Azetidines Kill Multidrug-Resistant Mycobacterium tuberculosis without Detectable Resistance by Blocking Mycolate Assembly.

Tuberculosis (TB) is the leading cause of global morbidity and mortality resulting from infectious disease, with over 10.6 million new cases and 1.4 million deaths in 2021. This global emergency is exacerbated by the emergence of multidrug-resistant MDR-TB and extensively drug-resistant XDR-TB; therefore, new drugs and new drug targets are urgently required. From a whole cell phenotypic screen, a series of azetidines derivatives termed BGAz, which elicit potent bactericidal activity with MIC99 values <10 µM against drug-sensitive Mycobacterium tuberculosis and MDR-TB, were identified. These compounds demonstrate no detectable drug resistance. The mode of action and target deconvolution studies suggest that these compounds inhibit mycobacterial growth by interfering with cell envelope biogenesis, specifically late-stage mycolic acid biosynthesis. Transcriptomic analysis demonstrates that the BGAz compounds tested display a mode of action distinct from the existing mycobacterial cell wall inhibitors. In addition, the compounds tested exhibit toxicological and PK/PD profiles that pave the way for their development as antitubercular chemotherapies.

Involvement of TLRs/NF-κB/ESE-1 signaling pathway in T-2 toxin-induced cartilage matrix degradation.

T-2 toxin, a highly toxic type A monotrichothecene mycotoxin, has been found in many different types of cereals and is considered to be one of the most dangerous naturally occurring forms of food contamination. Globally, consuming grain-based food tainted with T-2 toxin poses significant risks to animal and human health. Prior research has indicated that the presence of T-2 toxin may lead to the demise of chondrocytes and the deterioration of the extracellular matrix of cartilage in degenerative bone and joint conditions, such as Kashin-Beck disease. However, the mechanisms by which T-2 toxin exerts its biological toxicity on the degradation of the extracellular matrix in cartilage are not well understood. In the current study, we found original results that demonstrate an upregulation of Toll-Like Receptors (TLR-2, TLR-4) and ESE-1 expression levels in the articular cartilage of a rat model subjected to T-2 toxin exposure. Furthermore, it was revealed that the exposure to T-2 toxin resulted in an increase in the expression of TLR-2, TLR-4, and ESE-1 in human C28/I2 chondrocytes. The findings of this study indicate that the increased expression of TLR-2, TLR-4, and ESE-1 may contribute to the development of degenerative osteoarthritic disease caused by T-2 toxin. Consistent with our hypotheses, we discovered that T-2 toxin increased the expression of MMP-1 and MMP-13 in human C28/I2 chondrocytes. We used a luciferase reporter gene assay to measure the activity of the ESE-1 promoter and transfected cells with plasmids encoding TLR-2 and TLR-4 to investigate their effects on this activity. TLR-2 and TLR-4 can activate ESE-1 transcriptional gene expression, and this expression is mediated through the NF-κB pathway, additional evidence is provided for the participation of the TLRs/NF-κB/ESE-1 signaling pathway in T-2 toxin-induced cartilage matrix degradation. Together, the findings indicated that the TLRs/NF-κB/ESE-1 signaling pathway played an essential part in T-2 toxin-induced cartilage matrix degradation.

Metformin regulates the LIN28B­mediated JNK/STAT3 signaling pathway through miR­140­3p in subretinal fibrosis.

