Zinc finger Asp-His-His-Cys palmitoyl -acyltransferase 19 accelerates tumor progression through wnt/β-catenin pathway and is upregulated by miR-940 in osteosarcoma

Osteosarcoma (OS) is the most frequent malignant primary bone tumor in children and young adults. Zinc finger Asp-His-His-Cys palmitoyl-acyltransferase 19 (ZDHHC19) is a key enzyme in protein palmitoylation and plays crucial roles in tumor progression. However, its expression profile and biological function in OS have been unclear. In the present study, the expression level of ZDHHC19 in OS cell lines was determined by qRT-PCR and Western blot. The effect of ZDHHC19 in cell growth, invasion and migration was analyzed by CCK8, EDU, transwell, wound healing assay in vitro, and xenograft tumor model in vivo. In addition, bioinformatics analysis was used to explore the potential mechanism of ZDHHC19 in OS. Furthermore, the luciferase reporter assay was conducted to determine the direct binding between miR-940 and ZDHHC19. We discovered that ZDHHC19 was overexpressed in OS cells compared with the normal cells. The functional investigation demonstrated that ZDHHC19 silencing could inhibit proliferation, invasion and migration of OS in vitro and suppress tumorigenicity and lung metastasis in a xenograft model in vivo. Mechanistically, we identified that ZDHHC19 was a direct target of miR-940 and forced ZDHHC19 expressions partially rescue the suppression of proliferation, migration and invasion induced by miR-940. Moreover, bioinformatics analysis combined with validation experiments revealed that activating wnt/β-catenin pathway contributed to the pro-oncogenic effect induced by ZDHHC19. Furthermore, rescue experiments further verified that miR-940/ZDHHC19 axis regulated wnt/β-catenin pathway. Overall, these findings indicated that miR-940/ZDHHC19 axis played a significant role in OS progression and might be considered as a novel target for OS treatment. Abbreviations: OS, osteosarcoma; miRNAs, microRNAs; 3’-UTR, 3’- untranslated region; TARGET, Therapeutically Applicable Research To Generate Effective Treatments; qRT-PCR, quantitative real-time PCR; IHC, Immunohistochemistry; GSVA, Gene Set Variation Analysis; GSEA, Gene Set Enrichment Analysis; KEGG, Kyoto Encyclopedia of Genes and Genomes;</p

A Tale of Two Water Supplies in China: Finding Practical Solutions to Urban and Rural Water Supply Problems

ConspectusAccess to safe drinking water is among the 17 United Nations sustainable development goals. As the largest developing country, China has confronted large challenges to providing safe and sufficient drinking water to its population of 1.4 billion under the conditions of limited water sources and ubiquitous water contamination.This Account outlines these challenges as well as the practical solutions implemented by Chinese water professionals. We first provide a general introduction of the water supply in China. Next, we describe the main challenges of water source shortages and source water contamination. The practical solutions developed by Chinese water professionals are the core part of this Account, to which we have devoted ourselves to and contributed in some issues and cases.The water supply in China is a binary system that reflects the gap between urban and rural communities. Both urban and rural water supplies have been subject to water source shortages and contamination. Water shortages are mainly solved by long-distance water transportation projects. Urban water utilities generally pay attention to organic matter, ammonia, algae, and chemical spills in source water while also focusing on micro-organisms and disinfection byproducts in tap water. Micro-organisms are a widespread concern for rural water supplies, whereas arsenic, fluoride, and ammonia are an endemic concern in some rural communities. Investment in updating of treatment processes significantly benefits urban water supplies, and advanced treatment of ozonation and biologically activated carbon processes are now commonly used to ensure that strict drinking water quality standards are met. However, this is not the case for rural water supplies, where expensive advanced treatment is not affordable. Thus, improving rural water supplies requires approaches such as searching for sources with better water quality, using automated ultrafiltration instruments, or connecting to urban water supply distribution systems. For rural areas with high concentrations of arsenic or fluoride in source water, specific adsorbents are a practical way to help farmers.Similar challenges will be encountered elsewhere in the world; therefore, the practical solutions applied in China will be useful to other countries in different stages of development

Cascade catalytic nanoplatform for enhanced starvation and sonodynamic therapy

Background: Sonodynamic therapy (SDT) has emerged as an alternative to the traditional treatments of cancer. However, the oxygen consumption induced by SDT and glucose oxidase (GOx) mediated starvation therapy would worsen the hypoxic tumor environment, which further impeded therapeutic efficacy. Purpose: To develop a nanoplatform and investigate its anti-cancer mechanism for enhanced starvation and SDT. Methods: We constructed a cascade catalytic nanoplatform based on GOx modified the mesoporous MnO2 NPs loaded with hematoporphyrin monomethyl ether (HMME), which were designated as GOx-MnO2/HMME. We characterized them for their catalytic activity, and investigate the magnetic resonance imaging and anti-tumor efficiency in vitro and in vivo. Results: MnO2 NPs with catalase-like activity could oxidize H2O2 under acid condition to produce O2, which not only in turn was supplied to the glucose-depletion reaction for an efficient starvation therapy, but also enhanced the 1O2 generation for HMME mediated SDT effect. In addition, the released Mn2+ ions in the system were able to enhance the MRI signal. Both in vitro and in vivo experiments suggested the cascade catalytic-therapeutic effect between GOx, MnO2 NPs and HMME, demonstrating the enhanced starvation and SDT.</p

Additional file 3 of Integrated quality evaluation strategy for multi-species resourced herb medicine of Qinjiao by metabolomics analysis and genetic comparation

Additional file 3: Table S2. Part of the variable with VIP value > 1.0 from OPLS-DA analysis of G. crassicaulis and G. dahurica

