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The administration of nanodrugs can lead to metabolism related systemic toxicity due to the use of inert carriers in large quantities. Carrier materials that offer therapeutic effects are therefore a promising means of addressing this limitation. Herein, a hyaluronate-based nanocarrier was prepared from hyaluronic acid (HA) and solanesol. Solanesyl thiosalicylate (STS) derived from solanesol has certain antitumor effects and was used to modify HA. The conjugate (HA-STS) self-assembled into nanoparticles acting as a drug carrier. The synthesis of the conjugates was confirmed by

Background: Prader-Willi syndrome (PWS) is a multisystem disorder caused by aberrant genomics which silences genes in the 15q11-q13 region. It is characterized by multiple cognitive, behavioral, and endocrine abnormalities. Case presentation: We present a case of a 28-year-old male patient diagnosed with PWS with diabetes mellitus, nephrotic syndrome (proteinuria > 3.5 g/24 h) and acute kidney injury who eventually entered end-stage renal disease and started dialysis. Through genetic diagnosis, we found that the patient had heterozygous deficiency in the chr15 deletion segment. The patient’s mother was heterozygous and the father was wild-type, suggesting that the 4.86 Mb deletion in the 15q11.2-q13.1 segment of the patient was a paternal chromosomal deletion. Conclusion:PWS has various clinical manifestations and a poor prognosis. Early diagnosis, long-term follow-up, and in-time treatment could improve the quality of life and prognosis of PWS patients.

Aims: To investigate whether renal pathology is an independent predictor for end-stage renal disease (ESRD) in diabetic kidney diseases (DKD) with nephrotic range proteinuria. Methods: A total of 199 DKD patients with nephrotic range proteinuria underwent renal biopsy and were divided into an ESRD group and a non-ESRD group. A Kaplan–Meier analysis was used to compare renal survival rate, and univariate and multivariate Cox proportional hazard analyses were used to determine the predictors of the ESRD. Results: The mean age of included patients was 51.49 ± 9.12 years and 113 patients (56.8%) progressed to ESRD. The median follow-up period was 16 (12–28) months. The glomerular pathology class III is the most common type (54.3%). In the Kaplan–Meier analysis, compared with patients without ESRD, patients with ESRD had a longer duration of diabetes (≥6 years), lower eGFR (

Chunmei Qin,1– 3 Yiting Wang,1,2 Lijun Zhao,1,2 Junlin Zhang,1,2 Honghong Ren,1,2 Yutong Zou,1,2 Yucheng Wu,1,2 Tingli Wang,1,2 Yuancheng Zhao,1,2 Rui Zhang,1,2 Huan Xu,4 Jie Zhang,5 Mark E Cooper,6 Fang Liu1,2 1Division of Nephrology, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 2Laboratory of Diabetic Kidney Disease, Centre of Diabetes and Metabolism Research, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 3Department of Nephrology, Luzhou People’s Hospital, Luzhou, People’s Republic of China; 4Division of Pathology, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 5Key Laboratory of Transplant Engineering and Immunology, Chengdu, People’s Republic of China; 6Department of Diabetes, Central Clinical School, Monash University, Melbourne, AustraliaCorrespondence: Fang Liu, Division of Nephrology, West China Hospital of Sichuan University, No. 37, Guoxue Alley, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-28-18980601214, Fax +86-28-85422335, Email liufangfh@163.comObjective: The rate of kidney function decline in patients with diabetic kidney disease (DKD) is known to differ. This study analyzed the clinicopathologic features and related risk factors affecting long-term renal survival in Chinese type 2 diabetic patients with rapid estimated glomerular filtration rate (eGFR) decline.Methods: In this retrospective descriptive study, 191 DKD patients were first classified as rapid eGFR decliners and slow eGFR decliners on the basis of the median eGFR slope value (− 8.0 mL/min/1.73 m2/year). In total, 96 patients with rapid eGFR decline were included in the analyses and subsequently allocated to end-stage renal disease (ESRD) and non-ESRD groups. Baseline clinicopathological data of rapid eGFR decliners were collected. Cox proportional hazard analysis was performed to calculate the hazard ratios (HRs) for progression to ESRD.Results: During a median follow-up of 25 months, 52 (54.2%) rapid eGFR decliners progressed to ESRD. These 52 rapid eGFR decliners had poorer renal function, lower hemoglobin and albumin concentrations, higher total cholesterol and baseline proteinuria levels, and more severe interstitial inflammation than those who did not progress to ESRD. After adjustment for age, gender, baseline eGFR, proteinuria, hemoglobin level, serum albumin concentration, and histopathologic parameters, multivariate Cox proportional hazard analysis revealed that eGFR (HR 0.973, 95% CI 0.956– 0.989) and proteinuria (HR 1.125, 95% CI 1.030– 1.228) were associated with the increased risk of progression to ESRD.Conclusion: Higher proteinuria and lower eGFR were independent risk factors for renal progression in Chinese patients with type 2 diabetes and rapid eGFR decline.Keywords: diabetic kidney disease, rapid eGFR decline, clinical, pathological, type 2 diabetes

