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Objectives: Aldosterone-to-renin ratio (ARR) based screening is the first step in the diagnosis of primary aldosteronism (PA). However, the guideline-recommended ARR cutoff covers a wide range, from the equivalent of 1.3 to 4.9 ng·dl -1 /mIU∙l -1 . We aimed to optimize the ARR cutoff for PA screening based on the risk of cardiovascular diseases (CVD)., Methods: Longitudinally, we included hypertensive participants from the Framingham Offspring Study (FOS) who attended the sixth examination cycle and followed up until 2014. At baseline (1995-1998), we used circulating concentrations of aldosterone and renin to calculate ARR (unit: ng·dl -1 /mIU∙l -1 ) among 1,433 subjects who were free of CVD. We used spline regression to calculate the ARR threshold based on the incident CVD. We used cross-sectional data from the Chongqing Primary Aldosteronism Study (CONPASS) to explore whether the ARR cutoff selected from FOS is applicable to PA screening., Results: In FOS, CVD risk increased with an increasing ARR until a peak of ARR 1.0, followed by a plateau in CVD risk (hazard ratio 1.49, 95%CI 1.19-1.86). In CONPASS, when compared to essential hypertension with ARR < 1.0, PA with ARR ≥ 1.0 carried a higher CVD risk (odds ratio 2.24, 95%CI 1.41-3.55), while essential hypertension with ARR ≥ 1.0 had an unchanged CVD risk (1.02, 0.62-1.68). Setting ARR cutoff at 2.4 ~ 4.9, 10% ~30% of PA subjects would be unrecognized although they carried a 2.45 ~ 2.58-fold higher CVD risk than essential hypertension., Conclusions: The CVD risk-based optimal ARR cutoff is 1.0 ng·dl -1 /mIU∙l -1 for PA screening. The current guideline-recommended ARR cutoff may miss patients with PA and high CVD risk., Clinical Trial Registration: ClinicalTrials.gov (NCT03224312).

Background & Aims: Renin-independent aldosteronism (RIA) refers to a spectrum of autonomous aldosterone hypersecretion. We aimed to explore the genetical relationship between RIA and metabolic dysfunction-associated steatotic liver disease (MASLD) and cirrhosis., Methods: We included 125357 participants from the cohort of United Kingdom Biobank. We calculated a polygenic risk score (PRS) for RIA on the basis of reported data from genome-wide association studies, and performed an analysis of Phenome Wide Association Studies (PheWAS) on diverse outcomes. We explored the genetical relationship between RIA and MASLD or cirrhosis by using Mendelian randomization analysis., Results: An increased RIA PRS was associated with higher risks of MASLD and MASLD related cirrhosis, and the well-defined RIA related target organ damages such as hypertension or kidney diseases was also significant in the PheWAS analysis. When compared to individuals with low RIA PRS (tertile 1, 0.41-9.89), those with high RIA PRS (tertile 3, 13.58-23.16) showed significantly higher odds ratio (OR) of MASLD (OR 1.28, 95 % confidence interval [CI] 1.09-1.49) and cirrhosis (OR 1.49, 95%CI 1.03-2.16). In analyses of two-sample Mendelian randomization, genetically predicted RIA significantly correlated with elevated risks of MASLD and cirrhosis (inverse variance weighted odds ratio [95 % CI]: 1.05 [1.01-1.09]) for MASLD, 1.08 [1.02-1.13] for cirrhosis), meanwhile we observed no significant directional pleiotropy or heterogeneity., Conclusion: Renin-independent aldosteronism is genetically associated with higher risks of MASLD and cirrhosis. Targeted treatment of autonomous aldosterone secretion may alleviate MASLD progression., Competing Interests: Conflict of interest The authors report no conflicts of interest., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Although a range of renin-angiotensin-aldosterone system (RAAS) modulators are available for blood pressure lowering, the optimal choice within this class remains unclear. We aimed to compare the efficacy and safety of RAAS modulators in the adult hypertensive population., Methods: A systematic literature search was performed in PubMed, CENTRAL, and Embase. The primary efficacy outcome was all-cause mortality and the secondary efficacy outcome was cardiovascular mortality. Tolerability outcome was discontinuation due to adverse events. Safety outcomes included the occurrence of cough, dizziness, edema, hyperkalemia, and hypotension. Network meta-analyses were performed utilizing a random-effects model within a frequentist framework., Results: We finally identified 51 articles from 49 randomized controlled trials. When compared to placebo, mineralocorticoid receptor antagonists (MRAs) significantly reduced the risk of all-cause mortality (odds ratio (OR) 0.83; 95% confidence interval (CI) 0.74-0.92) and cardiovascular mortality (OR 0.79; 95% CI 0.68-0.93), while none of other RAAS modulators significantly lowered the risk of all-cause or cardiovascular mortality. Individual comparisons indicated that MRAs were associated with a significantly lower risk of all-cause mortality than the other RAAS modulators (reduction: 16% compared with angiotensin-converting enzyme inhibitors (ACEIs), 14% compared with angiotensin receptor blockers (ARBs), and 22% compared with direct renin inhibitors (DRIs)). No difference in discontinuation due to adverse events was found in a comparison of RAAS modulators with placebo. With regard to safety outcomes, ACEIs have a higher risk of cough (OR 4.68; 95% CI 1.61-13.60), ARBs have a higher risk of dizziness (OR 1.42; 95% CI 1.06-1.91), hypotension (OR 2.10; 95% CI 1.02-4.34), and hyperkalemia (OR 1.99; 95% CI 1.17-3.41), and MRAs had a higher risk of hyperkalemia (OR 2.68; 95% CI 1.99-3.62) when compared to placebo., Conclusions: MRAs were the only RAAS modulators with a survival benefit in adults with hypertension, although they carried a higher risk of hyperkalemia. Our data challenge current hypertension guidelines which recommend MRAs as fourth-line therapy, and suggest that MRAs should be prescribed earlier and more widely., Registration: PROSPERO identifier number CRD42023405714., Competing Interests: Declarations. Funding: his work was supported by the National Natural Science Foundation of China [Major Joint Project: U21A20355]; the national key research and development plan of China, major project of prevention and treatment for common diseases [2022YFC2505300, sub-project: 2022YFC2505302]; the National Natural Science Foundation of China [82270878, 81970720, 82170825]; Joint Medical Research Project of Chongqing Science and Technology Commission and Chongqing Health and Family Planning Commission [Major Project, 2022ZDXM003]; Chongqing Outstanding Youth Funds [CSTB2023NSCQ-JQX0028]; Program for Youth Innovation in Future Medicine, Chongqing Medical University [Jinbo Hu and Rufei Gao]; Program for Major Scientific and Technological Talents, Chongqing Medical University [Jinbo Hu and Shumin Yang]. Conflict of Interest: Xiaoyan Yi, Shumin Yang, Jun Yang, Xiangjun Chen, Aiping Zhang, Qinglian Zeng, Wenjin Luo, Qifu Li, and Jinbo Hu declare that they have no potential conflicts of interest that might be relevant to the contents of this article. Authors' Contributions: XY, SY, QL, and JH conceived of and designed the study. XY, SY, and WL did the analysis. XY and SY drafted the manuscript. XY, SY, JY, AZ, QL, and JH revised and edited the manuscript. All authors had full access to and verified the data, and had final responsibility for the decision to submit for publication. Data Availability Statement: All the data collected for the study, study protocol, and statistical code are available to approved persons through written agreements with the authors and the data partner with publication from QL (e-mail: liqifu@yeah.net) or JH (email: hujinbo@cqmu.edu.cn). Ethics Approval: Not applicable. Code Availability: Not applicable. Consent to Participate: Not applicable. Consent for Publication: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The strategic integration of low-dimensional InAs-based materials and emerging van der Waals systems is advancing in various scientific fields, including electronics, optics, and magnetics. With their unique properties, these InAs-based van der Waals materials and devices promise further miniaturization of semiconductor devices in line with Moore's Law. However, progress in this area lags behind other 2D materials like graphene and boron nitride. Challenges include synthesizing pure crystalline phase InAs nanostructures and single-atomic-layer 2D InAs films, both vital for advanced van der Waals heterostructures. Also, diverse surface state effects on InAs-based van der Waals devices complicate their performance evaluation. This review discusses the experimental advances in the van der Waals epitaxy of InAs-based materials and the working principles of InAs-based van der Waals devices. Theoretical achievements in understanding and guiding the design of InAs-based van der Waals systems are highlighted. Focusing on advancing novel selective area growth and remote epitaxy, exploring multi-functional applications, and incorporating deep learning into first-principles calculations are proposed. These initiatives aim to overcome existing bottlenecks and accelerate transformative advancements in integrating InAs and van der Waals heterostructures., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

