Comparative transcriptome and metabolome reveal the role of acidic electrolyzed oxidizing water in improving postharvest disease resistance of longan fruit.

Acidic electrolyzed oxidizing water (AEOW) was applied to suppress disease development and maintain good quality of fresh fruit. However, the involvement of AEOW in improving disease resistance of fresh longan remains unknown. Here, transcriptomic and metabolic analyses were performed to compare non-treated and AEOW-treated longan during storage. The transcriptome analysis showed AEOW-induced genes associated with phenylpropanoid and flavonoid biosynthesis. The metabolome analysis found the contents of coumarin, phenolic acid, and tannin maintained higher levels in AEOW-treated longan than non-treated longan. Moreover, the weighted correlation network analysis (WGCNA) was performed to identify hub genes, and a gene-metabolite correlation network associated with AEOW-improved disease resistance in longan was constructed by the co-analysis of transcriptomics and metabolomics. These findings identified a series of important genes and metabolites involving in AEOW-induced disease resistance of longan fruit, expanding our knowledges on fruit disease resistance and quality maintenance at the transcript and metabolic levels.

Acidic electrolyzed-oxidizing water treatment mitigated the disease progression in Phomopsis longanae Chi-infected longans by modulating ROS and membrane lipid metabolism.

Postharvest harmful pathogenic infestation leads to rapid decay in longan fruit. Compared with P. longanae-infected longans, AEOW alleviated fruit disease severity and diminished the O2-. production rate and MDA content. It also increased APX, CAT, and SOD activities, delayed the decrease in the levels of GSH and AsA, as well as the reducing power and DPPH radical scavenging ability, which resulted in a decline in membrane lipid peroxidation in P. longanae-infected longans. Additionally, AEOW reduced LOX, lipase, PI-PLC, PC-PLC, and PLD activities, maintained higher levels of PC, PI, IUFA, USFAs, and U/S, while reducing levels of PA, DAG, SFAs, and CMP. These effects alleviated membrane lipid degradation and peroxidation in P. longanae-infected longans. Consequently, AEOW effectively maintained membrane integrity via improving antioxidant capacity and suppressing membrane lipid peroxidation. This comprehensive coordination of ROS and membrane lipid metabolisms improved fruit resistance and delayed disease development in longans.

Development of the Low-Temperature Inducible System for Recombinant Protein Production in Escherichia coli Nissle 1917.

The pET system is commonly used for producing foreign proteins in Escherichia coli, but its reliance on the costly and metabolically demanding inducer IPTG limits its industrial use. This study engineered a low-temperature inducible system (LTIS) in E. coli Nissle 1917 (EcN) by combining the T7 expression system with the thermal inducible mechanism CI857-λPRPL to generate the new LTIS strain, ENL7P. The strain ENL7P-sfGFP-Km underwent overnight culture at 37 °C for 14-16 h, followed by subculturing at 30 °C for 24 h. This resulted in a notable 5.53-fold increase in the sfGFP induction rate when the strain was cultivated under 37-30 °C conditions. Moreover, gene expression was induced using a two-stage strategy. Initially, the strain was cultured overnight at 39 °C for 14-16 h, followed by a subculture at 30 °C for 6 h, and finally, another subculture at 30 °C for 24 h. This cultivation strategy led to an impressive 158.37-fold induction rate for sfGFP. Similar effects could be achieved through utilization of the LTIS system for inducing the production of thermophilic trehalose synthase from Thermus antranikianii (TaTS). The results of this study proved that the LTIS system has the potential for industrial applications.

Inflammatory myofibroblastic tumor of the heart in an older woman with paroxysmal atrial fibrillation: a case report and review of the literature.

Inflammatory myofibroblastic tumors (IMTs) of the heart are rarely observed in the eldly. We report a case involving an elderly woman with an IMT situated on the right atrial wall. The tumor was fully excised. The patient had a smooth recovery post-surgery and remained free of recurrence for three years.