Backgroud To investigate the protective effect of exogenous basic fibroblast growth factor (bFGF) treatment on the intestinal mucosa in scalded rats. Methods Thirty-six SD rats were randomly divided into 3 groups (n = 12): sham group, scald group and bFGF group (0.5 mg/kg). Intestinal barrier dysfunction was evaluated by permeability of intestinal mucosa to fluorescein isothiocyanate (FITC)-dextran and Chiu’s grading system. H&E staining was used to detect the morphological changes of intestinal mucosa. Immunohistochemistry was used to observe zonula occludens-1 (ZO-1) and occludin. Western blot assay was used to detect the expression of ZO-1, Claudin-1, occludin and myosin light-chain kinase (MLCK). Results The results demonstrated that following bFGF treatment, permeability of the intestinal epithelium barrier of was significantly decreased compared to scald group. H&E staining and Chiu’s grading were consistent with previous result. The expression of ZO-1, Claudin-1, occludin in bFGF group were significantly increased compared to scald group, while MLCK protein was decreased. Conclusions bFGF ameliorates permeability of intestinal mucosa after burns. The possible mechanism may be relate to bFGF could increase the expression level of tight junction proteins (TJPs).

To investigate the relationship between metabolic-associated fatty liver disease (MAFLD) and end-stage renal disease (ESRD) in patients with biopsy-confirmed diabetic nephropathy (DN).A total of 316 participants with biopsy-confirmed DN between January 2008 and December 2019 were retrospectively assessed. Kaplan-Meier curve and Cox proportional hazard models were used to compare the risk of incident ESRD in 50 patients with MAFLD and 50 patients without MAFLD, after using propensity score matching (PSM) to address the imbalances of sex, age, baseline-estimated glomerular filtration rate, serum albumin, 24-h urine protein, hemoglobin and systolic blood pressure.During the median follow-up period of 3 years, there were 19 ESRD outcome events (19%) in PSM cohort. Kaplan-Meier curve analysis suggested that renal survival significantly deteriorated in patients with MAFLD versus those without MAFLD (p = 0.021). Additionally, the hazard ratios (95% confidence interval) of MAFLD were 3.12 (1.09-8.95, p = 0.035), 3.36 (1.09-10.43, p = 0.036), 3.66 (1.22-10.98, p = 0.021), 4.25 (1.34-13.45, p = 0.014), 3.11 (1.08-8.96, p = 0.035) and 5.84 (1.94-18.5, p = 0.003) after adjustment for six models, including demographic, clinical and pathological characteristics as well as medication use at the time of renal biopsy, respectively. Besides, patients with higher liver fibrosis score had a greater possibility of ESRD, comparing to those with lower liver fibrosis score (p = 0.002).MAFLD increases the risk of incident ESRD in patients with biopsy-proven DN. Further research is needed to determine whether treatment targeting MAFLD improves the prognosis of DN.

Summary Observational studies on dietary or circulating magnesium and risk of cardiovascular disease (CVD) in Chronic Kidney Disease (CKD) stage 1–4 have reported no-to-modest inverse associations. 24 h Urinary magnesium concentration (24 h UMg), an indicator of intestinal magnesium absorption, may provide better insight into the connection of CKD progression. We examined 3179 participants aged 18–74 years with CKD stage 1–4 in the Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE) study, a prospective population-based cohort study. Data were analysed using Spearman rank-order correlation coefficients for all comparisons. We also performed a time-to-event analysis of the data using the Kaplan–Meier survival model, Cox proportional hazard model and competing risk Fine and Gray subdistribution hazard model. During a median follow-up of 4.19 years (interquartile range, 3.43–5.09 years), when modelling end-stage renal disease (ESRD), CVD and death, 24 h UMg was associated with risk of CVD (HR, 1.612 (95% CI, 1.056–2.460)), while no significant association with ESRD and death endpoints could be detected. 24 h UMg risk variants display a modest association with CVD in CKD stage 1–4 patients. Trial registration ClinicalTrials.gov Identifier NCT03041987. Registered January 1, 2012. (retrospectively registered) ( https://www.clinicaltrials.gov/ct2/show/NCT03041987?term=Chinese+Cohort+Study+of+Chronic+Kidney+Disease+%28C-STRIDE%29&rank=1 ).

Several studies show that patients with early-onset diabetes have higher risk of diabetic complications than those diagnosed in middle age. However, whether early-onset of type 2 diabetes mellitus (T2DM) is a risk factor for diabetic nephropathy (DN) progression remains unclear, especially a lack of data in biopsy-confirmed cohort. In This study, we enrolled 257 patients with T2DM and biopsy-confirmed DN to investigate the role of early-onset T2DM in DN progression. Participants were divided into two groups according to the age of T2DM diagnosis: early-onset group (less than 40 years) and later-onset group (40 years or older). We found that patients with early-onset T2DM had higher glomerular grades and arteriolar hyalinosis scores than those in later-onset group. After adjusted for confounding factors, early-onset of T2DM remained an independent predictor of end-stage renal disease (ESRD) for patients with DN. In conclusion, although with the comparable renal function and proteinuria, patients with early-onset T2DM and DN had worse renal pathological changes than those with later-onset. Early-onset of T2DM might be an important predictor of ESRD for patients with DN, which called more attention to early supervision and prevention for patients with early-onset T2DM and DN.

