DCAF13 promotes ovarian cancer progression by activating FRAS1-mediated FAK signaling pathway.

Cullin-RING ubiquitin ligase 4 (CRL4) is closely correlated with the incidence and progression of ovarian cancer. DDB1- and CUL4-associated factor 13 (DCAF13), a substrate-recognition protein in the CRL4 E3 ubiquitin ligase complex, is involved in the occurrence and development of ovarian cancer. However, its precise function and the underlying molecular mechanism in this disease remain unclear. In this study, we confirmed that DCAF13 is highly expressed in human ovarian cancer and its expression is negatively correlated with the overall survival rate of patients with ovarian cancer. We then used CRISPR/Cas9 to knockout DCAF13 and found that its deletion significantly inhibited the proliferation, colony formation, and migration of human ovarian cancer cells. In addition, DCAF13 deficiency inhibited tumor proliferation in nude mice. Mechanistically, CRL4-DCAF13 targeted Fraser extracellular matrix complex subunit 1 (FRAS1) for polyubiquitination and proteasomal degradation. FRAS1 influenced the proliferation and migration of ovarian cancer cell through induction of the focal adhesion kinase (FAK) signaling pathway. These findings collectively show that DCAF13 is an important oncogene that promotes tumorigenesis in ovarian cancer cells by mediating FRAS1/FAK signaling. Our findings provide a foundation for the development of targeted therapeutics for ovarian cancer.

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.

3-ketoacyl-CoA synthase 19 contributes to the biosynthesis of seed lipids and cuticular wax in Arabidopsis and abiotic stress tolerance.

Very-long-chain fatty acids (VLCFAs) are essential precursors for plant membrane lipids, cuticular waxes, suberin, and storage oils. Integral to the fatty acid elongase (FAE) complex, 3-ketoacyl-CoA synthases (KCSs) function as crucial enzymes in the VLCFA pathway, determining the chain length of VLCFA. This study explores the in-planta role of the KCS19 gene. KCS19 is predominantly expressed in leaves and stem epidermis, sepals, styles, early silique walls, beaks, pedicels, and mature embryos. Localized in the endoplasmic reticulum, KCS19 interacts with other FAE proteins. kcs19 knockout mutants displayed reduced total wax and wax crystals, particularly alkanes, while KCS19 overexpression increased these components and wax crystals. Moreover, the cuticle permeability was higher for the kcs19 mutants compared to the wild type, rendering them more susceptible to drought and salt stress, whereas KCS19 overexpression enhanced drought and salt tolerance. Disrupting KCS19 increased C18 species and decreased C20 and longer species in seed fatty acids, indicating its role in elongating C18 to C20 VLCFAs, potentially up to C24 for seed storage lipids. Collectively, KCS19-mediated VLCFA synthesis is required for cuticular wax biosynthesis and seed storage lipids, impacting plant responses to abiotic stress.

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.

Development of a short-term prognostic model for anti-N-methyl-D-aspartate receptor encephalitis in Chinese patients.

BACKGROUND: Recognizing the predictors of poor short-term prognosis after first-line immunotherapy in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is essential for individualized treatment strategy. The objective of this study was to ascertain the factors that forecast short-term prognosis in patients with anti-NMDAR encephalitis, develop a prognostic prediction model, and authenticate its efficacy in an external validation cohort. Further, all patients were followed-up long-term to assess the factors of long-term outcome and relapses. METHODS: A prospective enrollment of patients diagnosed with anti-NMDAR encephalitis was conducted across five clinical centers in China from June 2014 to Mar 2022. The enrolled patients were divided into the derivation and validation sets based on enrollment time. The short-term prognostic model was visualized using a nomogram. Further, all patients were followed-up long-term to assess the factors of long-term outcome. RESULTS: This study found that poor short-term prognosis was a risk factor for poor long-term outcome (6-month prognosis, OR 29.792, 95%CI 6.507-136.398, p < 0.001; 12-month prognosis, OR 15.756, 95%CI 3.384-73.075, p < 0.001; 24-month prognosis, OR 5.500, 95%CI 1.045-28.955, p = 0.044). Abnormal behavior or cognitive dysfunction (OR 8.57, 95%CI 1.48-49.79, p = 0.017), consciousness impairment (OR19.32, 95%CI 3.03-123.09, p = 0.002), autonomic dysfunction or central hypoventilation (OR 5.66, 95%CI 1.25-25.75, p = 0.025), CSF pleocytosis (OR 4.33, 95%CI 1.48-12.65, p = 0.007), abnormal EEG (OR 5.48, 95% CI 1.09-27.54, p = 0.039) were independent predictors for a poor short-term prognosis after first-line immunotherapy. A nomogram that incorporated those factors showed good discrimination and calibration abilities. The area under the curve (AUC) for the prognostic model were 0.866 (95%CI: 0.798-0.934) with a sensitivity of 0.761 and specificity of 0.869. CONCLUSION: We established and validated a prognostic model that can provide individual prediction of short-term prognosis after first-line immunotherapy for patients with anti-NMDAR encephalitis. This practical prognostic model may help neurologists to predict the short-term prognosis early and potentially assist in adjusting appropriate treatment timely.

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.

The influence of open disc repositioning surgery on the internal derangement of the contralateral temporomandibular joint: a prospective study of 96 patients.

OBJECTIVE: To assess the influence of unilateral open disc repositioning surgery (ODRS) of the temporomandibular joint (TMJ) on the internal derangement (ID) of the contralateral joint. METHODS: Patients with bilateral ID of TMJ who underwent unilateral ODRS were enrolled and followed-up for one year. They were divided into two groups based on the contralateral disease: the anterior disc displacement with reduction (ADDWR) and without reduction (ADDWoR). Postoperative evaluation included clinical and MRI evaluation. Indices measured were unilateral intermaxillary distance (UID), visual analogue scale (VAS), disc length (DL), condylar height (CH), and disc-condyle angle (DCA). Paired t tests were used to compare the clinical and MRI indices between different time points. RESULTS: Ninety-six patients were enrolled, including 47 in the ADDWR group and 49 in the ADDWoR group. One-year post-surgery, ODRS led to significant increases in MMO, DL, and CH, and decrease in VAS and DCA on the operated side (P < 0.05). In ADDWR group, UID, DL, and CH increased significantly, and VAS decreased (P < 0.05), with no significant change in DCA (P > 0.05). In ADDWoR group, clinical and MRI variables worsened slightly, except for UID, which remained unchanged (P > 0.05). CONCLUSIONS: ODRS is a promising method for correcting TMJ ID and may improve condition of ADDWR and decrease progress of ADDWoR at the contralateral joint. Preoperative bilateral TMJ evaluation is essential for better outcomes. CLINICAL RELEVANCE: ODRS can effectively treat TMJ ID and produce adaptive changes in the contralateral ID, for which continuous monitoring of the contralateral joint is essential.

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.