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Fabrication of curcumin-loaded emulgel and its application in low-calorie and functional cake
Direct B–H Bond Activation Polymerization of Boron Clusters
Revitalizing orphan crops to combat food insecurity
Root cause analysis investigation of visible particulates in therapeutic protein drug products using morphologically directed Raman spectroscopy
Abstract Visible particulate (VP) matter in therapeutic protein drug products (DPs) is a quality attribute that can impact product efficacy and patient safety across the product lifecycle. This study evaluates Morphologically Directed Raman Spectroscopy (MDRS) for detecting and characterizing VPs in therapeutic protein DPs. MDRS combines morphological and chemical analyses, which are essential for root cause analysis (RCA) during incident investigations of VP formation. We evaluated MDRS using polystyrene (PS) microsphere standards, candidate reference materials from the US National Institute of Standards and Technology (NIST), and stressed therapeutic protein DPs, insulin lispro and rituximab. Using MDRS, VPs were imaged and chemically characterized in insulin or rituximab drug products with varying morphologies and ranged from 100 to 400 μm in diameter. The intensity of Raman spectral peaks varied with VP size, transparency, morphological complexity, and between therapeutic protein drug classes. Principal component analysis (PCA) of morphological features (e.g., size, shape, and transparency) revealed that NIST ethylene tetrafluoroethylene (ETFE) particles displayed a range of morphologies, akin to stressed therapeutic protein VPs. These results highlight the potential of combining morphological analysis with Raman spectroscopy to support RCA in therapeutic protein DPs for both pre- and post-market quality assessments.
Polymerase theta repairs persistent G1-induced DNA breaks in S-phase during class switch recombination
Abstract Non-homologous end joining (NHEJ) is the primary pathway for repairing G1 phase-induced DNA double-strand breaks (DSBs) during immunoglobulin heavy chain ( Igh ) class switch recombination (CSR) in B lymphocytes. In B cells lacking NHEJ (XRCC4) or DSB end protection (SHLD1), end joining during CSR proceeds through an alternative end-joining pathway. Polymerase theta (Pol θ) is widely regarded as a mediator of this pathway, essential for repairing replication-associated DSBs during mitosis when homologous recombination is unavailable. In this study, we examined CSR in primary B cells lacking XRCC4, SHLD1, and/or Pol θ, revealing two repair pathways: Pol θ-independent productive switching and Pol θ-dependent unproductive switching characterized by end resection, inversion and microhomology. Furthermore, we show that Pol θ-mediated repair under NHEJ-deficiency coincides with G1-to-S phase transition and occurs independently of RHINO and PLK1. Thus, in the absence of NHEJ, Pol θ repairs persistent G1-phase DSBs during S-phase rather than mitosis.
Pelvic floor muscle exercise practice and its determinants among postpartum women in Central Ethiopia: as a strategy for preventing pelvic floor disorders
Enzymatic Anti-Baldwin Ring-Closure Cascade for Fused Bicyclic Ether Formation
H3K4me2 orchestrates H2A.Z and Polycomb repressive marks in Arabidopsis
Bacterial vaginosis, vaginal Candida colonization and antifungal susceptibility patterns in pregnant women of eastern Ethiopia: a prospective study
Strong Coupling of Iridium and Boron–Carbon-Nitride Support for Enhanced Acidic Water Oxidation
Integrating axis quantitative trait loci looks beyond cell types and offers insights into brain-related traits
Development and validation of a nomogram for predicting 30-day mortality in patients with severe acute pancreatitis and pneumonia
Conformational plasticity across phylogenetic clusters of RND multidrug efflux pumps and its impact on substrate specificity
Abstract Antibiotic efflux plays a key role for the multidrug resistance in Gram-negative bacteria. Multidrug efflux pumps of the resistance nodulation and cell division (RND) superfamily function as part of cell envelope spanning systems and provide resistance to diverse antibiotics. Here, we identify two phylogenetic clusters of RND proteins with conserved binding pocket residues and show that the transfer of a single conserved residue between both clusters affects the resistance phenotype not only due to changes in the physicochemical properties of the binding pocket, but also due to an altered equilibrium between the conformational states of the transport cycle. We demonstrate, using single-particle cryo-electron microscopy, that AcrB and OqxB, which represent both clusters, adopt fundamentally different apo states, implying distinct mechanisms for initial substrate binding. The observed conformational plasticity appears phylogenetically conserved and likely plays a role in the diversification of the resistance phenotype among homologous RND pumps.
Explainable machine learning and ensemble models for predicting fresh properties of self consolidating concrete
Palladium-Catalyzed Asymmetric Hydrogenolysis of Epoxides
Exploring organic chemical space for materials discovery using crystal structure prediction-informed evolutionary optimisation
Abstract Organic molecular crystals offer a broad spectrum of potential applications. The vast number of possible molecules is both an opportunity and a challenge, because of the prohibitive expense of exhaustively searching chemical space to find novel molecules with promising solid-state properties. Computational methods can be applied to direct experimental discovery programmes using high-throughput or guided searches of chemical space. However, to date, such approaches have largely focused on molecular properties, ignoring the often significant effects of the arrangement of molecules in their crystal structure on the molecule’s effectiveness for the chosen application. Here, we present an evolutionary algorithm for searching chemical space that incorporates crystal structure prediction into the evaluation of candidate molecules, allowing their fitness to be evaluated based on the predicted materials’ properties. As a demonstration, the crystal structure-aware evolutionary algorithm is applied here to a search space of organic molecular semiconductors, demonstrating that the inclusion of crystal structure prediction in the fitness assessment outperforms searches based on molecular properties alone in identifying molecules with high electron mobilities.
Workplace stressors and burnout among healthcare professionals: Insights from the pandemic and implications for future public health crises
Abstract This study evaluates the prevalence of burnout among healthcare professionals (HCPs) during the COVID-19 pandemic in Iran and examines its association with key occupational stressors (workload, job control, and leadership communication). Furthermore, it proposes relevant organisational interventions for future pandemic preparedness. A cross-sectional survey of HCPs (N = 723) was conducted in four hospitals in Tehran during the third peak of the COVID-19 pandemic in Iran, including the Copenhagen Burnout Inventory and items on perceived workload, job control, and leadership communication. The study found that 67.41% of HCPs reported substantial symptoms of burnout (moderate-to-high burnout, i.e. CBI ≥ 50), with a mean score of 59.6 points. The prevalence of burnout (CBI ≥ 50) was prominent across all three dimensions—personal, work, and patient-related—at 72.86%, 69.87%, and 65.37%, respectively. The analysis demonstrated significant associations between burnout and the three foundational workplace stressors. Multivariate linear regression analysis showed that frontline, female, and married HCPs reported the highest levels of burnout. This study provides practical implications for healthcare organisations and policy makers, highlighting the need for targeted organizational interventions that could mitigate burnout during ongoing and future health crises.