Zn Single-Atom Catalysts Enable the Catalytic Transfer Hydrogenation of α,ß-Unsaturated Aldehydes.

Highly active nonprecious-metal single-atom catalysts (SACs) toward catalytic transfer hydrogenation (CTH) of α,ß-unsaturated aldehydes are of great significance but still are deficient. Herein, we report that Zn-N-C SACs containing Zn-N3 moieties can catalyze the conversion of cinnamaldehyde to cinnamyl alcohol with a conversion of 95.5% and selectivity of 95.4% under a mild temperature and atmospheric pressure, which is the first case of Zn-species-based heterogeneous catalysts for the CTH reaction. Isotopic labeling, in situ FT-IR spectroscopy, and DFT calculations indicate that reactants, coabsorbed at the Zn sites, proceed CTH via a "Meerwein-Ponndorf-Verley" mechanism. DFT calculations also reveal that the high activity over Zn-N3 moieties stems from the suitable adsorption energy and favorable reaction energy of the rate-determining step at the Zn active sites. Our findings demonstrate that Zn-N-C SACs hold extraordinary activity toward CTH reactions and thus provide a promising approach to explore the advanced SACs for high-value-added chemicals.

Elevated circulating follicle stimulating hormone level is associated with dyslipidemia in male type 2 diabetes mellitus patients: A cross-sectional study.

AIMS: Type 2 diabetes mellitus (T2DM) commonly combines with dyslipidemia, and both are known as the risk factors of cardiovascular events and aggravate the arteriosclerosis progression. In this study, we investigated the relationship between follicle-stimulating hormone (FSH) and lipid profiles in male T2DM patients. MATERIALS AND METHODS: We collected clinical data of male T2DM patients in the Chinese Han population hospitalised from January 2018 to June 2020. A total of 963 patients with a mean age of 58.89 ± 12.25 years old were enroled in this study. RESULTS: The results showed that the levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL)-C levels were decreased gradually from the highest quartile groups (Q4) to Q1 group relevant to luteinising hormone and FSH, and no significant difference was observed in high-density lipoprotein-C levels among Q4-Q1 groups. Sub-groups analysis showed that, with the increased FSH level, TC, TG, and LDL-C levels were increased in the elder group (40-59 years old) than those in the younger group (20-39 years old). Spearman's analysis revealed a positive correlation between FSH and the levels of TC, TG, and LDL-C (r = 0.354, r = 0.336, r = 0.312, p < 0.001, respectively). The effect of FSH is independent of the changes in total testosterone level. Multivariate analysis found that increased FSH levels (≥9.26 mIU/mL) and decreased total testosterone levels (<13.30 nmol/L) were positively correlated with high TC, TG, and LDL-Cemia (OR = 4.014, 1.565, 1.602, 1.660, 2.127, 1.322, respectively, p < 0.05). CONCLUSIONS: Our data suggest that high serum FSH level in male T2DM patients could be a potential independent risk factor correlated with the elevated TC, TG, and LDL-C.

Long-term Use of Proton Pump Inhibitors is Associated With An Increased Risk of Nonalcoholic Fatty Liver Disease.

BACKGROUNDS: The adverse effects of long-term use of proton pump inhibitors (PPIs) have led to growing concern. The association between PPIs use and the risks of nonalcoholic fatty liver disease (NAFLD) remains controversial. GOAL: The aim of this study was to investigate the association between PPIs use and the risks of NAFLD among the general adult population in the United States. STUDY: We performed a cross-sectional study by extracting data from the National Health and Nutrition Examination Survey of 2017 to 2018. The association between PPIs use and NAFLD risks was analyzed by weighted multivariate logistic regression. RESULTS: Among the 4238 participants included in this study, 2167 were diagnosed with NAFLD. In the multivariate logistic regression model, PPIs use was associated with increased risks of NAFLD [odds ratio (OR): 1.318, 95% CI: 1.044-1.663; P=0.020]. This association was nonsignificant in participants taking PPIs for ˂5 years (OR: 0.846, 95% CI: 0.579-1.238; P=0.390), whereas it remained significant in participants taking PPIs for more than 5 years (OR: 2.016, 95% CI: 1.366-2.975; P=0.031). Further analysis showed that the use of PPIs was positively associated with risks of severe hepatic steatosis (OR: 1.451, 95% CI: 1.034-2.036; P=0.031) but not with mild-to-moderate steatosis (OR: 1.242, 95% CI: 0.886-1.741; P=0.208). CONCLUSIONS: This study indicated that taking PPIs was associated with increased risks of NAFLD, especially severe hepatic steatosis. Awareness should be raised regarding the potential risks of NAFLD when prescribing PPIs.

