Design, synthesis, and biological evaluation of liver-targeting phosphoric acid thyroid hormone receptor agonists for the treatment of metabolic dysfunction-associated steatohepatitis.

Metabolic dysfunction-associated steatohepatitis (MASH) represents a progressive stage of metabolic dysfunction-associated steatotic liver disease (MASLD) and is characterized by steatosis, inflammation, hepatocyte ballooning, and fibrosis. Resmetirom, a thyroid hormone receptor β (THR-β) agonist, is the first drug approved by the FDA for the treatment of MASH. The beneficial effects of THR-β agonists on lipid levels primarily result from their action on THR-β in the liver, whereas adverse effects, including impacts on cardiac and bone health, are mediated through thyroid hormone receptor α (THR-α).

The RNA degradation enzyme RNase E is essential for early flagellar assembly in .

endoribonuclease E (RNase E), encoded by the essential gene and conserved across γ-Proteobacteria, plays a central role in RNA processing and decay. We show here that -null strain, -null strain complemented with catalytic-null RNase E mutant, and C-terminal-truncated strain (Rned500) all lack flagellar biogenesis and motility under both aerobic and anaerobic conditions, which are restored by wild-type RNase E complementation. The Rned500 displays dysregulated expression of the three-tiered flagellar transcriptional cascade, increased stability of flagellar mRNAs, and reduced flagellar protein levels through sRNA-dependent translational inhibition.

Prognostic Risk Model of Megakaryocyte-Erythroid Progenitor (MEP) Signature Based on AHSP and MYB in Acute Myeloid Leukemia.

: Acute myeloid leukemia (AML) is a common and aggressive adults hematological malignancies. This study explored megakaryocyte-erythroid progenitors (MEPs) signature genes and constructed a prognostic model. : Uniform manifold approximation and projection (UMAP) identified distinct cell types, with differential analysis between AML-MEP and normal MEP groups.

ED and ED of hypobaric ropivacaine during unilateral spinal anesthesia in older patients undergoing hip replacement surgery.

Objective: The spinal block was limited to the operative side during unilateral spinal anesthesia, which has less physiological interference and fewer complications for the patient. The optimal dose of ropivacaine for unilateral spinal anesthesia is still unclear. The aim of this trial was to investigate the ED and ED of hypobaric ropivacaine during unilateral spinal anesthesia in older patients undergoing hip arthroplasty.

The Illness Experience of Patients With Knee Osteoarthritis: A Qualitative Study.

Objective: This study employed descriptive qualitative research methods to explore the experiences of patients with knee osteoarthritis.

Methods: Semi-structured interviews were conducted with 20 patients diagnosed with knee osteoarthritis and scheduled for joint replacement at a tertiary hospital in Shanghai between January 2024 and June 2024. Thematic content analysis was utilised to analyse the interview data.

Discovery and biochemical characterization of prenyltransferases in the biosynthetic pathway of hericenones from Hericium erinaceus.

Hericenones, neurotrophic meroterpenoids from the medicinal mushroom Hericium erinaceus, exhibit remarkable nerve growth factor-enhancing properties with therapeutic potential for neurodegenerative disorders. Biosynthesis of these compounds requires prenyltransferase (PT)-mediated geranylation of orsellinic acid (OA, 1), though the fungal enzymes catalyzing this pivotal step remain uncharacterised. Through comprehensive genome mining of H.

Global trends and sociodemographic inequalities in smoking and high-salt diet attributable to gastric cancer: a secondary analysis based on the global burden of disease 2021 study.

Background: Gastric cancer is a common malignancy worldwide. Smoking and a high-salt diet are behavioural risk factors for gastric cancer that can be easily controlled; however, comprehensive and systematic studies are lacking. This study reports the variation trend in the attribution of the burden of gastric cancer in different regions from 1990 to 2021 and suggests personalised recommendations developed for regions with different sociodemographic indices (SDI).

Single-cell and spatial transcriptomics reveal mechanisms of radioresistance and immune escape in recurrent nasopharyngeal carcinoma.

Radiotherapy resistance and immune evasion are prominent features of recurrent nasopharyngeal carcinoma (rNPC). However, their mechanisms remain incompletely understood. Here, we conducted single-cell and spatial transcriptomics analysis of 39 tumors from 24 patients to reveal the microenvironmental differences between primary and rNPC.

