Cost-Effectiveness of a Workplace-Based Hypertension Management Program in Real-World Practice in the Kailuan Study.

BACKGROUND: In 2009, a workplace-based hypertension management program was launched among men with hypertension in the Kailuan study. This program involved monitoring blood pressure semimonthly, providing free antihypertensive medications, and offering personalized health consultations. However, the cost-effectiveness of this program remains unclear. METHODS AND RESULTS: This analysis included 12 240 participants, with 6120 in each of the management and control groups. Using a microsimulation model derived from 10-year follow-up data, we estimated costs, quality-adjusted life years (QALYs), life-years, and incremental cost-effectiveness ratios (ICERs) for workplace-based management compared with routine care in both the study period and over a lifetime. Analyses are conducted from the societal perspective. Over the 10-year follow-up, patients in the management group experienced an average gain of 0.06 QALYs with associated incremental costs of $633.17 (4366.85 RMB). Projecting over a lifetime, the management group was estimated to increase by 0.88 QALYs or 0.92 life-years compared with the control group, with an incremental cost of $1638.64 (11 301.37 RMB). This results in an incremental cost-effectiveness ratio of $1855.47 per QALY gained and $1780.27 per life-year gained, respectively, when comparing workplace-based management with routine care. In probabilistic sensitivity analyses, with a threshold willingness-to-pay of $30 765 per QALY (3 times 2019 gross domestic product per capita), the management group showed a 100% likelihood of being cost-effective in 10 000 samples. CONCLUSIONS: Workplace-based management, compared with routine care for Chinese men with hypertension, could be cost-effective both during the study period and over a lifetime, and might be considered in working populations in China and elsewhere.

High-Power-Density Rechargeable Hybrid Alkali/Acid Zn-Air Battery Performance Through Value-Added Conversion Charging.

Rechargeable Zn-air batteries (ZABs) are considered highly competitive technologies for meeting the energy demands of the next generation, whether for energy storage or portable power. However, their practical application is hindered by critical challenges such as low voltage, CO2 poisoning at the cathode, low power density, and poor charging efficiency Herein, a rechargeable hybrid alkali/acid Zn-air battery (h-RZAB) that effectively separates the discharge process in an acidic environment from the charging process in an alkaline environment, utilizing oxygen reduction reaction (ORR) and glycerol oxidation reaction (GOR) respectively is reported. Compared to previously reported ZABs, this proof-of-concept device demonstrates impressive performance, exhibiting a high power density of 562.7 mW cm-2 and a high operating voltage during discharging. Moreover, the battery requires a significantly reduced charging voltage due to the concurrent utilization of biomass-derived glycerol, resulting in practical and cost-effective advantages. The decoupled system offers great flexibility for intermittently generated renewable power sources and presents cost advantages over traditional ZABs. As a result, this technology holds significant promise in opening avenues for the future development of renewable energy-compatible electrochemical devices.

Association of Ultraprocessed Food Consumption with Risk of Cardiovascular Disease Among Individuals with Type 2 Diabetes: Findings from the UK Biobank.

SCOPE: Among patients with diabetes, who have modified nutritional behavior and a higher risk of cardiovascular disease (CVD), the influence of ultraprocessed foods (UPFs) on CVD remains unknown. The study aims to evaluate the association between UPF intake and the risk of CVD among individuals with type 2 diabetes (T2D) and further examine the potential biological pathways linking the association. METHODS AND RESULTS: This study includes 5405 participants with T2D who provided at least one 24-h dietary recall from the UK Biobank study. In the fully adjusted models, a 10% increase in the proportion of UPFs is associated with higher hazards of overall CVD (hazard ratio [HR]: 1.10; 95% confidence interval [CI]: 1.04, 1.15), coronary heart disease (HR: 1.10; 95% CI: 1.04, 1.16), heart failure (HR: 1.14; 95% CI: 1.05, 1.25), but not stroke (HR: 1.01; 95% CI: 0.90, 1.12). Cystatin C, high-density lipoprotein cholesterol (HDL-C), apolipoprotein A, C-reactive protein, and body mass index collectively explain 26.9% (12.8%, 48.5%) of the association between UPF intake and the risk of overall CVD. CONCLUSION: Higher UPF intakes are associated with increased hazards of CVD among individuals with T2D, and the association is partly mediated through worsening biomarkers of renal function, lipid metabolism, inflammation, and body weight.

Gut microbiota-derived secondary bile acids, bile acids receptor polymorphisms, and risk of cardiovascular disease in individuals with newly diagnosed type 2 diabetes: a cohort study.

