Immunosuppressant-resistant nephrotic syndrome and primary amenorrhea: A case report of adult Frasier syndrome and literature review.

We present a case of a 19-year-old who developed nephrotic syndrome with preserved renal function. Renal biopsy confirmed focal segmental glomerular sclerosis (FSGS). No remission was achieved despite 2 years of treatment with glucocorticoids, mycophenolate mofetil, tacrolimus, and cyclophosphamide. After transfer to our center, we performed re-examination of renal pathology by electron microscope (EM), chromosomal karyotype, and gene analysis. EM revealed uneven thickness of the glomerular basement membrane without obvious stratification or fracture. Gene analysis revealed a splice mutation (1447+1G>A) in IVS9 and chromosomal karyotype was (46, XY), confirming the diagnosis of Frasier syndrome, which was consistent with primary amenorrhea overlooked by local nephrologists. Cyclosporin A was prescribed to reduce the proteinuria, but serum creatinine increased to 152 µmol/L.

Disparity of serum uric acid threshold for CKD among hypertensive and non-hypertensive individuals.

INTRODUCTION: Hypertension and rising serum uric acid (sUA) played a pivotal role in the development of Chronic Kidney Disease (CKD). This study investigates the interactive effect of sUA and hypertension on CKD and identifies the optimal threshold of sUA among individuals with and without hypertension in the Chinese community population. MATERIALS AND METHODS: The study included 4180 individuals aged 45-85 years, derived from the China Health and Retirement Longitudinal Study (CHARLS) between 2011 and 2015. Additionally, a hospital-based study enrolled subjects in the Department of Nephrology at Zhongshan Hospital, China from January 1, 2019, to December 31, 2021. The interaction effect analysis were used to assess the impact of sUA and hypertension on CKD. We also compared the distribution of sUA and the CKD risk in community populations, distinguishing between those with and without hypertension. For the hospital-based population, kidney injury was marked by a KIM-1 positive area. RESULTS: Our results indicate a higher prevalence of CKD in the community population with hypertension (10.2% vs. 3.9%, p < .001). A significant additive synergistic effects of the sUA and hypertension on the CKD risk were found. When the sUA level was < 4.55 mg/dL in the hypertensive population and < 5.58 mg/dL in the non-hypertensive population, the risk of CKD was comparable (p = .809). In the propensity score matched (PSM) population, the result remained roughly constant. CONCLUSION: Therefore, even moderate levels of sUA was associated with a higher risk of CKD in middle-aged hypertensive patients, who warrant stricter sUA control.

Weekend effect on the incidence and outcomes of cardiac surgery associated - acute kidney injury.

BACKGROUND: The effects of surgical day (workdays or weekends) on occurrence and outcome of cardiac surgery associated -acute kidney injury (CSA-AKI) remains unclear. This study aimed to compare the incidence and short-term outcomes of CSA-AKI in patients undergoing surgery on workdays and weekends. MATERIALS AND METHODS: Patients who underwent cardiac surgery from July 2020 to December 2020 were retrospectively enrolled in this study. These patients were divided into a weekend group and workday group. The primary endpoint was the incidence of CSA-AKI. The secondary endpoints included renal function recovery and in-hospital mortality. The logistic regression model was used to explore the risk factors for CSA-AKI. Stratification analysis was performed to estimate the association between CSA-AKI and weekend surgery stratified by emergency surgery. RESULTS: A total of 1974 patients undergoing cardiac surgery were enrolled. The incidence of CSA-AKI in the weekend group was significantly higher than that in the workday group (42.8% vs. 34.7%, P = 0.038). Further analysis of patients with CSA-AKI showed that there was no difference in renal function recovery between the workday AKI group and weekend AKI group. There was no difference in in-hospital mortality between the weekend group and workday group (3.6% vs. 2.4%, P = 0.327); however, the in-hospital mortality of the weekend AKI group was significantly higher than that of the workday AKI group (8.5% vs. 2.9%, P = 0.014). Weekend surgery and emergency surgery were independent risk factors for CSA-AKI. The multiplicative model showed an interaction between weekend surgery and emergency surgery; weekend surgery was related to an increased risk of AKI among patients undergoing emergency surgery [adjusted OR (95% CI): 1.96 (1.012-8.128)]. CONCLUSIONS: The incidence of CSA-AKI in patients undergoing cardiac surgery on weekends was significantly higher compared to that in patients undergoing cardiac surgery on workdays. Weekend surgery did not affect the in-hospital mortality of all patients but significantly increased the mortality of AKI patients. Weekend surgery and emergency surgery were independent risk factors for CSA-AKI. Weekend emergency surgery significantly increased the risk of CSA-AKI.

