Correlation between obesity and early vascular aging in middle-aged and young adult health check-up populations. / ä¸­é’å¹´å¥åº·ä½“æ£€äººç¾¤è‚¥èƒ–ä¸Žæ—©å‘è¡€ç®¡è€åŒ–çš„ç›¸å ³æ€§.

OBJECTIVES: The obesity rate among middle-aged and young adults in China is increasing annually, and the incidence of cardiovascular diseases is becoming more prevalent in younger populations. However, it has not yet been reported whether obesity is associated with early vascular aging (EVA). This study aims to explore the correlation between obesity and EVA in middle-aged and young adult health check-up populations, providing a reference for the prevention of cardiovascular diseases. METHODS: A total of 15 464 middle-aged and young adults aged 18-59 who completed brachial-ankle pulse wave velocity (baPWV) test in the Third Xiangya Hospital of Central South University from January to December 2020 were included. Among them, 1 965 individuals with normal blood pressure and no cardiovascular risk factors were selected as the healthy population. The baPWV thresholds for determining EVA in each age group for males and females were calculated based on the baPWV values of the healthy population. The number and percentage of individuals meeting the EVA criteria in the middle-aged and young adult health check-up populations were statistically analyzed by age and gender. The differences in obesity indicators [visceral adiposity index (VAI), body mass index (BMI), waist circumference (WC)] between the EVA and non-EVA groups for males and females were compared. Using EVA as the dependent variable, VAI, BMI, and WC were included as independent variables in a Logistic model to analyze the correlation between each obesity indicator and EVA before and after adjusting for other influencing factors. Furthermore, the correlation between each obesity indicator and EVA in each age group was analyzed. RESULTS: In the health check-up populations, the detection rate of EVA in different age groups was 1.65%-10.92% for males, and 1.16%-10.50% for females, the detection rate of EVA increased with age in both males and females. Except for the 40-<50 age group, the EVA detection rate was higher in males than in females in all other age groups. Regardless of gender, obesity indicators VAI, BMI, and WC were significantly higher in the EVA group than in the non-EVA group (all P<0.01). Before and after adjusting for other influencing factors, VAI and WC were both correlated with EVA (both P<0.05). BMI was a risk factor for EVA before adjusting for other influencing factors (P<0.01), but after adjustment, the correlation between BMI and EVA was not statistically significant (P=0.05). After adjusting for other influencing factors, the correlation between VAI and EVA was statistically significant in the 18-<40 and 50-<60 age groups (both P<0.05), while the correlation between BMI and WC with EVA was not statistically significant (both P>0.05). In the 40-<50 age group, the correlation between VAI and BMI with EVA was not statistically significant (both P>0.05), but the correlation between WC and EVA was statistically significant (P<0.01). CONCLUSIONS: VAI is closely related to the occurrence of EVA in middle-aged and young adults aged 18-<40 and 50-<60 years, while WC is closely related to the occurrence of EVA in those aged 40-<50 years.

Comparison and optimization of different CRISPR/Cas9 donor-adapting systems for gene editing.

Gene knock-in in mammalian cells usually uses homology-directed repair (HDR) mechanism to integrate exogenous DNA template into the target genome site. However, HDR efficiency is often low, and the co-localization of exogenous DNA template and target genome site is one of the key limiting factors. To improve the efficiency of HDR mediated by CRISPR/Cas9 system, our team and previous studies fused different adaptor proteins with SpCas9 protein and expressed them. By using their characteristics of binding to specific DNA sequences, many different CRISPR/SpCas9 donor adapter gene editing systems were constructed. In this study, we used them to knock-in eGFP gene at the 3'-end of the terminal exon of GAPDH and ACTB genes in HEK293T cells to facilitate a comparison and optimization of these systems. We utilized an optimized donor DNA template design method, validated the knock-in accuracy via PCR and Sanger sequencing, and assessed the efficiency using flow cytometry. The results showed that the fusion of yGal4BD, hGal4BD, hLacI, hTHAP11 as well as N57 and other adaptor proteins with the C-terminus of SpCas9 protein had no significant effect on its activity. At the GAPDH site, the donor adapter systems of SpCas9 fused with yGal4BD, hGal4BD, hLacI and hTHAP11 significantly improved the knock-in efficiency. At the ACTB site, SpCas9 fused with yGal4BD and hGal4BD significantly improved the knock-in efficiency. Furthermore, increasing the number of BS in the donor DNA template was beneficial to enhance the knock-in efficiency mediated by SpCas9-hTHAP11 system. In conclusion, this study compares and optimizes multiple CRISPR/Cas9 donor adapter gene editing systems, providing valuable insights for future gene editing applications.

