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An allosteric inhibitor of the Zika virus NS2B-NS3 protease with oral efficacy in mouse models

Abstract The mosquito-transmitted Zika virus (ZIKV) poses a global health threat, with no approved antiviral drugs or vaccines currently available. Here, we report the discovery of a series of ZIKV NS3 protease inhibitors identified through phenotypic high-throughput screening (HTS) using a ZIKV replicon-based cellular assay, and the subsequent selection of resistant mutants. These inhibitors, characterized by the presence of an N -acylsydnone imine group, bind to a previously undescribed allosteric pocket of the protease, locking the enzyme into a catalytically inactive conformation. We describe the characterization of IRBM-Z-1, our initial allosteric hit and IRBM-Z-2, a potent inhibitor of ZIKV infectivity and other orthoflavivirus proteases with a favourable in vitro and in vivo ADME profile, resulting in oral efficacy against ZIKV infection in mouse models, with potential as a prophylactic agent for human use.

Modified design TWCI-based high step-up DC-DC converter with reduced elements and low input current ripple for renewable applications

Effects of pentosan polysulfate sodium on joint structure and function out to six months in naturally-occurring canine osteoarthritis

Objective To evaluate the durability of effect and disease modification potential of a six-week course of pentosan polysulfate sodium (PPS) therapy out to 26 weeks (six months) in companion dogs with naturally-occurring osteoarthritis. Design Twenty mixed-breed companion dogs were enrolled and randomized to receive either subcutaneous 3 mg/kg PPS injections (n = 14) or placebo (n = 6) once weekly for six weeks. Dogs underwent assessments for pain, functional gait analysis, MRI, and biomarker analysis at baseline and selected timepoints. Results PPS treatment was well tolerated throughout the study. At baseline, the PPS-treated group had higher pain with Helsinki Chronic Pain Index (HCPI) scores of 15.14 compared to 8.83 in placebo. PPS-treated dogs experienced sustained HCPI reductions compared to placebo at 26 weeks after adjusting for differences in baseline pain. The PPS-treated group experienced normalization of gait symmetry up to week 26, indicating a reduction in lameness and an improvement in overall function. Total cartilage volume increased at weeks 8 and 26 from baseline in the PPS-treated group compared to placebo, and OA disease progression biomarker changes (CTX-I, HA, and TIMP-1) were consistent with slowed cartilage degradation at weeks 8 and 26. Conclusions PPS-treated dogs experienced improvements in pain, joint function, and cartilage volume compared to placebo, supported by changes in biomarkers at weeks 8 and 26. The 26-week timepoint in this translational canine model provides insights into the potential disease-modifying mechanisms and durability of PPS in long-term treatment outcomes in humans with OA.

What can I do if my idea has been plagiarized?

Photosynergetic ligand-exchange for modular synthesis of copper nanoclusters

Leveraging zeta potential as a surface charge metric for trapping and killing of airborne bacteria

Artificial intelligence agents in healthcare research: A scoping review

Introduction Artificial Intelligence (AI) agents are rapidly transforming healthcare delivery, enabling real-time decision support and sophisticated patient interaction at scale. However, the scientific landscape of this rapidly growing, multidisciplinary field remains fragmented, with technical innovation outpacing translational research and the establishment of ethical governance frameworks. To address this gap, we conducted a comprehensive scoping review analysis of AI agent research in healthcare. Methods We followed scoping review methodology (PRISMA-ScR guidelines). Searches across PubMed, Web of Science, arXiv, and medRxiv were conducted from January 2015 to December 7, 2025. Results The search identified 1,070 records, of which 43 studies were ultimately included after full-text review. Of these 43 included studies, 36 were published in 2025. Systems were categorized into 8 conversational agents, 17 workflow/automation assistants, and 18 multimodal decision support agents. The core mechanism across all archetypes was external tool use (e.g., retrieval-augmented generation or code execution) for grounding and iterative self-correction (e.g., multi-agent debate or self-debugging loops) for refinement. Evaluation settings were predominantly simulated environments or laboratory studies, with few clinical pilots or real-world deployments. Primary reported outcomes focused on process measures (efficiency) and diagnostic accuracy; clinical outcomes and safety endpoints were rarely addressed. Conclusion Agentic AI systems are rapidly evolving from conceptual frameworks to functional prototypes, primarily targeting complex decision-making and workflow automation. While agentic capabilities are increasingly integrated, research heavily favors simulated evaluations. Future research must prioritize clinical trials and the robust assessment of safety, usability, and clinical efficacy before widespread adoption.

