Xin Zhao

Background: Prospective evidence linking dietary aromatic amino acids (AAAs), including phenylalanine (Phe), tyrosine (Tyr), and tryptophan (Trp), to incident hypertension currently remains limited, particularly regarding their individual components and food sources. Herein, we examined the association between dietary AAAs, their food sources, and incident hypertension among Chinese adults. Methods: Using the China Health and Nutrition Survey database, this prospective cohort study collected data from 10,087 adults without hypertension at baseline. Baseline dietary intake was assessed using three consecutive 24-h dietary recalls, combined with household food weighing; the energy-adjusted AAA intake was expressed in g/1,000 kcal. Incident hypertension was defined as measured blood pressure, physician diagnosis, or use of antihypertensive medication. Mixed-effects Cox proportional hazards models with household identifiers as random intercepts were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Dose–response, food-source-specific, subgroup, and sensitivity analyses were performed. Results: During the 95,153 person-years of follow-up, 3,531 participants developed hypertension. In fully adjusted models, the highest quartile of total AAA intake was associated with a modestly higher risk of incident hypertension compared with the lowest quartile (HR, 1.16; 95% CI, 1.03–1.31; P for trend = 0.006). Positive associations were more consistent for Phe (HR for Q4 vs. Q1, 1.26; 95% CI, 1.11–1.44) and Trp (HR, 1.29; 95% CI, 1.14–1.46) individually, while Tyr intake showed no significant association with hypertension. Dose–response analyses indicated approximately linear positive associations for total AAA, Phe, and Trp. The association for total AAA was attenuated following additional adjustment for baseline province (HR for Q4 vs. Q1, 1.10; 95% CI, 0.97–1.24), while the positive associations for Phe and Trp persisted. Cereals were the predominant contributors to AAA intake, and plant-derived Phe and Trp were positively associated with the risk of hypertension. Conclusion: Higher dietary intakes of Phe and Trp showed consistent positive associations with incident hypertension, while Tyr showed no clear association. The modest association for total AAA was attenuated after adjusting for baseline province and should therefore be interpreted cautiously in relation to potential regional confounding factors. These findings support the component-specific interpretation of dietary AAAs and consideration of their regional and food source contexts.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is being increasingly recognized as a systemic cardiometabolic disorder rather than a live

Heat shock factor 2 (HSF2) and hypoxia‐inducible factor 1α are activated by angiotensin II (ANGII) in cardiomyocytes. The endoplasmic reticulum (ER) stress plays a critical role in cardiac hypertrophy. Moreover, HIF‐1α is known to be regulated by HSF2 in tumour cells. In this study, we hypothesised and clarified whether HSF2 trans‐activated HIF‐1α through initiation of ER stress in hypertrophic cardiomyocytes. Myocardial hypertrophy was induced by the treatment of ANGII. Expression of the gene or protein was assessed by applying RT‐PCR, WB, ICC and IHC. Luciferase and CHIP were applied to detect the transcription of HIF‐1α by HSF2. Both in vitro and in vivo, the expression of HIF‐1α, ER stress markers and HSF2 was increased in ANGII‐treated hypertrophic cardiomyocytes. Blocking ER stress suppressed the expression of HSF2 and HIF‐1α in ANGII‐treated cardiomyocytes. Silencing HSF2 inhibited HIF‐1α, thereby reducing hypertrophy but had no effect on ER stress. Similarly, silencing HIF‐1α reduced hypertrophy without affecting ER stress or HSF2 expression. HSF2 transcriptionally activated HIF‐1α. We concluded that ER stress induced by ANGII activates HSF2, which then trans‐activates HIF‐1α, promoting cardiac hypertrophy.

