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A novel combinatorial approach integrating experimental and computational analysis of antioxidant activity: Evaluating catechin and L-ascorbic acid in serum

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality globally, with oxidative stress playing a pivotal role in its progression. Free radicals produced via oxidative stress contribute to lipid peroxidation, leading to subsequent inflammatory responses, which then result in atherosclerosis. Antioxidants inhibit these harmful effects through their reducing ability, thereby preventing oxidative damage. In this study, we introduce computational models simulating hydrophilic and hydrophobic serum environments. We optimized the Ferric Reducing Ability of Plasma (FRAP) assay at a microscale level to evaluate the antioxidant activity of L-ascorbic acid (vitamin C) and catechin, a phytochemical found in green tea, in normal and hypertriglyceridemic serum. Hypertriglyceridemic serum, characterized by increased hydrophobic lipid content, provides a model to examine the impact of serum triglycerides on antioxidant activity. Additionally, we employed computational models using the Gaussian software to simulate the hydrogen atom transfer (HAT) mechanism, calculating free energy changes and bond dissociation energy (BDE) to assess the antioxidant potency of the studied compounds in both hydrophilic and hydrophobic environments. The computational results align with the experimental finding offering a unique combinatorial approach to assess antioxidant activity in both normal and hypertriglyceridemic serum, with potential implications for clinical interventions.

Enhancing the visual environment of urban coastal roads through deep learning analysis of street-view images: A perspective of aesthetic and distinctiveness

Urban waterfront areas, which are essential natural resources and highly perceived public areas in cities, play a crucial role in enhancing urban environment. This study integrates deep learning with human perception data sourced from street view images to study the relationship between visual landscape features and human perception of urban waterfront areas, employing linear regression and random forest models to predict human perception along urban coastal roads. Based on aesthetic and distinctiveness perception, urban coastal roads in Xiamen were classified into four types with different emphasis and priorities for improvement. The results showed that: 1) the degree of coastal openness had the greatest influence on human perception while the coastal landscape with a high green visual index decreases the distinctiveness perception; 2) the random forest model can effectively predict human perception on urban coastal roads with an accuracy rate of 87% and 77%; 3) The proportion of low perception road sections with potential for improvement is 60.6%, among which the proportion of low aesthetic perception and low distinctiveness perception road sections is 10.5%. These findings offer crucial evidence regarding human perception of urban coastal roads, and can provide targeted recommendations for enhancing the visual environment of urban coastal road landscapes.

Beekeepers’ perceptions toward a new omics tool for monitoring bee health in Europe

Pressures on honey bee health have substantially increased both colony mortality and beekeepers’ costs for hive management across Europe. Although technological advances could offer cost-effective solutions to these challenges, there is little research into the incentives and barriers to technological adoption by beekeepers in Europe. Our study is the first to investigate beekeepers’ willingness to adopt the Bee Health Card, a molecular diagnostic tool developed within the PoshBee EU project which can rapidly assess bee health by monitoring molecular changes in bees. The Bee Health Card, based on MALDI BeeTyping®, is currently on level six of the Technology Readiness Level scale, meaning that the technology has been demonstrated in relevant environments. Using an on-line survey from seven European countries, we show that beekeepers recognise the potential for the tool to improve colony health, and that targeted economic incentives, such as subsidises, may help reduce cost being a barrier to the adoption and frequent use of the tool. Based on the description of the tool, 43% of beekeepers appear to be moderately confident in the effectiveness of the Bee Health Card. This confidence could increase if the tool was easy to use and not time consuming, and a higher confidence could also contribute to raising the probability of accepting extra costs linked to it. We estimate that, in the worst-case scenario, the cost per single use of the Bee Health Card should be between €47–90 across a range of European countries, depending on the labour and postage costs. However, the monetary benefits in terms of honey production could exceed this. In order to successfully tackle colony health issues, it is recommended using the BHC five times per year, from the end to the beginning of winter. Finally, we discuss the knowledge needs for assessing beekeeper health tools in future research.

