A reactive oxygen species–related signature to predict prognosis and aid immunotherapy in clear cell renal cell carcinoma

BackgroundClear cell renal cell carcinoma (ccRCC) is a malignant disease containing tumor-infiltrating lymphocytes. Reactive oxygen species (ROS) are present in the tumor microenvironment and are strongly associated with cancer development. Nevertheless, the role of ROS-related genes in ccRCC remains unclear.MethodsWe describe the expression patterns of ROS-related genes in ccRCC from The Cancer Genome Atlas and their alterations in genetics and transcription. An ROS-related gene signature was constructed and verified in three datasets and immunohistochemical staining (IHC) analysis. The immune characteristics of the two risk groups divided by the signature were clarified. The sensitivity to immunotherapy and targeted therapy was investigated.ResultsOur signature was constructed on the basis of glutamate-cysteine ligase modifier subunit (GCLM), interaction protein for cytohesin exchange factors 1 (ICEF1), methionine sulfoxide reductase A (MsrA), and strawberry notch homolog 2 (SBNO2) genes. More importantly, protein expression levels of GCLM, MsrA, and SBNO2 were detected by IHC in our own ccRCC samples. The high-risk group of patients with ccRCC suffered lower overall survival rates. As an independent predictor of prognosis, our signature exhibited a strong association with clinicopathological features. An accurate nomogram for improving the clinical applicability of our signature was constructed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that the signature was closely related to immune response, immune activation, and immune pathways. The comprehensive results revealed that the high-risk group was associated with high infiltration of regulatory T cells and CD8+ T cells and more benefited from targeted therapy. In addition, immunotherapy had better therapeutic effects in the high-risk group.ConclusionOur signature paved the way for assessing prognosis and developing more effective strategies of immunotherapy and targeted therapy in ccRCC

Oxidation Kinetics Resolution of Racemic Aromatic Sulfoxides by Chiral Porphyrin-Inspired N4 Ligand with Manganese Complex

Oxidative kinetics resolution of racemic aromatic sulfoxide was studied by using chiral porphyrin-inspired N-4 ligands and manganese in situ complex as catalyst, environment-friendly H2O2 as oxidant and adamantanecarboxvlic acid as additive. The arylalkyl and arylbenzyl sulfoxide substrates were extended by this catalytic system. A maximum Yield of chiral sulfoxide was 40% and the enantioselectivity was 100%. In the meantime, the yield of sulfone a further oxidation products of sulfoxide, was up to 72%. It was found that the catalytic oxidation system is more prone to electron-rich sulfoxide through the competition experiment between electron-rich sulfoxide and electron-deficient sulfoxide substrates. In addition, the success of gram-scale oxidation kinetic resolution also shows that this method has a certain practical value in methodology

Relationships between the gelatinization of starches and the textural properties of extruded texturized soybean protein-starch systems

Starches from diverse sources have different thermal properties and, thus, show different gelatinization degrees under a specific extrusion condition, which affects the quality of the extrudates. To find the appropriate ingredients for extruding texturized soybean protein-starch mixtures, the thermal properties of commercial-grade starches (wheat starch, corn starch, potato starch, sweet potato starch, cassava starch, mung bean starch, pea starch, amylose from potato, and amylopectin from waxy corn), blends of starches with soybean protein isolate (SPI) and wheat gluten were assessed. The extrusion response parameters (torque, pressure change, specific mechanical energy (SME), and on-line apparent viscosity) during extrusion and the thermal and textural properties of the extrudates were determined. Pearson correlation analysis showed that the enthalpy changes of the blends were directly correlated with the torque, pressure change, specific mechanical energy, and on-line apparent viscosity, whereas those parameters were inversely correlated with the fibrous degree of the extrudates. The hardness, tensile strength, lengthwise strength, and fibrous degree of the extrudates were correlated with the enthalpy changes of the blends. The springiness and fibrous degree of the extrudates were correlated with the half-peak height of the blends. It was concluded that a higher enthalpy changes of blends leads to a higher SME and a pressure change, which results in a higher hardness and tensile strength and a lower fibrous degree of the extrudates.Fil: Zhang, Wei. Chinese Academy of Agricultural Sciences; ChinaFil: Li, Shujing. Chinese Academy of Agricultural Sciences; China. Chiping Food and Drug Administration; ChinaFil: Zhang, Bo. Chinese Academy of Agricultural Sciences; ChinaFil: Drago, Silvina Rosa. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Tecnología de los Alimentos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Zhang, Jinchuang. Chinese Academy of Agricultural Sciences; Chin