Mediation effect of sleep time on the association between outdoor activity and myopia in Chinese children and adolescents: a cross-sectional study.

BACKGROUND: This study aimed to assess the association between outdoor activity and myopia among children and adolescents and investigate whether sleep time could mediate this relationship. METHODS: This cross-sectional study was performed on students aged 4-16 years in China, from August 2021 to January 2022. Outdoor activity was assessed by the Assessment Questionnaire of Exposure to Sunlight Activities for Students (AQESAS). Binary logistic regression combined with the mediation analysis was used to analyze the association of AQESAS with myopia and the mediating effect of sleep time on this relationship. RESULTS: The prevalence of myopia was 53.51% (N = 1609). Multivariate logistic regression analysis showed that more sleep time (OR = 0.794, 95%CI: 0.707-0.893) and a higher score of AQESAS (OR = 0.989, 95%CI: 0.981-0.996) were significantly associated with a decreased risk of myopia. Mediation analysis revealed that sleep time plays a mediating role in the association between outdoor activity and myopia (ACME = -0.0006, P < 0.001), and the mediation proportion was 19.7%. CONCLUSION: Outdoor activity affects myopia directly and indirectly through sleep time. The result suggested that children may be able to reduce the risk of myopia by promoting sleep through increased awareness of outdoor activity and exposure to sunlight.

Effects of apparent temperature on daily outpatient and inpatient visits for cause-specific respiratory diseases in Ganzhou, China: a time series study.

BACKGROUND: Non-optimum temperatures are associated with increased risk of respiratory diseases, but the effects of apparent temperature (AT) on respiratory diseases remain to be investigated. METHODS: Using daily data from 2016 to 2020 in Ganzhou, a large city in southern China, we analyzed the impact of AT on outpatient and inpatient visits for respiratory diseases. We considered total respiratory diseases and five subtypes (influenza and pneumonia, upper respiratory tract infection (URTI), lower respiratory tract infection (LRTI), asthma and chronic obstructive pulmonary disease [COPD]). Our analysis employed a distributed lag nonlinear model (DLNM) combined with a generalized additive model (GAM). RESULTS: We recorded 94,952 outpatients and 72,410 inpatients for respiratory diseases. We found AT significantly non-linearly associated with daily outpatient and inpatient visits for total respiratory diseases, influenza and pneumonia, and URTI, primarily during comfortable AT levels, while it was exclusively related with daily inpatient visits for LRTI and COPD. Moderate heat (32.1 °C, the 75.0th centile) was observed with a significant effect on both daily outpatient and inpatient visits for total respiratory diseases at a relative risk of 1.561 (1.161, 2.098) and 1.276 (1.027, 1.585), respectively (both P < 0.05), while the results of inpatients became insignificant with the adjustment for CO and O3. The attributable fractions in outpatients and inpatients were as follows: total respiratory diseases (24.43% and 18.69%), influenza and pneumonia (31.54% and 17.33%), URTI (23.03% and 32.91%), LRTI (37.49% and 30.00%), asthma (9.83% and 3.39%), and COPD (30.67% and 10.65%). Stratified analyses showed that children ≤5 years old were more susceptible to moderate heat than older participants. CONCLUSIONS: In conclusion, our results indicated moderate heat increase the risk of daily outpatient and inpatient visits for respiratory diseases, especially among children under the age of 5.

