An imbalance between T helper 17 (Th17) and T regulatory (Treg) cell subsets contributes to the pathogenesis of diabetic kidney disease (DKD). However, the underlying regulatory mechanisms that cause ...this imbalance are unknown. Serum/glucocorticoid‐regulated kinase 1 (SGK1) has been suggested to affect Th17 polarization in a salt‐dependent manner, and sodium/glucose cotransporter 2 inhibitors (SGLT2i) have been demonstrated to regulate sodium‐mediated transportation in the renal tubules. This study aimed to evaluate the potential benefits of dapagliflozin (Dap) on DKD, as well as its influence on shifting renal T‐cell polarization and related cytokine secretion. We treated male db/db mice with Dap or voglibose (Vog) and measured blood and kidney levels of Th17 and Treg cells using flow cytometry. We found that Th17 cells were significantly increased, while Treg cells were significantly decreased in diabetic mice. Moreover, Dap suppressed the polarization of Th17/Treg cells by inhibiting SGK1 in diabetic kidneys, and this was accompanied by attenuation of albuminuria and tubulointerstitial fibrosis independent of glycemic control. Taken together, these results demonstrate that the imbalance of Th17/Treg cells plays an important role in the progression of DKD. Moreover, Dap protects against DKD by inhibiting SGK1 and reversing the T‐cell imbalance.
An imbalance between Th17 and Treg cell subsets contributes to the pathogenesis of diabetic kidney disease. We found that Th17 cells were increased, while Treg cells were decreased in diabetic mice. Dapagliflozin suppressed the polarization of Th17/Treg cells by inhibiting SGK1 in diabetic kidneys, and this was accompanied by attenuation of albuminuria and tubulointerstitial fibrosis independent of glycemic control.
The effect of exosomes on receptor cells participating in intercellular communication has been extensively studied, but the effect of exosomes on donor cells remains unclear. It has been reported ...that exosomes secreted by renal proximal tubular epithelial cells (PTECs) under different stimuli accelerate acute and chronic kidney diseases. This study aimed to explore whether inhibiting exosomal secretion in PTECs by knocking out Rab27a, a key exosome regulatory gene, inhibits the excessive inflammatory response in PTECs and delays diabetic kidney disease (DKD). First, we proved that the bovine serum albumin (BSA)-induced inflammatory response in HK-2 cells was inhibited by knocking out Rab27a and that Rab27a, IL-6, TNF-α and COL-1 expression was markedly increased in an HFD/STZ-induced diabetic mouse model. Furthermore, miR-26a-5p expression in exosomes secreted by BSA-treated HK-2 cells was significantly increased but correspondingly decreased in the cells; after knocking out Rab27a, miR-26a-5p levels in the cells rebounded. Next, we confirmed that a miR-26a-5p mimic suppressed the inflammatory response, while a miR-26a-5p inhibitor accelerated the inflammatory response. Then, we found that miR-26a-5p targets the 3′-untranslated region (UTR) of CHAC1. Furthermore, the inflammatory response and NF-κB signalling pathway activation induction by the miR-26a-5p inhibitor were abolished by CHAC1 knockout. Therefore, we conclude that inhibiting exosome secretion by BSA-induced PTECs promotes miR-26a-5p expression in cells, thereby inhibiting the CHAC1/NF-κB pathways to prevent the inflammatory response in PTECs and delaying the development of DKD. This study provides new insight into the pathogenic mechanism of exosomes and a new therapeutic target for DKD.
Background
Endothelial cell (EC) dysfunction leading to microvascular alterations is a hallmark of technique failure in peritoneal dialysis (PD). However, the mechanisms underlying EC dysfunction in ...PD are poorly defined.
Methods
We combined RNA sequencing with metabolite set analysis to characterize the metabolic profile of peritoneal ECs from a mouse model of PD. This was combined with EC‐selective blockade of glycolysis by genetic or pharmacological inhibition of 6‐phosphofructo‐2‐kinase/fructose‐2,6‐biphosphatase 3 (PFKFB3) in vivo and in vitro. We also investigated the association between peritoneal EC glycolysis and microvascular alterations in human peritoneal samples from patients with end‐stage kidney disease (ESKD).
