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Recent Insights into Signaling Responses to Cope Drought Stress in Rice 被引量:5
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作者 Muhammad Mahran ASLAM Muhammad Abdul Rehman RASHID +8 位作者 Mohammad Aquil SIDDIQUI Muhammad Tahir KHAN Fozia FARHAT Shafquat YASMEEN Imtiaz Ahmad KHAN Shameem RAJA Fatima RASOOL Mahboob Ali SIAL ZHAO Yan 《Rice science》 SCIE CSCD 2022年第2期105-117,共13页
Drought is one of the hot topics needing urgent attention in the current era of climate change.It massively disturbs the rice growth and productivity and is becoming a serious threat.The drought avoidance strategies i... Drought is one of the hot topics needing urgent attention in the current era of climate change.It massively disturbs the rice growth and productivity and is becoming a serious threat.The drought avoidance strategies in rice include stomatal closure,cellular adaptation and changes in root development.Moreover,the endogenous plant hormones(abscisic acid and jasmonic acid)and reactive oxygen species have paramount importance in drought tolerance in rice.The drought tolerance induces modification in biochemical,molecular and physiological properties of plants.At the molecular level,expression of several transcription-factors is modulated which further determine the activation of drought responsive gene families.Mitogen activated protein kinases and Ca signaling pathways initiate an array of signaling cascade for mediating the gene expression in rice.Approaches,conventional breeding methods combined with modern emerging techniques such as genetic engineering,to improve rice drought tolerance were discussed.This review provided recent insights into major regulatory factors against drought stress,signaling mechanisms and molecular engineering strategies(including conventional transgenic and recent genome editing approaches)to induce drought tolerance in rice. 展开更多
关键词 drought stress RICE signaling response regulatory factor
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Antidepressant effect of electroacupuncture regulates signal targeting in the brain and increases brain- derived neurotrophic factor levels 被引量:14
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作者 Dong-mei Duan Ya Tu +1 位作者 Ping Liu Shuang Jiao 《Neural Regeneration Research》 SCIE CAS CSCD 2016年第10期1595-1602,共8页
Electroacupuncture improves depressive behavior faster and with fewer adverse effects than antidepressant medication. However, the antidepressant mechanism of electroacupuncture remains poorly understood. Here, we est... Electroacupuncture improves depressive behavior faster and with fewer adverse effects than antidepressant medication. However, the antidepressant mechanism of electroacupuncture remains poorly understood. Here, we established a rat model of chronic unpredicted mild stress, and then treated these rats with electroacupuncture at Yintang (EX-HN3) and Baihui (DU20) with sparse waves at 2 Hz and 0.6 mA for 30 minutes, once a day. We found increased horizontal and vertical activity, and decreased immobility time, at 2 and 4 weeks after treatment. Moreover, levels of neurotransmitters (5-hydroxytryptamine, glutamate, and y-aminobutyric acid) and protein levels of brain-derived neurotrophic factor and brain-derived neurotrophic factor-related proteins (TrkB, protein kinase A, and phosphorylation of cyclic adenosine monophosphate response element binding protein) were increased in the hippocampus. Similarly, protein kinase A and TrkB mRNA levels were increased, and calcium-calmodulin-dependent protein kinase lI levels decreased. These findings suggest that electroacupuncture increases phosphorylation of cyclic adenosine monophosphate response element binding protein and brain-derived neurotrophic factor levels by regulating multiple targets in the cyclic adenosine rnonophosphate response element binding protein signal- ing pathway, thereby promoting nerve regeneration, and exerting an antidepressive effect. 展开更多
关键词 nerve regeneration depression chronic unexpected mild stress ELECTROACUPUNCTURE brain-derived neurotrophic factor NEUROTRANSMITTER cyclic adenosine monophosphate response element binding protein signal pathway protein kinase A TRKB FLUOXETINE neural regeneration
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RNA-Seq Study Reveals AP2-Domain-Containing Signalling Regulators Involved in Initial Imbibition of Seed Germination in Rice 被引量:3
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作者 HE Yongqi ZHAO Jia +6 位作者 FENG Defeng HUANG Zhibo LIANG Jiaming ZHENG Yufei CHENG Jinping YING Jifeng WANG Zhoufei 《Rice science》 SCIE CSCD 2020年第4期302-314,共13页