The car-following models are the research basis of traffic flow theory and microscopic traffic simulation. Among the previous work, the theory-driven models are dominant, while the data-driven ones are relatively rare. In recent years, the related technologies of Intelligent Transportation System (ITS) re- presented by the Vehicles to Everything (V2X) technology have been developing rapidly. Utilizing the related technologies of ITS, the large-scale vehicle microscopic trajectory data with high quality can be acquired, which provides the research foundation for modeling the car-following behavior based on the data-driven methods. According to this point, a data-driven car-following model based on the Random Forest (RF) method was constructed in this work, and the Next Generation Simulation (NGSIM) dataset was used to calibrate and train the constructed model. The Artificial Neural Network (ANN) model, GM model, and Full Velocity Difference (FVD) model are em- ployed to comparatively verify the proposed model. The research results suggest that the model proposed in this work can accurately describe the car- following behavior with better performance under multiple performance indicators.

Optimizing the intrinsic activity of active sites is an appealing strategy for accelerating the kinetics of the catalytic process. Here, a design principle, namely "dual self-built gating", is proposed to tailor the electronic structures of catalysts. Catalytic improvement is confirmed in a model catalyst with a ReS

The laser scanning method is one of the key factors in the process of selective laser sintering. Laser sintering and invalidating composite (LSIC) scanning method, which is composed of high tensile strength sintering scanning with large-spot and high accuracy invalidating scanning with small-spot, is able to improve the tensile strength, accuracy and fabrication efficiency of SLS parts. In this paper, the principle and implementation of this method were presented, and in order to prove the effectiveness of the method, the conventional scanning method was used to carry out the sintering forming experiments of the coated ceramics, and the relationship between the energy density, the tensile strength and accuracy of the parts was explored. Then based on the conclusion of this experiment, the composite scanning method is used for comparative sintering experiments. The results show that when the sintering process is carried out using the process parameters corresponding to the high tensile strength, a substantial amount of secondary sintered bodies is generated on the surface of the part and the accuracy is destroyed. The conventional scanning method cannot achieve high accuracy forming under this process condition. However, the composite scanning method can effectively eliminate the adverse influence of secondary sintering on accuracy, and achieve high tensile strength and high accuracy parts. Moreover, the method can also improve the fabrication efficiency. Therefore, this method is of great significance to realize high quality sand mould additive manufacturing and enrich the scanning method of SLS.

In the current study, we explored the associations of glomerular immunoglobulin G (IgG) deposit and further investigated the pattern of IgG subclass deposition in the renal biopsy specimens from patients with diabetic nephropathy (DN).A total of 170 inpatients with type 2 diabetes mellitus and biopsy-proven DN who were followed up for at least 1 year were retrospectively recruited. Renal outcomes were defined by DN progression (end-stage renal disease [ESRD] or ≥ 50% reduction in estimated glomerular filtration rate [eGFR] from baseline). Additionally, 38 renal biopsy specimens of patients with renal IgG deposit underwent the immunofluorescence IgG1-4 staining.The median follow-up period was 22 months. During follow-up, 38.23% (65) of patients progressed to ESRD, and 6.47% (11) of patients had an eGFR decline ≥50%. The multivariate Cox analysis demonstrated that the glomerular IgG deposit (hazard ratio, 1.835; 95% CI, 1.013-3.324, P = .045) was still significantly associated with DN progression when adjusted for the important clinical variables and pathological findings. In addition, a logistic regression showed that the glomerular IgG deposit was independently associated with glomerular basement membrane (GBM) thickness (odds ratio [OR], 1.276; 95% CI, 1.046-1.558; P = .016), Kimmelstiel-Wilson nodules formation (OR, 3.822; 95% CI, 1.052-13.881; P = .042), and C3 deposit in the glomeruli (OR, 124.883; 95% CI, 20.754-751.472; P .001). The IgG subclass staining showed that IgG1 deposit along the GBM tended to be dominant (28/38) in IgG (+) patients with DN.The glomerular IgG deposit affected glomerular structure and emerged as an independent risk factor for the renal clinical outcomes. In addition, IgG1 predominantly deposited along the GBM among the DN patients with IgG (+), which might be involved in the renal injury and progression of DN.目的: 在本研究中, 我们旨在探索肾小球免疫球蛋白G (immunoglobulin G, IgG)沉积与糖尿病肾病(diabetic Nephropathy, DN)患者临床病理特征的相关性, 并进一步研究DN患者肾活检标本中IgG亚型分布特点。 方法: 回顾性纳入2型糖尿病合并病理确诊的DN且随访超过1年的患者170例。以进展至终末期肾病(end-stage renal disease, ESRD)或估算的肾小球滤过率(estimated glomerular filtration rates, e-GFR)下降超过基线≥50%为研究终点。另外, 对38例肾小球IgG沉积的DN患者的病理切片进行IgG1-4免疫荧光染色。 结果: 随访中位时间为22个月。在随访期间, 38.23% (65例)的DN患者进展至ESRD, 6.47%(11例)的DN患者e-GFR下降≥50%。多因素COX回归分析显示:在校正重要的临床因素及病理结果后, 肾小球IgG沉积仍然与DN进展显著相关(HR, 1.835; 95%CI, 1.013-3.324, p=0.045)。另外, Logistic回归分析显示肾小球基底膜(glomerular basement membrane, GBM)厚度(OR, 1.276; 95%CI, 1.046-1.558; p=0.016)、Kimmelstiel-Wilson结节形成(OR, 3.822; 95%CI, 1.052-13.881; p=0.042) 以及肾小球C3沉积(OR, 124.883; 95%CI, 20.754-751.472; p0.001)与肾小球IgG沉积独立相关。IgG(+)DN患者的IgG亚型染色提示肾小球以IgG1在GBM沉积(28/38)为主。 结论: 肾小球IgG沉积与DN患者的肾小球结构改变相关, 且是DN患者肾脏预后不良的独立危险因素。此外, IgG(+)的DN患者以IgG1在GBM沉积为主, 其可能与肾脏损伤及DN进展有关。.

