Miracle-dz/UniFAR-FTUs huggingface dataset:
Low toxicity and high efficacy in use of novel approaches to control Aedes aegypti

ABSTRACT Arthropod-borne viruses are a group of etiologic agents accounting for different incapacitating diseases that progress to severe and lethal forms in animal and human targets consequently representing a significant burden on public health and global economies. Although attempts were undertaken to combat Aedes aegypti, the primary urban mosquito vector of several life-threatening diseases, the misuse of chemical pesticides, development of resistance, and toxicity on non-target species still need to be overcome. In this context, it is imperative for development of long-lasting, novel approaches envisioning effective control of Aedes aegypti, mainly in endemic regions. Thus, the present review was undertaken to describe safe and eco-friendly approaches as potential weapons against Aedes aegypti. Accordingly, the findings discussed indicated that biological larvicides and genetic engineering technologies constitute noteworthy alternatives of future mosquito-borne arbovirus disease control efforts.
Auto‐inhibition of Mif2/CENP‐C ensures centromere‐dependent kinetochore assembly in budding yeast

Kinetochores are chromatin‐bound multi‐protein complexes that allow high‐fidelity chromosome segregation during mitosis and meiosis. Kinetochore assembly is exclusively initiated at chromatin containing Cse4/CENP‐A nucleosomes. The molecular mechanisms ensuring that subcomplexes assemble efficiently into kinetochores only at centromeres, but not anywhere else, are incompletely understood. Here, we combine biochemical and genetic experiments to demonstrate that auto‐inhibition of the conserved kinetochore subunit Mif2/CENP‐C contributes to preventing unscheduled kinetochore assembly in budding yeast cells. We show that wild‐type Mif2 is attenuated in its ability to bind a key downstream component in the assembly pathway, the Mtw1 complex, and that addition of Cse4 nucleosomes overcomes this inhibition. By exchanging the N‐terminus of Mif2 with its functional counterpart from Ame1/CENP‐U, we have created a Mif2 mutant which bypasses the Cse4 requirement for Mtw1 binding in vitro, thereby shortcutting kinetochore assembly. Expression of this Mif2 mutant in cells leads to mis‐localization of the Mtw1 complex and causes pronounced chromosome segregation defects. We propose that auto‐inhibition of Mif2/CENP‐C constitutes a key concept underlying the molecular logic of kinetochore assembly.
Antimicrobial Susceptibility and Clonality of Vaginally Derived Multidrug-Resistant Mobiluncus Isolates in China

Here, the antimicrobial susceptibility, resistance mechanisms, and clonality of Mobiluncus sp. isolates recovered from gynecological outpatients in China were investigated. Compared to M. mulieris, M. curtisii exhibited higher antimicrobial resistance to metronidazole, clindamycin, and tetracycline. Whole-genome sequencing indicated that the clindamycin resistance gene erm(X) was located on a transposable element, Tn5432, which was composed of two IS1249 sequences. ABSTRACT Here, the antimicrobial susceptibility, resistance mechanisms, and clonality of Mobiluncus sp. isolates recovered from gynecological outpatients in China were investigated. Compared to M. mulieris, M. curtisii exhibited higher antimicrobial resistance to metronidazole, clindamycin, and tetracycline. Whole-genome sequencing indicated that the clindamycin resistance gene erm(X) was located on a transposable element, Tn5432, which was composed of two IS1249 sequences. Phylogenetic analysis indicated that Mobiluncus spp. had high diversity, with isolates being grouped into several sporadic clades.
Staphylococcus aureus Fatty Acid Kinase FakA Modulates Pathogenesis during Skin Infection via Proteases

