USP11 promotes renal tubular cell pyroptosis and fibrosis in UUO mice via inhibiting KLF4 ubiquitin degradation.

The pyroptosis of renal tubular epithelial cells leads to tubular loss and inflammation and then promotes renal fibrosis. The transcription factor Krüppel-like factor 4 (KLF4) can bidirectionally regulate the transcription of target genes. Our previous study revealed that sustained elevation of KLF4 is responsible for the transition of acute kidney injury (AKI) into chronic kidney disease (CKD) and renal fibrosis. In this study, we explored the upstream mechanisms of renal tubular epithelial cell pyroptosis from the perspective of posttranslational regulation and focused on the transcription factor KLF4. Mice were subjected to unilateral ureteral obstruction (UUO) surgery and euthanized on D7 or D14 for renal tissue harvesting. We showed that the pyroptosis of renal tubular epithelial cells mediated by both the Caspase-1/GSDMD and Caspase-3/GSDME pathways was time-dependently increased in UUO mouse kidneys. Furthermore, we found that the expression of the transcription factor KLF4 was also upregulated in a time-dependent manner in UUO mouse kidneys. Tubular epithelial cell-specific Klf4 knockout alleviated UUO-induced pyroptosis and renal fibrosis. In Ang II-treated mouse renal proximal tubular epithelial cells (MTECs), we demonstrated that KLF4 bound to the promoter regions of Caspase-3 and Caspase-1 and directly increased their transcription. In addition, we found that ubiquitin-specific protease 11 (USP11) was increased in UUO mouse kidneys. USP11 deubiquitinated KLF4. Knockout of Usp11 or pretreatment with the USP11 inhibitor mitoxantrone (3 mg/kg, i.p., twice a week for two weeks before UUO surgery) significantly alleviated the increases in KLF4 expression, pyroptosis and renal fibrosis. These results demonstrated that the increased expression of USP11 in renal tubular cells prevents the ubiquitin degradation of KLF4 and that elevated KLF4 promotes inflammation and renal fibrosis by initiating tubular cell pyroptosis.

Molecularly Imprinted Wearable Sensor with Paper Microfluidics for Real-Time Sweat Biomarker Analysis.

The urgent need for real-time and noninvasive monitoring of health-associated biochemical parameters has motivated the development of wearable sweat sensors. Existing electrochemical sensors show promise in real-time analysis of various chemical biomarkers. These sensors often rely on labels and redox probes to generate and amplify the signals for the detection and quantification of analytes with limited sensitivity. In this study, we introduce a molecularly imprinted polymer (MIP)-based biochemical sensor to quantify a molecular biomarker in sweat using electrochemical impedance spectroscopy, which eliminates the need for labels or redox probes. The molecularly imprinted biosensor can achieve sensitive and specific detection of cortisol at concentrations as low as 1 pM, 1000-fold lower than previously reported MIP cortisol sensors. We integrated multimodal electrochemical sensors with an iontophoresis sweat extraction module and paper microfluidics for real-time sweat analysis. Several parameters can be simultaneously quantified, including sweat volume, secretion rate, sodium ion, and cortisol concentration. Paper microfluidic modules not only quantify sweat volume and secretion rate but also facilitate continuous sweat analysis without user intervention. While we focus on cortisol sensing as a proof-of-concept, the molecularly imprinted wearable sensors can be extended to real-time detection of other biochemicals, such as protein biomarkers and therapeutic drugs.

Plasma-Enabled Process with Single-Atom Catalysts for Sustainable Plastic Waste Transformation.

