Disease-resistant varieties of Chinese cabbage (Brassica rapa L. ssp. pekinensis) inhibit Plasmodiophora brassicae infestation by stabilising root flora structure.

The application of disease-resistant varieties is the most cost-effective method for solving the problem of clubroot. "Shangpin," a disease-resistant variety of Chinese cabbage with broad-spectrum immunity to Plasmodiophora brassicae (P. brassicae), was screened in a previous study. Based on 16S rRNA sequencing technology, we annotated the compositional differences between the rhizosphere, rhizoplane, and endosphere bacterial communities of "Shangpin" and "83-1" under P. brassicae stress. Alpha diversity analysis showed that the abundance of microorganisms in the root system of "83-1" changed more than that of "Shangpin" after P. brassicae infestation, and Beta diversity analysis indicated that Flavobacterium and Sphingomonas may mediate clubroot resistance, while Nitrospira, Nitrosospira, and Pseudomonas may mediate P. brassicae infestation among the bacteria in the Top 10 abundances. Microbial functional analyses showed that the root microorganisms of "83-1" were metabolically weakened after P. brassicae inoculation and were inhibited in competition with pathogenic bacteria. Conversely, the root microorganisms of "Shangpin" maintained the strength of their metabolic capacity, which took a favorable position in competition with the pathogen and inhibited the growth and development of the pathogen, thus showing resistance. Root secretions of "Shangpin" significantly inhibited the incidence and disease index of clubroot, which indicated that under clubroot stress, resistant varieties maintain root microbial diversity and microbial community functions through specific root exudates, enriching the genera Flavobacterium and Sphingomonas, thus showing resistance. The results of this study reveal the resistance mechanism of resistant varieties to clubroot and provide new insights into the prevention and control of clubroot in Chinese cabbage.

Dapagliflozin attenuates the vulnerability to atrial fibrillation in rats with lipopolysaccharide-induced myocardial injury.

BACKGROUND: Oxidative stress is an essential component participating in the development and maintenance of atrial fibrillation (AF). Dapagliflozin, a SGLT2 inhibitor, has been shown to exert cardioprotective effects by ameliorating oxidative stress in multiple heart disease models. However, its potential to attenuate lipopolysaccharide (LPS)-induced myocardial injury in rats remains unknown. AIM: This study aims to investigate the role of dapagliflozin in LPS-induced myocardial injury and the potential mechanisms involved. METHODS: Rats were intraperitoneally administered LPS to induce sepsis-like condition. The intervention was conducted with intraperitoneal injection of dapagliflozin or saline 1 h in advance. The effects of dapagliflozin were detected by electrophysiological recordings, western blot, qPCR, ELISA, HE staining, immunohistochemistry and fluorescence. We further validated the mechanism in vitro using HL-1 cells. RESULTS: Dapagliflozin significantly improved LPS-induced myocardial injury, reduced susceptibility to AF, and mitigated atrial tissue inflammatory cell infiltration and atrial myocyte apoptosis. These were correlated with the Nrf2/HO-1 signaling pathway, which subsequently reduced oxidative stress. Subsequently, we used a specific inhibitor of the Nrf2/HO-1 pathway in vitro, reversed the anti-oxidative stress effects of dapagliflozin on HL-1 cells, further confirming the Nrf2/HO-1 pathway's pivotal role in dapagliflozin-mediated cardioprotection. CONCLUSION: Dapagliflozin ameliorated myocardial injury and susceptibility to AF induced by LPS through anti-oxidative stress, which relied on upregulation of the Nrf2/HO-1 pathway.

Dapagliflozin ameliorates sepsis-induced heart injury by inhibiting cardiomyocyte apoptosis and electrical remodeling through the PI3K/Akt pathway.

