摘要：
Building envelope dampness exposure is correlated with children's respiratory and allergic diseases. However, little research has compared the variation in the health impact of dampness exposure across multiple cities from a longitudinal perspective. A cross-sectional survey and a repeated one were conducted in children's residences in six cities: Chongqing, Shanghai, Nanjing, Wuhan, Changsha and Taiyuan, China, in 2010 (Phase I) and 2019 (Phase II). We selected 17,810 preschoolers during Phase I and 26,001 preschoolers during Phase II aged 3–6 years without changing residence since birth in the study. The proportion of residences with building envelope dampness exposure and the prevalence of respiratory and allergic diseases, except allergic rhinitis, in preschoolers significantly declined from Phase I to Phase II. Dampness exposure increased the risk for most childhood respiratory diseases in Phase II, with a 34% greater risk of lifetime-ever asthma in early residences and a 36% greater risk of current eczema in current residences. Most diseases showed a significantly positive exposure-response relationship to the cumulative period of building envelope dampness exposure (p < 0.05). The risk of developing current eczema was approximately 1.35 and 1.73 times higher in children exposed to both early and current dampness in Phase I and Phase II, respectively, than in children who had never been exposed. These findings provide new insights into the respiratory and allergic diseases in Chinese preschoolers because of building envelope dampness exposure over the last decade. The increased risk in Phase II raises concerns about the household's dampness environment.
摘要：
The toxicity of microplastics (MPs) to aquatic organisms has been extensively studied recently. However, few studies have investigated the effects of MPs in sediments on aquatic ecosystem functioning. In the present study, we conducted an in situ experiment to explore the concentration-dependent effects (0.025%, 0.25%, 2.5%) and size-dependent effects (150-300 μm and 500-1000 μm) of polypropylene microplastics (PP MPs) on Vallisneria natans litter decomposition dynamics, in particular, the process associated with macroinvertebrates, microorganisms, as well as microalgae and/or cyanobacteria. The results showed that exposure to high concentrations and large sizes of PP MPs can accelerate leaf litter biomass loss and nutrition release. Moreover, microbial respiration, microalgal and/or cyanobacteria chlorophyll-a were also significantly affected by PP MPs. However, PP MPs have no effect on the abundance of associated macroinvertebrate during the experiment, despite the collection of five macroinvertebrate taxa from two functional feeding groups (i.e., collectors and scrapers). Therefore, our experiment demonstrated that PP MPs may enhance leaf litter decomposition through effected microbial metabolic activity, microalgal and/or cyanobacteria biomass in the sedimentary lake. Overall, our findings highlight that PP MPs have the potential to interfere with the basic ecological functions such as plant litter decomposition in aquatic environments.
作者机构：
[Wang, Ruiqi; Li, Yingcan] Key Laboratory of Biodiversity and Environment on the Qinghai-Tibetan Plateau of the Ministry of Education, Frontier Science Center for Immunology and Metabolism, College of Life Sciences, Wuhan University, Wuhan 430072, China;[Jiao, Hengwu] School of Life Sciences, Central China Normal University, Wuhan 430079, China;[Sin, Simon Yung Wa] School of Biological Sciences, The University of Hong Kong, Hong Kong SAR 999077, China;[Rossiter, Stephen J] School of Biological and Behavioural Sciences, Queen Mary University of London, London E1 4NS, UK;[Zhao, Huabin] Key Laboratory of Biodiversity and Environment on the Qinghai-Tibetan Plateau of the Ministry of Education, Frontier Science Center for Immunology and Metabolism, College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: huabinzhao@whu.edu.cn
通讯机构：
[Huabin Zhao] K;Key Laboratory of Biodiversity and Environment on the Qinghai-Tibetan Plateau of Ministry of Education, Frontier Science Center for Immunology and Metabolism, College of Life Sciences, Wuhan University, Wuhan 430072, China
摘要：
Transgenic crops producing insecticidal proteins from Bacillus thuringiensis (Bt) have revolutionized control of some major pests. However, more than 25 cases of field-evolved practical resistance have reduced the efficacy of transgenic crops producing crystalline (Cry) Bt proteins, spurring adoption of alternatives including crops producing the Bt vegetative insecticidal protein Vip3Aa. Although practical resistance to Vip3Aa has not been reported yet, better understanding of the genetic basis of resistance to Vip3Aa is urgently needed to proactively monitor, delay, and counter pest resistance. This is especially important for fall armyworm (Spodoptera frugiperda), which has evolved practical resistance to Cry proteins and is one of the world's most damaging pests. Here, we report the identification of an association between downregulation of the transcription factor gene SfMyb and resistance to Vip3Aa in S. frugiperda. Results from a genome-wide association study, fine-scale mapping, and RNA-Seq identified this gene as a compelling candidate for contributing to the 206-fold resistance to Vip3Aa in a laboratory-selected strain. Experimental reduction of SfMyb expression in a susceptible strain using RNA interference (RNAi) or CRISPR/Cas9 gene editing decreased susceptibility to Vip3Aa, confirming that reduced expression of this gene can cause resistance to Vip3Aa. Relative to the wild-type promoter for SfMyb, the promoter in the resistant strain has deletions and lower activity. Data from yeast one-hybrid assays, genomics, RNA-Seq, RNAi, and proteomics identified genes that are strong candidates for mediating the effects of SfMyb on Vip3Aa resistance. The results reported here may facilitate progress in understanding and managing pest resistance to Vip3Aa.
