Divergent resistance pathways amongst SARS-CoV-2 PLpro inhibitors highlight the need for scaffold diversity.

Drug-escape, where a target evolves to escape inhibition from a drug, has the potential to lead to cross-resistance where drugs that are structurally related or share similar binding mechanisms all become less effective. PLpro inhibitors are currently under development and many emerging PLpro inhibitors are derived from GRL0617, a repurposed SARS-CoV PLpro inhibitor with moderate activity against SARS-CoV-2. Two leading derivatives, PF-07957472 and Jun12682, demonstrate low nanomolar activity and display activity in mice.

Insights from deep mutational scanning in the context of an emerging pathogen.

Deep mutational scanning (DMS), a high-throughput method leveraging next-generation sequencing, has been crucial in mapping the functional landscapes of key severe acquired respiratory syndrome-coronavirus 2 (SARS-CoV-2) proteins. By systematically assessing thousands of amino acid changes, DMS provides a framework to understand Angiotensin-converting enzyme 2 (ACE2) binding and immune evasion by the spike protein, mechanisms and drug escape potential of the main and papain-like viral proteases and has highlighted areas of concern in the nucleocapsid protein that may affect most currently available rapid antigen testing kits. Each application has required the design of bespoke assays in eukaryotic (yeast and mammalian) cell models, providing an exemplar for the application of this technique to future pandemics.

Directed protonation strategy for efficient electrochemical metaborate reduction to sodium borohydride at the interface of manganese single atoms and manganese oxide nanoparticles.

Sodium borohydride (NaBH) is considered as an outstanding hydrogen generation and storage material, whereas its widespread commercial application remains hindered by prohibitively high production cost and unsatisfied yield in the current production process. Electrochemical metaborate reduction reaction is a promising method to realize the low-cost and effective NaBH production, where the *H generation and the inhibition of HH coupling are critical but still remain challenging for suppressing competing hydrogen evolution reaction (HER). Herein, a core-shell structure with manganese oxide as a core and manganese single atom coordinated by nitrogen on the carbon substrate as a shell (MnO@Mn-N-C) was synthesized, where Mn-N-C enabled to boost water dissociation and electron donating as well as suppress HH coupling, thereby enhancing directed hydrogenation of reaction intermediate to generate NaBH.

Associations between perceived stress profiles, social connection and work engagement in clinical registered nurses: a mediation analysis and generalized additive models.

Background: Investigating the links between individual perceived stress, social connection, and work involvement plays a crucial role in enhancing the psychological health and overall well-being of clinical nurses, as well as elevating the quality of nursing care in clinical settings. This study incorporates the concepts of social connection and work engagement. By considering the potential heterogeneity of variables and applying a mediation model, we identified the influence pathways through which subgroups of perceived stress affect social connection and work engagement.

ALKBH5-mediated mA demethylation modification of RAD51 inhibits osteogenic differentiation via promoting DNA damage in osteoporosis.

Osteoporosis (OP) is a metabolic disorder characterized by reduced bone mineral density and degeneration of bone tissue microarchitecture. Osteogenic differentiation plays a pivotal role in OP pathogenesis by facilitating new bone formation, preserving bone strength and density, and counteracting bone resorption. RNA epigenetic modifications have been increasingly implicated in multiple aspects of bone metabolism.

Accuracy of Implant Placement with Robotic Surgery, Dynamic Navigation, Fully Static Guide, and Freehand Surgery: A Systematic Review and Network Meta-analysis.

Purpose: To evaluate the relative efficacy and estimate a treatment ranking of the positional accuracy of guided implant placement, including robotic surgery, dynamic navigation, static guide, and freehand surgery.

Materials And Methods: Electronic searches were performed in PubMed, Embase, and Cochrane CENTRAL. Randomized controlled trials comparing different guided approaches were included.

Methodological Innovation in Evaluating the Cost-Effectiveness of Simulation Training Combining Transfer Effectiveness and Change-Point Analysis.

Background: Simulation-based medical education has become increasingly prevalent. However, the high cost and lack of comprehensive effectiveness evaluations have raised questions about its feasibility. This study introduces a novel approach to assess the cost-effectiveness of simulation training.

An open-label phase II study: The efficiency and safety of anlotinib + eribulin in patients with HER2-negative metastatic breast cancer.

