MtrAB two-component system is crucial for the intrinsic resistance and virulence of Mycobacterium abscessus.

Mycobacterium abscessus (Mab) poses serious therapeutic challenges, largely due to its intrinsic resistance to many antibiotics. The development of targeted therapeutic strategies necessitates the identification of bacterial factors that contribute to its reduced susceptibility to antibiotics and/or to the killing by its host cells. In this study, we discovered that Mab strains with disrupted mtrA, mtrB or both, or a gene-edited mtrA encoding MtrA with Tyr102Cys mutation, exhibited highly increased sensitivity to various drugs compared to the wild-type Mab.

Ensemble learning-based predictor for driver synonymous mutation with sequence representation.

Synonymous mutations, once considered neutral, are now understood to have significant implications for a variety of diseases, particularly cancer. It is indispensable to identify these driver synonymous mutations in human cancers, yet current methods are constrained by data limitations. In this study, we initially investigate the impact of sequence-based features, including DNA shape, physicochemical properties and one-hot encoding of nucleotides, and deep learning-derived features from pre-trained chemical molecule language models based on BERT.

Tumor Mutation Signature Reveals the Risk Factors of Lung Adenocarcinoma with or Mutation.

Introduction: and mutations are frequently detected in lung adenocarcinoma (LUAD). Tumor mutational signature (TMS) determination is an approach to identify somatic mutational patterns associated with pathogenic factors. In this study, through the analysis of TMS, the underlying pathogenic factors of LUAD with and mutations were traced.

Inhibition of ASIC1a reduces ferroptosis in rheumatoid arthritis articular chondrocytes via the p53/NRF2/SLC7A11 pathway.

The activation of acid-sensing ion channel 1a (ASIC1a) in response to extracellular acidification leads to an increase in extracellular calcium influx, thereby exacerbating the degeneration of articular chondrocytes in rheumatoid arthritis (RA). It has been suggested that the inhibition of extracellular calcium influx could potentially impede chondrocyte ferroptosis. The cystine transporter, solute carrier family 7 member 11 (SLC7A11), is recognized as a key regulator of ferroptosis.

Copper-luteolin nanocomplexes for Mediating multifaceted regulation of oxidative stress, intestinal barrier, and gut microbiota in inflammatory bowel disease.

Oxidative stress, dysbiosis, and immune dysregulation have been confirmed to play pivotal roles in the complex pathogenesis of inflammatory bowel disease (IBD). Herein, we design copper ion-luteolin nanocomplexes (CuL NCs) through a metal-polyphenol coordination strategy, which plays a multifaceted role in the amelioration of IBD. The fabricated CuL NCs function as therapeutic agents with exceptional antioxidant and anti-inflammatory capabilities because of their great stability and capacity to scavenge reactive oxygen species (ROS).

Google Trends applications for COVID-19 pandemic: A bibliometric analysis.

Introduction: COVID-19 is one of the most severe global health events in recent years. Google Trends provides a comprehensive analysis of the search frequency for specific terms on Google, reflecting the public's areas of interest. As of now, there has been no bibliometric study on COVID-19 and Google Trends.

Copper-Based Nanozymes: Potential Therapies for Infectious Wounds.

Bacterial infections are a significant obstacle to the healing of acute and chronic wounds, such as diabetic ulcers and burn injuries. Traditional antibiotics are the primary treatment for bacterial infections, but they present issues such as antibiotic resistance, limited efficacy, and potential side effects. This challenge leads to the exploration of nanozymes as alternative therapeutic agents.

Responsive Degradable Bottlebrush Polymers Enable Drugs With Superior Efficacy and Minimal Systemic Toxicity.

Bottlebrush polymers (BBPs) have garnered significant attention as advanced drug delivery systems, capable of transporting a diverse range of therapeutic agents, including both chemical drugs and biologics. Despite their effectiveness, the empty BBP vectors post-drug release may pose long-term safety risks due to their difficult systemic clearance. Here, a responsive degradable BBP platform for cancer therapy is developed, featuring a poly(disulfide) backbone grafted with fluorine-terminated zwitterionic side chains.