Revolutionizing faculty’s intrinsic work motivation in China: A novel serial mediation model integrating value-based leadership, growth mindset, and teaching self-efficacy

This study presents a revolutionary understanding of how value-based leadership enhances the intrinsic work motivation of Chinese university faculty. A novel serial mediation model is introduced, highlighting the interplay between growth mindset and teaching self-efficacy in transmitting the impact of leadership to increased intrinsic motivation. Utilizing a comprehensive sample of 394 faculty members from across China, advanced SmartPLS 3.0 analytics were employed to validate the model. The results demonstrate a significant positive effect of value-based leadership on faculty intrinsic motivation, partially mediated by the sequential influence of nurturing a growth mindset and strong teaching self-efficacy. The findings provide fresh theoretical perspectives and practical strategies for researchers, university leaders, administrators, and policymakers seeking to elevate the intrinsic work motivation of China’s academic faculty to new levels.

Navigating adulthood: Exploring the transition needs of adolescents and young adults affected by Duchenne or Becker muscular dystrophy

For individuals with Duchenne or Becker muscular dystrophy (DMD and BMD, respectively), transitioning to adulthood presents significant challenges. Although considerable attention has been given to facilitating medical transitions due to the complexity of these conditions, less focus has been placed on other aspects of the transition, such as achieving independence. This study assessed the transition needs of people with DMD or BMD, exploring various domains including health, education, employment, living arrangements, transportation, daily activities, and independent personal life. Men with DMD or BMD participated in this cross-sectional study. Transition to adulthood was assessed using Transition Readiness Assessment for Young Adults with DMD. The questionnaire evaluates transitions in health care, education and employment, housing and transportation, activities of daily living, and independent life and autonomy. Factors associated with and predicting transition to adulthood were evaluated using Spearman’s correlations and multiple regression analysis. Forty-two people with DMD or BMD (mean age: 24.3±5.3) participated in this study. The transition domains in which most participants needed help were education and employment (52.5%) and activities of daily living (57.0%). Transition needs that stood out included palliative care (66.6%), employment and education support (76.1%), social worker consultation for housing assistance (76.1%), and assistive device consultation (64.2%). Mobility and breathing function did not correlate with transition level. Number of siblings positively correlated with and predicted most transition domains. Older age predicted only education and employment status. In conclusion, the analysis showed that the most problematic transition domains among people with DMD or BMD were activities of daily living and education and employment. In most transition domains, help needed did not decrease with age and was not affected by function. However, adolescents and adults with more siblings typically reported being more ready to transit to adult life.

A scoping review protocol on brain PaCO2 levels at altitude

Background Aeromedical transfer of patients with ischemic stroke to access hyperacute stroke treatment is becoming increasingly common. Little is known about how rapid changes of altitude and atmospheric pressure can impact cerebral perfusion and ischemic burden. In patients with ischemic stroke, there is a theoretical possibility that this physiologic response of hypoxia-driven hyperventilation at higher altitude can lead to a relative drop in PaCO2. This would ultimately result in cerebral vasoconstriction, and therefore worsening of the ischemic burden in patients with ischemic stroke. Currently, there are no specific recommendations in stroke guidelines for optimizing altitude of aeromedical transportation to minimize the rate of ischemic burden. In this scoping review, we aim to map the available literature that addressed whether PaCO2 changes with altitude. This would be the steppingstone for more in-depth analyses into the cerebral autoregulatory consequences of high altitude on cerebral ischemia to form future guidelines. Methods and analysis We will follow scoping review methods recommended by the Joanna Briggs Institute. Electronic databases MEDLINE, Embase, Web of Science, and Cochrane Central Register of Systematic will be systematically searched to identify articles that report on the acute response of PaCO2 on acute change in altitude. Two independent investigators will perform duplicate title and abstract screening and full-text review, followed by duplicate data extraction. We will present quantitative data using descriptive statistics. Key textual information will be synthesized in a tabular format Simple statistics on the frequency of papers, data will be presented via histogram. Ethics and dissemination This scoping review does not require ethical approval. The results of our scoping review will be published in academic medical journals and presented at medical conferences. The findings will highlight the current availability of literature on PaCO2 changes with altitude. Registration This scoping review protocol has been registered in Open Science Framework (DOI 10.17605/OSF.IO/UVK83).

