Juan Jin

Currently, renal cell carcinoma (RCC) is the most prevalent type of kidney cancer. Targeted therapy has replaced radiation therapy and chemotherapy as the main treatment option for RCC due to the lack of significant efficacy with these conventional therapeutic regimens. Sunitinib, a drug used to treat gastrointestinal tumors and renal cell carcinoma, inhibits the tyrosine kinase activity of a number of receptor tyrosine kinases, including vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), c-Kit, rearranged during transfection (RET) and fms-related receptor tyrosine kinase 3 (Flt3). Although sunitinib has been shown to be efficacious in the treatment of patients with advanced RCC, a significant number of patients have primary resistance to sunitinib or acquired drug resistance within the 6-15 months of therapy. Thus, in order to develop more efficacious and long-lasting treatment strategies for patients with advanced RCC, it will be crucial to ascertain how to overcome sunitinib resistance that is produced by various drug resistance mechanisms. In this review, we discuss: 1) molecular mechanisms of sunitinib resistance; 2) strategies to overcome sunitinib resistance and 3) potential predictive biomarkers of sunitinib resistance.

The role of gut-kidney crosstalk in the progression of diabetic nephropathy (DN) is receiving increasing concern. On one hand, the decline in renal function increases circulating uremic toxins and affects the composition and function of gut microbiota. On the other hand, intestinal dysbiosis destroys the epithelial barrier, leading to increased exposure to endotoxins, thereby exacerbating kidney damage by inducing systemic inflammation. Dietary inventions, such as higher fiber intake, prebiotics, probiotics, postbiotics, fecal microbial transplantation (FMT), and engineering bacteria and phages, are potential microbiota-based therapies for DN. Furthermore, novel diabetic agents, such as glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sodium-dependent glucose transporter-2 (SGLT-2) inhibitors, may affect the progression of DN partly through gut microbiota. In the current review, we mainly summarize the evidence concerning the gut-kidney axis in the advancement of DN and discuss therapies targeting the gut microbiota, expecting to provide new insight into the clinical treatment of DN.

Korean forests are highly vulnerable to forest fires, which can severely damage property and human life. This necessitates the establishment of a rapid response system and the construction of firebreaks to prevent the spread of fires and protect key facilities. The existing firebreak construction methods can be classified into prevention- and response-stage methods. In the prevention stage, the progression and spread of fire are delayed, while in the response stage, primitive manual methods involving tools such as hooks are used, in addition to aerial deployment of water and fire retardants through helicopters. Herein, we propose the use of “fire-extinguishing drones” for firebreak construction during the initial, low-intensity stage of a fire before the deployment of firefighting personnel. We implement a continuous fire-extinguishing module capable of carrying six fire-extinguishing balls to verify its deployment accuracy and stable hovering capabilities. Through the operation of multiple drones using a ground control system and real-time kinematics to precisely generate designated automatic flight paths, we conducted experiments to assess the feasibility of firebreak construction by using fire-extinguishing drones to prevent the spread of wildfires. A firebreak construction field test was conducted to evaluate the accuracy of continuous fire extinguisher deployment, hovering performance during deployment, accuracy of the RTK-designated paths, and GCS performance. The proposed system achieved 100% performance on all indicators, except the accuracy of the RTK-designated paths.

Coastal wetlands provide extensive ecological services for life on Earth but are facing rapid global disappearance influenced by human activities and climate change. From 1984 to 2018, approximately 28% of the natural coastal wetlands in China were lost due to seawater intrusion, reduced sediment acquisition, urbanization, and reclamation. Tiaozini wetland used to be reclaimed during 2010-2019, and quickly shifted for conservation with less than 3 years. We analyzed 3 years of top-down eco-governance and bottom-up activities in Tiaozini, one of the typical wetlands with wise use instead of reclamation. Collaboration of stakeholders, such as the management company, local residents, tourists, scientific committees, NGOs, and media, facilitated the wise use of Tiaozini wetland as a successvie way towards eco-governance, including public participation and environmental education. Adaptive management, ecosystem-based management, and natural-based solutions play very important roles in eco-governance from both bottom-up and top-down approaches. Results showed that 3-year eco-governance induced great achievements in both biodiversity conservation and ecotourism development, which outweighs the 10-year reclamation for coastal wetlands exploitation.

Centrosomal proteins play critical roles in ciliogenesis. Mutations in many centrosomal proteins have been documented to contribute to developmental defects and cilium-related diseases. Centrosomal protein fibroblast growth factor receptor 1 oncogene partner-related protein of 20 kDa (FOR20) is crucial for ciliogenesis in mammalian cells and the unicellular eukaryote Paramecium; however, the biologic significance of FOR20 in vertebrate development remains unclear. We cloned the zebrafish homolog of the for20 gene and found that for20 mRNA is enriched in ciliated tissues during early zebrafish development. Knockdown of for20 by morpholino oligonucleotides in zebrafish results in multiple ciliary phenotypes, including curved body, hydrocephaly, pericardial edema, kidney cysts, and left-right asymmetry defects. for20 morphants show reduced number and length of cilia in Kupffer's vesicle and pronephric ducts. High-speed video microscopy reveals that cilia in most for20 morphants are consistently paralyzed or beat arrhythmically. To confirm the ciliary phenotypes of for20 morphants, we used the CRISPR/Cas9 system to disrupt for20 gene in zebrafish. for20 mutants exhibit multiple ciliary phenotypes resembling the defects in for20 morphants. All of these phenotypes in for20 morphants and mutants are significantly reversed by exogenous expression of for20 mRNA. Taken together, these data suggest that FOR20 is required for cilium-mediated processes during zebrafish embryogenesis.-Xie, S., Jin, J., Xu, Z., Huang, Y., Zhang, W., Zhao, L., Lo, L. J., Peng, J., Liu, W., Wang, F., Shu, Q., Zhou, T. Centrosomal protein FOR20 is essential for cilia-dependent development in zebrafish embryos.