Gain-of-function ANXA11 mutation cause late-onset ALS with aberrant protein aggregation, neuroinflammation and autophagy impairment.

Mutations in the ANXA11 gene, encoding an RNA-binding protein, have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS), but the underlying in vivo mechanisms remain unclear. This study examines the clinical features of ALS patients harboring the ANXA11 hotspot mutation p.P36R, characterized by late-onset motor neuron disease and occasional multi-system involvement.

Global, regional, and national burden of primary liver cancer attributable to metabolic risks: an analysis of the Global Burden of Disease Study 1990-2021.

Background: The global burden of metabolic diseases is increasing, but estimates of their impact on primary liver cancer are uncertain. We aimed to assess the global burden of primary liver cancer attributable to metabolic risk factors, including high body mass index (BMI) and high fasting plasma glucose (FPG) levels, between 1990 and 2021.

Methods: The total number and age-standardized rates of deaths and disability-adjusted life years (DALYs) from primary liver cancer attributable to each metabolic risk factor were extracted from the Global Burden of Disease Study 1990-2021.

A hyaluronic acid nanogels based exosome production factory for tumor photothermal therapy and angiogenesis inhibition.

Exosomes as a unique drug delivery system provide a new choice for tumor therapy. However, the in vitro functionalization of exosomes and the process of circulating drug delivery can easily cause exosome degradation and drug loss, thus reducing the efficiency of drug delivery. In this work, based on the endocyto-fusion-exocytosis pathway of exosome formation, a multifunctional hyaluronic acid nanogel loaded with the antiangiogenic drug vatalanib and the near-infrared photothermal agent indocyanine green (ICG) was designed.

The de novo synthesis of GABA and its gene regulatory function control hepatocellular carcinoma metastasis.

The neurotransmitter gamma-aminobutyric acid (GABA) has been thought to be involved in the development of some types of cancer. Yet, the de novo synthesis of GABA and how it functions in hepatocellular carcinoma (HCC) remain unclear. Here, we report that SLC6A12 acts as a transporter of GABA, and that aldehyde dehydrogenase 9 family member A1 (ALDH9A1), not glutamate decarboxylase 1 (GAD1), generates GABA in human HCC.

Brain tumor and mood disorders: a retrospective analysis of anxiety and depression in patients with primary and metastatic brain tumors.

Brain tumors are associated with a dismal prognosis, and the diagnosis often evokes significant psychological distress. However, the progression of emotional well-being throughout the clinical course of brain tumors remains poorly understood. This study aims to assess the prevalence of anxiety and depression in brain tumor patients and to identify the risk factors associated with postoperative emotional derangement in glioma and metastatic groups seperately.

Kidney Gastrin/CCKBR Attenuates Type 2 Diabetes Mellitus by Inhibiting SGLT2-Mediated Glucose Reabsorption through Erk/NF-κB Signaling Pathway.

Background: Both sodium-glucose cotransporters (SGLTs) and Na+/H+ exchangers (NHEs) rely on a favorable Na-electrochemical gradient. Gastrin, through the cholecystokinin B receptor (CCKBR), can induce natriuresis and diuresis by inhibiting renal NHEs activity. The present study aims to unveil the role of renal CCKBR in diabetes through SGLT2-mediated glucose reabsorption.

Intravenous immunoglobulin ameliorates doxorubicin-induced intestinal mucositis by inhibiting the Syk/PI3K/Akt axis and ferroptosis.

Background: Chemotherapy-induced mucositis (CIM) significantly impacts quality of life and reduces survival in patients treated with specific chemotherapeutic agents. However, effective clinical treatments for CIM remain limited. Intravenous immunoglobulin (IVIg), a therapeutic derived from pooled human plasma, is widely used to treat inflammatory diseases.

The inhibitory impact of various total body irradiation doses on the hematopoietic system of mice.