Results
In a mouse model of PD, peritoneal ECs had a hyperglycolytic metabolism that shunts intermediates into nucleotide synthesis. Hyperglycolytic mouse peritoneal ECs displayed a unique active phenotype with increased proliferation, permeability and inflammation. The active phenotype of mouse peritoneal ECs can be recapitulated in human umbilical venous ECs and primary human peritoneal ECs by vascular endothelial growth factor that was released from high glucose‐treated mesothelial cells. Importantly, reduction of peritoneal EC glycolysis, via endothelial deficiency of the glycolytic activator PFKFB3, inhibited PD fluid‐induced increases in peritoneal capillary density, vascular permeability and monocyte extravasation, thereby protecting the peritoneum from the development of structural and functional damages. Mechanistically, endothelial PFKFB3 deficiency induced the protective effects in part by inhibiting cell proliferation, VE‐cadherin endocytosis and monocyte‐adhesion molecule expression. Pharmacological PFKFB3 blockade induced a similar therapeutic benefit in this PD model. Human peritoneal tissue from patients with ESKD also demonstrated evidence of increased EC PFKFB3 expression associated with microvascular alterations and peritoneal dysfunction.
Conclusions
These findings reveal a critical role of glycolysis in ECs in mediating the deterioration of peritoneal function and suggest that strategies targeting glycolysis in peritoneal ECs may be of therapeutic benefit for patients undergoing PD.
Peritoneal endothelial cells have a hyperglycolytic metabolism during peritoneal dialysis (PD).
Endothelial PFKFB3 deficiency/blockade inhibits PD fluid‐induced peritoneal microvascular alterations, thereby protecting the peritoneum from the development of structural and functional damages.
Mechanistically, endothelial PFKFB3 deficiency induces the protective effects in part by inhibiting cell proliferation, VE‐cadherin endocytosis and monocyte‐adhesion molecule expression.
Abstract This study aimed to explore the effects and mechanism of circ 0006282 in Diabetic nephropathy (DN) in vitro and in vivo. 6-week-old male db/db mice were induced by intraperitoneal (I.P) ...injection of STZ (50 mg/kg, S0130, Sigma, St. Louis, MO, USA) for five consecutive days. HK-2 cells was incubated with high glucose for vitro model. Western blotting, immunostaining, and biochemical assays were used to obtain that inflammatory factor and protein expressions. The current study demonstrated that the serum circ 0006282 expression were reduced, and serum miR-155 expression in patients with DN were increased. Circ 0006282 reduced inflammation in kidney cell by high glucose. MiR-155 promoted inflammation in kidney cell by high glucose. Circ 0006282 reduced inflammation via activation of SIRT1/NLRP3 signaling pathway by suppression of miR-155 expression. MiR-155 regulated the anti-inflammation effects of circ 0006282 on inflammation in kidney cell by high glucose by SIRT1/NLRP3 signaling pathway. Taken together, these results suggest that circ 0006282 may represent promising strategy for the therapy of DN.
Abstract This study aimed to explore the effects and mechanism of circ 0006282 in Diabetic nephropathy (DN) in vitro and in vivo. 6-week-old male db/db mice were induced by intraperitoneal (I.P) ...injection of STZ (50 mg/kg, S0130, Sigma, St. Louis, MO, USA) for five consecutive days. HK-2 cells was incubated with high glucose for vitro model. Western blotting, immunostaining, and biochemical assays were used to obtain that inflammatory factor and protein expressions. The current study demonstrated that the serum circ 0006282 expression were reduced, and serum miR-155 expression in patients with DN were increased. Circ 0006282 reduced inflammation in kidney cell by high glucose. MiR-155 promoted inflammation in kidney cell by high glucose. Circ 0006282 reduced inflammation via activation of SIRT1/NLRP3 signaling pathway by suppression of miR-155 expression. MiR-155 regulated the anti-inflammation effects of circ 0006282 on inflammation in kidney cell by high glucose by SIRT1/NLRP3 signaling pathway. Taken together, these results suggest that circ 0006282 may represent promising strategy for the therapy of DN.
