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Enhancing the strain limit of stretchable organic transistors by Schottky barrier-dominated transport mode
Barriers and facilitators to hepatitis C patient engagement: Interview study with general practitioner champions in England
There are people living with a previously diagnosed chronic hepatitis C infection who have been lost to follow up, and people who may have undiagnosed hepatitis C. General Practitioners (GPs) could help to support these patients into care, via offering testing, referring to secondary care, and facilitating prescribing. We conducted semi-structured interviews with 14 GPs, most of whom work with local Operational Delivery Networks (ODNs) with funding from the NHS England Viral Hepatitis Programme as hepatitis C GP Champions. A thematic analysis with a multi-level model (system, provider-levels) and the COM-B (capability, opportunity, motivation: behaviour) framework were used to identify barriers and facilitators to patient identification and (re)engagement. System-level barriers included a lack of hepatitis C incentives for GPs, pressures facing primary care, challenges searching patient records, and a perception that better processes are needed to re-engage patients lost to follow up. GP Champions expressed challenges coordinating regional patient (re)engagement strategies, but also reported successful collaborations with ODNs, other services, and outreach/community partners. Provider-level barriers for all GPs included lack of knowledge of hepatitis C and difficulty managing patient conversations (capability); and lack of GP capacity and difficulty contacting patients (opportunity). Provider-level facilitators included that primary care is holistic and accessible to patients (opportunity), and GP Champions reported how their roles have granted workload capacity and the support of other GPs/healthcare professionals (opportunity) and increased their feelings of personal reward (motivation). Interviewees’ reflections on shared care and their suggestions for the future of hepatitis C care are also presented. This study demonstrates numerous benefits to employing GP Champions to find and offer testing to patients, however system-level barriers are notably persistent. Interviewees said there is further need to address patients holistically, and joint efforts between services/sectors were suggested as means to overcome system and provider level barriers.
Forecasting USD PKR exchange rates using Urdu social media sentiment
Photosystem I-independent oxygenic photosynthesis in cyanobacteria
Abstract Oxygenic photosynthesis generates ATP and NADPH via linear electron flow from water to NADP + , a process thought to require photosystem I (PSI) for reductant formation. Here we demonstrate that oxygenic photosynthesis can operate without PSI in the cyanobacterium Synechocystis sp. PCC 6803. Using genetic engineering and adaptive laboratory evolution, we obtained PSI-deficient lineages capable of photoautotrophic growth, inorganic carbon fixation, and light-driven oxygen evolution. PSI-independent photoautotrophy arose from co-mutations in at least two proteins, including the translation elongation factor G (FusA), and required a functional NDH-1 complex. We propose that the light-driven electron transport in the evolved strains is reorganised in two branches: one involving terminal oxidases to generate proton motive force, and a second in which reverse NDH-1 activity exploits this gradient to produce reductant. These findings uncover unexpected plasticity in the thylakoid electron transport network and prompt a reassessment of the canonical requirement for PSI in oxygenic photosynthesis.
Heptapharmacological activity of Quercetin-3-O-phosphate against lung cancer pathways
Lung cancer is one of the leading causes of cancer-related deaths globally, with smoking being the primary risk factor, though environmental exposures and genetic mutations also play significant roles. Lung cancer arises when abnormal lung cells grow uncontrollably, leading to over 2 million new cases and nearly 1.8 million deaths globally. Drug resistance, especially to targeted therapies, is a key challenge, as tumours often adapt and become unresponsive. Multitargeted drug design, which targets multiple pathways involved in tumour growth, offers a promising solution to overcome resistance and improve treatment efficacy. In this study, we identified several lung cancer–associated proteins: CK2, Ran–Importin β complex, HNGF, Human Survivin, CRK-II adaptor protein, AKR1B10, and tRNA dihydrouridine synthase 2, with respective PDB IDs 1JWH, 1IBR, 1SG1, 1XOX, 2DVJ, 4XZL, and 4XP7. We conducted molecular docking using DrugBank’s library, employing HTVS, SP, and XP, followed by pose processing with MM/GBSA. Our multitarget docking analysis identified Quercetin-3-O-Phosphate as the top compound, a quercetin derivative found in fruits and vegetables such as onions, apples, berries, broccoli, and citrus. The compound showed docking and MM/GBSA scores ranging from −5.835 to −11.627 Kcal/mol and −14.28 to −47.07 Kcal/mol, respectively, and the key interacting residues with their counts include 10ASP, 9LEU, 9LYS, 7ALA, 7ARG, 7TYR, 6GLN, 5ASN, 5GLU, 5ILE, and 5VAL. We also performed and analysed DFT and pharmacokinetics in detail, which supported its further evaluation as it met all the required criteria. We conducted a 5 ns WaterMap simulation, which confirmed the interactions and highlighted key hydration sites that support the complex’s stability. A 100 ns MD simulation using the TIP3P water model showed minimal deviation and fluctuations, indicating stable interactions and the trajectories used for MM/GBSA calculations, assessing binding free, which reinforced the stability of the complexes and helped rank the best candidates. All results indicate that Quercetin-3-O-Phosphate holds strong potential for lung cancer treatment, though experimental validation is needed for clinical confirmation.
