Targeting UGT2B15 and NR1H4 interaction: a novel therapeutic strategy for polycystic ovary syndrome using naftopidil enantiomers.

Background: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder among women of reproductive age. It is characterized by hyperandrogenism, ovulatory dysfunction, and the presence of polycystic ovarian morphology (PCOM) on ultrasound, often accompanied by metabolic disturbances such as insulin resistance and obesity. Current treatments, including oral contraceptives and anti-androgen medications, often yield limited efficacy and undesirable side effects.

WTAP suppresses STAT3 via m6A methylation to regulate autophagy and inflammation in central nervous system injury.

Central nervous system (CNS) repair after injury is a challenging process limited by inflammation and neuronal apoptosis. This study identifies Wilms' tumor 1-associating protein (WTAP) as a pivotal regulator of neuronal protection and repair through m6A methylation of STAT3 mRNA. By employing spinal cord injury (SCI) as a representative model of CNS injury, transcriptomic analyses reveal WTAP as a key mediator of pathways related to neuronal autophagy and inflammation regulation.

Chimeric Peptide Functionalized Immunostimulant to Orchestrate Photodynamic Immunotherapeutic Effect by PD-L1 Deglycosylation and CD47 Inhibition.

Breast cancer utilizes diverse immunosuppressive mechanisms to evade immune surveillance, thereby impairing immunotherapeutic effects. In this work, a chimeric peptide functionalized immunostimulant (designated as aGlyR) is fabricated to boost photodynamic immunotherapy through PD-L1 deglycosylation and CD47 inhibition. The photosensitizer protoporphyrin IX (PpIX) is conjugated to a PD-L1 deglycosylation peptide via a hydrophilic PEG linker, yielding the chimeric peptide Fmoc-K(PpIX)-PEG-GFTATPPAPDSPQEP.

Multifidus fat infiltration negatively influences the postoperative outcomes in lumbar disc herniation following transforaminal approach percutaneous endoscopic lumbar discectomy.

Purpose: This study aims to investigate the influence of multifidus muscle fat infiltration on clinical outcomes in lumbar disc herniation (LDH) undergoing percutaneous endoscopic lumbar discectomy (PELD).

Methods: A retrospective analysis was conducted on 224 patients who underwent lateral PELD, with complete one-year follow-up data. Patients were divided into two groups based on preoperative MRI evaluation of L4 multifidus muscle fat infiltration: a mild group (< 25%) and a severe group (≥ 25%).

Complete genome sequence of Pseudomonas aeruginosa YK01, a sequence type 16 isolated from a patient with keratitis.

Objectives: Pseudomonas aeruginosa, a Gram-negative opportunistic pathogen, is frequently associated with multidrug resistance and global epidemic outbreaks, contributing significantly to morbidity and mortality in hospitalized patients. However, P. aeruginosa belonging to the sequence type (ST) 16 was rarely reported.

Versatile poly (deep eutectic solvents) electroactive chitosan eutectogel for infected wound healing and monitoring administration.

The treatment and monitoring of infected skin wounds present significant clinical challenges. Herein, a multifunctional poly(deep eutectic solvent) (PDES) electroactive hydrogel is developed by optimizing the components and the ratio of hydrogen donors and acceptors, achieving well wound hemostasis, wound healing, and monitoring administration performace. The PDES hydrogel dressing exhibits mechanical properties, including high toughness, fatigue resistance (over 9000 compression cycles), and superior skin adhesion (over 70 kPa).

The lysosome-related characteristics affects the prognosis and tumor microenvironment of lung adenocarcinoma.

Background: The lysosome plays a vitally crucial role in tumor development and is a major participant in the cell death process, involving aberrant functional and structural changes. However, there are few studies on lysosome-associated genes (LAGs) in lung adenocarcinoma (LUAD).

Methods: Bulk RNA-seq of LUAD was downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO).

Update on the treatment navigation for functional cure of chronic hepatitis B: expert consensus 2.0.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements.

Deciphering Immunometabolic Landscape in Rheumatoid Arthritis: Integrative Multiomics, Explainable Machine Learning and Experimental Validation.

Purpose: Immunometabolism is pivotal in rheumatoid arthritis (RA) pathogenesis, yet the intricacies of its pathological regulatory mechanisms remain poorly understood. This study explores the complex immunometabolic landscape of RA to identify potential therapeutic targets.