Subretinal fibrosis (SF) is an important cause of submacular neovascularization that leads to permanent vision loss, but has no effective clinical treatment. The present study examined the influence of metformin on SF, and investigated whether the mechanism involves the microRNA (miR)-140-3p/LIN28B/JNK/STAT3-mediated regulation of oxidative stress, angiogenesis and fibrosis-associated indicators. A mouse model of laser-induced SF was established. In addition, an ARPE-19 fibrotic cell model was established using TGF-ß1. A Cell Counting Kit-8 assay was used to examine cell viability. Flow cytometry was used to measure reactive oxygen species levels, and western blotting was used to detect the levels of proteins associated with epithelial-mesenchymal transition (EMT), signaling and fibrosis. The levels of superoxide dismutase, malondialdehyde, glutathione-peroxidase and catalase were measured using kits. Scratch assays and Transwell assays were used to assess cell migration and invasion, respectively, and reverse transcription-quantitative PCR was used to determine the levels of miR-140-3p and LIN28B. Dual-luciferase assays were used to verify the targeting relationship between miR-140-3p and LIN28B, and coimmunoprecipitation was used to confirm the interaction between LIN28B and JNK. Masson staining and hematoxylin and eosin staining were used to examine collagenous fibers and the histopathology of eye tissue. In ARPE-19 cells induced by TGF-ß1, metformin promoted miR-140-3p expression and inhibited LIN28B expression and JNK/STAT3 pathway activation, thereby inhibiting oxidative stress, EMT and fibrosis in ARPE-19 cells. The overexpression of LIN28B or treatment with the JNK/STAT3 agonist anisomycin partially reversed the inhibitory effect of metformin on oxidative stress and fibrosis in ARPE-19 cells. The dual-luciferase reporter assay and coimmunoprecipitation assay showed that miR-140-3p targeted the 3' untranslated region of LIN28B mRNA and inhibited LIN28B expression. LIN28B targeted and bound to JNK and regulated the JNK/STAT3 pathway. Therefore, it may be concluded that metformin can promote miR-140-3p expression, inhibit LIN28B and then inhibit the JNK/STAT3 pathway to alleviate SF.

Cluster analysis of antiphospholipid antibodies-associated adverse pregnancy outcome patients: based on a 13-years cohort study.

Antiphospholipid antibodies (aPLs) are the leading causes of adverse pregnancy outcomes (APOs). We conducted cluster analysis to identify distinct phenotypes among aPLs-associated APOs patients. This approach aims to facilitate risk stratification and improve pregnancy outcomes for obstetric APS. This was a retrospective study of persistent aPLs positive women cohort in Peking Union Medical College Hospital. Baseline demographic characteristics, clinical manifestation, previous APOs and antibodies profiles were included for hierarchical cluster analysis. Placentae from portions of patients were collected and performed the histopathologic diagnoses. Four clusters among 209 patients with 477 pregnancies were identified. Cluster 1 comprised patients with triple aPLs positivity and demonstrates a high incidence of gestational hypertension (34.92%, P < 0.05) and preterm delivery (20.63%, P < 0.05). Patients in cluster 2 were characterized by lupus anticoagulant (LA) positivity, with high risk of whole gestational APOs. Cluster 3 included patients with isolated aPLs-IgM isotype combined with early miscarriage (60.92%, P = 0.016). Patients in cluster 4 majorly presented aPLs-IgG isotype combined with placenta insufficiency (22.73%). During the follow-up, the live birth rate in cluster 1 and 2 was only 69.20%. Placenta pathology revealed the most severe impairment within cluster 1, whereas clusters 3 and 4 exhibited relatively milder damage. By cluster analysis, we identified four clinical subtypes of aPLs-associated APOs patients. Patients with triple antibodies or high-risk lupus characteristics were prone to occurred gestational hypertension and premature delivery. Isolated LA or aCL/aß2GPI positivity were found to be more frequently associated with early-stage fetal loss.

Toxic Effects of Methylene Blue on the Growth, Reproduction and Physiology of Daphnia magna.

Methylene blue (MB) is a disinfectant used in aquaculture to prevent and treat fish diseases. However, the release of MB can pose a risk to the receiving water bodies. Zooplankton are the most sensitive organisms among aquatic life. Hence, this study examined the acute and chronic toxic effects of MB on zooplankton using Daphnia magna (D. magna) as a test organism to provide basic data for risk assessment. The results show that 48 h-EC50 and 24 h-LC50 were 61.5 ± 2.3 and 149.0 ± 2.2 µg/L, respectively. Chronic exposure to MB affected the heart rate, beat frequency of the thoracic limbs, and reproductive ability of D. magna at environmental concentrations higher than 4.7 µg/L. The cumulative molts, time to production of the first brood, and total number of living offspring were affected at different MB concentrations, while "abortions" were observed in high-exposure groups. The activity of superoxide dismutase was increased, while glutathione S-transferase activity was stimulated at low concentrations and inhibited at high concentrations. In addition, the malondialdehyde content increased with increasing concentrations of MB. Our findings demonstrate the impact of MB on the reproduction and growth of freshwater species, as well as their physiological responses. These results have implications for establishing guidelines on the use of MB in aquaculture and setting discharge standards.

