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This study aims to predict the possible targets and related signaling pathways of Modified Huoluo Xiaoling Pills against colorectal cancer(CRC) by both network pharmacology and molecular docking and verify the mechanism of action by experiments. TCMSP was used to obtain the active ingredients and targets of Modified Huoluo Xiaoling Pills, and GeneCards, DrugBank, OMIM, and TTD were employed to acquire CRC-related targets. Cytoscape software was utilized to construct the drug-active ingredient-target network, and the STRING database was applied to establish the protein-protein interaction(PPI) network. DAVID platform was adopted to investigate the targets in terms of GO function and KEGG pathway enrichment analysis. Molecular docking was performed in AutoDock Vina. HCT 116 cells were intervened by different concentrations of Modified Huoluo Xiaoling Pills-containing serum, and CCK-8 was used to detect the proliferation inhibition of HCT 116 cells in each group. Transwell was employed to show the invasive abi-lity of HCT 116 cells, and Western blot was taken to reveal the expression levels of ß-catenin, cyclinD1, c-Myc, as well as epithelial-mesenchymal transition(EMT) marker proteins E-cadherin, N-cadherin, vimentin, MMP2, MMP7, MMP9, and TWIST in HCT 116 cells. The network pharmacological analysis yielded 242 active ingredients of Modified Huoluo Xiaoling Pills, 1 844 CRC targets, and 127 overlapping targets of CRC and Modified Huoluo Xiaoling Pills, and the signaling pathways related to CRC involved PI3K-Akt, TNF, HIF-1, IL-17, Wnt, etc. Molecular docking showed that the key active ingredients had a stable binding conformation with the core proteins. CCK-8 indicated that Modified Huoluo Xiaoling Pills significantly inhibited the proliferation of HCT 116 cells. Transwell assay showed that with increasing concentration of Modified Huoluo Xiaoling Pills containing serum, the invasive ability of HCT 116 cells was more obviously inhibited. The expression of ß-catenin, cyclinD1, c-Myc, N-cadherin, vimentin, MMP2, MMP7, MMP9, and TWIST proteins were suppressed, and the expression of E-cadherin was improved by the intervention of drug-containing serum. Thus, it can be seen that Modified Huoluo Xiaoling Pills restrains the proliferation, invasion, and metastasis of CRC cells through multiple components, multiple targets, and multiple pathways, and the mechanism of action may be related to the inhibition of the activation of the Wnt/ß-catenin signaling pathway, thereby affecting the occurrence of EMT.
Subject(s)
Cell Proliferation , Colorectal Neoplasms , Drugs, Chinese Herbal , Molecular Docking Simulation , Network Pharmacology , Humans , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/metabolism , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Cell Proliferation/drug effects , HCT116 Cells , Epithelial-Mesenchymal Transition/drug effects , Protein Interaction Maps/drug effects , Signal Transduction/drug effectsABSTRACT
The optimization of the adsorption of oxygen-containing intermediates on platinum (Pt) sites of Pt-based electrocatalysts is crucial for the oxygen reduction reaction process. Currently, a large amount of researches mainly focus on modifying the bulk structure of the electrocatalysts, however, the vital role of solvent effect on the phase interfaces is often overlooked. Here, we successfully developed an electrocatalyst in which the ordered PtCo alloy anchors on the cobalt (Co) single-atoms/clusters decorated support (Co1,nNC) and its surface is further optimized using hydrophobic ionic liquid (IL). Experimental studies and theoretical calculations indicate that compressive stress on Pt lattice contributed by intrinsic structure and the local hydrophobicity caused by IL on the surface can suppress the stabilization of *OH on Pt. This synergistic effect affords outstanding catalytic performance, exhibiting a half-wave potential (E1/2) of 0.916 V vs. RHE and a mass activity (MA) of 1350.3 mA mgPt-1 in 0.1 mol/L perchloric acid (0.1 M HClO4) electrolyte, much better than the commercial Pt/C (0.849 V vs. RHE and 145.5 mA mgPt-1 for E1/2 and MA, respectively). Moreover, the E1/2 of IL-PtCo/Co1,nNC only lost 5 mV after 10,000 cyclic voltammetry (CV) cycles due to a strong and synergistic contact of the intermetallic PtCo alloy with the Co1,nNC support and IL. This research provides an effective method for designing efficient electrocatalysts by combining intrinsic structure and surface modification.