Multi-omics analysis of kidney tissue metabolome and proteome reveals the protective effect of sheep milk against adenine-induced chronic kidney disease in mice.

Chronic kidney disease (CKD) is characterized by impaired renal function and is associated with inflammation, oxidative stress, and fibrosis. Sheep milk contains several bioactive molecules with protective effects against inflammation and oxidative stress. In the current study, we investigated the potential renoprotective effects of sheep milk and the associated mechanisms of action in an adenine-induced CKD murine model. Sheep milk delayed renal chronic inflammation (e.g., significant reduction in levels of inflammatory factors Vcam1, Icam1, Il6, and Tnfa), fibrosis (significant reduction in levels of fibrosis factors Col1a1, Fn1, and Tgfb), oxidative stress (significant increase in levels of antioxidants and decrease in oxidative markers), mineral disorders, and renal injury in adenine-treated mice (e.g. reduced levels of kidney injury markers NGAL and KIM-1). The combined proteomics and metabolomics analyses showed that sheep milk may affect the metabolic processes of several compounds, including proteins, lipids, minerals, and hormones in mice with adenine-induced chronic kidney disease. In addition, it may regulate the expression of fibrosis-related factors and inflammatory factors through the JAK1/STAT3/HIF-1α signaling pathway, thus exerting its renoprotective effects. Therefore, sheep milk may be beneficial for patients with CKD and should be evaluated in preclinical and clinical studies.

Serum levels of lipoprotein-associated phospholipase A2 are associated with coronary atherosclerotic plaque progression in diabetic and non-diabetic patients.

BACKGROUND: Lp-PLA2 is linked to cardiovascular diseases and poor outcomes, especially in diabetes, as it functions as a pro-inflammatory and oxidative mediator. OBJECTIVES: This research aimed to explore if there is a connection between the serum levels of Lp-PLA2 and the progression of coronary plaques (PP) in individuals with type 2 diabetes mellitus (T2DM) and those without the condition. MATERIALS AND METHODS: Serum Lp-PLA2 levels were measured in 137 T2DM patients with PP and 137 T2DM patients with no PP, and in 205 non-diabetic patients with PP and 205 non-diabetic patients with no PP. These individuals met the criteria for eligibility and underwent quantitative coronary angiography at the outset and again after about one year of follow-up. The attributes and parameters of the participants at the outset were recorded. RESULTS: Increased serum levels of Lp-PLA2 were closely associated with coronary artery PP, and also significantly correlated with change of MLD, change of diameter stenosis and change of cumulative coronary obstruction in both diabetic and non-diabetic groups, with higher correlation coefficients in diabetic patients as compared with non-diabetic patients. Moreover, multivariate logistic regression analysis showed that serum Lp-PLA2 level was an independent determinant of PP in both groups, with OR values more significant in diabetic patients than in non-diabetic patients. CONCLUSIONS: Levels of serum Lp-PLA2 show a significant association with the progression of coronary atherosclerotic plaque in patients with T2DM and those without, especially among individuals with diabetes.

Research progress and applications of epigenetic biomarkers in cancer.

