Low-Density Lipoprotein Cholesterol, Type 2 Diabetes and Progression of Aortic Stenosis: The RED-CARPET Heart Valve Subgroup Cohort Study.

Background: Low-density lipoprotein cholesterol (LDL-C) and type 2 diabetes (T2DM) are both independent risk factors for aortic stenosis (AS). In AS patients, whether LDL-C or T2DM is associated with fast AS progression (FASP) and their interaction is unknown. This study aims to test the hypothesis that there is a heightened risk of FASP when elevated LDL-C coexists with T2DM. Methods: The Real-world Data of Cardiometabolic Protections (RED-CARPET) study enrolled participants with mild (peak aortic velocity = 2-3 m/s), moderate (3-4 m/s) and severe ( ≥ 4 m/s) AS between January 2015 and December 2020 at a single center. Participants were further stratified by baseline LDL-C joint T2DM, follow-up echocardiography was performed after 6 months, and the primary outcome was FASP, defined as the annual change in aortic peak velocity ( ≥ 0.3 m/s/year). Results: Among the 170 participants included, 45.3% had mild AS, 41.2% had moderate AS, and 13.5% had severe AS. The mean age was 66.84 ± 12.64 years, and 64.1% were women. During the follow-up period of 2.60 ± 1.43 years, 35 (20.6%) cases of FASP were identified. Using non-T2DM with LDL-C < 2.15 mmol/L as reference, FASP risk was 1.30 [odds ratio (OR), 95% CI (0.99-7.78, p = 0.167)] for non-T2DM with LDL-C 2.15-3.14 mmol/L, 1.60 [OR, 95% CI (1.17-3.29, p = 0.040)] for non-T2DM with LDL-C ≥ 3.14 mmol/L, 2.21 [OR, 95% CI (0.49-4.32, p = 0.527)] for T2DM with LDL-C < 2.15 mmol/L, 2.67 [OR, 95% CI (1.65-7.10, p = 0.004)] for T2DM with LDL-C 2.15-3.14 mmol/L, and 3.20 [OR, 95% CI (1.07-5.34, p = 0.022)] for T2DM with LDL-C ≥ 3.14 mmol/L. Conclusions: LDL-C joint T2DM was associated with FASP. This investigation suggests that fast progression of AS may develop if LDL-C is poorly managed in T2DM. Additional research is needed to validate this finding and explore the possible biological mechanism to improve the cardiometabolic management of T2DM and seek possible prevention for AS progression for this population. Clinical Trial Registration: ChiCTR2000039901 (https://www.chictr.org.cn).

Causal Association of Golgi Protein 73 With Coronary Artery Disease: Evidence from Proteomics and Mendelian Randomization.

Background: Identification of the unknown pathogenic factor driving atherosclerosis not only enhances the development of disease biomarkers but also facilitates the discovery of new therapeutic targets, thus contributing to the improved management of coronary artery disease (CAD). We aimed to identify causative protein biomarkers in CAD etiology based on proteomics and 2-sample Mendelian randomization (MR) design. Methods: Serum samples from 33 first-onset CAD patients and 31 non-CAD controls were collected and detected using protein array. Differentially expressed analyses were used to identify candidate proteins for causal inference. We used 2-sample MR to detect the causal associations between the candidate proteins and CAD. Network MR was performed to explore whether metabolic risk factors for CAD mediated the risk of identified protein. Vascular expression of candidate protein in situ was also detected. Results: Among the differentially expressed proteins identified utilizing proteomics, we found that circulating Golgi protein 73 (GP73) was causally associated with incident CAD and other atherosclerotic events sharing similar etiology. Network MR approach showed low-density lipoprotein cholesterol and glycated hemoglobin serve as mediators in the causal pathway, transmitting 42.1% and 8.7% effects from GP73 to CAD, respectively. Apart from the circulating form of GP73, both mouse model and human specimens imply that vascular GP73 expression was also upregulated in atherosclerotic lesions and concomitant with markers of macrophage and phenotypic switching of vascular smooth muscle cells (VSMCs). Conclusions: Our study supported GP73 as a biomarker and causative for CAD. GP73 may involve in CAD pathogenesis mainly via dyslipidemia and hyperglycemia, which may enrich the etiological information and suggest future research direction on CAD.

Physical activity and the risk of developing 8 age-related diseases: epidemiological and Mendelian randomization studies.

