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The structure of the proteins of Camp Hill virus
Camp Hill virus (CHV), a newly identified henipavirus, was recently discovered in northern short-tailed shrews in Camp Hill, Alabama. This marks a significant event as it is the first henipavirus ever reported in North America. The significance of henipaviruses lies in their ability to cause severe and often fatal diseases, such as encephalitis and respiratory illness, with a high mortality rate in both humans and animals. The emergence of new henipavirus strains, like CHV, amplifies concerns about the possibility of future zoonotic spillovers—where diseases are transmitted from animals to humans. Because henipaviruses can be highly contagious and have no specific antiviral treatment, their emergence poses a potential threat to public health. The major proteins of CHV include attachment glycoprotein, fusion protein, X protein, C protein, matrix protein, nucleocapsid protein, phosphoprotein, and RNA polymerase. In our study, we focused on determining the three-dimensional structure of these major proteins, providing crucial insights into how they function at the molecular level. Understanding the precise structure of these proteins is vital, as it can inform efforts to block the virus’s ability to infect cells. Proteomic analysis confirmed that the proteins of CHV is similar to the proteins of Sollieres shrew parahenipa virus, Ninorex virus, Melian virus, Lechodon virus and Langya virus. We identified the B-cell and T-cell epitopes of these proteins. By characterizing these epitopes, our research contributes to the design of targeted vaccines that could stimulate a robust immune response against CHV. The identification of these epitopes also allows us to understand how the virus interacts with the immune system, which is essential for designing vaccines that can elicit both humoral and cellular immunity. Our study would lead to development of novel vaccines to protect against CHV.
A Sodium Iron Phosphate Nanocatalyst-Regulated High-Mobility Ion Reservoir Enables Tumor-Selective Immunotherapy
Computational discovery of BRD4 inhibitors for neuroblastoma therapy using pharmacophore screening and molecular simulations
Abstract BRD4 (“Bromodomain-containing protein 4”), a recognized gene regulator, is an attractive target for therapeutic development, particularly for the management of neuroblastoma. An integrated pharmacoinformatic strategy for the development of new BRD4 inhibitors is examined in this research. Pharmacophores were used to digitally screen five databases, and the current study aims to determine the best binding modes by docking the screened hits to the BRD4 active site. Using the BRD4 protein co-crystal ligand (73B) (PDB ID: 4BJX) as a template, pharmacophore hypotheses were produced. Five databases were subjected to a pharmacophore-based virtual screening process, and 1089 hits that satisfied the screening requirements were selected for docking against the BRD4 receptor by using the SP module of the Glide tool. The top ten docked compounds with the highest binding affinities, ranging from − 9.623 to − 8.894 kcal/mol, were selected. Further, the biological activity and ADMET analysis revealed that the selected compounds have values that fall in the acceptable range. The protein-ligand complexes’ stability was verified by performing molecular dynamics (MD) simulations of the binding positions of the top two compounds against the BRD4 receptor. The stability and binding free energies of the compounds indicate that these compounds may function as lead compounds to affect the biological activity of BRD4 in the in vitro studies.
Retraction: Ginkgo biloba Extract Decreases Non-Small Cell Lung Cancer Cell Migration by Downregulating Metastasis-Associated Factor Heat-Shock Protein 27
Predictive value of tidal volume and peak inspiratory pressure in normal frequency jet ventilation
Simulating the impact of methadone prescribing and pharmacy dispensing on opioid treatment and overdose in New York State: A study protocol for an agent-based modeling study
Amid the ongoing overdose crisis, U.S. lawmakers are considering policy reforms that could significantly change availability and accessibility of methadone treatment (MT) for opioid use disorder (OUD). However, uncertainty remains about which potential changes will lead to the greatest health benefits while minimizing unintended harms. In this protocol, we describe a planned NIH-funded study (R21DA061660) to simulate alternative MT delivery scenarios currently being considered in U.S. policy discussions, and estimate their impact on population-level rates of treatment initiation and retention and opioid overdose across different sociodemographic groups. We will use an agent-based model focused on 16 counties in NY State to simulate two alternative policy scenarios compared to the current status quo of opioid-treatment program (OTP) delivered MT: 1) office-based prescribing by addiction-certified providers with pharmacy and OTP dispensing; and 2) office-based prescribing by general practitioners with pharmacy and OTP dispensing. Agents will represent individuals with OUD and we will simulate access to MT based on alternative policy scenarios (e.g., locations of existing OTPs vs. provider offices and pharmacies). Probabilities of treatment initiation, retention, and opioid overdose will be informed by estimates from the scientific literature and administrative datasets from NY State. Multiple implementation scenarios will be considered to account for potential variation in adoption of office-based methadone by patients, providers, and pharmacies. To ensure relevance to directly impacted communities and policy makers, the study involves a collaboration between academic researchers and NY State government partners and relies on input from an Expert Advisory Board of people with lived and living experience with methadone, addiction medicine, and policy experts. Findings will be disseminated via a public dashboard. This study will inform ongoing policy discussions and shed light on the potential of researcher-policy partnerships to promote evidence-based policies that can reduce overdose and improve population health.
