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Four different high-entropy spinel oxide ferrite (HESO) electrode materials containing 5-6 distinct metals were synthesized by a simple, rapid combustion synthesis process and evaluated as conversion anode materials in lithium half-cells. All showed markedly superior electrochemical performance compared to conventional spinel ferrites such as Fe3O4 and MgFe2O4, having capacities that could be maintained above 600 mAh g-1 for 150 cycles, in most cases. X-ray absorption spectroscopy (XAS) results on pristine, discharged, and charged electrodes show that Fe, Co, Ni, and Cu are reduced to the elemental state during the first discharge (lithiation), while Mn is only slightly reduced. Upon recharge (delithiation), Fe is reoxidized to an average oxidation state of about 2.6+, while Co, Ni, and Cu are not reoxidized. The ability of Fe to be oxidized past 2+ accounts for the high capacities observed in these materials, while the presence of metallic elements after the initial lithiation provides an electronically conductive network that aids in charge transfer.

In Côte d’Ivoire, cassava is the source of calories for about 26 million people and generates significant income for stakeholders in the value chain. However, its production is threatened by Cassava Mosaic Disease (CMD), which causes yield losses of up to 70%. This disease remains poorly known among farmers, who often adopt poor cultivation practices that serve to amplify its spread. To address this issue, the Regional Center of Excellence for transboundary plant pathogens Central and West African Virus Epidemiology (WAVE) introduced an innovate android based plant disease detection smart application called “PlantVillage Nuru” to help farmers recognize the disease through real-time diagnosis in cassava fields. The present study analyzes the perceptions and adoption rate of this application by farmers in the diagnosis of CMD within three departments of Côte d’Ivoire. Quantitative and qualitative data were collected from 152 farmers and agricultural technicians, using a questionnaire and interview guide in Dabou, Bouaké and Man. Data obtained were analyzed through descriptive statistics on SPSS and content analysis. A binary logit regression model was then used to identify the determinants of Nuru application adoption with Stata version 12.1. The study revealed an adoption rate of 45%, focused mainly on monitoring the phytosanitary status of cassava fields (98%), selecting healthy cuttings as planting materials (52%), and accessing agricultural advice (21%). The use of the Nuru application was strongly influenced (P

Abstract Plant biomass is a fundamental ecosystem attribute that is sensitive to rapid climatic changes occurring in the Arctic. Nevertheless, measuring plant biomass in the Arctic is logistically challenging and resource intensive. Lack of accessible field data hinders efforts to understand the amount, composition, distribution, and changes in plant biomass in these northern ecosystems. Here, we present The Arctic plant aboveground biomass synthesis dataset, which includes field measurements of lichen, bryophyte, herb, shrub, and/or tree aboveground biomass (g m−2) on 2,327 sample plots from 636 field sites in seven countries. We created the synthesis dataset by assembling and harmonizing 32 individual datasets. Aboveground biomass was primarily quantified by harvesting sample plots during mid- to late-summer, though tree and often tall shrub biomass were quantified using surveys and allometric models. Each biomass measurement is associated with metadata including sample date, location, method, data source, and other information. This unique dataset can be leveraged to monitor, map, and model plant biomass across the rapidly warming Arctic.

Background: Pseudomonas aeruginosa is an opportunistic bacterium that causes serious hospital-acquired infections. To assess the risk of clinically isolated P. aeruginosa to human health, we analyzed the resistance and virulence mechanisms of a collection of clinical isolates. Methods: This was a retrospective study in which P. aeruginosa isolates collected from January 1, 2018 to August 31, 2019 were analyzed using phenotypic and whole-genome sequencing (WGS) methods. The analysis included 48 clinical samples. Median patient age was 54.0 (29.5) years, and 58.3% of patients were women. Data from the microbiology laboratory database were reviewed to identify P. aeruginosa isolates. All unique isolates available for further testing were included, and related clinical data were collected. Infections were defined as hospital acquired if the index culture was obtained at least 48 h after hospitalization. Results: High-risk P. aeruginosa clones, including sequence types (STs) ST235 and ST111, were identified, in addition to 12 new STs. The isolates showed varying degrees of biofilm formation ability when evaluated at room temperature, along with reduced metabolic activity, as measured by metabolic staining, suggesting their ability to evade antimicrobial therapy. Most isolates (77.1%) were multidrug resistant (MDR), with the highest resistance and susceptibility rates to beta-lactams and colistimethate sodium, respectively. Conclusions: The MDR phenotypes of the examined isolates can be explained by the high prevalence of efflux-mediated resistance- and hydrolytic enzyme-encoding genes. These isolates had high cytotoxic potential, as indicated by the detection of toxin production-related genes.