In this study, we present a novel plasma-enabled strategy for the rapid breakdown of various types of plastic wastes, including mixtures, into high-value carbon nanomaterials and hydrogen. The H2 yield and selectivity achieved through the catalyst-free plasma-enabled strategy are 14.2 and 5.9 times higher, respectively, compared to those obtained with conventional thermal pyrolysis. It is noteworthy that this catalyst-free plasma alone approach yields a significantly higher energy yield of H2 (gH2/kWh) compared to other pyrolysis processes. By coupling plasma pyrolysis with thermal catalytic process, employing of 1 wt.% M/CeO2 atomically dispersed catalysts can further enhance hydrogen production. Specifically, the 1 wt.% Co/CeO2 catalyst demonstrated excellent catalytic performance throughout the 10 cycles of plastic waste decomposition, achieving the highest H2 yield of 46.7 mmol/gplastic (equivalent to 64.4% of theoretical H2 production) and nearly 100% hydrogen atom recovery efficiency at the 7th cycle. Notably, the H2 yield achieved over the atomically dispersed Fe on CeO2 surface in the integrated plasma-thermal catalytic process is comparable to that obtained with Fe particles on CeO2 surface (10 wt.%). This innovative and straightforward approach provides a promising and expedient strategy for continuously converting diverse plastic waste streams into high-value products conducive to a circular plastic economy.

Decorin attenuates hypertrophic scar fibrosis via TGFß/Smad signalling.

The management of hypertrophic scars (HSs), characterized by excessive collagen production, involves various nonsurgical and surgical interventions. However, the absence of a well-defined molecular mechanism governing hypertrophic scarring has led to less-than-ideal results in clinical antifibrotic treatments. Therefore, our study focused on the role of decorin (DCN) and its regulatory role in the TGF-ß/Smad signalling pathway in the development of HSs. In our research, we observed a decrease in DCN expression within hypertrophic scar tissue and its derived cells (HSFc) compared to that in normal tissue. Then, the inhibitory effect of DCN on collagen synthesis was confirmed in Fc and HSFc via the detection of fibrosis markers such as COL-1 and COL-3 after the overexpression and knockdown of DCN. Moreover, functional assessments revealed that DCN suppresses the proliferation, migration and invasion of HSFc. We discovered that DCN significantly inhibits the TGF-ß1/Smad3 pathway by suppressing TGF-ß1 expression, as well as the formation and phosphorylation of Smad3. This finding suggested that DCN regulates the synthesis of collagen-based extracellular matrix and fibrosis through the TGF-ß1/Smad3 pathway.

Bioactive Alkaloids from the Mangrove-Derived Fungus Nigrospora oryzae SYSU-MS0024.

Chemical investigation of marine fungus Nigrospora oryzae SYSU-MS0024 cultured on solid-rice medium led to the isolation of three new alkaloids, including a pair of epimers, nigrosporines A (1) and B (2), and a pair of enantiomers, (+)-nigrosporine C (+)-3, and (-)-nigrosporine C (-)-3, together with eight known compounds (4-11). Their structures were elucidated based on extensive mass spectrometry (MS) and 1D/2D nuclear magnetic resonance (NMR) spectroscopic analyses and compared with data in the literature. The absolute configurations of compounds 1-3 were determined by a combination of electronic circular dichroism (ECD) calculations, Mosher's method, and X-ray single-crystal diffraction technique using Cu Kα radiation. In bioassays, compound 2 exhibited moderate inhibition on NO accumulation induced by lipopolysaccharide (LPS) on BV-2 cells in a dose-dependent manner at 20, 50, and 100 µmol/L and without cytotoxicity in a concentration of 100.0 µmol/L. Moreover, compound 2 also showed moderate acetylcholinesterase (AChE) inhibitory activities with IC50 values of 103.7 µmol/L. Compound 5 exhibited moderate antioxidant activity with EC50 values of 167.0 µmol/L.

Successful secukinumab treatment of generalized pustular psoriasis.

Generalized pustular psoriasis is a rare variant of psoriasis. Evidence recommending generalized pustular psoriasis treatment with secukinumab is limited. This report aims to evaluate the use of secukinumab in two patients with generalized pustular psoriasis. The standard treatment regimen for secukinumab was as follows: 300mg subcutaneously once weekly in weeks 0-4, followed by 300mg every four weeks. The efficacy was evaluated by analyzing the psoriasis area and severity index (PASI) and dermatology life quality index (DLQI). One patient had generalized pustular psoriasis, which had developed from palmoplantar pustulosis over 12 years. The second patient was an adolescent with recurrent generalized pustular psoriasis. The first patient achieved PASI-75 response by week 3 and both PASI-90 and a DLQI score of 0 were observed by week 8. The second patient achieved PASI-75 response by week 4 and complete clinical resolution, except for nail changes, and a DLQI of 0 by week 8, without any adverse events.