BACKGROUND: Sepsis-induced heart injury is one of the leading causes of circulation disorders worldwide. Dapagliflozin, a sodium-glucose cotransporter 2 inhibitor mainly used for controlling blood glucose, has been shown to exert a protective effect on cardiomyocytes. However, the protective effect of dapagliflozin against sepsis-induced cardiac injury and the underlying mechanism needs to be studied. AIM: This study aims to investigate the effect of dapagliflozin on sepsis-induced cardiomyopathy and the potential mechanisms involved. METHODS: The rat model of sepsis was constructed by intraperitoneal injection of lipopolysaccharide. Echocardiography and electrophysiological studies were performed to detect changes in cardiac function and electrical activity. Cardiac pathological alternation and cardiomyocyte apoptosis were measured by H&E staining, serological analysis, immunohistochemical, immunofluorescence, and TUNEL assays. Western blot and qRT-PCR were performed to elucidate the underlying mechanism of dapagliflozin. Additionally, corresponding experiments in H9c2 cells were performed to further validate the mechanisms in vitro. RESULTS: Dapagliflozin improved cardiac dysfunction and reduced the susceptibility to ventricular arrhythmias in sepsis rats by ameliorating cardiac inflammation, suppressing cardiomyocyte apoptosis, and alleviating ventricular electrical remodeling. The PI3K/Akt signaling pathway inhibitor inhibited the anti-apoptotic effect of dapagliflozin, indicating that the protective effect was related to the activation of the PI3K/Akt pathway. CONCLUSION: Dapagliflozin ameliorated sepsis-induced cardiac injury by suppressing electrical remodeling and cardiomyocyte apoptosis, which could be attributed to the PI3K/Akt pathway.

miR-216b-5p regulates proliferation and apoptosis of ox-LDL-stimulated VSMCs and HUVECs via IGF2.

Atherosclerosis (AS) is one of the principal causes of cardiovascular disorder. Reportedly, vascular smooth muscle cells (VSMCs) and human umbilical vein endothelial cells (HUVECs) play key roles in AS development, and microRNAs (miRNAs) regulate their functions. The function of miR-216b-5p in AS remains unknown. Human VSMCs and human HUVECs were treated with ox-LDL to establish the in vitro model of AS. MiR-216b-5p and IGF2 expressions in VSMCs and HUVECs were probed by qRT-PCR and western blot. The viability, cell cycle progression, and apoptosis of VSMCs and HUVECs were evaluated by Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine, and flow cytometry assays, respectively. The binding sites between IGF2 3'UTR and miR-216b-5p were validated by dual-luciferase reporter assay. miR-216b-5p expression was declined in ox-LDL-induced VSMCs and HUVECs. In VSMCs, miR-216b-5p overexpression inhibited excessive proliferation and induced apoptosis. MiR-216b-5p could markedly restrain the viabiblity of VSMCs induced by ox-LDL and enhanced the viability of HUVECs. Additionally, IGF2 was confirmed as the direct target of miR-216b-5p and transfection of IGF2 overexpression plasmids rescued the effects of miR-216b-5p on VSMCs and HUVECs. miR-216b-5p alleviates the dysfunction of VSMCs and HUVECs caused by ox-LDL via repressing IGF2, and exerts protective functions to block the development of AS.

Activation of the sigma-1 receptor exerts cardioprotection in a rodent model of chronic heart failure by stimulation of angiogenesis.

BACKGROUND: Angiogenesis plays a critical role on post-infarction heart failure (PIHF), the presence of which facilitates additional blood supply to maintain the survival of residual cardiomyocytes. The sigma-1 receptor (S1R) has been substantiated to stimulate angiogenesis, with the effect on a model of PIHF remaining unknown. AIMS: This study aims to investigate the effects of S1R on PIHF and the underlying mechanisms involved. METHODS: Rats were implemented left anterior descending artery ligation followed by rearing for 6 weeks to induce a phenotype of heart failure. Daily intraperitoneal injection of S1R agonist or antagonist for 5 weeks was applied from 2nd week after surgery. The effects exerted by S1R were detected by echocardiography, hemodynamic testing, western blot, Sirius red dyeing, ELISA, immunohistochemistry and fluorescence. We also cultured HUVECs to verify the mechanisms in vitro. RESULTS: Stimulation of S1R significantly ameliorated the cardiac function resulted from PIHF, in addition to the observation of reduced fibrosis in the peri-infarct region and the apoptosis of residual cardiomyocytes, which were associated with augmentation of microvascular density in peri-infarct region through activation of the JAK2/STAT3 pathway. We also indicated that suppression of JAK2/STAT3 pathway by specific inhibitor in vitro reversed the pro-angiogenic effects of S1R on HUVECs, which further confirmed that angiogenesis, responsible for PIHF amelioration, by S1R stimulation was in a JAK2/STAT3 pathway-dependent manner. CONCLUSION: S1R stimulation improved PIHF-induced cardiac dysfunction and ventricular remodeling through promoting angiogenesis by activating the JAK2/STAT3 pathway.

