TARGET OF EAT3 (TOE3) specifically regulates fruit spine initiation in cucumber (Cucumis sativus L.).

The presence or absence of spines is an important economic trait of cucumber fruit. Spines are believed to be a type of specialized trichome on the fruit surface, and all the identified cucumber trichome-less mutants lack fruit spines. However, genes that specifically regulate fruit spine initiation remain to be identified. Here, we found that knocking out cucumber TARGET OF EAT3 homolog (CsTOE3), belonging to the APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) family, affected flower development and, more interestingly, inhibited cucumber fruit spine initiation. On analyzing expression patterns by quantitative reverse transcriptase-polymerase chain reaction and in situ hybridization assay, CsTOE3 was found to be highly expressed in male and female flowers, and its mRNA accumulated in the tips of sepal and petal primordia and in the cells of fruit spines and peels. Biochemical analyses indicated that CsTOE3 directly interacts with GLABRA1 (CsGL1) and TRANSPARENT TESTA GLABRA1 (CsTTG1), which are positive regulators of trichome formation. In addition, RNA-seq showed that the transcription levels of eight ERFs were significantly upregulated in CsTOE3 knockout lines. Phytohormone content analysis also revealed a significant increase in the amount of ethylene released by CsTOE3 knockout line, and treatment with the ethylene synthesis inhibitor aminoethoxyvinyl-glycine partly restored the spineless phenotype. Our results suggest that CsTOE3 specifically regulates fruit spine initiation but does not affect the formation of trichomes on other organs in cucumber. Our findings may have a far-reaching significance for cucumber germplasm improvement and quality breeding using fruit spines as the target trait.

Meta-analysis of the association between interleukin-17 and ischemic cardiovascular disease.

BACKGROUND: Interleukin-17 (IL-17) has been hypothesized to be involved in ischemic cardiovascular disease (ICVD). However, the association of IL-17 with ICVD remained unclear. The aim of this study was to systematically analyze the available evidence regarding the association between IL-17 and ICVD. METHODS: We searched the PubMed, Web of Science, Cochrane Library, and Embase databases up to October 2023 to identify publications on the association between IL-17 and ICVD. The merged results were analyzed using a random effects model for meta-analysis and subgroup analysis. RESULTS: A total of 955 publications were initially identified in our search and screened; six studies were eventually included in the analysis. The average age of study participants was 60.3 ± 12.6 years and 65.5% were men. There was a high degree of heterogeneity among studies. The results showed that IL-17 level were higher in the case group than those in the control group (standardized mean difference, SMD = 1.60, 95% confidence interval (95% CI): 0.53-2.66, P = 0.003). In sensitivity analysis, the merged results showed good robustness. Additionally, subgroup analysis showed that race and ethnicity, sample size, and detection methods were significant factors influencing heterogeneity in the published studies. CONCLUSION: Our finding revealed that increased IL-17 level contributed to the development of ICVD, suggesting IL-17 as a potential risk marker. Further research is needed to establish IL-17 as a therapeutic biomarker of ICVD.

A human health risk assessment of rare earth elements through daily diet consumption from Bayan Obo Mining Area, China.

Rare earth elements (REEs) have been broad application in a range of industries, including the electronics industry, advanced materials, and medicine. However, health risks associated with REEs received increasing attention. 31 residents (16 males and 15 females) from Bayan Obo mining in Inner Mongolia, China, were enrolled in this study. In total, 677 food samples, the major human exposure matrices (drinking water and duplicate diets), and bio-samples (urine and blood) of 31 participants were obtained. The concentrations of REEs were measured to characterize their external and internal exposures, and the potential health risk of exposure to REE through the ingestion route was analyzed. The results revealed that the detection rate in blood samples (100%) is higher than in urine (32.86%), and only a few REEs were detected in water samples (8.06%), the urine concentrations were considerably lower than in blood. Exposure to REEs through drinking water was considered negligible compared to food intake. Lanthanum and cerium were the most concentrated REEs in food samples. Health risks were calculated based on a dose-response model, the total hazard quotients (THQ) values for all food groups were within normal levels, and the Monte Carlo simulation results show that the 5th, the 50th, and the 95th percentile values of HI were found as 1.45 × 10-2, 3.52 × 10-2, and 9.13 × 10-2, respectively, neither exceeds the threshold, indicating low health risks associated with food intake exposure for this area. The sensitivity results suggest that underweight people are at higher risk, cerium, lanthanum, and yttrium concentrations, and food intake contributes more to health risks. The use of probability distribution methods can improve the accuracy of the results. The cumulative health risk through food intake is negligible, and further attention should be paid to the health risk induced by other routes of exposure to REEs by the local residents.