The relationship between psoriasis and site-specific cancers remains unclear. Here, we aim to investigate whether psoriasis is causally associated with site-specific cancers. We use observational and genetic data from the UK Biobank, obtaining GWAS summary data, eQTL analysis data, TCGA data, and GTEx data from public datasets. We perform PheWAS, polygenic risk score analysis, and one-sample and two-sample Mendelian randomization analyses to investigate the potential causal associations between psoriasis and cancers. In the unselected PheWAS analysis, psoriasis is associated with higher risks of 16 types of cancer. Using one-sample Mendelian randomization analyses, it is found that genetically predicted psoriasis is associated with higher risks of anal canal cancer, breast cancer, follicular non-Hodgkin's lymphoma and nonmelanoma skin cancer in women; and lung cancer and kidney cancer in men. Our two-sample Mendelian randomization analysis indicates that psoriasis is causally associated with breast cancer and lung cancer. Gene annotation shows that psoriasis-related genes, such as ERAP1, are significantly different in lung and breast cancer tissues. Taken together, clinical attention to lung cancer and breast cancer may be warranted among patients with psoriasis., (© 2024. The Author(s).)

Background and Aims: The relationship between cereals intake and diabetes is unclear. We aimed to explore associations between individual cereals intake and risks of incident and progression of diabetes., Methods: We included 502,490 participants from UK Biobank at baseline. A single touchscreen food frequency questionnaire was used to estimate the intake of individual cereals (bran, biscuit, oat, muesli, and other cereals). Main outcomes included incident diabetes and diabetic complications of cardiovascular disease (CVD), chronic kidney disease (CKD) and diabetic retinopathy (DR). Polygenic risk score (PRS) of glycosylated hemoglobin (HbA1c) was calculated for mediating effects analysis., Results: Among participants without diabetes, when compared to subjects who never had cereals, hazard ratios (95%CI) of developing diabetes in those who had ≥6 bowls/week were 0.72 (0.67-0.78) for bran, 0.86 (0.81-0.92) for biscuit, 0.75(0.66-0.84) for oat, and 0.57(0.53,0.61) for muesli. Among people with diabetes without CVD, a higher intake of aforementioned four individual cereals was associated with a 13%-32 % lower risk of developing CVD. Among people with diabetes without CKD, a higher intake of aforementioned four individual cereals was associated with a 9%-28 % lower risk of developing CKD. We observed a significant mediating effect of the PRS of HbA1c for the association between aforementioned four individual cereals and developing diabetes., Conclusion: A higher consumption of cereals was significantly associated with lower risks of diabetes and diabetic complications. Polygenic of HbA1c mediates the effect of cereals on incident diabetes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Research Trust of DiabetesIndia (DiabetesIndia) and National Diabetes Obesity and Cholesterol Foundation (N-DOC). Published by Elsevier Ltd. All rights reserved.)