Respectful maternity care and mistreatment: Women’s experiences during induction of labor and childbirth in Ghana

Background Most studies on respectful maternity care (RMC) and mistreatment of women have focused on intrapartum care with limited information on how women are treated during induction of labor (IOL), pre-labor phase of the maternity care continuum. Emerging multi-country evidence indicates that nearly 30% of women who undergo IOL do not consent to the procedure and constitutes a violation of their rights to optimal maternal health. This study explored women’s lived experiences of respectful care and mistreatment during IOL in a tertiary setting in Ghana. Methods This was a qualitative phenomenological study conducted between September 2021 to October 2021 in Ghana. The eligibility criteria comprised women, aged ≥ 18 years who underwent IOL with singleton gestations. Purposive sampling was employed in recruiting the study participants (n = 17). Data analysis was performed based on thematic content using the inductive qualitative analytic framework approach. Results Nearly all the participants (94.1%) were first-timers to IOL. In general, we determined mixed findings relating to the experiences of RMC (respectful versus disrespectful care). Some women experienced respectful care including effective communication, optimal counseling and appropriate professionalism resulting in adequate client satisfaction with care. Conversely, we determined that some mothers experienced mistreatment of different types during labor induction and birth including verbal abuse, lack of privacy, neglect, ineffective communication, inadequate pain relief, non-consented care and inadequate professional standards. There were no reports of physical abuse. Mixed responses (positive and negative) were heartily described concerning future utilization of the health facility considering the quality of care they received. Personalized recommendations to improve the quality of care during IOL were provided by the affected women and these summed up to RMC (e.g. effective communication, adequate analgesia, shared-decision making). Conclusion Our study indicates that women experience varied forms of mistreatment during induction of labor and childbirth, and can be potentially traumatic psychologically considering their prolonged exposure to health facilities. Context specific strategies to expedite integration and adherence to RMC guidelines in maternity care are recommended to improve the quality of care during induction of labor and birth.

Re-evaluation of the Bahariya Formation carcharodontosaurid (Dinosauria: Theropoda) and its implications for allosauroid phylogeny

The first partial skeleton of a carcharodontosaurid theropod was described from the Egyptian Bahariya Oasis by Ernst Stromer in 1931. Stromer referred the specimen to the species Megalosaurus saharicus, originally described on the basis of isolated teeth from slightly older rocks in Algeria, under the new genus name Carcharodontosaurus saharicus. Unfortunately, almost all of the material from the Bahariya Oasis, including the specimen of Carcharodontosaurus was destroyed during World War II. In 1996, a relatively complete carcharodontosaurid cranium was described from similar aged rocks in Morocco and designated the neotype of the species Carcharodontosaurus saharicus in 2007. However, due to the destruction of the original material, comparisons of the neotype to the Egyptian fossils have so far only been done cursorily. A detailed reexamination of the available information on the Egyptian carcharodontosaurid, including a previously undescribed photograph of the exhibited specimen, reveals that it differs from the Moroccan neotype in numerous characters, such as the development of the emargination of the antorbital fossa on the nasals, the presence of a horn-like rugosity on the nasal, the lack of a dorsoventral expansion of the lacrimal contact on the frontals, and the relative enlargement of the cerebrum. The referability of the Egyptian specimen to the Algerian M. saharicus is found to be questionable, and the neotype designation of the Moroccan material for C. saharicus is accepted here under consideration of ICZN Atricle 75, as it both compares more favorably to M. saharicus and originates from a locality closer to the type locality. A new genus and species, Tameryraptor markgrafi gen. et sp. nov, is proposed for the Egyptian taxon. The theropods of the Bahariya Oasis and the Moroccan Kem Kem Group are thus not as closely related as previously thought, and the proposed faunal similarities between these two strata need further examination.