Development and validation of potential phenotypes of serum electrolyte disturbances in critically ill patients and a Web-based application.

BACKGROUND: Electrolyte disturbances are highly heterogeneous and severely affect the prognosis of critically ill patients. Our study was to determine whether data-driven phenotypes of seven electrolytes have prognostic relevance in critically ill patients. METHODS: We extracted patient information from three large independent public databases, and clustered the electrolyte distribution of ICU patients based on the extreme value, median value and coefficient of variation of electrolytes. Three plausible clinical phenotypes were calculated using K-means clustering algorithm as the basic clustering method. MIMIC-IV was considered a training set, and two others have been designated as verification set. The robustness of the model was then validated from different angles, providing dynamic and interactive visual charts for more detailed characterization of phenotypes. RESULTS: 15,340, 12,445 and 2147 ICU patients with electrolyte records during early ICU stay in MIMIC-IV, eICU-CRD and AmsterdamUMCdb were enrolled. After clustering, three reasonable and interpretable phenotypes are defined as α, ß and γ according to the order of clusters. The α and γ phenotype, with significant differences in electrolyte distribution and clinical variables, higher 28-day mortality and longer length of ICU stay (p < 0.001), was further demonstrated by robustness analysis. The α phenotype has significant kidney injury, while the ß phenotype has the best prognosis. In addition, the assignment methods of the three phenotypes were developed into a web-based tool for further verification and application. CONCLUSIONS: Three different clinical phenotypes were identified that correlated with electrolyte distribution and clinical outcomes. Further validation and characterization of these phenotypes is warranted.

Exercise preconditioning inhibits doxorubicin-induced cardiotoxicity via YAP/STAT3 signaling.

Doxorubicin (DOX) possesses strong anti-tumor effects but is limited by its irreversible cardiac toxicity. The relationship between exercise, a known enhancer of cardiovascular health, and DOX-induced cardiotoxicity has been a focus of recent research. Exercise has been suggested to mitigate DOX's cardiac harm by modulating the Yes-associated protein (YAP) and Signal transducer and activator of transcription 3 (STAT3) pathways, which are crucial in regulating cardiac cell functions and responses to damage. This study aimed to assess the protective role of exercise preconditioning against DOX-induced cardiac injury. We used Sprague-Dawley rats, divided into five groups (control, DOX, exercise preconditioning (EP), EP-DOX, and verteporfin + EP + DOX), to investigate the potential mechanisms. Our findings, including echocardiography, histological staining, Western blot, and q-PCR analysis, demonstrated that exercise preconditioning could alleviate DOX-induced cardiac dysfunction and structural damage. Notably, exercise preconditioning enhanced the nuclear localization and co-localization of YAP and STAT3. Our study suggests that exercise preconditioning may counteract DOX-induced cardiotoxicity by activating the YAP/STAT3 pathway, highlighting a potential therapeutic approach for reducing DOX's cardiac side effects.

Wearable photoacoustic watch for humans.

Longitudinal detection of hemodynamic changes based on wearable devices is imperative for monitoring human healthcare. Photoacoustic effect is extremely sensitive to variations in hemoglobin. Therefore, wearable photoacoustic devices are apt to monitor human healthcare via the observation of hemodynamics. However, the bulky system and difficulties in miniaturizing and optimizing the imaging interface restrict the development of wearable photoacoustic devices for human use. In this study, we developed a wearable photoacoustic watch with a fully integrated system in a backpack that has a size of 450 mm × 300 mm × 200 mm and an affordable weight of 7 kg for an adult to wear. The watch has a size of 43 mm × 30 mm × 24 mm, weighs 40 g, and features a lateral resolution of 8.7 µm, a field of view (FOV) of 3 mm in diameter, and a motorized adjustable focus for optimizing the imaging plane for different individuals. We recruited volunteers to wear the watch and the backpack and performed in vivo imaging of the vasculatures inside human wrists under the conditions of walking and human cuff occlusion to observe hemodynamic variations during different physiological states. The results suggest that the focus shifting capability of the watch makes it suitable for different individuals, and the compact and stable design of the entire system allows free movements of humans.

