Association between serum vitamin D concentration and liver fibrosis in diabetes mellitus patients: a cross-sectional study from the NHANES database.

AIM: Liver fibrosis (LF) is a common complication of diabetes mellitus (DM). Studies have found that vitamin D (VD), as a modifiable factor has been reported to be associated with LF. The relationship between serum VD concentration and LF in DM patients has rarely been reported. The aim of this study was to assess the association between serum VD concentration and LF in DM patients. METHODS: In this cross-sectional study, data of DM patients aged ≥ 45 years were extracted from the National Health and Nutrition Examination Survey (NHANES 2017-2018). Serum VD concentration was measured by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Vibration controlled transient elastography (VCTE) was used to measure liver stiffness. Covariates included sociodemographic information, lifestyles, laboratory data, diseases history were extracted from the database. The weighted univariable and multivariable logistic regression models were utilized to explore the association between serum VD concentration and LF in DM patients, and were described as odds ratio (ORs) and 95% confidence intervals (CIs). Subgroup analyses based on BMI, liver steatosis, hypertension and dyslipidemia were further assessed the association. RESULTS: A total of 799 patients were included, of which 188 (23.53%) had LF. Higher serum VD concentration was associated with the lower odds of LF (OR = 0.33, 95% CI 0.19-0.59) and advanced LF (OR = 0.31, 95% CI 0.17-0.55) in DM patients after adjustment for race, liver steatosis, BMI, smoking, drinking, AST, ALT and physical activity, especially in patients with liver steatosis (OR = 0.28, 95% CI 0.13-0.59) and dyslipidemia (OR = 0.31, 95% CI 0.14-0.66), respectively. CONCLUSIONS: High serum VD concentration may have a potential benefit for maintain the liver health in DM patients.

Elastic wave prospecting of water-conducting fractured zones in coal mining.

In order to understand the development law of water-conducting fractures in overlying strata during the mining process of coal seam, an elastic wave exploration method based on key stratum theory is proposed to predict the height of water-conducting fracture zone. Taking Yushen mining area as the background, the development and evolution of fractures and the three-dimensional distribution characteristics of water-conducting fracture zone are studied by combining well-ground microseismic monitoring, high-density three-dimensional seismic exploration, borehole investigation, FLAC3D numerical simulation and similar physical simulation tests. The results indicate that the trial mining face's fracture-to-coal ratio ranges from 25.86 to 30.76, with the maximum fracture-to-coal ratio near the cutting eye at 30.76 and the minimum in the central portion of the trial mining face at 25.86. The primary characteristics of rock mass fracture distribution in the mined area are the development of fractures predominantly along high-angle and even vertical bedding planes. Within the fracture zone, fractures increase from top to bottom, with high-angle fractures developing in the lower section and high-angle and horizontal fractures developing simultaneously in the upper section. The water-conducting fracture zone undergoes a developmental process from inception to development, reaching its maximum height, and eventually stabilizing as coal seam mining progresses, overlying rock subsides, strata separation, and damage formation. The three-dimensional shape of the water-conducting fracture zone in the roof of the Yushen mining area exhibits a morphological pattern where the height of the fracture zone gradually decreases from the cutting eye towards the goaf. It also transitions from high to low along both sides and from the periphery towards the interior of the working face. In the trend and strike directions, it exhibits saddle-like characteristics. By comparing the monitoring results, the rationality of the elastic wave prospecting method for predicting the height of water-conducting fracture zones based on critical layer theory was verified. This research holds significant reference value for coal mining under similar geological conditions, especially in terms of water preservation during mining operations.

Photocatalytic fuel cell based on integrated silicon nanowire arrays/zinc oxide heterojunction anode for simultaneous wastewater treatment and electricity production.