Protocol of the Inner Mongolian Healthy Aging Study (IMAGINS): a longitudinal cohort study.

BACKGROUND: Cardiovascular diseases (CVDs) remain the leading cause of premature mortality and burden of diseases in the world. The Inner Mongolia Autonomous Region is located in northern China, constitute 17.66% individuals with Mongolian, which have unique diet and lifestyles. Therefore, the Inner Mongolian Healthy Aging Study (IMAGINS) was designed to explore risk factors for chronic diseases and evaluate the effectiveness of health management on CVDs in population at high-risk. METHODS: The IMAGINS is an ongoing and prospective cohort study of men and women aged ≥35 years from Inner Mongolian Autonomous Region, northern China. This study performed in investigating risk factors for CVDs, screening and providing health management strategy for high-risk population of CVDs. The IMAGINS began in September 2015 and scheduled to recruiting and follow-up outcome until 2030. For general population, a long-term follow-up will be conducted every 5 years to collect the information above and data on clinical outcomes. For high-risk population, comprehensive health managements were performed and scheduled to follow-up annually. All IMAGINS participants are followed for incident CVDs and death. DISCUSSION: The IMAGINS is designed to increase understanding how cardiovascular-related risk factors contribute to the development of CVDs and the positive effect of health management strategy for high-risk CVD participants. Key features of this study include (i) a carefully characterized cohort between high risk of CVDs and non-high risk population; (ii) detailed measurement of CVDs risk factors and health management strategies for high risk population; (iii) long-term follow-up of CVDs and death. The IMAGINS represents a good research opportunity to investigate clinical and genetic factors in high-risk population, might providing basis for the prevention and control of non-communicable diseases.

Characterization of drinking groundwater quality in rural areas of Inner Mongolia and assessment of human health risks.

Groundwater is an important natural resource of drinking water in rural areas in Inner Mongolia, China. In this study, 4438 drinking groundwater samples were collected from the rural areas of 81 counties in Inner Mongolia, and were analyzed for 16 parameters, including pH, total hardness (TH), chemical oxygen demand (COD), total dissolved solids (TDS), sulfate (SO42-), chloride (Cl-), fluoride (F-), iron (Fe), manganese (Mn), arsenic (As), cadmium (Cd), hexavalent chromium (Cr), lead (Pb), aluminum (Al), cuprum (Cu), zinc (Zn). The groundwater quality was evaluated with water quality index (WQI) and human health risk assessment (HRA). Monte Carlo simulation were applied for the uncertainty and sensitivity analysis in the health risk assessment. The spatial map was employed based on the inverse distance weighted (IDW) interpolation technique. The results reveal that while the hazard quotient (HQ) suggests that the risk of single element contamination is feeble, the hazard index (HI) indicates a potential health risk for the local population. The observed cumulative carcinogenic risk (CCR) indicates a probable risks of carcinogenic health hazards in the study area. The sensitivity analysis revealed that daily ingestion rate (IR), exposure frequency (EF), and the concentrations of As, Mn, F-, and Cr are the most influential parameters for health hazards. The highly polluted areas are mainly distributed in the central and western regions of Inner Mongolia, including Xianghuangqi, New Barag Zuoqi, and Togtoh. It is observed that the groundwater may cause a potential health risk after long-term ingestion. The results of this study will contribute to groundwater management and protection in Inner Mongolia.

Effects of air pollutants and temperature on the number of asthma outpatient visits in Hohhot, China.