A number of internal signals are required for seed germination.However,the precise signalling responses in the initial imbibition of seed germination are not yet fully understood in rice.In this study,the RNA sequenci... A number of internal signals are required for seed germination.However,the precise signalling responses in the initial imbibition of seed germination are not yet fully understood in rice.In this study,the RNA sequencing(RNA-Seq)approach was conducted in 8 h imbibed seeds to understand the signalling responses in the initial imbibition of rice seed germination.A total of 563 differentially expressed genes(DEGs)with at least 4-fold change were identified in 8 h imbibed seeds compared to dry seeds.MapMan analysis revealed that the majority of signalling response-related DEGs were hormone-and transcription factor-related genes,in which the largest number of DEGs belong to the AP2-domain-containing regulators,and their expressions were significantly induced in the initial imbibition of seed germination in rice.Moreover,at least five AP2-domain-containing transcription factor OsDREBs were identified in the initial imbibition of rice seed germination,and the expressions of 251 DEGs were putatively regulated by OsDREBs through the dehydration-responsive element(DRE)cis-element assay.It suggested that the OsDREBs might play important roles in the regulation of initial seed imbibition in rice.The identified genes provide a valuable resource to study the signalling regulation of seed germination in the future. 展开更多
关键词 RICE seed imbibition signalling response plant hormone transcription factor RNA-sequencing
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TLR signaling that induces weak inflammatory response and SHIP1 enhances osteogenic functions 被引量:2
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作者 Manoj Muthukuru Richard P Darveau 《Bone Research》 SCIE CAS 2014年第4期218-230,共13页
Toll-like receptor (TLR)-mediated inflammatory response could negatively affect bone metabolism. In this study, we determined how osteogenesis is regulated during inflammatory responses that are downstream of TLR si... Toll-like receptor (TLR)-mediated inflammatory response could negatively affect bone metabolism. In this study, we determined how osteogenesis is regulated during inflammatory responses that are downstream of TLR signaling. Human primary osteoblasts were cultured in collagen gels. Pam3CSK4 (P3C) and Escherichia coli lipopolysaccharide (EcLPS) were used as TLR2 and TLR4 ligand respectively. Porphyromonas gingivalis LPS having TLR2 activity with either TLR4 agonism (Pg1690) or TLR4 antagonism (Pg1449) and mutant E. coli LPS (LPxE/LPxF/WSK) were used. IL-lp, SH2-containing inositol phosphatase-1 (SHIP1) that has regulatory roles in osteogenesis, alkaline phosphatase and mineralization were analyzed. 3α-Aminocholestane (3AC) was used to inhibit SHIP1. Our results suggest that osteoblasts stimulated by P3C, poorly induced IL-1β but strongly upregulated SHIP1 and enhanced osteogenic mediators. On the contrary, EcLPS significantly induced IL-1β and osteogenic mediators were not induced. While Pg1690 downmodulated osteogenic mediators, Pg1449 enhanced osteogenic responses, suggesting that TLR4 signaling annuls osteogenesis even with TLR2 activity. Interestingly, mutant E. coli LPS that induces weak inflammation upregulated osteogenesis, but SHIP1 was not induced. Moreover, inhibiting SHIP1 significantly upregulated TLR2-mediated inflammatory response and downmodulated osteogenesis. In conclusion, these results suggest that induction of weak inflammatory response through TLR2 (with SHIP1 activity) and mutant TLR4 ligands could enhance osteogenesis. 展开更多
关键词 TLR signaling that induces weak inflammatory response and SHIP1 enhances osteogenic functions SHIP FIGURE
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THE SENSITIVITY OF RESPONSE SIGNAL OF SPECTROELECTROCHEMISTRY(SEC)
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作者 Yuan Bao ZHU Qing Ji XIE +1 位作者 Lian Hong CHEN Shuang E HE Department of Chemistry and Chemical Engineering, Hunan University, Changsha 410082. 《Chinese Chemical Letters》 SCIE CAS CSCD 1992年第6期465-466,共2页
In this paper, we propose the use of the molar absorbance/ potential ratio to measure quantitatively the sensitivity of response signal of SEC cell and the system under study. A simple equation was developed, and the ... In this paper, we propose the use of the molar absorbance/ potential ratio to measure quantitatively the sensitivity of response signal of SEC cell and the system under study. A simple equation was developed, and the major factors influencing the sensitivity were also assessed. The results obtained this way were in good agreement with actual cases. 展开更多
关键词 SEC THE SENSITIVITY OF RESPONSE signal OF SPECTROELECTROCHEMISTRY LENGTH
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Effects of Shenling Baizhu powder on endoplasmic reticulum stress related signaling pathway in liver tissues of nonalcoholic fatty liver disease rats
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作者 Ling Jin Mao-Xing Pan +4 位作者 Yuan-Jun Deng Xue-Hua Luo Li Han Yu-Pei Zhang Qin-He Yang 《Traditional Medicine Research》 2022年第1期21-27,共7页
