作者机构：
[Liao, Cai-Yi; Liu, Wen-Cheng; Song, Ru-Feng; Chen, Hui-Hui; Zhang, Yu; Guo, Jia-Xing; Lu, Kai-Kai; Zuo, Jia-Xin; Hu, Xiao-Yu] Henan Univ, Coll Life Sci, Collaborat Innovat Ctr Crop Stress Biol, State Key Lab Crop Stress Adaptat & Improvement, Kaifeng 475004, Peoples R China.;[Ren, Feng] Cent China Normal Univ, Sch Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan 430079, Peoples R China.;[Lu, Ying-Tang] Wuhan Univ, Coll Life Sci, State Key Lab Hybrid Rice, Wuhan, Peoples R China.
通讯机构：
[Wen-Cheng Liu] S;State Key Laboratory of Crop Stress Adaptation and Improvement, Collaborative Innovation Center of Crop Stress Biology, College of Life Sciences, Henan University , Kaifeng 475004 , China
摘要：
SALT OVERLY SENSITIVE1 (SOS1) is a key component of plant salt tolerance. However, how SOS1 transcription is dynamically regulated in plant response to different salinity conditions remains elusive. Here, we report that C-type Cyclin1;1 (CycC1;1) negatively regulates salt tolerance by interfering with WRKY75-mediated transcriptional activation of SOS1 in Arabidopsis (Arabidopsis thaliana). Disruption of CycC1;1 promotes SOS1 expression and salt tolerance in Arabidopsis because CycC1;1 interferes with RNA polymerase II recruitment by occupying the SOS1 promoter. Enhanced salt tolerance of the cycc1;1 mutant was completely compromised by an SOS1 mutation. Moreover, CycC1;1 physically interacts with the transcription factor WRKY75, which can bind to the SOS1 promoter and activate SOS1 expression. In contrast to the cycc1;1 mutant, the wrky75 mutant has attenuated SOS1 expression and salt tolerance, whereas overexpression of SOS1 rescues the salt sensitivity of wrky75. Intriguingly, CycC1;1 inhibits WRKY75-mediated transcriptional activation of SOS1 via their interaction. Thus, increased SOS1 expression and salt tolerance in cycc1;1 were abolished by WRKY75 mutation. Our findings demonstrate that CycC1;1 forms a complex with WRKY75 to inactivate SOS1 transcription under low salinity conditions. By contrast, under high salinity conditions, SOS1 transcription and plant salt tolerance are activated at least partially by increased WRKY75 expression but decreased CycC1;1 expression. CycC1;1 forms a transcriptional repression complex with the transcription factor WRKY75 to downregulate SOS1 expression, thereby negatively regulating salt stress tolerance in Arabidopsis.
期刊：
Journal of Environmental Chemical Engineering,2023年11(3):109717 ISSN：2213-3437
通讯作者：
Liao, XM;Zhang, Lizhi;Sun, HW;Zhang, LZ
作者机构：
[Liao, Xiaomei; Liu, Qianhui; Chen, Yangyang; Mei, Ting; Wang, Shaohui] Cent China Normal Univ, Sch Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan 430079, Peoples R China.;[Zhang, Lizhi; Sun, Hongwei] Cent China Normal Univ, Inst Environm & Appl Chem, Coll Chem, Key Lab Pesticide & Chem Biol,Minist Educ, Wuhan 430079, Peoples R China.;[Zhang, Lizhi] Shanghai Jiao Tong Univ, Sch Environm Sci & Engn, Shanghai 200240, Peoples R China.;[Liao, XM] Cent China Normal Univ, Sch Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan 430079, Peoples R China.;[Zhang, LZ; Sun, Hongwei] Cent China Normal Univ, Inst Environm & Appl Chem, Coll Chem, Key Lab Pesticide & Chem Biol,Minist Educ, Wuhan 430079, Peoples R China.
通讯机构：
[Liao, XM ; Zhang, LZ; Sun, HW ; Zhang, LZ ] ;Cent China Normal Univ, Sch Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan 430079, Peoples R China.;Cent China Normal Univ, Inst Environm & Appl Chem, Coll Chem, Key Lab Pesticide & Chem Biol,Minist Educ, Wuhan 430079, Peoples R China.;Shanghai Jiao Tong Univ, Sch Environm Sci & Engn, Shanghai 200240, Peoples R China.