Competitive Cation Exchange and Etching Processes in Metal Sulfide Nanoparticles from Anion/Ligand Cooperativity and Exogenous Cations
Characterization of a phosphoinositide-binding protein containing a PHOX homology domain in the malaria parasite Plasmodium falciparum
Editorial Note: Does menstrual hygiene management and water, sanitation, and hygiene predict reproductive tract infections among reproductive women in urban areas in Ethiopia?
An Electron Donor–Acceptor Complex-Driven Strategy Enables Initiation of Photoiniferter RAFT Polymerization from Amines, Carboxylic Acids, and Alcohols
Image complexity-based fMRI-BOLD visual network categorization across visual datasets using topological descriptors and deep-hybrid learning
Neural mechanisms underlying reward processing and social cognition: A replication study with a Japanese sample
Neural functions underlying reward processing and social cognition play a critical role in everyday decision-making. Given that these processes may be shaped by cultural factors, it is essential to examine their cross-cultural generalizability. In this study, we used functional MRI to scan native Japanese speakers as they performed two well-established experimental paradigms: the Monetary Incentive Delay (MID) task for reward processing and the Theory of Mind (ToM) task for social cognition. We successfully replicated previous findings. Specifically, in the MID task, reward expectation and reward outcome were associated with neural activity in the ventral striatum and ventromedial prefrontal cortex. In the ToM task, social cognition was linked to activation in the temporoparietal junction. Notably, the posterior cingulate cortex was engaged in both tasks, suggesting its integrative role across cognitive domains. Together, these results replicate and extend earlier work, supporting the cross-cultural generalizability of the neural mechanisms underlying reward and social cognition, and further validating our fMRI protocol for future research.
Carbene Zipper Reaction for Cascade π-Extension
Biocontrol efficacy of Pochonia chlamydosporia against root-knot nematode Meloidogyne javanica in eggplant and its impact on plant growth
GMO approvals under pressure: How climate shocks shape policy across nations
While GMO cultivation is often viewed as a strategy to buffer agriculture against climate change, its regulation remains controversial across countries. This study explores how climate shocks influence global patterns of genetically modified organism (GMO) approval. We develop a theoretical model and predict that climate shocks reduce the likelihood of GMO approvals in countries lacking a comparative advantage in GMO production. To test this, a local projection method is used to estimate the cumulative effects of climate shocks on approval activity. The results show that climate shocks tend to delay approvals, especially in countries with low GMO development capacity. These findings suggest that climate change may amplify regulatory inertia and intensify global policy divides on GMOs, raising concerns about the adaptability of global food systems under increasing environmental stress.
Synergistic Programming of Macrophages by Hybrid Glycocalyx-Inspired Nanoparticles for Adoptive Cell Therapy
Lysosomal homeostasis regulates myocardial ischemia-reperfusion injury through autophagy pathway
Exploring perceived barriers, facilitators, and team roles in addressing prescribing cascades in primary care teams: Insights from interprofessional focus groups
Background Prescribing cascades are common contributors to medication-related harm. Primary care clinicians who practice in interprofessional teams may be well positioned to address cascades in practice; although, the factors that influence their ability to do so in this particular setting are largely unknown. Our study aimed to explore perceived barriers and facilitators that influence the identification, investigation, and management of prescribing cascades as experienced by primary care teams and each profession’s role in addressing cascades. Methods Physicians, nurse practitioners, and pharmacists practicing in primary care teams in Ontario, Canada participated in a series of intra-professional and interprofessional focus groups. The focus groups explored clinician perspectives about factors that influence their ability to address cascades. Discussion and analyses were guided by the Theoretical Domains Framework and the Behaviour Change Wheel. Results Sixteen clinicians participated in four intra-professional and one interprofessional focus groups. Thematic analysis resulted in two main themes. First, multiple factors influenced primary care teams’ ability to address prescribing cascades. Cascades were considered complex in terms of the processes required to identify, investigate, and manage them. Second, the role each profession was able or willing to play varied based on their capability, opportunity, and motivation. Nurse practitioners and physicians felt best equipped to prevent cascades within a patient visit, while pharmacists endorsed being able and willing to address existing cascades. Conclusion The ability to address prescribing cascades is influenced by multiple factors and varied across professions within interprofessional primary care teams. The study findings provide additional information necessary for the design of future interventions to assist clinicians with addressing cascades. Future research should engage patients, caregivers, and community pharmacists to further explore their roles in addressing prescribing cascades.