Expressions of uncertainty in invisible scientific and religious phenomena during naturalistic conversation.

Across cultures, studies report more confidence in the existence of unobservable scientific phenomena, such as germs, as compared to unobservable religious phenomena, such as angels. We investigated a potential cultural mechanism for the transmission of confidence in the existence of invisible entities. Specifically, we asked whether parents in societies with markedly different religious profiles-Iran and China-signal differential confidence across the domains of science and religion during unmoderated conversations with their children (N = 120 parent-child dyads in total; 5- to 11-year-olds). The results revealed that parents used fewer lexical cues to uncertainty when discussing scientific phenomena, as compared to religious phenomena. Unsurprisingly, this cross-domain distinction was observed among majority belief, secular parents in China (Study 2). More importantly, however, the same pattern was observed among parents in Iran, a highly religious society (Study 1), as well as among minority belief, religious parents in China (Study 2). Thus, adults in markedly different belief communities spontaneously express less confidence in religious, as compared to scientific, invisible entities in naturalistic conversation. These findings contribute to theories on the role of culture and testimony in the development of beliefs about unobservable phenomena.

Children who appeared or remained overweight or obese predict a higher follow-up blood pressure and higher risk of hypertension: a 6-year longitudinal study in Yantai, China.

Few longitudinal studies have examined the effect of weight status change on blood pressure change over time and incidence of hypertension among Chinese children. The longitudinal study enrolled 17,702 Chinese children aged 7 years in Yantai in 2014 as baseline, with a continuous 5 years of follow-up to 2019. Generalized estimating equation model was fitted to examine the main and interaction effects of weight status change and time with blood pressure and the incidence of hypertension. Compared with the participants who remained normal weight, the participants who remained overweight or obese had higher systolic blood pressure (SBP) (ß = 2.89, p < 0.001) and diastolic blood pressure (DBP) (ß = 1.79, p < 0.001). Significant interactions were identified between weight status change and time with SBP (χ2interaction = 697.77, p < 0.001) and DBP (χ2interaction = 270.49, p < 0.001). The odds ratio (OR) and 95% confidence interval (CI) of hypertension were 1.70 (1.59-1.82) for participants who appeared overweight or obese, 2.26 (2.14-2.40) for participants who remained overweight or obese, compared with the participants who remained normal weight. Those who switched from overweight or obesity to normal weight had almost the same risk of developing hypertension (OR = 1.13, 95% CI: 1.02 to 1.26) as children who remained normal weight. Children who appeared or remained overweight or obese predict a higher follow-up blood pressure and higher risk of hypertension, whereas losing weight could reduce blood pressure and the risk of hypertension. Children who appeared or remained overweight or obese predict a higher follow-up blood pressure and higher risk of hypertension, whereas losing weight could reduce blood pressure and the risk of hypertension.

Long-term exposure to arsenic in drinking water leads to myocardial damage by oxidative stress and reduction in NO.

Chronic arsenic exposure causes myocardial damage. The aim of this study is to investigate if oxidative stress and reduction in NO is involved in the myocardial damage induced by arsenic in drinking water. Rats were divided into a control group and different doses of sodium arsenite. With increasing sodium arsenite concentrations in drinking water, localised inflammatory foci and necrotic myocardial tissues were gradually observed. Compared to the control group, the activities and gene expression of antioxidant enzymes in arsenic-exposed rats decreased. NO content and the NOS activity as well as the expression of NOS mRNA in the myocardial tissue of exposed rats, decreased, and the extracellular NO content of cardiomyocytes treated with sodium arsenite also decreased. The rate of cell apoptosis induced by sodium arsenite decreased after treatment with sodium nitroprusside (an NO donor). In conclusion, arsenic exposure in drinking water can lead to myocardial injury and cardiomyocyte apoptosis through oxidative stress and a reduction in NO content.

Association between urinary phthalate metabolites and hyperuricemia in US adults.