关键词：
Sewage sludge;Ozonation;Zero-valent iron;Antibiotic resistance genes;Reactive oxygen species
摘要：
Wastewater treatment plants (WWTPs) are hotspots of antibiotic resistance genes (ARGs), and efficient technologies are needed to prevent the enrichment and spread of ARGs in municipal sludge. Herein, we demonstrated that oxalated zero-valent iron (OA-ZVIbm) catalyzed ozonation could effectively remove typical ARGs, tetG and sul1, from municipal sewage sludge, with the total abundance reduced by 3.02 and 2.00 log per gram sludge, respectively, surpassing the O-3 alone and O-3/ZVI(bm) counterparts. Meanwhile, the O-3/OA-ZVI(bm) treatment could simultaneously remove both intracellular and extracellular ARGs from the sludge, moreover, it also eliminated 1.83 log total Class 1 integron (total intI1), thus may suppress the horizontal gene transfer (HGT) potential of ARGs. The good performance of O-3/OA-ZVI(bm) was owing to the FeC2O4 center dot 2H(2)O shell of ZVI, which improved the accessibility of core iron species to catalyze the decomposition of O-3, producing more reactive oxygen species (ROSs) including center dot OH, center dot O-2(-), and O-1(2), for the removal of ARGs. This study provides a new method to control the dissemination of ARGs in sewage sludge.
作者：
Cao, Ya Ya;Chen, Yuan Yuan;Wang, Ming Shu;Tong, Jing Jing;Xu, Meng;...
期刊：
Redox Biology,2023年63:102751 ISSN：2213-2317
通讯作者：
Zhang, Dan;Yang, GF
作者机构：
[Chen, Yuan Yuan; Zhang, Wen Lin; Yang, Guang Fu; Lin, Hong Yan; Mei, Long Can; Wang, Ming Shu; Dong, Jin; Zhang, Dan; Zhang, D; Cao, Ya Ya; Huang, Wei; Qin, Yu Xuan; Zhao, Chi] Cent China Normal Univ, Int Joint Res Ctr Intelligent Biosensor Technol &, Natl Key Lab Green Pesticide, Wuhan 430079, Peoples R China.;[Tong, Jing Jing; Xu, Meng] Cent China Normal Univ, Sch Life Sci, Wuhan 430079, Peoples R China.;[Chen, Yuan Yuan] Hunan Univ, Inst Chem Biol & Nanomed, Coll Chem & Chem Engn, Changsha 410082, Peoples R China.
通讯机构：
[Zhang, D; Yang, GF ] C;Cent China Normal Univ, Int Joint Res Ctr Intelligent Biosensor Technol &, Natl Key Lab Green Pesticide, Wuhan 430079, Peoples R China.
关键词：
Catalase inhibitors;NADPH-Binding site;Ferroptosis;Castration-resistant prostate cancer
摘要：
Catalase (CAT) is an important antioxidant enzyme that breaks down H(2)O(2) into water and oxygen. Inhibitor-modulating CAT activity in cancer cells is emerging as a potential anticancer strategy. However, the discovery of CAT inhibitors towards the heme active center located at the bottom of long and narrow channel has made little progress. Therefore, targeting new binding site is of great importance for the development of efficient CAT inhibitors. Here, the first NADPH-binding site inhibitor of CAT, BT-Br, was designed and synthesized successfully. The cocrystal structure of BT-Br-bound CAT complex was determined with a resolution of 2.2Å (PDB ID:8HID), which showed clearly that BT-Br bound at the NADPH-binding site. Furthermore, BT-Br was demonstrated to induce ferroptosis in castration-resistant prostate cancer (CRPC) DU145cells and eventually reduce CRPC tumors in vivo effectively. The work indicates that CAT has potential as a novel target for CRPC therapy based on ferroptosis inducing.
