Development of hydroxamate-based histone deacetylase inhibitors containing 1,2,4-oxadiazole moiety core with antitumor activities

Histone deacetylases (HDACs) has proved to be promising target for the development of antitumor drugs. In this study, we reported the design and synthesis of a class of novel hydroxamate-based bis-substituted aromatic amide HDAC inhibitors with 1,2,4-oxadiazole core. Most newly synthesized compounds displayed excellent HDAC1 inhibitory effects and significant anti-proliferative activities. Among them, compounds 11a and 11c increased acetylation of histone H3 and H4 in dose-dependent manner. Furthermore, 11a and 11c remarkably induced apoptosis in HepG2 cancer cells. Finally, the high potency of compound 11a was rationalized by molecular docking studies.     

Identification and characterization of the ZRT,IRT-like protein (ZIP) family genes reveal their involvement in growth and kojic acid production in Aspergillus oryzae

Journal of Industrial Microbiology & Biotechnology - The ZRT, IRT-like protein (ZIP) family exists in many species and plays an important role in many biological processes, but little is known...     

Effect of coupled reduced irrigation and nitrogen fertilizer on soil mite community composition in a wheat field

Groundwater and nitrogen fertilizer overuse severely threatens crop productions; thus, current ecological agriculture requires low irrigation and nitrogen fertilizer inputs. The effects of combined reduced irrigation and nitrogen fertilizer addition on soil organism (e.g., mite) community and biodiversity remain poorly understood. We analyzed soil mite community composition, wheat grain yield, and soil characteristics in a 10‐year manipulation experiment with two levels of irrigation (reduced and conventional irrigation) and five nitrogen fertilizer levels (0, 70, 140, 210, and 280 kg N/ha). Reduced irrigation (20% reduction, from 280 to 220 mm) and nitrogen fertilizer (25% reduction, from 280 to 210 kg N/ha) addition did not significantly influence soil mite community and wheat yield. The relative abundances of fungivores and predators showed negative quadratic relationships with wheat yield, while that of plant parasites showed a positive relationship. The relationships between soil mite trophic groups and wheat yield revealed that we can evaluate the impacts of reduced irrigation and nitrogen fertilizer addition from the perspective of soil fauna. Soil mite community composition was altered by soil abiotic factors prior to reduced irrigation and nitrogen fertilizer addition. Overall, moderate reductions of irrigation and nitrogen fertilizer may not threaten to soil mite community and diversity or decrease crop production; in contrast, such reductions will benefit mite community development and the sustainable agriculture.     

Transcriptome sequencing and global analysis of blue light-responsive genes provide clues for high carotenoid yields in Blakeslea trispora

International Microbiology - Blakeslea trispora has great potential uses in industrial production because of the excellent capability of producing a large quantity of carotenoids. However, the...     

Growth-Promoting Ability of Rhodopseudomonas palustris G5 and Its Effect on Induced Resistance in Cucumber Against Salt Stress

The objective of this study was to investigate the potential of Rhodopseudomonas palustris G5 in promoting growth and inducing salt resistance in cucumber (Cucumis sativus L.). In this study, the growth-promoting potential of the bacteria was studied by measuring the ability to produce indole-3-acetic acid (IAA) and 5-aminolevulinic acid (ALA), fix nitrogen, and solubilize potassium and phosphate. The greenhouse pot experiments were set up to study how strain G5 affected growth and salt resistance of cucumber seedlings. The results showed that strain G5 exhibited plant growth-promoting attributes such as the production of IAA and ALA, as well as nitrogen-fixing, potassium-solubilizing, and phosphorus-solubilizing ability. In pot trials, strain G5 increased shoot height, root length, fresh weight, dry weight, total chlorophyll content, and soluble sugar content of cucumber seedlings under salt stress, compared to the seedlings that were exposed to salt stress in the absence of the strain G5. Furthermore, antioxidant enzyme activity analysis showed that strain G5 strongly increased the activity of superoxide dismutase, peroxidase, and polyphenol oxidase in cucumber seedlings under salt stress. In addition, strain G5 treatment decreased H₂O₂ and malondialdehyde contents of salt-stressed seedling. In sum, these results showed that strain G5 enhanced growth and induced systemic resistance in cucumber seedlings under salt stress by the production of IAA, ALA, and soluble sugars, the induction of antioxidant enzymes as well as nutrient adjustment of nitrogen, phosphorus, and potassium.