Background: Health literacy (HL) and health numeracy (HN), the ability to interpret and act on quantitative health information, are important for hypertension self-management such as limiting sodium intake. We examined associations of HL, HN, and Dietary Approaches to Stop Hypertension (DASH) diet accordance. Participants: Among 1,073 hypertensive adults enrolled in a Baltimore, Maryland-based cohort study, we performed a cross-sectional analysis. Rapid Estimate of Adult Literacy in Medicine (REALM) measured HL and Test of Functional Health Literacy in Adults (TOFHLA) numeracy score measured HN. Method: DASH accordance was based on nine key nutrients. Linear regression models estimated associations of HL and HN with DASH total and sodium score, inclusive of dietary supplement data. Results: In our sample, 39% of participants were male, 66% were Black, 40.2% lived in poverty, and 29.5% reported food insecurity. Fully, 32.5% had limited HL and 14.5% had limited HN. Mean DASH score overall was 2 (range = 0-7.5); only 6.9% were DASH accordant (score =4.5). In age and sex adjusted models, higher REALM was associated with a higher DASH score in the overall sample; the relationship of HN with DASH was statistically significant among White but not Black participants. Educational attainment appeared to explain both findings. There were no significant associations between HL or HN and DASH sodium scores. Conclusion: Differences in educational attainment explained the relation of higher HL and greater accordance to the DASH diet in a population of hypertensive adults. Understanding these factors is vital to reducing disparities in hypertension and its sequelae.

A major challenge in coronavirus vaccination and treatment is to counteract rapid viral evolution and mutations. Here we demonstrate that CRISPR-Cas13d offers a broad-spectrum antiviral (BSA) to inhibit many SARS-CoV-2 variants and diverse human coronavirus strains with >99% reduction of the viral titer. We show that Cas13d-mediated coronavirus inhibition is dependent on the crRNA cellular spatial colocalization with Cas13d and target viral RNA. Cas13d can significantly enhance the therapeutic effects of diverse small molecule drugs against coronaviruses for prophylaxis or treatment purposes, and the best combination reduced viral titer by over four orders of magnitude. Using lipid nanoparticle-mediated RNA delivery, we demonstrate that the Cas13d system can effectively treat infection from multiple variants of coronavirus, including Omicron SARS-CoV-2, in human primary airway epithelium air-liquid interface (ALI) cultures. Our study establishes CRISPR-Cas13 as a BSA which is highly complementary to existing vaccination and antiviral treatment strategies.

ObjectiveSome studies have suggested alterations of structural brain asymmetry in attention-deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left-right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium.MethodsWe analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries.ResultsThere was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen's d from -0.18 to 0.18) and would not survive study-wide correction for multiple testing.ConclusionPrior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.

Objective: Retinol saturase (RetSat) is an endoplasmic reticulum-localized oxidoreductase highly expressed in organs involved in lipid metabolism such as white (WAT) and brown adipose tissue (BAT). Cold exposure was shown to increase RETSAT protein in BAT but its relevance for non-shivering thermogenesis, a process with beneficial effects on metabolic health, is unknown. Methods: We analyzed the regulation of RetSat expression in white and brown adipocytes and different murine adipose tissue depots upon β-adrenergic stimulation and cold exposure. RetSat function during the differentiation and β-adrenergic stimulation of brown adipocytes was dissected by loss-of-function experiments. Mice with BAT-specific deletion of RetSat were generated and exposed to cold. Gene expression in human WAT was analyzed and the effect of RetSat depletion on adipocyte lipolysis investigated. Results: We show that cold exposure induces RetSat expression in both WAT and BAT of mice via β-adrenergic signaling. In brown adipocytes, RetSat has minor effects on differentiation but is required for maximal thermogenic gene and protein expression upon β-adrenergic stimulation and mitochondrial respiration. In mice, BAT-specific deletion of RetSat impaired acute but not long-term adaptation to cold exposure. RetSat expression in subcutaneous WAT of humans correlates with the expression of genes related to mitochondrial function. Mechanistically, we found that RetSat depletion impaired β-agonist-induced lipolysis, a major regulator of thermogenic gene expression in adipocytes. Conclusions: Thus, RetSat expression is under β-adrenergic control and determines thermogenic capacity of brown adipocytes and acute cold tolerance in mice. Modulating RetSat activity may allow for therapeutic interventions towards pathologies with inadequate metabolic activity.