摘要：
As a common adverse environmental factor, heat stress (HS) not only drastically changes the plant transcriptome at the transcription level but also increases alternative splicing (AS), especially intron retention (IR) events. However, the exact mechanisms are not yet well understood. Here, we reported that NTC-related protein 1 (NTR1), which acts as an accessory component for spliceosome disassembly, is necessary for this process. The mutants of NTR1, both the T-DNA insertion and the point mutation identified through ethyl methanesulfonate (EMS) mutagenesis screening, are vulnerable to HS, indicating that NTR1 is essential for plant HS tolerance. At the molecular level, genes of response to heat and response to temperature stimulus are highly enriched among those of heat-induced but less-expressed ntr1 mutants. Moreover, a large portion of HS response (HSR) genes such as heat shock transcription factors (HSFs) and heat shock proteins (HSPs) are less induced by heat treatment, and more AS events, especially IR events, were found in heat-treated ntr1 mutants. Furthermore, HS suppressed the expression of NTR1 and NTR1-associated complex components. Thus, it is very likely that upon HS, the plant reduces the expression of the NTR1-associated complex to fulfill the fast demands for transcription of HSR genes such as HSFs and HSPs, which in turn results in the accumulation of improperly spliced especially IR products and eventually causes harm to plants.
作者机构：
[Yan Peng; Yutao Xiao; Qi Xu; Peng Cui; Minghui Jin; Lei Zhang; Bo Liu; Hangwei Liu; Yongfeng Zhou; Bo Yang; Weigang Zheng; Kenneth Wilson] Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Key Laboratory of Gene Editing Technologies (Hainan), Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518116, China;[Yan Zhou; Minghui Jin; Kongming Wu] The State Key Laboratory for Biology of Plant Disease and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, West Yuanmingyuan Road, Beijing 100193, China;[Chris Jiggins; Henry L.North] Department of Zoology, University of Cambridge, Cambridge CB2 1SZ, UK;[Yan Peng] College of Plant Science and Technology, Huazhong Agricultural University, Wuhan 430070, China;[Ruiqing Pan] Berry Genomics Corporation, Beijing 102200, China
通讯机构：
[Chris Jiggins] D;[Kongming Wu] T;Department of Zoology, University of Cambridge, Cambridge CB2 1SZ, UK<&wdkj&>The State Key Laboratory for Biology of Plant Disease and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, West Yuanmingyuan Road, Beijing 100193, China
摘要：
The cotton bollworm, Helicoverpa armigera, is set to become the most economically devastating crop pest in the world, threatening food security and biosafety as its range expands across the globe. Key to understanding the eco-evolutionary dynamics of H.armigera, and thus its management, is an understanding of population connectivity and the adaptations that allow the pest to establish in unique environments. We assembled a chromosome-scale reference genome and re-sequenced 503 individuals spanning the species range to delineate global patterns of connectivity, uncovering a previously cryptic population structure. Using a genome-wide association study (GWAS) and cell line expression of major effect loci, we show that adaptive changes in a temperature- and light-sensitive developmental pathway enable facultative diapause and that adaptation of trehalose synthesis and transport underlies cold tolerance in extreme environments. Incorporating extensive pesticide resistance monitoring, we also characterize a suite of novel pesticide and Bt resistance alleles under selection in East China. These findings offer avenues for more effective management strategies and provide insight into how insects adapt to variable climatic conditions and newly colonized environments.
期刊：
Journal of Translational Medicine,2023年21(1):1-18 ISSN：1479-5876
通讯作者：
Zhenbo Song<&wdkj&>Lei Liu
作者机构：
[Sun, Ying; Li, Jingyi; Wang, Guannan; Huang, Yanxin; Zheng, Lihua; Song, Zhenbo; Yang, Qifang; Liu, Lei; Zhang, Ming] Northeast Normal Univ, Natl Engn Lab Druggable Gene & Prot Screening, Changchun, Peoples R China.;[Li, Aoqiang; Zhang, Ming] Cent China Normal Univ, Sch Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan, Peoples R China.;[Zhang, Muqing] Univ Illinois, Sch Mol & Cellular Biol, Urbana, IL USA.
