Copper-catalysed radical cascade reaction of -(2-oxo-2-phenylethyl) substituted 2-pyridones with styrene to access 1,6-carboannulated 2-pyridone scaffolds.

Herein, we present that treating -(2-oxo-2-phenylethyl) substituted 2-pyridones with styrenes in DMSO/HO at 120 °C affords 1,6-carboannulated 2-pyridone scaffolds with up to 79% yield. This protocol provides a simple and efficient method for obtaining complicated bicyclic 2-pyridones through a radical cascade reaction. Additionally, we have successfully synthesized 27 target compounds, which confirms the practicality and wide applicability of the proposed reaction.

Molecular Mechanisms of Humic Acid in Inhibiting Silica Scaling during Membrane Distillation.

Membrane distillation (MD) efficiently desalinizes and treats high-salinity water as well as addresses the challenges in handling concentrated brines and wastewater. However, silica scaling impeded the effectiveness of MD for treating hypersaline water and wastewater. Herein, the effects of humic acid (HA) on silica scaling behavior during MD are systematically investigated.

The Type III Secretion System (T3SS) of Escherichia Coli Promotes Atherosclerosis in Type 2 Diabetes Mellitus.

Large-scale studies indicate a strong relationship between the gut microbiome, type 2 diabetes mellitus (T2DM), and atherosclerotic cardiovascular disease (ASCVD). Here, a higher abundance of the type III secretion system (T3SS) virulence factors of Enterobacteriaceae/Escherichia-Shigella in patients with T2DM-related-ASCVD, which correlates with their atherosclerotic stenosis is reported. Overexpression of T3SS via Citrobacter rodentium (CR) infection in Apoe-/- T2DM mice exacerbated atherosclerotic lesion formation and increased gut permeability.

Amorphization Stabilizes Te-based Aqueous Batteries via Confining Free Water.

Tellurium (Te), with its rich valence states (-2 to +6), could endow aqueous batteries with potentially high specific capacity. However, achieving complete and stable hypervalent Te0/Te4+ electrochemistry in an aqueous environment poses significant challenges, owing to the sluggish reduction kinetics, the easy dissolution of Te4+ species, and a controversial energy storage mechanism. Herein, for the first time, we demonstrate an amorphous strategy for robust aqueous TeO2/Te electrochemistry.

Lipid nanoparticles deliver DNA-encoded biologics and induce potent protective immunity.

Lipid nanoparticles (LNPs) for mRNA delivery have advanced significantly, but LNP-mediated DNA delivery still faces clinical challenges. This study compared various LNP formulations for delivering DNA-encoded biologics, assessing their expression efficacy and the protective immunity generated by LNP-encapsulated DNA in different models. The LNP formulation used in Moderna's Spikevax mRNA vaccine (LNP-M) demonstrated a stable nanoparticle structure, high expression efficiency, and low toxicity.

Revolutionizing Heart Failure Therapy: Harnessing IVT mRNA and Fusion Protein Technology to Prolong rhBNP Half-Life.

Purpose: Recombinant human B-type natriuretic peptide (rhBNP) has been extensively proven to be an effective mean of heart failure (HF) therapy, but its clinical application is limited by its very short half-life. This study aims to combine in vitro transcribed mRNA (IVT mRNA) and fusion protein technology to develop a rhBNP-Fc mRNA drug with long half-life, high efficiency and few side effects to treat HF.

Methods: The rhBNP-Fc fusion mRNA with IgG4-Fc sequence was produced by IVT technology.

Biocompatible autonomous self-healing PVA-CS/TA hydrogels based on hydrogen bonding and electrostatic interaction.

The biocompatible autonomous self-healing hydrogels have great potential in biomedical applications. However, the fairly weak tensile strength of the hydrogels seriously hinders their application. Here, we introduced chitosan (CS) into the polyvinyl alcohol (PVA)-tannic acid (TA) hydrogel and investigated the effects of the CS content, as CS can not only form reversible H bonds with PVA and TA but also form reversible electrostatic interactions with TA.

[Evidence mapping of clinical research on traditional Chinese medicine in treatment of idiopathic pulmonary fibrosis].

This study systematically retrieved the clinical studies in the treatment of idiopathic pulmonary fibrosis(IPF) with traditional Chinese medicine(TCM) and employed evidence mapping to summarize the overall research status and deficiencies of TCM in treating IPF. CNKI, VIP, SinoMed, Wanfang, PubMed, Web of Science, Cochrane Library, and EMbase were searched for the relevant studies published from inception to February 20, 2024. The distribution characteristics of the evidence were analyzed and presented through charts combined with words.