[Risk factors for embolism in children with refractory Mycoplasmapneumoniae pneumonia and construction of a nomogram model for prediction of embolism]. / éš¾æ²»æ€§è‚ºç‚Žæ”¯åŽŸä½“è‚ºç‚Žæ‚£å„¿åˆå¹¶æ “å¡žçš„å±é™©å› ç´ åˆ†æžåŠåˆ—çº¿å›¾é¢„æµ‹æ¨¡åž‹çš„æž„å»º.

OBJECTIVES: To study the risk factors for embolism in children with refractory Mycoplasma pneumoniae pneumonia (RMPP) and to construct a nomogram model for prediction of embolism. METHODS: This retrospective study included 175 children diagnosed with RMPP at Children's Hospital Affiliated toZhengzhou University from January 2019 to October 2023. They were divided into two groups based on the presence of embolism: the embolism group (n=62) and the non-embolism group (n=113). Multivariate logistic regression analysis was used to screen for risk factors of embolism in children with RMPP, and the R software was applied to construct the nomogram model for prediction of embolism. RESULTS: Multivariate logistic regression analysis indicated that higher levels of D-dimer, interleukin-6 (IL-6) and neutrophil to lymphocyte ratio (NLR), lung necrosis, and pleural effusion were risk factors for embolism in children with RMPP (P<0.05). The area under the curve of the nomogram model for prediction of embolism constructed based on the aforementioned risk factors was 0.912 (95%CI: 0.871-0.952, P<0.05). The Hosmer-Lemeshow goodness-of-fit test showed that the model had a good fit with the actual situation (P<0.05). Calibration and decision curve analysis indicated that the model had high predictive efficacy and clinical applicability. CONCLUSIONS: Higher levels of D-dimer, IL-6 and NLR, lung necrosis, and pleural effusion are risk factors for embolism in children with RMPP. The nomogram model based on these risk factors has high clinical value for predicting embolism in children with RMPP.

Diversified chemical profiles of cuticular wax on alpine meadow plants of the Qinghai-Tibet Plateau.

MAIN CONCLUSION: The alpine meadow plants showed great intra- and inter-genera variations of chemical profiles of cuticular waxes. Developing an understanding of wax structure-function relationships that will help us tackle global climate change requires a detailed understanding of plant wax chemistry. The goal in this study was to provide a catalog of wax structures, abundances, and compositions on alpine meadow plants. Here, leaf waxes from 33 plant species belonging to 11 families were sampled from alpine meadows of the east side of the Qinghai-Tibet Plateau. Across these species, total wax coverage varied from 2.30 µg cm-2 to 40.70 µg cm-2, showing variation both within as well as between genera and suggesting that wax variation is subject to both environmental and genetic effects. Across all wax samples, more than 140 wax compounds belonging to 13 wax compound classes were identified, including both ubiquitous wax compounds and lineage-specific compounds. Among the ubiquitous compounds (primary alcohols, alkyl esters, aldehydes, alkanes, and fatty acids), chain length profiles across a wide range of species point to key differences in the chain length specificity of alcohol and alkane formation machinery. The lineage-specific wax compound classes (diols, secondary alcohols, lactones, iso-alkanes, alkyl resorcinols, phenylethyl esters, cinnamate esters, alkyl benzoates, and triterpenoids) nearly all consisted of isomers with varying chain lengths or functional group positions, making the diversity of specialized wax compounds immense. The comparison of species relationships between chemical data and genetic data highlighted the importance of inferring phylogenetic relationships from data sets that contain a large number of variables that do not respond to environmental stimuli.

Celastrol pretreatment attenuates concanavalin A-induced hepatitis in mice by suppressing interleukin-6/STAT3-interleukin-17 signaling.