Epigenetic changes are heritable changes in gene expression without changes in the nucleotide sequence of genes. Epigenetic changes play an important role in the development of cancer and in the process of malignancy metastasis. Previous studies have shown that abnormal epigenetic changes can be used as biomarkers for disease status and disease prediction. The reversibility and controllability of epigenetic modification changes also provide new strategies for early disease prevention and treatment. In addition, corresponding drug development has also reached the clinical stage. In this paper, we will discuss the recent progress and application status of tumor epigenetic biomarkers from three perspectives: DNA methylation, non-coding RNA, and histone modification, in order to provide new opportunities for additional tumor research and applications.

Remnant cholesterol trajectory and subclinical arteriosclerosis: a 10-year longitudinal study of Chinese adults.

We aimed to identify different trajectories of remnant cholesterol (RC) and investigate the association of RC trajectories with vascular endothelial function and atherosclerosis progression in a longitudinal cohort of the Chinese population. A total of 521 participants were included in the flow-mediated vasodilation (FMD) subcohort study, and 7775 participants were included in the brachial-ankle pulse wave velocity (baPWV) subcohort study. All participants had ≥ 3 medical examinations during the 10-year follow-up period. In the FMD subcohort study, three distinct RC trajectories were identified according to the RC range and changing pattern over time: "low" (57.58%), "moderate" (30.90%) and "high" (11.52%). The proportion of the three groups with vascular endothelial dysfunction (FMD < 7.0%) was 20.00%, 39.75% and 60.00% respectively. Taking the low group as a reference, participants in the moderate and high groups had over 1.88 and 2.94 times the odds of vascular endothelial dysfunction (P = 0.048). In the baPWV subcohort study, three distinct RC trajectories were also identified: "low" (54.29%), "moderate" (38.97%) and "high" (6.74%). The proportion of the three groups with atherosclerosis (baPWV > 1400 cm/s) was 38.79%, 51.26% and 59.01% respectively. Taking the low group as a reference, participants in the moderate and high groups had over 1.46 and 2.16 times the odds of atherosclerosis (P < 0.001). The findings indicated that distinct RC trajectories are significantly associated with vascular endothelial function and atherosclerosis. Regular monitoring to identify persistent increases in RC may be more helpful in identifying individuals with a high risk of cardiovascular disease.

A cost-effective, machine learning-driven approach for screening arterial functional aging in a large-scale Chinese population.

Introduction: An easily accessible and cost-free machine learning model based on prior probabilities of vascular aging enables an application to pinpoint high-risk populations before physical checks and optimize healthcare investment. Methods: A dataset containing questionnaire responses and physical measurement parameters from 77,134 adults was extracted from the electronic records of the Health Management Center at the Third Xiangya Hospital. The least absolute shrinkage and selection operator and recursive feature elimination-Lightweight Gradient Elevator were employed to select features from a pool of potential covariates. The participants were randomly divided into training (70%) and test cohorts (30%). Four machine learning algorithms were applied to build the screening models for elevated arterial stiffness (EAS), and the performance of models was evaluated by calculating the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy. Results: Fourteen easily accessible features were selected to construct the model, including "systolic blood pressure" (SBP), "age," "waist circumference," "history of hypertension," "sex," "exercise," "awareness of normal blood pressure," "eat fruit," "work intensity," "drink milk," "eat bean products," "smoking," "alcohol consumption," and "Irritableness." The extreme gradient boosting (XGBoost) model outperformed the other three models, achieving AUC values of 0.8722 and 0.8710 in the training and test sets, respectively. The most important five features are SBP, age, waist, history of hypertension, and sex. Conclusion: The XGBoost model ideally assesses the prior probability of the current EAS in the general population. The integration of the model into primary care facilities has the potential to lower medical expenses and enhance the management of arterial aging.

Simultaneous transapical transcatheter aortic and mitral valve replacement in patients with severe valve dysfunction: initial experience.