New Insights into Rate Control: Time in Target Range of Resting Heart Rate and Major Adverse Outcomes in Atrial Fibrillation.

Background: Few studies have examined the relationship between the fluctuation of heart rate control over time and cardiovascular outcomes in patients with atrial fibrillation. Our study sought to evaluate the independent association between time in target range (TIR) of resting heart rate and cardiovascular outcomes in the AFFIRM (Atrial Fibrillation Follow-Up Investigation of Rhythm Management) study. Methods: Target range of resting heart was defined as less than 80 beats per minute (bpm) for both rate and rhythm control groups. Time in target range was estimated over the first 8 months of follow-up using Rosendaal interpolation method. The association between TIR of resting heart rate and cardiovascular outcomes was estimated using adjusted Cox proportional hazards regression models. Results: Time in target range of resting heart rate (months 0 through 8) was 71 ± 34% in the rate control group and 83 ± 27% in the rhythm control group. Each 1-SD increase in TIR of resting heart rate was significantly associated with lower risk of major adverse cardiovascular events after full adjustment for demographics, medical history and history of prior heart surgery, as well as all-cause mortality. Conclusions: Time in target range of resting heart rate independently predicts the risk of cardiovascular outcomes in patients with atrial fibrillation. Long-term maintenance of heart rate on target is of great importance for patients with atrial fibrillation.

Serum Klotho Modifies the Associations of 25-Hydroxy Vitamin D With All-Cause and Cardiovascular Mortality.

BACKGROUND: The association between 25-hydroxyvitamin D and mortality remains controversial. Klotho, a biomarker of vitamin D activation and metabolism, may play a key role in this association. However, it is unclear whether the association between vitamin D deficiency and mortality risk is modified by klotho levels. Therefore, this study investigated the joint association of serum 25-hydroxyvitamin D [25(OH)D] and klotho with mortality risk in American community-dwelling adults. METHODS: A total of 9870 adults from the National Health and Nutrition Examination Survey (2007-2016) were included in our study. Mortality data were ascertained by linking participants to National Death Index records. Cox proportional hazards models were used to assess the association among serum 25(OH)D, serum klotho, and all-cause and cardiovascular disease (CVD) mortality. RESULTS: We found a significant interaction between klotho and serum 25(OH)D in all-cause mortality (P = .028). With klotho > 848.4 pg/mL (risk threshold on mortality), no significant all-cause and CVD mortality risk was observed at any level of serum 25(OH)D. However, with klotho < 848.4 pg/mL, a significant all-cause and CVD mortality risk was observed with serum 25(OH)D < 50 nmol/L [hazards ratio (HR), 1.36; 95% confidence interval (CI), 1.10-1.69; HR, 1.78; 95% CI, 1.16-3.45) and serum 25(OH)D of continuous variable (HR, 0.98; 95% CI, .97-.99; HR, 0.98; 95% CI, .98-.99). In addition, vitamin D metabolism disruption accessed by the combination of decreasing serum 25(OH)D (<50 nmol/L) and klotho (<848.4 pg/mL) was associated with significant all-cause mortality (HR, 1.48; 95% CI, 1.11-1.96) and CVD mortality (HR, 2.36; 95% CI, 1.48-3.75). CONCLUSIONS: Vitamin D-associated mortality risk is observed only with concurrently decreasing klotho, indicating that vitamin D metabolism dysfunction increases the risk of mortality. Klotho levels could help predict long-term mortality outcomes and thus may be useful concurrently for guiding vitamin D supplementation therapy decision-making in populations with vitamin D deficiency.

Intensive Glycemic Therapy in Type 2 Diabetes Patients With Cardiac Autonomic Dysfunction: The ACCORD Trial.