通讯机构：
[Zhenbo Song; Lei Liu] N;National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, China<&wdkj&>National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, China
摘要：
The realization of the “microbiota–gut–brain” axis plays a critical role in neuropsychiatric disorders, particularly depression, is advancing rapidly. Matrine is a natural bioactive compound, which has been found to possess potential antidepressant effect. However, the underlying mechanisms of regulation of the “microbiota–gut–brain” axis in the treatment of depression by oral matrine remain elusive. Its antidepressant effects were initially evaluated by behavioral tests and relative levels of monoamine neurotransmitters, and matrine has been observed to attenuate the depression-like behavior and increase neurotransmitter content in CUMS-induced mice. Subsequently, studies from the “gut” to “brain” were conducted, including detection of the composition of gut microbiota by 16S rRNA sequencing; the metabolomics detection of gut metabolites and the analysis of differential metabolic pathways; the assessment of relative levels of diamine oxidase, lipopolysaccharide, pro-inflammatory cytokines, and brain-derived neurotrophic factor (BDNF) by ELISA kits or immunofluorescence. Matrine could regulate the disturbance of gut microbiota and metabolites, restore intestinal permeability, and reduce intestinal inflammation, thereby reducing the levels of pro-inflammatory cytokines in peripheral blood circulation and brain regions, and ultimately increase the levels of BDNF in brain. Matrine may ameliorate CUMS-induced depression in mice by modulating the “microbiota–gut–brain” axis.
通讯机构：
[Haobin Zhao] H;Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, China<&wdkj&>Author to whom correspondence should be addressed.
通讯机构：
[Haobin Zhao] H;Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, China
摘要：
Mep50 as a partner promotes the activity and substrate affinity of Prmt5. Prmt5 and Mep50 function together in multiple bioprocesses of the cells. Both Prmt5 and Mep50 are necessary for maintenance of the stem cells and are indispensable in the embryogenesis in the mammals. However, the role of Mep50 is rarely studied in fish. This study was to investigate the role of Mep50 in embryonic development of medaka. Medaka mep50 was mutated by genomic editing with CRISPR-Cas9 technology. Two mutants with a deletion of 22 and 46 bp separately in mep50 caused premature stopping of translation. The homozygotes of these mutant fish were obtained by self-crossing of the heterozygotes. These homozygotic mutants could reproduce embryos but the offspring were not viable. The apoptotic cells were significantly more in the mutant embryos than that in the wild type indicated by TUNEL assay. Quantitative RT-PCR showed that the expression of oct4 and sox2 were significantly decreased, but p53 was increased in the mutant embryos. These results suggest that disruption of mep50 severely interferes with embryogenesis and mep50 is necessary for embryonic development by maintaining stem cells and repression of apoptosis in medaka.
摘要：
Algicidal bacteria can inhibit the growth of algae or lyse algal cells, thus playing roles in shaping aquatic microbial communities and maintaining the functions of aquatic ecosystems. Nevertheless, our understanding of their diversities and distributions remains limited. In this study, we collected water samples from 17 freshwater sites in 14 cities in China and screened a total of 77 algicidal bacterial strains using several prokaryotic cyanobacteria and eukaryotic algae as target strains. According to their target-specificities, these strains were classified into three subgroups, cyanobacterial algicidal bacteria, algal algicidal bacteria, and broad-target algicidal bacteria, each displaying distinctive compositions and geographical distribution patterns. They are assigned to Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes bacterial phyla, of which Pseudomonas and Bacillus are the most abundant gram-negative and gram-positive genus, respectively. A number of bacterial strains, such as Inhella inkyongensis and Massilia eburnean, are suggested as new algicidal bacteria. The diverse taxonomies, algal-inhibiting abilities and distributions of these isolates have suggested that there are rich algicidal bacterial resources in these aquatic environments. Our results provide new microbial resources for algal-bacterial interaction studies, and shed new insights into how algicidal bacteria can be used in the control of harmful algal blooms, as well as in algal biotechnology.
期刊：
Journal of Hazardous Materials,2023年448:130990 ISSN：0304-3894
通讯作者：
Kaiyao Huang
作者机构：
[Zhang, Baolong; Long, Huan; Huang, Kaiyao; Deng, Xuan] Chinese Acad Sci, Inst Hydrobiol, Key Lab Algal Biol, Wuhan 430072, Hubei, Peoples R China.;[Yu, Fei; Wang, Xun; Tang, Yuxin] Wuhan Univ Sci & Technol, Sch Urban Construct, Wuhan 430065, Hubei, Peoples R China.;[Peng, Zhao; Yao, Sheng] Cent China Normal Univ, Sch Life Sci, Wuhan 430079, Hubei, Peoples R China.;[Peng, Zhao; Yao, Sheng] Cent China Normal Univ, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan 430079, Hubei, Peoples R China.;[Huang, Kaiyao] Chinese Acad Sci, Inst Hydrobiol, Key Lab Algal Biol, 7 Donghu South Rd, Wuhan 430072, Hubei, Peoples R China.