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This study aimed to evaluate how the duration of travel affects the behavior of urban and rural residents regarding free COVID-19 vaccination, and provide scientific evidence for promoting free vaccination and building an immune barrier to cope with future epidemics. From August 3, 2022 to February,18,2023, A follow-up survey was conducted in urban and rural adults in four cities in China to collect information on socio-demographic factors, vaccination status and travel time for vaccination. Propensity score matching (PSM) analysis was deployed to measure the net difference of the enhanced vaccination rate between urban and rural residents in different traffic time distribution. A total of 5780 samples were included in the study. The vaccination rate of the booster dose of COVID-19 vaccine among rural residents was higher than that of urban residents with a significant P-value (69.36% VS 64.49%,p < .001). The traffic time had a significant negative impact on the COVID-19 booster vaccination behavior of urban and rural residents. There was a significant interaction between the travel time to the vaccination point and the level of trust in doctors. Travel time had a negative impact on the free vaccination behavior of both urban and rural residents. The government should optimize and expand the number of vaccination sites and enhance residents' trust in the medical system. This is crucial for promoting free vaccination and effective epidemic management in the future.
Subject(s)
COVID-19 Vaccines , COVID-19 , Immunization, Secondary , Rural Population , Travel , Urban Population , Humans , Male , China , COVID-19/prevention & control , Female , Travel/statistics & numerical data , Urban Population/statistics & numerical data , Rural Population/statistics & numerical data , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Middle Aged , Adult , Immunization, Secondary/statistics & numerical data , SARS-CoV-2/immunology , Vaccination/statistics & numerical data , Vaccination/psychology , Time Factors , Aged , Young Adult , Surveys and Questionnaires , East Asian PeopleABSTRACT
BACKGROUND: The public health service capability of primary healthcare personnel directly affects the utilization and delivery of health services, and is influenced by various factors. This study aimed to examine the status, factors, and urban-rural differences of public health service capability among primary healthcare personnel, and provided suggestions for improvement. METHODS: We used cluster sampling to survey 11,925 primary healthcare personnel in 18 regions of Henan Province from 20th to March 31, 2023. Data encompassing demographics and public health service capabilities, including health lifestyle guidance, chronic disease management, health management of special populations, and vaccination services. Multivariable regression analysis was employed to investigate influencing factors. Propensity Score Matching (PSM) quantified urban-rural differences. RESULTS: The total score of public health service capability was 80.17 points. Chronic disease management capability scored the lowest, only 19.60. Gender, education level, average monthly salary, professional title, health status, employment form, work unit type, category of practicing (assistant) physician significantly influenced the public health service capability (all P < 0.05). PSM analysis revealed rural primary healthcare personnel had higher public health service capability scores than urban ones. CONCLUSIONS: The public health service capability of primary healthcare personnel in Henan Province was relatively high, but chronic disease management required improvement. Additionally, implementing effective training methods for different subgroups, and improving the service capability of primary medical and health institutions were positive measures.