Analysis of the correlation between morphological classification of the middle glenohumeral ligament and subscapularis tears.

The purpose of this study was to evaluate the correlation between the morphological classification of the middle glenohumeral ligament (MGHL) and subscapularis tears and to evaluate whether surgical release of the MGHL is warranted in patients with subscapularis tears. A retrospective analysis was performed on the surgical videos of shoulder arthroscopic rotator cuff repair surgeries conducted by the same surgeon from September 2020 to September 2021. The MGHL was classified morphologically into two types: overall classification and lateral insertion classification, and the occurrence of subscapularis tears was recorded for each type.

Comprehensive analysis of repetitive extragenic palindrome sequences identified in bacteria and archaea using a new web-based tool, RepRanger.

Repetitive extragenic palindromic (REP) sequences were first discovered in the intergenic regions of and later found in phylogenetically distinct bacterial species. However, their biological roles and sequence conservation remain unclear. Considering the growing number of microbial genome sequencing and annotation projects, along with the lack of online tools for REP identification, we developed a new web-based platform, RepRanger, to rapidly identify and annotate putative palindromic elements, including REPs.

Comparison of postoperative analgesic effects of ultrasound-guided intercostal nerve block and transversus abdominis plane block in patients undergoing laparoscopic cholecystectomy: randomized clinical trial.

Background: The aim of this study was to compare the postoperative analgesic effects of ultrasound-guided intercostal nerve block and transversus abdominis plane block in patients undergoing laparoscopic cholecystectomy.

Methods: Patients undergoing laparoscopic cholecystectomy for chronic cholecystitis with gallstones were randomly allocated to ultrasound-guided T7-11 intercostal nerve block or subcostal transversus abdominis plane block (both with 40 ml 0.3% ropivacaine).

Tannic acid-mediated surface engineering of CNTs for enhanced bifunctional oxygen electrocatalysis.

Developing stable and efficient bifunctional electrocatalysts for oxygen reduction and evolution reactions is essential for rechargeable metal-air batteries. Here, we reported a facile surface modification strategy of carbon nanotubes (CNTs) as air electrocatalysts for zinc-air batteries (ZABs). By leveraging the versatile binding affinity of tannic acid with metal ions and carbon surfaces, the CNTs surface was coated with a uniform, thin layer of nitrogen-doped carbon featuring atomically dispersed cobalt.

Effect of regional nerve block on tourniquet-related injury in pediatric patients undergoing lower limb surgery: a randomized controlled study.

Background: The efficacy of regional nerve block for pain management has garnered considerable attention. However, few studies have explored their effectiveness in mitigating tourniquet-related injuries and promoting functional recovery in lower limb surgery patients.

Methods: : Sixty-four pediatric patients aged 6-12 undergoing knee arthroscopic surgery under general anesthesia.

Synergistic effects and mechanism of recombinant viral vector-mediated STAT1 overexpression and STAT3 silencing on glioma U251 apoptosis.

Background: In the present study, the synergistic effects and mechanism of recombinant viral vector-mediated co-expression plasmids stat1 and stat3-siRNA on glioma were investigated in vivo and in vitro.

Methods: Co-expression plasmids for stat1/stat3-siRNA were constructed and packaged into lentivirus and adenovirus for cell and animal experiments. Real-time PCR and Western blot analyses were used to detect the expression of STAT1 and STAT3 at gene and protein levels in U251 cells.

Associations of anti-inflammatory diet with cognitive impairment, physical dysfunction, depressive symptoms, and Multimorbidity in Chinese elderly: a national community-based study.

Objective: The health effects of anti-inflammatory diets have been less studied in the Chinese elderly. We aimed to investigate the association of an anti-inflammatory diet on cognitive function, physical function, depressive status, and multimorbidity.

Methods: A total of 11,123 participants aged 65 years and older from the 2017-2019 Chinese Longitudinal Healthy Longevity Survey (CLHLS) were included in this cross-sectional study.

Trichaptum biforme (Pallidohirschioporus biformis) genome decoding provides insights into carbohydrate degradation and polysaccharide synthesis.

Trichaptum biforme is a white-rot fungus that plays a key role in the process of cellulose degradation. In this study, we employed a suite of techniques to sequence the genome of T. biforme, and achieved high-quality assembly and detailed annotation.