BACKGROUND: We aimed to characterize the associations between physical activity levels and the risk of developing age-related diseases in the Coronary Artery Risk Development in Young Adults (CARDIA) study and used Mendelian randomization (MR) to assess whether there are causal relationships between physical activity levels and the risk of developing 8 age-related diseases (coronary atherosclerosis, ischemic heart disease, angina, Alzheimer's disease, hypertension, type 2 diabetes, hyperlipidemia, and venous thromboembolism). METHODS: Based on the data available in the CARDIA, we obtained data related to five disease states: coronary heart disease, hypertension, diabetes, hyperlipidemia, and venous thromboembolism. Binary logistic regression analysis estimated the multivariable-adjusted associations between different physical activity statuses and diseases. For the MR study, we used summary-level data from a recently published genome-wide association study on physical activity (including vigorous physical activity and accelerometer-based physical activity) conducted with participants from the UK Biobank study. We selected the above 8 age-related diseases as our outcomes. RESULTS: In the CARDIA-based analysis, the risk of developing coronary heart disease [OR (95% CI): 0.562 (0.397-0.795)], hypertension [OR (95% CI): 0.703 (0.601-0.821)], diabetes [OR (95% CI): 0.783 (0.620-0.988)], and hyperlipidemia [OR (95% CI): 0.792 (0.662-0.949)] was negatively related to physical activity status when participants achieved the physical activity target. Our MR results support a negative causal association between genetically determined vigorous physical activity levels and the risk of developing 3 age-related diseases, namely, angina, hypertension and type 2 diabetes. Moreover, our results also support a negative causal association between genetically determined accelerometer-based physical activity levels and the risk of developing angina. CONCLUSIONS: Promotion of physical activity is likely to prevent specific age-related diseases.

Healthy lifestyles ameliorate an increased risk of periodontitis associated with polycyclic aromatic hydrocarbons.

The risk of chronic inflammatory diseases has been linked to exposure to polycyclic aromatic hydrocarbons (PAHs). However, limited data are available regarding their impact on periodontitis. This study aims to explore the association between PAHs and periodontitis while also evaluating the potential modifying effects of healthy lifestyles. We included 17,031 participants from the US National Health and Nutrition Examination Survey (NHANES, 2001-2004 and 2009-2014). A meta-analysis-based environment-wide association study (EWAS) was adopted to identify environmental chemicals for the mean probing pocket depth (PPD) and the mean attachment loss (AL). PAHs were further evaluated concerning the cross-sectional association with Mod/Sev periodontitis using multivariable logistic regression models. Moreover, healthy lifestyle scores were estimated to assess their modifying effect on the PAH-periodontitis association. EWAS analysis identified several urinary PAH metabolites as significant risk factors for the mean PPD and AL (false discovery rate <0.05, Q > 0.05). Periodontitis severity was positively associated with eight individual and total PAH concentrations. Stratifying the participants in terms of healthy lifestyle scores did not reveal any association in the healthy group. Moreover, the association weakened in never-smokers and individuals with sufficient physical activity and normal weight. PAH exposure was a risk factor for periodontitis. A healthier lifestyle was observed to offset the risk potentials of PAHs for periodontitis. Smoking cessation, physical activity, and weight loss might be recommended as a healthy lifestyle strategy for ameliorating PAH-related periodontitis.

A Porous Li-Al Alloy Anode toward High-Performance Sulfide-Based All-Solid-State Lithium Batteries.

Compared to lithium (Li) anode, the alloy/Li-alloy anodes show more compatible with sulfide solid electrolytes (SSEs), and are promising candidates for practical SSE-based all-solid-state Li batteries (ASSLBs). In this work, a porous Li-Al alloy (LiAl-p) anode is crafted using a straightforward mechanical pressing method. Various characterizations confirm the porous nature of such anode, as well as rich oxygen species on its surface. To the best knowledge, such LiAl-p anode demonstrates the best room temperature cell performance in comparison with reported Li and alloy/Li-alloy anodes in SSE-based ASSLBs. For example, the LiAl-p symmetric cells deliver a record critical current density of 6.0 mA cm-2 and an ultralong cycling of 5000 h; the LiAl-p|LiNi0.8Co0.1Mn0.1O2 full cells achieve a high areal capacity of 11.9 mAh cm-2 and excellent durability of 1800 cycles. Further in situ and ex situ experiments reveal that the porous structure can accommodate volume changes of LiAl-p and ensure its integrity during cycling; and moreover, a robust Li inorganics-rich solid electrolyte interphase can be formed originated from the reaction between SSE and surface oxygen species of LiAl-p. This study offers inspiration for designing high-performance alloy anodes by focusing on designing special architecture to alleviate volume change and constructing stable interphase.

