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Abstract Background Early-life cardiovascular risk factors (CVRFs) are known to be associated with target organ damage during adolescence and premature cardiovascular morbidity and mortality during adulthood. However, contemporary data describing whether the prevalence of CVRFs and treatment and control rates have changed are limited. This study aimed to examine the temporal trends in the prevalence, treatment, and control of CVRFs among US adolescents over the past 2 decades. Methods This is a serial cross-sectional study using data from nine National Health and Nutrition Examination Survey cycles (January 2001—March 2020). US adolescents (aged 12 to 19 years) with information regarding CVRFs (including hypertension, elevated blood pressure [BP], diabetes, prediabetes, hyperlipidemia, obesity, overweight, cigarette use, inactive physical activity, and poor diet quality) were included. Age-adjusted trends in CVRF prevalence, treatment, and control were examined. Joinpoint regression analysis was performed to estimate changes in the prevalence, treatment, and control over time. The variation by sociodemographic characteristics were also described. Results A total of 15,155 US adolescents aged 12 to 19 years (representing ≈ 32.4 million people) were included. From 2001 to March 2020, there was an increase in the prevalence of prediabetes (from 12.5% [95% confidence interval (CI), 10.2%-14.9%] to 37.6% [95% CI, 29.1%-46.2%]) and overweight/obesity (from 21.1% [95% CI, 19.3%-22.8%] to 24.8% [95% CI, 21.4%-28.2%]; from 16.0% [95% CI, 14.1%-17.9%] to 20.3% [95% CI, 17.9%-22.7%]; respectively), no improvement in the prevalence of elevated BP (from 10.4% [95% CI, 8.9%-11.8%] to 11.0% [95% CI, 8.7%-13.4%]), diabetes (from 0.7% [95% CI, 0.2%-1.2%] to 1.2% [95% CI, 0.3%-2.2%]), and poor diet quality (from 76.1% [95% CI, 74.0%-78.2%] to 71.7% [95% CI, 68.5%-74.9%]), and a decrease in the prevalence of hypertension (from 8.1% [95% CI, 6.9%-9.4%] to 5.5% [95% CI, 3.7%-7.3%]), hyperlipidemia (from 34.2% [95% CI, 30.9%-37.5%] to 22.8% [95% CI, 18.7%-26.8%]), cigarette use (from 18.0% [95% CI, 15.7%-20.3%] to 3.5% [95% CI, 2.0%-5.0%]), and inactive physical activity (from 83.0% [95% CI, 80.7%-85.3%] to 9.5% [95% CI, 4.2%-14.8%]). Sex and race/ethnicity affected the evolution of CVRF prevalence differently. Whilst treatment rates for hypertension and diabetes did not improve significantly (from 9.6% [95% CI, 3.5%-15.8%] to 6.0% [95% CI, 1.4%-10.6%]; from 51.0% [95% CI, 23.3%-78.7%] to 26.5% [95% CI, 0.0%-54.7%]; respectively), BP control was relatively stable (from 75.7% [95% CI, 56.8%-94.7%] to 73.5% [95% CI, 40.3%-100.0%]), while glycemic control improved to a certain extent, although it remained suboptimal (from 11.8% [95% CI, 0.0%-31.5%] to 62.7% [95% CI, 62.7%-62.7%]). Conclusions From 2001 to March 2020, although prediabetes and overweight/obesity increased, hypertension, hyperlipidemia, cigarette use, and inactive physical activity decreased among US adolescents aged 12 to 19 years, whereas elevated BP, diabetes, and poor diet quality remained unchanged. There were disparities in CVRF prevalence and trends across sociodemographic subpopulations. While treatment and control rates for hypertension and diabetes plateaued, BP control were stable, and improved glycemic control was observed.

The pyrolysis behaviors and temperature evolution history of lignocellulosic biomass (Beech, BH) were characterized using a novel pyrolysis model—C-DAEM. The simulation results were validated through corresponding experimental data. Based on the simulation results, two distinct peaks were observed in the temperature difference between the surface and center (TDSC) curve, namely the thermal disturbance peak (TDP) and the pyrolysis reaction peak (PRP). The presence of TDP and PRP was confirmed by examining the heat flux ratio between the pyrolysis rate and the temperature rise rate. Moreover, the results indicated that three factors, namely heating temperature, particle size, and pyrolysis rate, influenced the relative intensity between TDP and PRP. By changing the values of each impact factor, conditions where TDP owns the same height with PRP were obtained under different working conditions. These findings have led to the development of a dimensionless number, naming the pyrolysis-heating surface-center number (PHSC number). This number could provide a comprehensive indication of the collective impact of the aforementioned factors when TDP and PRP exhibit equal peak heights.

The gas-sensing application potential of the TO8C monolayer for the target gases (NO, NO2, CO, CO2, NH3, CH4, H2O, and H2) was systematically investigated via DFT calculations. Only NO and NO2 adsorption can tune the electronic properties of the TO8C monolayer. Since the weak adsorption strength of NO and NO2 is unfavorable for the sensor device, E-field modulation was applied. Except as the enhancement of adsorption strength into desired ranges for NO and NO2, E-field modulation of −0.14 ∼ −0.21 V/Å for NO (0.08 ∼ 0.12 V/Å and −0.26 ∼ −0.29 V/Å for NO2) makes semiconducting transfer into conducting properties, indicating the sensitivity of the monolayer towards NO and NO2 gases was also effectively improved. However, the electronic properties of TO8C monolayer adsorbed with the other gases were hardly changed by the above-mentioned E-fields. When the applied E-fields were in −0.12 ∼ −0.17 V/Å (or −0.26 ∼ −0.29 V/Å), the conducting properties for NO (or NO2) adsorption were maintained in the existence of humidity, indicating that the determinate E-field is much favorable for the TO8C-based sensor to detect NO and NO2 gases without considering whether the humidity exists. Our findings reveal that the TO8C monolayers are compelling and feasible candidates for NO and NO2 resistance-type sensors at room temperature under the E-field modulation.

Summary: Background: The public health burden of cardiomyopathies and competency in their management by health agencies in China are not well understood. Methods: This study adopted a multi-stage sampling method for hospital selection. In the first stage, nationwide tertiary hospital recruitment was performed. As a result, 88 hospitals with the consent of the director of cardiology and access to an established electronic medical records system, were recruited. In the second stage, we sampled 66 hospitals within each geographic-economic stratification through a random sampling process. Data on (1) the outpatient and inpatient visits for cardiomyopathies between 2017 and 2021 and (2) the competency in the management of patients with cardiomyopathies, were collected. The competency of a hospital to provide cardiomyopathy care was evaluated using a specifically devised scale. Findings: The outpatient and inpatient visits for cardiomyopathies increased between 2017 and 2021 by 38.6% and 33.0%, respectively. Most hospitals had basic facilities for cardiomyopathy assessment. However, access to more complex procedures was limited, and the integrated management pathway needs improvement. Only 4 (6.1%) of the 66 participating hospitals met the criteria for being designated as a comprehensive cardiomyopathy center, and only 29 (43.9%) could be classified as a primary cardiomyopathy center. There were significant variations in competency between hospitals with different administrative and economic levels. Interpretation: The health burden of cardiomyopathies has increased significantly between 2017 and 2021 in China. Although most tertiary hospitals in China can offer basic cardiomyopathy care, more advanced facilities are not yet universally available. Moreover, inconsistencies in the management of cardiomyopathies across hospitals due to differing administrative and economic levels warrants a review of the nation allocation of medical resources. Funding: This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2023-I2M-1-001) and the National High Level Hospital Clinical Research Funding (2022-GSP-GG-17).

Abstract Background The influence of sarcopenic obesity (SO) on overall survival in older adults with hypertension has not been addressed. The aim of this study was to investigate the prevalence and mortality predictive value of various body composition phenotypes, focusing mainly on SO, in older adults with hypertension. Methods We included 1105 hypertensive patients aged ≥ 60 years from the National Health and Nutrition Examination Survey 1999–2004. Sarcopenia was broadly defined based on low lean mass (LLM; as measured by dual-energy X-ray absorptiometry), and was defined using appendicular lean mass (ALM) divided by height squared (ALM/height2), weight (ALM/weight), and body mass index (BMI; ALM/BMI), respectively. Obesity was defined as BMI ≥ 30 kg/m2, body fat percentage ≥ 30/42%, or waist circumference ≥ 102/88 cm. The prevalence of LLM with obesity was estimated according to each ALM index (ALMI). Multivariable Cox regression analysis and sensitivity analysis were used to examine the association between various body composition phenotypes and all-cause mortality. Results In older adults with hypertension, the prevalence of LLM with obesity by the ALM/height2 index (9.8%) was lower relative to the ALM/weight (11.7%) and ALM/BMI indexes (19.6%). After a median follow-up of 15.4 years, 642 deaths occurred. In the fully adjusted models, LLM with obesity was significantly associated with a higher risk of all-cause mortality (hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.14–2.49, P = 0.008; HR 1.48, 95% CI 1.04–2.10, P = 0.028; HR 1.30, 95% CI 1.02–1.66, P = 0.037; respectively) compared with the normal body phenotype, with no statistical differences found in individuals with LLM or obesity alone. Sensitivity analysis confirmed the robustness of the results. Conclusions The prevalence of LLM with obesity markedly differed in older adults with hypertension according to the 3 different ALMIs, varying from 9.8%, 11.7%, to 19.6%. Patients with both LLM and obesity had a higher risk of all-cause mortality. Further large, prospective, cohort studies are warranted to validate these findings and uncover underlying mechanisms.

