Nonlinear Nano-Imaging of Interlayer Coupling in 2D Graphene-Semiconductor Heterostructures.

The emergent electronic, spin, and other quantum properties of 2D heterostructures of graphene and transition metal dichalcogenides are controlled by the underlying interlayer coupling and associated charge and energy transfer dynamics. However, these processes are sensitive to interlayer distance and crystallographic orientation, which are in turn affected by defects, grain boundaries, or other nanoscale heterogeneities. This obfuscates the distinction between interlayer charge and energy transfer. Here, nanoscale imaging in coherent four-wave mixing (FWM) and incoherent two-photon photoluminescence (2PPL) is combined with a tip distance-dependent coupled rate equation model to resolve the underlying intra- and inter-layer dynamics while avoiding the influence of structural heterogeneities in mono- to multi-layer graphene/WSe2 heterostructures. With selective insertion of hBN spacer layers, it is shown that energy, as opposed to charge transfer, dominates the interlayer-coupled optical response. From the distinct nano-FWM and -2PPL tip-sample distance-dependent modification of interlayer and intralayer relaxation by tip-induced enhancement and quenching, an interlayer energy transfer time of τ ET ≈ ( 0 . 35 - 0.15 + 0.65 ) $\tau _{\rm ET} \approx (0.35^{+0.65}_{-0.15})$  ps consistent with recent reports is derived. As a local probe technique, this approach highlights the ability to determine intrinsic sample properties even in the presence of large sample heterogeneity.

Advancements and Challenges in the Integration of Indium Arsenide and Van der Waals Heterostructures.

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.

Confined and spontaneously transformed oxidation structures due to the intrinsic heterogeneous surface morphology of C3N monolayer.

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.

Optimizing the aldosterone-to-renin ratio cut-off for screening primary aldosteronism based on cardiovascular risk: a collaborative study.

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).

Ultrafast Nanoimaging of Electronic Coherence of Monolayer WSe2.

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 WSe2. We observe nanoscale heterogeneities at room temperature with dephasing ranging from T2 ≲ 5 to T2 ≳ 60 fs on length scales of 50-100 nm. We further observe a counterintuitive anticorrelation between FWM intensity and T2, 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.

Primary aldosteronism and lower-extremity arterial disease: a two-sample Mendelian randomization study.

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.

Emerging Single-Photon Detectors Based on Low-Dimensional Materials.

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.

Room-Temperature Single-Photon Detector Based on Single Nanowire.

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.

Visible Light-Assisted High-Performance Mid-Infrared Photodetectors Based on Single InAs Nanowire.

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 ∼1012 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 ∼1010 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.

Highly sensitive visible to infrared MoTe2 photodetectors enhanced by the photogating effect.

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.

Therapeutic efficacy of oral immunization with a non-genetically modified Lactococcus lactis-based vaccine CUE-GEM induces local immunity against Helicobacter pylori infection.

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.

Surface Plasmon-Enhanced Photodetection in Few Layer MoS2 Phototransistors with Au Nanostructure Arrays.

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.

An observational and genetic investigation into the association between psoriasis and risk of malignancy.

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.

Abdominal obesity and CKD: A potential mediating role of serum metabolites in the UK Biobank population.

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.

Renin-Angiotensin-Aldosterone System Modulators in Adults with Hypertension: A Network Meta-Analysis of Randomized Controlled Trials.

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.

Comparison of four confirmatory tests for the diagnosis of primary aldosteronism: Bayesian analysis in the absence of a gold standard.

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.

Secondhand smoke, genetic susceptibility, and incident chronic kidney disease in never smokers: A prospective study of a selected population from the UK Biobank.

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.

Risky working conditions and chronic kidney disease.

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.

Renin-independent aldosteronism and chronic kidney disease in diabetes: Observational and Mendelian randomization analyses.

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.

Association between fat mass and mortality: analysis of Mendelian randomization and lifestyle modification.

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.