BACKGROUND: Secondary bile acids (SBAs), the products of bacterial metabolism, are ligands of the nuclear farnesoid X receptor (FXR) and have been implicated in cardiovascular health. Diet can modulate gut microbiota composition and bile acid metabolism. OBJECTIVES: We aimed to examine the associations of circulating SBAs and their receptor polymorphisms with the risk of incident cardiovascular disease (CVD) among people with type 2 diabetes (T2D). METHODS: A total of 1234 participants with newly diagnosed T2D without CVD or cancer were included from the Dongfeng-Tongji Cohort study in China. Circulating SBAs and their conjugated forms were quantified using liquid chromatography-tandem mass spectrometry. Fifteen single-nucleotide polymorphisms in genes encoding bile acid receptors were genotyped. RESULTS: During a median follow-up of 5.7 y, 259 incident CVD cases were documented. After multivariable adjustment, higher levels of unconjugated SBAs [sum of deoxycholic acid (DCA), lithocholic acid, and ursodeoxycholic acid] and DCA were significantly associated with a higher risk of CVD among people with T2D, with hazard ratios (HRs) and 95% confidence intervals (CIs) of 1.62 (1.12, 2.35) and 1.46 (1.04, 2.06) comparing the extreme quartile of SBAs and DCA, respectively. Restricted cubic spline regression suggested a linear relationship of unconjugated SBAs and DCA with an elevated risk of CVD, and per standard deviation, an increment in natural log-transformed unconjugated SBAs and DCA was associated with an 18% (95% CI: 4%, 34%) and 16% (95% CI: 2%, 33%) higher risk of CVD, respectively. Moreover, genetic variants in FXR (rs56163822 TT compared with GG, and rs17030295 TT compared with CC) were significantly associated with a 121%-129% higher risk of CVD among individuals with T2D. CONCLUSIONS: A higher proportion of unconjugated SBAs, especially DCA, is linearly associated with a higher risk of CVD among people with newly diagnosed T2D. Our findings support the potential role of gut microbiota-derived SBAs in cardiovascular health in individuals with T2D.

Nonlinear relationship between high-density lipoprotein cholesterol and cardiovascular disease: an observational and Mendelian randomization analysis.

BACKGROUND: Clinical trials and Mendelian randomization (MR) studies reported null effects of high-density lipoprotein cholesterol (HDL-C) on risk of cardiovascular disease (CVD), which might have overlooked a nonlinear causal association. We aimed to investigate the dose-response relationship between circulating HDL-C concentrations and CVD in observational and MR frameworks. METHODS: We included 348,636 participants (52,919 CVD cases and 295,717 non-cases) of European ancestry with genetic data from the UK Biobank (UKB) and acquired genome-wide association summary data for HDL-C of Europeans from the Global Lipids Genetics Consortium (GLGC). Observational analyses were conducted in the UKB. Stratified MR analyses were conducted combing genetic data for CVD from UKB and lipids from GLGC. RESULTS: Observational analyses showed L-shaped associations of HDL-C with CVD, with no further risk reduction when HDL-C levels exceeded 70 mg/dL. Multivariable MR analyses across entire distribution of HDL-C found no association of HDL-C with CVD, after control of the pleiotropic effect on other lipids and unmeasured pleiotropism. However, in stratified MR analyses, significant inverse associations of HDL-C with CVD were observed in the stratum of participants with HDL-C ≤ 50 mg/dL (odds ratio per unit increase, 0.86; 95 % confidence interval, 0.79-0.94), while null associations were observed in any stratum above 50 mg/dL. CONCLUSIONS: Our data suggest a potentially causal inverse association of HDL-C at low levels with CVD risks. These findings advance our knowledge about the role of HDL as a potential target in CVD prevention and therapy.

Transbronchial cryoablation in peripheral lung parenchyma with a novel thin cryoprobe and initial clinical testing.