Photocatalytic fuel cells (PFCs) convert organic waste into electricity, thereby providing a potential solution for remediating environmental pollution and solving energy crises. Most PFCs for energy generation applications use powder photocatalysts, which have poor mechanical stability, high internal resistance, and may detach from the substrate during reactions, leading to unstable performance. Integrated photoelectrodes can overcome the drawbacks of powder catalysts. In this study, an integrated photoanode was prepared based on a silicon nanowire arrays/zinc oxide (Si NWs/ZnO) heterojunction by combining metal-assisted chemical etching (MACE) and hydrothermal methods. The resulting photoanode was used to assemble a PFC for simultaneous electricity generation and Rhodamine (RhB) dye wastewater degradation. This PFC showed excellent cell performance under irradiation, with a short-circuit current density of 0.183 Am-2, an open-circuit voltage (OCV) of 0.72 V, and a maximum power density of 0.87 W m-2. It could also be used continuously 20 times while degrading > 90% of RhB. This performance was ascribed to the three-dimensional (3D) structure and large surface area of Si NWs, as well as the matched band structure of ZnO, which facilitated the efficient separation and transport of photogenerated carriers in Si NWs/ZnO. The integrated structure also shortened the carrier transport pathways and suppressed carrier recombination. This research provides a foundation for the development of efficient, stable, low-cost, small-scale PFCs.

Dipeptidyl peptidase 3 is essential for maintaining osteoblastic differentiation under a high-glucose environment by inhibiting apoptosis, oxidative stress and inflammation through the modulation of the Keap1-Nrf2 pathway.

Dipeptidyl peptidase 3 (Dpp3) has emerged as a pivotal mediator of bone homeostasis and bone loss pathology. However, whether Dpp3 plays a role in diabetic osteoporosis has not been addressed. Therefore, this work explored the possible role of Dpp3 in osteoblast dysfunction evoked by high glucose (HG), a cellular model for studying diabetic osteoporosis in vitro. Dpp3 expression was decreased in the pre-osteoblast MC3T3-E1 during osteoblastic differentiation under the HG environment. The osteoblastic differentiation impaired by HG was reversed in Dpp3-overexpressing MC3T3-E1 cells. The migration and invasion of MC3T3-E1 cells impeded by HG were reversed by Dpp3 overexpression. Moreover, HG-evoked apoptosis, oxidative stress and inflammation were ameliorated in Dpp3-overexpressing MC3T3-E1 cells. A mechanistic study showed that Dpp3 up-regulated the activation of nuclear factor E2-related factor 2 (Nrf2) depending on Kelch-like ECH-associated protein 1 (Keap1). The blockade of Nrf2 reversed Dpp3-mediated effects on osteoblastic differentiation, apoptosis, oxidative stress and inflammation of HG-stimulated MC3T3-E1 cells. Therefore, Dpp3 plays an essential role in maintaining osteoblastic differentiation under a HG environment associated with the regulation of the Keap1-Nrf2 pathway. This work indicates a possible relationship between Dpp3 and diabetic osteoporosis.

Identification and analysis of hub genes of hypoxia-immunity in type 2 diabetes mellitus.

The chronic metabolic disease named type 2 diabetes (T2D) accounts for over 90% of diabetes mellitus. An increasing number of evidences have revealed that hypoxia has a significantly suppressive effect on cell-mediated immunity, as well as the utilization of glucose in diabetics. Therefore, we aimed to screen and identify hypoxia-immune-related hub genes in T2D through bioinformatic analysis. The Gene Expression Omnibus (GEO) database was used to get T2D gene expression profile data in the peripheral blood samples (GSE184050), and hypoxia-related genes were acquired from Molecular Signatures Database (MSigDB). Differentially expressed mRNAs (DEGs) and lncRNAs (DELs) between T2D and normal samples were identified by DeSeq2 package. The clusterProfiler package was used to perform enrichment analyses for the overlapped genes of DEGs and hypoxia-related genes. Further, Hypoxia-related hub genes were discovered using two machine learning algorithms. Next, the compositional patterns of immune and stromal cells in T2D and healthy groups were estimated by using xCell algorithm. Moreover, we used the weighted correlation network analysis (WGCNA) to examine the connection between genes and immune cells to screen immune-related genes. Gene Set Enrichment Analysis (GSEA) was used to investigate the functions of the hypoxia-immune-related hub genes. Finally, two peripheral blood cohorts of T2D (GSE184050 and GSE95849) as well as the quantitative real-time PCR (qRT-PCR) experiments for clicinal peripheral blood samples with T2D were used for verification analyses of hub genes. And meanwhile, a lncRNA-TF-mRNA network was constructed. Following the differentially expressed analysis, 38 out of 3822 DEGs were screened as hypoxia-related DEGs, and 493 DELs were found. These hypoxia-related DEGs were mainly enriched in the GO terms of pyruvate metabolic process, cytoplasmic vesicle lumen and monosaccharide binding, and the KEGG pathways of glycolysis/gluconeogenesis, pentose phosphate pathway and biosynthesis of nucleotide sugars. Moreover, 7 out of hypoxia-related DEGs were identified as hub genes. There were six differentially expressed immune cell types between T2D and healthy samples, which were further used as the clinical traits for WGCNA to identify AMPD3 and IER3 as the hypoxia-immune-related hub genes. The results of the KEGG pathways of genes in high-expression groups of AMPD3 and IER3 were mainly concentrated in glycosaminoglycan degradation and vasopressin-regulated water reabsorption, while the low-expression groups of AMPD3 and IER3 were mainly associated with RNA degradation and nucleotide excision repair. Finally, when compared to normal samples, both the AMPD3 and IER3 were highly expressed in the T2D groups in the GSE184050 and GSE95849 datasets. The result of lncRNA-TF-mRNA regulatory network showed that lncRNAs such as BACH1-IT1 and SNHG15 might induce the expression of the corresponding TFs such as TFAM and THAP12 and upregulate the expression of AMPD3. This study identified AMPD3 and IER3 as hypoxia-immune-related hub genes and potential regulatory mechanism for T2D, which provided a new perspective for elucidating the upstream molecular regulatory mechanism of diabetes mellitus.