Background: It is generally known that although a connection between abdominal obesity and chronic kidney disease (CKD) is well-established, there is a lack of systematic research investigating the specific roles of serum metabolites, including lipid metabolites, amino acid metabolites, carbohydrate metabolites and inflammatory substances in explaining this associations., Methods: We included 118,020 general patients with data of serum metabolites from UK Biobank. We defined abdominal obesity and CKD based on waist circumference and ICD-10 criteria. The serum metabolites were assessed by a high-throughput nuclear magnetic resonance (NMR) based metabolic biomarker profiling platform. We conducted mediation analysis by R software and used the proportion of mediation to quantify the mediation effect., Results: This study demonstrated that lipid metabolites played a more important role in mediating the relationship between abdominal obesity and CKD than amino acid metabolites and carbohydrate metabolites. And Glycoprotein Acetyls (GlycA) was the strongest mediator for the correlation between abdominal obesity and CKD, accounting for 26.4 %. And In the mediation analysis stratified by sex, we found that the mediating effects of lipid metabolites were mostly higher in men than in women, while GlycA accounted for the largest proportion of the mediation association in both two groups (31.0 % for women and 19.8 % for men)., Conclusion: Among lipid metabolites, amino acid metabolites, carbohydrate metabolites and inflammatory substances, our study showed that infammation marker GlycA was the novel and key mediator for the correlation between abdominal obesity and CKD., Competing Interests: Declaration of Competing Interest All authors have declared no conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Captopril challenge test (CCT), seated saline infusion test (SSIT), oral sodium loading test (OSLT) and fludrocortisone suppression test (FST) are widely used diagnostic tests for primary aldosteronism (PA). These tests differ in terms of safety and complexity. Whether the simpler tests (CCT and SSIT) are comparable in diagnostic performance to the more complex ones (FST and OSLT) is unclear., Purpose: To compare the diagnostic accuracy of the four tests., Methods: This is a retrospective study of hypertensive patients who were screened for PA and completed at least one confirmatory test. The patients were divided into two cohorts: one including those who completed one to three tests was used for the estimation of sensitivity and specificity. The other including those who completed four tests was used for the comparison of accuracy. Bayesian method was used to obtain the sensitivity, specificity, and Youden index of each test., Results: The study included 1011 hypertensive patients. Among them, 895 patients completed one to three tests (including 889 CCT, 605 FST, 611 SSIT and 69 OSLT), and 116 patients completed four tests. SSIT had the highest sensitivity of 0.82(95% CI 0.78-0.86) but the lowest specificity of 0.76(0.70-0.80). OSLT had the lowest sensitivity of 0.65(0.56-0.75) but the highest specificity of 0.91(0.82-0.96). The sensitivity and specificity were 0.78 (95% CI, 0.75-0.82), 0.82 (95% CI, 0.78-0.85), for CCT, and 0.77 (95% CI, 0.73-0.81), 0.87 (95% CI, 0.82-0.91) for FST, respectively. The Youden index was not significantly different among the four tests[0.60(0.55-0.65) for CCT; 0.58(0.51-0.64) for SSIT; (0.64(0.57-0.69) for FST; 0.56(0.43-0.67) for OSLT]., Conclusion: The accuracy of simpler tests is comparable to the more complex ones. Considering the safety and simplicity of CCT, it may be a reasonable first choice when confirming the diagnosis of PA., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Identifying the oxidation structure of two-dimensional interfaces is crucial to improve surface chemistry and electronic properties. Beyond graphene with only phenyl rings, a novel carbon-nitrogen material, C3N, presents an intrinsic heterogeneous surface morphology where each phenyl ring is encircled by six nitrogen atoms, yet its atomistic oxidation structure remains unclear. Here, combining a series of density functional theory calculations and ab initio molecular dynamics simulations, we demonstrate that thermodynamically favorable oxidation loci are confined to the phenyl ring, and kinetic transformations of oxidation structures are feasible along the phenyl ring, whereas those toward nitrogen atoms are proven to be extremely difficult. These results are attributed to the lower barrier of oxygen atom migration along the phenyl ring, while the significantly high barriers toward nitrogen atoms are due to the heterogeneous potential energy surface for oxygen-C3N interaction. This work highlights the significance of surface morphology on the characteristics of oxidation structure, offering insights into tunable electronic properties via confined interfacial oxidation., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Background and Aims: Primary aldosteronism (PA) is an adrenal disorder of autonomous aldosterone secretion which promotes arterial injury. We aimed to explore whether PA is causally associated with lower-extremity arterial disease (LEAD)., Methods: We included 39,713 patients with diabetes and 419,312 participants without diabetes from UK Biobank. We derived a polygenic risk score (PRS) for PA based on previous genome-wide association studies (GWAS). Outcomes included LEAD and LEAD related gangrene or amputation. We conducted a two-sample Mendelian randomization analysis for PA and outcomes to explore their potential causal relationship., Results: In whole population, individuals with a higher PA PRS had an increased risk of LEAD. Among patients with diabetes, compared to the subjects in the first tertile of PA PRS, subjects in the third tertile showed a 1.24-fold higher risk of LEAD (OR 1.24, 95% CI 1.03-1.49) and a 2.09-fold higher risk of gangrene (OR 2.09, 95% CI 1.27-3.44), and 1.72-fold higher risk of amputation (OR 1.72, 95% CI 1.10-2.67). Among subjects without diabetes, there was no significant association between PA PRS and LEAD, gangrene or amputation. Two-sample Mendelian randomization analysis indicated that genetically predictors of PA was significantly associated with higher risks of LEAD and gangrene (inverse variance weighted OR 1.20 [95% CI 1.08-1.34]) for LEAD, 1.48 [95% CI 1.28-1.70] for gangrene), with no evidence of significant heterogeneity or directional pleiotropy., Conclusions: Primary aldosteronism is genetically and causally associated with higher risks of LEAD and gangrene, especially among patients with diabetes. Targeting on the autonomous aldosterone secretion may prevent LEAD progression., (© 2023. The Author(s).)

Background: Individuals in the workplace are exposed to various environments, tasks, and schedules. Previous studies have indicated a link between occupational exposures and an increased risk of chronic kidney disease (CKD). However, the social conditions of the work environment may also be a crucial contributing factor to CKD. Furthermore, individuals may encounter multiple occupational-related risk factors simultaneously, underscoring the importance of investigating the joint risk of different working conditions on CKD., Methods: A prospective analysis of 65,069 UK Biobank participants aged 40 to 69 years without CKD at baseline (2006-2010) was performed. A self-administered questionnaire assessed working conditions and a working conditions risk score were developed. Participants who answered "sometimes" or "often" exposure to occupational heat or occupational secondhand cigarette smoke; involved in shift work or heavy workloads ("usually" or "always"), were grouped as high-risk working conditions. Each working condition was scored as 1 if grouped as high-risk, and 0 if not. The working conditions risk score was equal to the sum of these four working conditions. Cox proportional hazard regression models were used to estimate the associations between working conditions and CKD incidence., Results: The mean follow-up time was 6.7 years. After adjusting for demographic, lifestyle, and working time factors, the hazard ratios for the development of CKD for heavy workloads, shift work, occupational secondhand cigarette smoke exposure, and occupational heat exposure were 1.24 (95%CI = 1.03, 1.51), 1.33 (95%CI = 1.10, 1.62), 1.13 (95%CI = 1.01, 1.26), 1.11 (95%CI = 0.99, 1.24), respectively. The risk of CKD was found to be significantly associated with an increasing working conditions risk score. Individuals with a working conditions risk score of 4 had an 88.0% (95% CI = 1.05, 3.35) higher risk of developing CKD when compared to those with a working conditions risk score of 0., Conclusions: Adverse working conditions, particularly when considered in combination, can significantly elevate the risk of chronic kidney disease (CKD). These results provide a reference for implementing measures to prevent CKD., (© 2023. The Author(s).)