Phthalate metabolites have been detected from urine in most of the US population and have become a public health problem. However, the association between phthalate metabolites and hyperuricemia has been scarcely studied so far. We aimed to evaluate if phthalate metabolites were associated with hyperuricemia in US adults. A total of 8816 participants of the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018 were included in our study. We used multivariable logistic regression models and restricted cubic spline (RCS) models to explore the association between urinary phthalate metabolites and hyperuricemia. Then, stratified analyses were conducted by sex and age. The prevalence of hyperuricemia in the study sample was 20.35%. Compared to the lowest quantile, the odds ratios (ORs) and 95% confidence intervals (CIs) for hyperuricemia were all statistically significant in following phthalate metabolites: 1.34 (1.13-1.58) for the second quartile in Mono-isobutyl phthalate (MiBP), 1.21 (1.01-1.46) for the highest quartile in Mono-(carboxyoctyl) phthalate (MCOP), 0.66 (0.56-0.76) for the second quartile in Mono-(2-ethyl)-hexyl phthalate (MEHP), 1.22 (1.05-1.43) for quartile 2 in Benzyl butyl phthalate (ΣBBP), and 1.43 (1.22-1.66) for the third quartile in high molecular-weight phthalate (ΣHigh MWP), respectively. Our results indicate that several urinary phthalate metabolites are positively associated with the odds of hyperuricemia.

Miraculous, magical, or mundane? The development of beliefs about stories with divine, magical, or realistic causation.

Children's naïve theories about causal regularities enable them to differentiate factual narratives describing real events and characters from fictional narratives describing made-up events and characters (Corriveau, Kim, Schwalen, & Harris, Cognition 113 (2): 213-225, 2009). But what happens when children are consistently presented with accounts of miraculous and causally impossible events as real occurrences? Previous research has shown that preschoolers with consistent exposure to religious teaching tend to systematically judge characters involved in fantastical or religious events as real (Corriveau et al., Cognitive Science, 39 (2), 353-382, 2015; Davoodi et al., Developmental Psychology, 52 (2), 221, 2016). In the current study, we extended this line of work by asking about the scope of the impact of religious exposure on children's reality judgments. Specifically, we asked whether this effect is  domain-general or domain-specific. We tested children in Iran, where regular exposure to uniform religious beliefs might influence children's reasoning about possibility in non-religious domains, in addition to the domain of religion. Children with no or minimal schooling (5- to 6-year-olds) and older elementary school students (9- to 10-year-olds) judged the reality status of different kinds of stories, notably realistic, unusual (but nonetheless realistic), religious, and magical stories. We found that while younger children were not systematic in their judgments, older children often judged religious stories as real but rarely judged magical stories as real. This developmental pattern suggests that the impact of religious exposure on children's reality judgments does not extend beyond their reasoning about divine intervention. Children's justifications for their reality judgments provided further support for this domain-specific influence of religious teaching.

Concentrations, seasonal trends, sources, health risk and subchronic toxicity to the respiratory and immune system of PAHs in PM2.5 in Xi'an.

PM2.5-bound polycyclic aromatic hydrocarbons (PAHs) have been proved to be hazardous to health. Previous studies have focused on the distribution and sources of PAHs, whereas there is little knowledge of the damage to organs. Here we sought to investigate the pollution level and seasonal variation characteristics of PAHs in PM2.5 in Xi'an and assess the health risk, to establish a PAHs exposure model, and investigate the toxicological effects of PAHs on the respiratory and immune functions. A sub-chronic exposure model of PAHs was established by inhalation. The pathological changes of lung tissues were observed with a light microscope. Inflammatory reactions in alveolar lavage fluid were determined using the corresponding kit. The levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) were detected with enzyme linked immunosorbent assay (ELISA) kit; the proliferation of lymphocytes in spleen was detected with methyl tetrazolium (MTT); DNA immune damage was determined with DNA gel electrophoresis. The results showed that (1) the total concentration of 16 PAHs ranged from 41.1 to 387 ng/m3, with a mean value of 170 ng/m3, and the concentration of PAHs in PM2.5 was higher in winter than in other seasons. (2) The sources of PAHs in the atmosphere of Xi'an urban area were mainly coal combustion, and the equivalent carcinogenic concentration of PAHs in PM2.5 was 3.9 ng/m3. (3) Foreign body granuloma formation and inflammatory cell damage were observed in the lungs of rats infected with toxin; the levels of reactive oxygen species (ROS) and mobile device assistant (MDA) increased while nitric oxide synthase (NOS) decreased with the increase of dose; the expression levels of IL-6 and IL-8 elevated with the increase of toxin dose, showing an obvious dose-effect relationship; the level of PAHs damage to cells showed a dose-effect relationship. Sub-chronic exposure to PAHs could cause sustained inflammatory injury to the organism. Measures should be taken to counter the problems of PAHs in PM2.5 in Xi'an and relevant health promotion strategies should be developed.