Objective: Our study sought to investigate the clinicopathologic features and renal prognosis of patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) in different age groups. Methods: A total of 315 patients with T2DM and biopsy-proven DN were enrolled and divided into three groups by age: the Youth group (≤44 years old), the Middle-aged group (45 to 59 years old), and the Elderly group (≥60 years old). Results: The Youth group, Middle-aged group, and Elderly group accounted for 19.05% (60/315), 59.37% (187/315), and 21.59% (68/315) of the patients in our study, respectively. The patients in the Youth group had a higher estimated glomerular filtration rate (calculated using the Chronic Kidney Disease–Epidemiology collaboration formula) (P .05). Conclusion: This study indicated that there were different clinicopathologic features among Chinese DN patients in different age groups. Although the Youth group had a relatively lower rapid kidney disease progression rate, there were no significant differences in renal survival rate among the three groups, which calls more attention to early supervision and prevention for younger DN patients. Abbreviations: CKD = chronic kidney disease; DN = diabetic nephropathy; DR = diabetic retinopathy; eGFR = estimated glomerular filtration rate; ESRD = end-stage renal disease; GY IFTA = interstitial fibrosis and tubular atrophy; T2DM = type 2 diabetes mellitus

The Global Precipitation Measurement (GPM) mission provides satellite precipitation products with an unprecedented spatio-temporal resolution and spatial coverage. However, its near-real-time (NRT) product still suffers from low accuracy. This study aims to improve the early run of the Integrated Multi-satellitE Retrievals for GPM (IMERG) by using four machine learning approaches, i.e., support vector machine (SVM), random forest (RF), artificial neural network (ANN), and Extreme Gradient Boosting (XGB). The cloud properties are selected as the predictors in addition to the original IMERG in these approaches. All the four approaches show similar improvement, with 53%-60% reduction of root-mean-square error (RMSE) compared with the original IMERG in a humid area, i.e., the Dongjiang River Basin (DJR) in southeastern China. The improvements are even greater in a semi-arid area, i.e., the Fenhe River Basin (FHR) in central China, the RMSE reduction ranges from 63%-66%. The products generated by the machine learning methods performs similarly to or even outperform than the final run of IMERG. Feature importance analysis, a technique to evaluate input features based on how useful they are in predicting a target variable, indicates that the cloud height and the brightness temperature are the most useful information in improving satellite precipitation products, followed by the atmospheric reflectivity and the surface temperature. This study shows that a more accurate NRT precipitation product can be produced by combining machine learning approaches and cloud information, which is of importance for hydrological applications that requires NRT precipitation information including flood monitoring.

Background. The performance of various equations for estimated glomerular filtration rate (eGFR) in patients with diabetes remains controversial. We aimed to evaluate the performance of equations for eGFR in Chinese patients with diabetic nephropathy (DN).Methods. This is a retrospective study included in 308 patients with type 2 diabetes and biopsy-proven DN who were followed up at least one year. eGFR was calculated using chronic kidney disease epidemiology (CKD-EPI) equations based on serum creatinine (eGFRCKD-EPI-Cr), cystatin C (eGFRCKD-EPI-CysC), and joint equations (eGFRCKD-EPI-Cr-CysC), respectively. End-stage kidney disease was defined by initiation of renal replacement therapy. The eGFR concordance between equations was assessed by Bland-Altman plots. Log-rank and multivariable logistic regression were employed to evaluate the performance of equations.Results. Overall, the proportion of patients witheGFR<60 mL/min/1.73m2was 53%, 70%, and 61% by the equations of eGFRCKD-EPI-Cr, eGFRCKD-EPI-CysC, and eGFRCKD-EPI-Cr-CysC, respectively. Higher disconcordance was observed between equations wheneGFR>60 mL/min/1.73m2. Compared with eGFRCKD-EPI-Cr, 39% of patients were reclassified (reclassified group) from CKD 1-2 stages to CKD 3-5 stages by eGFRCKD-EPI-CysCand they presented significantly longer diabetic duration, heavier proteinuria, advanced pathological lesions, and poorer kidney outcomes. Multivariable logistic regression indicated cystatin C was independently associated with advanced glomerular classifications.Conclusion. eGFR equations incorporating cystatin C are superior to eGFR based on creatinine alone for detecting kidney injury in the early stage. The independent association between cystatin C and glomerular classifications might contribute to it.