BACKGROUND: Transbronchial cryoablation shows potential as a local therapy for inoperable peripheral lung cancer. However, its clinical application for peripheral pulmonary lesions has not been reported yet. METHODS: An improved cryoprobe with an 8-mm-long, 1.9-mm-wide cryotip was used. Initially, the safety and effectiveness of this cryoprobe were assessed in an in vivo porcine model. Transbronchial cryoablation with 2 or 3 freeze-thaw cycles (10 min or 15 min in each freezing time) was performed in 18 pigs under CT monitoring. Radiological and pathological examinations were performed to evaluate the extent of cryoablation. Subsequently, nine patients with stage IA peripheral lung cancer or metastases underwent transbronchial cryoablation with this cryoprobe under the guidance of navigation bronchoscopy and cone-beam CT. Technical success, safety and outcomes were assessed. RESULTS: 36 cryoablation procedures were performed successfully without any major complications in the porcine model. The extent of cryoablation increased with freezing time and the number of freeze-thaw cycles, which peaked at 24 hours and then gradually decreased. Pathological results showed a change from massive haemorrhage at 24 hours to fibrous hyperplasia with chronic inflammation after 4 weeks. In the clinical trial, 10 cryoablations were performed on 9 tumours with a technical success rate of 100%. One mild treatment-related complication occurred. Of the nine tumours, seven achieved complete ablation, while two exhibited incomplete ablation and subsequent local progression at 6 months. CONCLUSION: Our initial experience indicated that transbronchial cryoablation was a safe and feasible procedure for non-surgical peripheral stage IA lung cancer or pulmonary metastases. TRIAL REGISTRATION NUMBER: ChiCTR2200061544.

Controllable Electrochemical Liberation of Hydrogen from Sodium Borohydride.

Sodium borohydride (NaBH4 ) has earned recognition as a promising hydrogen carrier, attributed to its exceptional hydrogen storage capacity, boasting a high theoretical storage capacity of 10.8 wt %. Nonetheless, the utilization of traditional pyrolysis and hydrolysis methods still presents a formidable challenge in achieving controlled hydrogen generation especially under ambient conditions. In this work, we report an innovative electrochemical strategy for production H2 by coupling NaBH4 electrooxidation reaction (BOR) at anode in alkaline media with hydrogen evolution reaction (HER) at cathode in acidic media. To implement this, we have developed a bifunctional electrocatalyst denoted as Pd-Mo2 C@CNTs, wherein Pd nanoparticles are grown in situ on Mo2 C embedded within N-doped carbon nanotubes. This electrocatalyst demonstrates exceptional performance in catalyzing both alkaline BOR and acidic HER. We have developed a hybrid acid/alkali cell, utilizing Pd/Mo2 C@CNTs as the anode and cathode electrocatalysts. This configuration showcases remarkable capabilities for self-sustained, precise, and uninterrupted indirect release of H2 stored in NaBH4 , even at high current densities of 100 mA cm-2 with a Faraday efficiency approaching 100 %. Additionally, this electrochemical device exhibits significant promise as a fuel cell, with the ability to deliver a maximum power density of 20 mW cm-2 .

Cone-Beam Computed Tomography-Guided Cryobiopsy Combined with Conventional Biopsy for Ground Glass Opacity-Predominant Pulmonary Nodules.

INTRODUCTION: Cryobiopsy (CB) using a 1.1-mm cryoprobe under fluoroscopic guidance is feasible and safe for diagnosis of ground glass opacity (GGO) lesions. However, the efficacy of CB combined with cone-beam CT (CBCT) for GGO-predominant pulmonary nodules remains elusive. METHODS: We retrospectively studied patients who underwent CB combined with conventional biopsy under CBCT guidance for GGO-predominant pulmonary nodules with a consolidation-to-tumour ratio <50.0%. RESULTS: A total of 32 patients with GGO-predominant pulmonary nodules were enrolled: 17 pure GGOs and 15 mixed GGOs. The mean lesion diameter was 15.81 ± 5.52 mm and the overall diagnostic yield was 71.9%. Seven lesions were diagnosed by CB alone, which increased the diagnostic outcomes by 21.9%. Diagnostic yields for CB, forceps biopsy (FB), brushing, and guide sheath flushing were 65.6%, 46.9%, 15.6%, and 14.3%, respectively. Univariate analysis revealed that positive computed tomography (CT) bronchus sign (p = 0.035), positive CBCT sign (p < 0.01), and CB-first biopsy sequence (p = 0.036) were significant predictive factors for higher diagnostic yield. Specimens obtained by CB had larger mean sample size (p < 0.01), lower blood cell area (p < 0.01), and fewer crush artefacts (p < 0.01) than specimens from FB. No severe bleeding or other complications occurred. CONCLUSION: CB using a 1.1-mm cryoprobe under CBCT guidance increased diagnostic yield for GGO-predominant pulmonary nodules based on conventional biopsy. Further, it provided larger and nearly intact samples compared with forceps.

Nuclear Magnetic Resonance-Based Metabolomics and Risk of CKD.