Background:According to our previous studies,Shenling Baizhu powder has an excellent preventive and therapeutic effect on nonalcoholic fatty liver disease,but the prevention mechanism is still not clear.In this study,... Background:According to our previous studies,Shenling Baizhu powder has an excellent preventive and therapeutic effect on nonalcoholic fatty liver disease,but the prevention mechanism is still not clear.In this study,we intended to explore the effects of Shenling Baizhu powder on the endoplasmic reticulum stress related signaling pathway in nonalcoholic fatty liver disease rats’liver tissues.Methods:After 16 weeks,the levels of serum total cholesterol,triglyceride,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,alanine transaminase and aspartate transaminase were evaluated by an automatic biochemical analyzer,and the levels of serum free fatty acid and hepatic total cholesterol and triglyceride were evaluated by commercial kits.Then,histological changes of the liver were observed by hematoxylin and eosin and oil red-O staining.Protein expression related to the liver unfolded protein response signalling pathway was assessed using Western blot analysis.Results:The results showed that Shenling Baizhu powder supplementation reduced serum total cholesterol,triglyceride,free fatty acid,alanine transaminase,and aspartate transaminase(P<0.05 or P<0.01),as well as the levels of hepatic total cholesterol and triglyceride(P<0.01).Pathological examination showed that Shenling Baizhu powder improved hepatic steatosis and lipid accumulation.The results of biochemical parameters and histological changes indicated that Shenling Baizhu powder administration exerted protective effects against nonalcoholic fatty liver disease.In addition,Shenling Baizhu powder decreased the protein expression levels of binding immunoglobulin protein,activating transcription factor 6,phosphorylation of eukaryotic initiation factor 2 alpha,protein kinase RNA-like endoplasmic reticulum kinase and X-box binding protein 1s in the liver(P<0.05 or P<0.01).Conclusion:Shenling Baizhu powder can ameliorate high-fat diet-induced liver lipid metabolism disorder in nonalcoholic fatty liver disease rats.The mechanisms may be related to the inhibition of the expression of proteins related to unfolded protein response signaling pathways in endoplasmic reticulum stress. 展开更多
关键词 nonalcoholic fatty liver disease Shenling Baizhu powder endoplasmic reticulum stress unfolded protein response signaling pathways
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Insights into plant salt stress signaling and tolerance
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作者 Huapeng Zhou Haifan Shi +5 位作者 Yongqing Yang Xixian Feng Xi Chen Fei Xiao Honghui Lin Yan Guo 《Journal of Genetics and Genomics》 SCIE CAS CSCD 2024年第1期16-34,共19页
Soil salinization is an essential environmental stressor,threatening agricultural yield and ecological security worldwide.Saline soils accumulate excessive soluble salts which are detrimental to most plants by limitin... Soil salinization is an essential environmental stressor,threatening agricultural yield and ecological security worldwide.Saline soils accumulate excessive soluble salts which are detrimental to most plants by limiting plant growth and productivity.It is of great necessity for plants to efficiently deal with the adverse effects caused by salt stress for survival and successful reproduction.Multiple determinants of salt tolerance have been identified in plants,and the cellular and physiological mechanisms of plant salt response and adaption have been intensely characterized.Plants respond to salt stress signals and rapidly initiate signaling pathways to re-establish cellular homeostasis with adjusted growth and cellular metabolism.This review summarizes the advances in salt stress perception,signaling,and response in plants.A better under-standing of plant salt resistance will contribute to improving crop performance under saline conditions using multiple engineering approaches.The rhizosphere microbiome-mediated plant salt tolerance as well as chemical priming for enhanced plant salt resistance are also discussed in this review. 展开更多
关键词 Salt stress Salt perception Salt response and signaling Plant salt tolerance Chemical priming Rhizosphere microbiome
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Dynamic range and linearity improvement for zero-field single-beam atomic magnetometer 被引量:1
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作者 尹凯峰 陆吉玺 +3 位作者 逯斐 李博 周斌权 叶茂 《Chinese Physics B》 SCIE EI CAS CSCD 2022年第11期284-290,共7页