Nitrophenols are identified as the priority organic pollutants due to the chemical stability, water solubility, persistence, and toxicity to human health and the environment. Hence, removal of ...nitrophenols from waste water is vitally essential. In this study, amino-rich coordination polymer Cu2I2(MA)2 (MA = melamine) has been applied for efficient adsorption and catalytic reduction of nitrophenols, like 4-nitrophenol (4-NP), 2, 4-dinitrophenol (DNP) and 2, 4, 6-trinitrophenol (TNP). The effect of various parameters like contact time, initial concentrations, pH, and temperature on adsorption were investigated. The adsorption of nitrophenols fitted the pseudo-second-order kinetic model and Langmuir isotherms model well. The maximum adsorption capacities were 285.71, 232.02, and 131.57 mg g−1 for 4-NP, DNP, and TNP when initial concentrations were 50 mg L−1 at 293.15 K, respectively. The adsorption of nitrophenols is a spontaneous, endothermic, and entropy-driven process. The reduction reaction followed the pseudo-first-order kinetics, and the kinetic rate constants were 0.4413, 0.3167, and 0.17538 min−1 for 4-NP, DNP, and TNP, respectively. The effect of initial nitrophenols concentration, anions, and temperature on reduction process was investigated. The mechanism of adsorption and catalytic reduction of Cu2I2(MA)2 was studied. The results demonstrated that Cu2I2(MA)2 exhibits excellent adsorption and catalytic activity to remove nitrophenols.
Nitrophenols adsorption on Cu2I2(MA)2 by hydrogen bonding, electrostatic, electron donor-acceptor, π-π interaction, and electrons transfer from BH4− to nitrophenols then formation aromatic amines. Display omitted
•Cu2I2(MA)2 exhibits effective adsorption and catalytic activity for nitrophenols.•Effect of various factors on the adsorption and reduction were investigated.•The adsorption and reduction mechanisms of nitrophenols for Cu2I2(MA)2 were analyzed.•Adsorption is a monolayer, spontaneous, endothermic and entropy-driven process.•The existence of Cu2I2(MA)2 promotes the formation of H radicals in reduction.
Storm surge is a natural disaster, often causing economic damage and loss of human life in the coastal communities. In recent decades, with more people attracted to coastal areas, the potential ...economic losses resulted from storm surges are increasing. Therefore, it is important to make risk assessments to identify areas at risk and design risk reduction strategies. However, the quantitative risk assessment of storm surge for coastal cities in China is often difficult due to the lack of adequate data regarding the building footprint and vulnerability curves. This paper aims to provide a methodology for conducting the quantitative risk assessment of storm surge, estimating direct tangible damage, by using Geographical Information System (GIS) techniques and open data. The proposed methodology was applied to a coastal area with a high concentration of petroleum industries in the Daya Bay zone. At first, five individual typhoon scenarios with different return periods (1000, 100, 50, 20, and 10 years) were defined. Then, the Advanced Circulation model and the Simulating Waves Nearshore model were utilized to simulate storm surge. The model outputs were imported into GIS software, transformed into inundation area and inundation depth. Subsequently, the building footprint data were extracted by the use of GIS techniques, including spatial analysis and image analysis. The layer containing building footprints was superimposed on the inundation area layer to identify and quantify the exposed elements to storm surge hazard. Combining the exposed elements with their related depth–damage functions, the quantitative risk assessment translates the spatial extent and depth of storm surge into the estimation of economic losses. The quantitative risk assessment and zonation maps for sub-zones in the study area can help local decision-makers to prioritize the sub-zones that are more likely to be affected by storm surge, make risk mitigation strategies, and develop long-term urban plans.
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•The risk assessment was made by integrating three components with GIS techniques.•It is the first to make a risk assessment based on depth-damage functions in China.•The quantitative risk can be utilized to make a cost-benefit analysis.•The risk zonation maps are helpful to make strategies based on different risk levels.•The analysis and maps have been used in practice by the local decision-makers.