通讯机构：
[Kaiyao Huang] K;Key Laboratory of Algal Biology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, Hubei, China
关键词：
Algae;Ascorbate;Cd;IFR1;Ribo-seq
摘要：
Cadmium (Cd) is one of the most toxic pollutants found in aquatic ecosystems. Although gene expression in algae exposed to Cd has been studied at the transcriptional level, little is known about Cd impacts at the translational level. Ribosome profiling is a novel translatomics method that can directly monitor RNA translation in vivo. Here, we analyzed the translatome of the green alga Chlamydomonas reinhardtii following treatment with Cd to identify the cellular and physiological responses to Cd stress. Interestingly, we found that the cell morphology and cell wall structure were altered, and starch and high-electron-density particles accumulated in the cytoplasm. Several ATP-binding cassette transporters that responded to Cd exposure were identified. Redox homeostasis was adjusted to adapt to Cd toxicity, and GDP-L-galactose phosphorylase (VTC2), glutathione peroxidase (GPX5), and ascorbate were found to play important roles in maintaining reactive oxygen species homeostasis. Moreover, we found that the key enzyme of flavonoid metabolism, i.e., hydroxyisoflavone reductase (IFR1), is also involved in the detoxification of Cd. Thus, in this study, translatome and physiological analyses provided a complete picture of the molecular mechanisms of green algae cell responses to Cd.
摘要：
Successful phytoremediation of acidic metal-contaminated mine tailings requires amendments to condition tailings properties prior to plant establishment. This conditioning process is complex and includes multiple changes in tailings bio-physico-chemical properties. The objective of this project is to identify relationships between tailings properties, the soil microbiome, and plant stress response genes during growth of Atriplex lentiformis in compost-amended (10 %, 15 %, 20 % w/w) mine tailings. Analyses include RNA-Seq for plant root gene expression, 16S rRNA amplicon sequencing for bacterial/archaeal communities, metal concentrations in both tailings and plant organs, and phenotypic measures of plant stress. Zn accumulation in A. lentiformis leaves varied with compost levels and was the highest in the intermediate treatment (15 %, TC15). Microbial analysis identified Alicyclobacillus, Hydrotalea, and Pseudolabrys taxa with the highest relative abundance in TC15, and these taxa were strongly associated with Zn accumulation. Furthermore, we identified 190 root genes with significant gene expression changes. These root genes were associated with different pathways including, abscisic acid and auxin signaling, defense responses, ion channels, metal ion binding, oxidative stress, transcription regulation, and transmembrane transport. However, root gene expression changes were not driven by the increasing levels of compost. For example, there were 15 genes that were up-regulated in TC15, whereas 106 genes were down-regulated in TC15. The variables analyzed explained 86 % of the variance in Zn accumulation in A. lentiformis leaves. Importantly, Zn accumulation was driven by Zn shoot concentrations, leaf stress symptoms, plant root genes, and microbial taxa. Therefore, our results suggest there are strong plant-microbiome associations that drive Zn accumulation in A. lentiformis and different plant gene pathways are involved in alleviating varying levels of metal stress. Future work is needed to gain a mechanistic understanding of these plant-microbiome interactions to optimize phytoremediation strategies as they will govern the success or failure of the revegetation process.
