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Heart failure (HF) poses a significant global disease burden. The current evidence on the impact of air pollution on HF remains inconsistent. We aimed to conduct a systematic review of the literature and meta-analysis to provide a more comprehensive and multiperspective assessment of the associations between short- and long-term air pollution exposure and HF from epidemiological evidences. Three databases were searched up to 31 August 2022 for studies investigating the association between air pollutants ( , , , , CO, ) and HF hospitalization, incidence, or mortality. A random effects model was used to derive the risk estimations. Subgroup analysis was conducted by geographical location, age of participants, outcome, study design, covered area, the methods of exposure assessment, and the length of exposure window. Sensitivity analysis and adjustment for publication bias were performed to test the robustness of the results. Of 100 studies covering 20 countries worldwide, 81 were for short-term and 19 were for long-term exposure. Almost all air pollutants were adversely associated with the risk of HF in both short- and long-term exposure studies. For short-term exposures, we found the risk of HF increased by 1.8% [relative risk , 95% confidence interval (CI): 1.011, 1.025] and 1.6% ( , 95% CI: 1.011, 1.020) per increment of and , respectively. HF was also significantly associated with , , and CO, but not . Positive associations were stronger when exposure was considered over the previous 2 d (lag 0-1) rather than on the day of exposure only (lag 0). For long-term exposures, there were significant associations between several air pollutants and HF with RR (95% CI) of 1.748 (1.112, 2.747) per increment in , 1.212 (1.010, 1.454) per increment in , and 1.204 (1.069, 1.356) per increment in , respectively. The adverse associations of most pollutants with HF were greater in low- and middle-income countries than in high-income countries. Sensitivity analysis demonstrated the robustness of our results. Available evidence highlighted adverse associations between air pollution and HF regardless of short- and long-term exposure. Air pollution is still a prevalent public health issue globally and sustained policies and actions are called for to reduce the burden of HF. https://doi.org/10.1289/EHP11506.

Background Cardio-renal-metabolic (CRM) comorbidity, including cardiovascular disease, chronic kidney disease, and type 2 diabetes mellitus, is prevalent in the population and closely associated with biological aging. However, longitudinal evidence and potential proteomics mediator remain limited. Methods We studied 330,177 UK Biobank participants free of CRM diseases at baseline. Biological aging was measured by KDM-BA, PhenoAge, their accelerations, and frailty status, and its effects on CRM progression, including no CRM disease to first, double, and triple CRM diseases, were evaluated using multistate proportional hazards model. In the subpopulation with proteomics data (n = 35,118), 2911 plasma proteins were profiled, and mediation analyses were performed to identify potential mediators. Results All five biological aging indicators significantly predicted CRM progression. For example, each standard deviation increase in PhenoAge was associated with hazard ratios of 1.42 [95% confidence interval (CI) 1.40–1.44], 1.26 (95% CI 1.22–1.31), and 1.24 (95% CI 1.12–1.37) for the transitions to first, double, and triple CRM disease, respectively. Mediation analyses identified nine circulating key proteins that statistically mediated the associations between biological aging and CKM progression, with GDF15, ADM, and HAVCR1 showing the largest mediated proportion (13.10–43.23%). The neutralizing antibody ponsegroumab for GDF15 is currently undergoing clinical evaluation. Conclusion Biological aging was strongly associated with the progression of CRM comorbidity, and these associations were partly accounted for by specific circulating proteins. These findings highlight the potential of aging-centered strategies and proteomic biomarkers for improving the risk prediction of CRM health and identifying therapeutic targets.