Urinary N-Acetyl-Beta-D-Glucosaminidase levels predict immunoglobulin a nephropathy remission status.

BACKGROUND: Tubulointerstitial lesions play a pivotal role in the progression of IgA nephropathy (IgAN). Elevated N-acetyl-beta-D-glucosaminidase (NAG) in urine is released from damaged proximal tubular epithelial cells (PTEC) and may serve as a biomarker of renal progression in diseases with tubulointerstitial involvement. METHODS: We evaluated the predictive value of urinary NAG (uNAG) for disease progression in 213 biopsy-proven primary IgAN patients from January 2018 to December 2019 at Zhongshan Hospital, Fudan University. We compared the results with those of serum cystatin C (sCysC). RESULTS: Increased uNAG and sCysC levels were associated with worse clinical and histological manifestations. Only uNAG level was independently associated with remission status after adjustment. Patients with high uNAG levels (> 22.32 U/g Cr) had a 4.32-fold greater risk of disease progression. The combination of baseline uNAG and clinical data may achieve satisfactory risk prediction in IgAN patients with relatively preserved renal function (eGFR ≥ 60 ml/min/1.73 m2, area under the curve [AUC] 0.760). CONCLUSION: Our results suggest that uNAG is a promising biomarker for predicting IgAN remission status.

Knocking Out OsAAP11 to Improve Rice Grain Quality Using CRISPR/Cas9 System.

The demand for rice grain quality, particularly in terms of eating and cooking quality, is increasingly concerning at present. However, the limited availability of rice-quality-related gene resources and time-consuming and inefficient traditional breeding methods have severely hindered the pace of rice grain quality improvement. Exploring novel methods for improving rice grain quality and creating new germplasms is an urgent problem that needs to be addressed. In this study, an amino-acid-transporter-encoding gene OsAAP11 (Os11g0195600) mainly expressed in endosperm was selected as the target for gene editing using the CRISPR/Cas9 system in three japonica genetic backgrounds (Wuyungeng30, Nangeng9108, and Yanggeng158, hereafter referred to as WYG30, NG9108, and YG158). We successfully obtained homozygous osaap11 mutants without transgenic insertion. Subsequently, we conducted comprehensive investigations on the agronomic traits, rice grain quality traits, and transcriptomic analysis of these mutants. The results demonstrate that loss of OsAAP11 function led to a reduced amino acid content and total protein content in grains without affecting the agronomic traits of the plants; meanwhile, it significantly increased the peak viscosity, holding viscosity, and final viscosity values during the cooking process, thereby enhancing the eating and cooking quality. This study not only provides valuable genetic resources and fundamental materials for improving rice grain quality but also provides novel technical support for the rapid enhancement of rice grain quality.

Phosphoproteome Profiling of uEVs Reveals p-AQP2 and p-GSK3ß as Potential Markers for Diabetic Nephropathy.

Diabetic nephropathy (DN) contributes to increased morbidity and mortality among patients with diabetes and presents a considerable global health challenge. However, reliable biomarkers of DN have not yet been established. Phosphorylated proteins are crucial for disease progression. However, their diagnostic potential remains unexplored. In this study, we used ultra-high-sensitivity quantitative phosphoproteomics to identify phosphoproteins in urinary extracellular vesicles (uEVs) as potential biomarkers of DN. We detected 233 phosphopeptides within the uEVs, with 47 phosphoproteins exhibiting significant alterations in patients with DN compared to those in patients with diabetes. From these phosphoproteins, we selected phosphorylated aquaporin-2 (p-AQP2[S256]) and phosphorylated glycogen synthase kinase-3ß (p-GSK3ß[Y216]) for validation, as they were significantly overrepresented in pathway analyses and previously implicated in DN pathogenesis. Both phosphoproteins were successfully confirmed through Phos-tag western blotting in uEVs and immunohistochemistry staining in kidney sections, suggesting that phosphoprotein alterations in uEVs reflect corresponding changes within the kidney and their potential as candidate biomarkers for DN. Our research proposes the utilization of phosphoproteins in uEVs as a liquid biopsy, presenting a highly feasible diagnostic tool for kidney disease.