Ni-catalyzed asymmetric hydrophosphinylation of conjugated enynes and mechanistic studies.

The catalytic asymmetric synthesis of P-stereogenic phosphines is an efficient strategy to access structurally diverse chiral phosphines that could serve as organocatalysts and ligands to transition metals and motifs of antiviral drugs. Herein, we describe a Ni catalyzed highly regio and enantioselective hydrophosphinylation reaction of secondary phosphine oxides and enynes. This method afforded a plethora of alkenyl phosphine oxides which could serve as valuable precursors to bidentate ligands. A new type of mechanism was discovered by combined kinetic studies and density functional theory (DFT) calculations, which was opposed to the widely accepted Chalk-Harrod type mechanism. Notably, the alkene moiety which could serve as a directing group by coordinating with the Ni catalyst in the transition state, plays a vital role in determining the reactivity, regio and enantioselectivity.

Chronic Sigma 1 receptor activation alleviates right ventricular dysfunction secondary to pulmonary arterial hypertension.

Sigma 1 receptor (S1R) has shown a preferable protective effect on left ventricular function, but whether it protects right ventricular (RV) function is still elusive.This study aimed to determine the effects of S1R on RV dysfunction secondary to pulmonary arterial hypertension.Sixty wild-type male Sprague-Dawley rats were randomly divided into the control group, the fluvoxamine group, the pulmonary arterial hypertension group and the pulmonary arterial hypertension combined with fluvoxamine group. Monocrotaline (60 mg/kg) was administered to induce pulmonary arterial hypertension, and fluvoxamine was given for 21 consecutive days to activate S1R after one week of monocrotaline administration. Echocardiographic, serologic, and histologic parameters, qRT-PCR, and western blotting were conducted after 4 weeks of monocrotaline administration.The expression of S1R was decreased in the right ventricle in pulmonary arterial hypertension. TAPSE, and the FAC of the right ventricle were significantly decreased, and RV EDP and the plasma concentration of N-terminal pro-B-type natriuretic peptide was increased in the pulmonary arterial hypertension group, but fluvoxamine partly restored those abnormalities (all P < 0.05). Moreover, pulmonary arteriole remodeling, and fibrosis and hypertrophy in the RV were shown in the pulmonary arterial hypertension group; interestingly, fluvoxamine recovered RV structural remodeling (all P < 0.05) but neither alleviated pulmonary arteriole remodeling nor reduced pulmonary artery pressure. Furthermore, S1R activation protects RV function by upgrading the NRF 2/HO 1-mediated antioxidant stress pathway. In conclusion, chronic S1R activation ameliorates structural remodeling and RV dysfunction secondary to pulmonary arterial hypertension without altering pulmonary artery pressure.

[Physical activity and exercise status of adult residents with high risk of chronic diseases in Beijing in 2017].