Sulfur and Wavy-Stacking Boosted Superior Lithium Storage in 2D Covalent Organic Frameworks.

2D conjugated covalent organic frameworks (c-COFs) provide an attractive foundation as organic electrodes in energy storage devices, but their storage capability is long hindered by limited ion accessibility within densely π-π stacked interlayers. Herein, two kinds of 2D c-COFs based on dioxin and dithiine linkages are reported, which exhibit distinct in-plane configurations-fully planar and undulated layers. X-ray diffraction analysis reveals wavy square-planar networks in dithiine-bridged COF (COF-S), attributed to curved C─S─C bonds in the dithiine linkage, whereas dioxin-bridged COF (COF-O) features densely packed fully planar layers. Theoretical and experimental results elucidate that the undulated stacking within COF-S possesses an expanded layer distance of 3.8 Å and facilitates effective and rapid Li+ storage, yielding a superior specific capacity of 1305 mAh g-1 at 0.5 A g-1, surpassing that of COF-O (1180 mAh g-1 at 0.5 A g-1). COF-S also demonstrates an admirable cycle life with 80.4% capacity retention after 5000 cycles. As determined, self-expanded wavy-stacking geometry, S-enriched dithiine in COF-S enhances the accessibility and redox activity of Li storage, allowing each phthalocyanine core to store 12 Li+ compared to 8 Li+ in COF-O. These findings underscore the elements and stacking modes of 2D c-COFs, enabling tunable layer distance and modulation of accessible ions.

An atlas of the human liver diurnal transcriptome and its perturbation by hepatitis C virus infection.

Chronic liver disease and cancer are global health challenges. The role of the circadian clock as a regulator of liver physiology and disease is well established in rodents, however, the identity and epigenetic regulation of rhythmically expressed genes in human disease is less well studied. Here we unravel the rhythmic transcriptome and epigenome of human hepatocytes using male human liver chimeric mice. We identify a large number of rhythmically expressed protein coding genes in human hepatocytes of male chimeric mice, which includes key transcription factors, chromatin modifiers, and critical enzymes. We show that hepatitis C virus (HCV) infection, a major cause of liver disease and cancer, perturbs the transcriptome by altering the rhythmicity of the expression of more than 1000 genes, and affects the epigenome, leading to an activation of critical pathways mediating metabolic alterations, fibrosis, and cancer. HCV-perturbed rhythmic pathways remain dysregulated in patients with advanced liver disease. Collectively, these data support a role for virus-induced perturbation of the hepatic rhythmic transcriptome and pathways in cancer development and may provide opportunities for cancer prevention and biomarkers to predict HCC risk.

Enhanced Cardiomyocyte NLRP3 Inflammasome-Mediated Pyroptosis Promotes d-Galactose-Induced Cardiac Aging.

BACKGROUND: Cardiac aging represents an independent risk factor for aging-associated cardiovascular diseases. Although evidence suggests an association between NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome formation and numerous cardiovascular diseases, its role in cardiac aging remains largely unclear. METHODS AND RESULTS: The longevity of mice with wild-type and NLRP3 knockout (NLRP3-/-) genotypes was assessed, with or without d-galactose treatment. Cardiac function was evaluated using echocardiography, and cardiac histopathology was examined through hematoxylin and eosin and Masson's trichrome staining. Senescence-associated ß-galactosidase (SA-ß-gal) staining was employed to detect cardiac aging. Western blotting was used to assess aging-related proteins (p53, p21) and pyroptosis-related proteins. Additionally, dihydroethidium staining, lactate dehydrogenase release, and interleukin-1ß ELISA assays were performed, along with measurements of total superoxide dismutase and malondialdehyde levels. In vitro, H9c2 cells were exposed to d-galactose for 24 hours in the absence or presence of N-acetyl-l-cysteine (reactive oxygen species inhibitor), BAY-117082 (nuclear factor κ-light-chain enhancer of activated B cells inhibitor), MCC950 (NLRP3 inhibitor), and VX-765 (Caspase-1 inhibitor). Immunofluorescence staining was employed to detect p53, gasdermin D, and apoptosis-associated speck-like protein proteins. Intracellular reactive oxygen species levels were assessed using fluorescence microscopy and flow cytometry. Senescence-associated ß-galactosidase staining and Western blotting were also employed in vitro for the same purpose. The results showed that NLRP3 upregulation was implicated in aging and cardiovascular diseases. Inhibition of NLRP3 extended life span, mitigated the aging phenotype, improved cardiac function and blood pressure, ameliorated lipid metabolism abnormalities, inhibited pyroptosis in cardiomyocytes, and ultimately alleviated cardiac aging. In vitro, the inhibition of reactive oxygen species, nuclear factor κ-light-chain enhancer of activated B cells, NLRP3, or caspase-1 attenuated NLRP3 inflammasome-mediated pyroptosis. CONCLUSIONS: The reactive oxygen species/nuclear factor κ-light-chain enhancer of activated B cells/NLRP3 signaling pathway loop contributes to d-galactose-treated cardiomyocyte senescence and cardiac aging.