Abstract Aims The early identification and appropriate management may provide clinically meaningful and substained benefits in patients with acute heart failure (AHF). This study aimed to develop an integrative nomogram with myocardial perfusion imaging (MPI) for predicting the risk of all‐cause mortality in AHF patients. Methods and results Prospective study of 147 patients with AHF who received gated MPI (59.0 [47.5, 68.0] years; 78.2% males) were enrolled and followed for the primary endpoint of all‐cause mortality. We analysed the demographic information, laboratory tests, electrocardiogram, and transthoracic echocardiogram by the least absolute shrinkage and selection operator (LASSO) regression for selection of key features. A multivariate stepwise Cox analysis was performed to identify independent risk factors and construct a nomogram. The predictive values of the constructed model were compared by Kaplan–Meier curve, area under the curves (AUCs), calibration plots, continuous net reclassification improvement, integrated discrimination improvement, and decision curve analysis. The 1, 3, and 5 year cumulative rates of death were 10%, 22%, and 29%, respectively. Diastolic blood pressure [hazard ratio (HR) 0.96, 95% confidence interval (CI) 0.93–0.99; P = 0.017], valvular heart disease (HR 3.05, 95% CI 1.36–6.83; P = 0.007), cardiac resynchronization therapy (HR 0.37, 95% CI 0.17–0.82; P = 0.014), N‐terminal pro‐B‐type natriuretic peptide (per 100 pg/mL; HR 1.02, 95% CI 1.01–1.03; P

Abstract Background The triglyceride glucose (TyG) index, an indicator of insulin resistance, is often associated with adverse outcomes in various cardiovascular diseases, while hypertension is associated with an increased risk of cardiovascular diseases. As the loss of muscle mass in people with hypertension is poorly understood, the current study aimed to explore the relationship between TyG index and muscle mass in hypertensive population. Methods We analyzed data from hypertensive adult participants in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. The TyG index and body mass index (BMI)-adjusted skeletal muscle mass index (SMI) were calculated and the relationship between the two was evaluated using multivariable linear regression and restricted cubic spline (RCS) regression models. Results A total of 1633 participants in the dataset were included for the final analysis. In the multivariable regression analysis, the adjusted β of SMI with a 95% confidence interval (CI) for the highest TyG index quartile was − 5.27 (− 9.79 to − 0.75), compared with the lowest quartile. A negative linear relationship between TyG index and SMI was plotted by RCS regression (nonlinear P = 0.128). Stratified models of non-smoking women of different ages also demonstrated that SMI decreased as TyG index increased (all P for trend

Pulverized coal pyrolysis based on solid heat carrier has a huge advantage in high tar yield. In this study, pyrolysis experiments on pulverized coal were conducted in a lab-scale fluidized bed reactor at 650 °C, utilizing char as the solid heat carrier. The influence of mass ratio of char to coal (RATIO) was investigated. Results show that the incorporation of solid heat carrier of char significantly enhanced the primary pyrolysis reaction in coal pyrolysis, resulting in increasing yields of tar and gas but reducing one of char. The yield of tar maximally reached 148.80–262.22% of the Gray–King analysis value at the RATIO of 14.52 g/g. As the RATIO increased, the tar contained more light component content, indicating that incorporating solid heat carriers improved the tar quality. These findings offer significant insights for the design of fluidized bed pyrolysis unit utilizing char as solid heat carrier.

Abstract Background Traditional Chinese Medicine (TCM) is widely used to treat heart failure (HF). Syndrome differentiation is a unique and crucial component in TCM practice for guiding disease diagnosis and treatment strategies as well as clinical research. The major bottlenecks in TCM syndrome differentiation are the diversity of the syndrome differentiation criteria and the broad spectrum of syndrome patterns, hindering evidence-based studies for clinical research. In the present study, we aim to develop an evidence-based questionnaire for the diagnosis of HF and establish a definitive set of criteria for syndrome differentiation. Methods We designed a TCM syndrome differentiation questionnaire for heart failure (SDQHF) based on the "TCM expert consensus for diagnosis and treatment of heart failure" (expert consensus), literature review, and various clinical guidelines. To test the reliability and efficiency of the questionnaire, we performed a large-scale multiple-center clinical trial with the recruitment of 661 HF patients. Cronbach's alpha was used to assess the internal consistency of the SDQHF. Content validity was conducted through expert review. Principal component analysis (PCA) was applied to evaluate the construct validity. We constructed a proposed model for syndrome differentiation for HF based on the PCA results. Tongue analysis was performed to verify the accuracy of syndromes derived from the proposed model and the expert consensus. An evidence-based practical questionnaire for TCM syndrome differentiation patients was developed and validated with the data from 661 HF patients. Results The syndrome differentiation criteria were constructed with five syndrome elements (qi-deficiency, yang-deficiency, yin-deficiency, blood stasis, and phlegm retention). The results revealed good convergent and discriminant validity, satisfactory internal consistency, and feasibility. The significant discoveries include: (1) A total of 91% of the derived TCM syndromes from the proposed model matched with the characterized tongue images of the syndrome patterns; (2) Qi Deficiency Syndrome is the dominant syndrome pattern for HF patients, followed by Yang-Qi Deficiency Syndrome and Qi-yin deficiency Syndrome, and finally, Yin-Yang Dual Deficiency Syndrome; (3) The majority of the HF patients had the combination of Blood Stasis and Phlegm Retention Syndromes; (4) The "Yin-Yang Dual Deficiency" Syndrome was a valid syndrome for HF, suggesting that this syndrome pattern should be included in the criteria for syndrome differentiation; and (5) Through the validation of the expert consensus, several recommendations were proposed to improve the accuracy of syndrome differentiation of HF. Conclusions The proposed SDQHF and the criteria could be a reliable and valid tool for syndrome differentiation of heart failure with high accuracy. It is recommended to use the proposed model for evidence-based study on Chinese Medicine to diagnose and treat HF. Trial registration number: The trial was registered at the Chinese Clinical Trial Registry, http://www.chictr.org.cn . (Registration No.: ChiCTR1900021929); Date: 2019-03-16.

Background: Di(2-ethylhexyl) phthalate (DEHP) a parent compound that is metabolized into 4 phthalate metabolites, which correlate to adverse cardio-metabolic risk factors. This study aimed to explore the links between urinary DEHP metabolites and serum lipids in the U.S. general adult population. Methods: In this cross-sectional study, data on 11 urinary phthalate metabolites from the 2005–2018 National Health and Nutrition Examination Surveys (NHANES) were analyzed. Multivariate linear regression and restricted cubic spline (RCS) were used to examine the relationship between phthalate metabolites [specific DEHPs: mono-(2-ethyl-5-carboxy-pentyl) phthalate (MECPP), mono-(2-ethyl-5-hydroxy-hexyl) phthalate (MEHHP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-oxo-hexyl) phthalate (MEOHP)] and serum lipids (triglycerides [TG], total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], and high-density lipoprotein cholesterol [HDL-C]). To identify mixed exposure effects of phthalate metabolites, quantile g-computation (QG-C) and weighted quantile sum (WQS) regression were employed for the lipid profiles. Results: A total of 9141 adults were included in the analysis. MECPP, MEHHP, MEHP, and MEOHP in the highest quartile had a negative relationship with HDL-C compared to the lowest quartile (All P for trend 0.05). The WQS index of DEHP metabolites showed independent correlations with HDL-C [β = −0.26, 95%CI (−0.43, −0.09), P = 0.002], TC [β = 0.55, 95%CI (0.13, 0.98), P = 0.011], and TG [β = 2.40, 95%CI (0.85, 3.96), P = 0.003]. Conclusion: Our study suggests that environmental DEHP exposure may affect serum HDL-C and TG levels in the general adult population. Further research is warranted to confirm these findings and illuminate the underlying mechanisms of DEHP exposure on lipids.