作者机构：
[Wang, P; Wang, Peng; Grimm, Bernhard; Ji, Shuiling] Humboldt Univ, Inst Biol Plant Physiol, Philippstr13, Bldg 12, D-10099 Berlin, Germany.;[Ji, Shuiling] Cent China Normal Univ, Sch Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan 430079, Peoples R China.;[Wang, P; Wang, Peng] Univ Hong Kong, Sch Biol Sci, Hong Kong 999077, Peoples R China.;[Wang, P; Wang, Peng] Chinese Univ Hong Kong, State Key Lab Agrobiotechnol, Hong Kong 999077, Peoples R China.
通讯机构：
[Wang, P ; Grimm, B] H;Humboldt Univ, Inst Biol Plant Physiol, Philippstr13, Bldg 12, D-10099 Berlin, Germany.;Univ Hong Kong, Sch Biol Sci, Hong Kong 999077, Peoples R China.;Chinese Univ Hong Kong, State Key Lab Agrobiotechnol, Hong Kong 999077, Peoples R China.
关键词：
chlorophyll biosynthesis;post-translational control;chloroplast signal recognition particle;protein stability;molecular chaperone;chloroplast development
摘要：
Protochlorophyllide oxidoreductase (POR), which converts protochlorophyllide into chlorophyllide, is the only light-dependent enzyme in chlorophyll biosynthesis. While its catalytic reaction and importance for chloroplast development are well understood, little is known about the post-translational control of PORs. Here, we show that cpSRP43 and cpSRP54, two components of the chloroplast signal recognition particle pathway, play distinct roles in optimizing the function of PORB, the predominant POR isoform in Arabidopsis. The chaperone cpSRP43 stabilizes the enzyme and provides appropriate amounts of PORB during leaf greening and heat shock, whereas cpSRP54 enhances its binding to the thylakoid membrane, thereby ensuring adequate levels of metabolic flux in late chlorophyll biosynthesis. Furthermore, cpSRP43 and the DnaJ-like protein CHAPERONE-LIKE PROTEIN of POR1 concurrently act to stabilize PORB. Overall, these findings enhance our understanding of the coordinating role of cpSPR43 and cpSRP54 in the post-translational control of chlorophyll synthesis and assembly of photosynthetic chlorophyll-binding proteins.
期刊：
JOURNAL OF PROTEOME RESEARCH,2023年22(10):3254-3263 ISSN：1535-3893
通讯作者：
Li, YZ;Zhu, H
作者机构：
[Yan, Songxin; Li, YZ; Liu, Chenxi; Li, Liubing; Li, Yongzhe; Wen, Xiaoting] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Peking Union Med Coll, Dept Clin Lab, Beijing 100730, Peoples R China.;[Liu, Chenxi] Sichuan Univ, West China Univ Hosp 2, Dept Clin Lab, Chengdu 610041, Peoples R China.;[Song, Guang] Cent China Normal Univ, Sch Life Sci, Wuhan 430079, Peoples R China.;[Song, Guang; Zhu, Heng; Zhu, H] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA.;[He, Yangzhige] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Peking Union Med Coll, Cent Res Lab, Beijing 100730, Peoples R China.