Effect of social support on memory ageing of middle-aged and older cancer survivors: a marginal structural modelling approach.

Background: While social support is associated with better cognitive health among cancer-free individuals, this relationship is understudied among cancer survivors. We investigated whether overall social support before and after a cancer diagnosis is related to post-diagnosis memory ageing, overall and by sex/gender.

Methods: Data were from 2044 cancer survivors in the US Health and Retirement Study (HRS; n=1395) and English Longitudinal Study of Ageing (ELSA; n=649) from 2006 to 2018.

Chemerin loss-of-function attenuates glucagon-like peptide-1 secretion in exercised obese mice.

Aims: To investigate the role of chemerin reduction in mediating exercise-induced Glucagon-like peptide-1 (GLP-1) secretion and the amelioration of pancreatic β-cell function in obesity.

Materials And Methods: Obesity models were established using wild-type and chemerin systemic knockout mice, followed by 8 weeks of moderate-intensity continuous aerobic exercise training. Serum chemerin levels, GLP-1 synthesis, glucose tolerance, pancreatic β-cell function, structure, and apoptosis were assessed.

HER2-targeted ADC DX126-262 combined with chemotherapy demonstrates superior antitumor efficacy in HER2-positive gastric cancer.

Gastric cancer is a common malignant tumor with high incidence and mortality. The overexpression of Human epidermal growth factor receptor 2 (HER2) is associated with increased metastatic potential and poor clinical outcome in gastric cancer. Despite the proven clinical response rates of approved HER2-targeted therapies, including Trastuzumab combined with chemotherapy, their limited long-term clinical benefits and inevitable disease progression still pose significant challenges to the clinical treatment of gastric cancer.

Clair3-RNA: A deep learning-based small variant caller for long-read RNA sequencing data.

Variant calling using long-read RNA sequencing (lrRNA-seq) can be applied to diverse tasks, such as capturing full-length isoforms and gene expression profiling. It poses challenges, however, due to higher error rates than DNA data, the complexities of transcript diversity, RNA editing events, etc. In this paper, we propose Clair3-RNA, the first deep learning-based variant caller tailored for lrRNA-seq data.

Replication stress increases de novo CNVs across the malaria parasite genome.

Changes in the copy number of large genomic regions, termed copy number variations (CNVs), contribute to important phenotypes in many organisms. CNVs are readily identified using conventional approaches when present in a large fraction of the cell population. However, CNVs that are present in only a few genomes across a population are often overlooked but important; if beneficial under specific conditions, a de novo CNV that arises in a single genome can expand during selection to create a larger population of cells with novel characteristics.

Comparative Analysis of Seventeen Mitochondrial Genomes of Mileewinae Leafhoppers, Including the Unique Species (Hemiptera: Cicadellidae: Mileewinae) From Xizang, China, and New Insights Into Phylogenetic Relationships Within Mileewini.

The subfamily Mileewinae in China comprises one tribe (Mileewini), four genera (, , , ), and 71 species, yet only 11 mitochondrial genomes have been published. This study aimed to elucidate ambiguous diagnostic traits in traditional taxonomy and examined phylogenetic relationships among genera by sequencing mitochondrial genomes from 16 species. The lengths of the mitochondrial genomes ranged from 14,532 to 15,280 bp, exhibiting an AT content of 77.

Efficacy and safety of atezolizumab combined with bevacizumab, arterial chemoembolization, and hepatic artery infusion chemotherapy for advanced hepatocellular carcinoma: a meta-analysis.

Objective: Although the combination of atezolizumab and bevacizumab (A+B) shows promise for advanced hepatocellular carcinoma (HCC), its response rate is still inadequate. Previous studies indicate that the integration of FOLFOX-based hepatic arterial infusion chemotherapy (HAIC) with transarterial chemoembolization (TACE) is advantageous for the management of HCC. This meta-analysis aims to assess the safety and efficacy of the A+B+TACE or HAIC therapy protocol in patients with advanced HCC.

PET/CT guided tuberculosis treatment shortening: a randomized trial.

Six months of chemotherapy using current agents is standard of care for pulmonary, drug-sensitive tuberculosis (TB), even though some are believed to be cured more rapidly and others require longer therapy. Understanding what factors determine the length of treatment required for durable cure in individual patients would allow individualization of treatment durations, provide better clinical tools to determine the of appropriate duration of new regimens, as well as reduce the cost of large Phase III studies to determine the optimal combinations to use in TB control programs. We conducted a randomized clinical trial in South Africa and China that recruited 704 participants with newly diagnosed, drug-sensitive pulmonary tuberculosis and stratified them based on radiographic disease characteristics as assessed by FDG PET/CT scan readers.