Abdominal obesity is a risk factor of diabetes and hypertension. The aim of this study was to investigate the association between excessive abdominal fat and renal outcomes in patients with type 2 diabetes and diabetic kidney disease.Thirty-five patients with type 2 diabetes and diabetic kidney disease who were followed up on for at least 1 year were enrolled. Visceral fat area and subcutaneous fat area were assessed by computed tomography to evaluate the degree of abdominal fat. Patients were divided into 2 groups. Patients in group 1 had a ratio of visceral fat area to subcutaneous fat area (V/S ratio)0.70 (n=16), and those in group 2 had a V/S ratio ≥0.70 (n=19) according to the second quartile. Renal outcome was defined as end-stage renal disease and initiation of renal replacement therapy.At baseline, patients with a high V/S ratio had higher levels of triglycerides (p=0.060) and C-reactive protein (p=0.028), but lower high-density lipoprotein cholesterol levels (p=0.006). Strong correlations between V/S ratio and C-reactive protein (r=0.521, p=0.015) and high-density lipoprotein cholesterol (r=-0.576, p0.001) were observed. Univariate Cox regression indicated the higher the V/S ratio, the greater the risk for a poor renal outcome (hazard ratio, 3.536; 95% confidence interval, 1.140 to 10.960; p=0.029). However, multivariate Cox analysis demonstrated that a higher V/S ratio was not an independent risk factor for progression to end-stage renal disease (hazard ratio, 2.212; 95% confidence interval, 0.543 to 9.005; p=0.268) when adjustments were made for important clinical variables.The V/S ratio was positively correlated with C-reactive protein and high-density lipoprotein cholesterol. The higher V/S ratio was associated with a greater risk for progression to end-stage renal disease, although it did not emerge as an independent predictor of diabetic kidney disease progression.

Objective: To explore the relationship between serum bilirubin concentration and clinicopathologic features and renal outcome in biopsy-diagnosed diabetic nephropathy (DN) in patients with type 2 diabetes mellitus. Methods: In this retrospective study, 118 patients with DN were enrolled. Participants were divided into two groups according to their median baseline serum bilirubin concentration: Group 1 (serum bilirubin ≤7.5 μmol /L); Group 2 (serum bilirubin >7.5 μmol /L). Basic clinical parameters were measured at the time of renal biopsy, and the relationships between serum bilirubin and the clinicopathologic features and renal outcome were analyzed. Results: Patients in Group 1 often had inferior renal function. Compared with Group 2, the glomerular classification and interstitial inflammation were more severe in subjects of Group 1, while arteriolar hyalinosis and interstitial fibrosis and tubular atrophy (IFTA) were comparable between the groups. Serum bilirubin was negatively correlated with the severity of the glomerular classification, interstitial inflammation, and IFTA. In the prognostic analysis, higher serum bilirubin level was associated with a lower risk of progression to end-stage renal disease, which was independent of the effects of age, gender, duration of diabetes, anemia, serum glucose, and hypertension but not of estimated glomerular filtration rate (hazard ratio, 0.406; 95% confidence interval, 0.074 to 2.225; P = .299). Conclusion: Our study showed a negative correlation between serum bilirubin level and renal pathologic lesions in patients with DN; serum bilirubin showed an inverse association with DN progression, but this was not independent. Abbreviations: CI = confidence interval; CKD = chronic kidney disease; DM = diabetes mellitus; DN = diabetic nephropathy; DR = diabetic retinopathy; eGFR = estimated glomerular filtration rate; ESRD = end-stage renal disease; HbA1c = glycated hemoglobin; HO-1 = heme oxygenase 1; HR = hazard ratio; IFTA = interstitial fibrosis and tubular atrophy; log-BIL = log-transformed baseline serum bilirubin; T2DM = type 2 diabetes mellitus

Heavy proteinuria caused by non-diabetic renal disease (NDRD) is common in type 2 diabetes mellitus (T2DM). The aim of this study was to investigate specific predictors for NDRD in addition to traditional indicators in T2DM. A total of 341 patients with T2DM who underwent renal biopsy were retrospectively included. Eligible patients were divided into a nephrotic-range group (n = 194) and a non-nephrotic-range group (n = 147) based on proteinuria level. Risk factors for NDRD were evaluated using logistic regression, and the diagnostic implications of these variables were assessed by subgroup. Multivariate logistic regression indicated that serum IgG level (OR, 0.762; 95% CI, 0.628–0.924; p = 0.006) was an independent predictor of NDRD in the nephrotic-range group. However, in the non-nephrotic-range group, increased C3 level was an independent risk factor for NDRD (OR, 1.313; 95% CI, 1.028–1.678; p = 0.029). In the nephrotic-range group, the optimal cutoff value of IgG for predicting NDRD was 734.0 mg/dl, with 67.8% sensitivity and 74.8% specificity, and IgG ≤ 734.0 mg/dl was the best predictor of NDRD. In the non-nephrotic-range group, the optimal cutoff value of C3 for predicting NDRD was 122.0 mg/dl with low sensitivity (30.9%) but high specificity (97.8%). At different levels of proteinuria, reduced IgG and increased C3 levels were independent indicators of NDRD in T2DM. Insights into these factors will help to advance the clinical management of NDRD.