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder. Neuroanatomic heterogeneity limits our understanding of ADHD's etiology. This study aimed to parse heterogeneity of ADHD and to determine whether patient subgroups could be discerned based on subcortical brain volumes.MethodsUsing the large ENIGMA-ADHD Working Group dataset, four subsamples of 993 boys with and without ADHD and to subsamples of 653 adult men, 400 girls, and 447 women were included in analyses. We applied exploratory factor analysis (EFA) to seven subcortical volumes in order to constrain the complexity of the input variables and ensure more stable clustering results. Factor scores derived from the EFA were used to build networks. A community detection (CD) algorithm clustered participants into subgroups based on the networks.ResultsExploratory factor analysis revealed three factors (basal ganglia, limbic system, and thalamus) in boys and men with and without ADHD. Factor structures for girls and women differed from those in males. Given sample size considerations, we concentrated subsequent analyses on males. Male participants could be separated into four communities, of which one was absent in healthy men. Significant case-control differences of subcortical volumes were observed within communities in boys, often with stronger effect sizes compared to the entire sample. As in the entire sample, none were observed in men. Affected men in two of the communities presented comorbidities more frequently than those in other communities. There were no significant differences in ADHD symptom severity, IQ, and medication use between communities in either boys or men.ConclusionsOur results indicate that neuroanatomic heterogeneity in subcortical volumes exists, irrespective of ADHD diagnosis. Effect sizes of case-control differences appear more pronounced at least in some of the subgroups.

We previously established that vascular smooth muscle–derived adventitial progenitor cells (AdvSca1-SM) preferentially differentiate into myofibroblasts and contribute to fibrosis in response to acute vascular injury. However, the role of these progenitor cells in chronic atherosclerosis has not been defined. Using an AdvSca1-SM cell lineage tracing model, scRNA-Seq, flow cytometry, and histological approaches, we confirmed that AdvSca1-SM–derived cells localized throughout the vessel wall and atherosclerotic plaques, where they primarily differentiated into fibroblasts, smooth muscle cells (SMC), or remained in a stem-like state. Krüppel-like factor 4 (Klf4) knockout specifically in AdvSca1-SM cells induced transition to a more collagen-enriched fibroblast phenotype compared with WT mice. Additionally, Klf4 deletion drastically modified the phenotypes of non–AdvSca1-SM–derived cells, resulting in more contractile SMC and atheroprotective macrophages. Functionally, overall plaque burden was not altered with Klf4 deletion, but multiple indices of plaque composition complexity, including necrotic core area, macrophage accumulation, and fibrous cap thickness, were reduced. Collectively, these data support that modulation of AdvSca1-SM cells through KLF4 depletion confers increased protection from the development of potentially unstable atherosclerotic plaques.

ObjectiveAttention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. The authors sought to directly compare these disorders using structural brain imaging data from ENIGMA consortium data.MethodsStructural T1-weighted whole-brain MRI data from healthy control subjects (N=5,827) and from patients with ADHD (N=2,271), ASD (N=1,777), and OCD (N=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. The authors examined subcortical volume, cortical thickness, and cortical surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults, using linear mixed-effects models adjusting for age, sex, and site (and intracranial volume for subcortical and surface area measures).ResultsNo shared differences were found among all three disorders, and shared differences between any two disorders did not survive correction for multiple comparisons. Children with ADHD compared with those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller intracranial volume than control subjects and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared with adult control subjects and other clinical groups. No OCD-specific differences were observed across different age groups and surface area differences among all disorders in childhood and adulthood.ConclusionsThe study findings suggest robust but subtle differences across different age groups among ADHD, ASD, and OCD. ADHD-specific intracranial volume and hippocampal differences in children and adolescents, and ASD-specific cortical thickness differences in the frontal cortex in adults, support previous work emphasizing structural brain differences in these disorders.

The global demand for rapid identification of circulating SARS-CoV-2 variants of concern has led to a shortage of commercial kits. Therefore, this study aimed to develop and validate a rapid, cost-efficient genome sequencing protocol to identify circulating SARS-CoV-2 (variants of concern). Sets of primers flanking the SARS-CoV-2 spike gene were designed, verified and then validated using 282 nasopharyngeal positive samples for SARS-CoV-2. Protocol specificity was confirmed by comparing these results with SARS-CoV-2 whole-genome sequencing of the same samples. Out of 282 samples, 123 contained the alpha variant, 78 beta and 13 delta, which were indicted using in-house primers and next-generation sequencing; the numbers of variants found were 100% identical to the reference genome. This protocol is easily adaptable for detection of emerging variants during the pandemic.