通讯机构：
[Li, YZ ] C;[Zhu, H ] J;Chinese Acad Med Sci, Peking Union Med Coll Hosp, Peking Union Med Coll, Dept Clin Lab, Beijing 100730, Peoples R China.;Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA.
摘要：
Systemic sclerosis (SSc) is a systemic autoimmune disorder that leads to vasculopathy and tissue fibrosis. A lack of reliable biomarkers has been a challenge for clinical diagnosis of the disease. We employed a protein array-based approach to identify and validate SSc-specific autoantibodies. Phase I involved profiled autoimmunity using human proteome microarray (HuProt arrays) with 90 serum samples: 40 patients with SSc, 30 patients diagnosed with autoimmune diseases, and 20 healthy subjects. In Phase II, we constructed a focused array with candidates identified antigens and used this to profile a much larger cohort comprised of serum samples. Finally, we used a western blot analysis to validate the serum of validated proteins with high signal values. Bioinformatics analysis allowed us to identify 113 candidate autoantigens that were significantly associated with SSc. This two-phase strategy allowed us to identify and validate anti-small nuclear ribonucleoprotein polypeptide A (SNRPA) as a novel SSc-specific serological biomarker. The observed positive rate of anti-SNRPA antibody in patients with SSc was 11.25%, which was significantly higher than that of any disease control group (3.33%) or healthy controls (1%). In conclusion, anti-SNRPA autoantibody serves as a novel biomarker for SSc diagnosis and may be promising for clinical applications.
作者机构：
[Wu, H; Wu, Hua; Li, Yan-Peng] Cent China Normal Univ, Sch Life Sci, Wuhan 430079, Peoples R China.;[Huang, Zhi-Pang; Li, Yan-Peng; Xiao, Wen] Dali Univ, Inst Eastern Himalaya Biodivers Res, Dali 671003, Peoples R China.;[Huang, Zhi-Pang; Yang, Yin; Pan, Ru-Liang; Li, Yan-Peng; Xiao, Wen] Dali Univ, Int Ctr Biodivers & Primate Conservat, Dali 671003, Peoples R China.;[Yang, Yin] Yunnan Univ, Inst Int Rivers & Ecosecur, Kunming 650091, Peoples R China.;[He, Xiao-Bin; He, Xin-Ming] Adm Baimaxueshan Natl Nat Reserve, Diqing 674500, Peoples R China.
通讯机构：
[Wu, H ] C;[Cui, LW ] S;Cent China Normal Univ, Sch Life Sci, Wuhan 430079, Peoples R China.;Southwest Forestry Univ, Key Lab Wildlife Conservat Minimal Populat Univ Yu, Kunming 650224, Peoples R China.
关键词：
Rhinopithecus bieti;sexual bimaturism;environmental adaptation;multilevel social organization;sexual selection
摘要：
Sexual dimorphism widely exists in animals and is reflected in different forms; of these, body mass dimorphism is the most prominent. Studies on the development and adaptation mechanism of sexual dimorphism in body mass can help us to understand how animals adapt to their environment via sexual dimorphism. As this has not been widely reported in Rhinopithecus, this study explores the ontogenetic development pattern of sexual dimorphism in the body mass of R. bieti, and interprets the causes resulting in extreme sexual dimorphism. The results showed that a significant dimorphism appears when females enter the reproductive period, reaching the maximum when males are mature for reproduction. It was determined that a period of decline begins after 8 years of age, and that males had a longer growth period than females. The large sexual dimorphism in body mass in R. bieti can be explained by both Bergmann's and Rensch's rules; however, the females' choice for males may not be significantly related to it. Overall, environmental adaptation, a distinctive alimentary system, and complex social structure have allowed R. bieti to have remarkable sexual dimorphism in body mass compared to other colobines. This study will undoubtedly highlight the same issues on the other 26 primate species in China, particularly the colobines, which will enrich research designs and enlarge research focus on China's primatology.Sexual dimorphism exists widely in animals, manifesting in different forms, such as body size, color, shape, unique characteristics, behavior, and sound. Of these, body mass dimorphism is the most obvious. Studies of evolutionary and ontogenetic development and adaptation mechanisms of animals' sexual dimorphism in body mass (SDBM), allow us to understand how environment, social group size, diet, and other external factors have driven the selection of sexual dimorphism. There are fewer reports of the ontogenetic development of sexual dimorphism in body mass in Rhinopithecus. This study explores the ontogenetic development pattern of SDBM in wild black-and-white snub-nosed monkeys (R. bieti), and the causes resulting in extreme sexual dimorphism