Background Epidemiological studies demonstrated that multiple amino acids (AAs) were associated with cardiovascular diseases (CVDs), but whether these associations were causal remains unclear. This study aims to investigate the causal relationships between circulating levels of 20 AAs and 10 CVDs in European and East Asian populations by Mendelian randomization (MR). Methods This MR study utilized single-nucleotide polymorphisms that were significantly associated with AAs as instrumental variables. Summary-level data for AAs and CVDs were obtained from public genome-wide association studies. The causal effects were primarily estimated by inverse variance weighting with multiplicative random effect method. Sensitivity analyses, including weighted median, weighted mode, and MR Egger regression, were used to test the robustness of our results. Results In the European population, alanine and serine were inversely associated with angina pectoris (AP) and chronic heart failure, respectively. With each unit increase of leucine, the risk of ischemic stroke increased by 10%. Moreover, tyrosine was positively associated with AP and deep vein thrombosis. In the East Asian population, each unit increase in glycine was associated with 4.1% and 9.0% decreased risks of coronary artery disease (CAD) and myocardial infarction (MI), respectively. A unit increase in serine was associated with 13.1%, 12.6% and 15.5% decreased risks of AP, CAD and MI, respectively. Sensitivity analyses supported the robustness of our results. Conclusions This MR study demonstrated significant causal effects of circulating levels of AAs on CVDs, indicating the potential use of AAs as biomarkers or as therapeutic targets for CVD in clinical scenarios. Graphical Abstract

This study aims to investigate the roles of gut microbiota and plasma metabolites in salt sensitivity (SS) of blood pressure (SSBP) and hypertension. A 23-day, multicenter, dietary salt intervention trial (the MetaSalt study) recruited 528 participants who underwent a baseline observation, low-salt, and high-salt interventions. SSBP was assessed and used as the primary outcome, and fecal shotgun metagenome and plasma targeted metabolome were measured. We found that high salt significantly altered 85 gut-microbial species ( p  < 9.42 × 10 −5 ) and 70 metabolites ( p  < 2.26 × 10 −4 ). Among them, the changes in 22 species and 8 metabolites were associated with SSBP ( p  < 0.05), and a gut microbiota-acylcarnitine network implicated in SSBP was identified, with a gut microbiota-derived metabolite, isovalerylcarnitine, as the core metabolite. Isovalerylcarnitine was also inversely associated with SSBP in the GenSalt study ( p  = 0.0102). Importantly, increased isovalerylcarnitine attenuated SS hypertension and improved endothelial function in rats, and was associated with reduced risk (ranging from 13% to 19%) of BP progression and incident hypertension in a prospective cohort (n = 3907, median follow-up = 5.5 years). This study demonstrated that the gut-acylcarnitine axis may play roles in the development of SS hypertension. Trial number: ChiCTR1900025171. Here, combining data from a clinical trial and animal models, the authors show a role for a gut-acylcarnitine axis in the development of salt-sensitive hypertension, and identify isovalerylcarnitine as a key microbiota-derived modulator and potential target for the precision prevention of hypertension.

Background This study aims to assess the safety and efficacy of direct hemoperfusion using a new polymyxin B‐immobilized resin column (disposable endotoxin adsorber, KCEA) in an endotoxin/ lipopolysaccharide (LPS)‐induced sepsis model. Methods Eighteen beagles were randomized into 1 intervention group (KCEA group, n = 6) and 2 control groups (sham group and model group, n = 6 each). Sepsis was induced by continuous intravenous application of 0.5 mg/kg body weight of endotoxin for 60 min. An extracorporeal hemoperfusion device made with KCEA for endotoxin adsorption was used. Model group beagles received standard treatment with fluids and vasoactive drugs, KCEA group beagles received standard treatment and direct hemoperfusion of KCEA for 2 h, and sham group beagles were treated with standard treatment and direct hemoperfusion of a sham column for 2 h. Results Good blood compatibility of KCEA was confirmed by assessing clinical parameters. Blood endotoxin peak levels in the KCEA group were significantly lower, resulting in a significant suppression of IL‐6, TNF‐α and procalcitonin, which improved mean arterial pressure and significantly lowered vasopressor demand, thereby protecting organ function and improving survival time and rate. In the KCEA group, MAP was significantly higher over 6 h than those recorded both in the sham group and model group. The 7‐day survival rates of the KCEA, sham and model groups were 50%, 0% and 0%, respectively. Conclusion KCEA hemoadsorption was effective at detoxifying circulatory endotoxin and inflammatory mediators and contributed to the decreased mortality rate in the sepsis beagles. To produce sepsis, a beagle was given lipopolysaccharide (0.5 mg/kg) as a drip infusion. Direct hemoadsorption was performed with KCEA from right femoral artery to femoral vein by use of Y‐type 18 G venous indwelling needles. KCEA hemoadsorption is effective to detoxify circulatory endotoxin and inflammatory mediators, and contributes to the decreased mortality rate in the sepsis beagles.