This research (NCT04624711) evaluated the efficacy and safety of eribulin plus anlotinib in patients with HER2-negative metastatic breast cancer (mBC) and explored the potential synergistic benefits of this combination. A total of 70 women with HER2-negative breast cancer who had previously undergone anthracycline- or taxane-based therapies were enrolled. Hormone receptor-positive patients had also received CDK4/6 (Cyclin-dependent kinase 4/6) inhibitor-based endocrine therapy.

Pathology, immunosuppression and NK cell immunotherapy of non-small cell lung cancer.

Lung cancer is one of the leading causes of cancer incidence and mortality. Non-small lung cancer (NSCLC) makes up almost 80 % of lung cancer cases. Treatments for NSCLC have traditionally been restricted to surgeries, radiotherapy, and chemotherapy.

Evaluating the diagnostic accuracy of Tc-labeled somatostatin receptor imaging for suspected pheochromocytomas and paragangliomas.

Pheochromocytomas and paragangliomas (PPGLs) present diagnostic challenges due to their diverse clinical manifestations. This study aims to evaluate the diagnostic accuracy of [Tc]Tc-HYNIC-TOC SPECT/CT in patients with clinically suspected PPGLs. A retrospective analysis was conducted on 75 patients (36 males, 39 females, mean age 47.

Development of areal-level individualized homologous functional parcellations in youth.

Individualized functional brain networks from childhood to adolescence undergo varying patterns of maturation, associated with higher-order cognition outcomes. However, the developmental trajectory patterns based on homologous areal-level brain parcellations remain elusive. Here, we developed an individualized homologous functional parcellation technique (IHFP) to map brain functional development using resting-state functional magnetic resonance imaging data from the Lifespan Human Connectome Project in Development study (N = 591) aged 8-21 years.

The predictive value of total body PET/CT in high PD-L1 expression and immunotherapy in advanced non-small cell lung cancer patients.

Introduction: Total-body positron emission tomography/computed tomography (PET/CT) using uEXPLORER scanners demonstrates superior imaging capabilities for assessing programmed death ligand 1 (PD-L1) expression heterogeneity between primary tumors (PTs) and metastatic tumors (MTs) in advanced nonsmall cell lung cancer (NSCLC).

Methods: This retrospective study of 99 treatment-naïve NSCLC patients revealed that metabolic parameters (SUVmax, SUR-L, and SUR-BP) derived from biopsy-correlated PET/CT sites significantly predicted high PD-L1 expression (TC ≥ 50% or IC ≥ 10% by IHC).

Results: SUR-L exhibited the highest diagnostic accuracy (AUC = 0.

Urolithin A Attenuates Periodontitis in Mice via Dual Anti-Inflammatory and Osteoclastogenesis Inhibition: A Natural Metabolite-Based Therapeutic Strategy.

Periodontitis is an inflammatory disease that affects the periodontal supporting tissues. Its cardinal clinical manifestations encompass gingival inflammation, periodontal pocket formation, and alveolar bone resorption. Urolithin A (UA), a gut microbiota-derived metabolite of ellagitannins, is known for its anti-inflammatory and osseous-protective properties.

A key loop in the catalytic pocket of the PL17 family of alginate lyases determines minimal substrate recognition.

Alginate, a major component of brown macroalgae, is an alternative feedstock for biorefining. The degradation of alginate oligosaccharides (AOSs) is a key prerequisite for biorefining, which usually requires at least two oligo-alginate lyases (Oals). However, the function and minimal substrate recognition mechanisms of different Oals in alginate metabolism remain poorly understood.

Comparative analysis of the performance of the large language models DeepSeek-V3, DeepSeek-R1, open AI-O3 mini and open AI-O3 mini high in urology.

Objectives: We sought to compare how DeepSeek‑V3, DeepSeek‑R1, OpenAI o3‑mini, and OpenAI o3‑mini high handle urological questions, especially in areas such as benign prostatic enlargement, urinary stones, infections, and guideline updates. The intent was to identify how these text‑creation platforms might aid clinical practice without overlooking potential gaps in accuracy.

Methods: A set of 34 routinely asked questions plus 25 queries based on newly revised guidelines was assembled.

Divide-and-conquer strategy with engineered ossification center organoids for rapid bone healing through developmental cell recruitment.

Current approaches for bone repair predominantly target localized delivery of growth factors that are aimed at the coupling of angiogenesis and osteogenesis. However, delayed revascularization and regeneration of critical-sized bone defects are still challenging. In this study, we engineer an ossification center-like organoid (OCO) that consist of an inner-core bone morphogenetic and neurotrophic spheroid generated via MSCs-loaded 3D printing, alongside the interstitially distributed outer-shell proangiogenic neurotrophic phase.

