Computational design of highly signalling-active membrane receptors through solvent-mediated allosteric networks.

Protein catalysis and allostery require the atomic-level orchestration and motion of residues and ligand, solvent and protein effector molecules. However, the ability to design protein activity through precise protein-solvent cooperative interactions has not yet been demonstrated. Here we report the design of 14 membrane receptors that catalyse G protein nucleotide exchange through diverse engineered allosteric pathways mediated by cooperative networks of intraprotein, protein-ligand and -solvent molecule interactions.

Safety and Efficacy of Remote Ischemic Conditioning in Patients With Intravenous Thrombolysis: The SERIC-IVT Trial.

Background: Approximately half of the patients with acute ischemic stroke who receive intravenous thrombolysis (IVT) do not achieve an excellent outcome. Remote ischemic conditioning (RIC) as a promising neuroprotective treatment may improve clinical outcomes in this population. This study aimed to assess the efficacy and safety of RIC in patients with IVT.

Isolation of Plasma Extracellular Vesicles for High-Depth Analysis of Proteomic Biomarkers in Metastatic Castration-Resistant Prostate Cancer Patients.

: Prostate cancer treatment has been revolutionized by targeted therapies, including PARP inhibitors, checkpoint immunotherapies, and PSMA-targeted radiotherapies. Despite such advancements, accurate patient stratification remains a challenge, with current methods relying on genomic markers, tissue staining, and imaging. Extracellular vesicle (EV)-derived proteins offer a novel non-invasive alternative for biomarker discovery, holding promise for improving treatment precision.

Design of an equilibrative nucleoside transporter subtype 1 inhibitor for pain relief.

The current opioid crisis urgently calls for developing non-addictive pain medications. Progress has been slow, highlighting the need to uncover targets with unique mechanisms of action. Extracellular adenosine alleviates pain by activating the adenosine A1 receptor (A1R).

Diagnostic Efficacy of Ventilation-Perfusion Single Photo Emission Computed Tomography/Computed Tomography for Pulmonary Hypertension due to Fibrinous Mediastinitis.

Rationale And Objectives: Comprehensive data on the use of ventilation-perfusion single-photo emission computed tomography/computed tomography (V/Q SPECT/CT), an established diagnostic tool for chronic thromboembolic pulmonary hypertension, in identifying pulmonary hypertension secondary to fibrinous mediastinitis (PH-FM) is scarce. This study aimed to assess its diagnostic efficacy for PH-FM.

Materials And Methods: Patients with PH due to pulmonary artery stenosis were assessed using V/Q SPECT/CT, computed tomography pulmonary angiography (CTPA), and digital subtraction pulmonary angiography (PAG).

RNA-programmable cell type monitoring and manipulation in the human cortex with CellREADR.

Reliable and systematic experimental access to diverse cell types is necessary for understanding the neural circuit organization, function, and pathophysiology of the human brain. Methods for targeting human neural populations are scarce and currently center around identifying and engineering transcriptional enhancers and viral capsids. Here we demonstrate the utility of CellREADR, a programmable RNA sensor-effector technology that couples cellular RNA sensing to effector protein translation, for accessing, monitoring, and manipulating specific neuron types in human cortical tissues.

T cell dynamics with neoadjuvant immunotherapy in head and neck cancer.

Immune-checkpoint inhibitors (ICIs) are being tested as neoadjuvant therapies in various solid tumours, including in patients with head and neck squamous cell carcinoma (HNSCC), with promising results. Key findings thus far include that this approach is well-tolerated with favourable clinical outcomes including promising pathological response rates in initial studies. Pathological responses are likely to be increased by combining other agents with anti-PD-(L)1 antibodies.

Development and Validation of Multiparametric MRI-based Interpretable Deep Learning Radiomics Fusion Model for Predicting Lymph Node Metastasis and Prognosis in Rectal Cancer: A Two-center Study.

Rationale And Objectives: To develop interpretable machine learning models that utilize deep learning (DL) and radiomics based on multiparametric Magnetic resonance imaging (MRI) to predict preoperative lymph node (LN) metastasis in rectal cancer.

Materials And Methods: This retrospective study involved 286 cancer patients confirmed by histopathology from center 1 (Training set) and 66 patients from center 2 (External test set). Radiomics features were extracted from T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) sequences, whereas DL features were obtained using four models: MobileNet-V3-large, Inception-V3, ResNet50, and VGG16.

Relationship Between Physical Literacy and Cardiorespiratory Fitness in Children and Adolescents: A Systematic Review and Meta-analysis.

Background: Physical literacy (PL) can positively affect the health of children, adolescents, and adults, and is closely related to cardiorespiratory fitness (CRF).

Objective: To perform a systematic review and meta-analysis to examine the relationship between overall physical literacy (PL) and CRF in children and adolescents.

Methods: Cross-sectional, cohort and experimental studies on the relationship between PL and CRF in children and adolescents were collected by searching the Web of Science Core Collection, PubMed, EBSCOhost, ScienceDirect, Cochrane Library and China National Knowledge Infrastructure (CNKI) databases.

Middle Meningeal Artery Embolization for Nonacute Subdural Hematoma.