BACKGROUND: Simultaneous transcatheter mitral valve in valve (VIV) replacement and aortic valve replacement experience is limited. We report our initial experience with simultaneous transapical transcatheter aortic and mitral valve replacement in patients with severe valve dysfunction. METHODS: A total of 8 patients had simultaneous transcatheter heart valve implants for severe mitral bioprosthesis failure (VIV), with a second valve procedure that included native aortic regurgitation (n = 3) or degenerated bioprostheses in the aortic position (n = 5). All patients were treated with a self-expandable J-valve transcatheter valve, using the transapical approach. RESULTS: The mean age of the patients was 73.1 ± 6.2 years. The mean Society of Thoracic Surgeons score was 13.8 ± 6.3%. Device success was 100% according to Valve Academic Research Consortium-2 criteria. No other procedure-associated complications occurred, including left ventricular outflow tract obstruction and valve migration. The mean hospital lengths of stay after the procedure were 11.5 ± 8.0 days. No deaths occurred at 30 days. At a median follow-up period of 28.7 ± 22.3 months, no patients died. All patients were in New York Heart Association functional classes I-II. Echocardiographic parameters at follow-up showed a normofunctioning J valve in the mitral position and a mean max mitral flow velocity of 2.0 ± 0.5 m/s; the J valve in the aortic position was also normofunctioning, and the mean max aortic flow velocity was 2.3 ± 0.5 m/s. CONCLUSION: Simultaneous transapical transcatheter aortic and mitral valve replacement using the self-expandable J valve appears to be a feasible and effective alternative to redo surgery.

The effect of surgery started at different time point during the day on the clinical outcomes of mitral valve surgery.

Background: The clinical prognosis of mitral valve surgery at morning, afternoon, and evening is not yet clear. The aim of the study is to investigate the impact of different time periods of surgery in the morning, afternoon and evening on the short-term and long-term results of mitral valve surgery. Methods: From January 2018 to December 2020, 947 patients with mitral valve surgery in our department were selected. These patients were divided into 3 groups according to the starting time of surgery. Morning group (operation start time 8:00-10:30, n = 231), afternoon group (operation start time 12:00-14:30, n = 543), and evening group (operation start time 17:30-20:00, n = 173). The short-term and long-term results of the three groups were compared. Results: There were no significant difference in the long-term mortality, long-term risk of stroke and reoperation. And there were no significant difference in in-hospital outcomes, including mortality, stroke, cardiopulmonary bypass time, aortic cross clamp time, mitral valve repair convert to mitral valve replacement, number of aortic cross clamp ≥2 times, unplanned secondary surgery during hospitalization (including thoracotomy hemostasis, thoracotomy exploration, redo mitral valve surgery, and debridement), intra-aortic balloon pump, extracorporeal membrane oxygenation, continuous renal replacement therapy, mechanical ventilation time, and intensive care unit length of stay. Conclusion: There is no significant difference in the risk of short-term and long-term survival and adverse events after mitral valve surgery at different time periods in the morning, afternoon, and evening. Mitral valve surgery at night is safe.

Advances in Drug Therapy for Metastatic Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a notably poor prognosis. A large number of patients with PDAC develop metastases before they are diagnosed with metastatic pancreatic cancer (mPDAC). For mPDAC, FOLFIRINOX or gemcitabine plus nab-paclitaxel are the current first-line treatments. It is important to note, however, that many patients will fail chemotherapy because of drug resistance. ​Heterogeneous tumors and complex tumor microenvironments are key factors. As a result, clinical researchers are exploring a variety of alternative treatment modalities. Current understanding of the molecular signature and immune landscape of PDAC has motivated the emergence of different targeted and immune-based therapeutic approaches, some of which have shown promising results. The purpose of this review is to discuss the new targets and new drugs for mPDAC in terms of specific pathogenic factors such as metabolic vulnerability, DNA damage repair system, tumor microenvironment and immune system, in order to identify potential vulnerabilities in mPDAC patients and hopefully improve the prognosis of mPDAC patients.