Oxidative kinetic resolution of heterocyclic sulfoxides with a porphyrin-inspired manganese complex by hydrogen peroxide

We have successfully reported here the low loading porphyrin-inspired high-valent manganese (IV)-oxo complex was applied in oxidative kinetic resolution (OKR) of racemic heterocyclic sulfoxides using the environmentally benign hydrogen peroxide for the first time. This approach allows for rapid OKR (0.5 h) of a variety of racemic sulfoxides (including pyridine, pyrimidine, pyrazine, thiazole, benzothiazole, thiophene) in excellent enantioselectivity (up to > 99% ee), simultaneously generating the corresponding sulfones in high yield (up to 80%). The catalytic system also showed an unexceptionable chemoselectivity for the sulfoxide substrates with hydroxyl groups in which only the sulfoxide group was oxidized. The practical utility of the method has been demonstrated in the OKR of gram-scale sulfoxides. (C) 2017 Elsevier Ltd. All rights reserved

Preparation of Whole-Cut Plant-Based Pork Meat and Its Quality Evaluation with Animal Meat

Low-moisture (20~40%) and high-moisture (40~80%) textured vegetable proteins (TVPs) can be used as important components of plant-based lean meat, while plant-based fat can be characterized by the formation of gels from polysaccharides, proteins, etc. In this study, three kinds of whole-cut plant-based pork (PBP) were prepared based on the mixed gel system, which were from low-moisture TVP, high-moisture TVP, and their mixtures. The comparisons of these products with commercially available plant-based pork (C-PBP1 and C-PBP2) and animal pork meat (APM) were studied in terms of appearance, taste, and nutritional qualities. Results showed the color changes of PBPs after frying were similar to that of APM. The addition of high-moisture TVP would significantly improve hardness (3751.96~7297.21 g), springiness (0.84~0.89%), and chewiness (3162.44~6466.94 g) while also reducing the viscosity (3.89~10.56 g) of products. It was found that the use of high-moisture TVP led to a significant increase in water-holding capacity (WHC) from 150.25% to 161.01% compared with low-moisture TVP; however, oil-holding capacity (OHC) was reduced from 166.34% to 164.79%. Moreover, essential amino acids (EAAs), the essential amino acids index (EAAI), and biological value (BV) were significantly increased from 272.68 mg/g, 105.52, and 103.32 to 362.65 mg/g, 141.34, and 142.36, respectively, though in vitro protein digestibility (IVPD) reduced from 51.67% to 43.68% due to the high-moisture TVP. Thus, the high-moisture TVP could help to improve the appearance, textural properties, WHC, and nutritional qualities of PBPs compared to animal meat, which was also better than low-moisture TVP. These findings should be useful for the application of TVP and gels in plant-based pork products to improve the taste and nutritional qualities

Conversion to agroforestry and monoculture plantation is detrimental to the soil carbon and nitrogen cycles and microbial communities of a rainforest

The conversion of rainforests to plantations leads to about 50% loss in the organic carbon (C) content of the soil and strongly influences nitrogen (N) cycling, potentially increasing greenhouse gas emissions. However, the effect of land-use change in forests on the microbial communities responsible for C and N cycling processes remains poorly understood. This study quantified C and N fractions of soil organic matter in a tropical forest, rubber agroforestry system, 5- and 15-year-old rubber plantations. The community structure and abundance of fungi and bacteria were studied using high-throughput sequencing and q-PCR. Forest conversion substantially altered community structure and abundance of microbial communities. Rainforest conversion to plantation enhanced bacterial diversity and reduced the soil C mineralization rate. In addition, land-use change also enhanced the soil N mineralization rate in 5-year-old rubber plantation and agroforestry system. A structural equation modelling suggested that soil microbial communities played more dominant roles in driving the shift in C and N cycles caused by land-use change than soil C and N pools. These mechanistic insights into the differential control of soil fungal and bacterial communities on C and N mineralization has implications for managing land-use changes in tropical forest ecosystems

Applications of nitrate and ammonium fertilizers alter soil nematode food webs in a continuous cucumber cropping system in Southwestern Sichuan, China