RATIONALE & OBJECTIVE: Chronic kidney disease (CKD) leads to lipid and metabolic abnormalities, but a comprehensive investigation of lipids, lipoprotein particles, and circulating metabolites associated with the risk of CKD has been lacking. We examined the associations of nuclear magnetic resonance (NMR)-based metabolomics data with CKD risk in the UK Biobank study. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: A total of 91,532 participants in the UK Biobank Study without CKD and not receiving lipid-lowering therapy. EXPOSURE: Levels of metabolites including lipid concentration and composition within 14 lipoprotein subclasses, as well as other metabolic biomarkers were quantified via NMR spectroscopy. OUTCOME: Incident CKD identified using ICD codes in any primary care data, hospital admission records, or death register records. ANALYTICAL APPROACH: Cox proportional hazards regression models were used to estimate hazard ratios and 95% confidence intervals. RESULTS: We identified 2,269 CKD cases over a median follow-up period of 13.1 years via linkage with the electronic health records. After adjusting for covariates and correcting for multiple testing, 90 of 142 biomarkers were significantly associated with incident CKD. In general, higher concentrations of very-low-density lipoprotein (VLDL) particles were associated with a higher risk of CKD whereas higher concentrations of high-density lipoprotein (HDL) particles were associated with a lower risk of CKD. Higher concentrations of cholesterol, phospholipids, and total lipids within VLDL were associated with a higher risk of CKD, whereas within HDL they were associated with a lower risk of CKD. Further, higher triglyceride levels within all lipoprotein subclasses, including all HDL particles, were associated with greater risk of CKD. We also identified that several amino acids, fatty acids, and inflammatory biomarkers were associated with risk of CKD. LIMITATIONS: Potential underreporting of CKD cases because of case identification via electronic health records. CONCLUSIONS: Our findings highlight multiple known and novel pathways linking circulating metabolites to the risk of CKD. PLAIN-LANGUAGE SUMMARY: The relationship between individual lipoprotein particle subclasses and lipid-related traits and risk of chronic kidney disease (CKD) in general population is unclear. Using data from 91,532 participants in the UK Biobank, we evaluated the associations of metabolites measured using nuclear magnetic resonance testing with the risk of CKD. We identified that 90 out of 142 lipid biomarkers were significantly associated with incident CKD. We found that very-low-density lipoproteins, high-density lipoproteins, the lipid concentration and composition within these lipoproteins, triglycerides within all the lipoprotein subclasses, fatty acids, amino acids, and inflammation biomarkers were associated with CKD risk. These findings advance our knowledge about mechanistic pathways that may contribute to the development of CKD.

Discovery of PRDM16-Mediated TRPA1 Induction as the Mechanism for Low Tubulo-Interstitial Fibrosis in Diabetic Kidney Disease.

The pathogenesis of Diabetic kidney disease(DKD) involves pathological changes in both tubulo-interstitium and the glomerulus. Surprisingly, tubulo-interstitial fibrosis (TIF), does not develop significantly until the late stage of DKD. Here, it is demonstrated that PR domain-containing 16 (PRDM16) is a key to the low level of TIF in DKD. In the experiments, PRDM16 is upregulated in high glucose-treated renal tubular cells, DKD mouse kidneys, and renal biopsy of human DKD patients via activation of NF-κB signal pathway. High glucose-induced expression of fibrotic proteins in renal tubular cells is suppressed by PRDM16. Mechanistically, PRDM16 bound to the promotor region of Transient receptor potential ankyrin 1 (TRPA1) to transactivate its expression and then suppressed MAPK (P38, ERK1/2) activation and downstream expression of TGF-ß1. Knockout of PRDM16 from kidney proximal tubules in mice blocked TRPA1 expression and enhanced MAPK activation, TGF-ß1 production, TIF development, and DKD progression, whereas knock-in of PRDM16 has opposite effects. In addition, overexpression of PRDM16 or its induction by formononetin ameliorated renal dysfunction and fibrosis in db/db diabetic mice. Finally, the above finding are detected in renal biopsies of DKD patients. Together, these results unveil PRDM16/TRPA1 as the mechanism responsible for the low level of TIF in the early stage of DKD by suppressing and TGF-ß1 expression.

DrasCLR: A self-supervised framework of learning disease-related and anatomy-specific representation for 3D lung CT images.