To determine the prevalence of diabetic nephropathy (DN) and non-diabetic renal disease (NDRD) in patients with type 2 diabetes mellitus (T2DM), and the important clinical predictors of renal outcome and clinical course. We conducted a retrospective analysis of clinical, laboratory, and histopathologic data from T2DM patients with renal involvement confirmed by renal biopsy (n = 505). The outcome was defined as the progression to end-stage renal disease (ESRD). Renal biopsy revealed that 302 patients (59.8%) had DN, 174 (34.5%) had NDRD, and 29 (5.7%) had NDRD superimposed on DN. In multivariate analysis, the absence of diabetic retinopathy (DR) (odds ratio (OR) 4.171, 95% confidence interval (CI) 1.810–9.612; P = 0.001), absence of hypertension (OR 2.412, 95% CI 1.095–5.315; P = 0.029), shorter duration of diabetes (OR 1.015, 95% CI 1.008–1.022; P

A series of metal 1, 8, 15, 22-tetraaminophthalocyanines [1, 8, 15, 22-TAPcM, M = Mn(II), Fe(II), Ni(II), Cu(II), Zn(II)] are synthesized and used to chemically modify fluorinated multi-walled carbon nanotubes (F-MWCNTs) with the formation of certain chemical bonds on the surface of carbon nanotubes, and the corresponding composites 1, 8, 15, 22-TAPcM/MWCNTs are obtained. The electrocatalytic activities of the samples are studied by adding them into lithium/thionyl chloride (Li/SOCl2) batteries. The results indicate that the composites 1, 8, 15, 22-TAPcM/MWCNTs can improve the discharge voltage and lengthen the discharge time of the batteries much more than 1, 8, 15, 22-TAPcM, and the order of the electrocatalytic activities of 1, 8, 15, 22-TAPcM/MWCNTs and 1, 8, 15, 22-TAPcM with different metal ions in center is both Mn(II) > Ni(II) > Zn(II) > Fe(II) > Cu(II). It is also found that the discharge time and maximal discharge voltage and capacity for the battery contains 1, 8, 15, 22-TAPcMn/MWCNTs can be improved by 68.19%, 9.41%, and 82.6%, respectively.

Aims Although abnormal thyroid hormone metabolism is common in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN), the relationship between thyroid hormones and DN is unclear and has been ignored during clinical practice. This study aimed to investigate the relationship between thyroid hormones and clinicopathologic changes in biopsy-proven DN patients. Methods Clinical and pathological data for 146 biopsy-proven DN patients were collected. The patients were divided into four groups: euthyroid group, high-thyroid stimulating hormone (TSH) group (SCH), low-free triiodothyronine (FT3) group (with normal levels of TSH and FT4), and high-TSH + low-FT3 group (with normal levels of FT4). The clinicopathologic features among the four groups were investigated. We evaluated the risks of abnormal thyroid hormone levels on DN by logistic regression with multivariable adjustments for other risk factors. We also performed quarterback and eight-point analyses of TSH and FT3 levels to determine their influences on DN. Results The overt proteinuria (>5 g/24 h) (P = 0.008) and severity of glomerular lesions (P = 0.011) differed between euthyroid group and high-TSH group significantly. Moreover, the levels of estimated glomerular filtration rate (P =0.019), serum creatinine (P =0.014), and severity of glomerular lesions (P =0.003) differed between the euthyroid group and low-FT3 group significantly. There were also significant differences between high-TSH, low-FT3 and high-TSH + low-FT3 patients, respectively. Respective correlations between high-TSH, low-FT3 and renal clinicopathologic changes were found to be significant according to logistic regression analyses. Quarterback and eight-point analyses indicated that patients with TSH levels of 4.54-5.67 mU/L had the most severe renal clinicopathologic changes, and the severity of renal changes decreased with increased FT3 levels. Conclusions Diabetic nephropathy patients with high-TSH and/or low-FT3 had more severe proteinuria, renal insufficiency, and glomerular lesions, suggesting that regulating thyroid hormones might have a renoprotective effect.

The emergence of azole-resistant fungal pathogens has posed a great threat to public health worldwide. Although the molecular mechanism of azole resistance has been extensively investigated, the potential regulators of azole resistance remain largely unexplored. In this study, we identified a new function of the fungal specific C2H2 zinc finger transcription factor SltA (involved in the s a l t t olerance pathway) in the regulation of azole resistance of the human fungal pathogen Aspergillus fumigatus A lack of SltA results in an itraconazole hypersusceptibility phenotype. Transcriptional profiling combined with LacZ reporter analysis and electrophoretic mobility shift assays (EMSA) demonstrated that SltA is involved in its own transcriptional regulation and also regulates the expression of genes related to ergosterol biosynthesis (erg11A, erg13A, and erg24A) and drug efflux pumps (mdr1, mfsC, and abcE) by directly binding to the conserved 5'-AGGCA-3' motif in their promoter regions, and this binding is dependent on the conserved cysteine and histidine within the C2H2 DNA binding domain of SltA. Moreover, overexpression of erg11A or mdr1 rescues sltA deletion defects under itraconazole conditions, suggesting that erg11A and mdr1 are related to sltA-mediated itraconazole resistance. Most importantly, deletion of SltA in laboratory-derived and clinical azole-resistant isolates significantly attenuates drug resistance. Collectively, we have identified a new function of the transcription factor SltA in regulating azole resistance by coordinately mediating the key azole target Erg11A and the drug efflux pump Mdr1, and targeting SltA may provide a potential strategy for intervention of clinical azole-resistant isolates to improve the efficiency of currently approved antifungal drugs.