Nitrate (NO3--N) and ammonium (NH4+-N) fertilizers are the main forms of chemical inorganic nitrogen fertilizers that are widely used in agro-ecosystem for high yield. However, the responses of soil nematode food web to different forms and rates of inorganic nitrogen fertilizers are not well understood. The objective of this study was to determine the responses of soil nematode food web to the applications of inorganic nitrogen fertilizers in a continuous cucumber (Cucumis sativus L.) cropping system. Nitrate (NaNO3) and ammonium (NH4HCO3) fertilizers were applied to cucumber plants at the nitrogen (N) rate of 0, 67.5, 135.0 and 202.5 kg N hm-2 before planting. It was conducted in a randomized complete block design with 4 replications at Huaizi village, Leshan district, Sichuan province, Southwestern China. The effects were analyzed at the stages of seedling, blooming and fruiting, respectively. The results indicated that the numbers of nematodes were significantly higher in soils with the addition of 67.5 kg N hm-2 than the control at the seedling and blooming stages. Nematode number strongly increased at the seedling stage and decreased at the blooming and fruiting stages in nitrate-treated soils compared to the ammonium-treated. The percentage of herbivores to total nematodes significantly decreased while that of bacterivores increased with a fertilizer rate less than 135 kg N hm-2 at the seedling and fruiting stages. Nitrate significantly reduced the percentage of herbivores, and increased that of bacterivores to total nematodes by comparison with ammonium at the blooming and fruiting stages. The application of nitrate significantly increased nematode diversity and evenness, and decreased dominance at the blooming stage relative to ammonium. Nitrate significantly decreased the values of channel index at the blooming stage and maturity index at the seedling stage in comparison with ammonium, respectively. Enrichment index and structural index strongly increased at the seedling stage, and decreased at the blooming and fruiting stages under the treatment of nitrate relative to ammonium. The results suggested responses of nematode food web dependent on the rates and forms of inorganic nitrogen fertilizers and stages of cucumber growth.

Metformin escape in prostate cancer by activating the PTGR1 transcriptional program through a novel super-enhancer.

The therapeutic efficacy of metformin in prostate cancer (PCa) appears uncertain based on various clinical trials. Metformin treatment failure may be attributed to the high frequency of transcriptional dysregulation, which leads to drug resistance. However, the underlying mechanism is still unclear. In this study, we found evidences that metformin resistance in PCa cells may be linked to cell cycle reactivation. Super-enhancers (SEs), crucial regulatory elements, have been shown to be associated with drug resistance in various cancers. Our analysis of SEs in metformin-resistant (MetR) PCa cells revealed a correlation with Prostaglandin Reductase 1 (PTGR1) expression, which was identified as significantly increased in a cluster of cells with metformin resistance through single-cell transcriptome sequencing. Our functional experiments showed that PTGR1 overexpression accelerated cell cycle progression by promoting progression from the G0/G1 to the S and G2/M phases, resulting in reduced sensitivity to metformin. Additionally, we identified key transcription factors that significantly increase PTGR1 expression, such as SRF and RUNX3, providing potential new targets to address metformin resistance in PCa. In conclusion, our study sheds new light on the cellular mechanism underlying metformin resistance and the regulation of the SE-TFs-PTGR1 axis, offering potential avenues to enhance metformins therapeutic efficacy in PCa

Metformin escape in prostate cancer by activating the PTGR1 transcriptional program through a novel super-enhancer

Abstract The therapeutic efficacy of metformin in prostate cancer (PCa) appears uncertain based on various clinical trials. Metformin treatment failure may be attributed to the high frequency of transcriptional dysregulation, which leads to drug resistance. However, the underlying mechanism is still unclear. In this study, we found evidences that metformin resistance in PCa cells may be linked to cell cycle reactivation. Super-enhancers (SEs), crucial regulatory elements, have been shown to be associated with drug resistance in various cancers. Our analysis of SEs in metformin-resistant (MetR) PCa cells revealed a correlation with Prostaglandin Reductase 1 (PTGR1) expression, which was identified as significantly increased in a cluster of cells with metformin resistance through single-cell transcriptome sequencing. Our functional experiments showed that PTGR1 overexpression accelerated cell cycle progression by promoting progression from the G0/G1 to the S and G2/M phases, resulting in reduced sensitivity to metformin. Additionally, we identified key transcription factors that significantly increase PTGR1 expression, such as SRF and RUNX3, providing potential new targets to address metformin resistance in PCa. In conclusion, our study sheds new light on the cellular mechanism underlying metformin resistance and the regulation of the SE-TFs-PTGR1 axis, offering potential avenues to enhance metformin’s therapeutic efficacy in PCa