Zero-field single-beam atomic magnetometers with transverse parametric modulation for ultra-weak magnetic field detection have attracted widespread attention recently.In this study,we present a comprehensive response ... Zero-field single-beam atomic magnetometers with transverse parametric modulation for ultra-weak magnetic field detection have attracted widespread attention recently.In this study,we present a comprehensive response model and propose a modification method of conventional first harmonic response by introducing the second harmonic correction.The proposed modification method gives improvement in dynamic range and reduction of linearity error.Additionally,our modification method shows suppression of response instability caused by optical intensity and frequency fluctuations.An atomic magnetometer with single-beam configuration is built to compare the performance between our proposed method and the conventional method.The results indicate that our method’s magnetic field response signal achieves a 5-fold expansion of dynamic range from 2 nT to 10 nT,with the linearity error decreased from 5%to 1%.Under the fluctuations of 5%for optical intensity and±15 GHz detuning of frequency,the proposed modification method maintains intensityrelated instability less than 1%and frequency-related instability less than 8%while the conventional method suffers 15%and 38%,respectively.Our method is promising for future high-sensitive and long-term stable optically pumped atomic sensors. 展开更多
关键词 atomic magnetometer dynamic range linearity error response signal stability
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‘Outbreak Gold Standard’Selection to Provide Optimized Threshold for Infectious Diseases Early-alert Based on China Infectious Disease Automated-alert and Response System 被引量:5
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作者 王瑞平 姜永根 +2 位作者 赵根明 郭晓芹 Engelgau Michael 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2017年第6期833-841,共9页
The China Infectious Disease Automated-alert and Response System(CIDARS) was successfully implemented and became operational nationwide in 2008. The CIDARS plays an important role in and has been integrated into the... The China Infectious Disease Automated-alert and Response System(CIDARS) was successfully implemented and became operational nationwide in 2008. The CIDARS plays an important role in and has been integrated into the routine outbreak monitoring efforts of the Center for Disease Control(CDC) at all levels in China. In the CIDARS, thresholds are determined using the ?Mean+2SD? in the early stage which have limitations. This study compared the performance of optimized thresholds defined using the ?Mean +2SD? method to the performance of 5 novel algorithms to select optimal ?Outbreak Gold Standard(OGS)? and corresponding thresholds for outbreak detection. Data for infectious disease were organized by calendar week and year. The ?Mean+2 SD?, C1, C2, moving average(MA), seasonal model(SM), and cumulative sum(CUSUM) algorithms were applied. Outbreak signals for the predicted value(Px) were calculated using a percentile-based moving window. When the outbreak signals generated by an algorithm were in line with a Px generated outbreak signal for each week, this Px was then defined as the optimized threshold for that algorithm. In this study, six infectious diseases were selected and classified into TYPE A(chickenpox and mumps), TYPE B(influenza and rubella) and TYPE C [hand foot and mouth disease(HFMD) and scarlet fever]. Optimized thresholds for chickenpox(P_(55)), mumps(P_(50)), influenza(P_(40), P_(55), and P_(75)), rubella(P_(45) and P_(75)), HFMD(P_(65) and P_(70)), and scarlet fever(P_(75) and P_(80)) were identified. The C1, C2, CUSUM, SM, and MA algorithms were appropriate for TYPE A. All 6 algorithms were appropriate for TYPE B. C1 and CUSUM algorithms were appropriate for TYPE C. It is critical to incorporate more flexible algorithms as OGS into the CIDRAS and to identify the proper OGS and corresponding recommended optimized threshold by different infectious disease types. 展开更多
关键词 outbreak gold standard optimized threshold algorithms early-alert signal China Infectious Disease Automated-alert and Response System
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Reactive oxygen species signaling and stomatal movement in plant responses to drought stress and pathogen attack 被引量:59
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作者 Junsheng Qi Chun-Peng Song +4 位作者 Baoshan Wang Jianmin Zhou Jaakko Kangasjarvi Jian-Kang Zhu Zhizhong Gong 《Journal of Integrative Plant Biology》 SCIE CAS CSCD 2018年第9期805-826,共22页
Stomata, the pores formed by a pair of guard cells, are the main gateways for water transpiration and photosynthetic CO2 exchange, as well as pathogen invasion in land plants. Guard cell movement is regulated by a com... Stomata, the pores formed by a pair of guard cells, are the main gateways for water transpiration and photosynthetic CO2 exchange, as well as pathogen invasion in land plants. Guard cell movement is regulated by a combination of environmental factors, including water status, light, CO2 levels and pathogen attack, as well as endogenous signals, such as abscisic acid and apoplastic reactive oxygen species (ROS). Under abiotic and biotic stress conditions, extracellular ROS are mainly produced by plasma membrane-localized NADPH oxidases, whereas intracellular ROS are produced in multiple organelles. These ROS form a sophisticated cellular signaling network, with the accumulation of apoplastic ROS an early hallmark of stomatal movement. Here, we review recent progress in understanding the molecular mechanisms of the ROS signaling network, primarily during drought stress and pathogen attack. We summarize the roles of apoplastic ROS in regulating stomatal movement, ABA and CO2 signaling, and immunity responses. Finally, we discuss ROS accumulation and communication between organelles and cells. This information provides a conceptual framework for understanding how ROS signaling is integrated with various signaling pathways during plant responses to abiotic and biotic stress stimuli. 展开更多