Large-scale volumetric medical images with annotation are rare, costly, and time prohibitive to acquire. Self-supervised learning (SSL) offers a promising pre-training and feature extraction solution for many downstream tasks, as it only uses unlabeled data. Recently, SSL methods based on instance discrimination have gained popularity in the medical imaging domain. However, SSL pre-trained encoders may use many clues in the image to discriminate an instance that are not necessarily disease-related. Moreover, pathological patterns are often subtle and heterogeneous, requiring the ability of the desired method to represent anatomy-specific features that are sensitive to abnormal changes in different body parts. In this work, we present a novel SSL framework, named DrasCLR, for 3D lung CT images to overcome these challenges. We propose two domain-specific contrastive learning strategies: one aims to capture subtle disease patterns inside a local anatomical region, and the other aims to represent severe disease patterns that span larger regions. We formulate the encoder using conditional hyper-parameterized network, in which the parameters are dependant on the anatomical location, to extract anatomically sensitive features. Extensive experiments on large-scale datasets of lung CT scans show that our method improves the performance of many downstream prediction and segmentation tasks. The patient-level representation improves the performance of the patient survival prediction task. We show how our method can detect emphysema subtypes via dense prediction. We demonstrate that fine-tuning the pre-trained model can significantly reduce annotation efforts without sacrificing emphysema detection accuracy. Our ablation study highlights the importance of incorporating anatomical context into the SSL framework. Our codes are available at https://github.com/batmanlab/DrasCLR.

Global Burden of Ischemic Heart Disease in Adolescents and Young Adults, 1990-2019.

INTRODUCTION: Few studies have evaluated the global burden of ischemic heart disease (IHD) in adolescents and young adults (AYAs). METHODS: Age-standardized rates (ASRs) of incidence (ASIR), mortality (ASMR) and Disability-Adjusted Life Years (DALYs) (ASDR) were used to describe the burden of IHD in AYAs. Estimated Annual Percentage Changes (EAPCs) of ASRs were used to describe the trend from 1990 to 2019. Risk factors were calculated by population attributable fractions (PAFs). Analyses were conducted in 2023. RESULTS: In 2019, the ASIR, ASMR, and ASDR of IHD in AYAs were 26.81 (95% uncertainty interval [UI]: 20.36-34.54) per 100,000, 7.15 (95% UI: 6.56-7.87) per 100,000 and 409.51 (95% UI: 376.57-449.59) per 100,000. The ASIR and ASMR were higher among men than among women. From 1990 to 2019, the ASIR increased (EAPC=0.18%, 95% CI 0.14%-0.22%), while the ASMR (EAPC=-0.39%, -0.50% to -0.27%) and ASDR (EAPC=-0.40%, -0.52% to -0.29%) decreased. The largest increase in ASIR was observed in countries with a middle sociodemographic index (SDI) (EAPC=0.56%, 0.51%-0.60%). Globally, the proportional contribution of risk factors for DALY varied across regions, with the highest proportions of high low-density lipoprotein cholesterol in high SDI regions (PAF=74.26%) and high-middle (PAF=71.30%) and the highest proportions of air pollution in low (PAF=41.79%) and low-middle SDI regions (PAF=40.90%). CONCLUSIONS: The burden of IHD in AYAs remains high globally, and varies by age, sex, (male/female), region, and country. Targeted measures are needed to address the rising burden of IHD in AYAs, focusing on prevention, early diagnosis, and reduction in disparities.

Associations of socioeconomic status and healthy lifestyle with incident early-onset and late-onset dementia: a prospective cohort study.