BACKGROUND AND AIM: Celastrol is extracted from Tripterygium wilfordii Hook F. It has been reported to have protective effects against various liver diseases and immune regulation of autoimmune diseases. However, little is known about whether celastrol protects against immune-mediated hepatitis. This study aimed to investigate the effect of celastrol on liver injury induced by concanavalin A (ConA) and the potential mechanisms. METHODS: Intravenous administration of ConA was applied to induce acute liver injury in mice with or without pretreatment of celastrol. The effects of celastrol on ConA-induced liver injury were further demonstrated by biochemical and histopathological assessments, immunoblotting, and flow cytometry analysis. RESULTS: Both biochemical and histopathological observations showed that pretreatment of celastrol significantly ameliorated liver injury induced by ConA. Moreover, the hepatocyte apoptosis and inflammatory responses induced by ConA were also improved in celastrol-pretreated mice. Further studies revealed that these improvements were characterized as the celastrol-mediated suppression of total interleukin (IL)-17 from liver mononuclear cells in ConA-treated mice. Flow cytometry analysis suggested that celastrol specifically decreased IL-17 production by CD4+ T cells but not by CD8+ T cells. Fundamentally, pretreatment with celastrol inhibited both the IL-6 produced by F4/80+ macrophages and the IL-6 receptor on Th17 cells in the liver, which further led to the downregulated activation of STAT3, thus accounting for blocked Th17 signaling. CONCLUSIONS: Celastrol may exhibit immune regulatory effects by regulating IL-6/STAT3-IL-17 signaling in ConA-induced hepatitis, which suggested new potentials for celastrol to be applied in treating immune-mediated liver diseases.

The imbalance between Bregs, Tfh, and Tregs in patients with anti-N-methyl-D-aspartate receptor encephalitis.

OBJECTIVE: To detect the alteration of regulatory B cells (Bregs), follicular helper T cells (Tfh), and regulatory T cells (Tregs) frequencies in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. Analyze their association with clinical severity and activity, and explore the effects of different immunotherapies on those immune cell subsets. METHODS: We enrolled 21 patients with anti-NMDAR encephalitis, 22 patients with neuromyelitis optica spectrum disorder (NMOSD), 14 patients with idiopathic intracranial hypertension (IIH), and 20 healthy controls (HC) in our study. The frequencies of various immune cell subsets were determined using flow cytometry. RESULTS: Compared to patients with IIH and HC, the frequencies of CD24hiCD38hi transitional B cells as well as Tregs were significantly lower while the frequency of Tfh was significantly higher in patients with anti-NMDAR encephalitis. The frequency of CD24hiCD38hi transitional B cells was significantly lower in the acute stage than in the recovery stage, and was negatively correlated with the modified Rankin scale (mRS) and the clinical assessment scale for autoimmune encephalitis (CASE). The frequency of CD24hiCD38hi transitional B cells at the last follow-up after rituximab (RTX) treatment was significantly higher than those treated with oral immunosuppressants or untreated. There was no clear difference between anti-NMDAR encephalitis and NMOSD in the above immune cell subsets. CONCLUSION: We suggested that the frequencies of CD24hiCD38hi transitional B cells and Tregs were decreased while the frequency of Tfh was increased in patients with anti-NMDAR encephalitis. CD24hiCD38hi transitional B cells frequency may be a potential indicator to estimate the disease activity and severity.

Tailoring Amorphous PdCu Nanostructures for Efficient C-C Cleavage in Ethanol Electrooxidation.

The large-scale application of direct ethanol fuel cells has long been obstructed by the sluggish ethanol oxidation reaction at the anode. Current wisdom for designing and fabricating EOR electrocatalysts has been focused on crystalline materials, which result in only limited improvement in catalytic efficiency. Here, we report the amorphous PdCu (a-PdCu) nanomaterials as superior EOR electrocatalysts. The amorphization of PdCu catalysts can significantly facilitate the C-C bond cleavage, which thereby affords a C1 path faradic efficiency as high as 69.6%. Further tailoring the size and shape of a-PdCu nanocatalysts through the delicate kinetic control can result in a maximized mass activity up to 15.25 A/mgPd, outperforming most reported catalysts. Notably, accelerated durability tests indicate that both the isotropic structure and one-dimensional shape can dramatically enhance the catalytic durability of the catalysts. This work provides valuable guidance for the rational design and fabrication of amorphous noble metal-based electrocatalysts for fuel cells.