Correction: A prospective, multi-site, cohort study to estimate incidence of infection and disease due to Lassa fever virus in West African countries (the Enable Lassa research programme)–Study protocol

Efficacy of virtual reality balance training on rehabilitation outcomes following anterior cruciate ligament reconstruction: A systematic review and meta-analysis

Objective The objective of this systematic review and meta-analysis is to clarify the rehabilitation efficacy of virtual reality (VR) balance training after anterior cruciate ligament reconstruction (ACLR). Methods This meta-analysis was registered in PROSPERO with the registration number CRD42024520383. The electronic databases PubMed, Web of Science, Cochrane Library, MEDLINE, Embase, China National Knowledge Infrastructure, Chinese Biomedical Literature, China Science and Technology Journal Database, and Wanfang Digital Periodical database were systematically searched to identify eligible studies from their inception up to January 2024. The investigated outcomes included International Knee Documentation Committee (IKDC) score, visual analogue scale (VAS), Holden grading, Extensor peak torque (EPT), Flexor peak torque (FPT), knee reaction time, knee reproduction angle difference. The pooled mean difference (MD) and 95% confidence intervals (CIs) were calculated using the random-effects model. Results Six RCTs with a total of 464 patients after unilateral ACLR were included for 8–12 weeks of VR balance training intervention. Analysis of the results showed that compared with the conventional rehabilitation control group, the VR balance training group significantly improved the International Knee Documentation Committee (IKDC) score (MD = 3.88, 95%CI: 0.95~6.81), Holden grading (MD = 0.42, 95%CI: 0.33~0.51), Extensor peak torque (EPT) (MD = 12.03, 95%CI: 3.28~20.78)and Flexor peak torque (FPT) (MD = 14.57, 95%CI: 9.52~19.63) in postoperative ACLR patients, and significantly reduced knee reaction time (MD = -0.30, 95%CI: -0.35~-0.25), knee angle reproduction difference at 30° (MD = -0.88, 95%CI: -1.16~-0.61), knee angle reproduction difference at 60° (MD = -0.80, 95%CI: -1.09~-0.50), and VAS score (MD = -0.52, 95%CI: -0.65~-0.39). Conclusion Since many of the included results are based on low—or very—low—quality evidence, although the results show a certain trend, the conclusion has great uncertainty. In the rehabilitation training following ACLR and lower—limb balance training, the application of VR might be advantageous for the recovery of patients’ knee joint function, lower—limb muscle strength, proprioception, and pain management. The level of immersion may influence the rehabilitation outcome. Because of the limitations in data quality and heterogeneity as well as the small sample size, the strength of the conclusions is weakened. These findings should be verified in further large-scale prospective studies.

Patients’ attitudes toward artificial intelligence (AI) in cancer care: A scoping review protocol

Background Artificial intelligence broadly refers to computer systems that simulate intelligent behaviour with minimal human intervention. Emphasizing patient-centered care, research has explored patients’ perspectives on artificial intelligence in medical care, indicating general acceptance of the technology but also concerns about supervision. However, these views have not been systematically examined from the perspective of patients with cancer, whose opinions may differ given the distinct psychosocial toll of the disease. Objectives This protocol describes a scoping review aimed at summarizing the existing literature on the attitudes of patients with cancer toward the use of artificial intelligence in their medical care. The primary goal is to identify knowledge gaps and highlight opportunities for future research. Methods This scoping review protocol will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA-ScR). The electronic databases MEDLINE (OVID), EMBASE, PsycINFO, and CINAHL will be searched for peer-reviewed primary research articles published in academic journals. We will have two independent reviewers screen the articles retrieved from the literature search and select relevant studies based on our inclusion criteria, with a third reviewer resolving any disagreements. We will then compile the data from the included articles into a narrative summary and discuss the implications for clinical practice and future research. Discussion To our knowledge, this will be the first scoping review to map the existing literature on the attitudes of patients with cancer regarding artificial intelligence in their medical care.

“When I talk about it, my eyes light up!” Impacts of a national laboratory internship on community college student success

Participation in technical/research internships may improve undergraduate graduation rates and persistence in science, technology, engineering, and mathematics (STEM), yet little is known about the benefits of these activities a) for community college students, b) when hosted by national laboratories, and c) beyond the first few years after the internship. We applied Social Cognitive Career Theory (SCCT) to investigate alumni perspectives about how CCI at Lawrence Berkeley National Laboratory (LBNL) impacted their academic/career activities. We learned that alumni had low confidence and expectations of success in STEM as community college students. Participation in CCI increased their professional networks, expectations of success, and STEM skills, identity, and self-efficacy/confidence. Hispanic/Latinx alumni recalled the positive impact of mentors who prioritized personal connections, and women valued “warm” social environments. We propose several additions to the SCCT model, to better reflect the supports and barriers to STEM persistence for community college students.