Staphylococcus aureus fatty acid kinase FakA is necessary for the incorporation of exogenous fatty acids into the lipid membrane. We previously demonstrated that the inactivation of fakA leads to decreased α-hemolysin (Hla) production but increased expression of the proteases SspAB and aureolysin in vitro, and that the ΔfakA mutant causes larger lesions than the wild type (WT) during murine skin infection. As expected, necrosis is Hla dependent in the presence or absence of FakA, as both hla and hla ΔfakA mutants are unable to cause necrosis of the skin. ABSTRACT Staphylococcus aureus fatty acid kinase FakA is necessary for the incorporation of exogenous fatty acids into the lipid membrane. We previously demonstrated that the inactivation of fakA leads to decreased α-hemolysin (Hla) production but increased expression of the proteases SspAB and aureolysin in vitro, and that the ΔfakA mutant causes larger lesions than the wild type (WT) during murine skin infection. As expected, necrosis is Hla dependent in the presence or absence of FakA, as both hla and hla ΔfakA mutants are unable to cause necrosis of the skin. At day 4 postinfection, while the ΔfakA mutant maintains larger and more necrotic abscesses, bacterial numbers are similar to those of the WT, indicating the enhanced tissue damage of mice infected with the ΔfakA mutant is not due to an increase in bacterial burden. At this early stage of infection, skin infected with the ΔfakA mutant has decreased levels of proinflammatory cytokines, such as interleukin-17A (IL-17A) and IL-1α, compared to those of WT-infected skin. At a later stage of infection (day 7), abscess resolution and bacterial clearance are hindered in ΔfakA mutant-infected mice. The paradoxical findings of decreased Hla in vitro but increased necrosis in vivo led us to investigate the role of the proteases regulated by FakA. Utilizing Δaur and ΔsspAB mutants in both the WT and fakA mutant backgrounds, we found that the absence of these proteases in a fakA mutant reduced dermonecrosis to levels similar to those of the WT strain. These studies suggest that the overproduction of proteases is one factor contributing to the enhanced pathogenesis of the ΔfakA mutant during skin infection.
The Effect of Interactions between Folic Acid Supplementation and One Carbon Metabolism Gene Variants on Small-for-Gestational-Age Births in the Screening for Pregnancy Endpoints (SCOPE) Cohort Study

Small-for-gestational-age (SGA) is associated with significant perinatal morbidity and mortality. Our aim was to investigate gene-nutrient interactions between maternal one-carbon single nucleotide polymorphisms (SNPs) and folic acid supplement (FAS) use, and their association with SGA. Nulliparous New Zealand women with singleton pregnancy were recruited as part of the Screening for Pregnancy Endpoints prospective cohort study. Data on FAS use was collected via face-to-face interview at 15 weeks’ gestation; participants were followed prospectively and birth outcome data collected within 72 h of delivery. Participants were genotyped for MTHFR 677, MTHFR 1298, MTHFD1 1958, MTR 2756, MTRR 66 and TCN2 776 SNPs. Genotype data for at least one SNP was available for 1873 (93%) of eligible participants. Analysis showed a significant SNP-FAS interaction for MTHFR 1298 (p = 0.020), MTHFR 677 (p = 0.019) and TCN2 776 (p = 0.017) in relation to SGA: MTHFR 1298 CC variant non-FAS users had an increased likelihood [Odds Ratio (OR) = 2.91 (95% Confidence Interval (CI) = 1.52, 5.60] compared with wild-type (MTHFR 1298 AA) FAS users. MTHFR 677 variant allele carrier (MTHFR 677 CT + MTHFR 677 TT) non-FAS users had an increased likelihood [OR = 1.87 (95% CI = 1.21, 2.88)] compared to wild-type (MTHFR 677 CC) FAS users. TCN2 776 variant (TCN2 776 GG) non-FAS users had an increased likelihood [OR = 2.16 (95% CI = 1.26, 3.71)] compared with wild type homozygote + heterozygote (TCN2 776 CC + TCN2 776 CG) FAS users. No significant interactions were observed for MTHFD1 1958, MTR 2756 or MTRR 66 (p > 0.05). We observed an overall pattern of FAS attenuating differences in the likelihood of SGA seen between genotype groups in FAS non-users. Future research should focus on how intake of other one-carbon nutrients might mediate these gene-nutrient interactions.
Fixed dose rivaroxaban can be used in extremes of bodyweight: A population pharmacokinetic analysis

Emerging safety and efficacy data for rivaroxaban suggest traditional therapy and rivaroxaban are comparable in the morbidly obese. However, real‐world data that indicate pharmacokinetic (PK) parameters are comparable at the extremes of body size are lacking. The International Society of Thrombosis and Haemostasis Scientific and Standardisation Committee (ISTH SSC) suggests avoiding the use of direct oral anticoagulants (DOACs) in patients weighing >120 kg or with a body mass index >40 kg/m2 and gives no recommendation on the use of DOACs in those <50 kg.
Antioxidant Capacity and Phenolic Content of the Aqueous Extract of Commonly Consumed Cucurbits

