Discovery of an Ultralong-acting Nondepolarizing Neuromuscular Blocker That Displays Short Onset Time and On-Demand Rapid Reversal by a Biocompatible Antagonist.

The combination of ultralong-acting neuromuscular block and subsequent on-demand rapid reversal may provide prolonged surgeries with improved conditions by omitting continuous or repetitive blocker administration, enabling a more stable and predictable hemodynamic profile and eliminating residual block. For this target, we prepared 19 imidazolium-incorporated tetracationic macrocycles. In vivo studies with rats revealed that one macrocycle (IMC-14) displays extremely high blocking activity.

Ascertaining the Environmental Advantages of Pavement Designs Incorporating Recycled Content through a Parametric and Probabilistic Approach.

Reclaimed asphalt pavement (RAP) is a widely used end-of-life (EoL) material in asphalt pavements to increase the material circularity. However, the performance loss due to using RAP in the asphalt binder layer often requires a thicker layer, leading to additional material usage, energy consumption, and transportation effort. In this study, we developed a parametric and probabilistic life cycle assessment (LCA) framework to robustly compare various pavement designs incorporating recycled materials.

The value of ultrasound measured rectus femoris thickness, cross-sectional area and shear wave velocity in assessment of muscle in postmenopausal women with osteosarcopenia.

Objectives: To evaluate the value of ultrasound (US) and shear wave velocity (SWV) to assess muscle in postmenopausal women with osteosarcopenia (OSP).

Methods: This study included 145 postmenopausal women, comprising 115 osteopenia/osteoporosis participants without sarcopenia (OP alone) and 30 OSP participants. All received the evaluation of bone mineral density (BMD), appendicular skeletal muscle mass index (ASMI), handgrip strength, calf circumference, 6-meter walking speed, and 5-time chair stand test.

Diffusive topology preserving manifold distances for single-cell data analysis.

Manifold learning techniques have emerged as crucial tools for uncovering latent patterns in high-dimensional single-cell data. However, most existing dimensionality reduction methods primarily rely on 2D visualization, which can distort true data relationships and fail to extract reliable biological information. Here, we present DTNE (diffusive topology neighbor embedding), a dimensionality reduction framework that faithfully approximates manifold distance to enhance cellular relationships and dynamics.

A Multi-Scale Computational Model of the Hepatic Circulation Applied to Predict the Portal Pressure After Transjugular Intrahepatic Portosystemic Shunt (TIPS).

Transjugular intrahepatic portosystemic shunt (TIPS) is a widely used surgery for portal hypertension. In clinical practice, the diameter of the stent forming a shunt is usually selected empirically, which will influence the postoperative portal pressure. Clinical studies found that inappropriate portal pressure after TIPS is responsible for poor prognosis; however, there is no scheme to predict postoperative portal pressure.

Deep-Learning Generated Synthetic Material Decomposition Images Based on Single-Energy CT to Differentiate Intracranial Hemorrhage and Contrast Staining Within 24 Hours After Endovascular Thrombectomy.

Aims: To develop a transformer-based generative adversarial network (trans-GAN) that can generate synthetic material decomposition images from single-energy CT (SECT) for real-time detection of intracranial hemorrhage (ICH) after endovascular thrombectomy.

Materials: We retrospectively collected data from two hospitals, consisting of 237 dual-energy CT (DECT) scans, including matched iodine overlay maps, virtual noncontrast, and simulated SECT images. These scans were randomly divided into a training set (n = 190) and an internal validation set (n = 47) in a 4:1 ratio based on the proportion of ICH.

Discovery of SARS-CoV-2 Mpro inhibitors through rational design of novel fluorinated 1,3,4-oxadiazole amide derivatives: An in-silico study.

The main protease (Mpro) of SARS-CoV-2 is an evolutionarily conserved drug discovery target. The present study mainly focused on chemoinformatics computational methods to investigate the efficacy of our newly designed trifluoromethyl-1,3,4-oxadiazole amide derivatives as SARS-CoV-2 Mpro inhibitors. Drug-likeness ADMET analysis, molecular docking simulation, density functional theory (DFT) and molecular dynamics simulation methods were included.

Rationale and Design of the InsightPFA Trial: A Prospective, Multicenter, Randomized Controlled Trial of the Irreversible Electroporation-Based Pulsed Field Ablation Versus Radiofrequency Ablation in Chinese Patients With Symptomatic Paroxysmal Atrial Fibrillation.