OBJECTIVE: To assess whether the presence of cardiac autonomic dysfunction denoted by low heart rate variability (HRV) modifies the effect of intensive glycemic therapy on outcomes in patients with type 2 diabetes. PATIENTS AND METHODS: This study included 7946 participants in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial from January 2001 through June 2009. Heart rate variability measures included standard deviation of all normal-to-normal intervals (SDNN) and root mean square of successive differences between normal-to-normal intervals (rMSSD). Abnormal values were defined based on less than the 10th percentile for SDNN and rMSSD. RESULTS: Compared with standard therapy, intensive therapy was associated with improved primary outcome (composite of cardiovascular events) in the low-HRV group (SDNN: HR, 0.57; 95% CI, 0.39 to 0.84; rMSSD: HR, 0.57; 95% CI, 0.38 to 0.84), but not in the normal-HRV group (SDNN: HR, 0.90; 95% CI, 0.77 to 1.05; rMSSD: HR, 0.90; 95% CI, 0.77 to 1.05). A similar pattern was found for coronary heart disease. Conversely, intensive therapy had a neutral effect on all cause death in the low-HRV group (SDNN: HR, 0.88; 95% CI, 0.54 to 1.41; rMSSD: HR, 0.71; 95% CI, 0.43 to 1.17;), but increase risk of all-cause death in the normal-HRV group (SDNN: HR, 1.21; 95% CI, 1.00 to 1.46; rMSSD: HR, 1.25; 95% CI, 1.03 to 1.51). Intensive therapy induced a greater risk of hypoglycemia in the normal-HRV group than that in the low-HRV group. CONCLUSION: Cardiac autonomic dysfunction expressed as low HRV identified subpopulations in ACCORD with more benefits and less harms from intensive therapy.

Hydrogen peroxide induced changes in the levels of disease-resistant substances and activities of disease-resistant enzymes in relation to the storability of longan fruit.

The influences of hydrogen peroxide (H2O2) on the storability and metabolism of disease-resistant substances in fresh longan were investigated. Compared to the control samples, H2O2-treated longan exhibited a higher index of fruit disease, pericarp browning, and pulp breakdown, a higher rate of fruit weight loss, but lower chromaticity values (L*, a* and b*) in pericarp appearance, and a lower commercially acceptable fruit rate. Additionally, H2O2-treated longan showed a lower lignin content, lower activities of enzymes including phenylalnine ammonia lyase (PAL), cinnamate 4-hydroxylase (C4H), 4-coumaryl coenzyme A ligase (4-CL), cinnamate dehydrogenase (CAD), peroxidase (POD), chitinase (CHI), and ß-1,3-glucanase (GLU). These data collectively suggest that H2O2 negatively impacted the storability of fresh longan. This can be attributed to H2O2's role in reducing the levels of disease-resistant substances and suppressing the activities of disease-resistant enzymes, implying that H2O2 reduced the postharvest storability of longan by compromising its disease resistance.

Effect of blood pressure index on clinical outcomes in patients with heart failure and chronic kidney disease.