Oct-2-en-4-ynoyl-CoA as a Specific Inhibitor of Acyl-CoA Oxidase

Oct-2-en-4-ynoyl-CoA was found to be a specific inhibitor of acyl-CoA oxidase in fatty acid oxidation in peroxisomes that has no inhibitory effect on acyl-CoA dehydrogenase in mitochondria. The inhibition reaction involves a nucleophilic attack of Glu421 to the δ carbon of the inhibitor. The result indicates that acyl-CoA oxidase and acyl-CoA dehydrogenase have certain differences in active-site structure, which makes it possible to control fatty acid oxidation selectively in either mitochondria or peroxisomes with different enzyme inhibitors

Image_1_Development and Verification of a Combined Immune- and Metabolism-Related Prognostic Signature for Hepatocellular Carcinoma.tif

Immune escape and metabolic reprogramming are becoming important characteristics of tumor biology, which play critical roles in tumor initiation and progression. However, the integrative analysis of immune and metabolic characteristics for the tumor microenvironment in hepatocellular carcinoma (HCC) remains unclear. Herein, by univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses, a prognostic signature associated with tumor microenvironment was established based on five immune- and metabolism-related genes (IMRGs), which was fully verified and evaluated in both internal and external cohorts. The C-index was superior to previously published HCC signatures, indicating the robustness and reliability of IMRGs prognostic signature. A nomogram was built based on IMRGs prognostic signature and various clinical parameters, such as age and T stage. The AUCs of nomogram at 1-, 3-, and 5-year (AUC = 0.829, 0.749, 0.749) were slightly better than that of IMRGs signature (AUC = 0.809, 0.734, 0.711). The relationship of risk score (RS) with immune checkpoint expressions, immunophenoscore (IPS), as well as microsatellite instability (MSI) together accurately predicted the treatment efficacy. Collectively, the IMRGs signature might have the potential to better predict prognostic risk, evaluate immunotherapy efficacy, and help personalize immunotherapy for HCC patients.</p

DataSheet_2_Development and Verification of a Combined Immune- and Metabolism-Related Prognostic Signature for Hepatocellular Carcinoma.xlsx

Immune escape and metabolic reprogramming are becoming important characteristics of tumor biology, which play critical roles in tumor initiation and progression. However, the integrative analysis of immune and metabolic characteristics for the tumor microenvironment in hepatocellular carcinoma (HCC) remains unclear. Herein, by univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses, a prognostic signature associated with tumor microenvironment was established based on five immune- and metabolism-related genes (IMRGs), which was fully verified and evaluated in both internal and external cohorts. The C-index was superior to previously published HCC signatures, indicating the robustness and reliability of IMRGs prognostic signature. A nomogram was built based on IMRGs prognostic signature and various clinical parameters, such as age and T stage. The AUCs of nomogram at 1-, 3-, and 5-year (AUC = 0.829, 0.749, 0.749) were slightly better than that of IMRGs signature (AUC = 0.809, 0.734, 0.711). The relationship of risk score (RS) with immune checkpoint expressions, immunophenoscore (IPS), as well as microsatellite instability (MSI) together accurately predicted the treatment efficacy. Collectively, the IMRGs signature might have the potential to better predict prognostic risk, evaluate immunotherapy efficacy, and help personalize immunotherapy for HCC patients.</p

DataSheet1_Effectiveness and Nephrotoxicity of Intravenous Polymyxin B in Carbapenem-Resistant Gram-Negative Bacterial Infections Among Chinese Children.docx

Background: No clinical study on the use of polymyxin B in Chinese children has been reported, thus making it difficult for pediatric clinicians to rationally select these drugs.Methods: A retrospective analysis of children treated with polymyxin B during hospitalization in a hospital from June 2019 to June 2021 was conducted to analyze its effectiveness and the incidence of acute kidney injury (AKI) during treatment with polymyxin B.Results: A total of 55 children were included in this study, and the results showed that the intravenous polymyxin B-based regimen had an effective rate of 52.7% in the treatment of Carbapenem-resistant Gram-negative bacterial (CR-GNB) infection in children. The results of the subgroup analysis showed that the course of treatment was longer in the favorable clinical response group than in the unfavorable outcome group (p = 0.027) and that electrolyte disturbances in children during the course of treatment could lead to unfavorable clinical outcomes (p = 0.042). The risk of incidence of AKI during treatment was 27.3%, and the all-cause mortality rate in the children on their discharge from the hospital was 7.3%.Conclusion: Polymyxin B can be used as a salvage therapy for CR-GNB infection in children when no other susceptible antibiotics are available, and the monitoring of kidney function should be strengthened.</p

Additional file 1 of Integrated quality evaluation strategy for multi-species resourced herb medicine of Qinjiao by metabolomics analysis and genetic comparation

Additional file 1: Table S1. Drift of retention times, m/z and the RSD of peak areas of 5 selected characteristic features from QC samples during the analysis

Additional file 1 of An area under the concentration–time curve threshold as a predictor of efficacy and nephrotoxicity for individualizing polymyxin B dosing in patients with carbapenem-resistant gram-negative bacteria

Additional file 1: Figure S1. Scatterplot of polymyxin B AUCss,24h versus dosage. AUCss,24h, the area under the plasma concentration-time curve across 24 hours at steady state. Figure S2. Scatterplot of polymyxin B AUCss,24h (a) and C0h (b) stratified for different stages of acute kidney injury. AUCss,24h, the area under the plasma concentration-time curve across 24 hours at steady state; C0h, trough concentration. Figure S3. Kaplan-Meier estimates of survival to 30 days after administration of polymyxin B. Stratified by AUCss,24h (a) and C0h (b). AUCss,24h, the area under the plasma concentration-time curve across 24 hours at steady state; C0h, trough concentration