Patients And Methods: We integrated genome-wide association study (GWAS) data involving 1,400 plasma metabolites, 731 immune cell traits, and RA outcomes from over 58,000 participants.

Efficacy and safety of non-invasive low-frequency tibial nerve stimulator in overactive bladder.

Objectives: To evaluate the efficacy and safety of a non-invasive low-frequency tibial nerve stimulator (TNS-01) vs sham control in relieving the symptoms of overactive bladder (OAB) patients.

Patients: Participants who were diagnosed with primary OAB or exhibited at least one OAB symptom. All participants underwent three 30-min intervention sessions weekly.

Dehydrocorydaline maintains the vascular smooth muscle cell contractile phenotype by upregulating Spta1.

Vascular smooth muscle cell (VSMC) phenotypic switching plays a crucial role in the initiation and progression of atherosclerosis. Dehydrocorydaline (DHC), a major active component of the traditional Chinese herbal medicine Rhizoma Corydalis, exhibits diverse pharmacological effects. However, its impact on VSMCs remains largely unknown.

Differentiating Tangerine Peels from Other through GC-MS, UPLC-Q-Exactive Orbitrap-MS, and HPLC-PDA.

The nonvolatile and volatile compounds in the peels of 13 cultivars (4 mandarins, 5 tangerines, and 4 hybrids) and 5 (sweet oranges) cultivars were analyzed. Initially, 66 volatile compounds were detected using gas chromatography-mass spectrometry (GC-MS). Tangerines were distinguished from other citrus cultivars (mandarins, sweet oranges, hybrids) by having higher volatile oil extraction rates and higher relative contents of o-Cymene, α-Terpinene, d-α-Pinene, Terpinolene, γ-Terpinene, l-β-Pinene, and 3-Thujene.

IgA class switching enhances neutralizing potency against SARS-CoV-2 by increased antibody hinge flexibility.

IgA antibodies are critical components of the mucosal immune barrier, providing essential first-line defense against viral infections. In this study, we investigated the impact of antibody class switching on neutralization efficacy by engineering recombinant antibodies of different isotypes (IgA1, IgG1) with identical variable regions from SARS-CoV-2 convalescent patients. A potent, broad-spectrum neutralizing monoclonal antibody CAV-C65 exhibited a ten-fold increase in neutralization potency upon switching from IgG1 to IgA1 monomer.

D-mannose promotes diabetic wound healing through inhibiting advanced glycation end products formation in keratinocytes.

Background: Diabetic chronic foot ulcers pose a significant therapeutic challenge around the world, resulting in adverse effects and complications in patients. D-mannose is enriched in cirtus peel and exerts beneficial effects among various diseases, especially against inflammation-related disorders.

Methods: Here, we examined the potential effect of D-mannose during wound healing process in streptozotocin (STZ)-induced diabetes mice in vivo and by culturing keratinocytes under high glucose condition in vitro.

Nano-fibrous biopolymers as building blocks for gel networks: Interactions, characterization, and applications.

Biopolymers derived from natural resources are highly abundant, biodegradable, and biocompatible, making them promising candidates to replace non-renewable fossil fuels and mitigate environmental and health impacts. Nano-fibrous biopolymers possessing advantages of biopolymers entangle with each other through inter-/intra-molecular interactions, serving as ideal building blocks for gel construction. These biopolymer nanofibers often synergize with other nano-building blocks to enhance gels with desirable functions and eco-friendliness across various applications in biomedical, environmental, and energy sectors.

Biomimetic wrinkled prebiotic microspheres with enhanced intestinal retention for hyperphosphatemia and vascular calcification.

It is urgent for patients with chronic kidney disease (CKD) to develop a robust and facile therapy for effective control of serum phosphate and reasonable regulation of gut microbiota, which are aiming to prevent cardiovascular calcification and reduce cardiovascular complications. Here, bioinspired by intestinal microstructures, we developed biomimetic wrinkled prebiotic-containing microspheres with enhanced intestinal retention and absorption for reducing hyperphosphatemia and vascular calcification of CKD model rats. The resultant CSM@5 microspheres exhibited favorable phosphate binding capacity in vitro and could effectively reduce serum concentration of phosphorous in vivo.