AIMS: This study aimed to assess the effect of blood pressure (BP) index, in terms of level and variability, on the progression of cardiovascular and renal diseases in patients with both heart failure (HF) and chronic kidney disease (CKD). METHODS AND RESULTS: The study involved patients with HF and CKD from the database of the Chronic Renal Insufficiency Cohort (CRIC) study. The study endpoint includes the following: (i) primary endpoint, including cardiovascular disease (CVD) events, renal events, and all-cause death; (ii) CVD events; (iii) renal events; and (iv) all-cause death. Among 3939 participants in the CRIC study, a total of 382 patients were included. The duration of the follow-up was 6.3 ± 2.7 years, the age was 60.2 ± 8.9 years, and 57.6% were male. BP index included 20 indicators in relation to BP level and variability, 4 of which were analysed including baseline systolic BP (SBP), standard deviation of SBP, coefficient of variation of diastolic BP (DBP CV), and average real variability of pulse pressure. In the Cox regression analysis after adjustment, baseline SBP was significant for the risk of primary endpoint [hazard ratio (HR) 1.22, 95% confidence interval (CI) 1.03-1.44, P = 0.02] and renal events (HR 1.54, 95% CI 1.22-1.95, P < 0.001), and DBP CV was significant for the risk of primary endpoint (HR 1.03, 95% CI 1.01-1.06, P = 0.02) and CVD events (HR 1.04, 95% CI 1.02-1.07, P < 0.01). The result of the forest plot depicted that baseline SBP had a linear association with the risk of CVD and renal events (P = 0.04 and 0.001, respectively) and DBP CV with CVD events (P = 0.02). As the restricted cubic spline models displayed, DBP CV featured a J- or L-curved association with the primary endpoint, renal events, and all-cause death (P for nonlinearity = 0.01, <0.001, and 0.01, respectively). CONCLUSIONS: The baseline SBP and DBP CV may remain significant for clinical outcomes in patients with both HF and CKD. The increase in baseline SBP is associated with a higher risk of primary endpoint, CVD events, and renal events, and the increase in DBP CV with a higher risk of CVD events. Concerning nonlinear association, DBP CV features a J- or L-curved relationship with the primary endpoint, renal events, and all-cause death, with a higher risk at both low and high values. TRIAL REGISTRATION: https://www. CLINICALTRIALS: gov; unique identifier: NCT00304148.

GP73 enhances the ox-LDL-induced inflammatory response in THP-1 derived macrophages via affecting NLRP3 inflammasome signaling.

BACKGROUND: Atherosclerosis is a chronic inflammatory disease with its molecular basis incompletely understood. Here, we determined whether the Golgi phosphoprotein 73 (GP73), a novel protein highly related to inflammation and disrupted lipid metabolism, was involved in the development of atherosclerosis. METHODS: Public microarray databases of human vascular samples were analyzed for expression patterns. Apolipoprotein-E-gene-deficient (ApoE-/-) mice (8-week-old) were randomly assigned to either a chow diet group or a high-fat diet group. The levels of serum GP73, lipid profiles and key inflammatory cytokines were determined by ELISA. The aortic root plaque was isolated and used for by Oil Red O staining. PMA-differentiated THP-1 macrophages were transfected with GP73 small interfering RNA (siRNA) or infected with adenovirus expressing GP73, and then stimulated with oxidized low density lipoprotein (ox-LDL). The expressions of pro-inflammatory cytokines and signal pathway key targets were determined by ELISA kit and Western blot respectively. In addition, ichloro-dihydro-fluorescein diacetate (DCFH-DA) was used to measure the intracellular ROS levels. RESULTS: The expressions of GP73 and NLRP3 were substantially upregulated in human atherosclerotic lesions. There were significant linear correlations between GP73 and inflammatory cytokines expressions. High-fat diet-induced atherosclerosis and increased levels of plasma inflammatory mediators (IL-1ß, IL-18, and TNF-α) were observed in ApoE-/- mice. Besides, the expressions of GP73 in the aorta and serum were significantly upregulated and positively correlated with the NLRP3 expression. In the THP-1 derived macrophages, ox-LDL treatment upregulated the expressions of GP73 and NLRP3 proteins and activated the inflammatory responses in a concentration-dependent and time-dependent manner. Silencing of GP73 attenuated the inflammatory response and rescued the decreased migration induced by ox-LDL, inhibiting the NLRP3 inflammasome signaling and the ROS and p-NF-κB activation. CONCLUSIONS: We demonstrated that GP73 promoted the ox-LDL-induced inflammation in macrophages by affecting the NF-κB/NLRP3 inflammasome signaling, and may play a role in atherosclerosis.

Causal links between socioeconomic status, leisure sedentary behaviours and gastro-oesophageal reflux disease: a multivariable two-sample Mendelian randomisation study.

