PAM-free hairpin target binding activates trans-cleavage activity of Cas12a.

CRISPR-Cas12a has been demonstrated to be activated for its trans-cleavage activity by single- and double-stranded DNA containing a protospacer adjacent motif (PAM), but other types of activators have remained undiscovered. In this work, we found that a hairpin-structured substrate can activate the trans-cleavage activity of Cas12a without a PAM, and the parameters of the hairpin loop obviously affect the activity. Cas12a exhibits sequence preference for proximal loops, preferring to recognize polyadenine hairpin loop activators.

Lymphatic Contrast-enhanced Ultrasound as a Noninvasive Predictor of Sentinel Lymph Node Metastasis in Breast Cancer: A Prospective Diagnostic Study.

Background: Sentinel lymph node biopsy (SLNB) using radioisotopes/blue dye remains limited by radiation exposure and logistical constraints. This study prospectively evaluates lymphatic contrast-enhanced ultrasound (L-CEUS) for SLN mapping and metastasis detection in early-stage breast cancer.

Methods: A total of 251 consecutive patients underwent L-CEUS-guided SLN biopsy.

Understanding the correlation between benevolent childhood experiences, negative life events and mental health: The role of health risk behaviors.

Objectives: The relationship between individual benevolent childhood experiences (BCEs), negative life events (NLEs), and adolescent mental health, including anxiety and depression were discussed. Although ACEs has been extensively studied, less attention has been paid to the combination of BCEs, and the role of health risk behaviors (HRBs) also play an important part. Our goals were: 1) To explore whether HRBs moderate the relationship between BCEs and depression; 2) Whether NLEs also has this moderate effect.

Association of neutrophil/high-density lipoprotein cholesterol ratio with the cardiovascular-kidney-metabolic syndrome and its cardiovascular mortality.

Background: Cardiovascular-kidney-metabolic (CKM) syndrome is a novel multi-system disease defined by the American Heart Association (AHA). This study aims to investigate the associations between the neutrophil/high-density lipoprotein cholesterol ratio (NHR) and CKM syndrome and its association with cardiovascular disease (CVD) mortality.

Methods: The data for this study were derived from the National Health and Nutrition Examination Survey (NHANES) conducted from 2005 to 2018 and the National Death Index (NDI) database.

Contribution of Interleukin-1 Receptor-Associated Kinase 1 Gene Polymorphism to Systemic Lupus Erythematosus in Chinese Patients.

Introduction: Systemic lupus erythematosus (SLE) is a complex autoimmune condition distinguished by a wide range of clinical manifestations and numerous genetic predisposition factors. The aim of the current study was to analyze the association between the IRAK1 polymorphisms (rs3027898 and rs1059702) and SLE in a Chinese cohort.

Patients And Methods: A total of 150 SLE patients and 168 healthy controls of Chinese ethnicity were included in this study.

Association of HLA-G 14-bp Insertion/Deletion Polymorphism With Recurrent Spontaneous Abortion: A Meta-Analysis.

We performed a meta-analysis to study the relationship between HLA-G 14-bp insertion/deletion polymorphism and recurrent spontaneous abortion (RSA). All literature was searched from PubMed, Web of Science, Embase and Wanfang databases. Statistical analyses were performed by the STATA software (Version 16.

pH-Responsive bimetallic MOF nanoparticles enable triple-synergistic radiosensitization for enhanced radiotherapy.

Radiotherapy (RT) faces hypoxia-induced radioresistance, as oxygen-deficient tumor regions limit reactive oxygen species (ROS) generation. Current hypoxia-targeting strategies (, prodrugs, nanocarriers) struggle with inefficient delivery, off-target effects, and clinical translation barriers, necessitating advanced oxygenation or hypoxia-specific radiosensitization approaches. Herein, we developed pH-responsive BM-DOX@BSA nanoparticles (NPs) using a solvothermal method.

Efficacy and Safety of Ivarmacitinib, a Selective JAK1 Inhibitor, in Patients With Active Ankylosing Spondylitis: Results From an Adaptive Seamless Phase 2/3 Trial.

Objective: This randomized, double-blind, adaptive phase 2/3 trial aimed to evaluate the efficacy and safety of ivarmacitinib, a novel selective JAK1 inhibitor, in patients with active ankylosing spondylitis (AS).