Background: Renin-independent aldosteronism (RIA) describes the spectrum of autonomous aldosterone secretion from mild to overt. We aimed to explore whether RIA is causally associated with chronic kidney disease (CKD) in patients with diabetes., Methods: We cross-sectionally included 1027, 402 and 39,709 patients with any type of diabetes from cohorts of EIMDS, CONPASS and UK Biobank, respectively. In EIMDS, we defined RIA and renin-dependent aldosteronism based on plasma aldosterone and renin concentrations. We performed captopril challenge test to confirm renin-dependent or independent aldosteronism in CONPASS. In UK Biobank, we generated genetic instruments for RIA based on the genome-wide association studies (GWAS). We extracted the corresponding single nucleotide polymorphisms (SNPs) information from the GWAS data of CKD in diabetes. We harmonized the SNP-RIA and SNP-CKD data to conduct the two-sample Mendelian randomization analyses., Findings: In EIMDS and CONPASS, when compared to subjects with normal aldosterone concentration or renin-dependent aldosteronism, participants with RIA had a lower estimated glomerular filtration rate, a higher prevalence of CKD, and a higher multivariate-adjusted odds ratio (OR) of CKD (OR 2.62 [95%CI 1.09-6.32] in EIMDS, and 4.31 [1.39-13.35] in CONPASS). The two-sample Mendelian randomization analysis indicated that RIA was significantly associated with a higher risk of CKD (inverse variance weighted OR 1.10 [95 % CI 1.05-1.14]), with no evidence of significant heterogeneity or substantial directional pleiotropy., Interpretation: Among patients with diabetes, renin-independent aldosteronism is causally associated with a higher risk of CKD. Targeted treatment of autonomous aldosterone secretion may benefit renal function in diabetes., Competing Interests: Declaration of competing interest Authors have disclosed no conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: A large number of people around the world are exposed to the risks of passive smoking. This prospective study aimed to examine the association between secondhand smoke exposure, exposure time, and the incidence of chronic kidney disease (CKD) and determine whether this association was influenced by genetic susceptibility., Methods: The study included 214244 participants of the UK Biobank who were initially free of CKD. Cox proportional hazards model was used to estimate the associations between secondhand smoke exposure time and the risks of CKD in people who have never smoked. The genetic risk score for CKD was calculated by a weighted method. The likelihood ratio test comparing models was used to examine the cross-product term between secondhand smoke exposure and genetic susceptibility to CKD outcomes., Results: During a median of 11.9 years of follow-up, 6583 incidents of CKD were documented. Secondhand smoke exposure increased the risk of CKD (HR=1.09; 95% CI: 1.03-1.16, p<0.01), and a dose-response relationship between CKD prevalence and secondhand smoke exposure time was found (p for trend<0.01). Secondhand smoke exposure increases the risk of CKD even in people who never smoke and have a low genetic risk (HR=1.13; 95% CI: 1.02-1.26, p=0.02). There was no statistically significant interaction between secondhand smoke exposure and genetic susceptibility to CKD (p for interaction=0.80)., Conclusions: Secondhand smoke exposure is associated with higher risk of CKD, even in people with low genetic risk, and the relationship is dose dependent. These findings change the belief that people with low genetic susceptibility and without direct participation in smoking activities are not prone to CKD, emphasizing the need to avoid the harm of secondhand smoke in public places., Competing Interests: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors declare that they have no competing interests, financial or otherwise, related to the current work. All authors declare that since the initial planning of the work, support for the present work was provided by the entities as outlined in the Funding declaration., (© 2023 Lan R. et al.)

Transition-metal dichalcogenides (TMDs) have demonstrated a wide range of novel photonic, optoelectronic, and correlated electron phenomena for more than a decade. However, the coherent dynamics of their excitons, including possibly long dephasing times and their sensitivity to spatial heterogeneities, are still poorly understood. Here we implement adiabatic plasmonic nanofocused four-wave mixing (FWM) to image the coherent electron dynamics in monolayer WSe 2 . We observe nanoscale heterogeneities at room temperature with dephasing ranging from T 2 ≲ 5 to T 2 ≳ 60 fs on length scales of 50-100 nm. We further observe a counterintuitive anticorrelation between FWM intensity and T 2 , with the weakest FWM emission at locations of longest coherence. We interpret this behavior as a nonlocal nano-optical interplay between spatial coherence of the nonlinear polarization and disorder-induced scattering. The results highlight the challenges associated with heterogeneities in TMDs limiting their photophysical properties, yet also the potential of their novel nonlinear optical phenomena.