Enhancing stock index prediction: A hybrid LSTM-PSO model for improved forecasting accuracy

Stock price prediction is a challenging research domain. The long short-term memory neural network (LSTM) widely employed in stock price prediction due to its ability to address long-term dependence and transmission of historical time signals in time series data. However, manual tuning of LSTM parameters significantly impacts model performance. PSO-LSTM model leveraging PSO’s efficient swarm intelligence and strong optimization capabilities is proposed in this article. The experimental results on six global stock indices demonstrate that PSO-LSTM effectively fits real data, achieving high prediction accuracy. Moreover, increasing PSO iterations lead to gradual loss reduction, which indicates PSO-LSTM’s good convergence. Comparative analysis with seven other machine learning algorithms confirms the superior performance of PSO-LSTM. Furthermore, the impact of different retrospective periods on prediction accuracy and finding consistent results across varying time spans are. Conducted in the experiments.

Costs of outpatient services at selected primary healthcare centers in Bangladesh: A cross-sectional study

Background Upazila Health Complexes (UzHC) serve as the backbone of primary healthcare (PHC) at the sub-district level in Bangladesh, delivering comprehensive healthcare services including both inpatient and outpatient services to the grassroots levels. However, not all the prescribed medicines and diagnostics services are always available at these facilities for outpatient care. This results in out-of-pocket expenditure (OOPE) to the patients for getting prescribed medicines and diagnostics services which has not been properly explored. Thus, we aimed to estimate the overall provider and user costs for outpatient care services at selected UzHCs in Bangladesh. Methods An ingredient-based costing approach was applied to estimate the costs for the most commonly reported illnesses at outpatient of UzHCs from a societal perspective. We conducted a health facility survey at four purposively selected UzHCs to estimate provider costs and a patient exit survey among 452 patients of selected illnesses to estimate the user costs. Commonly reported illnesses were identified in consultation with healthcare providers of these facilities. The difference between costs of prescribed and provided medicines at UzHCs was estimated using the market prices. Data was collected between February to March 2021. Results The societal costs of the common outpatient illness or symptoms varied significantly, ranging from BDT 642 to BDT 1,384 per episode. Antenatal care had the highest cost burden at BDT 1,384, followed by respiratory illness at BDT 783 and urinary tract infection at BDT 670. On average, the provider spent BDT 289 for treating an outpatient, while a patient incurred BDT 446 as OOPE. Further, a patient was expected to spend an average of BDT 341 for purchasing medicines not provided from UzHCs. Conclusion Our study found significant gaps between prescribed and provided medicines at UzHCs, leading to higher OOPE for patients. The current healthcare resource allocation strategy does not consider the outpatient load and healthcare demand at PHC facilities, which further exacerbates this gap. Addressing this gap requires a fundamental shift towards a demand-driven resource allocation model within the healthcare financing strategy to improve healthcare access and achieve health for all.

Protective effect of luteinizing hormone on frozen-thawed ovarian follicles and granulosa cells

Ovarian tissue cryopreservation addresses critical challenges in fertility preservation for prepubertal female cancer patients, such as the lack of viable eggs and hormonal deficiencies. However, mitigating follicle and granulosa cell damage during freeze-thaw cycles remains an urgent issue. Luteinizing hormone (LH), upon binding to luteinizing hormone receptors (LHR) on granulosa cells, enhances estrogen synthesis and secretion, contributing to the growth of granulosa cells and follicles. This study examined mouse ovarian follicles and granulosa cells to identify optimal LH treatments using morphological assessments and LIVE/DEAD assays. The study found significant increases in the expression of Leucine-rich G-protein-coupled receptor 5 (Lgr5) and Forkhead box L2 (Foxl2) in mural and cumulus granulosa cells under LH influence, alongside marked reductions in active caspase-3 expression. Double immunofluorescence of Ki67 with Foxl2 and Lgr5 revealed ongoing proliferative activity in granulosa cells post freeze-thaw. In addition, LH treatment significantly boosted the expression of transforming growth factor (TGF-β) and its superfamily members in both granulosa cells and oocytes. These findings suggest that LH addition during cryopreservation can diminish damage to follicles and granulosa cells, offering new strategies to enhance the efficacy of mammalian ovarian cryopreservation.

