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Kidney fibrosis is a common fate of chronic kidney diseases (CKDs), eventually leading to renal dysfunction. Yet, no effective treatment for this pathological process has been achieved. During the bioassay‐guided chemical investigation of the medicinal plant Wikstroemia chamaedaphne, a daphne diterpenoid, daphnepedunin A (DA), is characterized as a promising anti‐renal fibrotic lead. DA shows significant anti‐kidney fibrosis effects in cultured renal fibroblasts and unilateral ureteral obstructed mice, being more potent than the clinical trial drug pirfenidone. Leveraging the thermal proteome profiling strategy, cell division cycle 42 (Cdc42) is identified as the direct target of DA. Mechanistically, DA targets to reduce Cdc42 activity and down‐regulates its downstream phospho‐protein kinase Cζ(p‐PKCζ)/phospho‐glycogen synthase kinase‐3β (p‐GSK‐3β), thereby promoting β‐catenin Ser33/37/Thr41 phosphorylation and ubiquitin‐dependent proteolysis to block classical pro‐fibrotic β‐catenin signaling. These findings suggest that Cdc42 is a promising therapeutic target for kidney fibrosis, and highlight DA as a potent Cdc42 inhibitor for combating CKDs. [ABSTRACT FROM AUTHOR]

Electrolysis technology is very effective in removing organic pollutants including dye wastewater and takes into account environmental friendliness. This paper deals with the electrochemical degradation of triphenylmethane dye crystal violet (DCV) from the aqueous solution using 304 stainless steel electrodes. The electrolytic cell device with a flotation column structure was set up and the electrolytic degradation process was studied. It could be found that the DCV removal efficiency and reaction rate constants were fitting the first‐order kinetic model. The process performance was analyzed in terms of degradation efficiency and energy consumption. Almost complete degradation (>98%) of 100 mg/L DCV was achieved after the 40 min reaction under the conditions of 300 mg/L NaCl dosage, nature pH (5–7), and 10 V applied voltage. Finally, the behaviours of degradation were studied. In the process of electrochemical degradation, the synergistic effects of electrode electrolysis, including indirect oxidation of electrolyte, hydroxyl radical, flocculation, and air flotation, removed the dye pollutants from the wastewater. The present study has proved the effectiveness and cleanness of electrochemical treatment for the triphenylmethane dye solution. [ABSTRACT FROM AUTHOR]

Lupus nephritis (LN) is one of the most severe manifestations of systemic lupus erythematosus (SLE). The chronic graft versus host disease (cGVHD) mouse model is a well‐established model of SLE. LC3‐associated autophagy plays a critical role in extracellular particle clearance, including pathogens and apoptotic cells. Lupus Recipe (LR) is a Chinese herbal compound that has been proven to be effective in treating SLE. In the study, we investigated the protective effects of LR or LR combined with prednisone on cGVHD mouse model and LC3‐associated autophagy in the kidney. The mice were subjected to six groups. The LR treatment group received LR at the dosage of 1.15 and 2.3 g/kg/day, respectively. The corticosteroid treatment group received prednisone at a dosage of 5 mg/kg/day. The combination treatment group received LR at a dosage of 2.3 g/kg/day, and prednisone at 2.5 mg/kg/day. LR treatment reduced proteinuria and serum triglyceride levels, as well as spleen weight. LR also alleviated pathologic damage and immunoglobulin G deposition in the kidney. LR combined with a low dose of prednisone significantly improved kidney function and decreased serum triglyceride, total cholesterol, and spleen weight. In addition, combination treatment relieved kidney injury more effectively than LR alone. Western blot revealed that LR treatment or LR combined with prednisone increased the LC3‐associated autophagy protein of Rubicon and Nox2, as well as LC3I levels in the kidney tissues. In conclusion, LR inhibited the manifestation of cGVHD‐induced LN, which may attribute to the increased levels of LC3‐associated autophagy. [ABSTRACT FROM AUTHOR]

Land reclamation has occurred extensively worldwide to accommodate urbanization and economic development, especially in developing countries like China. However, we have a limited understanding of the long‐term dynamics and key drivers of land use/cover change in the reclaimed area. In this study, we monitored the detailed spatiotemporal evolution of land reclamation from 1973 to 2018 in Qiantang New District using time‐series LANDSAT and SENTINEL‐2A images and then compared the differences of landscape changes between reclaimed, which are the new‐built land from Qiantang River, and inland areas. Key findings include: (1) A significant decreasing trend for areas near the Qiantang River along the coastline (212.21 to 80.99 km2) and an increasing trend for constructed land (10.05 to 120.89 km2) from 1973 to 2018 was detected; (2) The development modes of the inland area and reclaimed area were significantly different. Development in the inland area was similar to other Chinese cities, whereas the reclaimed area was relatively complex with two main changing paths; and (3) Year 2008 was an important turning point in the perspective of urbanization in the study area. Before 2008, urbanization was random and uncontrolled. After 2008, new governance on land appeared and changed the landscape into a compact and uniform pattern. The proposed framework should reveal the detailed trajectory of land reclamation in small areas and provide insights and tools for better understanding the impact of human activities on the landscape pattern in coastal regions under rapid urbanization. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is the leading cause of end‐stage kidney disease. TGF‐β1/Smad3 signalling plays a major pathological role in DN; however, the contribution of Smad4 has not been examined. Smad4 depletion in the kidney using anti‐Smad4 locked nucleic acid halted progressive podocyte damage and glomerulosclerosis in mouse type 2 DN, suggesting a pathogenic role of Smad4 in podocytes. Smad4 is upregulated in human and mouse podocytes during DN. Conditional Smad4 deletion in podocytes protects mice from type 2 DN, independent of obesity. Mechanistically, hyperglycaemia induces Smad4 localization to mitochondria in podocytes, resulting in reduced glycolysis and oxidative phosphorylation and increased production of reactive oxygen species. This operates, in part, via direct binding of Smad4 to the glycolytic enzyme PKM2 and reducing the active tetrameric form of PKM2. In addition, Smad4 interacts with ATPIF1, causing a reduction in ATPIF1 degradation. In conclusion, we have discovered a mitochondrial mechanism by which Smad4 causes diabetic podocyte injury. Synopsis: This study reveals a mitochondrial role of Smad4 in the pathogenesis of diabetic nephropathy. Hyperglycemia induces Smad4 localization to mitochondria of podocytes.Smad4 depletion in podocytes protects mice from glomerulosclerosis in type 2 diabetes models.Smad4 depletion promotes glycolysis and OXPHOS activity under high glucose conditions.Hyperglycemia promotes the interaction between Smad4 and PKM2, thereby increasing PKM2 tetramerization and activity.Smad4 directly interacts with ATP synthase inhibitor ATPIF1 and inhibits it degradation. [ABSTRACT FROM AUTHOR]