Differentiating GCA from its many mimickers remains a challenge in the daily clinical practice, especially in patients presenting with unspecific manifestations. We present the case of an 82-year-old woman who presented with a 3-week history of left eye vision loss secondary to bilateral edema and hemorrhage of the optic discs. Despite negative bilateral temporal artery biopsies, the elevation of the inflammatory markers and brain MRA findings suggestive of temporal arteritis as well as stenosis of the basilar artery led us to initiate treatment with high-dose steroids. Inflammatory markers remained elevated despite high-dose steroids which prompted additional work leading to a diagnosis of varicella-zoster encephalitis. Steroid treatment was quickly tapered off and treatment with acyclovir resulted in the normalization of the acute phase reactants. The persistence of elevated inflammatory markers despite high-dose steroids should prompt additional work up for the search of an alternative diagnosis of GCA mimickers.

IntroductionFeto-maternal cell transfer during pregnancy is called microchimerism (Mc). Its persistence in respective hosts is increasingly studied as to its potential role in immune tolerance, autoimmunity, cancer, and degenerative diseases. Murine models with transgenic reporter genes, heterozygously carried by the mother, allow maternal Mc tracking in wild-type (WT) offspring. However, as gestation in mice is multi-embryonic, an exchange of cells between fetuses carrying the same reporter gene as their mother and negative WT littermate, named littermate Mc (LMc), can occur and be confounded with the maternal source. We propose here to evaluate LMc contribution in mice.MethodsTo avoid the maternal confounding source of Mc, transgenic males, heterozygous for a reporter gene, here, the human leukocyte antigen DRB1*04 (DR4+/−), were crossed with WT females (DR4−/−). DR4+/− LMc was specifically quantified by HLA-DR4 quantitative PCR, i) in utero in main organs from 15 DR4−/− fetuses from three litters of 11, nine, and five; and ii) after birth in two litters of eight pups: in two DR4−/− stillborns and four DR4−/− adult mice.ResultsAt embryonic stages, DR4−/− fetuses having one or two nearby DR4+/− littermates in the same uterine horn were almost seven times more frequently positive for DR4− microchimerism in their organs (p = 0.01) and had quantitatively more LMc (p = 0.009) than those without nearby DR4+/− littermates. Furthermore, LMc persists at birth and into adulthood with interindividual heterogeneity.ConclusionsThis study identifies heterogeneity for LMc acquisition according to in utero position and different interpretation of previously published results on maternal Mc in mice.

In Saccharomyces cerevisiae, pH homeostasis is reliant on ATP due to the use of proton-translocating ATPase (H+-ATPase) which constitutes a major drain within cellular ATP supply. Here, an exogenous proton-translocating pyrophosphatase (H+-PPase) from Arabidopsis thaliana, which uses inorganic pyrophosphate (PPi) rather than ATP, was evaluated for its effect on reducing the ATP burden. The H+-Ppase was localized to the vacuolar membrane or to the cell membrane, and their impact was studied under acetate stress at a low pH. Biosensors (pHluorin and mQueen-2m) were used to observe changes in intracellular pH (pHi) and ATP levels during growth on either glucose or xylose. A significant improvement of 35% in the growth rate at a pH of 3.7 and 6 g·L−1 acetic acid stress was observed in the vacuolar membrane H+-PPase strain compared to the parent strain. ATP levels were elevated in the same strain during anaerobic glucose and xylose fermentations. During anaerobic xylose fermentations, co-expression of pHluorin and a vacuolar membrane H+-PPase improved the growth characteristics by means of an improved growth rate (11.4%) and elongated logarithmic growth duration. Our study identified a potential method for improving productivity in the use of S. cerevisiae as a cell factory under the harsh conditions present in industry.

ObjectiveNeuroimaging studies show structural alterations of various brain regions in children and adults with attention deficit hyperactivity disorder (ADHD), although nonreplications are frequent. The authors sought to identify cortical characteristics related to ADHD using large-scale studies.MethodsCortical thickness and surface area (based on the Desikan-Killiany atlas) were compared between case subjects with ADHD (N=2,246) and control subjects (N=1,934) for children, adolescents, and adults separately in ENIGMA-ADHD, a consortium of 36 centers. To assess familial effects on cortical measures, case subjects, unaffected siblings, and control subjects in the NeuroIMAGE study (N=506) were compared. Associations of the attention scale from the Child Behavior Checklist with cortical measures were determined in a pediatric population sample (Generation-R, N=2,707).ResultsIn the ENIGMA-ADHD sample, lower surface area values were found in children with ADHD, mainly in frontal, cingulate, and temporal regions; the largest significant effect was for total surface area (Cohen's d=-0.21). Fusiform gyrus and temporal pole cortical thickness was also lower in children with ADHD. Neither surface area nor thickness differences were found in the adolescent or adult groups. Familial effects were seen for surface area in several regions. In an overlapping set of regions, surface area, but not thickness, was associated with attention problems in the Generation-R sample.ConclusionsSubtle differences in cortical surface area are widespread in children but not adolescents and adults with ADHD, confirming involvement of the frontal cortex and highlighting regions deserving further attention. Notably, the alterations behave like endophenotypes in families and are linked to ADHD symptoms in the population, extending evidence that ADHD behaves as a continuous trait in the population. Future longitudinal studies should clarify individual lifespan trajectories that lead to nonsignificant findings in adolescent and adult groups despite the presence of an ADHD diagnosis.

