Nephrotic proteinuria and hematuria with newly diagnosed IgA nephropathy after liver transplant: A case report.

BACKGROUND: IgA nephropathy is a renal lesion in patients with end-stage liver disease, called hepatic IgA nephropathy. The common manifestation of hepatic IgA nephropathy is microscopic hematuria. Sirolimus, often used to prevent organ rejection, has been reported to induce proteinuria after organ transplantation. But few cases of nephrotic proteinuria and hematuria are reported. CASE PRESENTATION: In this case, a 45-year-old male with a long history of hepatic B virus infection and liver cirrhosis, received liver transplant and was taking sirolimus as one of his immunosuppression drugs. Overt proteinuria and hematuria occurred. With no proteinuria history before, renal biopsy was performed, which indicated IgA nephropathy. CONCLUSION: We reported a liver recipient, who was taking sirolimus, developing nephrotic proteinuria and hematuria with IgA nephropathy. Further studies need to be carried out to disclose mechanism behind this phenomenon.

MAGI2 ameliorates podocyte apoptosis of diabetic kidney disease through communication with TGF-ß-Smad3/nephrin pathway.

Podocytes, the key component of the glomerular filtration barrier (GFB), are gradually lost during the progression of diabetic kidney disease (DKD), severely compromising kidney functionality. The molecular mechanisms regulating the survival of podocytes in DKD are incompletely understood. Here, we show that membrane-associated guanylate kinase inverted 2 (MAGI2) is specifically expressed in renal podocytes, and promotes podocyte survival in DKD. We found that MAGI2 expression was downregulated in podocytes cultured with high-glucose in vitro, and in kidneys of db/db mice as well as DKD patients. Conversely, we found enforced expression of MAGI2 via AAV transduction protected podocytes from apoptosis, with concomitant improvement of renal functions. Mechanistically, we found that MAGI2 deficiency induced by high glucose levels activates TGF-ß signaling to decrease the expression of anti-apoptotic proteins. These results indicate that MAGI2 protects podocytes from cell death, and can be harnessed therapeutically to improve renal function in diabetic kidney disease.

Emerging Liquid Metal Catalysts.

Catalysts serve pivotal roles in facilitating the development of sustainable energy systems on a global scale. Liquid metal usually refers to metal that is liquid below 330 °C, also known as low melting point metal. Liquid metal has emerged as an intriguing catalyst due to its commendable electrical conductivity, favorable fluidity, solubility in metals, phase transition capabilities, and modifiable oxide surface, thereby presenting a plethora of prospects for diverse catalytic reactions. In this Perspective, we elucidate the four primary merits of liquid metal catalysts: resistance to coking, the ability to tune elemental composition, the potential for structural transformation, and the capacity to inhibit coalescence. In light of this, a comprehensive summary is presented on the research advancements pertaining to liquid metal in methane pyrolysis, alkane dehydrogenation, carbon dioxide reduction, alcohol oxidation, and various other catalytic reactions. Finally, the challenges and prospects of liquid metal catalysts are elucidated.

Metabolic-associated fatty liver disease increases the risk of end-stage renal disease in patients with biopsy-confirmed diabetic nephropathy: a propensity-matched cohort study.

AIMS: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Clinical and Pathological Features of Chinese Patients with Type 2 Diabetes, Biopsy-Proven Diabetic Kidney Disease, and Rapid eGFR Decline.

Objective: 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.

What is the prognosis of ANCA-associated glomerulonephritis with immune deposition?

OBJECTIVES: This study aimed to analyze histological and clinical characteristics of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) showing renal involvement to investigate the associations between immune complexes (IC) and clinicopathological indicators, and explore the renal outcomes of AAV. METHODS: We retrospectively evaluated the histopathological features and clinical characteristics of 80 renal biopsies of patients with AAV with renal involvement. Renal morphology was classified into two (with and without the presence of IC and complement deposition). Endpoints included end-stage kidney disease (ESKD) and death. RESULTS: Compared with patients without IC, patients with immune deposition had lower complement C3 (0.80 ± 0.27 vs. 0.93 ± 0.20, p = 0.024), more severe hematuria [133 (46-299) vs. 33 (15-115), p = 0.001] but had milder chronic pathology, including chronic tubular atrophy (p = 0.03), chronic interstitial fibrosis (p = 0.049). Patients in the immune deposition group showed a tendency to have more severe crescent formation and less glomerulosclerosis, but the difference was not statistically significant. Endpoints such as death and ESKD were not significantly different between the two groups. CONCLUSIONS: Immune deposition may indicate lower complement C3, more severe hematuria and glomerular lesions, milder tubular atrophy, and interstitial fibrosis, but it cannot predict the renal outcome.