Subject(s)
Health Personnel , Primary Health Care , Humans , China , Male , Female , Primary Health Care/statistics & numerical data , Adult , Health Personnel/statistics & numerical data , Middle Aged , Surveys and Questionnaires , Rural Health Services/statistics & numerical data , Rural Health Services/organization & administrationABSTRACT
BACKGROUND: Healthy lifestyle behaviors (LBs) have been widely recommended for the prevention and management of cardiovascular disease (CVD). Despite a large number of studies exploring the association between combined LBs and CVD, a notable gap exists in integration of relevant literatures. We conducted a systematic review and meta-analysis of prospective cohort studies to analyze the correlation between combined LBs and the occurrence of CVD, as well as to estimate the risk of various health complications in individuals already diagnosed with CVD. METHODS: Articles published up to February 10, 2023 were sourced through PubMed, EMBASE and Web of Science. Eligible prospective cohort studies that reported the relations of combined LBs with pre-determined outcomes were included. Summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated using either a fixed or random-effects model. Subgroup analysis, meta-regression, publication bias, and sensitivity analysis were as well performed. RESULTS: In the general population, individuals with the healthiest combination of LBs exhibited a significant risk reduction of 58% for CVD and 55% for CVD mortality. For individuals diagnosed with CVD, adherence to the healthiest combination of LBs corresponded to a significant risk reduction of 62% for CVD recurrence and 67% for all-cause mortality, when compared to those with the least-healthy combination of LBs. In the analysis of dose-response relationship, for each increment of 1 healthy LB, there was a corresponding decrease in risk of 17% for CVD and 19% for CVD mortality within the general population. Similarly, among individuals diagnosed with CVD, each additional healthy LB was associated with a risk reduction of 27% for CVD recurrence and 27% for all-cause mortality. CONCLUSIONS: Adopting healthy LBs is associated with substantial risk reduction in CVD, CVD mortality, and adverse outcomes among individuals diagnosed with CVD. Rather than focusing solely on individual healthy LB, it is advisable to advocate for the adoption of multiple LBs for the prevention and management of CVD. TRIAL REGISTRATION: PROSPERO: CRD42023431731.
Subject(s)
Cardiovascular Diseases , Life Style , Humans , Prospective Studies , Prognosis , Healthy Lifestyle , Health Behavior , Exercise , Risk Factors , Risk Reduction BehaviorABSTRACT
BACKGROUND: Health literacy measurement lays a solid foundation to identify associations with health outcomes and monitor population health literacy levels over time. In mainland China, most existing health literacy instruments are either knowledge-based or practice-based, making health literacy results incomparable between China and other countries. This study aimed to examine the reliability and validity of the 12-item Health Literacy Population Survey (HLS19-Q12) in a general population of Chinese adults. METHODS: A cross-sectional study was conducted to recruit primary carers of students from 11 schools in Zhengzhou, Henan Province, using convenience cluster sampling. Participants completed an online self-administered survey that collected information on key sociodemographics, health literacy (HLS19-Q12 and a comparison tool: Health Literacy Questionnaire (HLQ)), and health-related outcomes. Using the COnsensus-based Standards for the selection of health status Measurement Instruments (COSMIN) checklist as a guideline, we tested internal consistency, test-retest reliability, content validity, structural validity, concurrent predictive validity, and convergent validity of the HLS19-Q12. RESULTS: Overall, 14,184 participants completed the full survey. The HLS19-Q12 showed excellent internal consistency (Cronbach's α = 0.93), moderate test-retest reliability (intra-class correlation coefficient = 0.54), satisfactory content validity (based on the 12-matrix health literacy model), and strong structural validity (comparative fit index = 0.94, Tucker and Lewis's index of fit = 0.93, root mean square error of approximation = 0.095). Concurrent predictive validity results showed health literacy was associated with both health determinants and health-related outcomes. The HLS19-Q12 had weak to strong correlations (coefficients = 0.24 to 0.42) with the nine scales of the HLQ. Respondents had an average score of 81.6 (± 23.0) when using the HLS19-Q12, with 35.0% and 7.5% having problematic and inadequate levels of health literacy, respectively. CONCLUSIONS: The HLS19-Q12 is a reliable and valid instrument to measure health literacy in our sample. Further validation is needed with a more nationally representative sample of Chinese adults. The HLS19-Q12 could be used as a comprehensive, skills-based, and easy-to-administer health literacy assessment tool integrated into population surveys and intervention evaluations.