Long-term insulin resistance is associated with frailty, frailty progression, and cardiovascular disease.

BACKGROUND: Insulin resistance and diabetes are associated with an increased risk of frailty, and frailty is associated with cardiovascular disease and premature mortality. We aim to investigate the impact of long-term insulin resistance trajectories on future frailty and cardiovascular risk among young adults. METHODS: In total, 3168 participants with a 30-year follow-up period. The baseline period covered the first 15 years as the exposure period. Insulin resistance was determined using the homeostasis model assessment for insulin resistance (HOMA-IR), and three trajectories (low, moderate, and high) were constructed. The subsequent 15 years constituted the event accrual period. Frailty was assessed using a deficit accumulation mode, and cardiovascular outcomes were obtained from the 15-year event accrual period. RESULTS: The mean age of all 3168 participants was 41.0 (37.0-43.0) years, with 1750 (55.2%) being women. Participants in the high level of insulin resistance trajectory had an increased prevalence of frailty (OR: 1.55, 95% CI: 1.05-2.30, P = 0.028). Although no statistically significant associations were observed after full adjustment, single-factor analysis indicated association between the moderate and high trajectories and frailty progression. Additionally, participants with high level of insulin resistance trajectory were associated with an increased risk of cardiovascular disease, coronary heart disease, and stroke. A notable correlation between HOMA-IR trajectory and cardiovascular diseases was still discernible within the subgroup where the frailty index ≥0.12 (HR: 2.12, 95% CI: 1.17-3.83, P = 0.013) (P for interaction >0.05). CONCLUSIONS: Long-term high level of insulin resistance is associated with high prevalence of frailty, and an increased risk of cardiovascular events. Emphasizing the importance of early prevention and intervention for abnormal glucose metabolism in young adults to prevent frailty and cardiovascular disease.

Well-defined asymmetric nitrogen/carbon-coordinated single metal sites for carbon dioxide conversion.

Asymmetric nitrogen/carbon-coordinated single metal sites (M-NxC4-x) outperform symmetric M-N4 sites in carbon dioxide (CO2) electroreduction. However, the challenge of crafting well-defined M-NxC4-x sites complicates the understanding of their structure-catalytic performance relationship. In this study, we employ metallized N-confused tetraphenylporphyrin (M-NCTPP) to investigate CO2 conversion on M-N3C1 sites using both density functional theory and experimental methods. The optimal cobalt (Co)-N3C1 site (Co-NCTPP) achieves a current density of 500 mA cm-2 and a carbon monoxide Faraday efficiency exceeding 90 % at -1.25 V vs. the reversible hydrogen electrode, surpassing the performance of Co-N4 (Co-TPP). This research introduces a novel approach for designing and synthesizing high-activity heteroatom-anchored single metal sites, advancing fundamental understanding in the field.

Cardiac autonomic neuropathy modified the association between obesity and hypoglycemia in type 2 diabetes.