Dual Self-Built Gating Boosts the Hydrogen Evolution Reaction.

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 ReS2 -WS2 /WS2 hybridized heterostructure. As demonstrated in experimental and theoretical results, the dual gating can bidirectionally guide electron transfer and redistribute at the interface, endowing the model catalyst with an electron-rich region. The tailored electronic structures balance the adsorption of intermediates and the desorption of hydrogen synergistically to enhance the reaction kinetics for the hydrogen evolution reaction. Interestingly, the effect of dual gating can be easily amplified by the electric field. The overpotential and Tafel slope (49 mV, 35 mV dec-1 ) obtained under the electric field for ReS2 -WS2 /WS2 catalyst with the dual self-built gating effect are far below than those (210 mV, 116 mV dec-1 ) of the pure WS2 catalyst, which exhibits nearly four times improvement. The concept of dual gating can be applied to more systems, offering a new guideline for designing advanced electrocatalysts.

Development and internal validation of machine learning algorithms for end-stage renal disease risk prediction model of people with type 2 diabetes mellitus and diabetic kidney disease.

AIMS: Diabetic kidney disease (DKD) is the most common cause of end-stage renal disease (ESRD) and is associated with increased morbidity and mortality in patients with diabetes. Identification of risk factors involved in the progression of DKD to ESRD is expected to result in early detection and appropriate intervention and improve prognosis. Therefore, this study aimed to establish a risk prediction model for ESRD resulting from DKD in patients with type 2 diabetes mellitus (T2DM). METHODS: Between January 2008 and July 2019, a total of 390 Chinese patients with T2DM and DKD confirmed by percutaneous renal biopsy were enrolled and followed up for at least 1 year. Four machine learning algorithms (gradient boosting machine, support vector machine, logistic regression, and random forest (RF)) were used to identify the critical clinical and pathological features and to build a risk prediction model for ESRD. RESULTS: There were 158 renal outcome events (ESRD) (40.51%) during the 3-year median follow up. The RF algorithm showed the best performance at predicting progression to ESRD, showing the highest AUC (0.90) and ACC (82.65%). The RF algorithm identified five major factors: Cystatin-C, serum albumin (sAlb), hemoglobin (Hb), 24-hour urine urinary total protein, and estimated glomerular filtration rate. A nomogram according to the aforementioned five predictive factors was constructed to predict the incidence of ESRD. CONCLUSION: Machine learning algorithms can efficiently predict the incident ESRD in DKD participants. Compared with the previous models, the importance of sAlb and Hb were highlighted in the current model.HighlightsWhat is already known? Identification of risk factors for the progression of DKD to ESRD is expected to improve the prognosis by early detection and appropriate intervention.What this study has found? Machine learning algorithms were used to construct a risk prediction model of ESRD in patients with T2DM and DKD. The major predictive factors were found to be CysC, sAlb, Hb, eGFR, and UTP.What are the implications of the study? In contrast with the treatment of participants with early-phase T2DM with or without mild kidney damage, major emphasis should be placed on indicators of kidney function, nutrition, anemia, and proteinuria for participants with T2DM and advanced DKD to delay ESRD, rather than age, sex, and control of hypertension and glycemia.

Therapeutic carrier based on solanesol and hyaluronate for synergistic tumor treatment.

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 1H NMR spectroscopy. Doxorubicin (DOX) was loaded into the HA-STS nanoparticles with a relatively high content of 6.0%. pH-sensitive drug release behavior was achieved by introducing a hydroazone bond between STS and HA. A cytotoxicity assay indicated that the blank nanoparticles had an antitumor effect, which was enhanced by loading with an additional drug. Moreover, in vivo antitumor experiments indicated that the HA-STS-DOX showed superior tumor inhibition compared with free DOX, as well as lower cardiotoxicity and hepatotoxicity, demonstrating the advantages of the bioactive drug vehicles in cancer therapy.

