Background Long-term exposure to ambient fine particulate matter (PM_2.5) is a significant risk factor for cardiometabolic disorders. However, the mechanisms of its interaction with the endogenous circadian system remain incompletely understood. Objective To investigate whether chronic PM_2.5 exposure interferes with the rhythmic expression of the cardiac circadian clock, thereby disrupting downstream antioxidant defenses and metabolic homeostasis, and ultimately driving cardiometabolic dysfunction. Methods Seventy-two male C57BL/6 mice were randomly divided into a PM_2.5 exposure group (PM group) and a filtered air control group (FA group). Whole-body exposure was conducted for 8 weeks in a meteorological environmental animal exposure system. Samples were collected at six distinct zeitgeber time (ZT) points post-exposure. The 24 h ambulatory blood pressure and serum lipid profiles were monitored. Rhythm parameters were derived via cosinor analysis to compare differences in Midline statistic of rhythm (Mesor), amplitude, and phase between the two groups. The rhythmic expression of core circadian clock genes and antioxidant genes in the myocardium was detected by quantitative polymerase chain reaction (qPCR). Myocardial reactive oxygen species (ROS) levels and downstream pathway protein expression were analyzed by immunofluorescence and Western blot (WB), respectively. The expression changes of the clock gene retinoic acid receptor-related orphan receptor α (RORα) were assessed at both the mRNA and protein levels. Finally, Spearman correlation analysis was used to explore the relationships among myocardial RORα expression, lipid profiles, and oxidative stress indicators. Results Compared to the FA group, mice in the PM group exhibited a blunted circadian rhythm in blood pressure, characterized by sustained elevation throughout the day. Chronic PM_2.5 exposure showed a significant interaction with ZT on systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) (F-interaction=9.11, 5.70, and 6.02, respectively; P<0.05), as well as on serum triglycerides (TG), total cholesterol (T-CHO), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) (F-interaction=16.32, 11.12, 15.39, and 28.09, respectively; P<0.05). Cosinor analysis further revealed that the Mesor values of T-CHO, TG, and LDL-C were significantly increased (P<0.05), while that of HDL-C was significantly decreased in the PM group (P<0.05). The oscillation amplitudes of SBP, DBP, and MAP showed a decreasing trend, whereas those of TG and LDL-C were significantly increased (P<0.05). Furthermore, SBP, T-CHO, and HDL-C all exhibited a significant phase delay (P<0.05). Mechanistically, PM_2.5 exposure significantly suppressed the expression of the positive circadian regulator RORα in the myocardium, leading to disordered rhythmic expression of core clock genes (Bmal1, Clock, Per1/2, and Cry1/2). This exposure also inhibited the rhythmic expression of antioxidant genes (GPX1, SOD2, and CAT), resulting in increased ROS generation and elevated expression of calcium/calmodulin-dependent protein kinase II (CaMKII) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) proteins. Correlation analysis further revealed that myocardial RORα expression level was negatively correlated with T-CHO, TG, and LDL-C (r=−0.55, −0.63, and −0.51, respectively; P<0.001), and positively correlated with HDL-C (r=0.37, P=0.010), and antioxidant genes GPX1, SOD2, and CAT expression (r=0.34, 0.35, and 0.56, respectively; P < 0.001). Conclusion Chronic PM_2.5 exposure induces cardiometabolic dysfunction by suppressing myocardial RORα expression. This suppression disrupts the cardiac circadian clock and the diurnal balance of oxidative stress, triggering oxidative damage and elevating expression of CaMKII/NADPH pathway proteins. Collectively, these alterations precipitate the loss of cardiac metabolic rhythms and subsequent functional impairment.

