Developing the biomarker panels and drugs by proteomic analysis for autoimmune uveitis and posterior scleritis.

Autoimmune uveitis and posterior scleritis are ocular diseases caused by immune dysregulation. Their pathogenesis remains elusive, and delayed diagnosis can exacerbate vision loss. Our study analyzed proteomic profiles of 190 patients with Behcet's disease uveitis, posterior scleritis, and Vogt-Koyanagi-Harada syndrome.

Continuous augmentation of anaerobic digestion with electroactive microorganisms: Performance and stability.

The performance and stability of a bioelectrochemical anaerobic digester (BeAD), continuously augmented with electroactive microorganisms (EAMs), were investigated. The BeAD showcased superior performance, sustaining the high COD removal efficiency and methane production rate of 76.5 % and 0.

Strategies for the development of metalloimmunotherapies.

Metal ions play crucial roles in the regulation of immune pathways. In fact, metallodrugs have a long record of accomplishment as effective treatments for a wide range of diseases. Here we argue that the modulation of interactions of metal ions with molecules and cells involved in the immune system forms the basis of a new class of immunotherapies.

Five autism-associated transcriptional regulators target shared loci proximal to brain-expressed genes.

Many autism spectrum disorder (ASD)-associated genes act as transcriptional regulators (TRs). Chromatin immunoprecipitation sequencing (ChIP-seq) was used to identify the regulatory targets of ARID1B, BCL11A, FOXP1, TBR1, and TCF7L2, ASD-associated TRs in the developing human and mouse cortex. These TRs shared substantial overlap in the binding sites, especially within open chromatin.

Multimodal cell atlas of the ageing human skeletal muscle.

Muscle atrophy and functional decline (sarcopenia) are common manifestations of frailty and are critical contributors to morbidity and mortality in older people. Deciphering the molecular mechanisms underlying sarcopenia has major implications for understanding human ageing. Yet, progress has been slow, partly due to the difficulties of characterizing skeletal muscle niche heterogeneity (whereby myofibres are the most abundant) and obtaining well-characterized human samples.

QL1604 plus paclitaxel-cisplatin/carboplatin in patients with recurrent or metastatic cervical cancer: an open-label, single-arm, phase II trial.

Objective: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer.

Methods: This was a multicenter, open-label, single-arm, phase II study.

Significance Associated with Phenotype Score Aids in Variant Prioritization for Exome Sequencing Analysis.

Several in silico annotation-based methods have been developed to prioritize variants in exome sequencing analysis. This study introduced a novel metric Significance Associated with Phenotypes (SAP) score, which generates a statistical score by comparing an individual's observed phenotypes against existing gene-phenotype associations. To evaluate the SAP score, a retrospective analysis was performed on 219 exomes.

Deep Learning-Based Detection and Classification of Bone Lesions on Staging Computed Tomography in Prostate Cancer: A Development Study.

Rationale And Objectives: Efficiently detecting and characterizing metastatic bone lesions on staging CT is crucial for prostate cancer (PCa) care. However, it demands significant expert time and additional imaging such as PET/CT. We aimed to develop an ensemble of two automated deep learning AI models for 1) bone lesion detection and segmentation and 2) benign vs.

Serum Exosome-Derived microRNA-193a-5p and miR-381-3p Regulate Adenosine 5'-Monophosphate-Activated Protein Kinase/Transforming Growth Factor Beta/Smad2/3 Signaling Pathway and Promote Fibrogenesis.

Introduction: Liver fibrosis results from chronic liver injury and inflammation, often leading to cirrhosis, liver failure, portal hypertension, and hepatocellular carcinoma. Progress has been made in understanding the molecular mechanisms underlying hepatic fibrosis; however, translating this knowledge into effective therapies for disease regression remains a challenge, with considerably few interventions having entered clinical validation. The roles of exosomes during fibrogenesis and their potential as a therapeutic approach for reversing fibrosis have gained significant interest.

Efficacy and Safety of Mazdutide in Chinese Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial.

Objective: We conducted a randomized, double-blind, placebo-controlled phase 2 trial to evaluate the efficacy and safety of mazdutide, a once-weekly glucagon-like peptide 1 and glucagon receptor dual agonist, in Chinese patients with type 2 diabetes.

Research Design And Methods: Adults with type 2 diabetes inadequately controlled with diet and exercise alone or with stable metformin (glycated hemoglobin A1c [HbA1c] 7.0-10.

Vaccination with a replication-defective cytomegalovirus vaccine elicits a glycoprotein B-specific monoclonal antibody repertoire distinct from natural infection.

Human Cytomegalovirus (HCMV) is the leading infectious congenital infection globally and the most common viral infection in transplant recipients, therefore identifying a vaccine for HCMV is a top priority. Humoral immunity is a correlate of protection for HCMV infection. The most effective vaccine tested to date, which achieved 50% reduction in acquisition of HCMV, was comprised of the glycoprotein B protein given with an oil-in-water emulsion adjuvant MF59.