Sustainable and resource-efficient synthesis of zeolite membranes in a fluoride-free, organic template-free dilute solution.

Environmentally friendly and sustainable synthesis technologies hold considerable significance in the manufacturing of high-performance mordenite membranes. Herein, a high-performance mordenite membrane was successfully fabricated on a macroporous tube under fluoride-free and organic template-free conditions, using a highly diluted synthesis solution with a molar composition of HO/SiO = 250. This approach eliminated the necessity of fluoride and template agents while reducing chemical usage a highly diluted solution.

HSP 90-Alpha and Serotransferrin as Potential Biomarkers for Predicting IL-17 Inhibitor Response in Non-Radiographic Axial Spondyloarthritis: A Retrospective Analysis.

Background: Non-radiographic axial spondyloarthritis (nr-axSpA) is an early stage of axial spondyloarthritis characterized by the absence of definitive radiographic changes. Interleukin-17 inhibitors (IL-17i) have shown efficacy in treating nr-axSpA, but a significant proportion of patients fail to respond. Identifying predictive biomarkers for IL-17i response is crucial for optimizing treatment strategies.

Prognostic implication of dynamic platelet count in lung cancer patients with thrombocytosis: a retrospective analysis.

Background: Thrombocytosis is associated with poor prognosis in lung cancer patients. However, no studies have further assessed the effect of platelet-related parameters on the prognosis among lung cancer patients with thrombocytosis.

Methods: Between 2020 and 2021, lung cancer patients with a platelet count ≥ 300 *10/L or normal count were retrospectively reviewed.

Advancements and applications in radiopharmaceutical therapy.

Radiopharmaceuticals operate by combining radionuclides with carriers. The radiation energy emitted by radionuclides is utilized to selectively irradiate diseased tissues while minimizing damage to healthy tissues. In comparison to external beam radiation therapy, radionuclide drugs demonstrate research potential due to their biological targeting capabilities and reduced normal tissue toxicity.

PerioAI: A digital system for periodontal disease diagnosis from an intra-oral scan and cone-beam CT image.

Periodontal disease diagnosis and treatment planning are critical for preventing bone and tooth loss. Clinically, dentists manually measure periodontal pocket depth with probes while integrating bone structure from imaging to assess periodontal status, a process that is subjective, invasive, and cognitively burdensome. Here, we propose PerioAI, an accurate, automatic, and non-invasive system that directly measures the gingiva-bone distance (GBD) and provides soft and hard tissue information digitally.

Design, synthesis, and application of triazole-embedded maltose-neopentyl-glycol (TMNG) amphiphiles for membrane protein studies.

Understanding membrane protein (MP) structure and function is less advanced than that of soluble proteins. Detergents are the primary reagents used in membrane protein studies, yet only a limited selection is employed in both fundamental and applied research. This study presents the design, synthesis, and application of novel triazole-embedded maltose-neopentyl-glycol (TMNG) amphiphiles for membrane protein studies.

CircRNA Networks in CAD: Multi-Cellular Mechanisms and Clinical Potential.

Coronary artery disease (CAD), is a global cardiovascular disease that is characterized by myocardial ischemia and hypoxia caused by coronary artery occlusion. Circular RNAs (CircRNAs) is a particular kind of endogenous non-coding RNA, which can affect the occurrence and development of CAD. Concurrently, several circRNAs display stable persistence in CAD patients, attributable to their exceptional exonuclease resistance, thereby harboring the capacity to evolve into a biomarker for CAD diagnosis and prognosis.

Demethyleneberberine ameliorates pulmonary fibrosis by inhibiting the NLRP3 inflammasome and the epithelial-mesenchymal transition.

Background And Aims: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease characterized by inflammation and fibrosis. Demethyleneberberine (DMB), a natural compound derived from traditional Chinese medicine, possesses both anti-inflammatory and antifibrotic properties. This study investigated the therapeutic potential of DMB in pulmonary fibrosis and elucidated its underlying mechanisms of action.

Immunophenotypic Profiling Reveals Circulating Lymphocyte Dysregulation in Primary Sjögren's Syndrome.

Objectives: To investigate peripheral T and B cell subset alterations in primary Sjögren's syndrome (pSS) and their associations with disease activity (ESSDAI).

Methods: This study enrolled 43 patients with pSS and 46 healthy controls (HCs). Demographic data and clinical manifestations were collected for all participants.