compared to other colobines. A significant dimorphism with a ratio of 1.27 (p < 0.001) appears when females enter the reproductive period around six years old, reaching a peak (1.85, p < 0.001) when males become sexually mature. After the age of eight, the SDBM falls to 1.78, but is still significant (p < 0.001). The results also indicate that males had a longer body mass growth period than females (8 years vs. 5 years); females in larger breeding units had a significantly higher SDBM than those in smaller ones (2.12 vs. 1.93, p < 0.01). A comparative analysis with other colobines further clarifies that Rhinopithecus and Nasalis, which both have multilevel social organization, have the highest degree of SDBM among all colobines. The large SDBM in R. bieti can be explained through Bergman's and Rensch's rules. Overall, environmental adaptation, a distinctive alimentary system, and a complex social structure contribute to R. bieti having such a remarkable SDBM compared to other colobines. In addition, we found that females' choice for males may not be significantly related to the development of SDBM.
期刊：
Frontiers in Microbiology,2023年13:1112301 ISSN：1664-302X
通讯作者：
Wang, Q.;Liu, L.-N.;Qiu, B.-S.;Duanmu, D.;Ma, W.
作者机构：
[Ma, Weimin] College of Life Sciences, Shanghai Normal University, Shanghai, China;[Liu, Lu-Ning] Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom;[Wang, Qiang] State Key Laboratory of Crop Stress Adaptation and Improvement, School of Life Sciences, Henan University, Kaifeng, China;[Duanmu, Deqiang] State Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Shenzhen Institute of Nutrition and Health, Huazhong Agricultural University, Wuhan, China;[Qiu, Bao-Sheng] Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, China
通讯机构：
[Ma, W.] C;[Liu, L.-N.] I;[Wang, Q.; Duanmu, D.] S;[Qiu, B.-S.] H;Institute of Systems, United Kingdom
关键词：
algae;antioxidant mechanism;carbon dioxide-concentrating mechanism;carbon fixation;evolution;light energy harvesting;photosynthetic electron transfer;photosynthetic membrane complexes
作者机构：
[Song, Hang; Zhou, Lei; Wang, Shenqi; Ge, Jing; Xu, Pengxin] Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Wuhan 430074, Peoples R China.;[Wan, Ying; Tan, Ronghua] Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Natl Engn Res Ctr Nanomed, Wuhan 430074, Peoples R China.;[Gao, Qian] Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Key Lab Mol Biophys, Minist Educ, Wuhan 430074, Hubei, Peoples R China.;[Li, Rui] Cent China Normal Univ, Sch Life Sci, Wuhan 430079, Peoples R China.
通讯机构：
[Shenqi Wang; Lei Zhou; Shenqi Wang Shenqi Wang Shenqi Wang; Lei Zhou Lei Zhou Lei Zhou] C;[Ying Wan; Ying Wan Ying Wan Ying Wan] N;College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074 P. R. China<&wdkj&>National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074 P. R. China
摘要：
A new type of ketamine (KA)‐loaded nanoparticle (AC‐RM@HA‐MS‐KA) with specific targeting capabilities is developed to improve the efficacy of KA treatment. They can sustainably accumulate at the N‐methyl‐d‐aspartate receptor sites, effectively alleviate depressive symptoms, circumvent KA‐induced addiction, and significantly improve cognitive functions. Abstract Ketamine (KA), commonly used as an anesthetic, is now widely studied as an antidepressant for the treatment of depression. However, due to its side effects, such as addiction and cognitive impairment, the dosage and frequency of (S)‐ketamine approved by the FDA for the treatment of refractory depression is very low, which limits its efficacy. Here, a new multifunctional nanocarrier system (AC‐RM@HA‐MS) with specific targeting capabilities is developed to improve the efficacy of KA treatment. KA‐loaded NPs (AC‐RM@HA‐MS‐KA) are constructed with a multilayer core–shell structure. KA‐loaded mesoporous silica NPs are prepared, conjugated with hyaluronic acid (HA) as pore gatekeepers, and sheathed with an RBC‐membrane (RM) for camouflage. Finally, the surface is tagged with bifunctional peptides (Ang‐2‐Con‐G, AC) to achieve specific targeting. One peptide (Ang‐2) is acted as a guide to facilitate the crossing of the blood–brain barrier (BBB), while the other (Con‐G) is functioned as a ligand for the targeted delivery of KA to the N‐methyl‐D‐aspartate receptor sites. Animal experiments reveal that AC‐RM@HA‐MS‐KA NPs effectively cross the BBB and directionally accumulate in the curing areas, thereby alleviating the depressive symptoms and improving the cognitive functions of depressed mice. After treatment, the depressed mice almost completely return to normal without obvious symptoms of addiction.