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Health Literacy , Adult , Humans , China , Cross-Sectional Studies , Reproducibility of Results , Surveys and QuestionnairesABSTRACT
Objective: To evaluate the prevalence and influencing factors of long COVID, and measure the difference in health status between long COVID and non-long COVID cases. Methods: A cross-sectional survey was conducted from February 1 to 8, 2023, using a stratified random sampling method in four regions (eastern [Changzhou], central [Zhengzhou], western [Xining] and northeastern [Mudanjiang]) of China. The survey collected COVID-19 patients' socio-demographic characteristics and lifestyles information. The scores of lifestyles and health status range from 5 to 21 and 0 to 100 points, respectively. The criteria of "persistent health problems after 4 weeks of COVID-19 infection" issued by the US Centers for Disease Control and Prevention was used to assess long COVID. Multiple linear regression was used to analyze the influencing factors of the health. The bootstrap method was used to analyze the lifestyles' mediating effect. Propensity score matching (PSM) was used to evaluate the net difference in health scores between long COVID and non-long COVID cases. Results: The study included 3165 COVID-19 patients, with 308 (9.73%) long COVID cases. The health score of the long COVID cases (74.79) was lower than that of the non-long COVID cases (81.06). After adjusting for potential confounding variables, we found that never focused on mental decompression was a common risk factor for the health of both groups. Lifestyles was the mediating factor on individuals' health. After PSM, the non-long COVID cases' health scores remained higher than that of long COVID cases. Conclusion: The proportion of long COVID cases was low, but they were worse off in health. Given the positive moderating effect of healthy lifestyles on improving the health of long COVID cases, healthy lifestyles including mental decompression should be considered as the core strategy of primary prevention when the epidemic of COVID-19 is still at a low level.
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Excessive immune activation contributes to the onset of early dysfunction of the maternal-fetal interface, and it is closely linked to the development of pre-eclampsia. However, the effect of specific immune cells on the risk of pre-eclampsia and eclampsia remains controversial. We investigated the causal relationship between immune cells and pre-eclampsia and eclampsia. For exposure, we extracted genetic variants associated with immune cell-related traits, and for outcomes, we used summary genetic data of pre-eclampsia/eclampsia. A two-sample Mendelian randomization (MR) analysis was then performed to assess the causal relationship. Robustness of the MR results was then evaluated through colocalization analysis. We found that genetically proxied circulating lymphocyte absolute count was causally associated with total eclampsia (odds ratio (OR) = 1.53, 95% confidence interval (CI) (1.31-1.79), p = 1.15E - 07) and pre-eclampsia (OR = 1.50, 95% CI (1.28-1.77), p = 9.18E - 07); T cell absolute count was causally associated with total eclampsia (OR = 1.49, 95% CI (1.28-1.73), p = 2.73E - 07) and pre-eclampsia (OR = 1.47, 95% CI (1.25-1.72), p = 1.76E - 06). And CD28- CD25+ CD8+ T cell absolute count was causally associated with total eclampsia (OR = 1.83, 95% CI (1.44-2.32), p = 7.11E - 07) and pre-eclampsia (OR = 1.77, 95% CI (1.38-2.26), p = 6.55E - 06). Colocalization analysis revealed that immune cell-related traits shared the same variant with pre-eclampsia/eclampsia. Our study suggested causal effects of genetic predisposition to high lymphocyte absolute count levels, T cell absolute count, and CD28- CD25+ CD8+ T cell absolute count on eclampsia, particularly pre-eclampsia risk, providing crucial new insights into the potential prevention target for eclampsia and pre-eclampsia.
Subject(s)
Eclampsia , Pre-Eclampsia , Pregnancy , Female , Humans , CD28 Antigens , Incidence , LymphocytesABSTRACT
Background: COVID-19 vaccine hesitancy has been cited as one of the main obstacles impacting vaccine coverage. However, factors that affect hesitancy may change over time. Understanding these evolving concerns and adapting strategies accordingly are crucial for effectively addressing vaccine hesitancy effectively and promoting public health. We aimed to explore the temporal changes in factors associated with COVID-19 VH during the COVID-19 pandemic and assess the dynamic evolution of VH. Methods: In August 2022 and February 2023, repeated online surveys were undertaken to collect information from 5378 adults across four regions of China. Multiple linear regression models assessed the influencing factors of COVID-19 VH. The association between protective motive theory (PMT) (perceived severity, susceptibility, benefits, barriers, and self-efficacy) and VH was evaluated by structural equation modeling (SEM). Results: Repeated measures showed that 573 (10.7%) and 1598 (29.7%) of the 5378 participants reported COVID-19 VH in the baseline and follow-up surveys, respectively. Educational levels, chronic disease, history of allergy, COVID-19 infection, and trust in medical staff and vaccine developers were positively associated with COVID-19 VH (Pï¼0.05). The application of SEM revealed that perceived severity, susceptibility, vaccination barriers, and self-efficacy in the PMT directly impacted on VH (Pï¼0.05). In addition, severity, susceptibility, benefits, and barriers had a significant direct effect on self-efficacy as ß = 0.113, ß = 0.070, ß = 0.722, ß = -0.516 respectively with P < 0.001. Conclusion: The prevalence of COVID-19 VH was relatively low in the baseline survey and much higher in the follow-up survey, with a significant increase in hesitancy rates among mainland Chinese residents. Acknowledging the substantial impact on the shaping of COVID-19 VH, one must consider factors including perceived severity, susceptibility, vaccination barriers, and self-efficacy.