Association between mixed dietary B vitamin intake and insulin resistance in US middle-aged and older adults without diabetes: The Bayesian kernel machine regression approach.

BACKGROUND AND OBJECTIVES: In daily life, the intake of dietary nutrients is mixed. However, evidence for the association between mixed dietary B vitamin intake and insulin resistance is limited. In this study, we estimated the joint effect of intake of various dietary B vitamins on insulin resistance. METHODS AND STUDY DESIGN: This cross-sectional study used data from the National Health and Nutrition Examination Survey 2011-2018. We included 1,628 middle-aged and 1,058 older adults without diabetes. Multivariable logistic regression and Bayesian kernel machine regression models were constructed. RESULTS: In the multivariable logistic regression, when all B vitamins were included in the model, the ORs (95% CIs) of insulin resistance were 3.06 (1.00-9.37) and 0.42 (0.19- 0.93) for the highest quartile of vitamin B-1 and B-12 intake in the middle-aged group when the lowest quartile was the reference. In the older group, no significant association was observed. In the Bayesian kernel machine regression analysis, a negative trend was noted between mixed B vitamin intake and insulin resistance in both examined groups. The univariate exposure-response function indicated that vitamin B-12 intake was negatively associated with insulin resistance in the middle-aged group, and that vitamin B-6 and dietary folate equivalent intakes were negatively associated with insulin resistance in older group. The bivariate exposure-response function indicated a potential interaction effect between dietary intake of vitamin B-12 and those of vitamin B-1, B-2, niacin, and dietary folate equivalent on insulin resistance in older people. CONCLUSIONS: Our results suggest that mixed dietary B vitamin intake tends to decrease the OR of insulin resistance both in middle-aged and older people.

Mechanism of Action of Yin Nourishing and Heat Clearing Prescription in Treating Cough Variant Asthma Based on Network Pharmacology and Molecular Docking Verification.

Objective: To explore the mechanism of action of the yin nourishing and heat clearing prescription in treating cough variant asthma (CVA) based on network pharmacology (NP). Methods: The active ingredients and targets of the yin nourishing and heat clearing prescription were screened using the Traditional Chinese Medicine System Pharmacology Analysis Platform (TCMSP); CVA targets were screened by the GeneCards, NCBI gene, and OMIM databases to construct the component-target network and the protein-protein interaction (PPI) network. GO functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the target genes were performed to construct the component-disease-pathway-target biological network. Moreover, CVA-related core target structures with high values were subjected to molecular docking (MD) with the active components. Results: We found 265 eligible targets in the prescription and 1115 CVA-related genes. The medicine targets were intersected with disease targets, which yielded 148 common targets. After topology analysis, 66 key targets were screened. Upon GO functional annotation, 2408 biological processes, 153 molecular functions, and 162 KEGG pathways were enriched. Molecular docking results suggested that the major active ingredients of the prescription showed high affinity to the key targets, among which AKT1 might be the most important target. Conclusions: Active ingredients might act on AKT1, IL-6, VEGFA, IL-1B, and JUN to suppress eosinophil accumulation, decrease histamine release, suppress airway inflammation, regulate the airway immune microenvironment, increase autophagy in lung tissue, inhibit mucus production, and reduce airway resistance and hyperresponsiveness, thus treating CVA. Our findings provide a reference for further research and clinical applications of the prescription.

Association between mixed dioxin exposure and hyperuricemia in U.S. adults: A comparison of three statistical models.