In this work, to promote the separation of photogenerated carriers, prevent the catalyst from photo-corrosion, and improve the photo-Fenton synergistic degradation of organic pollutants, the coating structure of FeOOH/BiO2−x rich in oxygen vacancies was successfully synthesized by a facile and environmentally friendly two-step process of hydrothermal and chemical deposition. Through a series of degradation activity tests of synthesized materials under different conditions, it was found that FeOOH/BiO2−x demonstrated outstanding organic pollutant degradation activity under visible and near-infrared light when hydrogen peroxide was added. After 90 min of reaction under photo-Fenton conditions, the degradation rate of Methylene Blue by FeOOH/BiO2−x was 87.4%, significantly higher than the degradation efficiency under photocatalysis (60.3%) and Fenton (49.0%) conditions. The apparent rate constants of FeOOH/BiO2−x under photo-Fenton conditions were 2.33 times and 3.32 times higher than photocatalysis and Fenton catalysis, respectively. The amorphous FeOOH was tightly coated on the layered BiO2−x, which significantly increased the specific surface area and the number of active sites of the composites, and facilitated the improvement of the separation efficiency of the photogenerated carriers and the prevention of photo-corrosion of BiO2−x. The analysis of the mechanism of photo-Fenton synergistic degradation clarified that ·OH, h+, and ·O2− are the main active substances involved in the degradation of pollutants. The optimal degradation conditions were the addition of the FeOOH/BiO2−x composite catalyst loaded with 20% Fe at a concentration of 0.5 g/L, the addition of hydrogen peroxide at a concentration of 8 mM, and an initial pH of 4. This outstanding catalytic system offers a fresh approach to the creation and processing of iron-based photo-Fenton catalysts by quickly and efficiently degrading various organic contaminants.

Summary: The purpose of this study is to explore the prognostic values of ventricle epicardial fat volume (EFV) calculated by cardiac magnetic resonance in patients with chronic heart failure (CHF).A total of 516 patients with CHF (left ventricular ejection fraction ≤ 50%) were recruited, and 136 (26.4%) of whom experienced major adverse cardiovascular events (MACE) within median follow-up of 24 months. The target marker—EFV was found to be associated with MACE in both univariate and multivariable analysis adjusted for various clinical variables (p

Biomolecular abundance detection of fermentation microorganisms is significant for the accurate regulation of fermentation, which is conducive to reducing fermentation costs and improving the yield of target products. However, the development of an accurate analytical method for the detection of biomolecular abundance still faces important challenges. Herein, we present a non-invasive biomolecular abundance detection method based on Raman spectra combined with target extraction and multimodel fitting. The high gain of the eXtreme Gradient Boosting (XGBoost) algorithm was used to extract the characteristic Raman peaks of metabolically active proteins and nucleic acids within E. coli and yeast. The test accuracy for different culture times and cell cycles of E. coli was 94.4% and 98.2%, respectively. Simultaneously, the Gaussian multi-peak fitting algorithm was exploited to calculate peak intensity from mixed peaks, which can improve the accuracy of biomolecular abundance calculations. The accuracy of Gaussian multi-peak fitting was above 0.9, and the results of the analysis of variance (ANOVA) measurements for the lag phase, log phase, and stationary phase of E. coli growth demonstrated highly significant levels, indicating that the intracellular biomolecular abundance detection was consistent with the classical cell growth law. These results suggest the great potential of the combination of microbial intracellular abundance, Raman spectra analysis, target extraction, and multimodel fitting as a method for microbial fermentation engineering.

Abstract Background Gut microbiota plays important roles in health maintenance and diseases. Physical exercise has been demonstrated to be able to modulate gut microbiota. However, the potential role of gut microbiome in exercise protection to myocardial infarction (MI) remains unclear. Results Here, we discovered exercise training ameliorated cardiac dysfunction and changed gut microbial richness and community structure post-MI. Moreover, gut microbiota pre-depletion abolished the protective effects of exercise training in MI mice. Furthermore, mice receiving microbiota transplants from exercised MI mice had better cardiac function compared to mice receiving microbiota transplants from non-exercised MI mice. Mechanistically, we analyzed metabolomics in fecal samples from exercised mice post-MI and identified 3-Hydroxyphenylacetic acid (3-HPA) and 4-Hydroxybenzoic acid (4-HBA), which could be applied individually to protect cardiac dysfunction post-MI and apoptosis through NRF2. Conclusions Together, our study provides new insights into the role of gut microbiome in exercise protection to MI, offers opportunities to modulate cardiovascular diseases by exercise, microbiome and gut microbiota-derived 3-HPA and 4-HBA. Video Abstract

Background Systemic oxidative stress is involved in the development of hypertension, whereas carotenoids are a group of natural antioxidants. Our study aims to evaluate the relationships between the serum concentrations of major carotenoids and mortality in hypertensive adults. Methods and Results Data on 5 serum carotenoids from the National Health and Nutrition Examination Survey (NHANES) III and NHANES 2001–2006 were included. Outcome measures (all‐cause and cardiovascular mortality) were identified from the National Death Index through December 31, 2019. Multiple Cox proportional hazards regression and restricted cubic spline analyses were performed to determine the association between carotenoid levels and outcomes. A total of 8390 hypertensive adults were included in the analysis. At a median follow‐up duration of 16.6 years, all‐cause and cardiovascular mortality occurred in 4005 (47.74%) and 1205 (14.36%) participants, respectively. Compared with the lowest quartiles, the highest quartiles of 5 major serum carotenoids were associated with lower risk of all‐cause mortality, with multivariable‐adjusted hazard ratios (HRs) of 0.63 (95% CI, 0.56–0.71) for α‐carotene, 0.70 (95% CI, 0.61–0.80); for β‐carotene, 0.67 (95% CI, 0.58–0.76); for β‐cryptoxanthin, 0.74 (95% CI, 0.64–0.86) for lycopene; and 0.72 (95% CI, 0.63–0.83) for lutein/zeaxanthin. For cause‐specific mortality, this association with the fourth quartile of serum carotenoids was evident for a reduced rate of cardiovascular mortality, with a 32% reduction for α‐carotene (HR, 0.68 [95% CI, 0.55–0.86]), a 29% reduction for β‐cryptoxanthin (HR, 0.71 [95% CI, 0.56–0.89]), and a 26% reduction for lycopene (HR, 0.74 [95% CI, 0.59–0.94]), but not for β‐carotene and lutein/zeaxanthin. In addition, we found that serum α‐carotene, β‐carotene, β‐cryptoxanthin, and lutein/zeaxanthin levels were nonlinearly related to all‐cause mortality with inflection points of 2.43, 8.49, 5.12, and 14.17 μg/dL, respectively. Serum α‐carotene, β‐cryptoxanthin, and lutein/zeaxanthin concentrations showed nonlinear associations with cardiovascular mortality with inflection points of 2.31, 5.26, and 15.40 μg/dL, respectively. Conclusions Findings suggest that higher serum carotenoid concentrations were associated with lower risks of all‐cause and cardiovascular mortality in hypertensive adults.

As a life-essential coenzyme, nicotinamide adenine dinucleotide (NAD+) has been explored for more than a century. In Saccharomyces, the natural NAD+de novo biosynthetic pathway initiating from tryptophan has been well elucidated. To bypass this stringently controlled natural pathway in yeast, an economical C3N pathway that was developed in Escherichia coli previously was constructed in Saccharomyces as a short detour for de novo NAD+ biosynthesis. After the functional expressions of the C3N genes were identified in Saccharomyces cerevisiae BY4741 by in vitro enzymatic assays, the C3N module was introduced into an NAD+ auxotrophic S. cerevisiae strain BY01, in which the BNA2 gene encoding tryptophan 2,3-dioxygenase was inactivated. The efficient NAD+ synthesis via the C3N pathway was confirmed by both plate assays and fermentation analysis. The applicability of the C3N pathway in cofactor engineering was tested by introducing it into S. cerevisiae BY4741, which improved the cellular NAD(H) level considerably. Consequently, this study proved that the de novo NAD+ biosynthetic pathway can be replaced by an artificial pathway in yeast, which paves a way to design more promising schemes in eukaryotes for rational manipulation of the cellular NAD(H) levels.

A recombinant inbred line population including 371 lines was developed by a high kernel number per spike (KNPS) genotype T1208 and a low KNPS genotype Chuannong18 (CN18). A genetic linkage map consisting of 11,583 markers was constructed by the Wheat55K SNP Array. The quantitative trait loci (QTLs) related to KNPS were detected in three years. Eight, twenty-seven, and four QTLs were identified using the ICIM-BIP, ICIM-MET, and ICIM-EPI methods, respectively. One QTL, QKnps.sau-2D.1, which was mapped on chromosome 2D, can explain 18.10% of the phenotypic variation (PVE) on average and be considered a major and stable QTL for KNPS. This QTL was located in a 0.89 Mb interval on chromosome 2D and flanked by the markers AX-109283238 and AX-111606890. Moreover, KASP-AX-111462389, a Kompetitive Allele-Specific PCR (KASP) marker which closely linked to QKnps.sau-2D.1, was designed. The genetic effect of QKnps.sau-2D.1 on KNPS was successfully confirmed in two RIL populations. The results also showed that the significant increase of KNPS and 1000-kernel weight (TKW) was caused by QKnps.sau-2D.1 overcoming the disadvantage due to the decrease of spike number (SN) and finally lead to a significant increase of grain yield. In addition, within the interval in which QKnps.sau-2D.1 is located in Chinese Spring reference genomes, only fifteen genes were found, and two genes that might associate with KNPS were identified. QKnps.sau-2D.1 may provide a new resource for the high-yield breeding of wheat in the future.