Neutralizing antibody test supports booster strategy for young individuals after SARS-CoV-2 Omicron breakthrough.

Background: The SARS-CoV-2 Omicron variant, since its initial detection, has rapidly spread across the globe, becoming the dominant strain. It is important to study the immune response of SARS-CoV-2 Omicron variant due to its remarkable ability to escape the majority of existing SARS-CoV-2 neutralizing antibodies. The surge in SARS-CoV-2 Omicron infections among most Chinese residents by the end of 2022 provides a unique opportunity to understand immune system's response to Omicron in populations with limited exposure to prior SARS-CoV-2 variants.

Metabolic reprogramming and astrocytes polarization following ischemic stroke.

Astrocytes are critical for maintaining neuronal activity. Activation of astrocytes, occurs within minutes from ischemic stroke onset due to ischemic causes and subsequent inflammatory damage. Activated astrocytes, also known as reactive astrocytes, are divided into two different phenotypes: A1 (pro-inflammatory) and A2 (anti-inflammatory) astrocytes.

ADAMDEC1 promotes the malignant progression of cholangiocarcinoma by regulating NF-κB signaling pathway.

Cholangiocarcinoma (CCA), a highly aggressive form of cancer, is known for its high mortality rate. A Disintegrin and Metalloprotease Domain-like Protein Decysin-1 (ADAMDEC1) can promote the development and metastasis in various tumors by degrading the extracellular matrix. However, its regulatory mechanism in CCA remains unclear.

Small molecule-driven LKB1 deacetylation is responsible for the inhibition of hepatic lipid response in NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is a progressive condition characterized by ectopic fat accumulation in the liver, for which no FAD-approved drugs currently exist. Emerging evidence highlights the role of liver kinase B1 (LKB1), a key metabolic regulator, has been proposed in NAFLD, particularly in response to excessive nutrient levels. However, few agents have been identified that can prevent the progression of nonalcoholic steatohepatitis (NASH) by targeting LKB1 deacetylation.

Efficacy and safety of SHR8554 on postoperative pain in subjects with moderate to severe acute pain following orthopedic surgery: A multicenter, randomized, double-blind, dose-explored, active-controlled, phase II/III clinical trial.

Biased µ-opioid receptor (MOR) agonists enhance pain relief by selectively activating G protein-coupled receptor signaling and minimizing β-arrestin-2 activation, resulting in fewer side effects. This multicenter Phase II/III trial evaluated the optimal dosage, efficacy, and safety of SHR8554, a biased MOR agonist, for postoperative pain management following orthopedic surgery. In Phase II, 121 patients were divided into four groups to receive varying patient-controlled analgesia (PCA) doses of SHR8554 or morphine.

ABCF1-K430-Lactylation promotes HCC malignant progression via transcriptional activation of HIF1 signaling pathway.

Lysine lactylation plays critical roles in various diseases, including cancer. Our previous study showed that lactylation of non-histone ABCF1 may be involved in hepatocellular carcinoma (HCC) progression. In this study, we evaluated the prognostic value of ABCF1-K430la in HCC using immunohistochemical staining and performed amino acid point mutations, multi-omics crossover, and biochemical experiments to investigate its biological role and underlying mechanism.

LAPTM5 Confers the Resistance to Venetoclax via Promoting the Autophagosome-Lysosome Fusion in Multiple Myeloma.

Multiple myeloma (MM) is a haematological lymphoid malignancy marked by significant morbidity due to severe complications. Despite advances in targeted therapies, including proteasome inhibitors and the BCL-2 inhibitor venetoclax, drug resistance frequently occurs, with the underlying mechanisms poorly understood. This study investigates the role of lysosome-associated protein transmembrane 5 (LAPTM5) in conferring resistance to venetoclax in relapsed MM.

Infiltrating plasma cells maintain glioblastoma stem cells through IgG-Tumor binding.