BACKGROUND: Previous studies on the relationship between dioxin exposures and hyperuricemia have usually been based on multi-chemical linear models. However, the complex nonlinear relationship and interaction between mixed dioxin exposures and hyperuricemia have seldom been studied. In this study, we applied three different statistical models to assess the joint effect of 12 dioxins on hyperuricemia. METHODS: A total of 7 dioxin-like polychlorinated biphenyls (DL-PCBs), 3 polychlorinated dibenzo-p-dioxins (PCDDs), and 2 polychlorinated dibenzofurans (PCDFs) were measured in the serum of adults by the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2004. We fitted multivariable logistic regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models to estimate the association of individual and mixed dioxin exposures with hyperuricemia. RESULTS: Among the 1008 individuals included in our analysis, 20.04% had hyperuricemia. In the multivariable logistic regression established for each single dioxin, PCB28, PCB74, PCB105, PCB118, and 1,2,3,4,6,7,8-HPCDD were positively associated with hyperuricemia. With including all dioxins in the multivariable logistic regression model simultaneously, only PCB28 and 1,2,3,4,6,7,8-HPCDD were positively associated with hyperuricemia. In the WQS regression model, the WQS index was significantly associated (OR (95% CI): 2.32 (1.26, 4.28)) with hyperuricemia, and 1,2,3,4,6,7,8-HPCDD (weighted 0.22) had the largest contribution. In BKMR analysis, a significant positive association was found between mixed dioxin exposure and hyperuricemia when all dioxins were at their 60th percentile or above, compared to their 50th percentile. The univariate exposure-response function showed that PCB105 and PCB118 were positively associated with hyperuricemia. CONCLUSION: By comparing the three statistical models, we concluded that the whole-body burden of 12 dioxins was significantly positively associated with hyperuricemia. PCB105, PCB118, and 1,2,3,4,6,7,8-HPCDD played the most important roles in hyperuricemia.

Temporal Associations between Tri-Ponderal Mass Index and Blood Pressure in Chinese Children: A Cross-Lag Analysis.

Background: No longitudinal studies have explored the relationship between tri-ponderal mass index (TMI) and blood pressure (BP) in children. This study is aimed to investigate the temporal associations between TMI and BP among children in China. Methods: A longitudinal study was carried out with Chinese children from 2014 to 2019. Data of the anthropometric examination and blood pressure were collected annually. TMI was calculated by dividing weight by the cube of height. BP was measured using a standard mercury sphygmomanometer. We investigated temporal associations between TMI and BP with a cross-lagged panel model using repeated measure data from 2014 (Wave 1), 2016 (Wave 2), and 2018 (Wave 3). Results: Results of the cross-lagged panel model showed that TMI was associated with subsequent BP. Participants with higher levels of TMI presented higher levels of BP (Wave 1: ß = 0.737 for systolic blood pressure (SBP) and ß = 0.308 for diastolic blood pressure (DBP), Wave 2: ß = 0.422 for SBP and ß = 0.165 for DBP, p < 0.01). In addition, children with higher BP could also present higher TMI (Wave 1: ß = 0.004 for SBP and ß = 0.006 for DBP, Wave 2: ß = 0.003 for SBP and ß = 0.005 for DBP, p < 0.01), but the cross-lag path coefficient indicated that the influence of TMI on BP was stronger than the influence of BP on TMI. Conclusions: There was a temporal association between TMI and BP in Chinese children. Higher TMI predicted higher subsequent BP rather than the reverse relationship.

Threshold effects and interactive effects of total zinc and selenium intake on cognitive function in older adults.

BACKGROUND & AIMS: The aim of this study was to assess threshold effects and interactive effects of total zinc and selenium intake on cognitive function in older adults. METHODS: We used data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Zinc and selenium intake were obtained through two 24-h dietary recalls. Cognitive performance was evaluated by the Digit Symbol Substitution Test (DSST). Smooth curve fitting, two-piecewise multivariable linear regression models, binary logistic regression model, multiplicative interactions model, and additive interactions model were used to evaluate the association between zinc, selenium intake and their interactive effect on cognitive function. RESULTS: A total of 2450 participants aged 60 years or older were included. Zinc and selenium intake was non-linearly associated with cognitive function. The inflection point for zinc intake was 8.94 mg/d in males and 7.58 mg/d in females. When zinc intake was below inflection point, zinc intake was positively associated with the DSST test in males (ß = 1.02, 95% CI, 0.44 to 1.60) and females (ß = 0.94, 95% CI, 0.26 to 1.62). When zinc intake above inflection point, there is no association between zinc intake and the DSST test in both sexs. The inflection point for selenium intake was 186.33 µg/d in males and 68.40 µg/d in females. Among males, the ß (95% CIs) was 0.03 (0.01,0.06) to the left side of the inflection point and -0.06 (-0.10, -0.02) to the right of the inflection point. Among females, the ß (95% CIs) was 0.13 (0.04,0.22) to the left side of the inflection point and 0.01 (-0.01,0.04) to the right of the inflection point. Besides, zinc and selenium have significant interaction on DSST test only in females (P = 0.028, RERI = 0.418). CONCLUSIONS: The present study demonstrated that zinc and selenium intake was non-linearly associated with cognitive function in different sex. There was an interactive effect between zinc and selenium intake on improving cognitive function, especially in females.