作者机构：
[Wang, Wen-Shu; Gao, Xiang; Lu, Ying-Tang; Zhu, Jiang; Yan, Da-Wei; Li, Ting-Ting; Yuan, Ting-Ting; Hong, Li-Wei] Wuhan Univ, Renmin Hosp Wuhan Univ, Coll Life Sci, State Key Lab Hybrid Rice, Wuhan 430072, Peoples R China.;[Yang, Yun-Huang; Zhu, Jiang] Chinese Acad Sci, Innovat Acad Precis Measurement Sci & Technol, Natl Ctr Magnet Resonance Wuhan, State Key Lab Magnet Resonance & Atom Mol Phys, Wuhan 430071, Peoples R China.;[Ren, Feng] Cent China Normal Univ, Sch Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan 430079, Peoples R China.;[Wang, Wen-Shu] Wuhan Acad Agr Sci, Inst Crop Sci, Wuhan 430345, Peoples R China.
通讯机构：
[Ying-Tang Lu; Ting-Ting Yuan] S;State Key Laboratory of Hybrid Rice, College of Life Sciences, Renmin Hospital of Wuhan University, Wuhan University , Wuhan 430072, China
摘要：
Jasmonic acid (JA) signaling plays a pivotal role in plant development and defense. MYC2 is a master transcription factor in JA signaling, and was found to be phosphorylated and negatively regulated by MAP kinase and receptor-like kinase. However, the kinases that positively regulate MYC2 through phosphorylation and promote MYC2-mediated activation of JA response have not been identified. Here, we identified CK2 as a kinase that phosphorylates MYC2 and thus regulates the JA signaling. CK2 holoenzyme can interact with MYC2 using its regulatory subunits and phosphorylate MYC2 at multiple sites with its catalytic subunits. Inhibition of CK2 activity in a dominant-negative plant line, CK2mut, repressed JA response. On the other hand, increasing CK2 activity by overexpression of CKB4, a regulatory subunit gene of CK2, enhanced JA response in a MYC2-dependent manner. Substitution of the Ser and Thr residues at phosphorylation sites of MYC2 by CK2 with Ala impaired MYC2 function in activating JA response. Further investigations evidenced that CK2 facilitated the JA-induced increase of MYC2 binding to the promoters of JA-responsive genes in vivo. Our study demonstrated that CK2 plays a positive role in JA signaling, and reveals a previously undiscovered mechanism that regulates MYC2 function.