BACKGROUND: Previous studies have shown that increasing body mass index (BMI) was associated with decreased hypoglycemia in type 2 diabetes, but it remains uncertain whether this finding could be applied to patients with and without cardiac autonomic neuropathy (CAN). METHODS: The study included 7789 participants with type 2 diabetes from action to control cardiovascular risk in diabetes (ACCORD) trail. CAN was defined as SDNN < 8.2 ms and RMSSD < 8.0 ms. Obesity was defined as BMI ≥ 30 kg/m2. Outcomes were identified as severe hypoglycemia requiring any assistance (HAA) or requiring medical assistance (HMA). We assessed the association between obesity and severe hypoglycemia in type 2 diabetes with or without CAN using COX regression models adjusted for baseline characteristics. RESULTS: Over a median follow-up of 4.7 years, a total of 893 participants developed HAA and 584 participants developed HMA. Compared with non-obesity, obesity was associated with lower risk of severe hypoglycemia (HAA: hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.38-0.68, P < 0.001; HMA: HR 0.57, 95% CI 0.40-0.82, P = 0.002) in CAN present group, but not in CAN absent group (HAA: HR 0.98, 95% CI 0.83-1.16, P = 0.830; HMA: HR 0.97, 95% CI 0.79-1.19, P = 0.754). Similarly, increasing BMI was associated with reduced severe hypoglycemic events in participants with CAN, but not in participants without CAN. CONCLUSIONS: CAN modifies the association between obesity and hypoglycemia in type 2 diabetes. Type 2 diabetic individuals with CAN who are under weight control should pay attention to hypoglycemic events. TRIAL REGISTRY: http://www. CLINICALTRIALS: gov . Unique identifier: NCT00000620.

Elastic films of single-crystal two-dimensional covalent organic frameworks.

The properties of polycrystalline materials are often dominated by defects; two-dimensional (2D) crystals can even be divided and disrupted by a line defect1-3. However, 2D crystals are often required to be processed into films, which are inevitably polycrystalline and contain numerous grain boundaries, and therefore are brittle and fragile, hindering application in flexible electronics, optoelectronics and separation1-4. Moreover, similar to glass, wood and plastics, they suffer from trade-off effects between mechanical strength and toughness5,6. Here we report a method to produce highly strong, tough and elastic films of an emerging class of 2D crystals: 2D covalent organic frameworks (COFs) composed of single-crystal domains connected by an interwoven grain boundary on water surface using an aliphatic bi-amine as a sacrificial go-between. Films of two 2D COFs have been demonstrated, which show Young's moduli and breaking strengths of 56.7 ± 7.4 GPa and 73.4 ± 11.6 GPa, and 82.2 ± 9.1 N m-1 and 29.5 ± 7.2 N m-1, respectively. We predict that the sacrificial go-between guided synthesis method and the interwoven grain boundary will inspire grain boundary engineering of various polycrystalline materials, endowing them with new properties, enhancing their current applications and paving the way for new applications.

Effects of a competence-based approach for clerkship teaching under alternating clinical placements: An explanatory sequential mixed-methods research.

BACKGROUND: It is unclear whether alternating placements during clinical clerkship, without an explicit emphasis on clinical competencies, would bring about optimal educational outcomes. METHODS: This is an explanatory sequential mixed-methods research. We enrolled a convenience sample of 41 eight-year programme medical students in Sun Yat-sen University who received alternating placements during clerkship. The effects of competence-based approach (n = 21) versus traditional approach (n = 20) to clerkship teaching were compared. In the quantitative phase, course satisfaction was measured via an online survey and academic performance was determined through final scores on summative assessment. Then, in the qualitative phase, students were invited for semi-structured interviews about their learning experiences, and the transcripts were used for thematic analysis. RESULTS: Quantitative findings showed that students in the study group rated high course satisfaction and performed significantly better in their final scores compared with those in the control group. Qualitative findings from thematic analysis showed that students were relatively neutral about their preference on placement models, but clearly perceived, capitalised, and appreciated that their competencies were being cultivated by an instructor who was regarded as a positive role model. CONCLUSION: A competence-based approach to clerkship teaching resulted in better course satisfaction and academic performance, and was perceived, capitalised, and appreciated by students.

Simultaneously improving the pore structure and electron conductive network of the anode catalyst layer via SnO2 doping for proton exchange membrane water electrolysis.