Background: Pulsed field ablation (PFA) is gaining recognition as a nonthermal, tissue-specific technique for the treatment of atrial fibrillation (AF). The preclinical evaluation of the investigated novel PFA system from Insight Medtech Co. Ltd has demonstrated feasibility, safety, and 30-day efficacy for pulmonary vein isolation (PVI) in the swine model.

Chain of Risks Evaluation (CORE): A framework for safer large language models in public mental health.

Large language models (LLMs) have gained significant attention for their capabilities in natural language understanding and generation. However, their widespread adoption potentially raises public mental health concerns, including issues related to inequity, stigma, dependence, medical risks, and security threats. This review aims to offer a perspective within the actor-network framework, exploring the technical architectures, linguistic dynamics, and psychological effects underlying human-LLMs interactions.

Targeting p21-Positive Senescent Chondrocytes via IL-6R/JAK2 Inhibition to Alleviate Osteoarthritis.

Osteoarthritis (OA) is an age-related degenerative joint disease, prominently influenced by the pro-inflammatory cytokine interleukin-6 (IL-6). Although elevated IL-6 levels in joint fluid are well-documented, the uneven cartilage degeneration observed in knee OA patients suggests additional underlying mechanisms. This study investigates the role of interleukin-6 receptor (IL-6R) in mediating IL-6 signaling and its contribution to OA progression.

ACSL1 Aggravates Thromboinflammation by LPC/LPA Metabolic Axis in Hyperlipidemia Associated Myocardial Ischemia-Reperfusion Injury.

Acute myocardial infarction (AMI) is associated with well-established metabolic risk factors, especially hyperlipidemia and obesity. Myocardial ischemia-reperfusion injury (mIRI) significantly offsets the therapeutic efficacy of revascularization. Previous studies indicated that disrupted lipid homeostasis can lead to lipid peroxidation damage and inflammation, yet the underlying mechanisms remain unclear.

Efficacy and safety of JMT103 in patients with bone metastases from solid tumors: A randomized Phase Ib clinical trial.

This study aimed to assess the efficacy and safety of three dosing regimens of JMT103 in patients with bone metastases from solid tumors. Eligible patients were randomly assigned to receive JMT103 subcutaneously, 120 mg every 4 weeks (Cohort 1), 120 mg every 8 weeks (Cohort 2), or 180 mg every 8 weeks (Cohort 3) for up to 49 weeks. The primary endpoint was change from baseline to Week 13 in creatinine-adjusted urinary N-telopeptide (uNTx/Cr).

Neuroprotective Effects, Mechanisms of Action and Therapeutic Potential of the Kv7/KCNQ Channel Opener QO-83 in Ischemic Stroke.

Ischemic stroke is a worldwide disease with high mortality and morbidity. Kv7/KCNQ channels are key modulators of neuronal excitability and microglia function, and activation of Kv7/KCNQ channels has emerged as a potential therapeutic avenue for ischemic stroke. In the present study, we focused on a new Kv7/KCNQ channel opener QO-83 on the stroke outcomes and its therapeutic potential.

Fertility-sparing treatment outcomes using immune checkpoint inhibitors in endometrial cancer patients with Lynch syndrome.

Objective: To evaluate the efficacy of immune checkpoint inhibitors (ICIs) for fertility-sparing treatment in Lynch syndrome-associated endometrial cancer (LS-EC).

Methods: Four LS-EC cases received programmed cell death protein 1 (PD-1) inhibitors for fertility preservation at the Obstetrics and Gynecology Hospital of Fudan University from 2017 to 2023. The clinical data and long-term outcomes were retrospectively reviewed.

and activity of 1,2,3,4,6-O-pentagalloyl-glucose against .

Invasive fungal infections have become an increasingly serious threat to global human health, underscoring the urgent need for the development of new antifungal drugs. In this study, we found a natural polyphenolic compound 1,2,3,4,6-O-pentagalloyl-glucose (PGG), which is present in various plants and herbs. PGG showed broad-spectrum antifungal activities, enhancing the efficacy of fluconazole.

The Effects of Disinfection Byproduct 2,6-Dichloro-1,4-benzoquinone on the Cyanobacterium : From the Perspectives of Biochemistry and Non-Targeted Metabolomics.