Rice Crop Manager (RCM) is a decision support tool to help increase the yield of Filipino rice farmers. While there is evidence that following RCM recommendations significantly improve their yield, its uptake is far less than expected. This paper attempts to explain the complexities in the adoption of RCM by Filipino farmers. It draws insights from the Technology Acceptance Model and the Integrative Approach to Models of Technology Adoption in the analysis of its findings. This research employed a qualitative approach, using interviews (in-depth and key informant) and participant observation, in investigating its research questions. The main research participants were 30 farmers and 12 key informants composed of RCM focal persons, agricultural extension workers (AEWs), and municipal/city agriculturists. Overall, we argue that there is a need to tackle social system and socio-technical issues relating to RCM adoption. Examples of social system issues include the lack of resources of farmers and poor internet connectivity; of socio-technical issues are conflict with existing initiatives and overwhelming administrative issues in the local agriculture offices. Among the recommendations to improve RCM uptake in the Philippines are addressing the work overload issue of AEWs, improving rural internet access, and integrating a multi-sectoral agriculture extension system.

Various rational metabolic engineering and random approaches have been applied to introduce and improve xylose utilization and ethanol productivity by Saccharomyces cerevisiae. Among them, the BUD21 gene was identified as an interesting candidate for enhancing xylose consumption as its deletion appeared to be sufficient to improve growth, substrate utilization and ethanol productivity on xylose, even in a laboratory strain lacking a heterologous xylose pathway. The present study aimed at studying the influence of BUD21 deletion in recombinant strains carrying heterologous oxido-reductive xylose utilization pathway. The positive effect of BUD21 gene deletion on aerobic growth and xylose utilization could not be confirmed in two non-engineered laboratory strains (BY4741 and CEN.PK 113-7D) that were grown in YP rich medium with 20 g/L xylose as sole carbon source, despite the fact that effective deletion of BUD21 gene was confirmed using both genotypic (colony PCR) and phenotypic (heat sensitive phenotype of the BUD21 deletion mutant) control experiments. Therefore, the effect of BUD21 deletion on xylose fermentation might be strain- or medium-dependent.

Vascular smooth muscle–derived Sca1+ adventitial progenitor (AdvSca1-SM) cells are tissue-resident, multipotent stem cells that contribute to progression of vascular remodeling and fibrosis. Upon acute vascular injury, AdvSca1-SM cells differentiate into myofibroblasts and are embedded in perivascular collagen and the extracellular matrix. While the phenotypic properties of AdvSca1-SM–derived myofibroblasts have been defined, the underlying epigenetic regulators driving the AdvSca1-SM–to–myofibroblast transition are unclear. We show that the chromatin remodeler Smarca4/Brg1 facilitates AdvSca1-SM myofibroblast differentiation. Brg1 mRNA and protein were upregulated in AdvSca1-SM cells after acute vascular injury, and pharmacological inhibition of Brg1 by the small molecule PFI-3 attenuated perivascular fibrosis and adventitial expansion. TGF-β1 stimulation of AdvSca1-SM cells in vitro reduced expression of stemness genes while inducing expression of myofibroblast genes that was associated with enhanced contractility; PFI blocked TGF-β1–induced phenotypic transition. Similarly, genetic knockdown of Brg1 in vivo reduced adventitial remodeling and fibrosis and reversed AdvSca1-SM–to–myofibroblast transition in vitro. Mechanistically, TGF-β1 promoted redistribution of Brg1 from distal intergenic sites of stemness genes and recruitment to promoter regions of myofibroblast-related genes, which was blocked by PFI-3. These data provide insight into epigenetic regulation of resident vascular progenitor cell differentiation and support that manipulating the AdvSca1-SM phenotype will provide antifibrotic clinical benefits.