Although numerous studies have linked asthma to air temperature and pollution, few studies have examined their interactive effects on asthma outpatient visits. This study investigated how air pollutants and their interactions with temperature affect asthma outpatient visits in a city in northern Chinaduring the time period 2018 - 2020 . . As the results, 24,163 asthma outpatients were recorded, a 10-µg/m3 increase in PM10, PM2.5, SO2, and NO2 concentrations was associated with significant increases in visits of 3.47% (95% CI: 2.35%-4.60%), 0.83% (95% CI: 0.36%-1.30%), 3.17% (95% CI: 1.47%-4.90%), and 8.90% (95% CI: 6.09%-11.79%), respectively. The effect was stronger in females than males, and stronger in the elderly (≥65 years) than among the young. The interaction between low temperatures and high air pollution levels significantly increased the number of asthma outpatient visits. This study emphasizesthe importance of reducing air pollution in order to lessen the effects of cold.

Prevalence and treatment of high cardiovascular disease risk in Inner Mongolia, China.

Early identification of individuals with high risk is crucial to preventing cardiovascular disease (CVD). We aimed to determine the prevalence of high CVD risk in Inner Mongolia and to analyze the treatment of major risk factors among individuals with high CVD risk. We selected 70,380 participants aged 35-75 years in Inner Mongolia between 2015 and 2017 using multistage stratified sampling. All participants completed a questionnaire and their blood pressure, blood glucose and lipid levels, height, weight and waist circumference were measured. Participants without a history of CVD were defined as high CVD risk if the predicted 10-year risk for CVD exceeded 10%. We assessed rates of high CVD risk and the prevalence and treatment of major risk factors among individuals with high CVD risk. After excluding participants with previous CVD, 68,083 participants remained. The overall prevalence of high CVD risk was 24.96%. The age- and sex-standardized rate of high CVD risk was 22.92%. Among high-risk participants, the prevalence of risk factors was hypertension (91.9%), dyslipidemia (54.1%), obesity (34.6%), diabetes (27.6%), and smoking (24.5%); clustering of these risk factors was common. The percentage of high-risk individuals taking antihypertensive drugs was 45.94% in those with hypertension; 27.99% of those with diabetes took hypoglycemic drugs and only 5.01% of those with dyslipidemia took lipid-lowering drugs. Control rates of hypertension, diabetes, and dyslipidemia were 1.20%, 4.43%, and 2.78%, respectively. Therefore, the prevalence of high CVD risk was elevated in Inner Mongolia, and treatment and control rates were low.

Prevalence, awareness, treatment, and control of hypertension in Northern China: a cross-sectional study.

BACKGROUND: Hypertension has always been a worldwide health concern. The purpose of this study was to investigate the prevalence, awareness, treatment, and control rates of hypertension among adult residents of northern China, where people usually have a high-fat, high-salt diet and heavy alcohol consumption. METHODS: Through the Early Screening and Comprehensive Intervention Project for High Risk Groups of Cardiovascular Diseases in the Inner Mongolia of northern China, we collected data of 70,380 residents, from September 2015 to June 2017. We assessed the prevalence, awareness, treatment, and control of hypertension in the total population and sub-populations. Multivariable logistic regression analyses were used to identify the factors associated with the prevalence and control of hypertension. RESULTS: Among participants, only 13.4% had optimal blood pressure levels. About 55.7% (95% confidence interval (CI) = 55.3-56.1%) of the participants had hypertension. In addition, the awareness, treatment, control and control under-treatment rate of hypertension were 52.8% (95%CI = 52.3-53.3%), 43.3% (95%CI = 42.8-43.8%), 8.6% (95%CI = 8.3-8.9%) and 19.8% (95%CI = 19.2-20.4%), respectively. Multivariable logistic regression showed that older, male, Han, living in rural areas, current drinker, not married, lower educational level, lower annual income, diabetes, obesity, and dyslipidemia were more likely to be suffered from hypertension (P < 0.05). Controlled hypertension was less common in those younger, Mongol, not married, farmer, current drinker, lower educational level, obesity, diabetes, without prior CHD, and without prior CVD (P < 0.05). CONCLUSION: Among populations aged 35-75 years in Northern China, more than half have hypertension, fewer than one-tenth have successfully controlled hypertension, and fewer than one-fifth of hypertension patients receiving treatment have controlled hypertension.

Evaluating the treatment and control of modifiable cardiovascular disease risk factors among patients with diabetes in the Inner Mongolia, China: A cross-sectional study.