Global application of radiative cooling in grain storage

RHA/TiO2-[bip]-NH2+NO3− as an efficient catalyst for the solvent-free synthesis of 1,8-dioxo-decahydroacridine and 2,3-dihydroquinazolin-4(1H)-one derivatives

Sources of information on HIV/AIDS used by adolescents and young people: A scoping review protocol

Objective To describe the protocol for a scoping review of the main sources of information about HIV/AIDS used by adolescents and young people. Context Studies have shown that adolescents and young people are increasingly using digital technologies as a source of information about HIV/AIDS. Although these digital technologies offer potential benefits to the educational process, their implementation and use are not always free from challenges and implications. In this sense, it is essential to investigate the reliability of the information sources accessed by adolescents and young people. Design Scoping review protocol, conducted in accordance with JBI guidelines Method This is a protocol for a scoping review to be conducted following the JBI guidelines, in three phases and using the following data sources: Scopus, Cumulative Index to Nursing and Allied Health Literature, Medical Literature Analysis and Retrieval System Online (MEDLINE), Scientific Electronic Library Online (SciELO), Latin American and Caribbean Literature in Health Sciences (LILACS), Web of Science and later, Google School, Capes Catalog of Theses and Dissertations, Theses Canada and USP Digital Library of Theses and Dissertations. The inclusion criteria are studies that address the theme, available in full, free of charge and without time or language restrictions. The exclusion criteria are opinion articles, letters to the editor and editorials. The results will be presented through discussions, tables, graphs and percentages. Expected results: The results are expected to reveal the main sources of information used by adolescents and young people regarding HIV/AIDS, allowing the identification of their preferences regarding the means and formats of access to content. This protocol is available for access through the following electronic address: https://osf.io/aunkh/ with https://doi.org/10.17605/OSF.IO/AUNKH . Conclusion Data analysis will help to identify potentialities and limitations in strategies for accessing information about HIV/AIDS by adolescents and young people. This scoping review can foster knowledge about information needs, guiding the creation of more effective content, supporting health decision-making and strengthening communication between professionals, users and institutions, contributing to the access of reliable data.

Dozens of researchers will move to France from US following high-profile bid to lure talent

Chemoenzymatic synthesis of pentalenolactones via stereoselective Riley oxidation by engineered P450BM3

Experiences and coping strategies among patients with mild COVID-19 who develop post COVID conditions at a primary care centre

Associations of perioperative depression with sleep quality and physical activity levels in patients undergoing elective cardiac surgery: A prospective observational study