Background:This study aimed to investigate whether intracoronary administration of recombinant human prourokinase (rhPro-UK) improves coronary blood flow, attenuates post-reperfusion inflammatory responses, and enhances clinical outcomes in patients with acute myocardial infarction.Methods:In this prospective, single-blind, randomized, controlled clinical trial, 136 ST-segment elevation myocardial infarction (STEMI) patients undergoing emergency percutaneous coronary intervention (PCI) at Anqing Municipal Hospital (August 2021–June 2023) were randomized 1:1:1 to intracoronary rhPro-UK (n = 44), tirofiban (n = 44), or saline groups (n = 48). Perioperative serum levels of creatine kinase-MB (CK-MB), high-sensitivity cardiac troponin T (hs-cTnT), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α), and soluble suppression of tumorigenicity-2 (sST2) were measured. Serum sST2 was re-evaluated at 1 month (28 ± 7 days) post-PCI. Major adverse cardiovascular events (MACE) were assessed via clinic visits or telephone follow-up at 12 months.Results:The cohort had a mean age of 60.6 ± 11.5 years and was predominantly male (89.0%). At 12 months, the rhPro-UK group had the lowest MACE incidence (log-rank p = 0.039). Multivariable Cox regression confirmed reduced MACE risk in the rhPro-UK group (hazard ratio [HR] 0.22, 95% confidence interval [CI]: 0.05–0.99, p = 0.049). The final intra- and postoperative corrected TIMI frame count (cTFC) results demonstrated that both the tirofiban group and the rhPro-UK group exhibited superior efficacy in alleviating the slow/no-reflow phenomenon compared with the saline control group. At 48 hours post-PCI, rhPro-UK significantly reduced CK-MB and hs-cTnT levels compared to saline (p < 0.05). Both rhPro-UK and tirofiban groups exhibited lower IL-6, IL-8, and TNF-α levels at 24, 48, and 72 hours (p < 0.05). At 1-month follow-up, sST2 levels were markedly reduced in the rhPro-UK group (12.9 ± 3.3 pg/mL) versus tirofiban (18.7 ± 4.9 pg/mL) and saline (24.4 ± 15.7 pg/mL) (p = 0.001).Conclusion:Intracoronary rhPro-UK administration during emergency PCI in STEMI patients reduces post-reperfusion inflammation and fibrosis, limits infarct size, and improves clinical outcomes.Trial Registration:Chinese Clinical Trial Registry (ChiCTR; http://www.chictr.org.cn; Identifier: ChiCTR2100047095).

Mitochondria and endothelial cells engage in bidirectional crosstalk to maintain vascular tone, barrier integrity, and inflammatory quiescence. In cardiometabolic diseases (CMDs), metabolic overload and chronic inflammatory cues disrupt endothelial mitochondrial bioenergetics, dynamics, and quality-control mechanisms. As protective systems weaken, redox imbalance and impaired nitric oxide signaling—further exacerbated by barrier dysfunction—trigger endothelial activation and loss of homeostasis. Clinical translation has lagged largely because endothelial responses vary across vascular beds and microenvironments, and most clinical trials fail to align patient selection or endpoints with mitochondrial mechanisms. This review addresses a major translational gap: how mitochondrial stress programs map onto context-specific endothelial phenotypes in human CMDs, and how this mapping can inform the selection of actionable therapeutic strategies. Indeed, this review integrates single-cell and spatial multi-omics data to link mitochondrial stress and metabolic remodeling to specific anatomical niches, transforming the broad notion of “endothelial dysfunction” into defined biological programs for biomarker selection and target discovery. Moreover, this review categorizes translational opportunities by the strength of human evidence. Near-term priorities include repurposed cardiometabolic drugs (e.g., sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1(GLP-1) receptor agonists) and circulating biomarkers for patient stratification or pharmacodynamic monitoring (e.g., growth differentiation factor 15 (GDF15), cell-free mitochondrial DNA (cf-mtDNA), endothelium-derived extracellular vesicles). In contrast, gene and cell therapies, as well as advanced delivery and regenerative platforms, remain at the preclinical stage and require stronger mechanistic validation, improved safety profiles, and scalable delivery systems before clinical evaluation. Thus, a key unmet need is for multicenter, mechanism-informed trials that integrate endothelial functional endpoints (e.g., flow-mediated dilation (FMD)/peripheral arterial tonometry (PAT) with mitochondrial-associated molecular readouts under harmonized protocols and standardized reference criteria to enhance reproducibility and cross-study comparability. Collectively, these insights establish mitochondrial–endothelial biology as an evidence-based entry point for precision vascular medicine in CMDs.