The antioxidant capacity of commonly consumed cucurbits vegetable was determined by the DPPH, FRAP, Fe3+ reducing power, and hydrogen peroxide scavenging assay. The aqueous extract of Luffa cylindrica showed the highest value of phenolic content and antioxidant capacity based on FRAP, Fe3+ reducing power, and hydrogen peroxide scavenging assay. However, Laginaria siceraria extract showed the highest flavonoid and DPPH scavenging activities among all three cucurbits used in this study. Phenolic content in aqueous extracts of Luffa cylindrica and Laginaria siceraria was almost equal. Cucurbita maxima exhibited the lowest phenolic, flavonoid content, and exhibited the lowest power of antioxidant scavenging. The antioxidant capacity of cucurbits was significantly correlated (P < 0.05) with the phenolic content of their extracts. The antioxidant capacity of Luffa cylindrica and Laginaria siceraria have also shown a significant correlation (P < 0.05).
Focal cerebral ischemia induces changes in oligodendrocytic tau isoforms in the damaged area

Ischemic stroke is a major cause of death and the first leading cause of long‐term disability worldwide. The only therapeutic strategy available to date is reperfusion and not all the patients are suitable for this treatment. Blood flow blockage or reduction leads to considerable brain damage, affecting both gray and white matter. The detrimental effects of ischemia have been studied extensively in the former but not in the latter. Previous reports indicate that preservation of white matter integrity reduces deleterious effect of ischemia on the brain. Oligodendrocytes are sensitive to ischemic damage, however, some reports demonstrate that oligodendrogenesis occurs after ischemia. These glial cells have a complex cytoskeletal network, including tau, that plays a key role to proper myelination. 4R‐Tau/3R‐Tau, which differ in the presence/absence of Exon 10, are found in oligodendrocytes; but the precise role of each isoform is not understood. Using permanent middle cerebral artery occlusion model and immunofluorescence, we demonstrate that cerebral ischemia induces an increase in 3R‐Tau versus 4R‐Tau in oligodendrocytes in the damaged area. In addition, cellular distribution of Tau undergoes a change after ischemia, with some oligodendrocytic processes showing positive staining for 3R‐Tau. This occurs simultaneously with the amelioration of neurological damage in ischemic rats. We propose that ischemia triggers an endogenous mechanism involving 3R‐Tau, that induces colonization of the ischemic damaged area by oligodendrocytes in an attempt to myelinate‐injured axons. Understanding the molecular mechanism of this phenomenon could pave the way for the design of therapeutic strategies that exploit glial cells for the treatment of ischemia.
Characterization of microRNA profiles in the mammary gland tissue of dairy goats at the late lactation, dry period and late gestation stages

MicroRNAs (miRNAs) play an important role in regulating mammary gland development and lactation. We previously analyzed miRNA expression profiles in Laoshan dairy goat mammary glands at the early (20 d postpartum), peak (90 d postpartum) and late lactation (210 d postpartum) stages. To further enrich and clarify the miRNA expression profiles during the lactation physiological cycle, we sequenced miRNAs in the mammary gland tissues of Laoshan dairy goats at three newly selected stages: the late lactation (240 d postpartum), dry period (300 d postpartum) and late gestation (140 d after mating) stages. We obtained 4038 miRNAs and 385 important miRNA families, including mir-10, let-7 and mir-9. We also identified 754 differentially expressed miRNAs in the mammary gland tissue at the 3 different stages and 6 groups of miRNA clusters that had unique expression patterns. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that GO terms such as mammary gland development (GO:0030879) and mammary gland morphogenesis (GO:0060443) and important signaling pathways, including the insulin signaling pathway (chx04910), hippo signaling pathway (chx04390) and estrogen signaling pathway (chx04915), were enriched. We screened miRNAs and potential target genes that may be involved in the regulation of lactation, mammary gland growth and differentiation, cell apoptosis, and substance transport and synthesis and detected the expression patterns of important genes at the three stages. These miRNAs and critical target genes may be important factors for mammary gland development and lactation regulation and potentially valuable molecular markers, which may provide a theoretical reference for further investigation of mammary gland physiology.
Agricultural acceleration of soil carbonate weathering