Glioblastoma is a highly aggressive primary brain tumor with glioblastoma stem cells (GSCs) enforcing the intra-tumoral hierarchy. Plasma cells (PCs) are critical effectors of the B-lineage immune system, but their roles in glioblastoma remain largely unexplored. Here, we leverage single-cell RNA and B cell receptor sequencing of tumor-infiltrating B-lineage cells and reveal that PCs are aberrantly enriched in the glioblastoma-infiltrating B-lineage population, experience low level of somatic hypermutation, and are associated with poor prognosis.

Cbl-b inhibition improves manufacturing efficiency and antitumoral efficacy of anti-CD19 CAR-T cells.

Chimeric antigen receptor T (CAR-T) cells represent a promising approach for cancer immunotherapy, yet their efficacy is hindered by immunosuppressive signals in the tumor microenvironment. Casitas B-cell lymphoma protein b (Cbl-b) is a key negative regulator of T cell function. This study investigated whether inhibiting Cbl-b enhances the antitumor activity of human CAR-T cells.

Klp2-mediated Rsp1-Mto1 colocalization inhibits microtubule-dependent microtubule assembly in fission yeast.

Microtubule assembly takes place at the centrosome and noncentrosomal microtubule-organizing centers (MTOCs). However, the mechanisms controlling the activity of noncentrosomal MTOCs are poorly understood. Here, using the fission yeast as a model organism, we demonstrate that the kinesin-14 motor Klp2 interacts with the J-domain Hsp70/Ssa1 cochaperone Rsp1, an inhibitory factor of microtubule assembly, and that Klp2 is required for the proper localization of Rsp1 to microtubules.

Maternal phthalates exposure promotes neural stem cell differentiation into phagocytic astrocytes and synapse engulfment via IRE1α/XBP1s pathway.

Humans are widely exposed to phthalates, a common chemical plasticizer. Previous cohort studies have revealed that maternal exposure to monobutyl phthalate (MBP), a key metabolite of phthalates, is associated with neurodevelopmental defects. However, the molecular mechanism remains unclear.

Mass-spectrometry-based quantitative proteomic analysis reveals that methylglyoxal and carnosine influence oxidative stress and RNA-processing associated proteins in renal proximal tubule epithelial cells.

Background: Tubular injury triggered by hyperglycemia is an important pathological characteristic in diabetic nephropathy (DN). Accumulated advanced glycation end products and their precursor methylglyoxal (MGO), contribute to the development of DN. Carnosine has been shown to prevent the development of DN but the underlying mechanism still needs to be studied in depth.

Phase 2 study of serplulimab with the bevacizumab biosimilar HLX04 in the first-line treatment of advanced hepatocellular carcinoma.

Introduction: This study aimed to evaluate the safety and preliminary efficacy of serplulimab, a novel programmed death-1 inhibitor, with or without bevacizumab biosimilar HLX04 as first-line treatment in patients with advanced hepatocellular carcinoma.

Methods: This open-label, multicenter phase 2 study (clinicaltrials.gov identifier NCT03973112) was conducted in China and consisted of four treatment groups: group A (serplulimab 3 mg/kg plus HLX04 5 mg/kg, subsequent-line), group B (serplulimab 3 mg/kg plus HLX04 10 mg/kg, subsequent-line), group C (serplulimab 3 mg/kg, subsequent-line) and group D (serplulimab 3 mg/kg plus HLX04 10 mg/kg, first-line).

Lipophilicity Modulation of Fluorescent Probes for Imaging of Cellular Microvesicle Dynamics.

Real-time monitoring of dynamic microvesicles (MVs), vesicles associated with living cells, is of great significance in deeply understanding their origin, transport, and function. However, specific labeling MVs poses a challenge due to the lack of unique biomarkers that differentiate them from other cellular compartments. Here, we present a strategy to selectively label MVs by evaluating a series of lipid layer-sensitive cationic indolium-coumarin fluorescent probes (designated as IC-C, with ranging from 1 to 18) that feature varying aliphatic side chains (CH).