[Screening of bioactive components endowing hawthorn with turbidity-eliminating and lipid-lowering functions and development of quality control method of hawthorn].

Hawthorn has the efficacy of eliminating turbidity and lowering the blood lipid level, and it is used for treating hyperlipidemia in clinic. However, the bioactive components of hawthorn are still unclear. In this study, the spectrum-effect relationship was employed to screen the bioactive components of hawthorn in the treatment of hyperlipidemia, and then the bioactive components screened out were verified in vivo. Furthermore, the quality control method for hawthorn was developed based on liquid chromatography-mass spectrometry(LC-MS). The hyperlipidemia model of rats was built, and different polar fractions of hawthorn extracts and their combinations were administrated by gavage. The effects of different hawthorn extract fractions on the total cholesterol(TC), triglycerides(TG), and low-density lipoprotein-cholesterol(LDL-C) in the serum of model rats were studied. The orthogonal projections to latent structures(OPLS) algorithm was used to establish the spectrum-effect relationship model between the 24 chemical components of hawthorn and the pharmacodynamic indexes, and the bioactive components were screened out and verified in vivo. Finally, 10 chemical components of hawthorn, including citric acid and quinic acid, were selected to establish the method for evaluating hawthorn quality based on LC-MS. The results showed that different polar fractions of hawthorn extracts and their combinations regulated the TG, TC, and LDL-C levels in the serum of the model rats. The bioactive components of hawthorn screened by the OPLS model were vitexin-4″-O-glucoside, vitexin-2″-O-rhamnoside, rutin, citric acid, malic acid, and quinic acid. The 10 chemical components of hawthorn, i.e., citric acid, quinic acid, rutin, gallic acid, vitexin-4″-O-glucoside, vitexin-2″-O-rhamnoside, malic acid, vanillic acid, neochlorogenic acid, and fumaric acid were determined, with the average content of 38, 11, 0.018, 0.009 5, 0.037, 0.017, 8.1, 0.009 5, 0.073, and 0.98 mg·g~(-1), respectively. This study provided a scientific basis for elucidating the material basis of hawthorn in treating hyperlipidemia and developed a content determination method for evaluating the quality of hawthorn.

Utilization of 3D printing technology in hepatopancreatobiliary surgery. / 3D打印技术在肝胆胰外科中的应用进展.

The technology of three-dimensional (3D) printing emerged in the late 1970s and has since undergone considerable development to find numerous applications in mechanical engineering, industrial design, and biomedicine. In biomedical science, several studies have initially found that 3D printing technology can play an important role in the treatment of diseases in hepatopancreatobiliary surgery. For example, 3D printing technology has been applied to create detailed anatomical models of disease organs for preoperative personalized surgical strategies, surgical simulation, intraoperative navigation, medical training, and patient education. Moreover, cancer models have been created using 3D printing technology for the research and selection of chemotherapy drugs. With the aim to clarify the development and application of 3D printing technology in hepatopancreatobiliary surgery, we introduce seven common types of 3D printing technology and review the status of research and application of 3D printing technology in the field of hepatopancreatobiliary surgery.

Association of High-Sensitivity C-Reactive Protein and Lipoprotein-Associated Phospholipase A2 with Metabolically Unhealthy Phenotype: A Cross Sectional Study.

Objective: Whether the combination of high-sensitivity C-reactive protein (hs-CRP) and Lipoprotein-associated Phospholipase A2 (Lp-PLA2) was an independent risk factor for metabolic unhealthy is unknown. This study aimed to evaluate the association between combining hs-CRP and Lp-PLA2 and metabolic unhealthy. Methods: A total of 3198 participants who underwent routine health check-up examinations. The participants completed inflammation indicators (hs-CRP and Lp-PLA2) examination and physical assessments. Four phenotypes were determined according to obesity and metabolic health status. Meanwhile, the participants were divided into four groups according to the level of hs-CRP and Lp-PLA2. The cross-sectional association between hs-CRP, Lp-PLA2 and metabolic unhealthy was tested by logistic regression analysis. Results: About 30.48%, 17.35%, 17.32% and 34.83% had MHNO, MUNO, MHO, and MUO, respectively. The combination of the hs-CRP and Lp-PLA2 levels was significantly correlated with metabolic unhealthy in non-obese subjects. However, in obese subjects, only hs-CRP level was significantly correlated with metabolic unhealthy. Conclusion: The hs-CRP and Lp-PLA2 together were significantly associated with metabolic unhealthy in non-obese subjects. hs-CRP level was significantly correlated with metabolic unhealthy in obese subjects.