Pae/exo@PF-127 promote diabetic wound healing through miR-424-5p.

Background: Currently, chronic diabetic wound healing is one of the urgent clinical challenges. Choosing appropriate dressings loaded with stem cell-derived exosomes (exo) and traditional Chinese medicine extracts that promote healing is an effective method to accelerate skin healing in diabetes. Paeonol (Pae), possessing anti-inflammatory properties and vascular enhancement functions, can serve as a therapeutic herbal extract for treating diabetic wounds.

Discovery and optimization of ibuprofen derivatives as the NF-κB/iNOS pathway inhibitors for the treatment of ulcerative colitis.

In this study, a series of novel ibuprofen (Ibu) hybrid molecules with aminothiazole heterocycles were designed, synthesized and evaluated for their anti-inflammatory potency in vitro and in vivo. Among all these derivatives, compounds 6 and 8 effectively inhibited the production of NO (with 87 %, 79 % NO-inhibitory rates, respectively) with minimal cytotoxic effect in RAW 264.7 macrophages.

Atomic Ga triggers spatiotemporal coordination of oxygen radicals for efficient water oxidation on crystalline RuO.

Advancements in proton-exchange membrane water electrolyzer depend on developing oxygen evolution reaction electrocatalysts that synergize high activity with stability. Here, we introduce an approach aimed at elevating oxygen evolution reaction performance by enhancing the spatiotemporal coordination of oxygen radicals to promote efficient O-O coupling. A dense, single-atom configuration of oxygen radical donors within interconnected RuO nanocrystal framework is demonstrated.

Gastrodin Protects Neuronal Cells Against Oxidative Stress Through miRNA-125b-5p/Mamdc2 Axis.

Deregulated reactive oxygen species (ROS) levels trigger oxidative stress (OS) injury that is closely associated with the pathophysiology of various neurological disorders. Therefore, therapeutic efforts at oxidative events in the pathway of neuronal degeneration would be promisingly helpful for intervention and treatment of related diseases. Here, we report that gastrodin, the main bioactive constituent of Rhizoma Gastrodiae, protects the mouse hippocampal HT22 cells from OS caused by hydrogen peroxide (HO), including the increased cell viability, elevated Glutathione (GSH) levels, decreased Malondialdehyde (MDA) activity, and down-regulated ROS levels with restored cell morphology.

Smad4 loss identifies aggressive subtype with immunotherapy and anti-HER-2 treatment resistance in gastric cancer.

Background: SMAD4 mutation and homozygous deletion represent the most prevalent genomic events driving aggressive biological behavior in gastric cancer (GC). However, clinical outcome and therapeutic response in GC patients with Smad4-loss remains obscure.

Methods: This study included 990 GC patients from four independent clinical centers including the Zhongshan Hospital (ZSHS) cohort, the Cancer Genomic Atlas (TCGA) cohort, the Samsung Medical Center (SMC) cohort and the Memorial Sloan Kettering Cancer Center (MSKCC) cohort.

Induction versus Concurrent Chemotherapy for Advanced Nasopharyngeal Carcinoma.

Background: Cisplatin-based concurrent chemoradiotherapy (CCRT) is the mainstay treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC), which usually leads to intolerable toxicities. We investigated whether or not induction chemotherapy (IC) plus intensity-modulated radiation therapy (IMRT) could replace CCRT.

Methods: This is an open-label, phase 3, noninferiority trial.

Molecular features and diagnostic modeling of synovium- and IPFP-derived OA macrophages in the inflammatory microenvironment via scRNA-seq and machine learning.

Background: Osteoarthritis (OA) is the leading cause of degenerative joint disease, with total joint replacement as the only definitive cure. However, no disease-modifying therapy is currently available. Inflammation and fibrosis in the infrapatellar fat pad (IPFP) contribute to OA onset and progression.

Galangin exosomes induce cell apoptosis through miR-10b/P53 axis in gastric cancer.

Galangin is an extract of traditional Chinese medicine with anti-cancer effect. Exosomes (Exo) contain RNA, peptides, or proteins and communicate between cells through a bio-genesis pathway. In the present study, Gastric cancer (GC) cell exosomes containing galangin were obtained.