Background Cooking oil fumes are closely related to immune response, and adipose tissue also plays an important role in immune regulation. At present, the biological effect and mechanism of inflammation of adipose tissue induced by oil fume exposure are not clear yet. Objective To investigate the inflammatory effect of different exposure duration of cooking fumes on adipose tissue in mice and explore the role of Nod-like receptor pyrin domain 3 (NLRP3)/cysteinyl aspartate specific proteinase 1 (Caspase 1)/interleukin (IL)-1β signaling pathway. Methods Forty 8-week-old female C57BL/6J mice were randomly divided into 3-day control group (CON₃ group), 7-day control group (CON₇ group), 3-day oil fume exposure group (COF₃ group), and 7-day oil fume exposure group (COF₇ group), with 10 mice in each group. The mice were exposed to oil fumes in a cooking oil fume formation and exposure equipment (COFFEE) for 20 min, followed by a 10-min pause, 1 h a day for consecutive 3 d or 7 d. General condition of mice was observed and body weight was measured every day. After exposure, blood was sampled from the eyeball. Serum levels of IL-6, IL-27, and IL-1β were detected by enzyme-linked immunosorbent assay (ELISA). The adipose tissue of mice was collected and observed after hematoxylin-eosin (HE) staining. The percentages of CD4⁺ and CD8⁺T cells in adipose tissue were detected by flow cytometry. Real-time quantitative PCR (RT-qPCR) was used to detect the expression levels of nuclear factor-κB (NF-κB), NLRP3, Caspase 1, and IL-1β in adipose tissue. Western blot was used to detect the expression levels of NLRP3, Caspase 1, and IL-1β in adipose. Results Compared with the corresponding control group, serum IL-6, IL-27, and IL-1β contents in the COF₃ group and the COF₇ group were significantly increased (P<0.05) except IL-6 in the COF₃ group, and the levels in the COF₇ group were significantly higher than those in the COF₃ group (P<0.05). Vacuolar lipid droplets in adipocytes decreased, cytoplasm shrank, and inflammatory cells infiltrated in the COF₇ group after HE staining. The flow cytometry results showed that the proportions of CD4⁺ and CD8⁺T cells in adipocytes of the COF₃ group and the COF₇ group were increased compared to the corresponding control group, with a significant increase in the COF₇ group (P<0.05), and the CD4⁺/CD8⁺T ratio also significantly increased progressively in the two groups (P<0.05). The results of RT-qPCR showed that compared with the corresponding control group, the mRNA expression levels of NF-κB, NLRP3, Caspase 1, and IL-1β in adipose tissue of mice in the COF₃ group and the COF₇ group were significantly increased (P<0.05, P<0.01). The mRNA expression levels of mice in each exposure group gradually increased over time. The Western blot results showed that compared with the corresponding control group, the protein expressions of NLRP3 and Caspase 1 in the COF₃ group were significantly increased (P<0.01), and the expression of IL-1β protein also increased but without statistical significance. The protein expressions of NLRP3, Caspase 1, and IL-1β in the COF₇ group were significantly higher than those in the CON₇ group (P<0.05, P<0.01). Conclusion Acute exposure to cooking oil fumes can induce significant inflammatory response in adipose tissue, and the effect gradually increases with the extension of exposure time. The mechanism of action may be related to the activation of NLRP3 inflammasome signaling pathway.

Background It is unclear if there is any combined effect of air pollutants and non-optimal temperature on metabolic syndrome, or any molecular mechanisms of related signaling pathways in the process, which requires urgent systematic research. Objective To observe the effects of combined exposure to PM_2.5 and non-optimal temperature on metabolic damage at gene and protein levels in mice, and elucidate the role of related signaling pathway in crucial organs. Methods A total of 60 six-week-old male C57BL/6J mice were randomly divided into six groups: a normal temperature-filter air group (T_N-FA), a normal temperature-concentrated PM_2.5 group (T_N-PM), a heat-filter air group (T_H-FA), a heat-concentrated PM_2.5 group (T_H-PM), a cold-filter air group (T_C-FA), and a cold-concentrated PM_2.5 group (T_C-PM). The Shanghai Meteorological and Environmental Animal Exposure System (Shanghai-METAS) was used to provide combined exposure settings of air types [concentrated PM_2.5 and filter air (FA)] and temperatures [normal (22°C), cold (4°C), and heat (30°C)] for 4 weeks. Skeletal muscle and white adipose tissue (WAT) of the mice were sampled at the end of exposure, and transcriptomics and Western blot (WB) assay were adopted to observe selected gene and protein expression levels in the samples respectively. Results The transcriptomics results indicated that the PM_2.5 exposure enhanced the number of differentially expressed genes. Specifically, 4820 genes were differentially expressed in the T_N-PM mice compared to the T_N-FA mice at normal temperature, and 1143 genes were differentially expressed in the Tc-PM mice compared to the Tc-FA mice in the cold environment. The phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway and the endoplasmic reticulum protein processing pathway were identified as the most significant pathways in metabolic injury resulting from combined exposure to PM_2.5 and non-optimal temperature exposure. The WB results showed that exposure to PM_2.5 in the normal temperature and the cold environments led to a significant increase in the expression of p-AKT in WAT (P<0.01, P<0.05) and a significant decrease in the expression of GLUT4 (P<0.05, P<0.01). In skeletal muscle, exposure to PM_2.5 led to a significant decrease in GLUT4 (P<0.05) in all environments, with a consistent trend of change as observed in WAT. Conclusion Cold/heat exposure might promote PM_2.5-induced metabolic disorder through suppression of the AKT/GLUT4 pathway, aggravating metabolic damage.

