Natural Kaurane-class of Diterpenoid Alkaloids: Structure, Distribution, and Bioactivities.

Kaurane-class diterpenoid alkaloids (DAs), an important group of C20-DAs, include mainly veatchine-, napelline-, anopterine- and tricalysiamide-type DAs and several types of DAs with novel skeletons discovered in recent years. To date, approximately 81 compounds belonging to this class of DAs have been isolated from plants in 5 families and 7 genera. Among them, Aconitum is the most important source of this class of DAs.

Structural basis of phosphate export by human XPR1.

Phosphorus in crucial for all living organisms. In vertebrate, cellular phosphate homeostasis is partly controlled by XPR1, a poorly characterized inositol pyrophosphate-dependent phosphate exporter. Here, we report the cryo-EM structure of human XPR1, which forms a loose dimer with 10 transmembrane helices (TM) in each protomer.

Modeling early gastrulation in human blastoids with DNA methylation patterns of natural blastocysts.

Blastoids are a promising model for studying early human embryogenesis, but current models have limitations in post-implantation development and lack comprehensive epigenetic assessments, especially regarding genomic imprinting. These issues can lead to failures in accurately modeling early embryonic development. In this study, we developed a high-fidelity blastoid model using 4 chemicals + leukemia inhibitory factor (LIF) (4CL) naive human pluripotent stem cells (hPSCs) (4CL blastoids).

The ER protein CANX (calnexin)-mediated autophagy protects against alzheimer disease.

Although the relationship between macroautophagy/autophagy and Alzheimer disease (AD) is widely studied, the underlying mechanisms are poorly understood, especially the regulatory role of the initiation signaling of autophagy on AD. Here, we find that the ER transmembrane protein CANX (calnexin) is a novel interaction partner of the autophagy-inducing kinase ULK1 and is required for ULK1 recruitment to the ER under basal or starved conditions. Loss of CANX results in the inactivity of ULK1 kinase and inhibits autophagy flux.

Widely targeted metabolomics analysis reveals dynamic changes in metabolites of 'Hass' avocado during postharvest ripening period.

Avocado (Persea americana Mill) is a climacteric fruit harvested at the green stage that ripens postharvest to become edible. The 'Hass' cultivar, known for its rich, buttery flavor and pear-shaped appearance, was studied for metabolite changes during postharvest ripening using UPLC-MS/MS approach. The 16-day ripening period could be divided into three stages: evolution (days 1-9), edible ripe (days 10-15) and overripe (day 16).

An Injectable Multifunctional Nanosweeper Eliminates Cardiac Mitochondrial DNA to Reduce Inflammation.

Myocarditis, a leading cause of sudden cardiac death and heart transplantation, poses significant treatment challenges. The study of clinical samples from myocarditis patients reveals a correlation between the pathogenesis of myocarditis and cardiomyocyte mitochondrial DNA (mtDNA). During inflammation, the concentration of mtDNA in cardiomyocytes increases.

Study on metabolic disorders in rat liver induced by different times after scalds.

Previous studies have confirmed that burns and scalds can lead to metabolic disorders in the liver. However, the effects of severe burns at various time points on liver lipid metabolism disorders, as well as the relationship between these disorders and liver function, metabolism, and infection, have not yet been investigated.This study established a SD rat scald model, macroscopic observation of weight changes, histological staining, Western blot detection of fat browning and metabolic indicators, reverse transcription quantitative polymerase chain reaction analysis of the expression of liver new fat generation genes, determination of liver function and inflammatory indicators.

Transferrin Disassociates TCR from CD3 Signaling Apparatus to Promote Metastasis.

Immune recognition and activation by the peptide-laden major histocompatibility complex-T cell receptor (TCR)-CD3 complex is essential for anti-tumor immunity. Tumors may escape immune surveillance by dissembling the complex. Here, we report that transferrin, which is overexpressed in patients with liver metastasis, disassociates TCR from the CD3 signaling apparatus by targeting the constant domain (CD) of T cell receptor α (TCRα), consequently suppresses T cell activation, and inhibits anti-metastatic and anti-tumor immunity.

Transcriptome sequencing reveals regulatory genes associated with neurogenic hearing loss.

Hearing loss is a prevalent condition with a significant impact on individuals' quality of life. However, comprehensive studies investigating the differential gene expression and regulatory mechanisms associated with hearing loss are lacking, particularly in the context of diverse patient samples. In this study, we integrated data from 10 patients across different regions, age groups, and genders, with their data retrieved from a public transcriptome database, to explore the molecular basis of hearing loss.

