MicroRNA-126-3p as a predictive biomarker for patients with primary biliary cholangitis refractory to ursodeoxycholic acid.

Background: Ursodeoxycholic acid (UDCA) is the first-line therapeutic agent for primary biliary cholangitis (PBC). However, a subset of patients exhibit a suboptimal response to UDCA, and reliable predictive biomarkers remain elusive. Studies have implicated plasma microRNAs (miRNAs) in the pathophysiological progression of PBC, with certain miRNAs demonstrating potential as diagnostic and disease progression biomarkers.

Constructing and Using Cell Type Populations of the Human Reference Atlas.

The human body contains ~27-36 trillion cells of up to 10,000 cell types (CTs) within a volume of ~62-120 liters (males) and 52-89 liters (females). The Human Reference Atlas (HRA) v2.3 provides a quantitative 3D framework of CTs across 73 reference organs and 1,283 3D anatomical structures (ASs).

Dysfunction and Metabolic Reprogramming of Gut Regulatory T Cells in HIV-Infected Immunological Non-Responders.

Disruption of the gut microenvironment is a hallmark of HIV infection, where regulatory T cells (Tregs) play a critical role in maintaining gut homeostasis. However, the mechanisms by which gut Tregs contribute to immune reconstitution failure in HIV-infected individuals remain poorly understood. In this study, we employed single-cell RNA sequencing (scRNA-seq) to analyze gut Treg populations across three cohorts: eight immunological responders (IRs), three immunological non-responders (INRs), and four HIV-negative controls (NCs).

Establishment and validation of a screening and risk predication model for rotator cuff tear and shoulder stiffness.

Background: Rotator cuff tears (RCTs) with shoulder stiffness have a high association rate; however, the mechanism and possible risk factors are unclear. This study aims to collect the factors that may affect RCT and shoulder stiffness, screen out the relevant risk factors through statistical analysis, and establish a simple model to predict the risk of RCT combined with shoulder stiffness.

Methods: A retrospective analysis was conducted on 406 patients diagnosed with RCT through arthroscopic surgery at the Department of Joint and Sports Medicine, the First Affiliated Hospital of Dalian Medical University, from December 2019 to June 2023.

Significant Reduction of Chenodeoxycholic Acid and Glycochenodeoxycholic Acid in the Elderly with Severe COVID-19.

Elderly individuals infected with SARS-CoV-2 are at higher risk of developing cytokine storms and severe outcomes, yet specific biomarkers remain unclear. In this study, we investigated the alteration of primary bile acid metabolism in elderly patients with severe COVID-19 using untargeted metabolomics ( = 31), followed by targeted metabolomics to compare patients with disease progression ( = 16) to those without ( = 48). Significant reductions in chenodeoxycholic acid (CDCA) and glycochenodeoxycholic acid (GCDCA) levels were identified in severe cases, with GCDCA levels at admission correlating strongly with peak inflammatory markers.

Dose-escalation studies of mesenchymal stromal cell therapy for decompensated liver cirrhosis: phase Ia/Ib results and immune modulation insights.

Decompensated liver cirrhosis (DLC) is characterized by severe liver dysfunction and immune dysregulation, posing significant treatment challenges. Mesenchymal stromal cell (MSC) therapy has shown promise in DLC treatment, but the optimal dosing strategies and dose-dependent therapeutic mechanisms in humans remain unclear, limiting its clinical application. We conducted sequential Phase Ia/Ib trials using a single-arm, dose-escalation design to evaluate the safety and tolerability of MSC therapy in DLC patients while also exploring its immunomodulatory effects and gathering preliminary therapeutic signals.

Disruption of cell-intrinsic PCSK9 enhances the antitumor efficacy of CD8 T cells.

Background: Tumor-derived proprotein convertase subtilisin/kexin type 9 (PCSK9) facilitates tumor progression, but the role of immune cell-intrinsic PCSK9 in tumor control remains unclear.

Methods: Orthotopic models of pancreatic cancer and melanoma in -deficient mice were established and tumor-infiltrating immune cells were analyzed using single-cell RNA sequencing and flow cytometry. The effect of genetic disruptions of PCSK9 on murine CD8 T cells and human chimeric antigen receptor (CAR)-T cells was evaluated both in vitro and in vivo.

Serum IP-10 increase correlated with PEG-IFNα response in nucleot(s)ide analogs-treated patients with chronic hepatitis B.

Background And Aims: To investigate the association between serum IP-10 and HBsAg levels in chronic hepatitis B (CHB) patients previously treated with nucleot(s)ide analogs (NAs) followed by combined treatment with an NA and pegylated interferon alpha (PEG-IFNα).