摘要：
Native ethylene‐producing cyanobacterium Nostoc sphaeroides is hybridized with indium phosphide) nanomaterial via a self‐assembly strategy, and the resulting biohybrid system achieved high photosynthetic ethylene production. Advanced analytical techniques revealed that an InP‐modulated photosystem I activity underlined the augmented ethylene production of the biohybrid cyanobacterium. Abstract Biomanufacturing of ethylene is particularly important for modern society. Cyanobacterial cells are able to photosynthesize various valuable chemicals. A promising platform for next‐generation biomanufacturing, the semiconductor‐cyanobacterial hybrid systems are capable of enhancing the solar‐to‐chemical conversion efficiency. Herein, the native ethylene‐producing capability of a filamentous cyanobacterium Nostoc sphaeroides is confirmed experimentally. The self‐assembly characteristic of N. sphaeroides is exploited to facilitate its interaction with InP nanomaterial, and the resulting biohybrid system gave rise to further elevated photosynthetic ethylene production. Based on chlorophyll fluorescence measurement and metabolic analysis, the InP nanomaterial‐augmented photosystem I activity and enhanced ethylene production metabolism of biohybrid cells are confirmed, the mechanism underlying the material‐cell energy transduction as well as nanomaterial‐modulated photosynthetic light and dark reactions are established. This work not only demonstrates the potential application of semiconductor‐N. sphaeroides biohybrid system as a good platform for sustainable ethylene production but also provides an important reference for future studies to construct and optimize nano‐cell biohybrid systems for efficient solar‐driven valuable chemical production.
通讯机构：
[Xie, GS ] H;[Zhang, ZF ] C;Huazhong Agr Univ, Coll Plant Sci & Technol, Wuhan 430070, Peoples R China.;Cent China Normal Univ, Sch Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan 430079, Peoples R China.
关键词：
de novo fatty acid synthesis;fibrillin 7;galactolipids;KAS I;plastoglobule;rice
摘要：
Plastoglobules (PGs) contiguous with the outer leaflets of thylakoid membranes regulate lipid metabolism, plastid developmental transitions, and responses to environmental stimuli. However, the function of OsFBN7, a PG-core fibrillin gene in rice, has not been elucidated. Using molecular genetics and physiobiochemical approaches, we observed that OsFBN7 overexpression promoted PG clustering in rice chloroplasts. OsFBN7 interacted with two KAS I enzymes, namely OsKAS Ia and OsKAS Ib, in rice chloroplasts. Lipidomic analysis of chloroplast subcompartments, including PGs in the OsFBN7 overexpression lines, confirmed that levels of diacylglycerol (DAG), a chloroplast lipid precursor and monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG), the main chloroplast membrane lipids, were increased in PGs and chloroplasts. Furthermore, OsFBN7 enhanced the abundances of OsKAS Ia/Ib in planta and their stability under oxidative and heat stresses. In addition, RNA sequencing and real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analyses showed that the expression of the DAG synthetase gene PAP1 and MGDG synthase gene MDG2 was upregulated by OsFBN7. In conclusion, this study proposes a new model in which OsFBN7 binds to OsKAS Ia/Ib in chloroplast and enhances their abundance and stability, thereby regulating the chloroplast and PG membrane lipids involved in the formation of PG clusters.
作者机构：
[Mao, Bin; Chen, Meng-Yan; Wang, Qian; Shen, Wei; Li, Chao; Wang, Yu-Feng; Zheng, Ya; Duan, Xin] Cent China Normal Univ, Sch Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan 430079, Peoples R China.
通讯机构：
[Wang, YF ] C;Cent China Normal Univ, Sch Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan 430079, Peoples R China.
关键词：
Ocnus;Drosophila melanogaster;Proteomics;Phosphoproteomics;Testis development
摘要：
Testis is the only organ supporting sperm production and with the largest number of proteins and tissue-specific proteins in animals. In our previous studies, we have found that knockdown of ocnus (ocn), a testis-specific gene, resulted in much smaller testis with no germ cells in Drosophila melanogaster. However, the molecular consequences of ocn knockdown in fly testes are unknown. In this study, through iTRAQ quantitative proteomics sequencing, 606 proteins were identified from fly abdomens as having a significant and at least a 1.5-fold change in expression after ocn knockdown in fly testes, of which 85 were up-regulated and 521 were down-regulated. Among the differential expressed proteins (DEPs), apart from those proteins involved in spermatogenesis, the others extensively affected biological processes of generation of precursor metabolites and energy, metabolic process, and mitochondrial transport. Protein-protein interaction (PPI) analyses of DEPs showed that several kinases and/or phosphatases interacted with Ocn. Re-analyses of the transcriptome revealed 150 differential expressed genes (DEGs) appeared in the DEPs, and their changing trends in expressions after ocn knockdown were consistent. Many common down-regulated DEGs and DEPs were testis-specific or highly expressed in the testis of D. melanogaster. Quantitative RT-PCR (qRT-PCR) confirmed 12 genes appeared in both DEGs and DEPs were significantly down-regulated after ocn knockdown in fly testes. Furthermore, 153 differentially expressed phosphoproteins (DEPPs), including 72 up-regulated and 94 down-regulated phosphorylated proteins were also identified (13 phosphoproteins appeared in both up- and down-regulated groups due to having multiple phosphorylation sites). In addition to those DEPPs associated with spermatogenesis, the other DEPPs were enriched in actin filament-based process, protein folding, and mesoderm development. Some DEPs and DEPPs were involved in Notch, JAK/STAT, and cell death pathways. Given the drastic effect of the ocn knockdown on tissue development and testis cells composition, the differences in protein abundance in the ocn knockdown flies might not necessarily be the direct result of differential gene regulation due to the inactivation of ocn. Nevertheless, our results suggest that the expression of ocn is essential for Drosophila testis development and that its down-regulation disturbs key signaling pathways related to cell survival and differentiation. These DEPs and DEPPs identified may provide significant candidate set for future studies on the mechanism of male reproduction of animals, including humans.