Sociodemographic and health determinants of handgrip strength in adults living in rural Ecuador
Resting-state electroretinography reveals pathological retinal oscillations in retinitis pigmentosa mice and patients
Abstract Retinal remodeling occurs in both retinitis pigmentosa and age-related macular degeneration. However, it is still unknown whether spared retinal circuits are also functionally altered. Functional changes have been observed in animal models of retinitis pigmentosa, including the emergence of bursting oscillatory activity in retinal ganglion cells. Yet, comparable oscillatory activity, or other functional alterations, has not been demonstrated in patients. To address this gap, here we report a non-invasive corneal neurotechnology measuring in-vivo resting-state electroretinography and analyzing its frequency content and temporal characteristics to identify biomarkers of functional remodeling. We document that retinal remodeling induces bursting oscillatory activity in-vivo in retinitis pigmentosa mouse models and translate these results to patients. Moreover, we showed in mice that bursting oscillatory activity can be pharmacologically modulated in-vivo. Furthermore, reducing this oscillatory activity increases retinal excitability to electrical stimulation. These results are crucial for a better understanding of retinal degeneration and contribute to sight restoration efforts.
Modal analysis of the vibrational characteristics of a 12U nanosatellite in various deployers
Modulating the interfacial solvation structure to promote hydroxyl migration for alkaline hydrogen oxidation
Trade induced extinction risk footprints by European financial institutions
Abstract Biodiversity loss is increasingly recognized as a source of systemic financial risk. The financial sector enables economic activities that exert pressure on ecosystems, sometimes far from where capital is held, so institutions in one region can enable biodiversity loss elsewhere by financing seemingly harmless sectors with value-chain links to harmful activities. We establish a novel correspondence matrix linking 104 environmental pressures to 124 IUCN biodiversity threats, and combine it with the GLORIA input–output model to quantify species extinction-risk for 164 countries. Particulate matter, land-use change, and nitrogenous gases are the most damaging pressures, exerted mainly by agriculture, manufacturing, and construction. Seventy-four countries are net importers of extinction risk and twenty-three net exporters; all twelve European countries analysed are importers, with approximately 40% of their financial assets linked to extinction-risk sectors. Because these pressures are so embedded in production, a 1% reduction in the extinction-risk footprint propagates almost one-for-one through the economy: output falls by about 0.88% on average, while firms’ capacity to service debt weakens as revenues drop but interest obligations hold fixed. This exposes how structurally dependent financial systems are on nature-harming activity, supporting efforts to disclose and reduce holdings of assets linked to biodiversity loss.
Molecular mechanisms of mitochondrial Ca2+ exchanger NCLX
Abstract Mitochondrial Ca²⁺ homeostasis is maintained through coordinated influx and efflux processes, with NCLX long recognized as the primary Ca²⁺ extruder operating via Na⁺/Ca²⁺ exchange. Here, we report cryo-EM structures of rat NCLX in cytosolic-facing occluded and open states. The central transmembrane (TM) domain of NCLX comprises ten helices arranged in two inverted, structurally similar halves, with two α-repeats forming a central ion-binding pocket. Peripheral TMs 1 and 6 are loosely associated with the core and likely mediate alternative access to this site. These structural features closely resemble those of NCXs, indicating a conserved ion exchange mechanism. While NCLX retains the canonical Ca²⁺-binding site, it lacks several key Na⁺-binding residues found in NCXs, suggesting broader ion selectivity. Consistently, cell-based Ca²⁺ uptake assays show that NCLX mediates Ca²⁺ exchange using Na⁺, K⁺, Li⁺, and potentially protons as counterions. Based on the structural symmetry of NCLX and its bidirectional exchange capability, we propose a matrix-facing model and an alternating-access mechanism in which TMs 1 and 6 undergo sliding motions to enable ion exchange between cytosolic and matrix sides, analogous to NCX. These findings provide a structural and mechanistic framework for understanding NCLX-mediated Ca²⁺ transport in mitochondria.
Effect of probiotic Bacillus cereus PKA18 on the overall growth, gut microbiome, and immunity in Clarias magur (Hamilton, 1822)
A paired electrolysis for hydroxymethanesulfonate synthesis using sulfide waste as the sulfur source
An edge-AI framework with graph transformer learning for resilient microgrid topology attack identification
Segmental duplications and supernumerary chromosomes drive antifungal drug resistance in Candida auris
Correction: Examining the effects of cigarette smoke on mouse lens through a multi OMIC approach
Engineering trispecific IL-2 receptor agonistic antibodies through geometry optimization for enhanced Treg targeting
Lactiplantibacillus plantarum OP5: a novel strain with antioxidant properties for quality improvement of fermented sausage
Genetic drivers of etiologic heterogeneity in thyroid cancer
Abstract Thyroid cancer is the most common endocrine malignancy, yet its biological underpinnings remain incompletely understood. Here we show that common risk alleles for thyroid cancer point to distinct biological pathways underlying disease susceptibility. We perform a multi-ancestry genome-wide association meta-analysis of thyroid cancer (16,167 cases and 2,430,374 controls), identifying 51 independent loci, including 21 not previously reported. By integrating these loci with genetic associations for 151 thyroid-cancer-related traits, we identify pleiotropic mechanistic clusters linked to thyroid function, oncogenic pathways, and mixed physiological function. Two thyroid-specific clusters, associated with thyroid stimulating hormone or thyroid growth and function, are enriched in thyroid tissues. Oncogenic clusters include DNA repair ( ATM , CHEK2 , TP53 ) and telomere maintenance ( TERT ) genes, implicating shared cancer mechanisms. Cluster-specific polygenic scores are associated with thyroid disease, cancer, and metabolic traits across ancestry groups, suggesting distinct genetic subtypes of thyroid cancer risk and supporting pleiotropy-based approaches to genetic risk stratification.