Epoxy-rich Fe Single Atom Sites Boost Oxygen Reduction Electrocatalysis.

Electrocatalysts for highly efficient oxygen reduction reaction (ORR) are crucial for energy conversion and storage devices. Single-atom catalysts with maximized metal utilization and altered electronic structure are the most promising alternatives to replace current benchmark precious metals. However, the atomic level understanding of the functional role for each species at the anchoring sites is still unclear and poorly elucidated. Herein, we report Fe single atom catalysts with the sulfur and oxygen functional groups near the atomically dispersed metal centers (Fe1/NSOC) for highly efficient ORR. The Fe1/NSOC delivers a half-wave potential of 0.92 V vs. RHE, which is much better than those of commercial Pt/C (0.88 V), Fe single atoms on N-doped carbon (Fe1/NC, 0.89 V) and most reported nonprecious metal catalysts. The spectroscopic measurements reveal that the presence of sulfur group induces the formation of epoxy groups near the FeN4S2 centers, which not only modulate the electronic structure of Fe single atoms but also participate the catalytic process to improve the kinetics. The density functional theory calculations demonstrate the existence of sulfur and epoxy group engineer the charges of Fe reactive center and facilitate the reductive release of OH* (rate-limiting step), thus boosting the overall oxygen reduction efficiency.

Macro/Micro-Environment Regulating Carbon-Supported Single-Atom Catalysts for Hydrogen/Oxygen Conversion Reactions.

Single-atom catalysts (SACs) have attracted tremendous research interest due to their unique atomic structure, maximized atom utilization, and remarkable catalytic performance. Among the SACs, the carbon-supported SACs have been widely investigated due to their easily controlled properties of the carbon substrates, such as the tunable morphologies, ordered porosity, and abundant anchoring sites. The electrochemical performance of carbon-supported SACs is highly related to the morphological structure of carbon substrates (macro-environment) and the local coordination environments of center metals (micro-environment). This review aims to provide a comprehensive summary on the macro/micro-environment regulating carbon-supported SACs for highly efficient hydrogen/oxygen conversion reactions. The authors first summarize the macro-environment engineering strategies of carbon-supported SACs with altered specific surface areas and porous properties of the carbon substrates, facilitating the mass diffusion kinetics and structural stability. Then the micro-environment engineering strategies of carbon-supported SACs are discussed with the regulated atomic structure and electronic structure of metal centers, boosting the catalytic performance. Insights into the correlation between the co-boosted effect from the macro/micro-environments and catalytic activity for hydrogen/oxygen conversion reactions are summarized and discussed. Finally, the challenges and perspectives are addressed in building highly efficient carbon-supported SACs for practical applications.

Rapid improvement of rice eating and cooking quality through gene editing toward glutelin as target.

Rice eating and cooking quality (ECQ) is a major concern of breeders and consumers, determining market competitiveness worldwide. Rice grain protein content (GPC) is negatively related to ECQ, making it possible to improve ECQ by manipulating GPC. However, GPC is genetically complex and sensitive to environmental conditions; therefore, little progress has been made in traditional breeding for ECQ. Here, we report that CRISPR/Cas9-mediated knockout of genes encoding the grain storage protein glutelin rapidly produced lines with downregulated GPC and improved ECQ. Our finding provides a new strategy for improving rice ECQ.

Hydrogen sulfide attenuates renal fibrosis by inducing TET-dependent DNA demethylation on Klotho promoter.