Long-term PM2.5 exposure and early-onset diabetes: Does BMI link this risk?

OBJECTIVE: Limited studies investigated the association between high-level fine particulate matter (PM2.5) pollution and early-onset diabetes, leaving the possible metabolic mechanisms unclear. We assessed the association of cumulative PM2.5 exposure with diabetes, including early-onset, in high-pollution areas of China and explored whether metabolic factors mediated this association. METHODS: 124,204 participants (≥18 years) from 121 counties in Hunan province, China, were enrolled between 2005 and 2020, with follow-up until 2021. The ground-level air pollution concentrations at each participant's residence were calculated using a high-quality dataset in China. The independent association of PM2.5 with incident diabetes and early-onset diabetes was assessed by Cox proportional hazards models. Restricted cubic splines were utilized to establish the exposure-response relationships. The role of metabolism-related mediators was estimated by mediation analysis. RESULTS: During a median follow-up of 8.47 (IQR, 6.65-9.82) years, there were 3650 patients with new-onset diabetes. Each 1 µg/m3 increase in the level of cumulative PM2.5 exposure was positively related to an increased incidence of diabetes (HR 1.177, 95 % CI 1.172-1.181) among individuals in the PM2.5 > 50 µg/m3 group after adjusting for multiple variables. The relationship of the PM2.5 dose-response curve for diabetes was non-linear. Significant associations between PM2.5 exposure and early-onset diabetes risk were observed, with this risk showing an increase with the earlier age of early diabetes onset. Males, young individuals (≤45 years), and those with a lower body mass index (BMI <24 kg/m2) appeared to be more susceptible to diabetes. Moreover, change in BMI significantly mediated 31.06 % of the PM2.5-diabetes relationship. CONCLUSIONS: Long-term cumulative PM2.5 exposure increased the risk of early-onset diabetes, which is partially mediated by BMI. Sustained air pollution control measures, priority protection of vulnerable individuals, and effective management of BMI should be taken to reduce the burden of diabetes.

Scoring model based on cardiac CT and clinical factors to predict early good mitral valve repair in rheumatic mitral disease.

OBJECTIVE: We aimed to evaluate the mitral valve calcification and mitral structure detected by cardiac computed tomography (cardiac CT) and establish a scoring model based on cardiac CT and clinical factors to predict early good mitral valve repair (EGMR) and guide surgical strategy in rheumatic mitral disease (RMD). MATERIALS AND METHODS: This is a retrospective bi-center cohort study. Based on cardiac CT, mitral valve calcification and mitral structure in RMD were quantified and evaluated. The primary outcome was EGMR. A logical regression algorithm was applied to the scoring model. RESULTS: A total of 579 patients were enrolled in our study from January 1, 2019, to August 31, 2022. Of these, 443 had baseline cardiac CT scans of adequate quality. The calcification quality score, calcification and thinnest part of the anterior leaflet clean zone, and papillary muscle symmetry were the independent CT factors of EGMR. Coronary artery disease and pulmonary artery pressure were the independent clinical factors of EGMR. Based on the above six factors, a scoring model was established. Sensitivity = 95% and specificity = 95% were presented with a cutoff value of 0.85 and 0.30 respectively. The area under the receiver operating characteristic of external validation set was 0.84 (95% confidence interval [CI] 0.73-0.93). CONCLUSIONS: Mitral valve repair is recommended when the scoring model value > 0.85 and mitral valve replacement is prior when the scoring model value < 0.30. This model could assist in guiding surgical strategies for RMD. CLINICAL RELEVANCE STATEMENT: The model established in this study can serve as a reference indicator for surgical repair in rheumatic mitral valve disease. KEY POINTS: • Cardiac CT can reflect the mitral structure in detail, especially for valve calcification. • A model based on cardiac CT and clinical factors for predicting early good mitral valve repair was established. • The developed model can help cardiac surgeons formulate appropriate surgical strategies.