Charge transfer properties between 3D and 2D perovskite layers play a key role in determining the performance of 3D/2D heterostructure perovskite solar cells (PSCs). However, the exact photophysical behaviors at 3D/2D perovskite heterostructure remain ambiguous, which makes it challenging to form the desired 3D/2D heterostructure. Herein, via combining the state‐of‐the‐art ultrafast spectroscopies of femtosecond transient absorption spectroscopy, transient absorption microscopy and time‐resolved photoluminescence spectroscopy, charge transfer and recombination dynamics are unveiled at 3D/2D perovskite heterostructure, for comparison, where the 2D layers are fabricated through the two distinct approaches of organic ligand surface reaction (2DL) and 2D crystal seed direct deposition (2DS), respectively. 3D/2DS heterostructure exhibits superior hole transfer from 3D to 2DS, featuring a large spatial diffusion constant and high charge mobility compared to 3D/2DL, attributed to the higher phase purity and the lower defects in 2DS. Moreover, 3D/2DS heterostructure yields suppressed nonradiative recombination, reduced Langevin recombination, and increased quasi‐Fermi level splitting, significantly aiding fast photoinduced charge transfer at such heterostructure. These advantages are further confirmed by a remarkably improved PSC efficiency using 3D/2DS, especially in terms of enhanced open‐circuit voltage and diminished energy loss. This work sheds light on the dynamics at 3D/2D heterostructures, providing a promising guideline for designing 3D/2D high‐performance PSCs. Charge transfer and recombination dynamics at 3D/2D perovskite heterostructure have been fully investigated via combined state‐of‐the‐art ultrafast spectroscopies, aiding to design of the desired 3D/2D perovskite heterostructure and thus push 3D/2D perovskite solar cell technology forward.

Background Familial hypercholesterolemia (FH) is underrecognized, and its association with coronary artery disease (CAD) remains limited, especially in China. We aimed to investigate the prevalence of FH and its relationship with CAD in a large Chinese cohort. Methods FH was defined using the Make Early Diagnosis to Prevent Early Death (MEDPED) criteria. The crude and age‐sex standardized prevalence of FH were calculated based on surveys of the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China‐PAR) project during 2007−2008. The associations of FH with incident CAD and its major subtypes were estimated with the cohort‐stratified multivariate Cox proportional hazard models based on the data from the baseline to the last follow‐up (2018−2020). Results Among 98,885 included participants, 190 participants were defined as FH. Crude and age−sex standardized prevalence and 95% confidence interval (CI) of FH were 0.19% (0.17%–0.22%) and 0.13% (0.10%–0.16%), respectively. The prevalence varied across age groups and peaked in the group of 60–<70 years (0.28%), and the peak prevalence (0.18%) in males was earlier, yet lower than the peak crude prevalence in females (0.41%). During a mean follow‐up of 10.7 years, 2493 cases of incident CAD were identified. After multivariate adjustment, FH patients had a 2.03‐fold greater risk of developing CAD compared to non‐FH participants. Conclusions The prevalence of FH was estimated to be 0.19% in the participants, and it was associated with an elevated risk of incident CAD. Our study suggests that early screening of FH has certain public health significance for the prevention of CAD. Key points This study provided a precise estimate of familial hypercholesterolemia (FH) prevalence and strong evidence of the association between FH and coronary artery disease (CAD), based on a large population. Our research has important public health implications for the future prevention of FH and CAD. The flow diagram of the study participant selection for the final analysis.