Hypoxia is a key pathogenetic characteristic of chronic kidney disease (CKD). Klotho has renoprotective effect and its expression is commonly suppressed in CKD patients. We showed that chronic hypoxia in unilateral ureteral obstruction model mice is associated with renal Klotho promoter methylation and expression silencing. Administration of low-dose of sodium hydrosulfide (NaHS) effectively ameliorated renal tubulointerstitial fibrosis in the mouse model by demethylating Klotho promoter and restoring its expression. Mechanistically, hypoxia microenvironment in CKD reduced cellular oxygen availability and Fe2+ concentration, and led to impaired activity of ten-eleven translocation (TET), which is critical in maintaining Klotho promoter demethylation status. NaHS treatment greatly improved hypoxia condition, restored TET activity, reversed DNA methylation, and thus, increased Klotho expression. Our results strongly suggested that correcting hypoxia condition to restore TET activity could be a promising therapeutic strategy against CKD.

The effect of triglycerides to high-density lipoprotein cholesterol ratio on the reduction of renal function: findings from China health and retirement longitudinal study (CHARLS).

BACKGROUND: Previous studies show that abnormal lipoprotein metabolism can increase the prevalence of chronic kidney disease (CKD). This study prospectively investigated the association of triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio and renal dysfunction in the Chinese population. METHODS: This longitudinal cohort research examined 7,316 participants (age range: 22-93) from the China Health and Retirement Longitudinal Study (CHARLS), including 6,560 individuals with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 (normal renal function, NRF) group and 756 with eGFR < 60 mL/min/1.73 m2 (impaired renal function, IRF) group. In NRF group, reduction in renal function was defined as eGFR < 60 mL/min/1.73 m2 at exit visit and in IRF group, it was defined as decline in eGFR category, average eGFR decline > 5 mL/min/1.73 m2 per year or > 30 % decrease in eGFR from baseline. RESULTS: The study results showed that TG/HDL-C ratio was positively associated with the risk of renal function decline in the NRF group (OR 1.30, 95 %CI 1.03-1.65, P = 0.03) and the IRF group (OR 1.90, 95 %CI 1.21-3.23, P = 0.02) when adjusting for age, gender, obesity, diabetes, hypertension, waist circumference, drinking, smoking, history of heart disease and stroke, low-density lipoprotein cholesterol and eGFR category. Analysis of the IRF group indicated that relative to the group of TG/HDL-C < 1.60, the group of TG/HDL-C ≥ 2.97 had an increased risk for the decline of eGFR category (OR 1.89, 95 %CI 1.12-3.21, P = 0.02) and > 30 % decline in eGFR (OR 2.56, 95 %CI 1.05-6.38, P = 0.04). CONCLUSIONS: The high TG/HDL-C ratio was an independent risk factor for declining renal function in the Chinese population.

Association between exposure to the Chinese famine during early life and the risk of chronic kidney disease in adulthood.

BACKGROUND AND OBJECTIVES: Famine exposure in human early life is proven to be associated with urinary protein concentration and renal function but has not been studied with chronic kidney disease. We aimed to explore the association between exposure to the Chinese famine (from 1959 to 1962) in early life and the risk of chronic kidney disease in adulthood. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: We selected 6267 participants from the baseline survey of China Health and Retirement Longitudinal Study (CHARLS) 2011-2012. Based on the birth year, they were divided into fetal exposed, preschool exposed, school-aged exposed, and non-exposed groups. The estimated glomerular filtration rate (eGFR) was calculated according to Japanese coefficient-modified Chronic Kidney Disease Epidemiology Collaboration equation. Chronic kidney disease (CKD) was defined as eGFR less than 60 mL/min per 1.73 m2. RESULTS: The prevalence of CKD in fetal exposed, preschool exposed, school-aged exposed and non-exposed groups was 4.27%, 5.41%, 9.65% and 2.42%, respectively. The risk of CKD in fetal exposed, preschool exposed and school-aged exposed groups was significantly higher than the non-exposed group. In addition, after stratification by gender and famine severity, we found that only fetal exposure to the severe famine was associated with the elevated risk of CKD among male adults (OR 4.44, 95%CI 1.10-17.92, P < 0.05), even after adjusting for age, marital status, household per capita income, history of kidney disease, hypertension, diabetes or abnormal glucose tolerance, smoking, drinking, rural/urban residence and highest educational attainment of parents. CONCLUSIONS: Severe famine exposure as a fetus might increase the risk of chronic kidney disease in male adults.