Proton exchange membrane water electrolysis (PEMWE) is a promising technology for green hydrogen production. However, its large-scale commercial application is limited by its high precious metal loading, because low catalyst loading leads to reduced electron transport channels and decreased water transportation, etc. Herein, we study the electrode level strategy for reducing Ir loading by the optimization of the micro-structure of the anode catalyst layer via SnO2 doping. The pore structure and electron conductive network of the anode catalyst layer can be simultaneously improved by SnO2 doping, under appropriate conditions. Therefore, mass transfer polarization and ohmic polarization of the single cell are reduced. Moreover, the enhanced pore structure and improved electron conduction network collectively contribute to a decreased occurrence of charge transfer polarization. By this strategy, the performance of the single cell with the Ir loading of 1.5 mg cm-2 approaches the single cell with the higher Ir loading of 2.0 mg cm-2, which means that SnO2 doping saves about 25% loading of Ir. This paper provides a perspective at the electrode level to reduce the precious metal loading of the anode in PEMWE.

Optimizing Paclitaxel Oral Absorption and Bioavailability: TPGS Co-Coating via Supercritical Anti-Solvent Fluidized Bed Technology.

Supercritical anti-solvent fluidized bed (SAS-FB) coating technology has the advantages of reducing particle size, preventing high surface energy particle aggregation, improving the dissolution performance and bioavailability of insoluble drugs. The poor solubility of Biopharmaceutics Classification System (BCS) class IV drugs poses challenges in achieving optimal bioavailability. Numerous anti-cancer drugs including paclitaxel (PTX) belong to the BCS class IV, hindering their therapeutic efficacy. To address this concern, our study explored SAS-FB technology to coat PTX with D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) onto lactose. Under our optimized conditions, we achieved a PTX coating efficiency of 96.8%. Further characterization confirmed the crystalline state of PTX in the lactose surface coating by scanning electron microscopy and X-ray powder diffraction. Dissolution studies indicated that SAS-FB processed samples release over 95% of the drug within 1 min. Moreover, cell transmembrane transport assays demonstrated that SAS-FB processed PTX samples co-coated with TPGS had an enhanced PTX internalization into cells and a higher permeability coefficient compared to those without TPGS. Finally, compared to unprocessed PTX, SAS-FB (TPGS) and SAS-FB processed samples showed a 2.66- and 1.49-fold increase in oral bioavailability in vivo, respectively. Our study highlights the efficacy of SAS-FB co-coating for PTX and TPGS as a promising strategy to overcome bioavailability challenges inherent in BCS class IV drugs. Our approach holds broader implications for enhancing the performance of similarly classified medications.

Near-infrared Light-Induced Polymerizations: Mechanisms and Applications.

Photopolymerizations have garnered significant attention in polymer science due to their low polymerization temperature, high production efficiency, environmental friendliness, and spatial controllability. Despite these merits, the poor penetration and severe chemical damage from ultraviolet/visible (UV/Vis) light resources pose significant barriers to their success in conventional photopolymerizations. A recent breakthrough involving the utilization of near-infrared (NIR) laser with long wavelength has been exploited for diverse applications. With the combination of a NIR photosensitizer (PS), NIR-induced photopolymerizations have been successfully developed to alleviate the challenges in conventional methods. The enhancement of penetration depth and safety of NIR-induced photopolymerizations can contribute significantly to improving the efficiency of polymerization for production of intricate structures across various scales. In this concept, the typical types of PSs and polymerization mechanisms (PMs) within the NIR-induced photopolymerization systems have been classified in detail. Additionally, the applications of various polymers achieved by NIR-induced photopolymerizations are summarized. Furthermore, research directions and future challenges of this field are also discussed comprehensively.

Prognostic significance of aortic valve calcification in relation to coronary artery calcification for cardiovascular diseases.

AIMS: Both coronary artery calcification (CAC) and aortic valve calcification (AVC) are strongly associated with cardiovascular diseases (CVDs), but data about the prognostic significance of multiple cardiovascular calcifications are limited. We aim to investigate the interaction relationship between AVC and CAC for major events. METHODS AND RESULTS: We included 6695 participants from the Multi-Ethnic Study of Atherosclerosis at baseline and divided them into four groups: (i) no AVC or CAC; (ii) only AVC; (iii) only CAC; and (iv) with CAC and CAC. The Cox regression model and the Kaplan-Meier method were used to analyse CVD outcomes. We evaluated the interaction between AVC and CAC and their added predictive value based on the pooled cohort equations (PCEs). Subgroup analyses were also explored. Among 6695 participants (mean age 62.2 ± 10.2 years, 47.2% male), after follow-up, 943 cases (14.1%) of CVD and 1274 cases (19.0%) of all-cause death occurred. For participants with both AVC and CAC, the risk of CVD significantly increased [hazard ratio = 3.43 (2.69-4.37), P < 0.001], even higher than the sum of the ones with only AVC and only CAC. This trend remained the same for all-cause death and among subgroup analyses. The addictive interaction was statistically significant (P < 0.001). When AVC and CAC were added, the predictive value of PCEs increased. CONCLUSION: Our results indicated a synergistic interaction between valve calcification and coronary calcification in CVDs. Management for both AVC and CAC may bring health co-benefits in preventing poor outcomes.