Background Perioperative depression is very common in patients undergoing surgery, especially major surgeries. Previous studies have shown that perioperative depression could have a negative impact on postoperative recovery and quality of life. However, few papers have focused on the depressive characteristics of patients undergoing cardiac surgeries. Therefore, the objective of this study was to prospectively investigate the incidence of depression and its associations with sleep quality and physical activity levels in patients undergoing cardiac surgeries. Methods A total of 100 consecutive cardiac surgery patients were prospectively enrolled in the study. Perioperative depression was measured using the Patient Health Questionnaire-9 (PHQ-9). Sleep quality and physical activity levels were assessed using the Athens Insomnia Scale (AIS) questionnaire and the International Physical Activity Questionnaire-Short Form (IPQA-SF), respectively. All the data were collected and recorded preoperatively and at postoperative days 7 and 30. Independent-samples t tests and Spearman correlation analysis were used to explore the associations of depression status with sleep quality and physical activity levels. Both univariable and multivariable logistic regression were used to detect the risk factors for depression. Results The incidence of depression increased from the preoperative level (34%, 0.27–0.46), peaked at postoperative day 7 (51%, 0.41–0.61) and slightly decreased to (47%, 0.38–0.57) at postoperative day 30. Significantly higher preoperative AIS scores were found in patients with depression than in nondepressed patients (8.00 ± 1.39 vs. 5.32 ± 1.99, p  < 0.001). Moreover, patients with depression had significantly lower preoperative IPAQ-SF scores than did those without depression (948.32 ± 332.57 vs. 1461.65 ± 380.59, p  < 0.001). Spearman correlation analysis indicated that preoperative depression scores were strongly correlated with AIS scores (r = 0.64, p  < 0.001 ) and moderately correlated with IPAQ-SF scores (r = −0.44, p  < 0.001). Risk factors for preoperative depression were age, employment status, education level, NYHA class, AIS and IPAQ-SF scores. Conclusions Our study suggests significant associations of perioperative depression with sleep quality and physical activity levels in patients undergoing elective cardiac surgery. Patients with better sleep quality and higher levels of physical activity were significantly less likely to experience depression during the perioperative period. Trial registration This trial was registered on November 29, 2024, in the Chinese Clinical Trial Registry (ChiCTR2400093150).

Experimental quantification of hydrogen content in the Earth’s core

Abstract Earth’s core has long been speculated to be the largest reservoir of hydrogen (H) on the planet. However, current estimates of its H content involve substantial uncertainties, due to the challenge of quantifying H under extreme conditions. Here, we perform superliquidus metal-silicate partitioning experiments on H using laser-heated diamond anvil cells, and combine it with atom probe tomography. The direct observation of H at silicon- and oxygen-rich nanostructures in the iron alloy indicates coupled sequestration of silicon, oxygen and hydrogen into Earth’s core during its formation. With the observed molar Si/H ratio close to unity, Earth’s core is estimated to contain 0.07-0.36 wt.% H, equivalent to 9-45 oceans of water. Such an amount would require the Earth to obtain the majority of its water from the main stages of terrestrial accretion, instead of through comets during late addition.

Real-world evaluat ion of hybrid Green AI for sustainable and efficient smart supply chain distribution

Abstract This paper proposes a hybrid Green AI framework for achieving sustainable physical distribution in smart supply chains. The framework integrates real-world geospatial data, multi-objective optimization, and meta-inference algorithms. It aims to reduce transportation costs, delivery times, fuel consumption, and CO₂ emissions while maintaining operational efficiency, in line with Sustainable Development Goals 11 and 13. The new MOIAC algorithm enhances ant colony optimization by incorporating environmental weighting into pheromone updates. Real-world validation utilizes Google Maps API data from 19 Egyptian cities, with demand modeled using a Zipf distribution (α = 0.9). OR tools serve as a high-fidelity proxy to simulate the performance of MOIAC and MOIPS under real-world conditions. The results show a 26.7% reduction in total distance, operating costs, and CO₂ emissions compared to baseline methods, with MOIAC achieving the lowest average response time (120 ms). Comparisons with six algorithms—including Greedy, PSO, ACO, and Genetic—confirm the superiority of the proposed approach. This framework demonstrates how green AI and geospatial intelligence can contribute to theoretical optimization and practical logistics, providing a scalable, environmentally friendly, and operationally efficient solution for modern supply chain distribution.

Current practice in prescribing footwear and insoles to reduce the risk of neuropathic plantar forefoot ulceration and re-ulceration in people with diabetes