Volume-associated hemodynamic variables for prediction of cardiac surgery-associated acute kidney injury.

BACKGROUND: Delayed diagnosis of acute kidney injury (AKI) is common because the changes in renal function markers often lag injury. We aimed to find optimal non-invasive hemodynamic variables for the prediction of postoperative AKI and AKI renal replacement therapy (RRT). METHODS: The data were collected from 1,180 patients who underwent cardiac surgery in our hospital between March 2015 and Feb 2016. Postoperative central venous pressure (CVP), mean arterial pressure (MAP), heart rate, PaO2, and PaCO2 on ICU admission and daily fluid input and output (calculated as 24 h PFO) were monitored and compared between AKI vs. non-AKI and RRT vs non-RRT cases. RESULTS: The AKI and AKI-RRT incidences were 36.7% (n = 433) and 1.2% (n = 14). Low cardiac output syndromes (LCOSs) occurred significantly more in AKI and RRT than in non-AKI or non-RRT groups (13.2% vs. 3.9%, P < 0.01; 42.9% vs. 7.1%, P < 0.01). CVP on ICU admission was significantly higher in AKI and RRT than in non-AKI and non-RRT groups (11.5 vs. 9.0 mmHg, P < 0.01; 13.3 vs. 9.9 mmHg, P < 0.01). 24 h PFO in AKI and RRT cases were significantly higher than in non-AKI or non-RRT patients (1.6% vs. 0.9%, P < 0.01; 3.9% vs. 0.8%, P < 0.01). The areas under the ROC curves to predict postoperative AKI by CVP on ICU admission (> 11 mmHg) + LCOS + 24 h PFO (> 5%) and to predict AKI-RRT by CVP on ICU admission (> 13 mmHg) + LCOS + 24 h PFO (> 5%) were 0.763 and 0.886, respectively. CONCLUSION: The volume-associated hemodynamic variables, including CVP on ICU admission, LCOS, and 24 h PFO after surgery could predict postoperative AKI and AKI-RRT.

Application of group LASSO regression based Bayesian networks in risk factors exploration and disease prediction for acute kidney injury in hospitalized patients with hematologic malignancies.

BACKGROUND: Patients who were diagnosed with hematologic malignancies (HM) had a higher risk of acute kidney injury (AKI). This study applies the Bayesian networks (BNs) to investigate the interrelationships between AKI and its risk factors among HM patients, and to evaluate the predictive and inferential ability of BNs model in different clinical settings. METHODS: During 2014 and 2015, a total of 2501 inpatients with HM were recruited in this retrospective study conducted in a tertiary hospital, Shanghai of China. Patients' demographics, medical history, clinical and laboratory records on admission were extracted from the electronic medical records. Candidate predictors of AKI were screened in the group-LASSO (gLASSO) regression, and then they were incorporated into BNs analysis for further interrelationship modeling and disease prediction. RESULTS: Of 2395 eligible patients with HM, 370 episodes were diagnosed with AKI (15.4%). Patients with multiple myeloma (24.1%) and leukemia (23.9%) had higher incidences of AKI, followed by lymphoma (13.4%). Screened by the gLASSO regression, variables as age, gender, diabetes, HM category, anti-tumor treatment, hemoglobin, serum creatinine (SCr), the estimated glomerular filtration rate (eGFR), serum uric acid, serum sodium and potassium level were found with significant associations with the occurrence of AKI. Through BNs analysis, age, hemoglobin, eGFR, serum sodium and potassium had directed connections with AKI. HM category and anti-tumor treatment were indirectly linked to AKI via hemoglobin and eGFR, and diabetes was connected with AKI by affecting eGFR level. BNs inferences concluded that when poor eGFR, anemia and hyponatremia occurred simultaneously, the patients' probability of AKI was up to 78.5%. The area under the receiver operating characteristic curve (AUC) of BNs model was 0.835, higher than that in the logistic score model (0.763). It also showed a robust performance in 10-fold cross-validation (AUC: 0.812). CONCLUSION: Bayesian networks can provide a novel perspective to reveal the intrinsic connections between AKI and its risk factors in HM patients. The BNs predictive model could help us to calculate the probability of AKI at the individual level, and follow the tide of e-alert and big-data realize the early detection of AKI.