The Effects of Epicuticular Wax on Anthracnose Resistance of Sorghum bicolor.

Cuticular waxes are mixtures of hydrophobic compounds covering land plant surfaces and play key roles in plant resistance to abiotic and biotic stresses. However, it is still not clear whether the epicuticular wax could protect the plants from infection by anthracnose, one of the most important plant diseases worldwide, which seriously infects sorghum and causes great yield loss. In this study, Sorghum bicolor L., an important C4 crop with high wax coverage, was selected to analyze the relationship between epicuticular wax (EW) and anthracnose resistance. In vitro analysis indicated that the sorghum leaf wax significantly inhibited the anthracnose mycelium growth of anthracnose on potato dextrose agar (PDA) medium, with the plaque diameter smaller than that grown on medium without wax. Then, the EWs were removed from the intact leaf with gum acacia, followed by the inoculation of Colletotrichum sublineola. The results indicated that the disease lesion was remarkably aggravated on leaves without EW, which showed decreased net photosynthetic rate and increased intercellular CO2 concentrations and malonaldehyde content three days after inoculation. Transcriptome analysis further indicated that 1546 and 2843 differentially expressed genes (DEGs) were regulated by C. sublineola infection in plants with and without EW, respectively. Among the DEG encoded proteins and enriched pathways regulated by anthracnose infection, the cascade of the mitogen-activated protein kinases (MAPK) signaling pathway, ABC transporters, sulfur metabolism, benzoxazinoid biosynthesis, and photosynthesis were mainly regulated in plants without EW. Overall, the EW increases plant resistance to C. sublineola by affecting physiological and transcriptome responses through sorghum epicuticular wax, improving our understanding of its roles in defending plants from fungi and ultimately benefiting sorghum resistance breeding.

Alterations in the gut microbiome and metabolome profiles of septic rats treated with aminophylline.

The treatment of sepsis remains a major challenge worldwide. Aminophylline has been shown to have anti-inflammatory effects; however, the role of aminophylline in sepsis, a disease characterized by immune dysregulation, is unknown. In this study, we combined microbiome sequencing and metabolomic assays to investigate the effect of aminophylline administration on the intestinal flora and metabolites in septic rats. Sixty SD rats were randomly divided into three groups: a sham-operated (SC) group, a sepsis model (CLP) group and a CLP + aminophylline treatment (Amino) group. The intestinal flora and metabolic profile of rats in the CLP group were significantly different than those of the SC group, while aminophylline administration resulted in a return to a state similar to healthy rats. Differential abundance analysis showed that aminophylline significantly back-regulated the abundance of Firmicutes, unidentified_Bacteria, Proteobacteria, Lactobacillus, Escherichia-Shigella and other dominant bacteria (P < 0.05) and altered chenodeoxycholic acid, isolithocholic acid and a total of 26 metabolites (variable importance in the projection (VIP) > 1, P < 0.05). In addition, we found that there were significant correlations between differential metabolites and bacterial genera of the Amino and CLP groups. For example, Escherichia-Shigella was associated with 12 metabolites, and Lactobacillus was associated with two metabolites (P < 0.05), suggesting that differences in the metabolic profiles caused by aminophylline were partly dependent on its influence on the gutmicrobiome. In conclusion, this study identified a novel protective mechanism whereby aminophylline could regulate disordered intestinal flora and metabolites in septic rats.

Association of ambient fine particulate matter exposure with gestational diabetes mellitus and blood glucose levels during pregnancy.