OBJECTIVE: To understand the physical activity and regular exercise status and influencing factors of people with high risk of chronic diseases among Beijing residents, and to provide science basis for health education strategies and intervention measures. METHODS: 13 200 participants aged 18-79 were selected by stratified cluster sampling method for questionnaire survey in 2017.3448 participants without hypertension, diabetes and dyslipidemia met the criteria of high risk population. The metabolic equivalent of physical activity was calculated by referring to the summary of physical activity in the United States and the global physical activity questionnaire. RESULTS: 1794 male(52.0%) and 1654 female(48.0%) are included in this study. 862(25.0%) are 18-29 years old, 778(22.6%) are 30-39 years old, 640(18.6%) are 40-49 years old, 709(20.6%) are 50-59 years old, and 193(13.3%) are 60-79 years old. 684 participants(18.6%) are low physical activity level, 1480 participants(42.9%) are medium level and 1284 respondents(37.2%) are high level. The rate of never exercising is 60.2%. Multivariate analysis shows female(OR=1.32, 95%CI 1.11-1.55), aged 40-49(OR=1.34, 95%CI 1.04-1.72) and aged 50-59(OR=1.76, 95%CI 1.36-2.28) participants are likely to have high level physical activity. Participants with high education level(OR=0.78, 95%CI 0.66-0.93) and insufficient intake of fruits and vegetables(OR=0.73, 95%CI 0.64-0.84) are likely to have low physical activity level. Female(OR=1.46, 95%CI 1.22-1.76), participants with insufficient intake of fruits and vegetables(OR=1.44, 95%CI 1.24-1.69) are likely never to exercise. Participants with high education level(OR=0.46, 95%CI 0.38-0.55), high school education(OR=0.63, 95%CI 0.53-0.75), no job(OR=0.67, 95%CI 0.56-0.81) are likely to exercise. CONCLUSION: The population with high risk of chronic diseases in Beijing City was lack of physical activity. Gender, age, education level, fruit and vegetable intake are the influencing factors of physical activity level, while gender, fruit and vegetable intake, education level, marriage, employment and fruit and vegetable intake are the influencing factors of exercise.

Ni-Catalyzed Asymmetric Hydrophosphination of Unactivated Alkynes.

The practical synthesis of P-stereogenic tertiary phosphines, which have wide applications in asymmetric catalysis, materials, and pharmaceutical chemistry, represents a significant challenge. A regio- and enantioselective hydrophosphination using cheap and ubiquitous alkynes catalyzed by a nickel complex was designed, in which the toxic and air-sensitive secondary phosphines were prepared in situ from bench-stable secondary phosphine oxides. This methodology has been demonstrated with unprecedented substrate scope and functional group compatibility to afford electronically and structurally diversified P(III) compounds. The products could be easily converted into various precursors of bidentate ligands and organocatalysts, as well as a variety of transition-metal complexes containing both P- and metal-stereogenic centers.

Ni-Catalyzed Asymmetric Allylation of Secondary Phosphine Oxides.

A nickel-catalyzed asymmetric allylation of secondary phosphine oxides (SPO) for the synthesis of tertiary phosphine oxides (TPO) was realized with high enantioselectivity. The dynamic kinetic asymmetric transformation of SPO was accomplished in the presence of nickel complex. By elucidating the absolute configurations of the reacted SPO starting material and the TPO product, we confirmed that the allylation reaction proceeded through a P-stereo retention process. The protocol represents the first example of synthesizing P-stereogenic phosphine oxides by allylation reaction.

Hindering the impact of building characteristics on greenbelt cooling effects: A perspective of quantitative simulation with in situ measurements.

The urban environment, linked with human health, is a complex system disturbed by the roughness of the urban surface, unusually marked by buildings and greenbelts. The cooling effect of greenbelts inevitably responds to the distance from their locations to buildings and their characteristics, while the buildings are hardly independent of the greenbelts in terms of heat effects. To determine the role of building and greenbelt characteristics in mitigating heat stress, our study selected 3 greenbelts and 6 buildings in Beijing, China, and classified them into 2 clusters to compare the difference in monitored outdoor air temperatures (ATs) within two different building characteristics - height and length. One-way analysis of variance (ANOVA) and the least significant difference (LSD) were then employed to further test for significant difference. Our study indicates that each of the two characteristics (height and length) can bring about a significant hindering impact on greenbelt cooling effects. A greater building height or length has a greater hindering force to air (heat) flow. Knowing one or more of the characteristics of greenbelts or buildings is very critical to the improvement of the urban heat environment. Our study proposes an effective and practical outcome for facilitating governmental policy-making and planners' actions.