Objective:To investigate the global cognitive function and the function of specific cognitive domains in hypertensive patients at high risk of cardiovascular disease in China, and to explore the impact of cognition function on blood pressure control.Methods:This is a cross-sectional survey. Data were obtained from the ESPRIT study. Patients with a history of hypertension who participated in the ESPRIT study from September 2019 to July 2020 were selected. Mini-mental state examination (MMSE) was used to evaluate patients′ overall cognition and the function of each cognitive domain. According to the total MMSE score, patients were divided into the cognitive-intact group (MMSE total score=30 points), cognitive-declined group (MMSE total score<30 points, but did not reach the dementia screening threshold) and cognitive-impaired group (MMSE total score reached the dementia screening threshold). A multivariable logistic regression model was used to explore the effects of cognitive function and MMSE score on blood pressure control. The years of education were removed from the adjustment variables for sensitivity analysis. The interaction effect modeling of stratified variables and exposed variables was used for hierarchical analysis.Results:A total of 10 834 patients with hypertension at high risk of cardiovascular disease were enrolled, aged 65 (60, 69) years and 4 476 (41.3%) patients were female. There were 989 patients in cognitive-intact group, 8 676 patients in cognitive-declined group and 1 169 patients in cognitive-impaired group. The MMSE score of all included patients was (25.6±3.8) points. In the overall study population, 10.8% (1 169/10 834) of hypertensive patients had cognitive impairment, with an MMSE total score of (18.6±4.1) points. The cognitive domains with obvious impairment were recall memory (-80%), visuospatial function (-64%), attention and computation (-60%); 80.1% (8 676/10 834) of hypertensive patients did not meet the criteria for cognitive dysfunction, but had cognitive decline, and the cognitive domains with significant impairment were recall memory (-51%) and visuospatial structure (-23%). Multivariate logistic regression analysis showed that cognitive dysfunction ( OR=0.88, 95% CI: 0.72-1.08, P=0.212) and cognitive decline ( OR=0.96, 95% CI: 0.83-1.12, P=0.629) was not correlated with blood pressure control. MMSE total score and scores in each cognitive domain were not correlated with blood pressure control ( P>0.05). Sensitivity analysis showed that cognitive function was not related to blood pressure control (all P>0.05). Stratified analysis according to different frequency of medication showed that cognitive function and MMSE score were not correlated with blood pressure control ( P>0.05). Conclusion:One in ten hypertensive patients who were at high risk of cardiovascular disease have comorbid cognitive impairment. In patients with high risk of cardiovascular disease, the most affected cognitive domains were recall memory, visuospatial function, attention and calculation. Part of hypertensive patients have not reached the level of cognitive dysfunction, but have begun to show cognitive decline. Cognitive function is not an independent influencing factor on blood pressure control.