Reducing the risk of diabetes has been a great public health challenge in China. In this study, we aimed to estimate the treatment and control of FPG (fasting blood plasma glucose) as well as the other main modifiable cardiovascular disease (CVD) risk factors in patients with diabetes and to identify those characteristics associated with the treatment and control of diabetes, hypertension, and low-density lipoprotein cholesterol (LDL-C). Between 2015 and 2017, participants aged 35 to 75 years from Inner Mongolia in northern China were recruited. A total 13,644 participants with diabetes were enrolled in this study. We calculated rates and 95% confidence intervals for treatment and control of FPG, blood pressure, and LDL-C. We performed multivariate logistic regression to identify characteristics associated with the treatment and control of diabetes as well as hypertension and LDL-C. Overall, the treatment rates of diabetes, hypertension, and dyslipidemia were 30.76%, 50.75%, and 9.17%, respectively. Control rates of FPG, blood pressure, and LDL-C were 4.73%, 4.86%, and 57.83%, respectively. Patients who were younger, Mongol ethnicity and rural residents were less likely to be treated and controlled for diabetes and hypertension. Patients insured by NCMS (new rural cooperative medical scheme) were less likely to be treated and achieve the treatment target of blood pressure. Patients having prior CVD were more likely to be treated and have controlled FPG and blood pressure. Substantial efforts are urgently needed to improve the treatment and control of these modifiable CVD risk factors among patients with diabetes in Inner Mongolia.

Prevalence of dyslipidemia and associated risk factors among adults aged ≥35 years in northern China: a cross-sectional study.

BACKGROUND: Cardiovascular disease (CVD) prevalence has increased continuously over the last 30 years in China. Dyslipidemia is an important modifiable risk factor in CVD. We aimed to collect current data on the prevalence of dyslipidemia in northern China and explore potential influencing factors. METHODS: In this cross-sectional study, we selected a representative sample of 65,128 participants aged ≥35 years in Inner Mongolia during 2015-2017. All participants completed a questionnaire and were examined for risk factors. Dyslipidemia was defined according to 2016 Chinese guidelines for adults. The associated factors for dyslipidemia were estimated by multivariate logistic regression analysis. RESULTS: The age-standardized prevalence of dyslipidemia was 31.2% overall, with 4.3, 2.4, 14.7, and 17.4% for high total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and low high-density lipoprotein cholesterol (HDL-C), respectively. The dyslipidemia prevalence was significantly higher in men than women (37.9% vs. 27.5%, P < 0.001), but postmenopausal women had a higher prevalence of dyslipidemia components (except low HDL-C). Compared with Han participants, Mongol participants had a lower prevalence of dyslipidemia (29.1% vs. 31.4%, P < 0.001). Male sex, living in urban areas, Han ethnicity, smoking, obesity, central obesity, hypertension, and diabetes were all positively correlated with dyslipidemia; alcohol consumption was linked to lower risk of dyslipidemia. CONCLUSIONS: Our study revealed that dyslipidemia is a health problem in northern China. Greater efforts to prevent and manage dyslipidemia, especially in men under age 55 years, postmenopausal women, and people with unhealthy lifestyles or chronic diseases.

Assessment of cardiovascular disease risk in Northern China: a cross-sectional study.

Cardiovascular disease (CVD) is a life-threatening chronic illness. CVD risk may be influenced by environment and lifestyle. People in northern China usually consume high-fat, high-salt diets and alcohol and live in a cold climate over long periods. However, there are limited studies on CVD risk among people in northern China. In the present study, we sought to estimate the CVD risk profile among residents of northern China. Using the Programme of Screening and Intervention Subjects with High Risk Cardiovascular Diseases, we collected data from residents in six cities from September 2015 to June 2017. In total, 56,716 participants aged 40 years and above were finally included in the CVD risk assessment. To assess the 10-year risk of CVD among participants, we used World Health Organisation/International Society of Hypertension risk prediction charts. Among the study participants, 22.7% had a high 10-year risk of CVD. We identified differences in the 10-year CVD risk according to sex, socioeconomic status, and marital status. We conclude that individuals with high socioeconomic status should be encouraged to change their lifestyle habits, and greater medical resources should be invested for individuals residing in rural areas and those with low education levels.