Methods: Ninety-nine patients with serum levels of HBsAg <3000 IU/mL and HBV DNA <20 IU/mL who received prior NA treatment were enrolled. Participants were administered either NA monotherapy (NA group) or combination therapy with PEG-IFNα (Add-on group).

Assessment of significant hepatic damage in young patients with chronic hepatitis B to initiate the antiviral treatment: The APLB score.

Whether patients aged ≤30 years with chronic hepatitis B (CHB) and normal alanine transaminase (ALT) levels (<40 U/L) should receive antiviral therapy is controversial. In this study, we aimed to identify high-risk factors of significant hepatic damage (SHD) and established a scoring system to guide the decision to administer antiviral treatment. Eligible patients who underwent a liver biopsy were retrospectively screened and randomly assigned to either a training or validation set.

Stem cells therapies for liver diseases: for current practice and future goals.

Background: Stem cell therapy has emerged as a promising approach for treating severe chronic liver diseases, including decompensated liver cirrhosis (DLC) and liver failure(LF), with mesenchymal stem cells (MSCs) being the most extensively investigated cell type in both preclinical and clinical trials.

Objective: To summarize the research progress in clinical studies of stem cells therapy for chronic liver diseases, providing a comprehensive overview of current knowledge.

Methods: Research on stem cell therapy for liver diseases was searched from databases such as PubMed, Web of Science, Google Scholar, and ClinicalTrials.

Functional cure with new antiviral therapy for hepatitis B virus: a systematic review and meta-analysis.

Background: Achieving a "functional" cure for chronic hepatitis B (HBV) is primary goal for novel antiviral treatments. We sought to evaluate efficacy and safety of these novel treatments and identified emerging barriers to achieving a functional cure.

Approach: We systematically reviewed clinical trials from 2018 to 2023, identifying 244 trials from clinicaltrials.

PtrSAUR32 Interacts with PtrPP2C.Ds to Regulate Root Growth in Citrus.

Small auxin-up-regulated RNA () genes are involved in the regulation of dynamic and adaptive growth in higher plants. However, their function and mode of action in citrus root growth are still unknown. Here, we demonstrate that in , acted downstream of the auxin response factor PtrARF8 to regulate root growth by interacting with PtrPP2C.

Single-cell transcriptomic profiling reveals dysregulation of B-cell subset function in patients with chronic hepatitis B.

Background And Aim: The goal of this study was to investigate the immunological characteristics and potential clinical significance of B-cell subsets during different phases of hepatitis B virus (HBV) infection.

Methods: We conducted single-cell RNA sequencing on 23,967 B cells (including 1,677 plasma cells) derived from 46 liver and blood samples from 25 individuals. The study included six HBV-free healthy control (HC) cases, as well as subjects from four different HBV phases: six immune-tolerant (IT), six immune activation (IA), four acute recovery (AR), and three chronic resolved (CR) individuals.

CD300A CD8 T Cells as Predictive Biomarkers for Achieving Functional Cure in Chronic Hepatitis B Patients Undergoing Pegylated Interferon-Alpha Therapy.

Background & Aims: Pegylated interferon-alpha (PEG-IFN-α) is the first choice for achieving functional cure (FC) in chronic hepatitis B (CHB), but only about 30% of patients achieve this outcome within a defined treatment duration. Given the critical role of CD8 T cells as antiviral effectors, we investigated their changes during FC to identify novel predictive markers of treatment efficacy.

Methods: We enrolled CHB patients with serum HBsAg levels < 3000 IU/mL in a discovery cohort and collected their peripheral blood mononuclear cells after PEG-IFN-α therapy.

Early Immunological and Inflammation Proteomic Changes in Elderly COVID-19 Patients Predict Severe Disease Progression.

Elderly patients infected with SARS-CoV-2 are at higher risk of developing cytokine storm and severe outcomes; however, specific immunological and proteomic biomarkers for early prediction remain unclear in this vulnerable group. We enrolled 182 elderly COVID-19 patients from the Chinese PLA General Hospital between November 2022 and April 2023, categorizing them based on progression to respiratory failure requiring mechanical ventilation (defined as severe progression). Olink proteomic analysis was performed on admission serum from 40 propensity score-matched samples, with differentially expressed proteins (DEPs) validated by cytometric bead array (CBA) in 178 patients.

BadCLM: Backdoor Attack in Clinical Language Models for Electronic Health Records.

The advent of clinical language models integrated into electronic health records (EHR) for clinical decision support has marked a significant advancement, leveraging the depth of clinical notes for improved decision-making. Despite their success, the potential vulnerabilities of these models remain largely unexplored. This paper delves into the realm of backdoor attacks on clinical language models, introducing an innovative attention-based backdoor attack method, BadCLM (Bad Clinical Language Models).