Background: Cerebral ischemia-reperfusion injury (CIR) following a stroke results in secondary damage and is a leading cause of adult disability. The present study aimed to identify hub genes and networks in CIR to explore potential therapeutic agents for its treatment. Methods: Differentially expressed genes based on the GSE23163 dataset were identified, and weighted gene co-expression network analysis was performed to explore co-expression modules associated with CIR. Hub genes were identified by intersecting immune gene profiles, differentially expressed genes, and modular genes. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, and transcription factor-microRNA-gene regulatory network analyses were then conducted in selected crucial modules. Subsequently, their expression levels in animal models were verified using real-time quantitative polymerase chain reaction and Western blotting. Finally, potential drug molecules were screened for, and molecular docking simulations were performed to identify potential therapeutic targets. Results: Seven hub genes—namely, Ccl3, Ccl4, Ccl7, Cxcl1, Hspa1a, Cd14, and Socs3—were identified. Furthermore, we established a protein interaction network using the STRING database and found that the core genes selected through the cytohubba plugin remained consistent. Animal experiments showed that at the transcriptional level, all seven genes showed significant differences (p < 0.001, fold change vs sham, 5–200). At the translational level, however, only Ccl3, Ccl4, Ccl7, Hspa1a, and Socs3 showed significant differences, while Cxcl1 and Cd14 did not. Nifedipine, with the highest predicted score, was identified as a therapeutic agent and successfully docked with the protein encoded by the hub genes. Conclusions: The expression of Ccl3, Ccl4, Ccl7, Hspa1a, and Socs3 was significantly different in CIR tissues compared to normal tissues both at the transcriptional and translational levels. Systems biology approaches indicated that these could be possible CIR marker genes, providing a stepping stone for further experimental studies.

Some biologically active compounds isolated from sea cucumbers stimulate the body’s immune response by activating immune cells. Immune function is closely related to the integrity intestinal barrier and balanced gut microbiota. However, it is unknown whether the daily administration of holothurian wall hydrolysate (HWH) ameliorated intestinal dysbiosis and barrier injury induced by immunodeficiency. This study aimed to investigate the immunomodulatory effect and the underlying mechanism of HWH in cyclophosphamide (CTX)-induced immunocompromised mice. BALB/c mice received CTX (80 mg/kg, intraperitoneally) once a day for 3 days to induce immunodeficiency, and then they received the oral administration of HWH (80 or 240 mg/kg) or levamisole hydrochloride (LH, 40 mg/kg, positive control), respectively, once a day for 7 days. We utilized 16S rRNA sequencing for microbial composition alterations, histopathological analysis for splenic and colonic morphology, Western blotting for expressions of tight junction proteins (TJs), and quantitative real-time (qRT)-PCR for measurements of pro-inflammatory cytokines. HWH attenuated the immune organ damage induced by CTX, increased the secretions of interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α, and promoted the recovery of goblet cells and the production of TJs (claudin-1, occludin, and ZO-1) in the colon of the immunocompromised mice. Moreover, HWH promoted the growth of beneficial microorganisms such as Lactobacillus, Lachnospiraceae, Christensenellaceae, and Bifidobacterium, while it suppressed the populations of Ruminococcus, Staphylococcus, and Streptococcus. These results demonstrate that HWH elicits intestinal mucosal immunity, repairs the damage to intestinal mucosal integrity, and normalizes the imbalanced intestinal microbial profiles in immunocompromised mice. It may be helpful to identify the biological activities of HWH to support its potential use in new prebiotics, immunomodulatory agents, and medical additives for intestinal repair.

Abstract Background Syndrome differentiation is a commonly used methodology and practice in Traditional Chinese Medicine (TCM) guiding the diagnosis and treatment of diseases including heart failure (HF). However, previous clinical trials seldom consider the impact of syndrome patterns on the outcome evaluation of TCM formulae. Qiliqiangxin (QLQX) capsule is a TCM formula with cardiotonic effect to improve the cardiovascular function for heart failure with proven efficacy from well-designed clinical trials. Though, there is no clinical trial with a large sample size and long assessment period that considers the relationship between TCM syndrome differentiation and the treatment efficacy of QLQX. In the present study, we design a study protocol to evaluate the relationship between TCM syndrome differentiation and the severity of heart failure as well as its progression. Furthermore, we will evaluate the impact of the TCM syndrome patterns on the efficacy of QLQX in the outcome of heart failure. Methods This is a clinical study conducted in conjunction with an ongoing clinical trial (QUEST Study) by sharing the parent patient populations but with different aims and independent designed roadmaps to investigate the TCM syndrome pattern distributions and the impacts of syndrome pattern types on the efficacy of QLQX in HF treatment. The clinical trial involves over 100 hospitals in mainland China and Hong Kong SAR with 3080 HF patients. By assessing the morbidity and re-hospitalization, we will verify and apply a modified TCM Questionnaire to collect the clinical manifestations of HF and acquire the tongue images of the patients to facilitate the syndrome differentiation. We will base on the “2014 Consensus from TCM experts on diagnosis and treatment of chronic heart failure” to evaluate the TCM syndromes for the patients. A pilot study with at least 600 patients will be conducted to evaluate the reliability, feasibility and validity of the modified TCM questionnaire for syndrome differentiation of HF and the sample size is calculated based on the confidence level of 95%, population size of 3080 and 5% margin of error. Secondly, we will investigate the characteristic of TCM syndrome distribution of HF patients and its correlation with the functional and biochemical data. Furthermore, we will evaluate the relationship between the TCM syndrome patterns and the efficacy of QLQX in the treatment of heart failure. Lastly, we will investigate the implication of tongue diagnosis in the severity and therapeutic outcome of HF. Expect outcomes To our knowledge, this is the first large scale clinical trial to evaluate the impacts of TCM syndrome differentiation on the progression and therapeutic outcome of HF patients and explore the diagnostic value of TCM Tongue Diagnosis in HF patients. We expect to obtain direct clinical evidence to verify the importance of TCM syndrome differentiation for the diagnosis and treatment of HF. Trial Registration: The trial was registered at Chinese Clinical Trial Registry, http://www.chictr.org.cn . (Registration No.: ChiCTR1900021929); Date: 2019-03-16.

BackgroundUsing the CHA2DS2-VASc score to recognize the risk of stroke in patients with atrial fibrillation has been well-established. However, few studies have assessed whether the CHA2DS2-VASc score has a similar predictive value in recurrence after myocardial infarction (MI).MethodsWe conducted a retrospective observational cohort study of adult inpatients with MI. The CHA2DS2-VASc and modified CHA2DS2-VASc (MCHA2DS2-VASc) scores of all patients were calculated. The associations of both scores with recurrent MI were analyzed.ResultsA total of 6,700 patients with MI (60.0 ± 11.1 years, 77.2% men) were enrolled, and 759 (11.3%) presented a definite recurrence during hospitalization. After multivariable adjustment by logistic regression in patients with MI, the CHA2DS2-VASc and MCHA2DS2-VASc scores were independently associated with recurrence. The MCHA2DS2-VASc score showed a better predictive value for risk of recurrence than that of CHA2DS2-VASc in overall [area under the receiver operating characteristic curve (AUC) 0.757 vs. 0.676] or male patients (AUC 0.759 vs. 0.708). MCHA2DS2-VASc was superior to CHA2DS2-VASc for identifying “truly high-risk” patients with MI, regardless of overall patients or sex-specific subgroups. The two scores had a similar focus on the identification of “low-risk” patients in overall or women, but not in men.ConclusionThe CHA2DS2-VASc and MCHA2DS2-VASc scores for predicting recurrence are validated in patients with MI. However, MCHA2DS2-VASc could be more helpful to secondary prevention than CHA2DS2-VASc after MI, especially in men. The superiority of MCHA2DS2-VASc compared with CHA2DS2-VASc in women is just more discriminatory for “truly high-risk” patients.