INTRODUCTION: We implemented a two-sample multivariable Mendelian randomisation (MR) analyses to estimate the causal effect of socioeconomic status and leisure sedentary behaviours on gastro-oesophageal reflux disease (GERD). METHODS: Independent single-nucleotide polymorphisms associated with socioeconomic status and leisure sedentary behaviours at the genome-wide significance level from the Medical Research Council Integrative Epidemiology Unit (MRC-IEU) UK Biobank were selected as instrumental variables. Summary-level data for GERD were obtained from a recent publicly available genome-wide association involving 78 707 GERD cases and 288 734 controls of European descent. Univariable and multivariable two-sample MR analyses, using inverse variance weighted method for primary analyses, were performed to jointly evaluate the effect of socioeconomic status and leisure sedentary behaviours on GERD risk. RESULTS: Three socioeconomic status, including educational attainment (OR 0.46; 95% CI 0.30 to 0.69; p<0.001), average total household income before tax (OR 0.65; 95% CI 0.47 to 0.90; p=0.009) and Townsend Deprivation Index at recruitment (OR 1.60; 95% CI 1.06 to 2.41; p=0.026), were independently and predominately responsible for the genetic causal effect on GERD. In addition, one leisure sedentary behaviour, such as time spent watching television, was independently and predominately responsible for genetic causal effect on GERD (OR 3.74; 95% CI 2.89 to 4.84; p<0.001). No causal effects of social activities and driving on GERD were observed. CONCLUSIONS: Genetically predicted Townsend Deprivation Index at recruitment and leisure watching television were causally associated with increased risk of GERD, and age at completion of full-time education and average total household income before tax were causally associated with decreased risk of GERD.

Body weight time in target range and cardiovascular outcomes in adults with overweight/obesity and type 2 diabetes.

AIMS: Prescription of weight loss to individuals is often characterized by weight fluctuations. However, current body weight management metrics may have difficulty characterizing the changes in body weight over time. We aim to characterize the long-term changes using body weight time in target range (TTR) and test its independent association with cardiovascular outcomes. METHODS AND RESULTS: We included 4468 adults from the Look AHEAD (Action for Health in Diabetes) trial. Body weight TTR was defined as the percentage of time during which body weight was within the Look AHEAD weight loss goal range. The associations of body weight TTR with cardiovascular outcomes were analysed using multivariable Cox modelling and restricted cubic spline function. Among the participants (mean age 58.9 years, 58.5% women, 66.5% White), there were 721 incident primary outcomes [cumulative incidence: 17.5%, 95% confidence interval (CI): 16.3-18.8%] during a median of 9.5 years of follow-up. Each 1 SD increase in body weight TTR was significantly associated with a decreased risk of the primary outcome (hazard ratio: 0.84, 95% CI: 0.75-0.94) after adjusting for mean and variability of body weight and traditional cardiovascular risk factors. Further analyses using restricted cubic spline indicated the inverse association between body weight TTR and the primary outcome in a dose-dependent manner. Similar associations remained significant among the participants with lower baseline or mean body weight. CONCLUSION: In adults with overweight/obesity and type 2 diabetes, higher body weight TTR was independently associated with lower risks of cardiovascular adverse events in a dose-response manner.

We used time in target range (TTR) to characterize the long-term changes in body weight among 4468 adults with overweight/obesity and type 2 diabetes and assessed the associations of body weight TTR with cardiovascular outcomes.Participants with TTR of >50­100% achieved and maintained the target of body weight loss during the 10 years of follow-up.Higher body weight TTR was independently associated with lower risks of cardiovascular adverse events in a dose­response manner.

The difference of the cell wall metabolism between 'Fuyan' and 'Dongbi' longans and its relationship with the pulp breakdown.