BACKGROUND: Modifiable risk factor estimates are sparse for early-onset dementia incidence. This study aimed to estimate and compare the risk factor profiles of early-onset dementia and late-onset dementia, and to explore the complex relationships between socioeconomic status, lifestyles, and early-onset dementia risk. METHODS: In this prospective cohort study, we used data from the UK Biobank for analysis of early-onset dementia and late-onset dementia. For early-onset dementia analyses, data were collected on those aged younger than 60 years without prevalent dementia at baseline. For late-onset dementia analyses, data were collected on those aged 65 years or older at the end of follow-up. Participants with missing information on socioeconomic factors were excluded. Two models were used to test associations between early-onset dementia incidence and socioeconomic status. The first model tested associations between socioeconomic status and early-onset and late-onset dementia incidence, adjusting for covariates. Participant socioeconomic status was defined using education level, income, and employment status via latent class analysis. The second model additionally included a healthy lifestyle score, which was constructed using data on smoking, alcohol consumption, physical activity, and the Healthy Diet Index. Incident early-onset dementia was defined as a dementia case diagnosed before 65 years of age. Multivariable-adjusted Cox proportional hazard regression models were used to estimate the hazard ratio (HR) for risk of dementia. We used multivariable-adjusted Cox proportional-hazard regression models to estimate the HR for risk of both early-onset dementia and late-onset dementia. FINDINGS: Between 2007 and 2010, 257 345 individuals were included in the analysis of early-onset dementia, and 294 133 older individuals were included in the analysis of late-onset dementia. During a mean follow-up of 11·9-12·5 years, 502 early-onset dementia cases and 5768 late-onset dementia cases were documented. Risk factor profiles were typically dissimilar between early-onset dementia and late-onset dementia. For instance, the age and sex adjusted HR for low socioeconomic status (vs high) was 4·40 (95% CI 3·43-5·65) for early-onset dementia and 1·90 (1·74-2·07) for late-onset dementia, yielding a ratio of HRs of 2·32 (1·78-3·02). After adjusting for various risk factors, participants with low socioeconomic status (vs high) had increased risk for early-onset dementia (3·38, 2·61-4·37), and overall lifestyle mediated 3·2% (1·8-5·7) of the association. Individuals with both low socioeconomic status and unhealthy lifestyles had a higher risk of early-onset dementia (5·40, 3·66-7·97). No significant interaction was observed between lifestyle and socioeconomic status. The association between socioeconomic status and early-onset dementia seemed to be more pronounced in individuals with type 2 diabetes (HR 11·21, 95% CI 2·70-46·57). INTERPRETATION: Early-onset dementia and late-onset dementia might have different risk factor profiles; although risk factors were similar, the magnitude of associations between risk factors and dementia incidence was greater for early-onset dementia. Only a small proportion of the socioeconomic inequity in dementia risk was mediated by healthy lifestyles, which indicates that measures other than healthy lifestyle promotion to improve social determinants of health are warranted. FUNDING: The National Key Research and Development Program of China, the National Natural Science Foundation of China, the Hubei Province Science Fund for Distinguished Young Scholars, and the Fundamental Research Funds for the Central Universities.

Combined exposure to multiple air pollutants and incident ischemic heart disease in individuals with and without type 2 diabetes: A cohort study from the UK Biobank.

BACKGROUND: Air pollution and type 2 diabetes (T2D) are both associated with an increased risk of ischemic heart disease (IHD). Little is known about the combined effects of multiple air pollutants on IHD risk, especially among individuals with T2D. We sought to assess the association of combined exposure to multiple air pollutants with incident IHD and examine the modification effect of T2D. METHODS: This study included 388780 individuals (20036 individuals with T2D) free of cardiovascular disease and cancer from the UK Biobank. The combined exposure to multiple air pollutants, including particulate matter (PM) with diameters ≤ 2.5 µm (PM2.5), PM with diameters between 2.5 and 10 µm (PMcoarse), PM with diameters ≤ 10 µm (PM10), nitrogen dioxide (NO2), and nitrogen dioxides (NOx), was assessed by creating a weighted air pollution score (APS), with a higher APS representing a higher level of air pollution exposure. Hazard ratios (HR) and 95 % confidence intervals (CI) for incident IHD were assessed by multivariable-adjusted Cox proportional hazard models. RESULTS: During a median of 12.9 years of follow-up, 27333 incident IHD cases were observed. Compared with the lowest tertile of the APS, the multivariable-adjusted HR (95 % CI) of IHD risk for the highest tertile was 1.13 (1.03-1.23) among individuals with T2D, while the HR was 1.06 (1.03-1.10) among individuals without T2D. Additionally, the associations between APS and IHD incidence showed a linear relationship among individuals with T2D (nonlinearity: P = 0.37), whereas a non-linear relationship was observed among individuals without T2D (nonlinearity: P = 0.02). For the joint analysis, individuals in the highest tertile of APS and with T2D had a 54 % higher risk of IHD compared to individuals in the lowest tertile of APS and without T2D, with a significant additive interaction (Pinteraction < 0.01). The proportion of relative excess risk was 17 % due to the interaction in categorical analyses. CONCLUSIONS: The combined exposure to multiple air pollutants has been associated with an elevated risk of incident IHD, and the association is more pronounced among individuals with T2D.

Associations of lipoprotein subclasses with risk of all-cause and cardiovascular disease mortality in individuals with type 2 diabetes: A prospective cohort study.