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During the COVID-19 pandemic, the vaccine hesitancy has significantly affected the vaccination. To evaluate the booster vaccine hesitancy and its influencing factors among urban and rural residents, as well as to estimate the net difference of booster vaccine hesitancy between urban and rural residents. We conducted a nationwide, cross-sectional Internet survey on 1-8 February 2023, and employed stratified random sampling technique to select participants (≥18 years old) from urban and rural areas. Multivariate logistic regression was used to determine the factors impacting booster vaccine hesitancy. Propensity Score Matching was used to estimate the net difference of COVID-19 booster vaccine hesitancy between urban and rural residents. The overall COVID-19 booster vaccine hesitancy rate of residents was 28.43%. The COVID-19 booster vaccine hesitancy rate among urban residents was found to be 34.70%, among rural residents was 20.25%. Chronic diseases, infection status, vaccination benefits, and trust in vaccine developers were associated with booster vaccine hesitancy among urban residents. Barriers of vaccination were associated with booster vaccine hesitancy among rural residents. PSM analysis showed that the urban residents have a higher booster vaccine hesitancy rate than rural residents, with a net difference of 6.20%. The vaccine hesitancy rate increased significantly, and the urban residents have a higher COVID-19 booster vaccine hesitancy than rural residents. It becomes crucial to enhance the dissemination of information regarding the advantages of vaccination and foster greater trust among urban residents toward the healthcare system.
Subject(s)
COVID-19 , Rural Population , Humans , Adolescent , COVID-19/epidemiology , COVID-19/prevention & control , Cross-Sectional Studies , Pandemics , Propensity Score , Vaccination Hesitancy , VaccinationABSTRACT
The sensitizing ability of a catalytic system is closely related to the visible-light absorption ability, excited-state lifetime, redox potential, and electron-transfer rate of photosensitizers (PSs), however it remains a great challenge to concurrently mediate these factors to boost CO2 photoreduction. Herein, a series of Ir(III)-based PSs (Ir-1-Ir-6) were prepared as molecular platforms to understand the interplay of these factors and identify the primary factors for efficient CO2 photoreduction. Among them, less efficient visible-light absorption capacity results in lower CO yields of Ir-1, Ir-2 or Ir-4. Ir-3 shows the most efficient photocatalytic activity among these mononuclear PSs due to some comprehensive parameters. Although the Kobs of Ir-3 is ≈10â times higher than that of Ir-5, the CO yield of Ir-3 is slightly higher than that of Ir-5 due to the compensation of Ir-5's strong visible-light-absorbing ability. Ir-6 exhibits excellent photocatalytic performance due to the strong visible-light absorption ability, comparable thermodynamic driving force, and electron transfer rate among these PSs. Remarkably, the CO2 photoreduction to CO with Ir-6 can achieve 91.5â µmol, over 54â times higher than Ir-1, and the optimized TONC-1 can reach up to 28160. Various photophysical properties of the PSs were concurrently adjusted by fine ligand modification to promote CO2 photoreduction.