Background: The association between fat mass and mortality has been equivocally shown to be linear, J-shaped, and U-shaped. We aimed to clarify this relationship based on Mendelian randomization (MR) analysis and lifestyle modification., Methods: This prospective analysis included 449,831 participants from UK Biobank. Linear MR analysis was used to estimate the linear relationship between fat mass and mortality. We assessed whole body fat mass by bioimpedance analysis at baseline and categorized subjects into five equal groups based on fat mass index (FMI). The association between FMI and mortality were investigated among whole population and in subgroups stratified by individual lifestyle factors, including diet, physical activity, smoking, alcohol, sleep and psychological health., Findings: Linear MR analyses indicated a positive association between genetically predicted fat mass and all-cause mortality (HR 1.10, 95 % CI 1.08-1.12, P < 0.001). The association between FMI and all-cause mortality was manifested as J-shaped (HRs across FMI categories: 1.04, 1.00, 1.07, 1.21, 1.54), which was significantly modified by the number of low-risk lifestyle factors (P for interaction<0.001). When evaluating individual lifestyle factors, we observed a nonlinear relationship between FMI and all-cause mortality among participants who had high-risk lifestyle factors, while a linear relationship was observed among participants who had low-risk lifestyle factors, especially for those with adequate physical activity (HRs across FMI categories: 0.95, 1.00, 1.05, 1.17, 1.44) and who never smoked (0.96, 1.00, 1.03, 1.14, 1.51)., Interpretation: Genetically determined fat mass is causally and linearly associated with mortality. The J-shape association between anthropometric FMI and mortality is caused by high-risk lifestyle factors., Competing Interests: Declaration of competing interest Authors have disclosed no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Obesity has become a global problem that poses a serious threat to human health. Laparoscopic sleeve gastrectomy (LSG) is an effective long-term treatment. However, the weight loss of some patients after LSG is still insufficient. It is necessary to investigate the factors associated with inadequate weight loss after LSG., Objective: The objective of this study was to explore whether preoperative insulin secretion could be associated with weight loss after LSG in patients with obesity., Setting: This is a single-center prospective cohort study conducted in a university hospital., Methods: Patients from a prospective database who underwent LSG were analyzed. All 178 participants underwent a 75-g oral glucose tolerance test (OGTT) to assess preoperative insulin and c-peptide secretion before LSG. The areas under the curve (AUCs) for glucose, insulin, and c-peptide were determined in the OGTT. The percentage of excess weight loss (%EWL) and the percentage of total weight loss (%TWL) were used to estimate the effect of weight loss after LSG. Regression models were used to assess the correlation between preoperative insulin and c-peptide secretion with %EWL ≥75% and TWL ≥35% at 12 months after LSG., Results: The AUCs of insulin and c-peptide were significantly lower in the %EWL ≥75% and %TWL ≥35% groups at 0-30 minutes, 0-60 minutes, and 0-120 minutes during the OGTT. At 30, 60, and 120 minutes during the OGTT, c-peptide levels were significantly lower in the %EWL ≥75% group and %TWL ≥35% group. The preoperative c-peptide level at 30 minutes during the OGTT (C 30 ) was significantly negatively correlated with %EWL (β = -.37, P < .001) and %TWL (β = -.28, P = .011). Univariate logistic regression analysis showed that preoperative C 30 was associated with %EWL ≥75% and %TWL ≥35% after LSG. According to multiple logistic regression analysis, patients with a low preoperative C 30 had an 8-fold higher %TWL ≥35% after LSG than those with a high C 30 (odds ratio: 8.41 [95% confidence interval: 1.46-48.58], P = .017). Similarly, patients with a low preoperative C 30 had a 7-fold higher EWL% ≥75% after LSG than patients with a high C 30 (odds ratio: 7.25 [95% confidence interval: 1.11-47.50], P = .039)., Conclusions: The rate of weight loss after LSG is low among patients with preoperative hyperinsulinemia. The preoperative c-peptide level at 30 minutes during the OGTT is associated with weight loss after LSG., (Copyright © 2022 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Backgrounds: Ectopic fat deposition is closely related to chronic kidney disease (CKD). Currently, there are few population studies that have been conducted to determine the relationship between renal parenchyma fat deposition and the risk of CKD among patients with type 2 diabetes mellitus (T2DM). Therefore, we employed magnetic resonance imaging (MRI) to detect renal parenchyma fat content in individuals with T2DM, expressed as renal fat fraction (FF), to explore whether renal FF is an important risk factor for CKD in patients with T2DM., Methods: In this cross-sectional study, 189 subjects with T2DM were enrolled. CKD was defined as the estimated glomerular filtration rate (eGFR)<60 mL/min/1.73m 2 . Measurement of the renal FF was performed on a 3.0-T MRI (MAGNETOM Skyra, Siemens, Erlangen, Germany). Binary logistic regression was used to determine the association between tertiles of renal FF and risk of CKD. Receiver-operator characteristic (ROC) curves were constructed to evaluate the sensitivity and specificity of renal FF in detecting CKD in T2DM patients., Results: The patients were divided into three groups according to tertiles of the renal FF level (2.498 - 7.434). As renal FF increases, patients tend to be older, and more abdominally obese, with a decreased eGFR (p<0.05). After adjustment for potential confounders, patients in the highest tertile of renal FF had a significantly increased risk of CKD than those in the lowest tertile (odds ratio (OR) = 3.98, 95% confidence interval (CI) = 1.12 - 14.09, p = 0.032), and the area under the ROC curve for this model was 0.836 (0.765-0.907)., Conclusions: The renal FF is significantly independently associated with CKD in patients with T2DM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shen, Xie, Chen, Mao, Qin, Lan, Yang, Hu, Li, Ye, Luo, Gong, Li, Mao and Wang.)

Background: Individual lifestyle varies in the real world, and the comparative efficacy of lifestyles to preserve renal function remains indeterminate. We aimed to systematically compare the effects of lifestyles on chronic kidney disease (CKD) incidence, and establish a lifestyle scoring system for CKD risk identification., Methods: Using the data of the UK Biobank cohort, we included 470,778 participants who were free of CKD at the baseline. We harnessed the light gradient boosting machine algorithm to rank the importance of 37 lifestyle factors (such as dietary patterns, physical activity (PA), sleep, psychological health, smoking, and alcohol) on the risk of CKD. The lifestyle score was calculated by a combination of machine learning and the Cox proportional-hazards model. A CKD event was defined as an estimated glomerular filtration rate <60 ml/min/1.73 m 2 , mortality and hospitalization due to chronic renal failure, and self-reported chronic renal failure, initiated renal replacement therapy., Results: During a median of the 11-year follow-up, 13,555 participants developed the CKD event. Bread, walking time, moderate activity, and vigorous activity ranked as the top four risk factors of CKD. A healthy lifestyle mainly consisted of whole grain bread, walking, moderate physical activity, oat cereal, and muesli, which have scored 12, 12, 10, 7, and 7, respectively. An unhealthy lifestyle mainly included white bread, tea >4 cups/day, biscuit cereal, low drink temperature, and processed meat, which have scored -12, -9, -7, -4, and -3, respectively. In restricted cubic spline regression analysis, a higher lifestyle score was associated with a lower risk of CKD event ( p for linear relation < 0.001). Compared to participants with the lifestyle score < 0, participants scoring 0-20, 20-40, 40-60, and >60 exhibited 25, 42, 55, and 70% lower risk of CKD event, respectively. The C-statistic of the age-adjusted lifestyle score for predicting CKD events was 0.710 (0.703-0.718)., Conclusion: A lifestyle scoring system for CKD prevention was established. Based on the system, individuals could flexibly choose healthy lifestyles and avoid unhealthy lifestyles to prevent CKD., (Copyright © 2022 Luo, Gong, Chen, Gao, Peng, Wang, Luo, Yang, Kang, Peng, Ma, Mei, Liu, Li, Yang, Wang and Hu.)