Single-cell transcriptomic analysis reveals characteristic feature of macrophage reprogramming in liver Mallory-Denk bodies pathogenesis.

Chronic liver diseases are highly linked with mitochondrial dysfunction and macrophage infiltration. Mallory-Denk bodies (MDBs) are protein aggregates associated with hepatic inflammation, and MDBs pathogenesis could be induced in mice by feeding 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). Here, we investigate the macrophage heterogeneity and the role of macrophage during MDBs pathogenesis on DDC-induced MDBs mouse model by single-nucleus RNA sequencing (snRNA-seq).

Warm and humid environment induces gut microbiota dysbiosis and bacterial translocation leading to inflammatory state and promotes proliferation and biofilm formation of certain bacteria, potentially causing sticky stool.

Background And Aims Of The Study: Fluctuations in environmental temperature and humidity significantly affect human physiology and disease manifestation. In the Lingnan region of China, high summer temperatures and humidity often cause symptoms like diminished appetite, sticky tongue coating, sticky stool, unsatisfactory defecation, lethargy, and joint heaviness. These are referred to as "Dampness Syndrome" in Traditional Chinese Medicine (TCM).

An analysis of the global burden of gallbladder and biliary tract cancer attributable to high BMI in 204 countries and territories: 1990-2021.

Background: Gallbladder and biliary tract cancers (GBTCs) are aggressive with poor prognosis, often undetected until advanced stages. High Body Mass Index (BMI) is a significant risk factor, contributing substantially to GBTC mortality and Disability-Adjusted Life Years (DALYs). This study aimed to quantify the global burdens of GBTCs attributable to high BMI from 1990 to 2021, thereby developing more rational prevention and treatment strategies for GBTC.

Citrobacter rodentium promotes brain cognitive dysfunction of type 2 diabetes mice by activating FXR mediated gut barrier damage.

Type 2 diabetes (T2D) is an important risk factor for brain cognitive impairment, but the specific mechanism is still unclear. The imbalance of gut microbiota under pathological conditions (such as an increase in pathogenic bacteria) may be involved in the occurrence of various diseases. The purpose of this study is to investigate the effect of increased abundance of gut Citrobacter rodentium on cognitive function in T2D mice.

The Type III Secretion System (T3SS) of Escherichia Coli Promotes Atherosclerosis in Type 2 Diabetes Mellitus.

Large-scale studies indicate a strong relationship between the gut microbiome, type 2 diabetes mellitus (T2DM), and atherosclerotic cardiovascular disease (ASCVD). Here, a higher abundance of the type III secretion system (T3SS) virulence factors of Enterobacteriaceae/Escherichia-Shigella in patients with T2DM-related-ASCVD, which correlates with their atherosclerotic stenosis is reported. Overexpression of T3SS via Citrobacter rodentium (CR) infection in Apoe-/- T2DM mice exacerbated atherosclerotic lesion formation and increased gut permeability.

Integrating Enzymes with Reticular Frameworks To Govern Biocatalysis.

Integrating enzymes with reticular frameworks offers promising avenues for access to functionally tailorable biocatalysis. This Minireview explores recent advances in enzyme-reticular framework hybrid biocomposites, focusing on the utilization of porous reticular frameworks, including metal-organic frameworks, covalent-organic frameworks, and hydrogen-bonded organic frameworks, to regulate the reactivity of an enzyme encapsulated inside mainly by pore infiltration and in situ encapsulation strategies. We highlight how pore engineering and host-guest interfacial interactions within reticular frameworks create tailored microenvironments that substantially impact the mass transfer and enzyme conformation, leading to biocatalytic rate enhancement, or imparting enzymes with non-native biocatalytic functions, including substrate selectivity and new activity.

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.

Identification of pyrimidine metabolism-based molecular subtypes and prognostic signature to predict immune landscape and guide clinical treatment in prostate cancer.

Background: We previously described the enrichment of plasma exosome metabolites in CRPC, PCa, and TFC cohorts, and found significant differences in pyrimidine metabolites. The PMGs is associated with the clinical prognosis of several cancers, but its biological role in PCa is still unclear.

Methods: This study extracted 98 reliable PMGs, and analyzed their somatic mutations, expression levels, and prognostic significance.