Long-Term Cardiovascular Risk Associated With Stage 1 Hypertension Defined by the 2017 ACC/AHA Hypertension Guideline.

BACKGROUND: Systolic/diastolic blood pressure (BP) of 130 to 139/80 to 89 mm Hg has been recently defined as stage 1 hypertension by the 2017 American College of Cardiology/American Heart Association hypertension guideline. To what extent this BP stratum affects cardiovascular risk needs to be quantified in considering its adoption in China. OBJECTIVES: The purpose of this study was to assess the relative risk and population-attributable risk of cardiovascular disease (CVD) associated with stage 1 hypertension and age-specific differences. METHODS: In total, 21,441 participants age ≥35 years and free of CVD at baseline were followed for up to 20 years in the Chinese Multi-provincial Cohort Study. The adjusted hazard ratio (HR) and population-attributable risk for CVD associated with stage 1 hypertension were calculated. RESULTS: Participants with stage 1 hypertension accounted for 25.8% of the cohort. Among participants age 35 to 59 years, the HR comparing stage 1 hypertension to BP <120/<80 mm Hg for CVD incidence was 1.78 (95% confidence interval [CI]: 1.50 to 2.11), coronary heart disease incidence was HR: 1.77 (95% CI: 1.33 to 2.36), stroke incidence was HR: 1.79 (95% CI: 1.45 to 2.22), and CVD mortality was HR: 2.50 (95% CI: 1.66 to 3.77). The proportions of cardiovascular deaths and events attributable to stage 1 hypertension were 26.5% and 13.4% among participants age 35 to 59 years, respectively. Among participants age ≥60 years, however, stage 1 hypertension was not related to increased risk compared with BP <120/<80 mm Hg, and population-attributable risk associated with this stratum was not found. Over a 15-year period, 65.0% of participants age 35 to 59 years with stage 1 hypertension experienced an increase in BP to 140/90 mm Hg or higher, and they had a 3.01-fold increased cardiovascular risk compared with those who maintained BP <130/<80 mm Hg. CONCLUSIONS: The effect of 2017 American College of Cardiology/American Heart Association stage 1 hypertension on cardiovascular risk is evidenced in young and middle-aged Chinese adults, but not in those age ≥60 years.

Association Between Circulating Oxidized LDL and Atherosclerotic Cardiovascular Disease: A Meta-analysis of Observational Studies.

BACKGROUND: Although basic research has suggested that oxidized low-density lipoprotein (ox-LDL) is involved in the pathogenesis of atherosclerosis, population observational studies have yielded conflicting results about the association between circulating ox-LDL and atherosclerotic cardiovascular disease (ASCVD). Therefore, we performed a systematic review and meta-analysis of currently available observational studies to verify the association between circulating ox-LDL and ASCVD. METHODS: We systematically searched PubMed and the Cochrane Library from their inception to March 27, 2017, for nested case-control studies, case-cohort studies, and prospective cohort studies on the relationship between ox-LDL and ASCVD. Studies that did not assess the hazard ratio, relative risk, or odds ratio of ox-LDL or did not adjust for other risk factors, or those without examination of ox-LDL before collection of ASCVD occurrences were excluded. The summarized effect size was combined using fixed effect models. Subgroup analyses were performed on the basis of study quality, study design, definition of ASCVD events, effect size types, types of ox-LDL assay, ox-LDL contrast level, and whether low-density lipoprotein cholesterol was adjusted in a multivariate model. RESULTS: A total of 12 included studies consisted of 3 nested case-control studies, 1 case-cohort study, 5 hospital-based cohort studies, and 3 community-based cohort studies. The summary effect size of increased circulating ox-LDL was 1.79 (95% confidence interval, 1.56-2.05) for ASCVD. Similar associations were shown in all subgroups. CONCLUSIONS: Our findings indicate that increased levels of circulating ox-LDL are associated with clinical ASCVD events. Further well designed community-based cohort studies or intervention studies are needed to confirm our findings.