The aims of present works were to explore the difference in pulp breakdown of 'Fuyan' and 'Dongbi' longans and its relationship with cell wall metabolism. Comparison with 'Fuyan' longan fruit, postharvest 'Dongbi' longan fruit showed lower pulp breakdown index, lower activities of PE, PG, cellulase, ß-Gal, XET, and lower expression levels of their corresponding genes. In addition, higher levels of cell wall polysaccharides including ISP, CSP, cellulose and hemicellulose were exhibited in 'Dongbi' longan pulp. These findings implied that, the reduced activities of enzymes and the down-regulated expressions of genes-involved in cell wall disassembly were shown in 'Dongbi' longan pulp, which might reduce the dissolution of polysaccharides and maintain a higher structural integrity in 'Dongbi' longan pulp cell wall, and consequently the mitigated pulp breakdown was displayed in 'Dongbi' longan during storage.

Predictive performance of established cardiovascular risk scores in the prediabetic population: external validation using the UK Biobank data set.

AIMS: Prediabetes is a highly heterogenous metabolic state with increased risk of cardiovascular disease (CVD). Current guidelines raised the necessity of CVD risk scoring for prediabetes without clear recommendations. Thus, this study aimed to systematically assess the performance of 11 models, including five general population-based and six diabetes-specific CVD risk scores, in prediabetes. METHODS AND RESULTS: A cohort of individuals aged 40-69 years with prediabetes (HbA1c ≥ 5.7 and <6.5%) and without baseline CVD or known diabetes was identified from the UK Biobank, which was used to validate 11 prediction models for estimating 10- or 5-year risk of CVD. Model discrimination and calibration were evaluated by Harrell's C-statistic and calibration plots, respectively. We further performed decision curve analyses to assess the clinical usefulness.Overall, 56 831 prediabetic individuals were included, of which 4303 incident CVD events occurred within a median follow-up of 8.9 years. All the 11 risk scores assessed had modest C-statistics for discrimination ranging from 0.647 to 0.680 in prediabetes. Scores developed in the general population did not outperform those diabetes-specific models (C-statistics, 0.647-0.675 vs. 0.647-0.680), while the PREDICT-1° Diabetes equation developed for Type 2 diabetes performed best [0.680 (95% confidence interval, 0.672-0.689)]. The calibration plots suggested overall poor calibration except that the PREDICT-1° Diabetes equation calibrated well after recalibration. The decision curves generally indicated moderate clinical usefulness of each model, especially worse within high threshold probabilities. CONCLUSION: Neither risk stratification schemes for the general population nor those specific for Type 2 diabetes performed well in the prediabetic population. The PREDICT-1° Diabetes equation could be a substitute in the absence of better alternatives, rather than the general population-based scores. More precise and targeted risk assessment tools for this population remain to be established.

Comprehensive analyses of membrane lipids and phenolics metabolisms reveal the developments of chilling injury and browning in Chinese olives during cold storage.

The impacts of chilling injury (CI) temperature (2 °C) and non-CI temperature (8 °C) on the CI development, browning occurrence, and its underlying mechanism in Chinese olives were investigated. The results showed that, 2 °C induced higher levels of CI index, browning degree, chromaticity a* and b* values, but lower values of h°, chlorophyll and carotenoid contents in Chinese olives as compared to 8 °C. Furthermore, 2 °C raised cell membrane permeability, increased the activities of phospholipase D, lipase and lipoxygenase, accelerated the hydrolyses of phosphatidylcholine and phosphatidylinositol to phosphatidic acid, and promoted the conversions of unsaturated fatty acids to saturated fatty acids in Chinese olives. Moreover, 2 °C-stored Chinese olives showed higher activities of peroxidase and polyphenol oxidase, but lower contents of tanin, flavonoid and phenolics. These findings demonstrated that the CI and browning developments in Chinese olives were closely associated with the metabolisms of membrane lipid and phenolics.

The effect of ε-poly-l-lysine treatment on molecular, physiological and biochemical indicators related to resistance in longan fruit infected by Phomopsis longanae Chi.