Few histological prognostic indicators for end-stage renal disease (ESRD) have been validated in diabetic patients. This biopsy-based study aimed to identify nephropathological risk factors for ESRD in Chinese patients with type 2 diabetes. Histological features of 322 Chinese type 2 diabetic patients with biopsy-confirmed diabetic nephropathy (DN) were retrospectively analysed. Cox proportional hazards analysis was used to estimate the hazard ratio (HR) for ESRD. Single glomerular proteomics and immunohistochemistry were used to identify differentially expressed proteins and enriched pathways in glomeruli. During the median follow-up period of 24 months, 144 (45%) patients progressed to ESRD. In multivariable models, the Renal Pathology Society classification failed to predict ESRD, although the solidified glomerulosclerosis (score 1: HR 1.65, 95% confidence interval [CI] 1.04–2.60; score 2: HR 2.48, 95% CI 1.40–4.37) and extracapillary hypercellularity (HR 2.68, 95% CI 1.55–4.62) were identified as independent risk factors. Additionally, single glomerular proteomics, combined with immunohistochemistry, revealed that complement C9 and apolipoprotein E were highly expressed in solidified glomerulosclerosis. Therefore, solidified glomerulosclerosis and extracapillary hypercellularity predict diabetic ESRD in Chinese patients. Single glomerular proteomics identified solidified glomerulosclerosis as a unique pathological change that may be associated with complement overactivation and abnormal lipid metabolism.

Zhao, Lijun, Xi Wang, Tingli Wang, Wenxin Fan, Honghong Ren, Rui Zhang, Yutong Zou, Huan Xu, Jie Zhang, Yunhong Wu, and Fang Liu. Associations between high-altitude residence and end-stage kidney disease in Chinese patients with type 2 diabetes.

The emergence of azole-resistant fungal pathogens has posed a great threat to public health worldwide. Although the molecular mechanism of azole resistance has been extensively investigated, the potential regulators of azole resistance remain largely unexplored. In this study, we identified a new function of the fungal specific C(2)H(2) zinc finger transcription factor SltA (involved in the salt tolerance pathway) in the regulation of azole resistance of the human fungal pathogen Aspergillus fumigatus. A lack of SltA results in an itraconazole hypersusceptibility phenotype. Transcriptional profiling combined with LacZ reporter analysis and electrophoretic mobility shift assays (EMSA) demonstrated that SltA is involved in its own transcriptional regulation and also regulates the expression of genes related to ergosterol biosynthesis (erg11A, erg13A, and erg24A) and drug efflux pumps (mdr1, mfsC, and abcE) by directly binding to the conserved 5′-AGGCA-3′ motif in their promoter regions, and this binding is dependent on the conserved cysteine and histidine within the C(2)H(2) DNA binding domain of SltA. Moreover, overexpression of erg11A or mdr1 rescues sltA deletion defects under itraconazole conditions, suggesting that erg11A and mdr1 are related to sltA-mediated itraconazole resistance. Most importantly, deletion of SltA in laboratory-derived and clinical azole-resistant isolates significantly attenuates drug resistance. Collectively, we have identified a new function of the transcription factor SltA in regulating azole resistance by coordinately mediating the key azole target Erg11A and the drug efflux pump Mdr1, and targeting SltA may provide a potential strategy for intervention of clinical azole-resistant isolates to improve the efficiency of currently approved antifungal drugs.

Background It is unclear whether short‐term blood pressure variability is associated with renal outcomes in patients with chronic kidney disease. Methods and Results This study analyzed data from participants in the C‐ STRIDE (Chinese Cohort Study of Chronic Kidney Disease) who had chronic kidney disease stages 1 to 4. Short‐term blood pressure variability was measured by calculating the weighted SD (w‐ SD ) of systolic blood pressure ( SBP ). Renal outcomes were defined as dialysis initiation and/or transplantation. Risk factors associated with w‐ SD of SBP were evaluated by linear regression. Associations of short‐term SBP variability with renal outcomes were evaluated by Cox regression. In total, 1421 patients with chronic kidney disease were included in this study (mean age, 49.4±13.6 years; 56.2% men; estimated glomerular filtration rate, 50.5±29.3 mL/min per 1.73 m 2 ; proteinuria, 0.9 [0.3–2.0] g/d). Mean w‐ SD of SBP was 12.6±4.4 mm Hg. w‐ SD of SBP was independently associated with older age, 24‐hour SBP , blood pressure circadian pattern, and angiotensin II receptor blocker treatment. During a median follow‐up of 4.9 years, 237 patients developed renal outcomes (37.01 per 1000 patient‐years). The incidence rate increased across the quartiles of w‐ SD (log‐rank P =0.005). w‐ SD of SBP was associated with an increased risk of renal outcomes, both as a continuous variable (hazard ratio [HR], 1.47; 95% CI, 1.09–1.99) and as a categorical variable (quartile 4 versus quartile 1: HR, 1.60; 95% CI, 1.08–2.36), independent of 24‐hour SBP , daytime SBP , and nighttime SBP . Conclusions Short‐term SBP was independently associated with the risk of dialysis initiation and/or transplantation in patients with chronic kidney disease .