Heterogeneously Catalyzed Hydrothermal Processing of C5-C6 Sugars.

Biomass has been long exploited as an anthropogenic energy source; however, the 21st century challenges of energy security and climate change are driving resurgence in its utilization both as a renewable alternative to fossil fuels and as a sustainable carbon feedstock for chemicals production. Deconstruction of cellulose and hemicellulose carbohydrate polymers into their constituent C5 and C6 sugars, and subsequent heterogeneously catalyzed transformations, offer the promise of unlocking diverse oxygenates such as furfural, 5-hydroxymethylfurfural, xylitol, sorbitol, mannitol, and gluconic acid as biorefinery platform chemicals. Here, we review recent advances in the design and development of catalysts and processes for C5-C6 sugar reforming into chemical intermediates and products, and highlight the challenges of aqueous phase operation and catalyst evaluation, in addition to process considerations such as solvent and reactor selection.

Association between TNF, IL1B, IL6, IL10 and IFNG polymorphisms and recurrent miscarriage: a case control study.

BACKGROUND: Approximately half of recurrent miscarriages have unexplained etiology. Recent evidences suggest that cytokines are important determinants in pregnancy maintenance and as such, cytokine gene polymorphisms, which can affect cytokine production and/or functionality, could play a role in the disorder. Thus, we aimed to investigate the association of selected cytokine gene polymorphisms with risk of recurrent miscarriage among Chinese. METHODS: TNF -238G > A, TNF -308G > A, IL1B -511 T > C, IL1B 3954C > T, IL6 -174G > C, IL6 -634C > G, IL10 -1082A > G and IFNG 874A > T polymorphisms were genotyped on 775 women with idiopathic recurrent miscarriage and 805 healthy parous control women. Logistic regression analysis was performed to determine the odds ratios (ORs) of the association between the polymorphisms and recurrent miscarriage risk. RESULTS: Among the eight polymorphisms studied, only the IL1B -511 T > C and IL6 -634C > G polymorphisms showed statistically significant associations with recurrent miscarriage risk. For the former, a significantly increased risk of recurrent miscarriage was observed for the mutant (CC) genotype (OR: 1.377; 95% CI: 1.039-1.824; P = 0.026). However, for the IL6 -634C > G polymorphism, a decreased recurrent miscarriage risk was observed for the heterozygous (CG) genotype (OR: 0.614; 95% CI: 0.493-0.765; P < 0.001) and the mutant (GG) genotype (OR: 0.414; 95% CI: 0.251-0.684; P = 0.001). CONCLUSIONS: The IL1B -511 T > C polymorphism may serve as important risk factor for recurrent miscarriage while the IL6 -634C > G polymorphism may protect against the risk of recurrent miscarriage.

Impact of glucose fluctuation on acute cerebral infarction in type 2 diabetes.

OBJECTIVE: This study aimed to describe the frequency and temporal profile of acute cerebral infarction (ACI) using a continuous glucose monitoring system (CGMS) in patients with and without type 2 diabetes mellitus (T2DM) and explore the impact of blood glucose fluctuations on the short-term prognosis of ACI. METHODS: The subjects were divided into four groups: T2DM with acute cerebral infarction (DMCI, Group A, n=56); T2DM without acute cerebral infarction (DM-NCI, Group B, n=36); Acute cerebral infarction patients without T2DM (NDM-CI, Group C, n=54); Healthy control group (NG, Group D, n=36). The National Institutes of Health Stoke Scale (NIHSS) and modified Rankin scale (mRs) were collected in Group A and C. All subjects were monitored for 72 hours using the CGMS. Indices such as fasting blood glucose (FBG) and mean amplitude of glycemic excursions (MAGE) were calculated. Glycemic excursions were compared between Group A, B, C and Group D, respectively. Multiple linear regression analysis and logistic analysis was applied. RESULTS: MAGE is related to NIHSS, homocysteine (HCY), HOMA-IR, FBG, CRP and IMT, while NIHSS is related to CRP, HCY, HOMA-IR, IMT. The factors impacting the short-term prognosis of ACI were NIHSS, HBA1C and MAGE. CONCLUSION: Larger glucose fluctuations are associated with more stroke risk factors and are associated with a poorer short-term prognosis. More attention should be paid to glucose fluctuations in patients with ACI and a history of T2DM.