Neuroprotective Effects of Eugenol Acetate Against Ischemic Stroke.

Objective: To explore the neuroprotective effect of Eugenol Acetate (EA) on post-stroke neuroinflammation and investigate the underlying mechanisms.

Methods: For in vitro experiments, primary microglia were pre-incubated with EA for 2 hours, followed by lipopolysaccharide (LPS) stimulation for 24 hours or Oxygen-Glucose Deprivation (OGD) treatment for 4 hours. Real-time quantitative PCR, enzyme-linked immunosorbent assay (ELISA) and Western blot were performed to examine the expression levels of inflammatory cytokines in primary microglia.

Coal Worker's Pneumoconiosis-Targeted Lipidomics Reveals Aberrant Phospholipid Metabolism for Early-Stage Diagnosis.

Introduction: Pneumoconiosis is the most prevalent occupational disease in China, with coal worker pneumoconiosis (CWP) demonstrating the highest incidence. Studies have indicated that phospholipids may be associated with CWP.

Methods: In this study, serum was obtained from 62 patients with pneumoconiosis, 105 coal dust-exposed workers, and 50 healthy individuals and analyzed via targeted lipidomics using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).

A novel small-molecule fluorescent probe caused by minimal structural modifications for specific staining of the cell nuclear membrane.

The nuclear membrane is a double-layered structure that physically protects the cell's DNA from the chemical reactions occurring in other parts of the cell. In this study, we present the first brand-new small-molecule fluorescent probe that selectively stains the nuclear membrane, allowing for the visualization of nuclear morphology without interfering with the DNA's activity.

Influence of endoscopic sphincterotomy on hepatolithiasis with Oddi sphincter-preserved cholangioplasty with hepatico-subcutaneous stoma: A three-decade, real word cohort study.

Background: Hepatolithiasis frequently presents with recurring cholangitis and complications. Oddi sphincter-preserved cholangioplasty with hepatico-subcutaneous stoma (OSPCHS), introduced in 1993, has shown favorable long-term results. Endoscopic sphincterotomy (EST) is commonly used, but its impact on OSPCHS outcomes remains unclear.

Network characteristics of comorbid symptoms in alcohol use disorder.

Background: Individuals with alcohol use disorder (AUD) often experience symptoms such as anxiety, depression, and decreased sleep quality. Although these are not diagnostic criteria, they may increase dependence risk and complicate treatment. This study aims to analyze comorbidities and their complex relationships in AUD patients through epidemiological surveys and network analysis.

Unveiling the Contribution of Hydrogen Radicals to Per- and Polyfluoroalkyl Substances (PFASs) Defluorination: Applicability and Degradation Mechanisms.

At present, the defluorination of per- and polyfluoroalkyl substances (PFASs), including perfluoroether compounds as substitutes of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonate, is limited by the effective active species produced during the oxidation-reduction process. The contribution of the hydrogen radical (•H) as a companion active substance in the photoreduction and electrocatalytic degradation of PFASs has been neglected. Herein, we demonstrate that perfluorocarboxylic acids and perfluoroether compounds such as PFOA and hexafluoropropylene oxide dimer acid (GenX) underwent near-complete photodegradation and effective defluorination by continuously generating •H through perfluoroalkyl radical activation of water under UV irradiation without any reagents and catalysts.

A multicenter, randomized, double-blind, placebo-controlled phase 3 study of Socazolimab or placebo combined with carboplatin and etoposide in the first-line treatment of extensive-stage small cell lung cancer.

This is a randomized, double-blind, placebo-controlled phase 3 clinical trial (ClinicalTrials.gov, NCT04878016) conducted in 54 hospitals in China. Adults who were histologically diagnosed and never treated for extensive-stage small cell lung cancer (ES-SCLC) were enrolled.

Advancements of astaxanthin production in Haematococcus pluvialis: Update insight and way forward.

The global market demand for natural astaxanthin (AXT) is growing rapidly owing to its potential human health benefits and diverse industry applications, driven by its safety, unique structure, and special function. Currently, the alga Haematococcus pluvialis (alternative name H. lacustris) has been considered as one of the best large-scale producers of natural AXT.

Comprehensive analysis of the xbp1 gene in Pacific abalone Haliotis discus hannai: Structure, expression, and role in heat stress response.

The present study explores the x-box binding protein 1 (xbp1) gene in Haliotis discus hannai (Pacific abalone), focusing on its structure, expression, and functional role under heat stress. Southern blot revealed two copies of xbp1 in the intestine and mantle, one in the gill and muscle, and no detection in the digestive gland. mRNA expression levels were highest in the gill, followed by the mantle, intestine, and muscle, with the digestive gland showing the lowest expression.