Upregulation of BRD7 protects podocytes against high glucose-induced apoptosis by enhancing Nrf2 in a GSK-3ß-dependent manner.

Bromodomain-containing protein 7 (BRD7) is linked to a variety of pathophysiological conditions. However, it is still unclear whether BRD7 is connected with diabetic nephropathy. This research explored the relevance of BRD7 in diabetic nephropathy using high glucose (HG)-stimulated podocytes in vitro. BRD7 expression in podocytes was decreased after HG stimulation. Podocytes with forced BRD7 expression were protected from HG-induced apoptosis, oxidative stress and inflammation. Further data revealed that forced expression of BRD7 led to enhanced nuclear factor erythroid-2-related factor 2 (Nrf2) activation in HG-stimulated podocytes, associated with the upregulation of glycogen synthase kinase-3ß (GSK-3ß) phosphorylation. Reactivation of GSK-3ß diminished BRD7-elicited Nrf2 activation. In addition, restraining of Nrf2 diminished the BRD7 overexpression-induced beneficial effects on HG-induced podocyte damage. Taken together, these data document that BRD7 defends against HG-induced podocyte damage by enhancing Nrf2 via regulation of GSK-3ß. Our work indicates that the BRD7/GSK-3ß/Nrf2 axis may play a key role in mediating podocyte injury in diabetic nephropathy.

Efficacy of low-protein diet in diabetic nephropathy: a meta-analysis of randomized controlled trials.

PURPOSE: We aimed to systematically assess the efficacy of low-protein diet preventing progression of diabetic nephropathy based on randomized controlled trials (RCTs). METHODS: A systematic and electronic search was conducted. Initial searches of literature updated to September 2018 were made using the following databases including CNKI, VIP, Wanfang, Cochrane, PubMed, and Embase using the index words for qualified RCTs. Additional searches were performed to identify linked literature sources. Data of RCTs on low-protein diet versus control diet, efficacy analysis of kidney function, nutritional status or proteinuria were extracted. Random effects model and fixed effects model were applied to combine the data which were further analyzed by Chi-squared test and I2tests. The main outcomes were then analyzed through the use of relative risks (RR), mean difference (MD) and its 95% confidence interval (95% CI). RESULTS: Twenty articles were included in the present meta-analysis with a total of 690 patients in the low-protein diet group (LPD) and a total of 682 patients in the control group. Moderate to strong evidence indicated that LPD was significantly effective for decreasing the urinary albumin excretion rate (SMD:0.62, 95%CI:0.06-1.19) and proteinuria (SMD:0.69, 95%CI:0.22-1.16) versus the control group. No statistical difference, however, was found in glycosylated hemoglobin (SMD:0.17, 95%CI:-0.18-0.51), serum creatinine (SMD:0.20, 95%CI:-0.26-0.66), as well as glomerular filtration rate (SMD:0.21, 95%CI:-0.29-0.71) between the two groups. CONCLUSION: The current meta-analysis reveals an effective role of low-protein diet in improving diabetic nephropathy. However, the small number of involved patients may limit the accuracy of results. High-quality RCTs with a larger sample size in the future are required to confirm the current findings.