Investigating the role of backward walking therapy in alleviating plantar pressure of patients with diabetic peripheral neuropathy.

OBJECTIVE: To investigate the effect of combination therapy of backward walking training and alpha-lipoic acid (ALA) treatment on the distribution of plantar pressure in patients with diabetic peripheral neuropathy (DPN). DESIGN: This study is a double-blinded, randomized controlled trial. The test group was treated with combination therapy of backward walking exercise and ALA (ALA for 2wk, backward walking exercise for 12wk), and the control group only received ALA treatment. SETTING: Clinical and laboratory setting. PARTICIPANTS: Patients with DPN (N=60) were divided into the test group (n=30) or control group (n=30). INTERVENTIONS: Backward walking exercise with ALA treatment for the test group; lipoic acid treatment for the control group. MAIN OUTCOME MEASURE: Plantar pressure before and after treatment was tested and analyzed with the flatbed plantar pressure measurement system. RESULTS: After treatment, peak plantar pressure in the forefoot dropped for both the test and control groups; peak plantar pressure for the test group dropped significantly. Peak plantar pressure in the medial foot slightly increased for the test group, suggesting a more even distribution of plantar pressure in the test group after treatment. CONCLUSIONS: The combination therapy of ALA and backward walking proved to be more effective than ALA monotherapy. Backward walking also proved to have an ameliorating effect on balance ability and muscle strength of patients with DPN.

Systematic Investigation on Supported Gold Catalysts Prepared by Fluorine-Free Basic Etching Ti3AlC2 in Selective Oxidation of Aromatic Alcohols to Aldehydes.

Conventional methods to prepare supported metal catalysts are chemical reduction and wet impregnation. This study developed and systematically investigated a novel reduction method based on simultaneous Ti3AlC2 fluorine-free etching and metal deposition to prepare gold catalysts. The new series of Aupre/Ti3AlxC2Ty catalysts were characterized by XRD, XPS, TEM, and SEM and were tested in the selective oxidation of representative aromatic alcohols to aldehydes. The catalytic results demonstrate the effectiveness of the preparation method and better catalytic performances of Aupre/Ti3AlxC2Ty, compared with those of catalysts prepared by traditional methods. Moreover, this work presents a comprehensive study on the influence of calcination in air, H2, and Ar, and we found that the catalyst of Aupre/Ti3AlxC2Ty-Air600 obtained by calcination in air at 600 °C performed the best, owing to the synergistic effect between tiny surface TiO2 species and Au NPs. The tests of reusability and hot filtration confirmed the catalyst stability.

Review on supported metal catalysts with partial/porous overlayers for stabilization.

Heterogeneous catalysts of supported metals are important for both liquid-phase and gas-phase chemical transformations which underpin the petrochemical sector and manufacture of bulk or fine chemicals and pharmaceuticals. Conventional supported metal catalysts (SMC) suffer from deactivation resulting from sintering, leaching, coking and so on. Besides the choice of active species (e.g. atoms, clusters, nanoparticles) to maximize catalytic performances, strategies to stabilize active species are imperative for rational design of catalysts, particularly for those catalysts that work under heated and corrosive reaction conditions. The complete encapsulation of metal active species within a matrix (e.g. zeolites, MOFs, carbon, etc.) or core-shell arrangements is popular. However, the use of partial/porous overlayers (PO) to preserve metals, which simultaneously ensures the accessibility of active sites through controlling the size/shape of diffusing reactants and products, has not been systematically reviewed. The present review identifies the key design principles for fabricating supported metal catalysts with partial/porous overlayers (SMCPO) and demonstrates their advantages versus conventional supported metals in catalytic reactions.

Effects of dulaglutide combined with insulin degludec on glucose fluctuations and appetite in type 2 diabetes.