Association between dietary diversity, sedentary time outside of work and depressive symptoms among knowledge workers: a multi-center cross-sectional study.

BACKGROUND: Low-diversity diets and sedentary status are risk factors for depressive symptoms, while knowledge workers were ignored before. The purpose of this current study was to examine the relationship between dietary diversity, sedentary time spent outside of work, and depressive symptoms among knowledge workers. STUDY DESIGN AND METHODS: This was a multicenter and cross-sectional design that included 118,723 knowledge workers. Participants self-reported online between January 2018 and December 2020. Demographic information, the Dietary Diversity Scale, the Patient Health Questionnaire-9, dietary habits (which included eating three meals on time, midnight snacking, overeating, social engagement, coffee consumption, sugary drink consumption, smoking and alcohol use), sedentary time spent outside of work and physical activity were investigated. RESULTS: The relationships between demographic information, dietary habits and dietary diversity, and depressive symptoms were estimated. Compared with the first and second levels of dietary diversity, the third level of dietary diversity (OR: 0.91; 95% CI: 0.84-0.98) reduced the risk of depressive symptoms. Knowledge workers with different degrees of sedentary status (2-4 h (OR: 1.11; 95% CI: 1.07-1.14), 4-6 h (OR: 1.21; 95% CI: 1.17-1.26), and > 6 h (OR: 1.49; 95% CI: 1.43-1.56), presented a progressively higher risk of depressive symptoms. CONCLUSION: High amounts of sedentary time spent after work and low levels of dietary diversity are risk factors for depressive symptoms. In addition, an irregular diet and overeating are also major risk factors for knowledge workers.

Novel Local-Chiral Metamaterial: Effective Modulation of Amplitude & Phase for Wideband Polarization-Insensitive Absorption.

Metamaterial has received widespread research in the fields of electromagnetic stealth due to its characteristics of strong resonance and flexible designability. However, a lack of a comprehensive understanding of the internal physical mechanism still imposes certain limitations on broadband absorption designs. Hence, this work proposes a new strategy for the broadening of the working frequency band of metamaterial absorbers by constructing local-chiral features to regulate the amplitude and phase information. The absorber consists of staggered cut-wire metal patterns with lumped resistors placed at the center position determined by characteristic mode analysis. Combining the modal significance, equivalent circuit, surface current, electric field distribution, and symmetry model theory, the working mechanism for wideband absorption performance has been analyzed in detail. The experimental results are in good agreement with the simulation results; the absorption rate exceeds 82% in the frequency range of 4.5-11.7 GHz and surpasses about 90% in the frequency range of 4.7-10.8 GHz under transverse electric (TE) or transverse-magnetic (TM) polarizations. Compared to the case without chiral features, the proposed design can achieve a 28% increase in operating bandwidth. The proposed design method is applicable for the optimization of various typical dipole-type metamaterial absorbers and provides a novel strategy for future wideband metamaterial absorption.

The burden of cardiovascular disease attributable to high body mass index-an observational study.