Whether Renal Pathology Is an Independent Predictor for End-Stage Renal Disease in Diabetic Kidney Disease Patients with Nephrotic Range Proteinuria: A Biopsy-Based Study.

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 (<60 mL/min/1.73 m2), lower albumin (<30 g/L), lower hemoglobin (<120 g/L), and a higher grade of glomerular stage (class III + IV vs. class I + II) (p < 0.05). The hemoglobin and e-GFR, but not the histopathological damage, were significantly associated with a higher risk of ESRD in both the univariate and multivariate Cox analyses. Conclusions: In patients with diabetic kidney disease characterized by nephrotic range proteinuria, histopathological damage (glomerular alterations, interstitial fibrosis and tubular atrophy (IFTA), interstitial inflammation, and arteriolar hyalinosis) is not associated with poor renal outcomes, but hemoglobin and e-GFR could predict poor renal outcomes.

Association between serum uric acid and renal outcome in patients with biopsy-confirmed diabetic nephropathy.

OBJECTIVE: To investigate the relationship between serum uric acid (SUA) level and renal outcome in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN). METHODS: A total of 393 Chinese patients with T2DM and biopsy-proven DN and followed at least 1 year were enrolled in this study. Patients were stratified by the quartiles of baseline level of SUA: Q1 group: 286.02 ± 46.66 µmol/L (n = 98); Q2 group: 358.23 ± 14.03 µmol/L (n = 99); Q3 group: 405.50 ± 14.59 µmol/L (n = 98) and Q4 group: 499.14 ± 56.97µmol/L (n = 98). Renal outcome was defined by progression to end-stage renal disease (ESRD). Kaplan-Meier survival analysis and Cox proportional hazards model were used to analyze the association between SUA quartiles and the renal outcomes. RESULTS: During the median 3-year follow-up period, there were 173 ESRD outcome events (44.02%). No significant difference between SUA level and the risk of progression of DN (P = 0.747) was shown in the Kaplan-Meier survival analysis. In multivariable-adjusted model, hazard ratios for developing ESRD were 1.364 (0.621-2.992; P = 0.439), 1.518 (0.768-3.002; P = 0.230) and 1.411 (0.706-2.821; P = 0.330) for the Q2, Q3 and Q4, respectively, in comparison with the Q1 (P = 0.652). CONCLUSIONS: No significant association between SUA level and renal outcome of ESRD in Chinese patients with T2DM and DN was found in our study. Besides, the role of uric acid-lowering therapy in delaying DN progression and improving ESRD outcome had not yet been proven. Further study was needed to clarify the renal benefit of the uric acid-lowering therapy in the treatment of DN.

Early-onset of type 2 diabetes mellitus is a risk factor for diabetic nephropathy progression: a biopsy-based study.

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.

Association between atherosclerotic cardiovascular diseases risk and renal outcome in patients with type 2 diabetes mellitus.

AIMS: Chronic kidney disease (CKD) and diabetes mellitus increase atherosclerotic cardiovascular diseases (ASCVD) risk. However, the association between renal outcome of diabetic kidney disease (DKD) and ASCVD risk is unclear. METHODS: This retrospective study enrolled 218 type 2 diabetic patients with biopsy-proven DKD, and without known cardiovascular diseases. Baseline characteristics were obtained and the 10-year ASCVD risk score was calculated using the Pooled Cohort Equation (PCE). Renal outcome was defined as progression to end-stage renal disease (ESRD). The association between ASCVD risk and renal function and outcome was analyzed with logistic regression and Cox analysis. RESULTS: Among all patients, the median 10-year ASCVD risk score was 14.1%. The median of ASCVD risk score in CKD stage 1, 2, 3, and 4 was 10.9%, 12.3%, 16.5%, and 14.8%, respectively (p = 0.268). Compared with patients with lower ASCVD risk (＜14.1%), those with higher ASCVD risk had lower eGFR, higher systolic blood pressure, and more severe renal interstitial inflammation. High ASCVD risk (>14.1%) was an independent indicator of renal dysfunction in multivariable-adjusted logistic analysis (OR, 3.997; 95%CI, 1.385-11.530; p = 0.010), though failed to be an independent risk factor for ESRD in patients with DKD in univariate and multivariate Cox analysis. CONCLUSIONS: DKD patients even in CKD stage 1 had comparable ASCVD risk score to patients in CKD stage 2, 3, and 4. Higher ASCVD risk indicated severe renal insufficiency, while no prognostic value of ASVCD risk for renal outcome was observed, which implied macroangiopathy and microangiopathy in patients with DKD were related, but relatively independent.

