify hypoxic computed tomography (CT) radiomic features and create an artificial intelligence (AI) model for NSCLC through the integration of multi-modal data.

Enhanced sensitivity and scalability with a Chip-Tip workflow enables deep single-cell proteomics.

Single-cell proteomics (SCP) promises to revolutionize biomedicine by providing an unparalleled view of the proteome in individual cells. Here, we present a high-sensitivity SCP workflow named Chip-Tip, identifying >5,000 proteins in individual HeLa cells. It also facilitated direct detection of post-translational modifications in single cells, making the need for specific post-translational modification-enrichment unnecessary.

Nuclear adenine activates hnRNPA2B1 to enhance antibacterial innate immunity.

Bacterial infection reprograms cellular metabolism and epigenetic status, but how the metabolic-epigenetic crosstalk empowers host antibacterial defense remains unclear. Here, we report that heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) is a sensor for metabolite adenine to launch an antimicrobial innate response through increasing Il1b transcription. Myeloid cell-specific Hnrnpa2b1-cKO mice are more susceptible to bacterial infection, while interleukin 1 beta (IL-1β) supplementation rescues the phenotype.

CPSF6-RARγ interacts with histone deacetylase 3 to promote myeloid transformation in RARG-fusion acute myeloid leukemia.

Acute myeloid leukemia (AML) with retinoic acid receptor gamma (RARG) fusions, which exhibits clinical features resembling acute promyelocytic leukemia (APL), has been identified as a new subtype with poor clinical outcomes. The underlying mechanism of RARG-fusion leukemia remains poorly understood, and needs to be explored urgently to instruct developing effective therapeutic strategies. Here, using the most prevalent RARG fusion, CPSF6-RARG (CR), as a representative, we reveal that the CR fusion, enhances the expansion of myeloid progenitors, impairs their maturation and synergizes with RAS mutations to drive more aggressive myeloid malignancies.

RTP4 restricts influenza A virus infection by targeting the viral NS1 protein.

The influenza A virus evades the host innate immune response to establish infection by inhibiting RIG-I activation through its nonstructural protein 1 (NS1). Here, we reported that receptor-transporting protein 4 (RTP4), an interferon-stimulated gene (ISG), targets NS1 to inhibit influenza A virus infection. Depletion of RTP4 significantly increased influenza A virus multiplication, while NS1-deficient viruses were unaffected.

USP5 inhibits anti-RNA viral innate immunity by deconjugating K48-linked unanchored and K63-linked anchored ubiquitin on IRF3.

Interferon regulatory factor 3 (IRF3) is a central hub transcription factor that controls host antiviral innate immunity. The expression and function of IRF3 are tightly regulated by the post-translational modifications. However, it is unknown whether unanchored ubiquitination and deubiquitination of IRF3 involve modulating antiviral innate immunity against RNA viruses.

Nonenzymatic lysine D-lactylation induced by glyoxalase II substrate SLG dampens inflammatory immune responses.

Immunometabolism is critical in the regulation of immunity and inflammation; however, the mechanism of preventing aberrant activation-induced immunopathology remains largely unclear. Here, we report that glyoxalase II (GLO2) in the glycolysis branching pathway is specifically downregulated by NF-κB signaling during innate immune activation via tristetraprolin (TTP)-mediated mRNA decay. As a result, its substrate S-D-lactoylglutathione (SLG) accumulates in the cytosol and directly induces D-lactyllysine modification of proteins.

Turning cold into hot: emerging strategies to fire up the tumor microenvironment.

The tumor microenvironment (TME) is a complex, highly structured, and dynamic ecosystem that plays a pivotal role in the progression of both primary and metastatic tumors. Precise assessment of the dynamic spatiotemporal features of the TME is crucial for understanding cancer evolution and designing effective therapeutic strategies. Cancer is increasingly recognized as a systemic disease, influenced not only by the TME, but also by a multitude of systemic factors, including whole-body metabolism, gut microbiome, endocrine signaling, and circadian rhythm.

The activation of complement C5a-C5aR1 axis in astrocytes facilitates the neuropathogenesis due to EV-A71 infection by upregulating CXCL1.