Prediction models for acute kidney injury in patients with gastrointestinal cancers: a real-world study based on Bayesian networks.

BACKGROUND: This study attempts to establish a Bayesian networks (BNs) based model for inferring the risk of AKI in gastrointestinal cancer (GI) patients, and to compare its predictive capacity with other machine learning (ML) models. METHODS: From 1 October 2014 to 30 September 2015, we recruited 6495 inpatients with GI cancers in a tertiary hospital in eastern China. Data on demographics, clinical and laboratory indicators were retrospectively extracted from the electronic medical record system. Predictors of AKI were selected in gLASSO regression, and further incorporated into BNs analysis. RESULTS: The incidences of AKI in patients with esophagus, stomach, and intestine cancer were 20.5%, 13.9%, and 12.5%, respectively. Through gLASSO, 11 predictors were screened out, including diabetes, cancer category, anti-tumor treatment, ALT, serum creatinine, estimated glomerular filtration rate (eGFR), serum uric acid (SUA), hypoalbuminemia, anemia, abnormal sodium, and potassium. BNs model revealed that cancer category, treatment, eGFR, and hypoalbuminemia had direct connections with AKI. Diabetes and SUA were indirectly linked to AKI through eGFR, and anemia created connections with AKI through affecting album level. Compared with other ML models, BNs model maintained a higher AUC value in both the internal and external validation (AUC: 0.823/0.790). CONCLUSION: BNs model not only delineates the qualitative and quantitative relationship between AKI and its associated factors but shows the more robust generalizability in AKI prediction.

Electrolyte and acid-base disorders in cancer patients and its impact on clinical outcomes: evidence from a real-world study in China.

Background: This study aims to delineate the incidence of electrolyte and acid-base disorders (EAD) in cancer patients, to figure out the risk factors of EAD, then to assess the impact of EAD on patients' in-hospital clinical outcomes.Methods: Patients with the diagnosis of malignancies hospitalized during 1 October 2014 and 30 September 2015 were recruited in Zhongshan Hospital, Fudan University in Shanghai of China. Demographic characteristics, comorbidities, and clinical data, including survival, length of stay and hospital cost, were extracted from the electronic medical record system. Electrolyte and acid-base data were acquired from the hospital laboratory database.Results: Of 25,881 cancer patients with electrolyte data, 15,000 (58.0%) cases had at least one electrolyte and acid-base abnormity. Hypocalcemia (27.8%) was the most common electrolyte disorder, followed by hypophosphatemia (26.7%), hypochloremia (24.5%) and hyponatremia (22.5%). The incidence of simple metabolic acidosis (MAC) and metabolic alkalosis (MAL) was 12.8% and 22.1% respectively. Patients with mixed metabolic acid-base disorders (MAC + MAL) accounted for 30.2%. Lower BMI score, preexisting hypertension and diabetes, renal dysfunction, receiving surgery/chemotherapy, anemia and hypoalbuminemia were screened out as the major risk factors of EAD. In-hospital mortality in patients with EAD was 2.1% as compared to those with normal electrolytes (0.3%). The risk of death significantly increased among patients with severe EAD. Similarly, the length of stay and hospital cost also tripled as the number and grade of EAD increased.Conclusion: EAD is commonly encountered in cancer patients and associated with an ominous prognosis. Patients with comorbidities, renal/liver dysfunction, and anti-tumor therapy have a higher risk of EAD. Regular monitoring of electrolytes, optimum regimen for intravenous infusion, timely correction of modifiable factors and appropriate management of EAD should not be neglected during anti-tumor treatment.

Low Plasma Hydrogen Sulfide Is Associated with Impaired Renal Function and Cardiac Dysfunction.