Background and Objectives: The study aimed to evaluate the performance of a predictive model using the kidney failure risk equation (KFRE) for end-stage renal disease (ESRD) in diabetes and to investigate the impact of glomerular filtration rate (GFR) as estimated by different equations on the performance of the KFRE model in diabetes., Design Setting Participants and Measurements: A total of 18,928 individuals with diabetes without ESRD history from the UK Biobank, a prospective cohort study initiated in 2006-2010, were included in this study. Modification of diet in renal disease (MDRD), chronic kidney disease epidemiology collaboration (CKD-EPI) or revised Lund-Malmö (r-LM) were used to estimate GFR in the KFRE model. Cox proportional risk regression was used to determine the correlation coefficients between each variable and ESRD risk in each model. Harrell's C-index and net reclassification improvement (NRI) index were used to evaluate the differentiation of the models. Analysis was repeated in subgroups based on albuminuria and hemoglobin A1C (HbA1c) levels., Results: Overall, 132 of the 18,928 patients developed ESRD after a median follow-up of 12 years. The Harrell's C-index based on GFR estimated by CKD-EPI, MDRD, and r-LM was 0.914 (95% CI = 0.8812-0.9459), 0.908 (95% CI = 0.8727-0.9423), and 0.917 (95% CI = 0.8837-0.9496), respectively. Subgroup analysis revealed that in diabetic patients with macroalbuminuria, the KFRE model based on GFR estimated by r-LM (KFRE-eGFR r-LM ) had better differentiation compared to the KFRE model based on GFR estimated by CKD-EPI (KFRE-eGFR CKD-EPI ) with a KFRE-eGFR r-LM C-index of 0.846 (95% CI = 0.797-0.894, p = 0.025), while the KFRE model based on GFR estimated by MDRD (KFRE-eGFR MDRD ) showed no significant difference compared to the KFRE-eGFR CKD-EPI (KFRE-eGFR MDRD C-index of 0.837, 95% CI = 0.785-0.889, p = 0.765). Subgroup analysis of poor glycemic control (HbA1c >8.5%) demonstrated the same trend. Compared to KFRE-eGFR CKD-EPI (C-index = 0.925, 95% CI = 0.874-0.976), KFRE-eGFR r-LM had a C-index of 0.935 (95% CI = 0.888-0.982, p = 0.071), and KFRE-eGFR MDRD had a C-index of 0.925 (95% CI = 0.874-0.976, p = 0.498)., Conclusions: In adults with diabetes, the r-LM equation performs better than the CKD-EPI and MDRD equations in the KFRE model for predicting ESRD, especially for those with macroalbuminuria and poor glycemic control (HbA1c >8.5%)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lv, Chen, Hu, Wu, Luo, Shen, Lan, Li, Wang, Luo, Yang, Li and Wang.)

Single-photon detectors (SPDs) that can sense individual photons are the most sensitive instruments for photodetection. Established SPDs such as conventional silicon or III-V compound semiconductor avalanche diodes and photomultiplier tubes have been used in a wide range of time-correlated photon-counting applications, including quantum information technologies, in vivo biomedical imaging, time-of-flight 3D scanners, and deep-space optical communications. However, further development of these fields requires more sophisticated detectors with high detection efficiency, fast response, and photon-number-resolving ability, etc. Thereby, significant efforts have been made to improve the performance of conventional SPDs and to develop new photon-counting technologies. In this review, the working mechanisms and key performance metrics of conventional SPDs are first summarized. Then emerging photon-counting detectors (in the visible to infrared range) based on 0D quantum dots, 1D quantum nanowires, and 2D layered materials are discussed. These low-dimensional materials exhibit many exotic properties due to the quantum confinement effect. And photodetectors built from these nD-materials (n = 0, 1, 2) can potentially be used for ultra-weak light detection. By reviewing the status and discussing the challenges faced by SPDs, this review aims to provide future perspectives on the research directions of emerging photon-counting technologies., (© 2021 Wiley-VCH GmbH.)

Background: Diabetic kidney disease (DKD) lacks a simple and relatively accurate predictor. The Triglyceride-Glucose (TyG) Index is a proxy of insulin resistance, but the association between the TyG Index and DKD is less certain. We investigated if the TyG Index can predict DKD onset effectively., Materials and Methods: Cross-sectional and longitudinal analyses were undertaken. In total, 1432 type-2 diabetes mellitus (T2DM) patients were included in the cross-sectional analysis. The TyG Index (calculated by ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]) was split into three tertiles. Associations of the TyG Index with microalbuminuria and estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m 2 were calculated. Longitudinally, 424 patients without DKD at baseline were followed up for 21 (range, 12-24) months. The main outcome was DKD prevalence as defined with eGFR <60 mL/min/1.73 m 2 or continuously increased urinary microalbuminuria: creatinine ratio (>30 mg/mL) over 3 months. Cox regression was used to analyze the association between the TyG Index at baseline and DKD. Receiver operating characteristics curve (ROC) analysis was used to assess the sensitivity and specificity of the TyG Index in predicting DKD., Results: In cross-sectional analysis, patients with a higher TyG Index had a higher risk of microalbuminuria (OR = 2.342, 95% CI = 1.744-3.144, p < 0.001), and eGFR <60 mL/min/1.73 m 2 (1.696, 95% CI =1.096-2.625, p = 0.018). Longitudinally, 94 of 424 participants developed DKD. After confounder adjustment, patients in the high tertile of the TyG Index at baseline had a greater risk to developing DKD than those in the low tertile (HR = 1.727, 95% CI = 1.042-2.863, p = 0.034). The area under the ROC curve was 0.69 (0.63-0.76)., Conclusion: The TyG Index is a potential predictor for DKD in T2DM patients., Clinical Trial: Clinical Trials identification number = NCT03692884., Competing Interests: Liangjing Lv, Yangmei Zhou, Xiangjun Chen, Lilin Gong, Jinshan Wu, Wenjin Luo, Yan Shen, Shichao Han, Jinbo Hu, Yue Wang, Qifu Li, Zhihong Wang, and Chongqing Diabetes Registry Group declare that they have no relevant conflicts of interest., (© 2021 Lv et al.)