Methods: In phase 2, patients were randomized (1:1:1:1) to receive ivarmacitinib at a dose of 2, 4, or 8 mg or placebo once daily for 12 weeks. Based on interim analysis, ivarmacitinib 4 mg was selected as the recommended dose.

Identification and genomic characterization of Enterobacter kobei ST56 co-carrying mcr-9, bla, and bla resistance genes.

Objectives: This study reports the complete genome sequence of Enterobacter kobei (E. kobei) L5089hy of ST56 isolated from China, carrying mcr-9, bla, and bla. It aims to investigate its molecular characteristics and antibiotic resistance mechanisms.

Improved management of hospital-acquired infections with DRG-based payment system: an interrupted time‑series analysis.

Background: While diagnosis-related group (DRG) payment system has been shown to improve healthcare quality and reduce costs in high-income countries, its effectiveness in developing countries, particularly in terms of hospital-acquired infection (HAI) management, remains unclear.

Methods: HAI surveillance data were collected from nine public hospitals in Zhejiang province, China, that implemented the DRG system in 2020. Changes in HAI incidence rates following DRG adoption were assessed using interrupted time-series analysis with a generalized additive model, covering the period from January 2016 to September 2023.

Resistance characteristics of culture-positive tuberculosis from 2015 to 2022.

Introduction: This study aimed to investigate the prevalence of resistance to first-line anti-tuberculosis (TB) drugs and the molecular mechanisms underlying resistance mutations in patients with culture-positive complex (MTBC). The findings provide a data basis for developing more precise and regionally tailored anti-TB treatment regimens.

Methods: From 2015 to 2022, a total of 3,605 strains isolated from 10 designated TB medical institutions in the main urban and county/township areas of Luoyang City, China, were confirmed as MTBC members through polymerase chain reaction (PCR) targeting a specific insertion sequence IS6110.

Mazdutide, a dual agonist targeting GLP-1R and GCGR, mitigates diabetes-associated cognitive dysfunction: mechanistic insights from multi-omics analysis.

Background: Cognitive impairment and dementia are highly associated with obesity and type 2 diabetes mellitus (T2DM). Recent studies have demonstrated that GLP-1 receptor agonists can improve cognitive function through brain activation in patients with T2DM, compared to other oral glucose-lowering drugs. Mazdutide, a dual agonist of the glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR), has been shown to simultaneously reduce body weight, blood glucose levels, and other comorbidities associated with obesity in patients with T2DM.

Association of neutrophil to high-density lipoprotein cholesterol ratio with overactive bladder: a population-based study.

Background: Inflammation is involved in the progression of overactive bladder (OAB). This study aimed to investigate the association between the neutrophil to high-density lipoprotein cholesterol ratio (NHR) and OAB.

Methods: Data from seven cycles of the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018 were analyzed to examine the relationship between NHR and OAB.

Dolutegravir Derivatives Alleviate LPS-Induced Microglial Inflammation by Suppressing STAT1/3 Nuclear Translocation.

Purpose: Microglial inflammation plays a significant role in a variety of neurological disorders. Dolutegravir as a antiretroviral drug has been reported to inhibit the secretion of pro-inflammatory cytokines. Meanwhile, compounds containing 1,2,3-triazole have shown potential anti-inflammatory properties.

Therapeutic Effects and Molecular Mechanisms of KD025 in Intraocular Pressure Regulation.

Aim: To quantitatively evaluate the IOP-lowering efficacy of topical KD025 in normotensive and steroid-induced ocular hypertensive rat models, and to elucidate its mechanisms concerning TM cytoskeletal remodeling, fibrotic modulation, and cell behavior using primary human TM cells.

Methods: Normotensive and steroid-induced (dexamethasone) ocular hypertensive Sprague-Dawley rats received topical KD025; IOP was monitored using rebound tonometry. TM morphology was assessed by H&E staining.

Association of dietary intake of folate, serum folate, and red blood cell folate with mortality risk in patients with depression: a population-based longitudinal cohort study.

Background: Folate level is associated with depression, yet prospective evidence is lacking on the relationship of dietary intake, serum, and red blood cell (RBC) folate levels with mortality risk in patients with depression.

Methods: Dietary intake, serum, and RBC folate data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018 were included. Depression was diagnosed using the PHQ-9 with a cutoff value of 5.