Correlation between early intracranial pressure and cerebral perfusion pressure with 28-day intensive care unit mortality in patients with hemorrhagic stroke.

INTRODUCTION: Hemorrhagic stroke may cause changes in intracranial pressure (ICP) and cerebral perfusion pressure (CPP), which may influence the prognosis of patients. The aim of this study was to investigate the relationship between early ICP, CPP, and 28-day mortality in the intensive care unit (ICU) of patients with hemorrhagic stroke. PATIENTS AND METHODS: A retrospective study was performed using the Medical Information Mart for Intensive Care (MIMIC-IV) and the eICU Collaborative Research Database (eICU-CRD), including hemorrhagic stroke patients in the ICU with recorded ICP monitoring. The median values of ICP and CPP were collected for the first 24 h of the patient's monitoring. The primary outcome was 28-day ICU mortality. Multivariable Cox proportional hazards models were used to analyze the relationship between ICP, CPP, and 28-day ICU mortality. Restricted cubic regression splines were used to analyze nonlinear relationships. RESULTS: The study included 837 patients with a 28-day ICU mortality rate of 19.4%. Multivariable analysis revealed a significant correlation between early ICP and 28-day ICU mortality (HR 1.08, 95% CI 1.04-1.12, p < 0.01), whereas early CPP showed no correlation with 28-day ICU mortality (HR 1.00, 95% CI 0.98-1.01, p = 0.57), with a correlation only evident when CPP < 60 mmHg (HR 1.99, 95% CI 1.14-3.48, p = 0.01). The study also identified an early ICP threshold of 16.5 mmHg. DISCUSSION AND CONCLUSION: Early ICP shows a correlation with 28-day mortality in hemorrhagic stroke patients, with a potential intervention threshold of 16.5 mmHg. In contrast, early CPP showed no correlation with patient prognosis.

Mutability landscape guided engineering of a promiscuous microbial glycosyltransferase for regioselective synthesis of salidroside and icariside D2.

Microbial glycosyltransferases efficiently synthesize glucosides and have garnered increasing interest. However, limited regioselectivity has impeded their broad application, particularly in the pharmaceutical industry. In this study, the UDP-glycosyltransferase YjiC from Bacillus licheniformis (BlYjiC) was engineered to achieve the bidirectional regioselective glycosylation of tyrosol and its derivatives. Initially, site-directed saturation mutagenesis was performed on two newly identified substrate-binding cavities in the acceptor pocket of BlYjiC to provide a comprehensive blueprint of the interplay between mutations and function (mutability landscape). Iterative saturation mutagenesis was performed, guided by the mutability landscape. Two highly regioselective mutants M6 (M112L/I325Y/L70R/Q136E/I67E/M77R) and M2' (M112D/I62L) were generated, exhibiting >99 % regioselectivity toward the alcoholic and phenolic hydroxyl of tyrosol, respectively, compared with the wild-type (product mixture: 51:49 %). Both mutants exhibited excellent regioselectivity toward several dihydroxy phenolic substrates, offering valuable biocatalysts for the regioselective synthesis of glucosides. Their application was confirmed in a short synthesis of salidroside (3.6 g/L) and icariside D2 (2.4 g/L), which exhibited near-perfect regioselectivity. This study provides valuable insights into future protein engineering of similar enzymes and opens new avenues for their practical applications.

Effects of CYP3A4*22 and POR*28 variations on the pharmacokinetics of tacrolimus in renal transplant recipients: a meta-analysis of 18 observational studies.