2,6-Dichloro-1,4-benzoquinone (2,6-DCBQ) is an emerging chlorinated disinfection byproduct (DBP) in bodies of water. However, this compound poses an unknown toxic effect on cyanobacteria. In this study, the toxicological mechanisms of 2,6-DCBQ in () were investigated through physiological and nontargeted metabolomic assessments.

Short-Term Effect of Air Pollution on Daily Hospital Visits for Anxiety Disorders in Southern China with Low Pollution Concentrations.

The global prevalence and burden of anxiety disorders (ADs) are increasing. However, findings on the acute effects of air pollution on ADs remain inconclusive. We evaluated the effects of short-term exposure to ambient air pollutants, including fine particulate matter (PM), inhalable particulate matter (PM), nitrogen dioxide (NO), carbon monoxide (CO), sulfur dioxide (SO), and ozone (O), on daily hospital visits for ADs.

Activation of ClO by Nanoscale Zero-Valent Iron for Efficient Soil Polycyclic Aromatic Hydrocarbon Degradation: New Insight into the Relative Contribution of Fe(IV) and Hydroxyl Radicals.

Recently, the activation of chlorine dioxide (ClO) by metal(oxide) for soil remediation has gained notable attention. However, the related activation mechanisms are still not clear. Herein, the variation of iron species and ClO, the generated reactive oxygen species, and the toxicity of the degradation intermediates were explored and evaluated with nanoscale zero-valent iron (nFe) being employed to activate ClO for soil polycyclic aromatic hydrocarbon (PAH) removal.

Enhancing DNA Vaccine Delivery Through Stearyl-Modified Cell-Penetrating Peptides: Improved Antigen Expression and Immune Response In Vitro and In Vivo.

Background: Inefficient cellular uptake is a significant limitation to the efficacy of DNA vaccines. In this study, we introduce S-Cr9T, a stearyl-modified cell-penetrating peptide (CPP) designed to enhance DNA vaccine delivery by forming stable complexes with plasmid DNA, thereby protecting it from degradation and promoting efficient intracellular uptake.

Methods And Results: In vitro studies showed that S-Cr9T significantly improved plasmid stability and transfection efficiency, with optimal performance at an N/P ratio of 0.

Optimization of CuO/GaO Heterojunction Diodes for High-Voltage Power Electronics.

This study optimizes the CuO/GaO heterojunction diodes (HJDs) by tailoring the structural parameters of CuO layers. The hole concentration in the sputtered CuO was precisely controlled by adjusting the Ar/O gas ratio. Experimental investigations and TCAD simulations were employed to systematically evaluate the impact of the CuO layer dimension and hole concentration on the electrical performance of HJDs.

Deep learning analyses of splicing variants identify the link of PCP4 with amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disease, with most sporadic cases lacking clear genetic causes. Abnormal pre-mRNA splicing is a fundamental mechanism in neurodegenerative diseases. For example, TAR DNA-binding protein 43 (TDP-43) loss-of-function (LOF) causes widespread RNA mis-splicing events in ALS.

Stress-Driven Production of γ-Aminobutyric Acid Using Non-Conventional Yeast Strains JMY140K and JMY075.

γ-Aminobutyric acid (GABA) is a valuable amino acid widely used in food, healthcare, and agriculture. GABA bioproduction by budding yeasts has been commonly reported, but related studies using non-conventional yeasts remain limited. In this study, two non-conventional natural yeast strains, namely, JMY140K and JMY075, were identified as promising GABA producers, and JMY075 was discovered to be a GABA producer.

Osteopenia Metabolomic Biomarkers for Early Warning of Osteoporosis.

: This study aimed to capture the early metabolic changes before osteoporosis occurs and identify metabolomic biomarkers at the osteopenia stage for the early prevention of osteoporosis. : Metabolomic data were generated from normal, osteopenia, and osteoporosis groups with 320 participants recruited from the Nicheng community in Shanghai. We conducted individual edge network analysis (iENA) combined with a random forest to detect metabolomic biomarkers for the early warning of osteoporosis.

Exerkines and Sarcopenia: Unveiling the Mechanism Behind Exercise-Induced Mitochondrial Homeostasis.

: Sarcopenia, characterized by the progressive loss of muscle mass and strength, is linked to physical disability, metabolic dysfunction, and an increased risk of mortality. Exercise therapy is currently acknowledged as a viable approach for addressing sarcopenia. Nevertheless, the molecular mechanisms behind exercise training or physical activity remain poorly understood.