Objective::Home blood pressure monitoring (HBPM) is viewed as a facilitating factor in the initial diagnosis and long-term management of treated hypertension. However, evidence remains scarce about the effectiveness of HBPM use in the real world. This study aimed to examine the associations of HBPM use with blood pressure (BP) control and medication adherence.Methods::This prospective cohort study included hypertensive patients with high cardiovascular risk who were aged ≥50 years. At baseline, information about types of BP monitor, frequency of HBPM, perception of anti-hypertensive treatment, and measured office BP were collected. During the 1-year follow-up (visits at 1, 2, 3, 6, and 12 months), information on medication adherence was collected at each visit. The 2 major outcomes were BP control at baseline and medication adherence during the 1-year follow-up. A log-binomial regression model was used to examine the association between frequency of HBPM and outcomes, stratified by the perceptions of anti-hypertensive treatment.Results::A total of 5,363 hypertensive patients were included in the analysis. The age was (64.6 ± 7.2) years, and 41.2% (2,208) were female. Of the total patients, 85.9% (4,606) had a home BP monitor and 47.8% (2,564) had an incorrect perception of antihypertensive treatment. Overall, 24.2% (1,299) of patients monitored their BP daily, 37.6% (2,015) weekly, 17.3% (926) monthly, and 20.9% (1,123) less than monthly. At baseline, the systolic BP and diastolic BP were (146.6 ± 10.8) mmHg and (81.9 ± 10.6) mmHg, respectively, and 28.5% (1,527) of patients had their BP controlled. Regardless of whether the patients had correct or incorrect perceptions of anti-hypertensive treatment, there is no significant association between HBPM frequency and BP control at baseline. During the 1-year follow-up, 23.9% (1,280) of patients had non-adherence to medications at least once. In patients with an incorrect perception of anti-hypertensive treatment, those monitoring BP most frequently (daily) had the highest non-adherence rate (29.9%, 175/585). Compared with those monitoring their BP less than monthly, patients who monitored their BP daily were more likely not to adhere to anti-hypertensive medications (adjusted relative risk = 1.38, 95% confidence interval: 1.11-1.72, P = 0.004). Conclusions::HBPM performance among hypertensive patients in China is, in general, sub-optimal. No association was observed between using HBPM alone and hypertension control, indicating that the effects of HBPM could be conditional. Patients' misconceptions about anti-hypertensive treatment may impair the role of BP monitoring in achieving medication adherence. Fully incorporating the correct perception of hypertension into the management of hypertensive patients is needed.

Objective::Home blood pressure monitoring (HBPM) is viewed as a facilitating factor in the initial diagnosis and long-term management of treated hypertension. However, evidence remains scarce about the effectiveness of HBPM use in the real world. This study aimed to examine the associations of HBPM use with blood pressure (BP) control and medication adherence.Methods::This prospective cohort study included hypertensive patients with high cardiovascular risk who were aged ≥50 years. At baseline, information about types of BP monitor, frequency of HBPM, perception of anti-hypertensive treatment, and measured office BP were collected. During the 1-year follow-up (visits at 1, 2, 3, 6, and 12 months), information on medication adherence was collected at each visit. The 2 major outcomes were BP control at baseline and medication adherence during the 1-year follow-up. A log-binomial regression model was used to examine the association between frequency of HBPM and outcomes, stratified by the perceptions of anti-hypertensive treatment.Results::A total of 5,363 hypertensive patients were included in the analysis. The age was (64.6 ± 7.2) years, and 41.2% (2,208) were female. Of the total patients, 85.9% (4,606) had a home BP monitor and 47.8% (2,564) had an incorrect perception of antihypertensive treatment. Overall, 24.2% (1,299) of patients monitored their BP daily, 37.6% (2,015) weekly, 17.3% (926) monthly, and 20.9% (1,123) less than monthly. At baseline, the systolic BP and diastolic BP were (146.6 ± 10.8) mmHg and (81.9 ± 10.6) mmHg, respectively, and 28.5% (1,527) of patients had their BP controlled. Regardless of whether the patients had correct or incorrect perceptions of anti-hypertensive treatment, there is no significant association between HBPM frequency and BP control at baseline. During the 1-year follow-up, 23.9% (1,280) of patients had non-adherence to medications at least once. In patients with an incorrect perception of anti-hypertensive treatment, those monitoring BP most frequently (daily) had the highest non-adherence rate (29.9%, 175/585). Compared with those monitoring their BP less than monthly, patients who monitored their BP daily were more likely not to adhere to anti-hypertensive medications (adjusted relative risk = 1.38, 95% confidence interval: 1.11-1.72, P = 0.004). Conclusions::HBPM performance among hypertensive patients in China is, in general, sub-optimal. No association was observed between using HBPM alone and hypertension control, indicating that the effects of HBPM could be conditional. Patients' misconceptions about anti-hypertensive treatment may impair the role of BP monitoring in achieving medication adherence. Fully incorporating the correct perception of hypertension into the management of hypertensive patients is needed.