Irradiation with X-rays has been widely utilized in the clinical treatment of solid tumors and certain hematopoietic malignancies. However, this method fails to completely distinguish between malignant and normal cells. Prolonged or repeated exposure to radiation, whether due to occupational hazards or therapeutical interventions, can cause damage to normal tissues, particularly impacting the hematopoietic system.

Heterogeneous immune landscapes and macrophage dynamics in primary and lung metastatic adenoid cystic carcinoma of the head and neck.

Introduction: Recurrent or metastatic adenoid cystic carcinoma (ACC) of the head and neck is rare and highly aggressive. Due to the ineffectiveness of immune checkpoint therapies, this study aims to investigate the tumor immune microenvironment of primary tumor tissues and lung metastatic tissues and to comprehend the challenges of immunotherapy.

Methods: We analyzed RNA sequencing data and constructed immune landscapes from 25 primary tumors and 34 lung metastases.

Interaction between sex and one-hour post-load glucose on metabolic syndrome and its components among Chinese people at high risk of diabetes.

Background: Recently, International Diabetes Federation position statement has adopted one-hour post-load glucose (1hPG) ≥ 8.6 mmol/L for diagnosing intermediate hyperglycemia. We aimed to assess the association of 1hPG ≥ 8.

Metagenomic analysis reveals the community composition of the microbiome in different segments of the digestive tract in donkeys and cows: implications for microbiome research.

Introduction: The intestinal microbiota plays a crucial role in health and disease. This study aimed to assess the composition and functional diversity of the intestinal microbiota in donkeys and cows by examining samples collected from different segments of the digestive tract using two distinct techniques: direct swab sampling and faecal sampling.

Results: In this study, we investigated and compared the effects of multiple factors on the composition and function of the intestinal microbial community.

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.

Single-Nucleus and Spatial Transcriptomics Revealing Host Response Differences Triggered by Mutated Virus in Severe Dengue.

Dengue virus (DENV) infection causes various disease manifestations ranging from an asymptomatic state to severe, life-threatening dengue. Despite intensive research, the molecular mechanisms underlying the abnormal host responses and severe disease symptoms caused by evolved DENV strains is not fully understood. First, the spatial structure of mutant DENV was compared via in silico molecular modeling analysis.

Identification of BMVC-8C3O as a novel Pks13 inhibitor with anti-tuberculosis activity.

Given the increasing prevalence of drug-resistant tuberculosis (TB), there is an urgent demand in developing novel anti-TB medications with highly effective, safe, and utilize innovative mechanisms of action. Blocking the mycolic acid synthesis pathway is well-established to be a significant strategy in developing anti-TB drugs, and Pks13 was identified as a crucial enzyme in this process. Importantly, the modes of action of recognized Pks13 inhibitors differ from traditional anti-TB medications, highlighting Pks13 as a potential and promising target in drug development within TB treatment.

Prognostic risk prediction model for patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD): a systematic review and meta-analysis.

Background: Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory condition and a leading cause of mortality, with acute exacerbations (AECOPD) significantly complicating its management and prognosis. Despite the development of various prognostic prediction models for patients with AECOPD, their performance and clinical applicability remain unclear, necessitating a systematic review to evaluate these models and provide guidance for their future improvement and clinical use.

Method: PubMed, Web of Science, CINAHL, Scopus, EMBASE, and Medline were searched for studies published from their inception until February 5, 2024.

Anti-obesity effect of irreversible MAO-B inhibitors in patients with Parkinson's disease.

We read with great interest the report on the new anti-obesity potential in mice models of reversible monoamine oxidase B inhibitors by Moonsun et al., as opposed to the lack of such effects observed with irreversible MAO-B inhibitors (iMAO-Bi). Our research aimed to explore the potential anti-obesity effects of iMAO-Bi in patients with Parkinson's disease (PD).

GNG5 is a novel regulator of Aβ42 production in Alzheimer's disease.