AIM: Although lipoproteins are well-established risk factors for cardiovascular disease (CVD) mortality, conventional measurements failed to identify lipoprotein particle sizes. This study aimed to investigate associations of lipoprotein subclasses categorized by particle sizes with risk of all-cause and CVD mortality in individuals with type 2 diabetes. METHODS: This study included 6575 individuals with type 2 diabetes from the UK Biobank. Concentrations of very low-, low-, intermediate- and high-density lipoprotein [very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), intermediate-density lipoprotein and high-density lipoprotein (HDL)] particles in 14 subclasses and lipid constituents within each subclass were measured by quantitative nuclear magnetic resonance. Multivariable-adjusted Cox proportional-hazard regression models were used to estimate the hazard ratio (HR) for per standard deviation increment of log-transformed lipoprotein subclasses with risk of mortality. All p-values were adjusted by the false discovery rate method. RESULTS: During a median follow-up of 11.4 years, 943 deaths were documented, including 310 CVD deaths. Small HDL particles were inversely associated with CVD mortality, with HR (95% CI) of 0.78 (0.69, 0.87), whereas very large and large HDL particles were positively associated with CVD mortality with HR (95% CI) of 1.28 (1.12, 1.45) and 1.19 (1.05, 1.35), respectively. A similar pattern was observed for all-cause mortality [small HDL particle (HR, 95% CI): 0.79, 0.74-0.85; large HDL particle: 1.15, 1.07-1.24; very large HDL particle: 1.26, 1.17-1.36]. For VLDL and LDL, very small VLDL particle was positively, while medium LDL particle was inversely associated with all-cause mortality, but not associated with CVD mortality. The pattern of association with all-cause and CVD mortality for cholesterol and triglyceride within lipoprotein particles was similar to those for lipoprotein particles themselves. CONCLUSIONS: The associations between lipoprotein particles, particularly HDL particles, with all-cause and CVD mortality among patients with type 2 diabetes were significantly varied by particle sizes, highlighting the importance of particle size as a lipoprotein metric in mortality risk discrimination.

Associations of Clinical Risk Factors and Novel Biomarkers With Age at Onset of Type 2 Diabetes.

CONTEXT: Younger onset of type 2 diabetes (T2D) was associated with higher risks of vascular complications and mortality. OBJECTIVE: To prospectively assess risk profiles for incident T2D stratified by age at onset. METHODS: A total of 471 269 participants free of T2D at baseline were included from the UK Biobank. Approximately 70 clinical, lipid, lipoprotein, inflammatory, and metabolic markers, and genetic risk scores (GRSs) were analyzed. Stratified Cox proportional-hazards regression models were used to estimate hazard ratios (HRs) for T2D with age of diagnosis divided into 4 groups (≤50.0, 50.1-60.0, 60.1-70.0, and >70.0 years). RESULTS: During 11 years of follow-up, 15 805 incident T2D were identified. Among clinical risk factors, obesity had the highest HR at any age, ranging from 13.16 (95% CI, 9.67-17.91) for 50.0 years and younger to 4.13 (3.78-4.51) for older than 70.0 years. Other risks associated with T2D onset at age 50.0 years and younger included dyslipidemia (3.50, 2.91-4.20), hypertension (3.21, 2.71-3.80), cardiovascular disease (2.87, 2.13-3.87), parental history of diabetes (2.42, 2.04-2.86), education lower than college (1.89, 1.57-2.27), physical inactivity (1.73, 1.43-2.10), smoking (1.38, 1.13-1.68), several lipoprotein particles, inflammatory markers, liver enzymes, fatty acids, amino acids, as well as GRS. Associations of most risk factors and biomarkers were markedly attenuated with increasing age at onset (P interaction <.05), and some were not significant for onset at age older than 70.0 years, such as smoking, systolic blood pressure, and apolipoprotein B. CONCLUSION: Most risk factors or biomarkers had stronger relative risks for T2D at younger ages, which emphasizes the necessity of promoting primary prevention among younger individuals. Moreover, obesity should be prioritized.

Covalent organic framework-derived fluorine, nitrogen dual-doped carbon as metal-free bifunctional oxygen electrocatalysts.

The construction of heteroatom-doped metal-free carbon catalysts with bifunctional catalytic activity for oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) is highly desired for Zn-air batteries, but remains a great challenge owing to the sluggish kinetics of OER and ORR. Herein, a self-sacrificing template engineering strategy was employed to fabricate fluorine (F), nitrogen (N) co-doped porous carbon (F-NPC) catalyst by direct pyrolysis of F, N containing covalent organic framework (F-COF). The predesigned F and N elements were integrated into the skeletons of COF precursor, thus achieving uniformly distributed heteroatom active sites. The introduction of F is beneficial for the formation of edge-defects, contributing to the enhancement of the electrocatalytic activity. Attributing to the porous feature, abundant defect sites induced by F doping, as well as the strong synergistic effect between N and F atoms to afford a high intrinsic catalytic activity, the resulting F-NPC catalyst exhibits excellent bifunctional catalytic activities for both ORR and OER in alkaline mediums. Furthermore, the assembled Zn-air battery with F-NPC catalyst shows a high peak power density of 206.3 mW cm-2 and great stability, surpassing the commercial Pt/C + RuO2 catalysts.