     

氧化甾醇结合蛋白相关蛋白家族的研究进展

膜脂是细胞膜的主要组分, 也是参与信号转导的重要信号分子。不同脂质分子在细胞膜上的不均等分布需要特殊类型的通道蛋白和运输蛋白来实现。氧化甾醇结合蛋白相关蛋白(ORPs)是一类非常保守的蛋白分子, 能够对磷脂酰肌醇和固醇等脂类分子进行识别并转运, 参与细胞中的许多生理过程, 包括信号转导、囊泡运输、脂类代谢和非囊泡运输等...     

Improving the Genome Annotation of Rhizoctonia solani Using Proteogenomics

Background Rhizoctonia solani is a pathogenic fungus that causes serious diseases in many crops, including rice, wheat, and soybeans. In crop production, it is very important to understand the pathogenicity of this fungus, which is still elusive. It might be helpful to comprehensively understand its genomic information using different genome annotation strategies.MethodsAiming to improve the genome annotation of R. solani, we performed a proteogenomic study based on the existing data. Based on our study, a total of 1060 newly identified genes, 36 revised genes, 139 single amino acid variants (SAAVs), 8 alternative splicing genes, and diverse post-translational modifications (PTMs) events were identified in R. solani AG3. Further functional annotation on these 1060 newly identified genes was performed through homology analysis with its 5 closest relative fungi.ResultsBased on this, 2 novel candidate pathogenic genes, which might be associated with pathogen-host interaction, were discovered. In addition, in order to increase the reliability and novelty of the newly identified genes in R. solani AG3, 1060 newly identified genes were compared with the newly published available R. solani genome sequences of AG1, AG2, AG4, AG5, AG6, and AG8. There are 490 homologous sequences. We combined the proteogenomic results with the genome alignment results and finally identified 570 novel genes in R. solani.ConclusionThese findings extended R. solani genome annotation and provided a wealth of resources for research on R. solani.     

Ascorbic acid induced TET2 enzyme activation enhances cancer immunotherapy efficacy in renal cell carcinoma

Exploring the regulatory mechanism of PD-L1 in renal cancer is one of the key strategies to improve the response of renal cancer patients to checkpoint blockade therapy. In this study, the synergistic effect of ascorbic acid (vitamin C) supplementation and the impact of TET2 depletion on anti-PD-L1 therapy were determined in xenograft model experiments. Lymphocyte infiltration and chemokine expression were determined using flow cytometry and qRT-PCR. To determine the downstream targets of TET2, we performed hMeDip-seq and RNA-seq analyses. The molecular mechanism was further confirmed by hMeDip-qPCR, MeDip-qPCR, bisulfite sequencing, Western blotting, qRT-PCR and xenograft model experiments in vitro and in vivo. The present study demonstrated that ascorbic acid enhanced the efficacy of immunotherapy and that the loss of TET2 function enabled renal cancer cells to evade antitumor immunity. Ascorbic acid treatment significantly increased the intratumoral infiltration of T cells and the expression of cytokines and chemokines, while the loss of TET2 impaired the infiltration of T cells and the expression of cytokines and chemokines. TET2 was recruited to IRF1 by IFN-γ-STAT1 signaling, thereby maintaining IRF1 demethylation and ultimately inducing PD-L1 expression. These results suggest a new strategy of stimulating TET activity to improve immunotherapy for renal cell carcinoma.