Vitrification of 3D-MSCs encapsulated in GelMA hydrogel: Improved cryosurvival, reduced cryoprotectant concentration, and enhanced wound healing.

Compared to traditional 2D-cultured mesenchymal stem cells (MSCs), 3D-MSCs offer distinct advantages in disease treatment. However, large-scale culture of 3D-MSCs remains labor-intensive and time-consuming. Thus, developing cryopreservation method for 3D-MSCs is essential for clinical application.

Evidence from Mendelian randomization analysis combined with meta-analysis for the causal validation of the relationship between 91 inflammatory factors and lumbar disc herniation.

Lumbar disc herniation (LDH) is a common spinal disease. In recent years, an increasing number of observational studies have reported the impact of inflammatory factors on LDH. By conducting Mendelian randomization (MR) analysis on 91 inflammatory factors, it is possible to reveal their causal relationship with LDH, providing new insights for prevention and treatment strategies.

Development and validation of a preoperative nomogram for predicting gallbladder adenoma.

Background: Gallbladder cholesterol polyp (GCP) and gallbladder adenoma (GA) are easily confused in clinical diagnosis. This study aims to establish a nomogram prediction model for preoperative prediction of the risk of GA patients.

Study Design: We retrospectively collected clinical data of GCP or GA patients who underwent laparoscopic cholecystectomy (LC) between January 2020 and April 2023.

Tumor Vaccine Exploiting Membranes with Influenza Virus-Induced Immunogenic Cell Death to Decorate Polylactic Coglycolic Acid Nanoparticles.

Immunogenic cell death (ICD) of tumor cells, which is characterized by releasing immunostimulatory "find me" and "eat me" signals, expressing proinflammatory cytokines and providing personalized and broad-spectrum tumor antigens draws increasing attention in developing a tumor vaccine. In this study, we aimed to investigate whether the influenza virus (IAV) is efficient enough to induce ICD in tumor cells and an extra modification of IAV components such as hemeagglutinin (HA) will be helpful for the ICD-induced cells to elicit robust antitumor effects; in addition, to evaluate whether the membrane-engineering polylactic coglycolic acid nanoparticles (PLGA NPs) simulating ICD immune stimulation mechanisms hold the potential to be a promising vaccine candidate, a mouse melanoma cell line (B16-F10 cell) was infected with IAV rescued by the reverse genetic system, and the prepared cells and membrane-modified PLGA NPs were used separately to immunize the melanoma-bearing mice. IAV-infected tumor cells exhibit dying status, releasing high mobility group box-1 (HMGB1) and adenosine triphosphate (ATP), and exposing calreticulin (CRT), IAV hemeagglutinin (HA), and tumor antigens like tyrosinase-related protein 2 (TRP2).

A novel technique of cryodenervation for murine vagus nerve: implications for acute lung inflammation.

Background: Neuroimmune interaction is an underestimated mechanism for lung diseases, and cryoablation is a competitive advantageous technique than other non-pharmacologic interventions for peripheral nerve innervating the lung. However, a lack of cryodenervation model in laboratory rodents leads to the obscure mechanisms for techniques used in clinic.

Method: Herein, we developed a novel practical method for mouse peripheral nerve cryoablation, named visualized and simple cryodenervation (VSCD).

Efficacy and safety of indocyanine green fluorescence navigation versus conventional laparoscopic hepatectomy for hepatocellular carcinoma: a systematic review and meta-analysis.

Background: Indocyanine green (ICG) fluorescence imaging technology is increasingly widely used in laparoscopic hepatectomy. However, previous studies have produced conflicting results regarding whether it is truly superior to traditional laparoscopic hepatectomy. This study investigated the clinical effect of laparoscopic hepatectomy for hepatocellular carcinoma (HCC) using ICG imaging technology.

[Cloning and application in synthetic biology of chalcone synthase gene from Lithocarpus litseifolius].

Lithocarpus litseifolius is rich in the chalcones phloridzin and trilobatin, the biosynthesis pathways of which have not been fully demonstrated. Chalcone synthase(CHS) is the first key rate-limiting enzyme in the biosynthesis of flavonoids in plants. To explore the functions of CHS gene family in chalcone synthesis of L.

Baseline characteristics of patients in the Chinese Bronchiectasis Registry (BE-China): a multicentre prospective cohort study.

Background: Bronchiectasis is a disease with a global impact, but most published data come from high-income countries. We aimed to describe the clinical characteristics of patients with bronchiectasis in China.