PURPOSE: This study aimed to investigate the association between cytochrome P450 (CYP) 3A4*22 and cytochrome P450 oxidoreductase (POR)*28 variations and the pharmacokinetics of tacrolimus. METHODS: Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science (SCI), MEDLINE, and Embase were systematically searched from inception to August 2022. The outcomes were weight-adjusted daily dose and dose-adjusted trough concentration (C0/Dose). RESULTS: The study included 2931 renal transplant recipients from 18 publications. Weight-adjusted daily dose of CYP3A4*1/*1 carriers was 0.04 (WMD = 0.04, 95% CI: 0.02 to 0.06), 0.03 (WMD = 0.03, 95% CI: 0.02 to 0.05), 0.02 (WMD = 0.02, 95% CI: 0.01 to 0.03), or 0.02 mg/kg/day (WMD = 0.02, 95% CI: 0.00 to 0.04) higher than CYP3A4*22 carriers in Caucasians at 1 month, 3 months, 6 months, or 12 months post-transplantation. Conversely, C0/Dose was lower for CYP3A4*1/*1 carriers at 3 days (SMD = -0.35, 95% CI: -0.65 to -0.06), 1 month (SMD = -0.67, 95% CI: -1.16 to -0.18), 3 months (SMD = -0.60, 95% CI: -0.89 to -0.31), 6 months (SMD = -0.76, 95% CI: -1.49 to -0.04), or 12 months post-transplantation (SMD = -0.69, 95% CI: -1.37 to 0.00). Furthermore, C0/Dose of POR*1/*1 carriers was 22.64 (WMD = 22.64, 95% CI: 2.54 to 42.74) or 19.41 (ng/ml)/(mg/kg/day) (WMD = 19.41, 95% CI: 9.58 to 29.24) higher than POR*28 carriers in CYP3A5 expressers at 3 days or 7 days post-transplantation, and higher in Asians at 6 months post-transplantation (SMD = 0.96, 95% CI: 0.50 to 1.43). CONCLUSIONS: CYP3A4*22 variant in Caucasians restrains the metabolism of tacrolimus, while POR*28 variant in CYP3A5 expressers enhances the metabolism of tacrolimus for renal transplant recipients. However, further well-designed prospective studies are necessary to substantiate these conclusions given some limitations.

Photoacoustic expansion microscopy of melanosomes.

Optical resolution photoacoustic microscopy (OR-PAM) is a hybrid imaging method for visualizing organelles due to the high spatial resolution and abundant optical contrast. Usually, OR-PAM employs high numerical aperture (NA) objectives and high-frequency ultrasonic detectors to resolve three-dimensional (3D) microstructures of cells. Expansion microscopy (ExM) provides a nanoscale resolution by isotropically enlarging cells instead of utilizing ultrahigh NA objectives. In this Letter, we report the development of photoacoustic expansion microscopy (PA-ExM) that combines the advantages of OR-PAM and ExM for 3D organelle imaging using near-infrared light. We evaluate the performance of PA-ExM using label-free melanoma cells, where the image quality of melanosome distributions in expanded cells using a 40× objective is comparable to that of unexpanded cells using an oil-immersed 100× objective. The results suggest that PA-ExM possesses the great potential to study organelles.

Comparison of the effects of imputation methods for missing data in predictive modelling of cohort study datasets.

BACKGROUND: Missing data is frequently an inevitable issue in cohort studies and it can adversely affect the study's findings. We assess the effectiveness of eight frequently utilized statistical and machine learning (ML) imputation methods for dealing with missing data in predictive modelling of cohort study datasets. This evaluation is based on real data and predictive models for cardiovascular disease (CVD) risk. METHODS: The data is from a real-world cohort study in Xinjiang, China. It includes personal information, physical examination data, questionnaires, and laboratory biochemical results from 10,164 subjects with a total of 37 variables. Simple imputation (Simple), regression imputation (Regression), expectation-maximization(EM), multiple imputation (MICE) , K nearest neighbor classification (KNN), clustering imputation (Cluster), random forest (RF), and decision tree (Cart) were the chosen imputation methods. Root Mean Square Error (RMSE) and Mean Absolute Error (MAE) are utilised to assess the performance of different methods for missing data imputation at a missing rate of 20%. The datasets processed with different missing data imputation methods were employed to construct a CVD risk prediction model utilizing the support vector machine (SVM). The predictive performance was then compared using the area under the curve (AUC). RESULTS: The most effective imputation results were attained by KNN (MAE: 0.2032, RMSE: 0.7438, AUC: 0.730, CI: 0.719-0.741) and RF (MAE: 0.3944, RMSE: 1.4866, AUC: 0.777, CI: 0.769-0.785). The subsequent best performances were achieved by EM, Cart, and MICE, while Simple, Regression, and Cluster attained the worst performances. The CVD risk prediction model was constructed using the complete data (AUC:0.804, CI:0.796-0.812) in comparison with all other models with p<0.05. CONCLUSION: KNN and RF exhibit superior performance and are more adept at imputing missing data in predictive modelling of cohort study datasets.