The older population has increased sharply in China. However, renal clinical and histopathological data in this population are lacking. This study investigated the clinicopathologic features and the related risk factors for long-term renal survival in older patients with diabetic nephropathy (DN). In this retrospective observational study, 74 older patients (≥ 60 years old) with type 2 diabetes mellitus and biopsy-proven DN from 2007 to 2019 were included. Clinical data were extracted from electronic records. Renal biopsy specimens were semiquantitatively evaluated using the Renal Pathology Society (RPS) classification system. Cox proportional hazard analysis was used to estimate hazard ratios (HRs) for progression to end-stage renal disease (ESRD). During the median follow-up period of 22 months, 24 (32%) older patients progressed to ESRD. Older patients who progressed to ESRD had poorer renal function, lower hemoglobin and albumin concentrations, more severe glomerular lesions, and higher percentages of Kimmelstiel–Wilson lesions than those who did not progress to ESRD. After adjusting for age, sex, baseline renal function, and pathological parameters, multivariate Cox proportional hazard analysis showed that RPS glomerular classification (HR 2.49, 95% confidence interval [CI] 1.03–6.04), estimated glomerular filtration rate (eGFR) (HR 0.76, 95% CI 0.58–0.99), and proteinuria (HR 3.85, 95% CI 1.44–10.27) were independent risk factors for progression to ESRD. Lower eGFR, heavier proteinuria, and more severe RPS glomerular lesions were associated with ESRD in older patients with type 2 diabetes mellitus and DN.

Background and objectives Despite advances in identifying genetic factors of diabetic kidney disease (DKD), much of the heritability remains unexplained. Nine maturity-onset diabetes in young (MODY) probands with kidney biopsy-proven DKD were selected and included in this study. The probands had more severe DKD compared with their parents with MODY, with overt proteinuria or rapid progression to ESKD. We aimed to explore the contribution of the variants in susceptibility genes of DKD to the severity of kidney phenotype between the probands and their parents. Design, setting, participants, & measurements Whole-exome sequencing was performed to identify suspected MODY probands and their families. Known DKD susceptibility genes were reviewed. Variants reported to be associated with DKD, or those with minor allele frequency Results HNF1B-MODY, CEL-MODY, PAX4-MODY, and WFS1-MODY were diagnosed among nine families. We identified 196 selected variants of 25 DKD susceptibility genes among the participants. Analysis of phenotype between probands and parents, gene function, and protein–protein interaction networks revealed that COL4A3 variants were involved in the progression of DKD. Weak granular staining of COL4α3 was observed in the glomerular basement membrane of patients with the R408H and M1209I variants, whereas strong consecutive staining was observed in patients without these variants. Moreover, more number of DKD variants were identified in probands than in their parents with MODY. Conclusions The genetic effect of more pathogenic variants in various DKD susceptibility genes, especially variants in the COL4A3 gene, partially explained the more severe kidney phenotype in probands with kidney biopsy-proven DKD.

Glomerular basement membrane (GBM) thickening is considered as one of the earliest detectable pathological features of diabetic nephropathy (DN). However, whether the thickness of GBM will impact the prognosis of DN remains largely unknown. Our aim was to explore the relationship between thickness of GBM and DN progression in patients with type 2 diabetes mellitus (T2DM). A total of 118 patients with T2DM and biopsy-proven DN who received follow-up for at least 1 year were recruited. The patients were divided into two groups according to the median (787 nm) of the GBM thickness: Group 1: GBM thickness

The serum complement 3 (C3) level was reduced in many patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN). However, the clinical implications of such change are still less understood. This study was aimed to explore the association between C3 level and the baseline clinicopathological characteristics and the prognosis of T2DM patients with DN. A total of 171 T2DM patients with biopsy-proven DN who received follow-up for at least 1 year were recruited. The patients were divided into two groups based on the C3 level: decreased C3 group

The submerged gate filling processes were investigated through the use of particle image velocimetry (PIV) measurements, numerical simulation and castings production. The results showed that the submerged gate filling can improve the mold filling conditions, which may reduce the occurrence of inclusion defects during casting production. The liquid free surface in the mold rose slowly and smoothly during the filling process, which could reduce the occurrence of oxide film inclusion defects. The flow velocity decreased from the gate to the mold, which may reduce the severity of the liquid impingement that causes sand wash defects. The liquid flow inside the mold, with the exception of the flow path region, was primarily quiescent and the distance from the submerged gate to the free surface was relatively small. Therefore, low density slag in the liquid could be carried to the liquid free surface by the fluid flow and by the slag’s buoyancy.