Background Armeniaca sibirica seed kernel oil is rich in oleic acid and linoleic acid, thus holding potential value as a source of high-quality edible oils. However, some regulatory factors involved in fatty acids accumulation in A. sibirica seed kernels remain largely elusive. Thus, the aim of this study was to elucidate the regulatory mechanisms underlying fatty acids biosynthesis in A. sibirica developing seed kernels. Methods Seed kernels from six plants from a single A. sibirica clone were taken at five different developmental stages (days 30, 41, 52, 63, and 73 after anthesis). Fatty acid composition in seed kernel oil was determined by gas chromatography-mass spectrometry (GC-MS). In addition, transcriptome analysis was conducted using second-generation sequencing (SGS) and single-molecule real-time sequencing (SMRT). Results Rapid accumulation of fatty acids occurred throughout the different stages of seed kernels development, with oleic acid and linoleic acid as the main fatty acids. A total of 10,024, 9,803, 6,004, 6,719 and 9,688 unigenes were matched in the Nt, Nr, KOG, GO and KEGG databases, respectively. In the category lipid metabolism, 228 differentially expressed genes (DEGs) were annotated into 13 KEGG pathways. Specific unigenes encoding 12 key enzymes related to fatty acids biosynthesis were determined. Co-expression network analysis identified 11 transcription factors (TFs) and 13 long non-coding RNAs (lncRNAs) which putatively participate in the regulation of fatty acid biosynthesis. This study provides insights into the molecular regulatory mechanisms of fatty acids biosynthesis in A. sibirica developing seed kernels, and enabled the identification of novel candidate factors for future improvement of the production and quality of seed kernel oil by breeding.

BackgroundEthylene oxide (EO) has been shown to associate with increased cardiovascular risk. This study aimed to explore the relationship and its meditating factors between EO exposure and the major cardiovascular risk factor of obesity among the general adult population.MethodsCross-sectional data of 3,220 participants from National Health and Nutritional Examination Survey (NHANES) 2013–2016 were enrolled. Obesity was defined as body mass index (BMI) ≥30 kg/m2, and abdominal obesity was defined as waist circumference (WC) ≥102 cm in men and ≥88 cm in women. The association among hemoglobin adduct of EO (HbEO), inflammatory biomarkers, and obesity was evaluated using restricted cubic splines and the multivariable linear regression model. Mediation analysis was used to further assess their association.ResultsThe increased quartiles of HbEO were inversely associated with BMI and WC [Q1 vs. Q4, BMI: β = −2.98 (−3.74, −2.22), WC: β = −6.50 (−8.60, −4.39); all p for trend < 0.05], and were inversely associated with obesity after full adjustment [obesity: OR = 0.43 (0.31, 0.58), abdominal obesity: OR = 0.42 (0.27, 0.65); all p for trend < 0.05]. The levels of alkaline phosphatase, white blood cells, lymphocytes, and neutrophils were also positively associated with BMI and WC (all p < 0.05). Mediation analysis showed that exposure of EO not only had a negative direct effect on BMI and WC, but also generated an inverse indirect effect.ConclusionsCurrent findings showed an inverse association between HbEO and obesity, and suggested that systemic inflammation may not be their only mediator. Additional research is required to explore the underlying link of EO and system metabolism.

Carotenoid levels are inversely associated with blood pressure (BP). This study focused on the effects of individual and combined serum carotenoids on BP and hypertension, which have not been established to date. Data from National Health and Nutrition Examination Survey (NHANES) 2001–2006 were analyzed in this cross-sectional study. Multivariate logistic, linear, and weighted quantile sum (WQS) regression analyses were applied to explore the associations of six serum carotenoids (α-carotene, β-cryptoxanthin, lutein/zeaxanthin, trans-lycopene, trans-β-carotene, and cis-β-carotene), individually and in combination, with BP/hypertension. The linearity of correlations was further assessed using restricted cubic spline (RCS) regression. A total of 11,336 adults were included for analysis. Data from multivariate models showed that all six carotenoids were independently and negatively associated with both systolic blood pressure (SBP) and diastolic blood pressure (DBP; all p < 0.05). Compared to the first quartile, the fourth quartile of α-carotene (odds ratio [OR] = 0.64 [0.52–0.77]), β-cryptoxanthin (OR = 0.74 [0.60–0.90]), trans-β-carotene (OR = 0.50 [0.40–0.61]), and cis-β-carotene (OR = 0.47 [0.35–0.64]) were significantly and inversely related to hypertension (all p < 0.05). Moreover, WQS analysis revealed that the combination of all six serum carotenoids was negatively associated with BP and hypertension (all P 0.05). Our collective findings indicate that higher levels of all six mixed serum carotenoids are correlated with decreased prevalence of hypertension, among which β-carotene exerts the most significant effect, which may provide a basis and direction for further studies.

ObjectiveSystemic inflammation is associated with a poor prognosis in acute heart failure (AHF). This study was to assess the long-term prognostic value of combining the accessible inflammatory markers in relation to all-cause mortality in patients with AHF.MethodsConsecutive patients with AHF who were hospitalized between March 2012 and April 2016 at the Department of Cardiology of the First Affiliated Hospital of Nanjing Medical University were enrolled in this prospective study. The LASSO regression model was used to select the most valuable inflammatory biomarkers to develop an inflammatory prognostic scoring (IPS) system. Kaplan-Meier method, multivariate COX regression and time-dependent ROC analysis were used to assess the relationship between inflammatory markers and AHF prognosis. A randomized survival forest model was used to estimate the relative importance of each inflammatory marker in the prognostic risks of AHF.ResultsA total of 538 patients with AHF were included in the analysis (mean age, 61.1 ± 16.0 years; 357 [66.4%] men). During a median follow-up of 34 months, there were 227 all-cause deaths (42.2%). C-reactive protein (CRP), red blood cell distribution width (RDW) and neutrophil-to-lymphocyte ratio (NLR) were incorporated into the IPS system (IPS = 0.301×CRP + 0.263×RDW + 0.091×NLR). A higher IPS meant a significantly worse long-term prognosis in Kaplan-Meier analysis, with 0.301 points as the optimal cut-off value (P log-rank

Diabetic cardiomyopathy (DCM) is a pathophysiological condition induced by diabetes mellitus that often causes heart failure (HF). However, their mechanistic relationships remain unclear. This study aimed to identify immune gene signatures and molecular mechanisms of DCM. Microarray data from the Gene Expression Omnibus (GEO) database from patients with DCM were subjected to weighted gene co-expression network analysis (WGCNA) identify co-expression modules. Core expression modules were intersected with the immune gene database. We analyzed and mapped protein-protein interaction (PPI) networks using the STRING database and MCODE and filtering out 17 hub genes using cytoHubba software. Finally, potential transcriptional regulatory factors and therapeutic drugs were identified and molecular docking between gene targets and small molecules was performed. We identified five potential immune biomarkers: proteosome subunit beta type-8 (PSMB8), nuclear factor kappa B1 (NFKB1), albumin (ALB), endothelin 1 (EDN1), and estrogen receptor 1 (ESR1). Their expression levels in animal models were consistent with the changes observed in the datasets. EDN1 showed significant differences in expression in both the dataset and the validation model by real-time quantitative PCR (qPCR) and Western blotting(WB). Subsequently, we confirmed that the potential transcription factors upstream of EDN1 were PRDM5 and KLF4, as its expression was positively correlated with the expression of the two transcription factors. To repurpose known therapeutic drugs, a connectivity map (CMap) database was retrieved, and nine candidate compounds were identified. Finally, molecular docking simulations of the proteins encoded by the five genes with small-molecule drugs were performed. Our data suggest that EDN1 may play a key role in the development of DCM and is a potential DCM biomarker.

Background: There are strong association between remnant cholesterol (RC)/non-high density lipoprotein cholesterol (NHDL-C) and increase cardiovascular (CV) risk. The aim of present study was to investigate the association between target lipid parameters (RC and NHDL-C) and the risk of CV mortality in general population. Methods: Data set from an open database—National Health and Nutrition Examination Surveys (NHANES) 2003–2014 were extracted (n = 14992). Kaplan-Meier, multivariable COX regression, and restricted cubic spline (RCS) parameters. Results: Compared to the lowest quartile, RC (adjusted hazard ratio [HR] = 1.63 95%CI 1.05–2.52, P for trend = 0.037) and triglycerides (TG: Model 3: HR = 1.69 95%CI 1.10–2.60, P for trend = 0.049) in the highest quartile were independently associated with the increased cardiovascular mortality, while NHDL-C and apolipoprotein B (ApoB) in adjusted models did not show association (P for trend >0.05). In addition, RCS regression demonstrated that RC (P for nonlinearity = 0.011) and TG (P for nonlinearity = 0.010) levels had a similar J-shape association with CV mortality. Threshold effect analysis showed that when RC ≤ 29.3 mg/dL, the level of RC and CV mortality risk were positively correlated. Conclusions: Our findings suggest high RC levels are associated with an increased risk of CV mortality, which support that the integration of TG-rich lipoproteins parameters in risk assessment might optimize the identification and management of selected population.

To investigate the potential role of apple polyphenol extract (APE) in the prevention and alleviation of circadian rhythm disturbances, eighty male C57BL/6 mice fed a high-fat diet (HFD) were randomized into four groups: 24 h ad libitum feeding (AL), 12 h restricted nighttime feeding (NF) or daytime feeding (DF), and daytime feeding with APE intragastric administration (DF-APE). Five weeks later, the mice were sacrificed at 6 h intervals over 24 h. Disrupted fluctuations in serum lipid profiles and hormones, along with desynchronization of circadian clock genes and metabolic genes were observed after daytime HFD feeding. However, APE treatment improved hepatic steatosis and recovered circadian rhythms of Cry1/2, and genes Acc and Hsl related to lipid synthesis and hydrolysis of cholesteryl esters, and Cyp7a1 in bile acid synthesis. In conclusion, the present study provides new evidence revealing that the circadian clock might be a novel target for APE to regulate metabolic homeostasis.