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BACKGROUND: People with hypertension have a higher risk of developing Parkinson's disease (PD), epidemiological evidence suggests that multiple antihypertensives may affect the occurrence and development of PD with inconsistent results. With multisource data, we sought to determine whether specific antihypertensive classes elevated or reduced the risk for PD. METHODS: We used a mixed methods approach that combines 4 methodologies. First, we conducted a disproportionality analysis using the reports causing adverse events in the US Food and Drug Administration Adverse Events Reporting System (FAERS) to explore the effect of different classes of antihypertensive medications on the risk of PD; based on the findings from FAERS, a meta-analysis and a UK Biobank cohort analysis were used to further assess the association of drug use with PD; finally, we employed Mendelian randomization (MR) analysis to validate the causal relationship between the drug target and the occurrence of PD. RESULTS: In the disproportionality analysis using the FAERS (N = 187,266), nonselective beta-adrenoceptor blockers (NBBs) were demonstrated to have a significant association with PD (reporting odds ratio (ROR) = 3.13; 95% CI 2.33-4.22). In the meta-analysis of 12 studies with 12,183,809 participants, PD risk was elevated in NBBs (RR, 1.64; 95% CI, 1.19-2.09) when stratified by subtypes of BBs. Among the 105,763 participants included in the cohort analysis using data from the UK Biobank, individuals who used NBBs had a significantly increased risk of PD compared to nonusers (HR, 1.47; 95% CI 1.04-2.06). The MR analysis revealed a significant association between higher expression of the ß2 adrenergic receptor (ADRB2) gene, a drug target blocked by NBBs, and a reduced risk of PD (OR, 0.85; 95% CI 0.73-0.99). CONCLUSIONS: Our comprehensive study indicated that regular NBB use is associated with an increased risk of PD. In light of the detrimental effects of NBBs on PD, some people should choose alternative antihypertensive treatments.
Subject(s)
Antihypertensive Agents , Benzenesulfonamides , Parkinson Disease , Humans , Antihypertensive Agents/therapeutic use , Parkinson Disease/drug therapy , Parkinson Disease/epidemiology , Adrenergic beta-Antagonists/adverse effects , Receptors, AdrenergicABSTRACT
The association of various air pollutants exposure during adolescence with blood pressure (BP) in young adulthood is uncertain. We intended to evaluate the long-term association of individual and joint air pollutants exposure during adolescence with BP in young adulthood. This cross-sectional study of incoming students was conducted in five geographically disperse universities in China during September and October 2018. Mean concentrations of particulate matter with diameters ≤2.5 µm (PM2.5 ), ≤10 µm (PM10 ), nitrogen dioxides (NO2 ), carbon monoxide (CO), sulfur dioxide (SO2 ), and ozone (O3 ) at participants' residential addresses during 2013-2018 were collected from the Chinese Air Quality Reanalysis dataset. Generalized linear mixed models (GLM) and quantile g-computation (QgC) models were utilized to estimate the association between individual and joint air pollutants exposure and systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP). A total of 16,242 participants were included in the analysis. The GLM analyses showed that PM2.5 , PM10 , NO2 , CO, and SO2 were significantly positively associated with SBP and PP, while O3 was positively associated with DBP. The QgC analyses indicated that long-term exposure to a mixture of the six air pollutants had a significant positive joint association with SBP and PP. In conclusion, air pollutant co-exposure during adolescence may influence BP in young adulthood. The findings of this study emphasized the impacts of multiple air pollutants interactions on potential health and the need of minimizing pollution exposures in the environment.
Subject(s)
Air Pollutants , Environmental Pollutants , Hypertension , Adolescent , Humans , Young Adult , Air Pollutants/adverse effects , Air Pollutants/analysis , Blood Pressure , China/epidemiology , Cross-Sectional Studies , Environmental Exposure/adverse effects , Environmental Exposure/analysis , Environmental Pollutants/analysis , Hypertension/epidemiology , Hypertension/etiology , Nitrogen Dioxide/analysis , Particulate Matter/adverse effects , Particulate Matter/analysisABSTRACT
Background: Genetic risk factors substantially contributed to the development of coronary atherosclerosis. Genome-wide association study (GWAS) has identified many risk loci for coronary atherosclerosis, but the translation of these loci into therapeutic targets is limited for their location in non-coding regions. Here, we aimed to screen the potential coronary atherosclerosis pathogenic genes expressed though TWAS (transcriptome wide association study) and explore the underlying mechanism association. Methods: Four TWAS approaches (PrediXcan, JTI, UTMOST, and FUSION) were used to screen genes associated with coronary atherosclerosis. Enrichment analysis of TWAS-identified genes was applied through the Metascape website. The summary-data-based Mendelian randomization (SMR) analysis was conducted to provide the evidence of causal relationship between the candidate genes and coronary atherosclerosis. At last, the cell type-specific expression of the intersection genes was examined by using human coronary artery single-cell RNA-seq, interrogating the immune microenvironment of human coronary atherosclerotic plaque at different stages of maturity. Results: We identified 19 genes by at least three approaches and 1 gene (NBEAL1) by four approaches. Enrichment analysis enriching the genes identified at least by two TWAS approaches, suggesting that these genes were markedly enriched in asthma and leukocyte mediated immunity reaction. Further, the summary-data-based Mendelian randomization (SMR) analysis provided the evidence of causal relationship between NBEAL1 gene and coronary atherosclerosis, confirming the protecting effects of NBEAL1 gene and coronary atherosclerosis. At last, the single cell cluster analysis demonstrated that NBEAL1 gene has differential expressions in macrophages, plasma cells and endothelial cells. Conclusion: Our study identified the novel genes associated with coronary atherosclerosis and suggested the potential biological function for these genes, providing insightful guidance for further biological investigation and therapeutic approaches development in atherosclerosis-related diseases.