AIM: This study aims to provide a timely and comprehensive estimate of the current burden and temporal trend of cardiovascular disease (CVD) attributable to high body mass index (HBMI). METHODS: We systematically assessed the current burden and temporal trend of CVD attributable to HBMI by calendar year, age, sex, region, nation, socioeconomic status, and specific CVD based on the most recent Global Burden of Disease Study (GBD) 2019. RESULTS: Globally, the numbers of CVD-related disability-adjusted life years (DALYs) and deaths attributable to HBMI has more than doubled from 1990 to 2019. Conversely, the age-standardized rates (ASRs) of CVD-related DALYs and deaths attributable to HBMI showed a slight downward trend, with estimated annual percentage change (EAPC) of -0.18 and -0.43, respectively. The ASRs of CVD-related DALYs and deaths attributable to HBMI were lower in low and high Socio-demographic Index (SDI) regions in 2019, but higher in middle and high-middle SDI regions. The ASRs of CVD-related DALYs and deaths attributable to HBMI showed a downward trend in the high SDI regions from 1990 to 2019, but showed an upward trend in the low and low-middle SDI regions. The leading causes of CVD burden attributable to HBMI were ischemic heart disease, stroke, hypertensive heart disease, and atrial fibrillation/flutter in 2019. CONCLUSION: The CVD burden attributable to HBMI remains a challenging global health concern. Policymakers in high and increasing burden regions can learn from some valuable experiences of low and decreasing burden regions and develop more targeted and specific strategies to prevent and reduce CVD burden attributable to HBMI.

Effects of physical activity on the levels of remnant cholesterol: A population-based study.

Physical activity (PA) has the potential to bring about favourable changes in plasma lipid profile. However, the relationship between PA and remnant cholesterol (RC) remains unclear. We aimed to study the link between PA and RC using the database of the 2007-2020 National Health and Nutrition Examination Survey (NHANES). PA was categorized based on Physical Activity Guidelines for Americans. A multivariate linear regression model was used to determine the correlations between PA and RC. The study involved a total of 18,396 participants and revealed that individuals whose PA met the guidelines by engaging in moderate-intensity PA at least 150 min per week had lower body mass index and showed decreased levels of triglyceride, TC, and haemoglobin A1c compared to those who were physically inactive, exercising <150 min per week. Participants whose intensity of PA meets PA guidelines had a lower level of RC than those who did not met PA guidelines (ß = -1.3, 95% confidence interval [CI]: -1.9 to -0.7, p < 0.001), even after adjusting for confounders. During subgroup analysis, we observed that race (pinteraction = 0.0089) emerged as a significant factor of interaction.

The repeated administration of rhIL-12 for 14 weeks in rhesus monkeys: A toxicity assessment.

Interleukin-12 (IL-12) is known to exert antitumor immune effects by promoting the activation and proliferation of T cells and NK cells within the immune system. However, clinical trials have observed systemic toxicity associated with the administration of IL-12. This has shelved development plans for its use as a cancer therapeutic drug. Therefore, it is critical that we perform a systematic evaluation of the toxicity and safety of repeated IL-12 administration. In this study, we conducted a comprehensive evaluation of the toxicity and safety of repeated rhIL-12 (recombinant human interleukin-12) administration in rhesus monkeys by assessing its effects on the immune system, organ function, and vital signs. Rhesus monkeys were subcutaneously injected with 0.5, 2.5, and 12.5 µg/kg of rhIL-12 for up to for 14 consecutive weeks. The low dose exhibited no signs of toxicity, whereas animals receiving higher doses displayed symptoms such as loose stools, reduced activity, anemia, and elevated liver function indicators (AST and TBIL). Following three administrations of 12.5 µg/kg, high dosing was adjusted to 7.5 µg/kg due to manifestations of symptoms like loose stools, decreased activity, and huddling in the cage. Furthermore, rhesus monkeys exhibited marked immunogenic responses to recombinant human interleukin-12 (rhIL-12). However, based on overall study findings, the No Observed Adverse Effect Level (NOAEL) for the subcutaneous injection of rhIL-12, when repeatedly administered for 3 months in rhesus monkeys, was considered to be 0.5 µg/kg. The Highest Non-Severely Toxic Dose (HNSTD) was considered to be 7.5 µg/kg.