Epidemiological trends and healthcare disparities in onychomycosis: An analysis of the All of Us research program

Onychomycosis is a common, difficult to treat nail disorder. Our objective was to explore disparities in current clinical management practices for onychomycosis in patients from underrepresented groups and with specific comorbidities. We conducted a cross-sectional study using the All of Us (AoU) research program. The AoU program gathers survey, and electronic health records from participants in the United States with the aim of increasing the representation of minorities groups in health research under the framework of precision medicine. We identified 18,763 onychomycosis patients (2017–2022) and compared the rates of diagnostic testing, prescription medications and surgical procedures. Younger patients were more likely to receive oral medications, while older patients were more likely to undergo surgical nail procedures. Patients with lower income and education, Black and Hispanic patients were less likely to receive testing to confirm diagnosis, and less likely to receive prescription medications (topical and/or oral) except in the case of fluconazole. Lower income and education were associated with a higher likelihood of debridement and trimming procedures, while Black and Hispanic patients were less likely to undergo these procedures. Patients with disabilities also received different treatments when compared to able-bodied individuals, being less likely to receive ciclopirox, efinaconazole and terbinafine, but more likely to undergo debridement and trimming procedures. There are clear differences in the management of onychomycosis in the different demographic and comorbid populations that we studied. Efforts to reduce these inequalities, such as expanded health coverage, reducing communication barriers and increasing patient and physician education are needed.

Psychological detachment from work predicts mental wellbeing of working-age adults: Findings from the ‘Wellbeing of the Workforce’ (WoW) prospective longitudinal cohort study

Background There is an urgent need to better understand the factors that predict mental wellbeing in vocationally active adults during globally turbulent times. Aim To explore the relationship between psychological detachment from work (postulated as a key recovery activity from work) in the first national COVID-19 lockdown with health, wellbeing, and life satisfaction of working age-adults one year later, within the context of a global pandemic. Methods Wellbeing of the Workforce (WoW) was a prospective longitudinal cohort study, with two waves of data collection (Time 1, April-June 2020: T1 n = 337; Time 2, March-April 2021: T2 = 169) corresponding with the first and third national COVID-19 lockdowns in the UK. Participants were >18 years, who were employed or self-employed and working in the UK. Descriptive and parametric (t-tests and linear regression) and nonparametric (chi square tests) inferential statistics were employed. Results Risk for major depression (T1: 20.0% to T2: 29.0%, p = .002), poor general health (T1: 4.7% to T2: 0%, p = .002) and poor life satisfaction (T1: 15.4% to T2: 25.4%, p = .002) worsened over time, moderate-to-severe anxiety remained stable (T1: 26.1% to T2: 30.2%, p = .15). Low psychological detachment from work was more prevalent in the first wave (T1: 21.4% and T2: 16.0%), with a moderate improvement observed from T1 to T2 (t (129) = -7.09, p < .001). No differences were observed with work status (employed/self-employed), except for self-employed workers being more likely to report poor general health at T1 (16.1%, p = .002). Better psychological wellbeing, lower anxiety and higher life satisfaction at T2 were observed in those who reported better psychological detachment from work at T1 (β = .21, p = .01; β = -.43, p < .001; β = .32, p = .003, respectively), and in those who improved in this recovery activity from T1 to T2 (β = .36, p < .001; β = -.27, p < .001; β = .27, p = .008, respectively), controlling for age, gender and ethnicity. Conclusion The ability to psychologically detach from work during the first pandemic lockdown, and improvement in this recovery activity over time, predicted better mental wellbeing and quality of life in vocationally active adults after one year of a global crisis, irrespective of work status. Interventions to encourage workers to psychologically detach from work may help to support employee wellbeing at all times, not only in the extreme circumstances of pandemics and economic uncertainty.