We aim to explore the relationship between early-onset diabetes and proliferative diabetic retinopathy (PDR) in type 2 diabetes mellitus (T2DM) patients with microalbuminuria.A total of 461 T2DM patients with microalbuminuria were enrolled. Subjects were defined as early-onset or late-onset based on the age at which they were diagnosed with diabetes (<40 and ≥40 years, respectively). Medical history, anthropometry, and laboratory indicators were documented. PDR was defined as the presence of any of the following changes on fundus photography: neovascularization, vitreous hemorrhage, or preretinal hemorrhage.The prevalence of PDR was 6-fold higher in patients with early-onset than late-onset T2DM [(6.1% vs 1.0%), P = .004]. Univariate correlation analysis showed that early-onset diabetes, use of oral hypoglycemic drugs, and insulin therapy were risk factors for PDR. In multivariate logistic analysis, patients with early-onset diabetes exhibited a 7.00-fold [(95% confidence interval 1.40-38.26), P = .019] higher risk of PDR than subjects with late-onset diabetes after adjusting for sex; T2DM duration; systolic blood pressure; total triglyceride; glycated hemoglobin; insulin therapy; and the use of oral hypoglycemic drugs, antihypertensive drugs, and lipid-lowering drugs.In T2DM patients with microalbuminuria, early-onset diabetes is an independent risk factor for the development of PDR.

Metal-semiconductor-metal (MSM)-structured GaAs-based nanowire photodetectors have been widely reported because they are promising as an alternative for high-performance devices. Owing to the Schottky built-in electric fields in the MSM structure photodetectors, enhancements in photoresponsivity can be realized. Thus, strengthening the built-in electric field is an efficacious way to make the detection capability better. In this study, we fabricate a single GaAs nanowire MSM photodetector with superior performance by doping-adjusting the Fermi level to strengthen the built-in electric field. An outstanding responsivity of 1175 A/W is obtained. This is two orders of magnitude better than the responsivity of the undoped sample. Scanning photocurrent mappings and simulations are performed to confirm that the enhancement in responsivity is because of the increase in the hole Schottky built-in electric field, which can separate and collect the photogenerated carriers more effectively. The eloquent evidence clearly proves that doping-adjusting the Fermi level has great potential applications in high-performance GaAs nanowire photodetectors and other functional photodetectors.

Single-photon detectors that can resolve photon number play a key role in advanced quantum information technologies. Despite significant progress in improving conventional photon-counting detectors and developing novel device concepts, single-photon detectors that are capable of distinguishing incident photon number at room temperature are still very limited. We demonstrate a room-temperature photon-number-resolving detector by integrating a field-effect transistor configuration with core/shell-like nanowires. The shell serves as a photosensitive gate, shielding negative back-gated voltage, and leads to a persistent photocurrent. At room temperature, our detector is demonstrated to identify 1, 2, and 3 photon-number states with a confidence of >82%. The detection efficiency is determined to be 23%, and the dark count rate is 1.87 × 10 -3 Hz. Importantly, benefiting from the anisotropic nature of 1D nanowires, the detector shows an intrinsic photon-polarization selection, which distinguishes itself from existing intensity single-photon detectors. The unique performance for the single-photon detectors based on single nanowire demonstrates the great potential for future single-photon detection applications.

Molybdenum disulfide (MoS 2 ), a typical 2D metal dichalcogenide (2DMD), has exhibited tremendous potential in optoelectronic device applications, especially in photodetection. However, due to the weak light absorption of planar mono-/multilayers, limited cutoff wavelength edge, and lack of high-quality junctions, most reported MoS 2 -based photodetectors show undesirable performance. Here, a structurized 3D heterojunction of RGO-MoS 2 /pyramid Si is demonstrated via a simple solution-processing method. Owing to the improved light absorption by the pyramid structure, the narrowed bandgap of the MoS 2 by the imperfect crystallinity, and the enhanced charge separation/transportation by the inserted reduced graphene oxide (RGO), the assembled photodetector exhibits excellent performance in terms of a large responsivity of 21.8 A W -1 , extremely high detectivity up to 3.8 × 10 15 Jones (Jones = cm Hz 1/2 W -1 ) and ultrabroad spectrum response ranging from 350 nm (ultraviolet) to 4.3 µm (midwave infrared). These device parameters represent the best results for MoS 2 -based self-driven photodetectors, and the detectivity value sets a new record for the 2DMD-based photodetectors reported thus far. Prospectively, the design of novel 3D heterojunction can be extended to other 2DMDs, opening up the opportunities for a host of high-performance optoelectronic devices., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

An advanced visible/infrared dual-band photodetector with high-resolution imaging at room temperature is proposed and demonstrated for intelligent identification based on the 2D GaSe/GaSb vertical heterostructure. It resolves the challenges of producing large-scale 2D growth, achieving fast response speed, outstanding detectivity, and lower manufacture cost, which are the main obstacles for industrialization of 2D-materials-based photodetection., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Two-dimensional materials are promising candidates for electronic and optoelectronic applications. MoTe2 has an appropriate bandgap for both visible and infrared light photodetection. Here we fabricate a high-performance photodetector based on few-layer MoTe2. Raman spectral properties have been studied for different thicknesses of MoTe2. The photodetector based on few-layer MoTe2 exhibits broad spectral range photodetection (0.6-1.55 μm) and a stable and fast photoresponse. The detectivity is calculated to be 3.1 × 10(9) cm Hz(1/2) W(-1) for 637 nm light and 1.3 × 10(9) cm Hz(1/2) W(-1) for 1060 nm light at a backgate voltage of 10 V. The mechanisms of photocurrent generation have been analyzed in detail, and it is considered that a photogating effect plays an important role in photodetection. The appreciable performance and detection over a broad spectral range make it a promising material for high-performance photodetectors.