Molecular mechanisms underlying the BIRC6-mediated regulation of apoptosis and autophagy.

Procaspase 9 is the initiator caspase for apoptosis, but how its levels and activities are maintained remains unclear. The gigantic Inhibitor-of-Apoptosis Protein BIRC6/BRUCE/Apollon inhibits both apoptosis and autophagy by promoting ubiquitylation of proapoptotic factors and the key autophagic protein LC3, respectively. Here we show that BIRC6 forms an anti-parallel U-shaped dimer with multiple previously unannotated domains, including a ubiquitin-like domain, and the proapoptotic factor Smac/DIABLO binds BIRC6 in the central cavity. Notably, Smac outcompetes the effector caspase 3 and the pro-apoptotic protease HtrA2, but not procaspase 9, for binding BIRC6 in cells. BIRC6 also binds LC3 through its LC3-interacting region, probably following dimer disruption of this BIRC6 region. Mutation at LC3 ubiquitylation site promotes autophagy and autophagic degradation of BIRC6. Moreover, induction of autophagy promotes autophagic degradation of BIRC6 and caspase 9, but not of other effector caspases. These results are important to understand how the balance between apoptosis and autophagy is regulated under pathophysiological conditions.

PGAM5 exacerbates acute renal injury by initiating mitochondria-dependent apoptosis by facilitating mitochondrial cytochrome c release.

Acute kidney injury (AKI) is a worldwide public health problem characterized by the massive loss of tubular cells. However, the precise mechanism for initiating tubular cell death has not been fully elucidated. Here, we reported that phosphoglycerate mutase 5 (PGAM5) was upregulated in renal tubular epithelial cells during ischaemia/reperfusion or cisplatin-induced AKI in mice. PGAM5 knockout significantly alleviated the activation of the mitochondria-dependent apoptosis pathway and tubular apoptosis. Apoptosis inhibitors alleviated the activation of the mitochondria-dependent apoptosis pathway. Mechanistically, as a protein phosphatase, PGAM5 could dephosphorylate Bax and facilitate Bax translocation to the mitochondrial membrane. The translocation of Bax to mitochondria increased membrane permeability, decreased mitochondrial membrane potential and facilitated the release of mitochondrial cytochrome c (Cyt c) into the cytoplasm. Knockdown of Bax attenuated PGAM5 overexpression-induced Cyt c release and tubular cell apoptosis. Our results demonstrated that the increase in PGAM5-mediated Bax dephosphorylation and mitochondrial translocation was implicated in the development of AKI by initiating mitochondrial Cyt c release and activating the mitochondria-dependent apoptosis pathway. Targeting this axis might be beneficial for alleviating AKI.