BACKGROUND: Chronic kidney disease (CKD) has been proposed to associate with decreased hydrogen sulfide (H2S) level. Nevertheless, the role of H2S in the pathogenesis of CKD has not been fully investigated. Our study aimed to investigate the plasma level of endogenous H2S in patients with different stages of CKD, and to identify the role of H2S in the progression of CKD and its relationship with cardiovascular diseases. METHODS: A total of 157 non-dialysis CKD patients were recruited in our study, with 37 age- and sex-matched healthy individuals as control. Plasma concentration of H2S was measured with spectrophotometry. Sulfhemoglobin, the integration of H2S and hemoglobin, was characterized and measured by dual wavelength spectrophotometry. Serum levels of homocysteine (Hcy), cardiac troponin T (cTnT), and N-terminal pro B type natriuretic peptide were measured using automated analyzers. Conventional transthoracic echocardiography was performed and left ventricular ejection fraction (LVEF) was analyzed as a sensitive parameter of cardiac dysfunction. RESULTS: The plasma H2S level (µmol/L) in CKD patients was significantly lower than those in healthy controls (7.32 ± 4.02 vs. 14.11 ± 5.24 µmol/L, p < 0.01). Plasma H2S level was positively associated with estimated glomerular filtration rate (eGFR; ρ = 0.577, p < 0.01) and negatively associated with plasma indoxyl sulfate concentration (ρ = -0.554, p < 0.01). The mRNA levels of cystathionine ß-synthase and cystathionine γ-lyase, 2 catalytic enzymes of H2S formation, were significantly lower in blood mononuclear cells of CKD patients with respect to controls; however, the mRNA level of 3-mercaptopyruvate sulfurtransferase, as another H2S-producing enzyme, was significantly higher in CKD patients. The serum concentration of Hcy, acting as the substrate of H2S synthetase, was higher in the CKD group (p < 0.01). Specifically, the content of serum Hcy in CKD stages 3-5 patients was significantly higher than that in CKD stages 1-2, indicating an increasing trend of serum Hcy with the decline of renal function. Examination of ultrasonic cardiogram revealed a negative -correlation between plasma H2S level and LVEF (ρ = -0.204, p < 0.05) in CKD patients. The H2S level also correlated negatively with cTnT concentration (ρ = -0.249, p < 0.01). CONCLUSIONS: Plasma H2S level decreased with the decline of eGFR, which may contribute to the cardiac dysfunction in CKD -patients.

Synthesis of symmetrical methylene-bridged imidazoheterocycles using DMSO as methylene source under metal-free conditions.

A facile H3PO4-promoted bridging methylenation of imidazopyridines or similar heterocycles has been described for the synthesis of symmetrical methylene-bridged imidazoheterocycles, in which DMSO was used as the carbon source. The reaction obtained good yields for most substrates with high C3-regioselectivity. This method also features metal-free, practicability and low cost.

Regioselective Fluorination of Imidazo[1,2-a]pyridines with Selectfluor in Aqueous Condition.

A regioselective synthesis of 3-fluorinated imidazo[1,2-a]pyridines using 1-chloromethyl-4-fluoro-1,4-diazoniabi cyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor) as the fluorinating reagent in aqueous condition is described. In the presence of DMAP, the reaction mainly gave monofluorinated product via electrophilic fluorinated process in moderate to good yields.

Ordered mesoporous carbon with binary CoFe atomic species for highly efficient oxygen reduction electrocatalysis.

The exploration of powerful, efficient and precious metal-free electrocatalysts for facilitating the sluggish kinetics of the oxygen reduction reaction (ORR) is a crucial endeavor in the development and application of energy conversion and storage devices. Herein, we have rationally designed and synthesized bimetallic CoFe species consisting of CoFe nanoparticles and atomically dispersed dual atoms anchored on an ordered mesoporous carbon matrix (CoFe/NC) as highly efficient ORR electrocatalysts. The pyrolyzation temperature for CoFe/NC plays a vital role in regulating the morphology and composition of both the carbon matrix and CoFe species. The optimized CoFe/NC-750 exhibits a favorable ORR performance in 0.1 M KOH with a high half-wave potential (E1/2) of 0.87 V vs. RHE, excellent tolerance to methanol and remarkable durability (no obvious decrease in E1/2 value after 3000 cycles), all of which are superior to the performance of commercial Pt/C. Experimental measurements and density functional theory (DFT) calculations reveal that the improved ORR performance of CoFe/NC-750 is mainly attributed to the electronic structure of atomically dispersed Fe active sites modulated by the surrounding CoFe alloys and Co single atoms, which accelerates the dissociation and reduction of intermediate OH* species and promotes the ORR process.