Purpose This study aims to improve the sensitivity of magnetic detection. In this article, a multi-frequency modulation technique is used to increase the magnetic detection sensitivity of diamond nitrogen vacancy (NV) centers sensors. Design/methodology/approach In the field of magnetic detection, NV centers have corresponding advantages due to their unique long coherence property at room temperature. The important indicators for NV centers magnetometers are the magnetic detection sensitivity of the NV centers and the integration of the magnetometer. To solve this problem, the authors propose a multi-frequency modulated magnetic detection technique, using an integrated probe as well as a lock-in amplifier for the double enhancement of sensitivity as well as integration. Findings The following results can be obtained by processing and calculating the experimental data with an integrated lock-in amplifier circuit with an area of 27.50 cm2 and a probe volume of 3.12 cm3. The multi-frequency modulation technique was used to increase the magnetic detection sensitivity of the NV centers from 8.59 nT/Hz1 / 2–2.42 nT/Hz1 / 2. Research limitations/implications The authors propose a signal modulation technique with an integrated design, which achieves an improvement in the sensitivity of the sensor’s magnetic detection through practical testing. Originality/value The authors propose a signal modulation technique with an integrated design, which achieves an improvement in the sensitivity of the sensor’s magnetic detection through practical testing. This technique provides new research solution for the subsequent improvement of the magnetic detection sensitivity.

Individuals with a high degree of salt sensitivity (SS) have a greater risk of cardiovascular disease (CVD), but whether SS fosters CVD by influencing metabolomics homeostasis remains unclear. This study aimed to reveal the role of the SS-related metabolomics signature in the development of CVDs, based on the MetaSalt study, which was a dietary salt-intervention trial conducted at four centers in China in 2019. A total of 528 participants were recruited and underwent 3 days of baseline observations, a 10-day low-salt intervention, and a 10-day high-salt intervention. Plasma untargeted metabolomics, lipidomics, and BP measurements were scheduled at each stage. Participants were grouped into extreme SS, moderate SS, and salt-resistant (SR) individuals according to their BP responses to salt. Linear mixed models were used to identify SS-related metabolites and determine the relationship between the SS-related metabolomics signature and arterial stiffness. Mendelian randomization (MR) analyses were applied to establish the causal pathways among the SS-related metabolites, BP, and CVDs. Among the 713 metabolites, 467 were significantly changed after the high-salt intervention. Among them, the changes in 30 metabolites from the low-salt to the high-salt intervention differed among the SS groups. Of the remaining nonsalt-related metabolites, the baseline levels of 11 metabolites were related to SS. These 41 metabolites explained 23% of the variance in SS. Moreover, SS and its metabolomics signature were positively correlated with arterial stiffness. MR analyses demonstrated that the SS-related metabolites may affect CVD risk by altering BP, indicating that the increase in BP was the consequence of the changes in SS-related metabolites rather than the cause. Our study revealed that the metabolomics signature of SS individuals differs from that of SR individuals and that the changes in SS-related metabolites may increase arterial stiffness and foster CVDs. This study provides insight into understanding the biology and targets of SS and its role in CVDs.

Background::Familial hypercholesterolemia (FH) is underrecognized, and its association with coronary artery disease (CAD) remains limited, especially in China. We aimed to investigate the prevalence of FH and its relationship with CAD in a large Chinese cohort.Methods::FH was defined using the Make Early Diagnosis to Prevent Early Death (MEDPED) criteria. The crude and age-sex standardized prevalence of FH were calculated based on surveys of the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) project during 2007-2008. The associations of FH with incident CAD and its major subtypes were estimated with the cohort-stratified multivariate Cox proportional hazard models based on the data from the baseline to the last follow-up (2018-2020).Results::Among 98,885 included participants, 190 participants were defined as FH. Crude and age-sex standardized prevalence and 95% confidence interval (CI) of FH were 0.19% (0.17%–0.22%) and 0.13% (0.10%–0.16%), respectively. The prevalence varied