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The design of Pt-based electrocatalysts with high efficiency towards acid oxygen reduction reactions is the priority to promote the development and application of proton exchange membrane fuel cells. Considering that the Pt atoms on the surfaces of the electrocatalysts face the problems of interference of non-active species (such as OHad, OOHad, CO, etc.), high resistance of mass transfer at the liquid-solid interfaces, and easy corrosion when working in harsh acid. Researchers have modified the surfaces' local environment of the electrocatalysts by introducing surface modifiers such as silicon or carbon layers, amine molecules, and ionic liquids on the surfaces of electrocatalysts, which show significant performance improvement. In this review, we summarized the research progress of surface modified Pt-based electrocatalysts, focusing on the surface modification strategies and their mechanisms. In addition, the development prospects of surface modification strategies of Pt-based electrocatalysts and the limitations of current research are pointed out.
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As the boom of data storage and processing, brain-inspired computing provides an effective approach to solve the current problem. Various emerging materials and devices have been reported to promote the development of neuromorphic computing. Thereinto, the neuromorphic device represented by memristor has attracted extensive research due to its outstanding property to emulate the brain's functions from synaptic plasticity, sensory-memory neurons to some intelligent behaviors of living creatures. Herein, we mainly review the progress of these brain functions mimicked by neuromorphic devices, concentrating on synapse (i.e. various synaptic plasticity trigger by electricity and/or light), neurons (including the various sensory nervous system) and intelligent behaviors (such as conditioned reflex represented by Pavlov's dog experiment). Finally, some challenges and prospects related to neuromorphic devices are presented.
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Obesity is regarded as an abnormal or excessive buildup of fat that may be bad for health and is influenced by a combination of intestinal flora, genetic background, physical activity level and environment. Symbiotic supplementation may be a realistic and easy therapy for the reversal of obesity and associated metabolic problems. In this study, we chose two Bifidobacterium species, three Lactobacilli species and four prebiotics to make a new symbiotic formulation. High or low doses of the symbiotic were administered to rats, and biochemical indicators were recorded to assess the biological effects in a high-fat-diet-induced rat model. The underlying mechanisms were explored by integrating 16S rRNA sequencing with an extensively targeted metabolome. High-dose symbiotic supplementation was effective in reducing obesity and concomitant metabolic syndrome. The high-dose symbiotic also significantly increased the abundance of Blautia, which was negatively correlated with taurocholic acid and the main differential metabolites involved in amino acid and bile acid metabolism. While the low-dose symbiotic had some therapeutic effects, they were not as strong as those at the high dose, demonstrating that the effects were dose-dependent. Overall, our novel symbiotic combination improved plasma glucose and lipid levels, shrunk adipocyte size, restored liver function, increased the abundance of Blautia and adjusted bile acid and amino acid metabolism.