Soil carbonates (i.e., soil inorganic carbon or SIC) represent more than a quarter of the terrestrial carbon pool and are often considered to be relatively stable, with fluxes significant only on geologic timescales. However, given the importance of climatic water balance on SIC accumulation, we tested the hypothesis that increased soil water storage and transport resulting from cultivation may enhance dissolution of SIC, altering their local stock at decadal timescales. We compared SIC storage to 7.3 m depth in eight sites, each having paired plots of native vegetation and rain‐fed croplands, and half the sites having additional irrigated cropland plots. Rain‐fed and irrigated croplands had 328 and 730 Mg C/ha less SIC storage, respectively, compared to their native vegetation (grassland or woodland) pairs, and irrigated croplands had 402 Mg C/ha less than their rain‐fed pairs (p < .0001). SIC contents were negatively correlated with estimated groundwater recharge, suggesting that dissolution and leaching may be responsible for SIC losses observed. Under croplands, the remaining SIC had more modern radiocarbon and a δ13C composition that was closer to crop inputs than under native vegetation, suggesting that cultivation has led to faster turnover and incorporation of recent crop carbon into the SIC pool (p < .0001). The losses occurred just 30–100 years after land‐use changes, indicating SIC stocks that were stable for millennia can rapidly adjust to increased soil water flows. Large SIC losses (194–242 Mg C/ha) also occurred below 4.9 m deep under irrigated croplands, with SIC losses lagging behind the downward‐advancing wetting front by ~30 years, suggesting that even deep SIC were affected. These observations suggest that the vertical distribution of SIC in dry ecosystems is dynamic on decadal timescales, highlighting its potential role as a carbon sink or source to be examined in the context of land use and climate change.
Discrepancy between post-treatment infarct volume and 90-day outcome in the ESCAPE randomized controlled trial

Background Some patients with ischemic stroke have poor outcomes despite small infarcts after endovascular thrombectomy, while others with large infarcts sometimes fare better. Aims We explored factors associated with such discrepancies between post-treatment infarct volume (PIV) and functional outcome. Methods We identified patients with small PIV (volume ≤ 25th percentile) and large PIV (volume ≥ 75th percentile) on 24–48-h CT/MRI in the ESCAPE randomized-controlled trial. Demographics, comorbidities, baseline, and 24–48-h stroke severity (NIHSS), stroke location, treatment type, post-stroke complications, and other outcome scales like Barthel Index, and EQ-5D were compared between “discrepant cases” – those with 90-day modified Rankin Scale(mRS) ≤ 2 despite large PIV or mRS ≥ 3 despite small PIV – and “non-discrepant cases”. Multi-variable logistic regression was used to identify pre-treatment and post-treatment factors associated with small-PIV/mRS ≥ 3 and large-PIV/mRS ≤ 2. Sensitivity analyses used different definitions of small/large PIV and good/poor outcome. Results Among 315 patients, median PIV was 21 mL; 27/79 (34.2%) patients with PIV ≤ 7 mL (25th percentile) had mRS ≥ 3; 12/80 (15.0%) with PIV ≥ 72 mL (75th percentile) had mRS ≤ 2. Discrepant cases did not differ by CT versus MRI-based PIV ascertainment, or right versus left-hemisphere involvement (p = 0.39, p = 0.81, respectively, for PIV ≤ 7 mL/mRS ≥ 3). Pre-treatment factors independently associated with small-PIV/mRS ≥ 3 included older age (p = 0.010), cancer, and vascular risk-factors; post-treatment factors included 48-h NIHSS (p = 0.007) and post-stroke complications (p = 0.026). Absence of vascular risk-factors (p = 0.004), CT-based lentiform nucleus sparing (p = 0.002), lower 24-hour NIHSS (p = 0.001), and absence of complications (p = 0.013) were associated with large-PIV/mRS ≤ 2. Sensitivity analyses yielded similar results. Conclusions Discrepancies between functional ability and PIV are likely explained by differences in age, comorbidities, and post-stroke complications, emphasizing the need for high-quality post-thrombectomy stroke care. Clinical trial registration https://clinicaltrials.gov/ct2/show/NCT01778335.
LOMIX, a Mixture of Flaxseed Linusorbs, Exerts Anti-Inflammatory Effects through Src and Syk in the NF-κB Pathway