ObjectiveUsing a newly released National Health and Nutrition Examination Survey (NHANES) data of serum Klotho, this study aimed to explore the relationship between Klotho and specific cardiovascular diseases (CVD), as well as the mediation effect of renal function, among middle-aged and older individuals within the general population.MethodsThis nationally representative cross-sectional study analyzed data from the 2007–2016 NHANES. A total of 13,765 participants, who aged 40 years or older, from the general population were examined. Klotho were divided into four groups based on median and interquartile range. The associations among Klotho (exposure), congestive heart failure (CHF; outcome), and renal function markers [estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), uric acid (UA), and urine albumin-to-creatinine ratio (UACR); mediators] were investigated using mediation analysis.ResultsIn comparison to the lowest quartile, Klotho in the highest quartile was independently associated with the prevalence of CHF (OR 0.59; 95% CI 0.46–0.77, p for trend = 0.001), but not with other individual CVDs. Klotho had a significant direct effect on the prevalence of CHF (all p < 0.001), while eGFR, BUN, UA, and UACR partly mediated the indirect effect of Klotho on the prevalence of CHF (all p < 0.05), explaining 19.51, 6.98, 13.93, and 0.71% of the association between Klotho and CHF, respectively. Additionally, restricted cubic spline regression demonstrated a linear association and negative correlation between Klotho level and CHF.ConclusionThese findings suggest that Klotho is closely linked to CHF and renal function may be a key mediator of this association.

Abstract Background Liver and renal function evaluated by the model for end-stage liver disease (MELD) score, the MELD excluding the international normalized ratio (MELD_XI) score and the MELD including sodium (MELD_sodium) score have been considered predictors of adverse events for patients with acute heart failure (AHF). However, the prognostic value of the MELD including albumin (MELD_albumin) score in patients with AHF has not been assessed. Methods A total of 466 patients with AHF were prospectively evaluated. We compared the accuracy of the 4 MELD score formulas using the time-dependent receiver operating characteristic (ROC) curve and corresponding areas under the curve (AUC). Results During a median follow-up period of 34 months, 196 deaths occurred. In the fully adjusted Cox regression model, standardized hazard ratios with 95% confidence interval expressing the risk of all-cause mortality were 1.22 (1.06–1.40), 1.20 (1.04–1.39), 1.23 (1.06–1.42) and 1.21 (1.05–1.41) for MELD, MELD_XI, MELD_sodium and MELD_albumin scores, respectively. The MELD_albumin score showed the best prognostic accuracy (AUC = 0.658) for the prediction of long-term all-cause mortality, followed by the MELD_sodium score (AUC = 0.590), the MELD score (AUC = 0.580), and the MELD_XI score (AUC = 0.544); the MELD_albumin score performs significantly more accurate than MELD and MELD_XI score for predicting the risk of all-cause mortality. Considering reclassification, MELD_albumin score increased the net reclassification improvement over and beyond MELD (13.1%, P = 0.003), MELD_XI (14.8%, P = 0.002), and MELD_sodium (11.9%, P = 0.006) scores for all-cause mortality. Conclusions The MELD_albumin score increases risk stratification of all-cause mortality over and beyond the MELD score and the other modified MELD scores in patients with acute heart failure.

Cardiovascular disease has become a major public health problem. The concept of “cardiovascular continuum” refers to the continuous process from the risk factors that lead to arteriosclerosis, vulnerable plaque rupture, myocardial infarction, arrhythmia, heart failure, and death. These characteristics of etiology and progressive development coincide with the idea of “preventing disease” in traditional Chinese medicine (TCM), which corresponds to the process of systemic intervention. With the update of the understanding via translational medicine, this article reviews the current evidence of the TCM collateral disease theory set prescriptions in both mechanical and clinical aspects, which could lead to the development of new therapeutic strategies for prevention and treatment.

Background: The occurrence of proteinuria is one of the evaluation indicators of transplanted kidney damage and becomes an independent risk factor for poor prognosis after kidney transplantation. Our research sought to understand these potential associations and detect the underlying impact of single-nucleotide polymorphisms (SNPs) on proteinuria in kidney transplant recipients.Materials and Methods: There were 200 recipients enrolled in this study, from which blood samples were extracted for SNP mutation–related gene detection. RNA sequencing was performed in kidney tissues after kidney transplantation, and the significantly differentially expressed genes (DEGs) were analyzed between the control group and the proteinuria group. Then, the intersection of genes with SNP mutations and DEGs was conducted to obtain the target genes. Multiple genetic models were used to investigate the relationship between SNPs and proteinuria. In addition, the effect of SNP mutation in the target gene was further validated in human renal podocytes.Results: According to the sequencing results, 26 significant SNP mutated genes and 532 DEGs were found associated with proteinuria after kidney transplantation. The intersection of SNP mutated genes and DEGs showed that the Toll-like receptor 2 (TLR2) gene was significantly increased in the transplanted renal tissues of patients with proteinuria after kidney transplantation, which was consistent with the results of immunohistochemical staining. Further inheritance model results confirmed that mutations at rs3804099 of the TLR2 gene had significant influence on the occurrence of proteinuria after kidney transplantation. In the in vitro validation, we found that, after the mutation of rs3804099 on the TLR2 gene, the protein expressions of podocalyxin and nephrin in podocytes were significantly decreased, while the protein expressions of desmin and apoptosis markers were significantly increased. The results of flow cytometry also showed that the mutation of rs3804099 on the TLR2 gene significantly increased the apoptotic rate of podocytes.Conclusion: Our study suggested that the mutation of rs3804099 on the TLR2 gene was significantly related to the generation of proteinuria after kidney transplantation. Our data provide insights into the prediction of proteinuria and may imply potential individualized therapy for patients after kidney transplantation.

Background: Antioxidant micronutrients represent an important therapeutic option for the treatment of oxidative stress-associated cardiovascular diseases (CVDs). However, few studies have evaluated the relationship between the levels of multiple dietary antioxidants and CVDs.Objective: The study therefore aimed to evaluate associations between dietary antioxidants and total and specific CVDs among a nationally representative sample of adults in the US.Design: In total, 39,757 adults (>20 years) were included in this cross-sectional study from the 2005–2018 National Health and Nutrition Examination Survey. We analyzed dietary recall of 11 antioxidant micronutrients in this population. Multivariate logistic and weighted quantile sum (WQS) regression were both applied to examine the relationships between these antioxidants, alone and in combination, with the prevalence of all CVDs and specific CVDs. The linearity of these correlations was also explored using restricted cubic spline (RCS) regression.Results: Multivariate logistic models showed that, compared with the lowest quartile, the levels of 11 antioxidants in the highest quartile were independently associated with decreased total CVD (all P < 0.05). The WQS index showed that, when considered together, the 11 micronutrients were negatively correlated with total CVD (P < 0.001) and five specific CVDs (all P < 0.05), and selenium had the strongest association (weight = 0.219) with total CVD. Moreover, the RCS model demonstrated that iron, zinc and copper were all negatively and non-linearly correlated with total CVD, while the eight other micronutrients had non-significant, linear, negative relationships with total CVD (P for non-linearity >0.05). A piecewise binary logistic regression analysis showed that the inflection points in the relationships between CVD and iron, zinc and copper were 7.71, 6.61, and 0.74 mg/day, respectively.Conclusions: Our findings suggested that high levels of combined dietary antioxidant micronutrients are associated with decreased prevalence of CVDs, and that selenium has the greatest contribution to this association.

Abstract Background Qiliqiangxin (QLQX) capsule is a Traditional Chinese Medicine (TCM) that has been approved in China for the treatment of chronic heart failure (CHF). Our previous study showed with a background of standard HF treatment, QLQX capsules further reduced the levels of NT-proBNP and the incidence of composite cardiac events (CCEs) in CHF patients. This study aims to further assess the reduction in mortality when using QLQX compared with placebo for heart failure with reduced ejection fraction (HFrEF) patients. Methods This study is a randomized, double-blind, placebo-controlled, parallel-group, multi-center, event-driven clinical study of approximately 3080 patients for a targeted 620 events. Patients must have a diagnosis of heart failure for at least 3 months prior to screening. Patients will be randomized 1:1 to receive the placebo or QLQX in addition to their standard medications of CHF. The primary efficacy outcome event is a composite cardiovascular death and re-hospitalization due to the worsening of heart failure. Discussion The QUEST study is a randomized control study of TCM in chronic heart failure. It will determine the place of QLQX as an new treatment approach and provide additional and innovative information regarding TCM - and the specific used of QLQX in HFrEF. Trial registration The trial was registered at http://www.chictr.org.cn. ( Registration No.: ChiCTR1900021929); Date: 2019-03-16.