Postharvest longan fruits are subjected to Phomopsis longanae Chi (P. longanae) infection that lead to fruit quality deterioration. We hypothesized that ε-poly-l-lysine (ε-PL) could enhance fruit disease resistance in longans. Through physiological and transcriptomic analyses, the results showed that, compared to P. longanae-infected longan fruit, ε-PL + P. longanae treatment reduced the disease development of longan fruits. Additionally, ε-PL + P. longanae treatment increased the contents of disease-resistant substances (lignin and H2O2) and the activities of disease-resistance enzymes (CHI, PAL, PPO, C4H, CAD, GLU, 4CL, and POD). Furthermore, the expressions of genes relevant to the phenylpropanoid biosynthesis pathway and plant-pathogen interaction pathway (Rboh, FLS2, WRKY29, FRK1, and PR1) were up-regulated by ε-PL + P. longanae treatment. These findings demonstrated that ε-PL treatment inhibited the disease development of postharvest longan fruits were associated with the increased accumulation of disease-resistant related substances, as well as the raised activities and genes expressions of disease-resistance related enzymes.

Changes in Cardiovascular Health during Young Adulthood and Subclinical Atherosclerosis in Middle Age: The CARDIA Study.

Background and aims: The benefits of reaching ideal cardiovascular health (CVH) are well known, but it is unclear whether positive CVH changes from young adulthood to middle age reduce subclinical atherosclerosis risk. This study examined associations of changes in CVH from young adulthood to middle age and CVH in young adulthood with subclinical atherosclerosis. Methods: Data was analyzed from the Coronary Artery Risk Development in Young Adults (CARDIA) study. CVH was examined at years 0 and 20 using Life Simple 7 metrics from AHA guideline. Coronary artery calcium (CAC) was identified at years 20 and 25. Carotid intima-media thickness (IMT) was identified at year 20. Results: Among 2,935 participants (56.2% women, 46.7% black), the change of CVH score was -1.26 (2.13). For per 1-unit increase in CVH at baseline, the adjusted odds ratios (ORs) of presence of CAC and IMT were 0.81 (95% CI 0.78, 0.86) and 0.85 (95% CI 0.76, 0.94), respectively. For per 1-unit increase in CVH changes, the adjusted ORs of CAC and IMT were 0.86 (95% CI 0.82, 0.90) and 0.81 (95% CI 0.73, 0.90). Compared with stable moderate CVH, improvement from moderate to high was associated with a lower risk of CAC (0.64 [95% CI 0.43, 0.96]), while retrogression from moderate to low was associated with a higher risk of CAC (1.45 [95% CI 1.19, 1.76]). Conclusions: Positive changes of CVH during young adulthood are associated with negative subclinical atherosclerosis risk in middle age, indicating the importance of reaching an ideal cardiovascular health status through young adulthood.

Effect of intensive lifestyle intervention on the association between weight variability and major adverse cardiovascular events in overweight or obese adults with type 2 diabetes mellitus.

AIMS/INTRODUCTION: Weight variability is associated with cardiovascular outcomes in diabetic patients. However, whether the guideline-recommended intensive lifestyle intervention (ILI) will affect this association in overweight or obese adults with diabetes is not well established. MATERIALS AND METHODS: In 3,859 participants from the Action for Health in Diabetes (Look AHEAD) trial, the associations of 4 year weight variability measured by variability independent of the mean (VIM) with major adverse cardiovascular event (MACE) and secondary outcomes in ILI and diabetes support & education (DSE) arm were evaluated. RESULTS: During a median follow-up of 9.6 years, 255 (12.9%) participants in the ILI arm and 247 (13.2%) participants in the DSE arm developed MACE. Participants with the highest quartile of weight variability (VIM Q4) experienced a 2.23-fold higher risk of MACE compared with the lowest quartile (VIM Q1) in the DSE arm (hazard ratio [HR] 2.23; 95% CI 1.51-3.30). Compared with the lowest weight variability (VIM Q1), participants with the highest weight variability (VIM Q4) were associated with higher risks of secondary cardiovascular composite outcome (HR 1.88; 95% CI 1.20-2.95), all-cause mortality (HR 3.19; 95% CI 1.75-5.82), and myocardial infarction (HR 1.95; 95% CI 1.12-3.37) in the DSE arm. CONCLUSIONS: Among the overweight or obese individuals with type 2 diabetes mellitus, rising weight variability was independently associated with increased MACE risks in the DSE arm. Therefore, a guideline-recommended ILI strategy for weight loss should be adopted to improve cardiovascular outcomes without worrying about the effect of weight fluctuations.