Mitochondria and endothelial cells engage in bidirectional crosstalk to maintain vascular tone, barrier integrity, and inflammatory quiescence. In cardiometabolic diseases (CMDs), metabolic overload and chronic inflammatory cues disrupt endothelial mitochondrial bioenergetics, dynamics, and quality-control mechanisms. As protective systems weaken, redox imbalance and impaired nitric oxide signaling—further exacerbated by barrier dysfunction—trigger endothelial activation and loss of homeostasis. Clinical translation has lagged largely because endothelial responses vary across vascular beds and microenvironments, and most clinical trials fail to align patient selection or endpoints with mitochondrial mechanisms. This review addresses a major translational gap: how mitochondrial stress programs map onto context-specific endothelial phenotypes in human CMDs, and how this mapping can inform the selection of actionable therapeutic strategies. Indeed, this review integrates single-cell and spatial multi-omics data to link mitochondrial stress and metabolic remodeling to specific anatomical niches, transforming the broad notion of “endothelial dysfunction” into defined biological programs for biomarker selection and target discovery. Moreover, this review categorizes translational opportunities by the strength of human evidence. Near-term priorities include repurposed cardiometabolic drugs (e.g., sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1(GLP-1) receptor agonists) and circulating biomarkers for patient stratification or pharmacodynamic monitoring (e.g., growth differentiation factor 15 (GDF15), cell-free mitochondrial DNA (cf-mtDNA), endothelium-derived extracellular vesicles). In contrast, gene and cell therapies, as well as advanced delivery and regenerative platforms, remain at the preclinical stage and require stronger mechanistic validation, improved safety profiles, and scalable delivery systems before clinical evaluation. Thus, a key unmet need is for multicenter, mechanism-informed trials that integrate endothelial functional endpoints (e.g., flow-mediated dilation (FMD)/peripheral arterial tonometry (PAT) with mitochondrial-associated molecular readouts under harmonized protocols and standardized reference criteria to enhance reproducibility and cross-study comparability. Collectively, these insights establish mitochondrial–endothelial biology as an evidence-based entry point for precision vascular medicine in CMDs.

Background: Few studies have explored the associations of body mass index and waist circumference with mortality risk in patients with depression. In particular, the emergence of the obesity paradox in recent years has drawn renewed attention to the potential relationship between overweight or obesity and mortality across different populations. Objective: This study aimed to investigate the associations of body mass index and waist circumference with mortality risk in individuals with depression. Methods: This was a population-based retrospective cohort study, and participants with a body mass index 2 (underweight) were excluded from the analyses. Weighted Cox regression analyses were conducted to examine the associations of body mass index and waist circumference with mortality risk in individuals with depression. Restricted cubic spline models were applied to evaluate the dose–response relationships of body mass index and waist circumference with mortality. Subgroup analyses were further conducted to explore variations in these associations across different populations, along with interaction tests to assess potential effect modification. Results: Weighted Cox regression analysis showed that compared with individuals with a normal body mass index, those who were overweight or obese had a 53% (Model 3: hazard ratio = 0.47, 95% confidence interval: 0.29–0.76, p = 0.002) and 58% (hazard ratio = 0.42, 95% confidence interval: 0.27–0.67, p < 0.001) lower risk of all-cause mortality, respectively. Similar results were observed when waist circumference was used as the covariate for analysis, with participants in the abdominal obesity group showing a significantly lower risk of mortality than those with normal waist circumference (Model 3: hazard ratio = 0.58, 95% confidence interval: 0.37–0.89, p = 0.01). In the combined analysis of body mass index and waist circumference, compared with participants with normal values for these parameters, those who were overweight and had a high waist circumference had a 55% lower mortality risk (hazard ratio = 0.45, 95% confidence interval: 0.26–0.80, p = 0.01). Similarly, participants who were obese and had a high waist circumference had a 59% lower mortality risk (hazard ratio = 0.41, 95% confidence interval: 0.25–0.69, p < 0.001). Conclusions: We found that both body mass index and waist circumference were inversely associated with mortality risk in individuals with depression, and this inverse association remained robust even when body mass index and waist circumference were jointly analyzed according to their respective categories.

Background: The neutrophil-to-lymphocyte ratio (NLR) has been linked as a marker of systemic inflammation to adverse outcomes in various metabolic diseases. However, the association of the NLR with mortality risk among patients with hyperlipidemia remains inconclusive. Thus, this research aimed to investigate whether the NLR is associated with mortality risk among individuals with hyperlipidemia and to examine how glycemic status influences this relationship. Methods: Weighted Cox regression, restricted cubic splines (RCS), and subgroup analyses were employed to evaluate the association between the NLR and mortality risk in patients with hyperlipidemia. Time-dependent receiver operating characteristic (ROC) analysis was conducted to assess the predictive accuracy for mortality risk. Results: In Model 3, individuals in the highest NLR quartile had a 40% higher risk of all-cause mortality (95% confidence interval (CI): 1.19–1.65; p for trend <0.001) and an 86% higher risk of cardiovascular mortality (95% CI: 1.28–2.68; p for trend <0.001) compared with those in the lowest quartile. Time-dependent ROC analysis confirmed the superior performance of the NLR in predicting cardiovascular mortality risk. A significant interaction between the NLR and diabetes mellitus (DM) was observed for both all-cause and cardiovascular mortality in the subgroup analyses. Given this finding, we further examined the association between the NLR and mortality, stratified by glycemic status. The results indicated that the association between the NLR and mortality was stronger among individuals with DM. Conclusions: An elevated NLR is closely associated with an increased risk of mortality among individuals with hyperlipidemia, and the presence of DM significantly strengthens this association.