BACKGROUND: Previous studies have examined the associations between ambient fine particulate matter (PM2.5) exposure and gestational diabetes mellitus (GDM). However, limited studies explored the relationships between PM2.5 exposure and blood glucose levels during pregnancy, especially in highly polluted areas. OBJECTIVES: To examine the associations of prenatal ambient PM2.5 exposure with GDM and blood glucose levels, and to identify the sensitive exposure windows in a highly air-polluted area. METHODS: From July 2016 to October 2017, a birth cohort study was conducted in Beijing, China. Participants were interviewed in each trimester regarding demographics, lifestyle, living and working environment, and medical conditions. Participant's daily ambient PM2.5 levels from 3 m before last menstrual period (LMP) to the third trimester was estimated by a hybrid spatiotemporal model. Indoor air quality index was calculated based on environmental tobacco smoke, ventilation, cooking, painting, pesticide, and herbicide use. Distributed lag non-linear model was applied to explore the sensitive weeks of PM2.5 exposure. RESULTS: Of 165 pregnant women, 23 (13.94%) developed GDM. After adjusting for potential confounders, PM2.5 exposure during the 1st trimester was associated with higher odds of GDM (10 µg/m3 increase: OR = 1.89, 95% CI: 1.04-3.49). Each 10 µg/m3 increase in PM2.5 during the 2nd trimester was associated with 17.70% (2.21-33.20), 15.99% (2.96-29.01), 18.82% (4.11-33.52), and 17.10% (3.28-30.92) increase in 1-h, 2-h, Δ1h-fasting (1-h minus fasting), and Δ2h-fasting (2-h minus fasting) blood glucose levels, respectively. PM2.5 exposure at 24th-27th weeks after LMP was associated with increased GDM risk. We identified sensitive exposure windows of 21st-24th weeks for higher 1-h and 2-h blood glucose levels and of 20th-22nd weeks for increased Δ1h-fasting and Δ2h-fasting. CONCLUSIONS: Ambient PM2.5 exposure during the second trimester was associated with higher odds of GDM and higher blood glucose levels. Avoiding exposure to high air pollution levels during the sensitive windows might prevent women from developing GDM.

GhMYB7 promotes secondary wall cellulose deposition in cotton fibres by regulating GhCesA gene expression through three distinct cis-elements.

Cotton fibre is the most important source for natural textiles. The secondary cell walls (SCWs) of mature cotton fibres contain the highest proportion of cellulose content (> 90%) in any plant. The onset and progression of SCW cellulose synthesis need to be tightly controlled to balance fibre elongation and cell wall deposition. However, regulatory mechanisms that control cellulose synthesis during cotton fibre growth remain elusive. Here, we conducted genetic and functional analyses demonstrating that the R2R3-MYB GhMYB7 controls cotton fibre cellulose synthesis. Overexpression of GhMYB7 in cotton sped up SCW cellulose biosynthesis in fibre cells, and led to shorter fibres with thicker walls. By contrast, RNA interference (RNAi) silencing of GhMYB7 delayed fibre SCW cellulose synthesis and resulted in elongated fibres with thinner walls. Furthermore, we demonstrated that GhMYB7 regulated cotton fibre SCW cellulose synthases by directly binding to three distinct cis-elements in the respective GhCesA4, GhCesA7 and GhCesA8 promoters. We found that this regulatory mechanism of cellulose synthesis was 'hi-jacked' also by other GhMYBs. Together, our findings uncover a hitherto-unknown mechanism that cotton fibre employs to regulate SCW cellulose synthesis. Our results also provide a strategy for genetic improvement of SCW thickness of cotton fibre.

CGRP-modulated M2 macrophages regulate osteogenesis of MC3T3-E1 via Yap1.

Bone fractures are one of the most frequent injuries in the musculoskeletal system. Despite the best treatment efforts, a large proportion of bone fracture cases still display undesirable outcomes. Here, we verified that calcitonin gene-related peptide (CGRP), a 37-amino acid neuropeptides, might be a critical regulator that link the nervous, immune and skeletal systems during bone healing. We used a CGRP overexpression lentiviral system and stably transfected M2 macrophages. Then, we investigated the biological function and the intrinsic mechanisms of CGRP on M2 macrophages. We confirmed that CGRP downregulated osteogenic factors (BMP2, BMP6, WNT10b and OSM) secretion at first and promoted them late on (p < 0.05). In addition, we utilized an indirect coculture system and further ascertain the influences of CGRP-induced M2 macrophages on MC3T3 osteogenesis. The results implied that CGRP-modulated osteoimmune environment elicit multiple effects on osteogenesis of MC3T3 during the entire observation period. Notably, verteporfin, a yes-associated protein 1 (Yap1) inhibitor, impaired CGRP effects significantly in our experiments. Taken together, our findings illustrated that CGRP might regulate osteogenesis by modulating the osteoimmune response of M2 macrophages via Yap1.