A conifer metabolite corrects episodic ataxia type 1 by voltage sensor–mediated ligand activation of Kv1.1

Loss-of-function sequence variants in KCNA1 , which encodes the voltage-gated potassium channel Kv1.1, cause Episodic Ataxia Type 1 (EA1) and epilepsy. Due to a paucity of drugs that directly rescue mutant Kv1.1 channel function, current therapeutic strategies for KCNA1 -linked disorders involve indirect modulation of neuronal excitability. Native Americans have traditionally used conifer extracts to treat paralysis, weakness, and pain, all of which may involve altered electrical activity and/or Kv1.1 dysfunction specifically. Here, screening conifer extracts, we found that Chamaecyparis pisifera increases wild-type (WT) Kv1.1 activity, as does its prominent metabolite, the abietane diterpenoid pisiferic acid. Uniquely, pisiferic acid also restored function in 12/12 EA1-linked mutant Kv1.1 channels tested in vitro. Crucially, pisiferic acid (1 mg/kg) restored WT function in Kv1.1 E283K/+ mice, a model of human EA1. Experimentally validated all-atom molecular dynamics simulations in a neuron-like membrane revealed that the Kv1.1 voltage-sensing domain (VSD) also acts as a ligand-binding domain akin to those of classic ligand-gated channels; binding of pisiferic acid induces a conformational shift in the VSD that ligand-dependently opens the pore. Conifer metabolite pisiferic acid is a promising and versatile therapeutic lead for EA1 and other Kv1.1-linked disorders.

Decoupling evolution of water footprint of energy and its driving factors: Evidence from Northeast China

Energy and water are interlinked and inseparable resources of vital importance to the survival and development of human society. Exploring the relationship between energy and water is of great practical significance for the sustainable development of resources. The uneven regional distribution of energy and water in China has exacerbated energy-related water shortages. Base on the water footprint of energy (WFE), this paper takes Northeast China, the old industrial base, as the research object, and explores the regional distribution characteristics and development trend of WFE, so as to provide quantitative basis for the development of regional energy transformation in coordination with energy and water. This study uses the ISO model and the decoupling model, and analyzes the spatial and temporal changes in the water footprint (WF) of energies and the decoupling effects in Northeast China from the perspective of energy production. The findings show: (1) the WFE grew slowly, and the WF of power gradually exceeded that of fossil energy; (2) the spatial distribution of WFE was unbalanced, with higher WF of fossil energy in Heilongjiang and higher WF of power in Jilin and Liaoning; (3) the decoupling status of WFE from GDP was better than that of WFE from total water consumption. This study also analyzes the driving factors of indicators of water endowment, economic development, energy consumption, environmental governance and life quality, on the WFE based on the Lasso model, and provide policy implications for the coordinated development of energy and water in Northeast China.

Deciphering mixed infections by plant RNA virus and reconstructing complete genomes simultaneously present within-host

Local co-circulation of multiple phylogenetic lineages is particularly likely for rapidly evolving pathogens in the current context of globalisation. When different phylogenetic lineages co-occur in the same fields, they may be simultaneously present in the same host plant (i.e. mixed infection), with potentially important consequences for disease outcome. This is the case in Burkina Faso for the rice yellow mottle virus (RYMV), which is endemic to Africa and a major constraint on rice production. We aimed to decipher the distinct RYMV isolates that simultaneously infect a single rice plant and to sequence their genomes. To this end, we tested different sequencing strategies, and we finally combined direct cDNA ONT (Oxford Nanopore Technology) sequencing with the bioinformatics tool RVhaplo. This method was validated by the successful reconstruction of two viral genomes that were less than a hundred nucleotides apart (out of a genome of 4450nt length, i.e. 2–3%), and present in artificial mixes at a ratio of up to a 99/1. We then used this method to subsequently analyze mixed infections from field samples, revealing up to three RYMV isolates within one single rice plant sample from Burkina Faso. In most cases, the complete genome sequences were obtained, which is particularly important for a better estimation of viral diversity and the detection of recombination events. The method described thus allows to identify various haplotypes of RYMV simultaneously infecting a single rice plant, obtaining their full-length sequences, as well as a rough estimate of relative frequencies within the sample. It is efficient, cost-effective, as well as portable, so that it could further be implemented where RYMV is endemic. Prospects include unravelling mixed infections with other RNA viruses that threaten crop production worldwide.