Climate change drives NDVI variations at multiple spatiotemporal levels rather than human disturbance in Northwest China.

Changes in land management and climate alter vegetation dynamics; however, the factors driving vegetation changes remain elusive at multiple spatiotemporal levels. Here, we assess the drivers of changes in greenness from 2000 to 2015 in Northwest China (NW China). We used multiple stepwise linear regression (MSLR), redundancy analysis (RDA), and 12 other models to quantify the impacts of precipitation and temperature metrics, gross domestic product (GDP), population, and grazing intensity on the normalized difference vegetation index (NDVI) at three administrative levels (county, town, and village), four temporal levels (yearly, May, July, and September), two vegetation types (woodland and grassland), and at annual precipitation gradients of <200, 200-400, and >400 mm. The results suggest that NW China underwent vegetation greening from 2000 to 2015. Precipitation and temperature were the most influential factors contributing to the NDVI change. Population was the main determinant of NDVI under the precipitation gradient of <200 mm, and the effect of GDP on NDVI was moderate. On the temporal scale, annual precipitation, precipitation before the previous year, and precipitation in the current year determined the NDVI in May, July, and September, respectively, for both woodland and grassland. At multiple scales, climate change was the primary driver of vegetation change in NW China, rather than human disturbance. These findings expand our understanding on drivers of NDVI at multiple levels over a long period. Measures to manage decreasing vegetation coverage may be more effective and could be implemented sooner based on predicted climate change in drylands worldwide.

Children's Ideas About What Can Really Happen: The Impact of Age and Religious Background.

Five- to 11-year-old U.S. children, from either a religious or secular background, judged whether story events could really happen. There were four different types of stories: magical stories violating ordinary causal regularities; religious stories also violating ordinary causal regularities but via a divine agent; unusual stories not violating ordinary causal regularities but with an improbable event; and realistic stories not violating ordinary causal regularities and with no improbable event. Overall, children were less likely to judge that religious and magical stories could really happen than unusual and realistic stories although religious children were more likely than secular children to judge that religious stories could really happen. Irrespective of background, children frequently invoked causal regularities in justifying their judgments. Thus, in justifying their conclusion that a story could really happen, children often invoked a causal regularity, whereas in justifying their conclusion that a story could not really happen, they often pointed to the violation of causal regularity. Overall, the findings show that children appraise the likelihood of story events actually happening in light of their beliefs about causal regularities. A religious upbringing does not impact the frequency with which children invoke causal regularities in judging what can happen, even if it does impact the type of causal factors that children endorse.

Diagnostic Value of Urinary MicroRNAs for Bladder Cancer in Asia.

This study aimed to explore the diagnostic performance of urinary microRNAs (miRNAs) in bladder cancer (BC) in the Asian population. PubMed, Embase, Web of Science and Cochrane Library were searched for relevant literature on the diagnostic performance of miRNAs for BC in the Asian population. Subsequently, quality assessment on diagnostic accuracy studies-2 (QUADAS-2) was used for evaluating the quality of the included literature, and Stata version 15.0 for statistical analysis. Eleven published studies, including 1,220 BC patients, met the inclusion and exclusion criteria and, therefore, were investigated in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of urinary miRNAs in the diagnosis of BC were 0.80 (95%CI: 0.74-0.85), 0.76 (95%CI: 0.69-0.81), 3.28 (95%CI: 2.63-4.10), 0.26(95%CI: 0.21-0.33), respectively. Additionally, the area under the curve (AUC) was 0.85 in the summary receiver operating characteristic (SROC) curve, and the diagnostic odds ratio (DOR) was 12.39 (95%CI: 9.00-17.07). In conclusion, urinary miRNAs show good performance in diagnosing BC in Asia, and, therefore, can serve as effective biomarkers for early clinical screening and auxiliary diagnosis of BC. Key Words: MicroRNAs, Bladder cancer, Diagnostic value, Meta-analysis.