Introduction: The aim of this study was to describe appetite and glucose fluctuation in type 2 diabetes mellitus patients initiating treatment with dulaglutide combined with insulin degludec. Methods: This retrospective study of patients identified adults starting treatment with once-weekly (QW) dulaglutide combined with insulin degludec (experimental group) or insulin degludec alone (control group). Patients were followed for up to 6 months from treatment initiation. The clinical characteristics of patients, treatment patterns, CGM data, and appetite scores were obtained for the two groups. Results: A total of 236 patients were included in this study. SDBG, MAGE, LAGE, and PPGE of the experimental group were lower than the control group's (P < 0.05). The proportions of patients achieving a time in range (TIR) of ≥70% in the experimental group were higher than in the control group, with 43% and 10% on the second day, 88% and 47% on the fourth day, 95% and 47% on the seventh day, and 100% and 67% on the tenth day, respectively. Significant associations existed between TIR and the prevalence of islet function. At six months, 89.2% of patients in the experimental group were still using dulaglutide. Appetite decreased significantly at 1 week and increased at 3 months after treatment with dulaglutide. Conclusion: Dulaglutide combined with insulin degludec significantly reduces glucose fluctuations in patients with type 2 diabetes mellitus and improves the TIR rate. However, the treatment on appetite could decrease in the first three months.

Association between intracerebral hemorrhage and cholesterol levels, and molecular mechanism underlying low cholesterol inhibiting autophagy in cerebral arterial smooth muscle cells leading to cell necrosis.

BACKGROUND: An association between cholesterol and intracerebral hemorrhage (ICH) has been reported, but the mechanism is unclear. METHODS: In this cross-sectional study, participants aged 50-75 years were selected using multistage stratified cluster sampling. All samples completed a questionnaire (age, gender, medication, etc.) and were examined (blood lipid, height, blood pressure, etc.) for risk factors. Multivariable logistic regression was used to analyze the association between cholesterol levels and ICH risk, after adjusting for age, smoking, hypertension, and other factors. We cultured rat cerebral artery smooth muscle cells at different cholesterol concentrations. The autophagy pathway was identified by transcriptome sequencing. The results were then validated using real-time polymerase chain reaction and western blot. RESULTS: We included 39,595 patients, among whom 286 had ICH. The study showed that a low level of low-density lipoprotein cholesterol (LDL-C) was a risk factor of ICH (odds ratio 2.912, 95% confidence interval 1.460-5.806; P = 0.002). Cell experiments showed that lower cholesterol levels could significantly induce rat cerebral artery smooth muscle cell necrosis. In low-cholesterol groups, expression of the autophagy marker LC3 protein was significantly decreased and p62 protein was significantly increased. In western blot and comparison with the control group, the low cholesterol PI3K/Akt/mTOR signaling pathway was significantly activated in the autophagy pathway, resulting in its inhibition, which in turn led to smooth muscle cell death. CONCLUSION: Low cholesterol levels may inhibit autophagy through PI3K/Akt/mTOR signaling and induce arterial smooth muscle cell necrosis, thereby increasing the risk of ICH.

Hydrangea paniculata coumarins attenuate experimental membranous nephritis by bidirectional interactions with the gut microbiota.

Coumarins isolated from Hydrangea paniculata (HP) had a renal protective effect in experimental membranous nephritis (MN), but the mechanisms are not clear. Currently, we investigate whether the modulation of gut dysbiosis by HP contributes to its renal protection. Experimental MN rats were treated with HP for six weeks. Fecal 16S rDNA sequencing and metabolomics were performed. Fecal microbiota transplantation (FMT) was used for the evaluation study. The results demonstrate that deteriorated renal function and gut dysbiosis are found in MN rats, as manifested by a higher Firmicutes/Bacteroidetes ratio and reduced diversity and richness, but both changes were reversed by HP treatment. Reduced gut dysbiosis is correlated with improved colonic integrity and lower endotoxemia in HP-treated rats. HP normalized the abnormal level of fecal metabolites by increasing short-chain fatty acid production and hindering the production of uremic toxin precursors. FMT of HP-treated feces to MN animals moderately reduced endotoxemia and albuminuria. Moreover, major coumarins in HP were only biotransformed into more bioactive 7-hydroxycoumarin by gut microbiota, which strengthened the effect of HP in vivo. Depletion of the gut microbiota partially abolished its renal protective effect. In conclusion, the bidirectional interaction between HP and the gut microbiota contributes to its beneficial effect.