Subject(s)
Metabolic Syndrome , Rats , Animals , RNA, Ribosomal, 16S , Obesity/metabolism , Diet, High-Fat , Bile Acids and SaltsABSTRACT
Background: The causal direction and magnitude of the associations between blood cell count and coronary heart disease (CHD) remain uncertain due to susceptibility of reverse causation and confounding. This study aimed to investigate the associations between blood cell count and CHD using Mendelian randomization (MR). Methods: In this two-sample MR study, we identified independent blood cell count associated genetic variants from a genome-wide association studies (GWAS) among European ancestry individuals. Summary level data of CHD was obtained from a GWAS consisting of 547261 subjects. Methods of inverse variance weighted (IVW), Mendelian Randomization-Egger (MR-Egger), weighted median, and outlier test (MR-PRESSO) were conducted to investigate the associations between blood cell and CHD. Results: Among all cardiovascular outcomes of interest, blood cell counts were only associated with CHD. Our findings indicated that white blood cell count and neutrophil cell count were significantly associated with increased risk of CHD [odds ratio (OR) = 1.07, 95% confidence interval (CI), 1.01-1.14; OR = 1.09, 1.02-1.16). However, there was no significant association between monocyte cell count, basophil cell count, lymphocyte cell count, eosinophil cell count, and CHD (p > 0.05). The results after excluding outliers were consistent with main results and the sensitivity analyses showed no evidence of pleiotropy (MR-Egger intercept, p > 0.05). Conclusion: Our MR study suggested that greater white blood cell count and neutrophil cell count were associated with a higher risk of CHD. Future studies are still warranted to validate the results and investigate the mechanisms underlying these associations.
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OBJECTIVE: We aimed to assess hypertension prevalence and management in Central China. METHODS: In this cross-sectional study conducted from February 2019 to February 2020, we applied stratified multistage random sampling to investigate residents aged 35 to 75 years in Dancheng county of Zhoukou city and Xincai county of Zhumadian city, both in Central China. RESULTS: We enrolled 63,940 participants in this survey. A total of 43.6% (95% confidence interval [CI]: 43.2-44.0) of participants had hypertension. Of these, 49.3% (95% CI: 48.7-49.9) were aware of their diagnosis, 36.5% (95% CI: 35.9-37.1) took antihypertensive medication, and 14.3% (95% CI: 13.9-14.7) had their blood pressure under control. Only 31.4% of hypertensive people receiving antihypertensive treatment had achieved control. The hypertension prevalence was lower in urban areas than in rural areas, with higher rates of awareness, treatment, and control. Among subgroups, rural men had the highest prevalence of hypertension. Prevalence, awareness, and treatment rates all increased with age, except for control rates, which declined in the 65- to 75-year-old group. CONCLUSIONS: People in Central China have a high hypertension prevalence but low rates of awareness, treatment, and control. Great effort is needed to improve the prevention and management of hypertension in this region.
Subject(s)
Antihypertensive Agents , Hypertension , Male , Humans , Aged , Cross-Sectional Studies , Antihypertensive Agents/therapeutic use , Prevalence , Health Knowledge, Attitudes, Practice , Hypertension/drug therapy , Hypertension/epidemiology , Blood Pressure , China/epidemiology , Rural PopulationABSTRACT
Aim: To determine the pharmacoeconomics of empagliflozin for the treatment of heart failure (HF) with reduced ejection fraction in China and to provide evidence-based reference for clinical rational drug selection and medical decision-making. Research design and methods: We used the Markov model to evaluate the cost-effectiveness of empagliflozin for the treatment of HF with reduced ejection fraction (HFrEF). We evaluated the cost-effectiveness of the standard treatment in addition to empagliflozin (empagliflozin group) vs. the cost-effectiveness of the standard treatment alone (standard treatment group). Results: We found that each additional quality-adjusted life year (QALY) in the empagliflozin group costed $3,842.20 more, which was less than China's gross domestic product (GDP) per capita in 2021 ($11,981). The steady-state mortality in the two groups was the key factor affecting the incremental cost-effectiveness ratio (ICER). Probabilistic sensitivity analysis revealed that when the willingness-to-pay (WTP) threshold was one time the GDP per capita in 2021 ($11,981) and three times the GDP per capita in 2021 ($35,943), the probability of the empagliflozin group being cost-effective was 85.8 and 91.6%, respectively. Conclusion: Compared with the standard treatment alone, the addition of empagliflozin to the standard treatment was more cost-effective for the treatment of HFrEF in China.