Effect of Platelet Function Testing Guidance on Clinical Outcomes for Patients with Intracranial Aneurysms Undergoing Endovascular Treatment.

Background: Platelet function testing has been proposed to better adjust individualized antiplatelet treatment for patients undergoing endovascular treatment for intracranial aneurysms. Its clinical significance needs to be comprehensively evaluated.

Purpose: Our aim was to evaluate the impact of platelet function testing-guided versus standard antiplatelet treatment in patients receiving endovascular treatment for intracranial aneurysms.

The Genus : An Updated Review of Phytochemistry, Pharmacology and Applications.

The genus (Moraceae), recognized for its value in many Chinese traditional herbs, mainly includes (L.) L'Hér. ex Vent.

SLC1A1-mediated cellular and mitochondrial influx of R-2-hydroxyglutarate in vascular endothelial cells promotes tumor angiogenesis in IDH1-mutant solid tumors.

Mutant isocitrate dehydrogenase 1 (mIDH1) drives tumorigenesis via producing oncometabolite R-2-hydroxyglutarate (R-2-HG) across various tumor types. However, mIDH1 inhibitors appear only effective in hematological tumors. The therapeutic benefit in solid tumors remains elusive, likely due to the complex tumor microenvironment.

Multiethnic Genome-Wide Association Study of Subclinical Atherosclerosis in Individuals With Type 2 Diabetes.

Background: Coronary artery calcification (CAC) and carotid artery intima-media thickness (cIMT) are measures of subclinical atherosclerosis in asymptomatic individuals and strong risk factors for cardiovascular disease. Type 2 diabetes (T2D) is an independent cardiovascular disease risk factor that accelerates atherosclerosis.

Methods: We performed meta-analyses of genome-wide association studies in up to 2500 T2D individuals of European ancestry (EA) and 1590 T2D individuals of African ancestry with or without exclusion of prevalent cardiovascular disease, for CAC measured by cardiac computed tomography, and 3608 individuals of EA and 838 individuals of African ancestry with T2D for cIMT measured by ultrasonography within the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium.

A Gastrointestinal Endoscopy Quality Control System Incorporated With Deep Learning Improved Endoscopist Performance in a Pretest and Post-Test Trial.

Introduction: Gastrointestinal endoscopic quality is operator-dependent. To ensure the endoscopy quality, we constructed an endoscopic audit and feedback system named Endo.Adm and evaluated its effect in a form of pretest and posttest trial.

PKM1 Exerts Critical Roles in Cardiac Remodeling Under Pressure Overload in the Heart.

Background: Metabolic remodeling precedes most alterations during cardiac hypertrophic growth under hemodynamic stress. The elevation of glucose utilization has been recognized as a hallmark of metabolic remodeling. However, its role in cardiac hypertrophic growth and heart failure in response to pressure overload remains to be fully illustrated.

A conditionally replication-defective cytomegalovirus vaccine elicits potent and diverse functional monoclonal antibodies in a phase I clinical trial.

A conditionally replication-defective human cytomegalovirus (HCMV) vaccine, V160, was shown to be safe and immunogenic in a two-part, double-blind, randomized, placebo-controlled phase I clinical trial (NCT01986010). However, the specificities and functional properties of V160-elicited antibodies remain undefined. Here, we characterized 272 monoclonal antibodies (mAbs) isolated from single memory B cells of six V160-vaccinated subjects.

Low-Temperature Molten Salts Synthesis: CsPbBr Nanocrystals with High Photoluminescence Emission Buried in Mesoporous SiO.

Using mesoporous SiO to encapsulate CsPbBr nanocrystals is one of the best strategies to exploit such materials in devices. However, the CsPbBr/SiO composites produced so far do not exhibit strong photoluminescence emission and, simultaneously, high stability against heat and water. We demonstrate a molten-salts-based approach delivering CsPbBr/mesoporous-SiO composites with high PLQY (89 ± 10%) and high stability against heat, water, and aqua regia.

Safety and efficacy of remote ischemic postconditioning after thrombolysis in patients with stroke.

Objective: To determine the effect of remote ischemic postconditioning (RIPC) on patients with acute ischemic stroke (AIS) undergoing IV thrombolysis (IVT).

Methods: A single-center randomized controlled trial was performed with patients with AIS receiving IVT. Patients in the RIPC group were administered RIPC treatment (after IVT) during hospitalization.

Systemic Messenger RNA Therapy as a Treatment for Methylmalonic Acidemia.

Isolated methylmalonic acidemia/aciduria (MMA) is a devastating metabolic disorder with poor outcomes despite current medical treatments. Like other mitochondrial enzymopathies, enzyme replacement therapy (ERT) is not available, and although promising, AAV gene therapy can be limited by pre-existing immunity and has been associated with genotoxicity in mice. To develop a new class of therapy for MMA, we generated a pseudoU-modified codon-optimized mRNA encoding human methylmalonyl-CoA mutase (hMUT), the enzyme most frequently mutated in MMA, and encapsulated it into biodegradable lipid nanoparticles (LNPs).