Luminescent copper(I) iodide (CuI)-based coordination polymers (CPs) are well-known for their structural diversity and strong photoluminescence and are considered as promising candidates for optical ...applications. Here, a fluorescent Cu2I2(2-ap)2(1) (2-ap = 2-aminopyridine) CP was designed, synthesized, and applied to the effective detection of biothiols and antimicrobial study. Based on the strong thiaphilicity of copper (I), the CP 1 was used as a fluorescent probe to detect biothiols, which play important roles in regulating normal physiological processes due to their vital biological functions. Results revealed that the probe was able to achieve selective and sensitive detection of cysteine (Cys), glutathione (GSH), and homocysteine (Hcy) with low detection limits of 1.013 μM, 1.051 μM, and 1.034 μM, respectively. Moreover, the probe was successfully applied to the detection of thiols in human urine, fetal bovine serum, and bovine serum albumin, which demonstrated the potential application in biological samples. Furthermore, a CP/cellulose nanofibers (CP/CNFs) composite film was fabricated for visual detection of biothiols and antimicrobial study. The developed composite film showed good antimicrobial activity against tested bacteria in vitro conditions, thus opening up the antimicrobial application of CP-doped composite film and providing a new perspective and prospect for potential application in food packaging.
A fluorescent copper(I) iodide (CuI) coordination polymer (CP) Cu2I2(2-ap)2(1) (2-ap = 2-aminopyridine) was designed, synthesized and applied to the effective detection of biothiols and antimicrobial study. Display omitted
•CuI-based coordination polymer (CP) was designed and synthesized.•The CP was used as fluorescent probe for selective and sensitive detection of biothiols.•The low detection limits of probe for Cys, GSH and Hcy were 1.013, 1.051 and 1.034 μM, respectively.•A CP@CNFs film was used for visual detection of biothiols and antimicrobial study.•Film with good antimicrobial activity against gram-positive and gram-negative bacteria.
In this paper, an end-to-end lane detection method based on the polynomial regression is proposed, combining CNNs and Transformer. Transformer proposes a self-attentive mechanism to model nonlocal ...interactions to capture global context. Then, an effective Global-Local training strategy is presented to capture a multi-scale feature, which is capable of capturing richer lane information involving structure and context, especially as the lane marking point is remote. And the obtained multi-scale feature map can be fused by utilizing different scale guidance. Finally, the proposed method is validated on the TuSimple benchmark, whose results show the accuracy can achieve 96.33% in models, and 11.1x faster than the popular Line-CNN model in “compute” time.
Abstract
Background
Chronic obstructive pulmonary disease (COPD) represents a prevalent ailment, progressively surging within the ranks of coal mine laborers. The current study endeavors to elucidate ...the effects of dust exposure and smoking on COPD incidence amongst coal mine workers, while concurrently devising preventive strategies for this affliction.
Method
A nested case–control study was conducted encompassing 1,416 participants aged ≥ 18 years, spanning the duration from (2017–2018) until 2020. A meticulous matching process yielded a cohort of 708 COPD patients, each paired with a control subject, forming a harmonious 1:1 ratio. Multiple logistic regression analysis was employed to scrutinize the associations between smoking, dust exposure with COPD among coal workers.
Results
The COPD prevalence within the cohort of coal workers under investigation amounted to 22.66%, with an accompanying incidence density of 0.09/person-year. Following meticulous adjustment for confounding variables, it was discerned that cumulative dust exposure within the range of 47.19 ~ (OR: 1.90, 95% CI: 1.05, 3.44), 101.27 ~ (OR: 1.99, 95% CI: 1.17, 3.39), as well as smoking indices of 72 ~ (OR: 1.85, 95% CI: 1.19, 2.88), 145 ~ (OR: 1.74, 95% CI: 1.17, 2.61), 310 ~ (OR: 1.85, 95% CI: 1.23, 2.77) engender an escalated vulnerability to COPD among coal workers. Furthermore, interaction analysis discerned an absence of both multiplicative and additive interactions between dust exposure, smoking, and COPD occurrence amidst coal workers.
Conclusion
Dust exposure and smoking were unequivocally identified as precipitating risk factors for COPD incidence within the population of coal workers, albeit devoid of any discernible interaction between these two causal agents.
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