Heat shock protein 90α may serve as a biomarker for mild cognitive impairment in type 2 diabetes mellitus patients without diabetic nephropathy.

Aim: Chronic inflammation associated oxidative stress is a key factor in complications of type 2 diabetes mellitus (T2DM), including mild cognitive impairment (MCI), partly associated with cerebrovascular lesions including both macrovascular and microvascular changes, and diabetic nephropathy (DN), a kind of diabetic microvascular complication. Heat shock protein 90α (Hsp90α) is known to play a significant role in inflammation associated oxidative stress and DN. This study aims to explore the role of Hsp90α in MCI and its potential as a diagnostic marker for MCI in T2DM patients.

A comprehensive bibliometric analysis of ferroptosis in tumor resistance: development and emerging trends.

Background: Ferroptosis is a regulated form of cell death characterized by iron dependency, lipid peroxidation, and oxidative stress. Since its discovery in 2012, ferroptosis has attracted significant interest for its potential to counteract tumor resistance across various therapeutic modalities, including chemotherapy, radiotherapy, immunotherapy, and targeted therapy. Despite notable progress, a systematic understanding of its underlying molecular mechanisms and translational potential remains underdeveloped, thus necessitating a comprehensive bibliometric analysis.

Ginsenoside Rk1 improves mitochondrial function and alleviates myocardial ischemia-reperfusion injury by regulating SIRT3.

Myocardial ischemia/reperfusion (I/R) injury can lead to heart damage and poor prognosis. The potential value of natural medicines in combating I/R damage is receiving increasing attention, however, more effective medicines still need to be developed to further improve I/R damage. Ginsenoside Rk1 is a major rare saponin obtained from hot processed ginseng, which has a variety of biological effects.

The value of a combined model based on ultra-radiomics and multi-modal ultrasound in the benign-malignant differentiation of C-TIRADS 4A thyroid nodules: a prospective multicenter study.

Objective: To establish a combined model based on ultrasound radiomics combined with multimodal ultrasound and evaluate its value in diagnosing benign and malignant nodules classified as Chinese-Thyroid Imaging Report and Data System (C-TIRADS) 4A.

Methods: Prospective collection of data from 446 patients with thyroid nodules classified as C-TIRADS 4A between December 2023 and August 2024. Based on the enrollment timeline, patients were divided into a training set (n=312) and a test set (n=134) in a 7:3 ratio.

Cholesteatoma: An Updated Review of Molecular Pathogenesis and Potential Therapeutic Directions.

Cholesteatoma, an abnormal accumulation of keratinized squamous epithelium in the middle ear, occurs as a locally invasive but histologically benign lesion. Its capacity for bone erosion leads to significant complications, including hearing loss, facial nerve paralysis, and intracranial infections. Chronic inflammation is central to its pathogenesis, with proinflammatory mediators like TNF-α, IL-1β, and IL-6 activating signaling pathways, such as NF-κB, JAK/STAT, and MAPK.

The SP1/SNHG16/GLUT1 axis promotes prostate cancer proliferation and invasion by regulating glucose metabolism.

Introduction: The SP1/SNHG16/GLUT1 axis is involved in diverse cancer-related processes. This study was designed to study the role of the SP1/SNHG16/GLUT1 axis in prostate cancer (PCa) via modulation of glucose metabolism.

Material And Methods: The expression profile of SNHG16 in PCa tissues was obtained from the online public database GEPIA (http://gepia.

Burden of pulmonary arterial hypertension in Asia from 1990 to 2021: Findings from Global Burden of Disease Study 2021.

Background: Pulmonary arterial hypertension (PAH) presents a significant health burden in Asia and remains a critical challenge. This study aims to delineate the PAH burden in Asia from 1990 to 2021.

Methods: Using the latest data from the Global Burden of Disease 2021, we evaluated and analyzed the distributions and patterns of PAH disease burden among various age groups, sexes, regions, and countries in Asia.

Association between the serum alpha-1-acid glycoprotein concentrations and depression in US adult women: a cross-sectional study.

Background: Emerging evidence has demonstrated a positive association of inflammation with depression. As an acute-phase reactant predominantly synthesized in hepatocytes, alpha-1-acid glycoprotein (AGP) serves as a sensitive biomarker of inflammation. However, there is a limited study to explore the relationship between AGP and depression.