A bespoke reagent free amperometric chloride sensor for drinking water.

Chloride quantification is important in drinking water quality control. A bespoke, rapid and reagent free electrochemical method is reported for a simple and accurate chloride sensor specifically for mineral water without the need for added electrolyte. The voltammetry used embraces first the reduction of oxygen to clean and activate the electrode surface and ensure reproducibility without the requirement for any mechanical polishing, followed by silver chloride formation and stripping. A linear correlation was found with silver chloride stripping peak currents and chloride concentrations within the range of 0.4 mM to 3.2 mM on a silver macro disc electrode. The chloride concentrations in two different mineral water samples were measured giving excellent agreement with independent analysis.

The effects and safety of activators of glucokinase versus placebo in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

We undertook a systematic review and meta-analysis to assess the effects and safety of activators of glucokinase (GKAs) in patients with type 2 diabetes mellitus (T2DM). 11 RCTs, including 2,429 participants, are enrolled in our study. According to different doses, we divided the studies into 3 groups: low-dose group, medium-dose group and high-dose group for subgroup analysis. There were decreases of HbA1c in all dose group (WMD = -0.27, 95%CI (-0.51~ -0.03), Z = 2.17, p = 0.03; WMD = -0.37, 95%CI (-0.58~ -0.16), Z = 3.41, p = 0.0006; WMD = -0.60, 95%CI (-0.86~ -0.33), Z = 4.43, p < 0.00001). Though the total risk of hypoglycemia is absolutely low, in the high-dose group higher hypoglycemia than the placebo can be observed (RR = 0.03, 95%CI (0.00~0.06), Z = 2.27, p = 0.02). In addition, the study found that the drug was less likely to have adverse reactions such as diarrhea, headache and dizziness, nasopharyngitis and upper respiratory tract infection (RR = 0.76, 95%CI (0.36~1.60), Z = 0.73, p = 0.47; RR = 1.26, 95%CI (0.73~2.17), Z = 0.83, p = 0.41; RR = 0.71, 95%CI (0.41~1.22), Z = 1.25, p = 0.21; RR = 1.61, 95%CI (0.77~3.36), Z = 1.26, p = 0.21). It concludes that GKAs are relatively effective and safe in the treatment of patients with T2DM, but in consideration of the potential risk of hypoglycemia in the high-dose group, the low-dose and medium-dose group, in the clinical practice, can be an excellent choice.

Shared genetic and experimental links between obesity-related traits and asthma subtypes in UK Biobank.

BACKGROUND: Clinical and epidemiologic studies have shown that obesity is associated with asthma and that these associations differ by asthma subtype. Little is known about the shared genetic components between obesity and asthma. OBJECTIVE: We sought to identify shared genetic associations between obesity-related traits and asthma subtypes in adults. METHODS: A cross-trait genome-wide association study (GWAS) was performed using 457,822 subjects of European ancestry from the UK Biobank. Experimental evidence to support the role of genes significantly associated with both obesity-related traits and asthma through a GWAS was sought by using results from obese versus lean mouse RNA sequencing and RT-PCR experiments. RESULTS: We found a substantial positive genetic correlation between body mass index and later-onset asthma defined by asthma age of onset at 16 years or greater (Rg = 0.25, P = 9.56 × 10-22). Mendelian randomization analysis provided strong evidence in support of body mass index causally increasing asthma risk. Cross-trait meta-analysis identified 34 shared loci among 3 obesity-related traits and 2 asthma subtypes. GWAS functional analyses identified potential causal relationships between the shared loci and Genotype-Tissue Expression (GTEx) quantitative trait loci and shared immune- and cell differentiation-related pathways between obesity and asthma. Finally, RNA sequencing data from lungs of obese versus control mice found that 2 genes (acyl-coenzyme A oxidase-like [ACOXL] and myosin light chain 6 [MYL6]) from the cross-trait meta-analysis were differentially expressed, and these findings were validated by using RT-PCR in an independent set of mice. CONCLUSIONS: Our work identified shared genetic components between obesity-related traits and specific asthma subtypes, reinforcing the hypothesis that obesity causally increases the risk of asthma and identifying molecular pathways that might underlie both obesity and asthma.