Deep Learning Integration of Chest Computed Tomography Imaging and Gene Expression Identifies Novel Aspects of COPD.

Rationale: Chronic obstructive pulmonary disease (COPD) is characterized by pathologic changes in the airways, lung parenchyma, and persistent inflammation, but the links between lung structural changes and blood transcriptome patterns have not been fully described. Objections: The objective of this study was to identify novel relationships between lung structural changes measured by chest computed tomography (CT) and blood transcriptome patterns measured by blood RNA sequencing (RNA-seq). Methods: CT scan images and blood RNA-seq gene expression from 1223 participants in the COPD Genetic Epidemiology (COPDGene®) study were jointly analyzed using deep learning to identify shared aspects of inflammation and lung structural changes that we labeled image-expression axes (IEAs). We related IEAs to COPD-related measurements and prospective health outcomes through regression and Cox proportional hazards models and tested them for biological pathway enrichment. Results: We identified 2 distinct IEAs: IEAemph which captures an emphysema-predominant process with a strong positive correlation to CT emphysema and a negative correlation to forced expiratory volume in 1 second and body mass index (BMI); and IEAairway which captures an airway-predominant process with a positive correlation to BMI and airway wall thickness and a negative correlation to emphysema. Pathway enrichment analysis identified 29 and 13 pathways significantly associated with IEAemph and IEAairway, respectively (adjusted p<0.001). Conclusions: Integration of CT scans and blood RNA-seq data identified 2 IEAs that capture distinct inflammatory processes associated with emphysema and airway-predominant COPD.

Single-atom Iron Catalyst with Biomimetic Active Center to Accelerate Proton Spillover for Medical-level Electrosynthesis of H2 O2 Disinfectant.

Electrosynthesis of H2 O2 has great potential for directly converting O2 into disinfectant, yet it is still a big challenge to develop effective electrocatalysts for medical-level H2 O2 production. Herein, we report the design and fabrication of electrocatalysts with biomimetic active centers, consisting of single atomic iron asymmetrically coordinated with both nitrogen and sulfur, dispersed on hierarchically porous carbon (FeSA -NS/C). The newly-developed FeSA -NS/C catalyst exhibited a high catalytic activity and selectivity for oxygen reduction to produce H2 O2 at a high current of 100 mA cm-2 with a record high H2 O2 selectivity of 90 %. An accumulated H2 O2 concentration of 5.8 wt.% is obtained for the electrocatalysis process, which is sufficient for medical disinfection. Combined theoretical calculations and experimental characterizations verified the rationally-designed catalytic active center with the atomic Fe site stabilized by three-coordinated nitrogen atoms and one-sulfur atom (Fe-N3 S-C). It was further found that the replacement of one N atom with S atom in the classical Fe-N4 -C active center could induce an asymmetric charge distribution over N atoms surrounding the Fe reactive center to accelerate proton spillover for a rapid formation of the OOH* intermediate, thus speeding up the whole reaction kinetics of oxygen reduction for H2 O2 electrosynthesis.

Engineering carbon semi-tubes supported platinum catalyst for efficient oxygen reduction electrocatalysis.

Innovation of catalyst structure is extremely important to develop the high-performance electrocatalysts for oxygen-reduction reaction (ORR). Herein, nitrogen-doped carbon semi-tube (N-CST) is used as a functional support for stabilizing the microwave-reduced Pt nanoparticles with an average size of ∼2.8 nm to synthesize the semi-tubular Pt/N-CST catalyst. The contribution of interfacial Pt-N bond between N-CST support and Pt nanoparticles with electrons transfer from N-CST support to Pt nanoparticles is found by electron paramagnetic resonance (EPR) and X-ray absorption fine structure (XAFS) spectroscopy. This bridged Pt-N coordination can simultaneously help ORR electrocatalysis and promote electrochemical stability. As a result, the innovative Pt/N-CST catalyst exhibits excellent catalytic performance, realizing ORR activity and electrochemical stability superior to the commercial Pt/C catalyst. Furthermore, density functional theoretical (DFT) calculations suggest that the interfacial Pt-N-C site with unique affinity of O∗ + OH∗ can provide new active routes for the enhanced electrocatalytic ORR capacity.