Solidified glomerulosclerosis, identified using single glomerular proteomics, predicts end-stage renal disease in Chinese patients with type 2 diabetes.

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.

bFGF ameliorates intestinal mucosal permeability and barrier function through tight junction proteins in burn injury rats.

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).

Advances allowing feasible pyrG gene editing by a CRISPR-Cas9 system for the edible mushroom Pleurotus eryngii.

For decades, the edible mushroom Pleurotus eryngii (P. eryngii) has been cultivated as important raw materials for food and pharmaceutical industries in most of Asian countries, especially in China. Unfortunately, the generation and improvement of new cultivars are very difficult since there are many barriers which have not been solved thoroughly by gene editing tools, even though the CRISPR-Cas9 technique has been widely applied in other species. In this study, we identified the point-mutated variant of the endogenous sdhB gene (cbxr) as a more stable selection marker than hygromycin B resistance gene (hph) in P. eryngii. Furthermore, using a codon-optimized Cas9, a predicted native U6 promoter-guided sgRNA, as well as an optimized protoplast transformation system, a highly efficient pyrG gene editing system was established in P. eryngii, that incorporated varied insertions and deletions (indels) by non-homologous end joining (NHEJ) and homology-directed repair (HDR). Findings for a successful targeted gene editing strategy in the edible mushroom P. eryngii may open a new chapter for the improvement of edible mushroom cultivars.

Clinicopathologic features and prognostic factors in older patients with biopsy-proven diabetic nephropathy.

PURPOSE: 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). METHODS: 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). RESULTS: 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. CONCLUSION: Lower eGFR, heavier proteinuria, and more severe RPS glomerular lesions were associated with ESRD in older patients with type 2 diabetes mellitus and DN.

The C2H2 Transcription Factor SltA Contributes to Azole Resistance by Coregulating the Expression of the Drug Target Erg11A and the Drug Efflux Pump Mdr1 in Aspergillus fumigatus.

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 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 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.

Associations Between High-Altitude Residence and End-Stage Kidney Disease in Chinese Patients with Type 2 Diabetes.

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. High Alt Med Biol. 21:396-405, 2020. Background: This study investigated whether living at high altitude was associated with progression to end-stage kidney disease (ESKD) in Chinese patients with diabetic nephropathy (DN). Materials and Methods: This retrospective study included 369 patients with type 2 diabetes mellitus (T2DM) and biopsy-confirmed DN. Cox proportional hazards models were used to estimate hazard ratios (HRs) for the influence of living at high altitude on ESKD. Results: Patients living at ≥2,000 m above sea level were more likely to be Tibetan, and they had higher mean body mass indexes, glycosylated hemoglobin, hemoglobin concentrations, and baseline estimated glomerular filtration rates than those living at lower altitudes. During a median follow-up period of 20 months, 141 (38%) patients progressed to ESKD. In multivariable Cox analysis adjusted for age, sex, ethnicity, and clinical and pathological parameters, living at high altitude was independently associated with progression to ESKD in Chinese DN patients [HR 2.83, 95% confidence interval (CI) 1.05-7.58]. Compared with Han Chinese, Tibetans were at a lower risk of progression to ESKD (HR 0.15, 95% CI 0.04-0.59). Conclusions: Living at high altitude was independently associated with renal outcome in Han Chinese patients with T2DM and DN, but not native Tibetans.

Corrigendum to "FcgRIII Deficiency and FcgRIIb Defeciency Promote Renal Injury in Diabetic Mice".

[This corrects the article DOI: 10.1155/2019/3514574.].