Methods: The Chinese Bronchiectasis Registry (BE-China) is a prospective, observational cohort enrolling patients from 111 hospitals in China.

Intra-Arterial Urokinase After Endovascular Reperfusion for Acute Ischemic Stroke: The POST-UK Randomized Clinical Trial.

Importance: Persisting or new thrombi in the distal arteries and the microcirculation have been reported to limit the benefits of successful endovascular thrombectomy for patients with acute ischemic stroke. It remains uncertain whether intra-arterial thrombolysis by urokinase following near-complete to complete reperfusion by thrombectomy improves outcomes among patients with ischemic stroke due to large vessel occlusion.

Objective: To assess the efficacy and adverse events of intra-arterial urokinase after near-complete to complete reperfusion by thrombectomy for acute ischemic stroke due to large vessel occlusion.

Quality of guidelines for hyperthyroidism: systematic quality assessment using the AGREE II tool.

Objectives: The aim of this study was to systematically assess the quality of different guidelines for the management of patients with hyperthyroidism and to explore and analyze the recommendations and key evidence in different guidelines.

Methods: A systematic search of databases and websites was conducted to identify treatment guidelines for hyperthyroidism. The quality of the included guidelines was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool.

ALKBH3-mediated m1A demethylation promotes the malignant progression of acute myeloid leukemia by regulating ferroptosis through the upregulation of ATF4 expression.

To investigate the role of ALKBH3 in acute myeloid leukemia (AML), we constructed an animal model of xenotransplantation of AML. Our study demonstrated that ALKBH3-mediated m1A demethylation inhibits ferroptosis in KG-1 cells by increasing ATF4 expression, thus promoting the development of AML. These findings suggest that reducing ALKBH3 expression may be a potential strategy to mitigate AML progression.

: Empowering artificial intelligence for respiratory diseases diagnosis based on electronic health records, a multicenter study.

Respiratory diseases pose a significant global health burden, with challenges in early and accurate diagnosis due to overlapping clinical symptoms, which often leads to misdiagnosis or delayed treatment. To address this issue, we developed , an artificial intelligence (AI)-based diagnostic system that utilizes natural language processing (NLP) to extract key clinical features from electronic health records (EHRs) for the accurate classification of respiratory diseases. This study employed a large cohort of 31,267 EHRs from multiple centers for model training and internal testing.

Inorganic arsenic modulates cell apoptosis by regulating Argonaute 2 expression via the p53 pathway.

This study explores the role of Argonaute 2 (AGO2) in the induction of apoptosis by arsenic in 16HBE cells and investigates the association between AGO2 expression and arsenic exposure in a human population. By silencing AGO2 with siRNA, we examined its impact on cell viability and apoptosis using CCK-8, HO-PI, and JC-1 assays, complemented by qRT-PCR and Western blot analyses for gene and protein expressions. Our findings revealed a significant correlation between AGO2 expression and levels of exposure to inorganic arsenic (iAs), which was more pronounced than with other arsenic forms such as monomethylarsonic (MMA) and dimethylarsinic acids (DMA).

Chinese guidelines for the diagnosis and treatment of rheumatoid arthritis: 2024 update.

Rheumatoid arthritis (RA) is an autoimmune disease with destructive arthritis as its main clinical manifestation, which is a major cause of disability. It is very important to formulate and update a guideline for the diagnosis and treatment of RA that adhere to international guideline development standards and can be applied to clinical practice in China. This guideline is endorsed and developed by the National Clinical Research Center for Dermatologic and Immunologic Diseases, collaborated with Rheumatologists Branch of Chinese Medical Doctor Association, Rheumatology Rehabilitation Branch of Chinese Association of Rehabilitation Medicine, Rheumatology Branch of Chinese Research Hospital Association, and Rheumatology Branch of Beijing Association of Holistic Integrative Medicine, based on grading of recommendations assessment, development and evaluation (GRADE) and reporting items for practice guidelines in healthcare (RIGHT).

Prevalence and Risk Factors of Lower Extremity Musculoskeletal Disorders Among Occupational Groups in Key Industries - China, 2018-2023.

What Is Already Known About This Topic?: Lower extremity musculoskeletal diseases (LE-MSDs) have emerged as a significant contributor to the global disease economic burden and worker absenteeism, becoming a global public health concern. However, the epidemic characteristics of LE-MSDs among occupational populations in China are unknown.

What Is Added By This Report?: This report finds that the LE-MSDs prevalence rate among key occupational groups in China is 17.