Background Footwear and insoles are frequently used to offload the neuropathic diabetic foot at risk of ulceration and re-ulceration. This study aims to explore the prescription habits of Australian pedorthists and the variations in footwear and insole design due to variations in foot pathology, comorbidities and patient-specific factors consideration. Methods An online survey link was sent to Australian pedorthists (n = 42), who were asked to answer questions relating to four hypothetical cases exploring current footwear and insole prescribing habits. Qualtrics research and data analysis software was used for the online survey and data analysis tool. Results Custom-made footwear was commonly prescribed in more complex cases, with recommendations ranging from 47% to 80% across scenarios (e.g., 80% in Case-4). In simpler cases, prefabricated medical-grade footwear with modifications was more frequently recommended (e.g., 53% in Case-1). Custom-made insoles were recommended by 84% to 100% of participants across all cases. Variations in prescriptions were largely influenced by differences in pathology, comorbidities, and individual patient preferences. Common barriers to patient adherence included concerns about appearance, bulkiness, and difficulty putting on or removing the footwear. To address these, pedorthists employed strategies such as involving family members in design choices, offering dual-purpose footwear (e.g., for indoor and outdoor use), incorporating culturally or gender-sensitive designs, and using in-shoe pressure mapping to demonstrate clinical benefits. Discussion and conclusion Australian pedorthists follow national and international guidelines for footwear and insole prescriptions with some variations when they encounter patient-specific factors such as preferences and lifestyle. The majority of them follow the best practices when evaluating the efficacy of the recommended devices, such as in-shoe pressure mapping systems. They also employ various practical techniques to increase adherence towards improved patient outcomes by engaging family or partners and through motivational interviews and interdisciplinary team approaches.

Virus glycoprotein nanodisc platform for vaccine analytics

Abstract Transmembrane glycoproteins of enveloped viruses are targets of neutralizing antibodies and essential vaccine antigens. mRNA-LNP technology allows in vivo expression of transmembrane glycoproteins, but in vitro biophysical characterization of transmembrane antigens and analysis of post-immunization antibody responses typically rely on soluble proteins. Here, we present a platform for assembling transmembrane glycoprotein vaccine candidates into lipid nanodiscs. We demonstrate the utility of nanodiscs in HIV membrane proximal external region (MPER)-targeting vaccine development by binding assays using surface plasmon resonance (SPR), ex vivo B cell sorting with fluorescence-activated cell sorting (FACS), and by determining the structure of a prototypical HIV MPER-targeting immunogen nanodisc in complex with three broadly neutralizing antibodies (bnAbs), including MPER bnAb 10E8, to 3.5 Å by cryogenic electron microscopy (cryo-EM), providing a template for structure-based immunogen design. To demonstrate general applicability we characterize Ebola virus glycoprotein nanodiscs. Overall, the platform offers a tool for accelerating development of next-generation vaccines.

Integrative profiling of transcriptome and H3K27ac modification reveals changes associated with BCG-induced trained immunity in bovine immune cells

The multi-faceted effects of technology-driven productivity surge in the crop & livestock sector in Greece: Evidence from the FABLE Calculator

This paper the effects of a technology-driven increase in crop and livestock productivity on key agricultural, land-use, and environmental indicators in Greece, using the FABLE (Food, Agriculture, Biodiversity, Land Use, and Energy) Calculator. Through empirical evidence and sophisticated modelling techniques, we analyze the intricate interplay between agricultural productivity and environmental sustainability. Our scenario-based projections show that higher agricultural productivity substantially reduces greenhouse gas emissions, primarily through lower livestock emissions, diminished pressure on pastureland, and increased emission withdrawals from land-use changes. Enhancing productivity in the livestock and crop sector reduces GHG emissions from agriculture by 29% until 2030 and 62% until 2050, compared to a business-as-usual scenario. The result is amplified when we embed the productivity surge in a holistic transformational strategy following Greece’s national commitment including a shift to healthy dietary consumption. Moreover, costs decline markedly, by almost 50% in the long run, driven mainly by the reduction in pesticide use. In addition to its empirical findings, this paper delineates policy recommendations to support cutting-edge technologies within the Greek agricultural sector, focusing on horizontal and vertical measures. We highlight key precision agriculture technologies that align with current trends in Greece, particularly in the areas of drone applications, advanced sensors, and variable rate technology, alongside innovations in precision livestock management. Overall, our findings demonstrate that boosting agricultural productivity can generate a double dividend—lower emissions and enhanced competitiveness—particularly when supported by holistic policy measures.