DNP and ATP regulate the breakdown occurrence in the pulp of Phomopsis longanae Chi-infected longan fruit through modulating the metabolism of membrane lipid.

This study aimed to illustrate how DNP and ATP affected the pulp breakdown occurrence in P. longanae-infected longan and their relationship with the membrane lipid metabolism. Compared with P. longanae-inoculated samples, the pulp of DNP-treated P. longanae-infected longan exhibited higher cellular membrane permeability, breakdown index, activities of PI-PLC, PLD, PC-PLC, LOX, and lipase, and values of SFAs, PA, and DAG, while lower levels of PI, PC, USFAs, IUFA and U/S. However, the opposite findings were observed in ATP-treated P. longanae-infected longan. The data manifested that DNP-increased the pulp breakdown occurrence in P. longanae-inoculated samples was due to the elevated MLDEs activities that reduced the contents of phospholipids (PI, PC) and USFAs, disrupting the cell membrane structures. Nevertheless, ATP decreased the pulp breakdown occurrence in P. longanae-inoculated samples, which was ascribed to the reduced MLDEs activities that raised phospholipids (PI, PC) and USFAs contents, thus maintaining the cell membrane structures.

Targeting efficacy of spironolactone in patients with heart failure with preserved ejection fraction: the TOPCAT study.

AIMS: We aimed to explore the heterogeneous treatment effects (HTEs) for spironolactone treatment in patients with Heart failure with preserved ejection fraction (HFpEF) and examine the efficacy and safety of spironolactone medication, ensuring a better individualized therapy. METHODS AND RESULTS: We used the causal forest algorithm to discover the heterogeneous treatment effects (HTEs) from patients in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. Cox regressions were performed to assess the hazard ratios (HRs) of spironolactone medication for cardiovascular death and drug discontinuation in each group. The causal forest model revealed three representative covariates and participants were partitioned into four subgroups which were Group 1 (baseline BMI ≤ 31.71 kg/m2 and baseline ALP ≤ 80 U/L, n = 759); Group 2 (BMI ≤ 31.71 kg/m2 and ALP > 80 U/L, n = 1088); Group 3 (BMI > 31.71 kg/m2 , and WBC ≤ 6.6 cells/µL, n = 633); Group 4 (BMI > 31.71 kg/m2 and WBC > 6.6 cells/µL, n = 832), respectively. In the four subgroups, spironolactone therapy reduced the risk of cardiovascular death in high-risk group (Group 4) with both high BMI and WBC count (HR: 0.76; 95% CI 0.58 to 0.99; P = 0.045) but increased the risk in low-risk group (Group 1) with both low BMI and ALP (HR: 1.45; 95% CI 1.02 to 2.07; P = 0.041; P for interaction = 0.020) but showed similar risk of drug discontinuation (P for interaction = 0.498). CONCLUSION: Our study manifested the HTEs of spironolactone in patients with HFpEF. Spironolactone treatment in HFpEF patients is feasible and effective in patients with high BMI and WBC while harmful in patients with low BMI and ALP. Machine learning model could be meaningful for improved categorization of patients with HFpEF, ensuring a better individualized therapy in the clinical setting.