Background: Diabetic cardiomyopathy is the primary complication associated with diabetes mellitus and also is a major cause of death and disability. Limited pharmacological therapies are available for diabetic cardiomyopathy. Qiliqiangxin (QLQX), a Chinese medication, has been proven to be beneficial for heart failure patients. However, the role and the underlying protective mechanisms of QLQX in diabetic cardiomyopathy remain largely unexplored.Methods: Primary neonatal rat cardiomyocytes (NRCMs) were treated with glucose (HG, 40 mM) to establish the hyperglycemia-induced apoptosis model in vitro. Streptozotocin (STZ, 50 mg/kg/day for 5 consecutive days) was intraperitoneally injected into mice to establish the diabetic cardiomyopathy model in vivo. Various analyses including qRT-PCR, western blot, immunofluorescence [terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining] histology (hematoxylin–eosin and Masson's trichrome staining), and cardiac function (echocardiography) were performed in these mice. QLQX (0.5 μg/ml in vitro and 0.5 g/kg/day in vivo) was used in this study.Results: QLQX attenuated hyperglycemia-induced cardiomyocyte apoptosis via activating peroxisome proliferation-activated receptor γ (PPARγ). In vivo, QLQX treatment protected mice against STZ-induced cardiac dysfunction and pathological remodeling.Conclusions: QLQX attenuates diabetic cardiomyopathy via activating PPARγ.

Background: Dilated cardiomyopathy (DCM) is one of the main causes of systolic heart failure and frequently has a genetic component. The molecular mechanisms underlying the onset and progression of DCM remain unclear. This study aimed to identify novel diagnostic biomarkers to aid in the treatment and diagnosis of DCM. Method: The Gene Expression Omnibus (GEO) database was explored to extract two microarray datasets, GSE120895 and GSE17800, which were subsequently merged into a single cohort. Differentially expressed genes were analyzed in the DCM and control groups, followed by weighted gene coexpression network analysis to determine the core modules. Core nodes were identified by gene significance (GS) and module membership (MM) values, and four hub genes were predicted by the Lasso regression model. The expression levels and diagnostic values of the four hub genes were further validated in the datasets GSE19303. Finally, potential therapeutic drugs and upstream molecules regulating genes were identified. Results: The turquoise module is the core module of DCM. Four hub genes were identified: GYPC (glycophorin C), MLF2 (myeloid leukemia factor 2), COPS7A (COP9 signalosome subunit 7A) and ARL2 (ADP ribosylation factor like GTPase 2). Subsequently, Hub genes showed significant differences in expression in both the dataset and the validation model by real-time quantitative PCR (qPCR). Four potential modulators and seven chemicals were also identified. Finally, molecular docking simulations of the gene-encoded proteins with small-molecule drugs were successfully performed. Conclusions: The results suggested that ARL2, MLF2, GYPC and COPS7A could be potential gene biomarkers for DCM.

The aim of present study was to investigate the association of acrylamide (AA) hemoglobin biomarkers and serum lipids level in a general population. Data set of our study were extracted from an open database - National Health and Nutrition Examination Surveys (NHANES) 2013–2016. In total 2899 participants were enrolled. The associations between AA hemoglobin parameters [hemoglobin adducts of AA (HbAA) and glycidamide (HbGA), total of HbAA and HbGA (HbAA+HbGA), and ratio of HbGA to HbAA (HbGA/HbAA)] and lipid levels [total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C)] were analyzed. Generalized linear models and restricted cubic spline plots were conducted to address the relationship between lipid levels and acrylamide markers. Comparing the lowest quantiles, HbGA and HbGA/HbAA both remained a significant trend regardless of lipid types. Analyses using a generalized linear model with restricted cubic spline and validated with regression models, all 4 AA parameters demonstrated a linear association and positive correlation with TG. Furthermore, there were also opposite nonlinear association between HbGA/HbAA and LDL-C (positive correlation), and HbGA/HbAA and HDL-C (negative correlation). Further analysis with threshold effect analysis or regression analysis showed HbGA and HbGA/HbAA remained significant association with all TC, TG, LDL-C, and HDL-C. The hemoglobin adducts AA parameters as long-term exposure biomarkers are associated with the atherosclerotic lipid changes in a population of US adults.

Abstract Nicotinamide adenine dinucleotide (NAD+) is a life essential molecule involved in versatile biological processes. To date, only two de novo biosynthetic routes to NAD+ are described, both of which start from a proteinogenic amino acid and are tightly controlled. Here, a de novo quinolinic acid pathway starting from chorismate, which provides an alternative route (named as the C3N pathway) to NAD+ biosynthesis, is established. Significantly, the C3N pathway yields extremely high cellular concentrations of NAD(H) in E. coli. Its utility in cofactor engineering is demonstrated by introducing the four‐gene C3N module to cell factories to achieve higher production of 2,5‐dimethylpyrazine and develop an efficient C3N‐based whole‐cell bioconversion system for preparing chiral amines. The wide distribution and abundance of chorismate in most kingdoms of life implies a general utility of the C3N pathway for modulating cellular levels of NAD(H) in versatile organisms.

Objective: Arterial stiffness indices measured by pulse wave velocity and pulse wave analysis have been widely studied in different populations. Only a few small studies have been reported regarding these two measurement methods. Therefore, the aim of our study was to compare the arterial stiffness indices measured by pulse wave velocity and pulse wave analysis in a randomly selected Chinese population. Methods: A total of 4285 subjects were recruited from Gaoyou County, Jiangsu Province, China. There were 2017 (47.1%) participants with hypertension. Pulse wave velocity was assessed by using a VP-1000 Automatic Arteriosclerosis Measurement System. Large artery elasticity and small artery elasticity were measured by pulse wave analysis with an HDI/PulseWave CR-2000 Research CardioVascular Profiling System using the modified Windkessel model. Results: Brachial-ankle pulse wave velocity, large artery elasticity and small artery elasticity were all significantly associated with the Framingham risk score (r = 0.588, −0.387, −0.448; p

Doping of Ru has been used to enhance the performance of LiNi0.5Mn1.5O4 cathode materials. However, the effects of Ru doping on the two types of LiNi0.5Mn1.5O4 are rarely studied. In this study, Ru4+ with a stoichiometric ratio of 0.05 is introduced into LiNi0.5Mn1.5O4 with different space groups (Fd3¯m, P4332). The influence of Ru doping on the properties of LiNi0.5Mn1.5O4 (Fd3¯m, P4332) is comprehensively studied using multiple techniques such as XRD, Raman, and SEM methods. Electrochemical tests show that Ru4+-doped LiNi0.5Mn1.5O4 (P4332) delivers the optimal electrochemical performance. Its initial specific capacity reaches 132.8 mAh g−1, and 97.7% of this is retained after 300 cycles at a 1 C rate at room temperature. Even at a rate of 10 C, the capacity of Ru4+-LiNi0.5Mn1.5O4 (P4332) is still 100.7 mAh g−1. Raman spectroscopy shows that the Ni/Mn arrangement of Ru4+-LiNi0.5Mn1.5O4 (Fd3¯m) is not significantly affected by Ru4+ doping. However, LiNi0.5Mn1.5O4 (P4332) is transformed to semi-ordered LiNi0.5Mn1.5O4 after the incorporation of Ru4+. Ru4+ doping hinders the ordering process of Ni/Mn during the heat treatment process, to an extent.

The trim flap is an aerodynamic control surface capable of allowing Mars entry vehicles to improve landing performance during the most dangerous entry, descent, and landing (EDL) phase. In present work, a deployable trim flap system was proposed to meet the aerodynamical trim requirement of the Tianwen-1 Mars probe, which provided a mass-saving alternative to the conventional use of the center-of-gravity (CG) offset of ballast mass. In order to guide the trim flap design, theoretical and finite element (FE) models were established to predict and evaluate the deployment performance. Then, a full-scale physical prototype was manufactured for deployment experiments to verify the design effectiveness as well as validate the theoretical and FE models. Results predicted by theoretical and FE models were in good agreement with deployment experiments. Furthermore, the effects of three factors on the deployment performance were investigated, including the non-linear behavior of the damping, acceleration environment, and backshell flexibility. The manufactured prototype was installed on the Tianwen-1 Mars probe, saving more than 300 kg when compared to the conventional use of ballast mass CG offset, and assisted Tianwen-1 in achieving a successful landing, making China the first country in the world to utilize the trim flap technology for Mars EDL.