Unlabelled: Enterovirus A71 (EV-A71) is a common small RNA virus that is highly neuroinvasive. Emerging evidence indicates that the complement fragment C5a and its receptor C5aR1 are important drivers of neuroinflammation. However, the potential role of the C5a-C5aR1 axis in EV-A71 encephalitis remains largely elusive.

Mapping functional elements of the DNA damage response through base editor screens.

Maintaining genomic stability is vital for cellular equilibrium. In this study, we combined CRISPR-mediated base editing with pooled screening technologies to identify numerous mutations in lysine residues and protein-coding genes. The loss of these lysine residues and genes resulted in either sensitivity or resistance to DNA-damaging agents.

CIP2A inhibitors TD52 and Ethoxysanguinarine promote macrophage autophagy and alleviates acute pancreatitis by modulating the AKT-mTOR pathway.

Background: Acute pancreatitis (AP) is a prevalent and serious condition within the digestive system, with approximately 20 % to 30 % of cases advancing to severe acute pancreatitis (SAP). During the initial phases of SAP, macrophages are activated in response to the substantial amounts of acinar cell contents and damage-associated molecular patterns (DAMPs) resulting from acinar cell destruction. Subsequently, activated macrophages release a significant array of pro-inflammatory factors that exacerbate the progression of SAP.

IL-2-inducible T cell kinase deficiency sustains chimeric antigen receptor T cell therapy against tumor cells.

Despite the revolutionary achievements of chimeric antigen receptor (CAR) T cell therapy in treating cancers, especially leukemia, several key challenges still limit its therapeutic efficacy. Of particular relevance is the relapse of cancer in large part, as a result of exhaustion and short persistence of CAR-T cells in vivo. IL-2-inducible T cell kinase (ITK) is a critical modulator of the strength of T-cell receptor (TCR) signaling, while its role in CAR signaling is unknown.

N6-methyladenosine RNA modification promotes Severe Fever with Thrombocytopenia Syndrome Virus infection.

Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV), a novel bunyavirus primarily transmitted by Haemaphysalis longicornis, induces severe disease with a high mortality rate. N6-methyladenosine (m6A) is a prevalent internal chemical modification in eukaryotic mRNA that has been reported to regulate viral infection. However, the role of m6A modification during SFTSV infection remains elusive.

DeepGR: a deep-learning prognostic model based on glycolytic radiomics for non-small cell lung cancer.

Background: Glycolysis proved to have a prognostic value in lung cancer; however, to identify glycolysis-related genomic markers is expensive and challenging. This study aimed at identifying glycolysis-related computed tomography (CT) radiomics features to develop a deep-learning prognostic model for non-small cell lung cancer (NSCLC).

Methods: The study included 274 NSCLC patients from cohorts of The Second Affiliated Hospital of Soochow University (SZ; n=64), the Cancer Genome Atlas (TCGA)-NSCLC dataset (n=74), and the Gene Expression Omnibus dataset (n=136).

Comprehensive detection and dissection of interlineage recombination events in the SARS-CoV-2 pandemic.

The global prevalence of the XBB lineage presents a formidable challenge posed by the recombinant SARS-CoV-2 virus. The understanding of SARS-CoV-2's recombination preference assumes utmost significance in predicting future recombinant variants and adequately preparing for subsequent pandemics. Thus, an urgent need arises to establish a comprehensive landscape concerning SARS-CoV-2 recombinants worldwide and elucidate their evolutionary mechanisms.

Transcriptome analysis reveals that defects in cell cycle regulation contribute to preimplantation embryo arrest.

Patients with preimplantation embryo arrest (PREMBA) often experience assisted reproductive failure primarily due to the lack of transferable embryos, and the molecular mechanisms underlying PREMBA remain unclear. In our study, the embryos from five women with recurrent preimplantation embryo arrest and three women with tubal factor infertility were used for single-embryo transcriptome sequencing. Meanwhile, the transcriptomes of normal human preimplantation embryos obtained from GSE36552 were utilized to perform a comparative analysis with the transcriptomes of PREMBA embryos.

Functional profiling of serine, threonine and tyrosine sites.

Systematic perturbation of amino acids at endogenous loci provides diverse insights into protein function. Here, we performed a genome-wide screen to globally assess the cell fitness dependency of serine, threonine and tyrosine residues. Using an adenine base editor, we designed a whole-genome library comprising 817,089 single guide RNAs to perturb 584,337 S, T and Y sites.