作者机构：
[Jiming Cheng; Huimin He; Min Zhang; Baiqi Gan; Hongyu Niu; Hongmao Zhang; Min Zhang (张敏) Min Zhang 张敏 Min Zhang] Institute of Evolution and Ecology, School of Life Sciences, Central China Normal University, Wuhan, China
通讯机构：
[Hongyu Niu; Hongmao Zhang; Hongyu Niu (牛红玉) Hongyu Niu 牛红玉 Hongyu Niu; Hongmao Zhang (张洪茂) Hongmao Zhang 张洪茂 Hongmao Zhang] I;Institute of Evolution and Ecology, School of Life Sciences, Central China Normal University, Wuhan, China
摘要：
One of the challenges in animal personality study is finding a suitable method to measure personality. Here, we outlined three methods (traits rating, behavioral coding, and experimentation) used in animal personality measurement. We found that traits rating was commonly used to test large‐sized animals (e.g., primates), behavioral coding was conducted for both large‐ and small‐sized animals (e.g., primates, birds, rodents, and fishes), whereas experimentation was more used for small‐sized animals (e.g., rodents, birds, amphibians, and insects). Abstract One of the challenges in the study of animal personalities is to select a suitable method to measure personality. Here, we reviewed the three common methods (traits rating, behavioral coding, and experimentation) used in animal personality measurement in wild animals. For each method, we summarized its experimental animals and conditions, advantages, and disadvantages in personality measurement. One method could be used to measure the personalities of different animal species, and different methods could be used to measure the personality of one animal species. Overall, traits rating was used to test the personalities of large animals (e.g., primates), behavioral coding was conducted both in large and small animals (e.g., primates, birds, rodents, and fishes), whereas experimentation was used in small animals (e.g., rodents, birds, amphibians, and insects). Although the methods of experimentation were originally designed for model animals (e.g., mice and rats), some of them were used to test the personalities of wild animals under indoor conditions, in which the experimental animals were transferred from the field to the laboratory. Unfortunately, few studies have estimated the applicability of these methods to wild animals. In the future, effective methods of personality measurement are needed for wild animals, especially the methods that can be used in the field. 摘要 如何确定适用的个性测量方法是动物个性研究的一大挑战。本文概述了三类常用于野生动物个性评估的方法，即特征评定法、行为编码及实验法。通过总结每种方法所使用的动物和场景，以及每种方法的应用条件与优缺点，我们发现，同一种方法可以用来测量不同物种的个性；反之，同一种动物的个性也可以用不同的方法来测量。总之，特征评定法常常被用于大型动物，如灵长类的个性评定，行为编码则同时可被用于大型及小型动物，如灵长类、鸟类、啮齿类以及鱼类，而实验法则多被用于小型动物，如啮齿类、鸟类、两栖类以及昆虫。虽然实验法最初针对模式动物，如大鼠和小鼠所设计，但其中一些内容也可用于研究圈养条件下的野生动物。然而，很少有研究评估这些方法在野生动物研究中的适用性。因此，需要有测量野生动物个性的有效方法。
摘要：
The responsive control of energy transfer (ET) plays a key role in the broad applications of lanthanide-doped nanomaterials. Photonic crystals (PCs) are excellent materials for ET regulation. Among the numerous materials that can be used to fabricate PCs, chiral nematic liquid crystals are highly attractive due to their good photoelectric responsiveness and biocompatibility. Here, the mechanisms of ET and the photonic effect of chiral nematic structures on ET are introduced; the regulation methods of chiral nematic structures and the resulting changes in ET of lanthanide-doped nanomaterials are highlighted; and the challenges and promising opportunities for ET in chiral nematic structures are discussed.
作者机构：
[Fu, Zi-Ying; Fu, ZY] Cent China Normal Univ, Sch Life Sci, Wuhan 430079, Peoples R China.;Cent China Normal Univ, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan 430079, Peoples R China.
通讯机构：
[Fu, ZY ] C;Cent China Normal Univ, Sch Life Sci, Wuhan 430079, Peoples R China.
作者：
Su, Hongxia;Geng, Hui;Cai, Linkang;Xu, Minjie;Xing, Wenpin;...
期刊：
Cancer Medicine,2023年12(12):13573-13585 ISSN：2045-7634
通讯作者：
Li, YK;Liu, BL
作者机构：
[Su, Hongxia; Li, Yankun] Hubei Univ Sci & Technol, Sch Pharm, Xianning, Peoples R China.;[Xu, Minjie; Xing, Wenpin; Geng, Hui] Huazhong Normal Univ, Sch Life Sci, Wuhan, Peoples R China.;[Long, Wei; Liu, Binlei; Cai, Linkang] Wuhan Binhui Biopharmaceut Co Ltd, Wuhan, Peoples R China.;[Liu, Binlei; Liu, Biao] Hubei Univ Technol, Wuhan, Peoples R China.;[Li, Yankun; Li, YK] Hubei Univ Sci & Technol, Coll Pharm, Hubei Engn Res Ctr Hubei Specialty Chinese Med, Xianning 437100, Peoples R China.