Background: The effect of embolization of the middle meningeal artery in patients with subacute or chronic subdural hematoma is uncertain.

Methods: We performed a multicenter, open-label, randomized trial in China, involving patients with symptomatic nonacute subdural hematoma with mass effect. Patients were assigned to undergo burr-hole drainage or receive nonsurgical treatment at the surgeon's discretion, and patients in each group were then randomly assigned, in a 1:1 ratio, to undergo middle meningeal artery embolization with liquid embolic material or to receive usual care.

Belimumab safety in adult and paediatric Chinese patients with systemic lupus erythematosus: A Phase 4, multicentre, observational study.

Objective: Although belimumab has been widely used in patients with systemic lupus erythematosus (SLE) globally, real-world safety data among Chinese patients are limited, particularly for children. This study assessed the safety and tolerability of belimumab in adult and paediatric patients with SLE in China in real-world clinical practice.

Methods: This Phase 4, multicentre, prospective, observational study enrolled patients prescribed intravenous belimumab by their physicians in tertiary hospitals, independent of a clinical study, during routine clinical visits between May 2021 and May 2022.

Associations Between Dry Eye Disease and Mental Health Conditions in the All of Us Research Program.

Purpose: To determine the association between dry eye disease (DED) and mental health conditions in a sociodemographically diverse nationwide population of Americans.

Design: Cross-sectional study.

Methods: We used the National Institute of Health's All of Us Research Program database to identify 18257 participants with DED who were propensity score matched in a 1:3 ratio to participants without DED.

UV-induced reactive species dynamics and product formation by chlorite.

Chlorite (ClO) is a regulated byproduct of chlorine dioxide water treatment processes. The transformation of chlorite under UV irradiation into chloride (Cl) and chlorate (ClO) involves reactive species chain reactions that could enhance chlorine dioxide water treatment efficiency while reducing residual chlorite levels. This study conducted a mechanistic investigation of chlorite phototransformation by analyzing reaction intermediates and stable end products, including chlorine dioxide (ClO), free chlorine (HOCl/OCl), hydroxyl‑radical (OH), Cl, and ClO through combined experimental and modeling approaches.

Discordant High Remnant Cholesterol With LDL-C Increases the Risk of Stroke: A Chinese Prospective Cohort Study.

Background: Previous studies focusing on assessing the effects of remnant cholesterol (RC) and low-density lipoprotein cholesterol (LDL-C) on stroke may not consider their mutual influence. We aimed to explore the associations of RC and discordant high RC with LDL-C with stroke, ischemic stroke (IS), and hemorrhagic stroke.

Methods: This prospective cohort study was conducted based on 3 cohorts of the China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) project.

The Gut Microbiota and Diabetes: Research, Translation, and Clinical Applications-2023 Diabetes, Diabetes Care, and Diabetologia Expert Forum.

This article summarizes the state of the science on the role of the gut microbiota (GM) in diabetes from a recent international expert forum organized by Diabetes, Diabetes Care, and Diabetologia, which was held at the European Association for the Study of Diabetes 2023 Annual Meeting in Hamburg, Germany. Forum participants included clinicians and basic scientists who are leading investigators in the field of the intestinal microbiome and metabolism. Their conclusions were as follows: 1) the GM may be involved in the pathophysiology of type 2 diabetes, as microbially produced metabolites associate both positively and negatively with the disease, and mechanistic links of GM functions (e.

Visualization of the Extracranial Branches of the Trigeminal Nerve Using Improved Motion-Sensitized Driven Equilibrium-Prepared 3D Inversion Recovery TSE Sequence.

Background And Purpose: Visualization of the extracranial trigeminal nerve is crucial to detect nerve pathologic alterations. This study aimed to evaluate visualization of the extracranial trigeminal nerve using 3D inversion recovery TSE with an improved motion-sensitized driven equilibrium (iMSDE) pulse.

Materials And Methods: In this prospective study, 35 subjects underwent imaging of the trigeminal nerve using conventional 3D inversion recovery TSE, 3D inversion recovery TSE with an iMSDE pulse, and contrast-enhanced 3D inversion recovery TSE.

The Gut Microbiota and Diabetes: Research, Translation, and Clinical Applications-2023 Diabetes, Diabetes Care, and Diabetologia Expert Forum.

This article summarizes the state of the science on the role of the gut microbiota (GM) in diabetes from a recent international expert forum organized by Diabetes, Diabetes Care, and Diabetologia, which was held at the European Association for the Study of Diabetes 2023 Annual Meeting in Hamburg, Germany. Forum participants included clinicians and basic scientists who are leading investigators in the field of the intestinal microbiome and metabolism. Their conclusions were as follows: 1) the GM may be involved in the pathophysiology of type 2 diabetes, as microbially produced metabolites associate both positively and negatively with the disease, and mechanistic links of GM functions (e.

Use of Diagnostic Codes for Primary Open-Angle Glaucoma Polygenic Risk Score Construction in Electronic Health Record-Linked Biobanks.

Purpose: Polygenic risk scores (PRSs) likely predict risk and prognosis of glaucoma. We compared the PRS performance for primary open-angle glaucoma (POAG), defined using International Classification of Diseases (ICD) codes vs manual medical record review.

Design: Retrospective cohort study.