The therapeutic options for Alzheimer's disease (AD) are limited, underscoring the critical need for finding an effective regulator of Aβ42 production. In this study, with 489 human postmortem brains, we revealed that homotrimer G protein subunit gamma 5 (GNG5) expression is upregulated in the hippocampal-entorhinal region of pathological AD compared with normal controls, and is positively correlated with Aβ pathology. In vivo and in vitro experiments confirm that increased GNG5 significantly promotes Aβ pathology and Aβ42 production.

Transformation zone at the vallate papillae: a significant source of papillomavirus infection at the base of the tongue?

Objective: The aim of this study was to investigate whether the base of the tongue harbours a transformation zone (TZ), i.e., an initiation site for papillomavirus infection, analogous to that in the uterine cervix by examining the histological structure of Von Ebner's gland ducts in the vallate papillae.

AP001885.4 promotes the proliferation of esophageal squamous cell carcinoma cells by histone lactylation- and NF-κB (p65)-dependent transcription activation and METTL3-mediated mRNA stability of c-myc.

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignant neoplasm, and up to now, the role of long non-coding RNA (lncRNA) AP001885.4 in cancer, including ESCC, is absolutely unclear. The GEPIA database was applied to identify differentially expressed and prognosis-associated genes in esophageal cancer (ESCA).

Early Cancer Detection Through Comprehensive Mapping of Dynamic Tumorigenesis.

Current strategies for early cancer detection and diagnosis need updating to achieve greater precision, necessitating the creation of a comprehensive evolutionary map of tumorigenesis. This requires establishing high-quality prospective cohorts, systematically collecting samples for integrated spatiotemporal multiomics analyses, and efficiently translating laboratory findings into clinical applications.

The application of Chinese version of SARC-F and SARC-CalF in sarcopenia screening against five definitions: a diagnostic test accuracy study.

Background: SARC-F questionnaire is a simple and convenient tool for sarcopenia screening, and SARC-CalF is a modified version of it. The developments of their Chinese versions are warranted for the clinical use for Chinese population. This study aimed to culturally adapt the SARC-F questionnaire into Chinese using standardized methods, validate the reliability and diagnostic accuracy of the Chinese version SARC-F and SARC-CalF against five sarcopenia diagnosis criteria, and determine optimal cut-off values for clinical practice in Chinese population.

Evaluation of Angiotensin-Converting Enzyme 2 Expression with Novel Ga-Labeled Peptides Originated from the Coronavirus Receptor-Binding Domain.

Angiotensin-converting enzyme 2 (ACE2) is not only a key to the renin-angiotensin-aldosterone system and related diseases, but also the main entry point on cell surfaces for certain coronaviruses, including severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. By analyzing the different key binding sites from the receptor-binding domain (RBD) of SARS-CoV and SARS-CoV-2, nine new ACE2-targeting peptides (A to A) were designed, synthesized and connected with a chelator, 1,4,7-triazacyclononane-'-triacetic acid (NOTA). NOTA-A, NOTA-A, NOTA-A, NOTA-A, and NOTA-A were successfully labeled with [Ga]Ga and were used for biological evaluation.

Lysine succinylation precisely controls normal erythropoiesis.

Lysine succinylation (Ksu) has recently emerged as a protein modification that regulates diverse functions in various biological processes. However, the systemically and precise role of lysine succinylation in erythropoiesis remains to be fully elucidated. In this study, we noted a prominent increase of succinyl-CoA and lysine succinylation during human erythroid differentiation.

Critical Threshold of Average Weekly Weight Gain in Overweight Pregnant Women During the Second and Third Trimesters: A Strategy to Prevent Macrosomia.

Objective: The study aimed to obtain more evidence on the association of gestational weight gain and pre-pregnancy body mass index (BMI) with macrosomia.

Methods: The data on 5409 live births delivered at Peking Union Medical College Hospital from July 2020 to June 2022 were collected. Group analyses were performed according to the presence or absence of macrosomia.