通讯机构：
[Liu, BL ; Li, YK ] H;Hubei Univ Sci & Technol, Coll Pharm, Hubei Engn Res Ctr Hubei Specialty Chinese Med, Xianning 437100, Peoples R China.;Hubei Univ Technol, Coll Bioengn, Wuhan 430068, Peoples R China.
关键词：
GM-CSF;IL-12;IL-2/15;PD-1v;tumor immunity
摘要：
The combination of immune check blockade and multiple cytokine therapy can significantly activate the body's immune response and inhibit tumor growth. Our manuscript provides a paradigm for future tumor immunotherapy. Abstract Objective In order to ensure the stable transcription of target genes, we constructed a eukaryotic high expression vector carrying an immune‐check inhibitor PD‐1v and a variety of cytokines, and studied their effects on activating immune response to inhibit tumor growth. Methods A novel eukaryotic expression plasmid vector named pT7AMPCE containing T7RNA polymerase, T7 promoter, internal ribosome entry site (IRES), and poly A tailing signal was constructed by T4 DNA ligase, on which homologous recombination was used to clone and construct the vector carrying PD‐1v, IL‐2/15, IL‐12, GM‐CSF, and GFP. In vitro transfection of CT26 cells was performed, and the protein expression of PD‐1v, IL‐12 and GM‐CSF was detected by Western blot and ELISA after 48 h. Mice were subcutaneously inoculated with CT26‐IRFP tumor cells in the rib abdomen, and the tumor tissues were injected with PD‐1v, IL‐2/15, IL‐12, and GM‐CSF recombinant plasmids for treatment during the experimental period. The efficacy of the treatment was evaluated by assay tumor size and survival time of tumor‐bearing mice during the experiment. Expression levels of IFN‐γ, TNF, IL‐4, IL‐2, and IL‐5 in mouse blood were measured using the CBA method. Tumor tissues were extracted and immune cell infiltration in tumor tissues was detected by HE staining and the IHC method. Results The recombinant plasmids carrying PD‐1v, IL‐2/15, IL‐12, and GM‐CSF were successfully constructed, and the Western blot and ELISA results showed that PD‐1v, IL‐12, and GM‐CSF were expressed in the supernatant of CT26 cells 48 h after in vitro cell transfection. The combined application of PD‐1v, IL‐2/15, IL‐12, and GM‐CSF recombinant plasmids significantly inhibited tumor growth in mice, and the tumor growth rate was significantly lower than that in the blank control group and GFP plasmid control group (p < 0.05). Cytometric bead array data suggested that the combination of PD‐1v and various cytokines can effectively activate immune cells. HE and IHC analysis revealed plenty of immune cell infiltrates in the tumor tissue, and a large proportion of tumor cells showed the necrotic phenotype in the combination treatment group. Conclusion The combination of immune check blockade and multiple cytokine therapy can significantly activate the body's immune response and inhibit tumor growth.
摘要：
Increasing attention has been paid to the potential impact of microplastics (MPs) pollution on human health. MPs and phthalates coexist in the environment, however, the effects of exposure to MPs alone or to a combination of di-(2-ethylhexyl) phthalate (DEHP) and MPs on allergic asthma are unclear. This study investigates the effects of exposure to polystyrene microplastics (PS-MPs) or co-exposure with DEHP, on allergic asthma, and the underlying molecular mechanisms. We established an allergic asthma model using ovalbumin, and mice were exposed to PS-MPs (5mg/kg bw/day) alone, or combined with DEHP (0.5, 5mg/kg bw/day), for 28 days. The results showed that in the presence of ovalbumin (OVA) sensitization, exposure to PS-MPs alone slightly affected airway inflammation, and airway hyperresponsiveness, while co-exposure to PS-MPs and DEHP caused more significant damage. Co-exposure also induced more oxidative stress and Th2 immune responses, and activation of the TRPA1 and p38 MAPK pathways. The aggravation of asthmatic symptoms induced by co-exposure to PS-MPs and DEHP were inhibited by blocking TRPA1 ion channel or p38 MAPK pathway. The results demonstrated that co-exposure to PS-MPs and DEHP exacerbates allergic asthma, by exacerbating oxidative stress and inflammatory responses, and activating the TRPA1-p38 MAPK pathway.