Evolution and characteristics of tetracycline resistance in .

Macrolide resistance in is becoming prevalent. Tetracyclines are an important alternative for patients with macrolide-resistant infections. Tetracycline-resistant has never been reported in clinical isolates or -induced strains.

Antioxidant interventions reduced cytokine-induced pyroptosis of peripheral MAIT cells in patients with HBV-related cirrhosis.

Background: Mucosal-associated invariant T (MAIT) cells are diminished in various liver diseases, but the underlying mechanism remains unclear. This study aimed to investigate the characteristics and underlying mechanisms of MAIT cell depletion in HBV-related cirrhosis.

Methods: Peripheral blood samples were collected from 20 healthy controls and 40 patients with HBV-related cirrhosis, divided into compensated (20) and decompensated (20) liver cirrhosis groups.

PRMT3 reverses HIV-1 latency by increasing chromatin accessibility to form a TEAD4-P-TEFb-containing transcriptional hub.

Latent HIV-1 presents a formidable challenge for viral eradication. HIV-1 transcription and latency reversal require interactions between the viral promoter and host proteins. Here, we perform the dCas9-targeted locus-specific protein analysis and discover the interaction of human arginine methyltransferase 3 (PRMT3) with the HIV-1 promoter.

CgABR1-CgFAD negatively regulates the fruit neck length in citrus.

Pummelo (Citrus maxima) is a fundamental species of Citrus which contributes to most of the cultivated citrus, including sweet orange, lemon and etc. The fruit neck is a structural feature of pummelo, and a long fruit neck reduces the edible rate of the fruit. In this study, we assembled a telomere-to-telomere (T2T) gap-free reference genome for the typical short fruit neck cultivar, 'Pingshan' pummelo, and a chromosome-level genome for the typical long fruit neck cultivar, 'Shatian' pummelo.

Characterization of Competitive Adsorption of Multicomponent Gases Injected with CO in a Coal Mine Goaf.

Injection of CO into a coal mine goaf is the primary method for inhibiting coal spontaneous combustion and for driving outgas, and gases such as N, O, and CH in coal are in competition with it, which in turn affects its adsorption effect in coal. In order to enhance the CO suppression and expulsion effect, the competitive adsorption characteristics of multicomponent gases in the coal mine goaf were investigated. We carried out adsorption experiments with a specific surface area analyzer to clarify the adsorption law of coal on different gases, conducted CO adsorption experiments with an in situ infrared device to reveal the role of functional groups, verified the single-component adsorption law with molecular dynamics simulation, elucidated the effect of temperature on the adsorption of multicomponent gases, and summarized the law of CO competition under different pressures.

Cadonilimab, a PD-1/CTLA-4 bispecific antibody in unresectable hepatocellular carcinoma: a real-world study.

Objective: This study retrospectively evaluated the safety and efficacy of cadonilimab combined with tyrosine kinase inhibitors (TKI) for the treatment of unresectable hepatocellular carcinoma (uHCC).

Patients And Methods: Seventy-eight patients who received cadonilimab + TKI were included; 42 and 36 received it as first-line (1 L) and second-line and above (≥ 2 L) systemic treatment, respectively. Besides, ninety-five patients who received PD-1 inhibitor + TKI as first-line treatments were included.

Demographic disparities, temporal trends, and geographic patterns of HPV vaccination on Long Island, New York: A comprehensive analysis of immunization registry data (2012-2023).

The Advisory Committee on Immunization Practices (ACIP) advised vaccinating children, adolescents and young adults against Human Papillomavirus (HPV) in 2006, aiming to prevent HPV-related cancers and genital warts. As HPV vaccination rates remained low even 10 years after it was introduced, understanding vaccination patterns is essential for informing targeted public health interventions. This study explores the demographic disparities (age, gender, race and ethnicity), temporal trends, and geographical patterns of HPV vaccine administration by analyzing large-scale immunization registry data for Long Island (LI) (Nassau and Suffolk Counties), New York (NY).

Density-Dependent Difference in Serum Levels of Immunoglobulin G in Brandt's Voles and Its Potential Influencing Factors.

Understanding the density-dependent immune response is an important theme in ecological and evolutionary studies. Animals may elevate their immune response with an increase in population density. There is substantial evidence supporting the density-dependent immune response in some insects, reptiles, and birds, but evidence is still lacking in wild rodents.

Grand Challenges on HIV/AIDS in China - The 5th Symposium, Yunnan 2024.

HIV-1 infection has led to 1.329 million people living with the virus and 0.474 millions of deaths by the middle of 2024 in China.