Although flax (Linum usitatissimum L.) has long been used as Ayurvedic medicine, its anti-inflammatory role is still unclear. Therefore, we aimed to investigate the anti-inflammatory role of a linusorb mixture (LOMIX) recovered from flaxseed oil. Effects of LOMIX on inflammation and its mechanism of action were examined using several in vitro assays (i.e., NO production, real-time PCR analysis, luciferase-reporter assay, Western blot analysis, and kinase assay) and in vivo analysis with animal inflammation models as well as acute toxicity test. Results: LOMIX inhibited NO production, cell shape change, and inflammatory gene expression in stimulated RAW264.7 cells through direct targeting of Src and Syk in the NF-κB pathway. In vivo study further showed that LOMIX alleviated symptoms of gastritis, colitis, and hepatitis in murine model systems. In accordance with in vitro results, the in vivo anti-inflammatory effects were mediated by inhibition of Src and Syk. LOMIX was neither cytotoxic nor did it cause acute toxicity in mice. In addition, it was found that LOB3, LOB2, and LOA2 are active components included in LOMIX, as assessed by NO assay. These in vitro and in vivo results suggest that LOMIX exerts an anti-inflammatory effect by inhibiting the inflammatory responses of macrophages and ameliorating symptoms of inflammatory diseases without acute toxicity and is a promising anti-inflammatory medication for inflammatory diseases.
Impact of COVID‐19 stay‐at‐home orders on weight‐related behaviours among patients with obesity

How the impact of the COVID‐19 stay‐at‐home orders is influencing physical, mental and financial health among vulnerable populations, including those with obesity is unknown. The aim of the current study was to explore the health implications of COVID‐19 among a sample of adults with obesity. A retrospective medical chart review identified patients with obesity from an obesity medicine clinic and a bariatric surgery (MBS) practice. Patients completed an online survey from April 15, 2020 to May 31, 2020 to assess COVID‐19 status and health behaviours during stay‐at‐home orders. Logistic regression models examined the impact of these orders on anxiety and depression by ethnic group. A total of 123 patients (87% female, mean age 51.2 years [SD 13.0]), mean BMI 40.2 [SD 6.7], 49.2% non‐Hispanic white (NHW), 28.7% non‐Hispanic black, 16.4% Hispanic, 7% other ethnicity and 33.1% completed MBS were included. Two patients tested positive for severe acute respiratory syndrome coronavirus 2 and 14.6% reported symptoms. Then, 72.8% reported increased anxiety and 83.6% increased depression since stay‐at‐home orders were initiated. Also 69.6% reported more difficultly in achieving weight loss goals, less exercise time (47.9%) and intensity (55.8%), increased stockpiling of food (49.6%) and stress eating (61.2%). Hispanics were less likely to report anxiety vs NHWs (adjusted odds ratios 0.16; 95% CI, 0.05‐0.49; P = .009). Results here showed the COVID‐19 pandemic is having a significant impact on patients with obesity regardless of infection status. These results can inform clinicians and healthcare professionals about effective strategies to minimize COVID‐19 negative outcomes for this vulnerable population now and in post‐COVID‐19 recovery efforts.
Social Capital as a Mediator through the Effect of Education on Depression and Obesity among the Elderly in China

Objectives: Global aging is an increasingly serious problem. The health problems faced by the elderly, such as depression and obesity, require serious consideration. Education, depression and obesity are inextricably linked; for the elderly, education is constant, and the factors which can mediate the relationship between education, depression and obesity are still being discussed by scholars. The mediating effect of social capital is rarely studied. The objective of this study was to assess the mediating role of cognitive social capital and structural social capital, as well as the effect of education on depression and obesity among the elderly using China Family Panel Studies (CFPS) data. Methods: In total, 4919 respondents were included in the final analysis. Education was measured by years of schooling. Trust and participation were used as measures of cognitive social capital and structural social capital. Depression symptoms and BMI were used as outcomes. Structural equation models were developed to examine the direct and indirect effect of social capital and education on health outcomes. Results: Education was negatively correlated with depression symptom (r = −0.15, p < 0.001), while education was positively correlated with BMI (r = 0.08, p < 0.001). Older adults with a higher education level have higher cognitive social capital (r = 0.11, p < 0.001) and structural social capital (r = 0.20, p < 0.001). Social capital plays a mediatory role. Older adults with higher social capital have a lower risk of depression (cognitive: r = −0.23, p < 0.001; structural: r = −0.03, p < 0.01) but a higher risk of obesity (cognitive: r = 0.06, p < 0.01; structural: r = 0.03, p < 0.01). For depression, the mediating function of cognitive social capital (a1b1= −0.025) is stronger than that of structural social capital (a2b2 = −0.006). While, for obesity, the effects of both cognitive and structural social capital are the same (a1c1 = a2c2 = 0.005). Conclusions: Social capital as a mediator through the effect of education on depression and obesity among the elderly in China. Meanwhile, using the positive effects of social capital to avoid negative effects should also be seriously considered.