Effects of nitrogen fertilization and drought on hydrocyanic acid accumulation and morpho-physiological parameters of sorghums.

BACKGROUND: Nitrogen fertilization can increase sorghum yield and quality and the hydrocyanic acid (HCN) accumulation in plants, increasing the risk of animal toxicity, particularly under drought conditions. In this study, plants of three sorghum genotypes (sweet sorghum, sudangrass and hybrid sorghum) were supplemented with nitrogen (0, 60, 90 and 120 kg N ha-1 ) under well-watered and drought-stressed conditions, aiming to investigate the responses of morpho-physiological parameters and HCN accumulation to drought and nitrogen fertilization. RESULTS: Drought caused a decline in growth and photosynthesis. Average HCN content increased by 27.85% in drought-stressed plants when compared with those in well-watered plants. Drought increased the proline and soluble protein content, the content of O2 - , H2 O2 and malondialdehyde (MDA), and the activities of antioxidant enzymes in leaves of all three genotypes. Maximum plant growth and higher plant nutrient content (nitrogen and phosphorus) were observed at 120 kg N ha-1 , followed by 90 and 60 kg N ha-1 . However, a sharp increase in HCN content and a decrease in antioxidant enzyme activities were observed when nitrogen rates increased from 90 to 120 kg N ha-1 , suggesting that 90 kg N ha-1 might be better for sorghums under drought conditions. CONCLUSION: These results suggest that optimum nitrogen application on sorghum under drought conditions could achieve a balance between plant defense and food safety, attributed to the reduced MDA, O2 - and H2 O2 accumulation, the improvement in photosynthesis parameters, the increase in soluble protein and proline content, and the increase in antioxidant enzyme activities. © 2020 Society of Chemical Industry.

Alpinetin Inhibits Oral Squamous Cell Carcinoma Proliferation via miR-211-5p Upregulation and Notch Pathway Deactivation.

Background: The effect of alpinetin (ALP) on miR-211-5p level and function in oral squamous cell carcinoma (OSCC) remains unclear.Materials and methods: Human OSCC cell lines (CAL-27 and TCA-8113) and a mouse xenograft model with subcutaneously injected TCA-8113 cells were used. Effect of ALP treatment on cell viability, cell cycle distributions, and p-p53, p21, c-PARP, cyclin D1, NICD, HES1, and miR-211-5p expression levels was analyzed. Influence of ALP on tumor volume and weight was determined.Results: ALP treatment (at doses 400 and 500 µM) significantly decreased the viability of CAL-27 and TCA-8113 cells (P < 0.05). It upregulated the number of cells in G1 phase and miR-211-5p expression, increased p-p53, p21, and c-PARP levels, and decreased cyclin D1 levels. Furthermore, miR-211-5p mimic treatment increased the number of cells in G1 phase, and p53, p21, and c-PARP levels, and decreased cyclin D1 levels. Contrasting effects were observed under anti-miR-211-5p treatment. ALP downregulated NICD and HES1, whereas anti-miR-211-5p increased NICD and HES1 expression. ALP effects were alleviated in both cell lines under Jagged-1 overexpression plasmid treatment. Finally, ALP inhibited tumor growth and increased miR-211-5p expression in vivo.Conclusion: ALP-induced miR-211-5p upregulation and Notch pathway deactivation may be involved in its anti-proliferative effects in OSCC.