作者机构：
[Yang, Decai; Zhang, Bin; Zhang, Yuanyuan; Li, Chenxi; Nie, Guohui; Yang, DC; Fang, Xueyang] Shenzhen Univ, Shenzhen Peoples Hosp 2, Affiliated Hosp 1, Shenzhen Inst Translat Med,Guangdong Key Lab Biome, Shenzhen 518035, Peoples R China.;[Lo, Wai-Sum; Wong, Wing-Tak; Lui, Kwok-Ho; Gu, Yanjuan; Li, Xin; Wong, WT; Fang, Xueyang; Gu, YJ] Hong Kong Polytech Univ, Dept Appl Biol & Chem Technol, Hong Kong, Peoples R China.;[Wu, Xianlin] Guangzhou Univ Chinese Med, Shenzhen Hosp, Canc Ctr, Shenzhen 518000, Peoples R China.;[Wu, Xianlin] Jinan Univ, Affiliated Hosp 1, Inst Clin Med, Guangzhou 510632, Peoples R China.;[Jiang, Lijun] Cent China Normal Univ, Sch Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan 430079, Peoples R China.
通讯机构：
[Zhang, B ; Yang, DC] S;[Jiang, LJ ] C;[Gu, YJ; Wong, WT ] H;Shenzhen Univ, Shenzhen Peoples Hosp 2, Affiliated Hosp 1, Shenzhen Inst Translat Med,Guangdong Key Lab Biome, Shenzhen 518035, Peoples R China.;Hong Kong Polytech Univ, Dept Appl Biol & Chem Technol, Hong Kong, Peoples R China.
关键词：
Dual single-atom catalysts;Tumor microenvironment;H2O2 activation;Hypoxia alleviation;Synergistic cancer therapy
摘要：
Tumor therapy employing metal-based nanomaterials to convert the abundant H2O2 in tumor microenvironment (TME) to oxygen (O2) and hydroxy radical (& BULL;OH) has attracted substantial attention. However, the generally complex structure of metal nanosystems may have poor catalytic selectivity towards the target and hence cause undesired side reactions. Single-atom catalysts (SACs) with high atomic utilization, composition of identical active site and tunable reaction pathway can be harnessed to realize the well-controlled and highly-selective conversion of H2O2 for cancer therapy. Herein, a series of dual single-atom catalysts (DSACs) containing two metal centers (Fe-Se6, Mn-Se6) are proposed. As guided by theoretical calculations, DSACs with equal proportions of Fe and Mn (termed as Fe/Mn@PSe3) exhibit the optimal reaction barriers towards the production of both & BULL;OH and O2 by catalyzing H2O2. In response to the elevated TME H2O2, Fe/Mn@PSe3 can produce & BULL;OH to trigger chemodynamic therapy (CDT), and boost O2 generation to alleviate tumor hypoxia and its mediated immunosuppression. In addition, its mild hyperthermia feature enhances the anti-tumor effects of CDT and immune therapy, causing an efficient synergistic tumor suppression outcome. The study provides new insights into highly selective nanomaterial design that preferentially activating specific catalytic processes within tumor, functioning as promising candidates for cancer therapy.