In this paper, using four carbonates as raw materials, the cathode material LiNi0.5Co0.2Mn0.3O2 was prepared with the “ball milling-calcining” solid-phase synthesis method. The specific reaction process, which consists of the decomposition of the raw materials and the generation of target products, was investigated thoroughly using the TG-DSC technique. XRD, SEM and charge/discharge test methods were utilized to explore the influence of different sintering temperatures on the structure, morphology and electrochemical performance of the LiNi0.5Co0.2Mn0.3O2 cathode. The results show that 900~1000 °C is the appropriate synthesis temperature range. LiNi0.5Co0.2Mn0.3O2 synthesized at 1000 °C delivers optimal cycling stability at 0.5 C. Meanwhile, its initial discharge specific capacity and coulomb efficiency reached 167.2 mAh g−1 and 97.89%, respectively. In addition, the high-rate performance of the cathode sample prepared at 900 °C is particularly noteworthy. Cycling at 0.5 C, 1 C, 1.5 C and 2 C, the corresponding discharge specific capacity of the sample exhibited 148.1 mAh g−1, 143.1 mAh g−1, 140 mAh g−1 and 138.9 mAh g−1, respectively.

Abstract Background Epidemiological evidence suggests sex difference in serum uric acid (SUA) and alanine aminotransferase (ALT) might be a potential explanation for the gender difference in prevalence of non-alcoholic fatty liver disease (NAFLD). However, few epidemiology data in China have tested this hypothesis. Methods We conducted a cross-sectional study to assess the joint associations between SUA and serum ALT with NAFLD among elderly Chinese men and women. Results Among 7569 participants with a mean age of 59.8 years (± 13.4 years), 56.6% of women and 43.4% of men were diagnosed as NAFLD, respectively. A positive association between SUA and NAFLD prevalence was observed in both men and women. NAFLD prevalence was 2.74 times (95% CI 2.00–3.76) higher for men and 4.60 times (95% CI 3.39–6.24) higher for women with the highest quintiles of SUA levels compared to those with the lowest levels. SUA levels were significantly associated with prevalence of mild- and severe-steatosis (P

BackgroundTelomere length and telomerase are associated in development of cardiovascular diseases. Study aims to investigate the associations of TERC and TERT gene polymorphism and leukocyte telomere length (LTL) in the prognosis of acute heart failure (AHF).MethodsTotal 322 patients with AHF were enrolled and divided into death and survival group according to all-cause mortality within 18 months. Seven single nucleotide polymorphisms (SNPs) of TERC and TERT were selected. Baseline characteristics, genotype distribution and polymorphic allele frequency, and genetic model were initially analyzed. Genotypes and the LTL were determined for further analysis.ResultsCompared to carrying homozygous wild genotype, the risk of death in patients with mutated alleles of four SNPs- rs12696304(G>C), rs10936599(T>C), rs1317082(G>A), and rs10936601(T>C) of TERC were significantly higher. The dominant models of above were independently associated with mortality. In recessive models, rs10936599 and rs1317082 of TERC, rs7726159 of TERT were independently associated with long-term mortality. Further analysis showed, in haplotype consisting with TERC - rs12696304, rs10936599, rs1317082, and rs10936601, mutant alleles CCAC and wild alleles GTGT were significant difference between groups (P

The chemical composition in the precipitation is constantly changing, thus acid rain type is gradually changing from sulfuric type to mixed type and then nitric type. The influence of the changing acid rain type on the rhizosphere soil of tree species remains unclear. A pot experiment was performed with two-year-old Pinus massoniana, Cunninghamia lanceolate, Cyclobalanpsis glauca and Phyllostachys edulis seedlings with similar growth condition. Simulated acid rain consists of sulfuric(S/N = 5), mixed(S/N = 1) and nitric(S/N = 0.2) acid rain, and each type acid rain diluted to three acid rain intensity: pH = 2.5, 3.5, 4.5. Soil pH, soil organic matter, cation exchange capacity, the exchangeable Na+, K+, Ca2+, Mg2+ and enzyme activity were inhibited by acid rain intensity, while exchangeable Al3+ and H+ were promoted. Mg2+ was most relevant index to the tolerance to acid rain and the correlation degree of soil chemical index was higher than that of enzyme activity. Response of soil chemical properties differed in tree species under different acid rain types. Soil enzyme activity of Pinus massoniana, Cunninghamia lanceolate, and Phyllostachys edulis reached lowest under nitric acid rain, and that of Cyclobalanpsis glauca reached highest. Rhizosphere soil of Cunninghamia lanceolate is tolerant to sulfuric and nitric acid rain, and that of Cyclobalanpsis glauca is tolerant to mixed acid rain.

Rationale. Pathological cardiac remodeling serves as a vital mechanism during the progression from myocardial infarction (MI) to chronic heart failure (CHF). Nobiletin (NOB), an active monomer extracted from the peel of citrus fruit, has been reported to have beneficial effects in cardiovascular diseases. Our study was aimed at describing the specific mechanisms through which NOB protects against pathological cardiac remodeling after MI. Materials and Methods. C57BL/6 mice were treated with coronary artery ligation to generate an MI model, followed by treatment for 3 weeks with NOB (50 mg/kg/d) or vehicle (50 mg/kg/d), with or without the peroxisome proliferator-activated receptor gamma (PPARγ) inhibitor T0070907 (1 mg/kg/d). Cardiac function (echocardiography, survival rate, Evans blue, and triphenyl tetrazolium chloride staining), fibrosis (Masson’s trichrome staining, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot (WB)), hypertrophy (haematoxylin-eosin staining, wheat germ agglutinin staining, and qRT-PCR), and apoptosis (WB and terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) staining) were evaluated. Hypoxia-induced apoptosis (TUNEL, WB) and phenylephrine- (PE-) induced pathological hypertrophy (immunofluorescence staining, qRT-PCR) models were established in primary neonatal rat ventricular myocytes (NRVMs). The effects of NOB with or without T0070907 were examined for the expression of PPARγ and PPARγ coactivator 1α (PGC1α) by WB in mice and NRVMs. The potential downstream effectors of PPARγ were further analyzed by WB in mice. Results. Following MI in mice, NOB intervention enhanced cardiac function across three predominant dimensions of pathological cardiac remodeling, which reflected in decreasing cardiac fibrosis, apoptosis, and hypertrophy decompensation. NOB intervention also alleviated apoptosis and hypertrophy in NRVMs. NOB intervention upregulated PPARγ and PGC1α in vivo and in vitro. Furthermore, the PPARγ inhibitor abolished the protective effects of NOB against pathological cardiac remodeling during the progression from MI to CHF. The potential downstream effectors of PPARγ were nuclear factor erythroid 2-related factor 2 (Nrf-2) and heme oxygenase 1 (HO-1). Conclusions. Our findings suggested that NOB alleviates pathological cardiac remodeling after MI via PPARγ and PGC1α upregulation.

Accumulated evidence on the clinical roles of microRNAs (miRNAs) in cancer prevention and control has revealed the emergence of new genetic techniques that have improved the understanding of the mechanisms essential for pathology induction and progression. Comprehension of the modifications and individual differences of miRNAs and their interactions in the pathogenesis of gynecological malignancies, together with an understanding of the phenotypic variations have considerably improved the management of the diagnosis and personalized treatment for different forms of cancer. In recent years, miRNAs have emerged as signaling molecules in biological pathways involved in different categories of cancer and it has been demonstrated that these molecules could regulate cancer-relevant processes, our focus being on malignancies of the gynecologic tract. The aim of this paper is to summarize novel research findings in the literature regarding the parts that miRNAs play in cancer-relevant processes, specifically regarding gynecological malignancy, while emphasizing their pivotal role in the disruption of cancer-related signaling pathways.

Bovine mastitis is an inflammatory condition of the mammary gland often caused by (Staphylococcus aureus) S. aureus infection. The aim of this study was to identify mastitis-related miRNAs and their downstream target genes, and therefore elucidate the regulatory mechanisms involved in disease progression and resistance. Three healthy and three mastitic cows were identified on the basis of the somatic cell count and bacterial culture of their milk, and the histological examination of udder tissues. High-throughput RNA sequencing and bioinformatic analyses revealed that 48 differentially expressed miRNAs (DEMs) in the mastitic udder tissues relative to the healthy tissues. Among 48 DEMs, the expression level of bta-miR-223 was the most up-regulated. Overexpression of the bta-miR-223 in Mac-T cells mitigated the inflammatory pathways induced by S. aureus-derived lipoteichoic acid (LTA). The Cbl proto-oncogene B (CBLB) was identified as the target gene of bta-miR-223, and the direct binding of the miRNA to the CBLB promoter was confirmed by dual luciferase reporter assay using wild-type and mutant 3'-UTR constructs. Furthermore, overexpression of CBLB in the LTA-stimulated Mac-T cells significantly upregulated PI3K, AKT, and phosphorylated NF-κB p65, whereas CBLB knockdown had the opposite effect. Consistent with the in vitro findings, the mammary glands of mice infected with 108CFU/100 μL S. aureus showed high levels of CBLB, PI3K, AKT, and p-NF-κB p65 48 h after infection. Taken together, bta-miR-223 is a predominant miRNA involved in mastitis, and bta-miR-223 likely mitigates the inflammatory progression by targeting CBLB and inhibiting the downstream PI3K/AKT/NF-κB pathway.