We investigated the interaction relationship between aortic valve calcification (AVC) and coronary artery calcification (CAC) in 6695 participants with measurements for cardiovascular calcifications at baseline in the MESA study and the prognostic significance of AVC in relation to CAC.Our study found that CAC and AVC worked independently and synergistically to predict the risk of cardiovascular diseases and all-cause death.Our results have shown that patients suffering from both CAC and AVC are more likely to develop a poor prognosis; therefore, it is necessary to implement earlier and more positive intervention for cardiovascular disease prevention in this certain subpopulation.

Epitaxial Growth of Two-Dimensional Nonlayered AuCrS2 Materials via Au-Assisted Chemical Vapor Deposition.

Two-dimensional (2D) nonlayered transition metal dichalcogenide (TMD) materials are emergent platforms for various applications from catalysis to quantum devices. However, their limited availability and nonstraightforward synthesis methods hinder our understanding of these materials. Here, we present a novel technique for synthesizing 2D nonlayered AuCrS2 via Au-assisted chemical vapor deposition (CVD). Our detailed structural analysis reveals the layer-by-layer growth of [AuCrS2] units atop an initial CrS2 monolayer, with Au binding to the adjacent monolayer of CrS2, which is in stark contrast with the well-known metal intercalation mechanism in the synthesis of many other 2D nonlayered materials. Theoretical calculations further back the crucial role of Cr in increasing the mobility of Au species and strengthening the adsorption energy of Au on CrS2, thereby aiding the growth throughout the CVD process. Additionally, the resulting free-standing nanoporous AuCrS2 (NP-AuCrS2) exhibits exceptional electrocatalytic properties for the hydrogen evolution reaction.

Physical Activity and Weight Loss Among Adults With Type 2 Diabetes and Overweight or Obesity: A Post Hoc Analysis of the Look AHEAD Trial.

Importance: Prior findings from the Look AHEAD trial showed no significant reduction in the risk of cardiovascular events by lifestyle-induced weight loss among individuals with type 2 diabetes (T2D) and overweight or obesity. However, physical activity (PA) may modify the changes in cardiovascular risk associated with weight loss. Objective: To examine the joint association of weight loss and PA with the risk of adverse cardiovascular events in patients with T2D and overweight or obesity. Design, Setting, and Participants: This cohort study was a post hoc analysis of the Look AHEAD randomized clinical trial, which compared the cardiovascular effects of weight loss by intensive lifestyle intervention vs diabetes support and education among individuals with T2D and overweight or obesity. The study was conducted from June 2001 to September 2012, and participants were patients in the substudy of accelerometry-measured PA from 8 locations in the United States. Data were analyzed from June to August 2023. Exposures: Body weight change and accelerometer-derived PA volume across the first 4 years. Main Outcomes and Measures: The primary outcome was a composite cardiovascular outcome including cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for angina. Results: Among a total of 1229 participants (mean [SD] age, 60 [7] years; 533 male [43%]), 333 (27%) achieved and maintained weight loss for the first 4 years. Among the individuals who maintained weight loss, 105 (32%) maintained high PA volume. During a median of 9.5 years of follow-up, 198 participants (16.1%) experienced the primary outcome. Compared with those with low PA volume and no weight loss (105 [15.8%]), maintaining high PA volume and weight loss was associated with a 61% lower risk of the primary end point (hazard ratio, 0.39; 95% CI, 0.19-0.81; P = .01). However, there was no significant difference in the risk of the primary end point among those with either weight loss only or high PA only. The multiplicative interaction between weight loss and PA for the risk of cardiovascular events was also significant (P for interaction = .01). Conclusions and Relevance: In this cohort study, maintaining weight loss and higher PA volume was associated with a lower risk of the composite cardiovascular outcome. The findings suggest that the cardiovascular benefits of PA may vary and be enhanced by weight loss among individuals with T2D and overweight or obesity.