Validation of non-invasive indicators in the screening of metabolic dysfunction-associated fatty liver disease: a cross-sectional study among Uighurs in rural Xinjiang.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common chronic liver disease in China. Our study aimed to evaluate the screening value of the fatty liver index (FLI), hepatic steatosis index (HSI), lipid accumulation product (LAP), visceral adiposity index (VAI), and Zhejiang University index (ZJU), as well as other single indicators for MAFLD. We aimed to find the optimal screening tool and its appropriate cut-off values for rural Uyghur adults. METHODS: We completed a survey of 14,321 Uyghur adults in 51 groups in Kashgar, Xinjiang, in 2016 using a typical sampling method, with 12,794 patients ultimately included in statistical analyses. Fatty liver was diagnosed using ultrasonography. RESULTS: The prevalence of fatty liver disease (FLD) and MAFLD was 16.73% and 16.55%, respectively, and the FLI, HSI, LAP, VAI, and ZJU were all independently associated with an increased risk of MAFLD. The areas under the receiver operating characteristic curves (AUCs) of the FLI for diagnosing MAFLD in men and women were 0.853 and 0.847, respectively. The AUCs of the body mass index (BMI) for diagnosing MAFLD in men and women were 0.850 and 0.852, respectively. Compared with other metabolic-related markers, FLI had the largest AUC. In men, the optimal cut-off values of FLI and BMI for diagnosing MAFLD were 45 (sensitivity 84.83%, specificity 69.57%) and 27.4 (sensitivity 78.47%, specificity 76.30%), respectively. In women, the optimal cut-off values of FLI and BMI for diagnosing MAFLD were 45 (sensitivity 80.11%, specificity 74.23%) and 28.0 (sensitivity 79.56%, specificity 75.41%), respectively. In men and women, an FLI score of < 30 ruled out MAFLD, while a score of ≥ 50 was a basis for diagnosis. CONCLUSION: FLI and BMI had good screening ability for MAFLD and were superior to HSI, LAP, VAI, and ZJU in both sexes.

Vacancy-Mediated Control of Local Electronic Structure for High-Efficiency Electrocatalytic Conversion of N2 to NH3.

Ambient electrocatalytic nitrogen (N2 ) reduction has gained significant recognition as a potential substitute for producing ammonia (NH3 ). However, N2 adsorption and *NN protonation for N2 activation reaction with the competing hydrogen evolution reaction remain a daunting challenge. Herein, a defect-rich TiO2 nanosheet electrocatalyst with PdCu alloy nanoparticles (PdCu/TiO2-x ) is designed to elucidate the reactivity and selectivity trends of N2 cleavage path for N2 -to-NH3 catalytic conversion. The introduction of oxygen vacancy (OV) not only acts as active sites but also effectively promotes the electron transfer from Pd-Cu sites to high-concentration Ti3+ sites, and thus lends to the N2 activation via electron donation of PdCu. OVs-mediated control effectively lowers the reaction barrier of *N2 H and *H adsorption and facilitates the first hydrogenation process of N2 activation. Consequently, PdCu/TiO2-x catalyst attains a high rate of NH3 evolution, reaching 5.0 mmol gcat. -1  h-1 . This work paves a pathway of defect-engineering metal-supported electrocatalysts for high-efficient ammonia electrosynthesis.

Enhanced Carrier Dynamics of CsPbBr3 Nanocrystals Enabled by Short-Ligand Ethanedithiol for Efficient Photoelectrocatalytic Photoanodes.

Photoelectrochemical (PEC) water splitting is a potential solution for a low-carbon society and clean energy storage due to its ability to produce hydrogen and oxygen. However, the slow oxidation half-reaction of the process has limited its overall efficacy, necessitating the development of an efficient photoanode. Colloidal CsPbBr3 nanocrystals (NCs) have been identified as promising candidates due to their high light absorption and valence band position. However, the presence of the electrical insulator, long-chain oleate molecules, on the surface of the CsPbBr3 NCs has hindered efficient charge carrier separation and transport. To solve this problem, short-chain 1,2-ethanedithiol (EDT) ligands were used to replace the oleate ligands on the surface of the CsPbBr3 NCs through a solid-state ligand exchange method. This resulted in a reduction of the nanocrystal spacing and a cross-linking reaction, which improved the photogenerated carrier separation and transport while still passivating the dangling bonds on the CsPbBr3 NC surface. Ultimately, this led to a remarkable photocurrent density of 3.34 mA cm-2 (1.23 VRHE), which was 5.2 times higher than that of the pristine oleate-CsPbBr3 NC (0.64 mA cm-2)-based device. This work presents an efficient way of developing inorganic lead halide perovskite colloidal nanocrystal-based photoanodes through surface ligand engineering.