One-dimensional InAs nanowires (NWs) have been widely researched in recent years. Features of high mobility and narrow bandgap reveal its great potential of optoelectronic applications. However, most reported work about InAs NW-based photodetectors is limited to the visible waveband. Although some work shows certain response for near-infrared light, the problems of large dark current and small light on/off ratio are unsolved, thus significantly restricting the detectivity. Here in this work, a novel "visible light-assisted dark-current suppressing method" is proposed for the first time to reduce the dark current and enhance the infrared photodetection of single InAs NW photodetectors. This method effectively increases the barrier height of the metal-semiconductor contact, thus significantly making the device a metal-semiconductor-metal (MSM) photodiode. These MSM photodiodes demonstrate broadband detection from less than 1 μm to more than 3 μm and a fast response of tens of microseconds. A high detectivity of ∼10 12 Jones has been achieved for the wavelength of 2000 nm at a low bias voltage of 0.1 V with corresponding responsivity of as much as 40 A/W. Even for the incident wavelength of 3113 nm, a detectivity of ∼10 10 Jones and a responsivity of 0.6 A/W have been obtained. Our work has achieved an extended detection waveband for single InAs NW photodetector from visible and near-infrared to mid-infrared. The excellent performance for infrared detection demonstrated the great potential of narrow bandgap NWs for future infrared optoelectronic applications.

Graphene, a two-dimensional material, is expected to enable broad-spectrum and high-speed photodetection because of its gapless band structure, ultrafast carrier dynamics and high mobility. We demonstrate a multispectral active infrared imaging by using a graphene photodetector based on hybrid response mechanisms at room temperature. The high-quality images with optical resolutions of 418 nm, 657 nm and 877 nm and close-to-theoretical-limit Michelson contrasts of 0.997, 0.994, and 0.996 have been acquired for 565 nm, 1550 nm, and 1815 nm light imaging measurements by using an unbiased graphene photodetector, respectively. Importantly, by carefully analyzing the results of Raman mapping and numerical simulations for the response process, the formation of hybrid photocurrents in graphene detectors is attributed to the synergistic action of photovoltaic and photo-thermoelectric effects. The initial application to infrared imaging will help promote the development of high performance graphene-based infrared multispectral detectors.

All-inorganic cesium lead halide perovskite (CsPbX3, X = Cl, Br, and I) nanocrystals (NCs) are emerging as an important class of semiconductor materials with superior photophysical properties and wide potential applications in optoelectronic devices. So far, only a few studies have been conducted to control the shape and geometry of CsPbX3 NCs. Here we report a general approach to directly synthesize two-dimensional (2D) CsPbX3 perovskite and mixed perovskite nanosheets with uniform and ultrathin thicknesses down to a few monolayers. The key to the high-yield synthesis of perovskite nanosheets is the development of a new Cs-oleate precursor. The as-synthesized CsPbX3 nanosheets exhibit bright photoluminescence with broad wavelength tunability by composition modulation. The excellent optoelectronic properties of CsPbX3 nanosheets combined with their unique 2D geometry and large lateral dimensions make them ideal building blocks for building functional devices. To demonstrate their potential applications in optoelectronics, photodetectors based on CsPbBr3 nanosheets are fabricated, which exhibit high on/off ratios with a fast response time.

The gastric bacterial pathogen Helicobacter pylori persistently colonizes the gastric mucosa of humans and plays a critical role in the development of gastritis, peptic ulceration and gastric adenocarcinoma. Consequently, the eradication of H. pylori might contribute to the prevention of H. pylori-associated gastric diseases. In this study, a multi-epitope vaccine CTB-UE (CUE) was displayed on the surface of non-genetically modified Lactococcus lactis particles (GEM) to enhance immunogenicity. This particulate vaccine CUE-GEM induced serum and mucosal specific antibody responses against native H. pylori urease and provided potent protection to eliminate H. pylori colonization and relieve gastritis in an H. pylori-infected BALB/c mouse model. The immuno-protective mechanisms are highly associated with CD4(+) Th cell-mediated and humoral immunity, especially local immunity. There might be two main aspects of this association. One aspect is related to the suppression of urease activity by promotion of the production of specific mucosal neutralizing antibody. The other aspect is correlated with alleviating gastritis by regulating the gastric pro-inflammatory cytokine profile, especially IFN-γ and IL-17. These results demonstrated that conjugating antigen vaccines with GEM particles could lead to promising oral therapeutic vaccine formulations against H. pylori infection.

2D Molybdenum disulfide (MoS2 ) is a promising candidate material for high-speed and flexible optoelectronic devices, but only with low photoresponsivity. Here, a large enhancement of photocurrent response is obtained by coupling few-layer MoS2 with Au plasmonic nanostructure arrays. Au nanoparticles or nanoplates placed onto few-layer MoS2 surface can enhance the local optical field in the MoS2 layer, due to the localized surface plasmon (LSP) resonance. After depositing 4 nm thick Au nanoparticles sparsely onto few-layer MoS2 phototransistors, a doubled increase in the photocurrent response is observed. The photocurrent of few-layer MoS2 phototransistors exhibits a threefold enhancement with periodic Au nanoarrays. The simulated optical field distribution confirms that light can be trapped and enhanced near the Au nanoplates. These findings offer an avenue for practical applications of high performance MoS2 -based optoelectronic devices or systems in the future., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Epidemiologic studies have provided solid evidence for the neurotoxic effect of lead for decades of years. In view of the fact that children are more vulnerable to the neurotoxicity of lead, lead exposure has been an urgent public health concern. The modes of action of lead neurotoxic effects include disturbance of neurotransmitter storage and release, damage of mitochondria, as well as induction of apoptosis in neurons, cerebrovascular endothelial cells, astroglia and oligodendroglia. Our studies here, from a novel point of view, demonstrates that lead specifically caused induction of COX-2, a well known inflammatory mediator in neurons and glia cells. Furthermore, we revealed that COX-2 was induced by lead in a transcription-dependent manner, which relayed on transcription factor NFAT, rather than AP-1 and NFκB, in glial cells. Considering the important functions of COX-2 in mediation of inflammation reaction and oxidative stress, our studies here provide a mechanistic insight into the understanding of lead-associated inflammatory neurotoxicity effect via activation of pro-inflammatory NFAT3/COX-2 axis., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)