关键词 ROS Reactive oxygen species signaling and stomatal movement in plant responses to drought stress and pathogen attack ABA
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The“depict”strategy for discovering new compounds in complex matrices:Lycibarbarspermidines as a case
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作者 Chen Han Zhixin Zhang +8 位作者 Zhiyang Feng Chuanjia Zhai Xuejiao Li Yulian Shi Xiang Li Miao Li Ying Wang Gan Luo Xiaoyan Gao 《Journal of Pharmaceutical Analysis》 SCIE CAS 2024年第3期416-426,共11页
The comprehensive detection and identification of active ingredients in complex matrices is a crucial challenge.Liquid chromatography coupled with high-resolution mass spectrometry(LC-HRMS)is the most prominent analyt... The comprehensive detection and identification of active ingredients in complex matrices is a crucial challenge.Liquid chromatography coupled with high-resolution mass spectrometry(LC-HRMS)is the most prominent analytical platform for the exploration of novel active compounds from complex matrices.However,the LC-HRMS-based analysis workflow suffers from several bottleneck issues,such as trace content of target compounds,limited acquisition for fragment information,and uncertainty in interpreting relevant MS2 spectra.Lycibarbarspermidines are vital antioxidant active ingredients in Lycii Fructus,while the reported structures are merely focused on dicaffeoylspermidines due to their low content.To comprehensively detect the new structures of lycibarbarspermidine derivatives,a“depict”strategy was developed in this study.First,potential new lycibarbarspermidine derivatives were designed according to the biosynthetic pathway,and a comprehensive database was established,which enlarged the coverage of lycibarbarspermidine derivatives.Second,the polarity-oriented sample preparation of potential new compounds increased the concentration of the target compounds.Third,the construction of the molecular network based on the fragmentation pathway of lycibarbarspermidine derivatives broadened the comprehensiveness of identification.Finally,the weak response signals were captured by data-dependent scanning(DDA)followed by parallel reaction monitoring(PRM),and the efficiency of acquiring MS2 fragment ions of target compounds was significantly improved.Based on the integrated strategy above,210 lycibarbarspermidine derivatives were detected and identified from Lycii Fructus,and in particular,170 potential new compounds were structurally characterized.The integrated strategy improved the sensitivity of detection and the coverage of low-response components,and it is expected to be a promising pipeline for discovering new compounds. 展开更多
关键词 Mass spectrometric detection Weak response signals Complex matrices Novel lycibarbarspermidines
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Molecular characterization and developmental expression patterns of thyroid hormone receptors(TRs) and their responsiveness to TR agonist and antagonist in Rana nigromaculata 被引量:3
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作者 Qinqin Lou Yinfeng Zhang +4 位作者 Dongkai Ren Haiming Xu Yaxian Zhao Zhanfen Qin Wuji Wei 《Journal of Environmental Sciences》 SCIE EI CAS CSCD 2014年第10期2084-2094,共11页
Considering some advantages of Rana nigromaculata as an experimental species, we propose that this species, like Xenopus laevis, could be used to assay thyroid hormone(TH) signaling disrupting actions. To validate t... Considering some advantages of Rana nigromaculata as an experimental species, we propose that this species, like Xenopus laevis, could be used to assay thyroid hormone(TH) signaling disrupting actions. To validate the utilizability of R. nigromaculata, we investigated the responsiveness of R. nigromaculata to a TH receptor(TR) agonist(T3) and antagonist(amiodarone) by analyzing expression, based on characterizing TR cDNA and developmental expression patterns. With high levels of identity with the corresponding genes in X. laevis, both TRα and TRβ in R. nigromaculata exhibited roughly similar developmental expression patterns to those of X. laevis, in spite of some species-specific differences. Both TRα and TRβ expression had greater changes in the liver and intestine than in the tail and brain during metamorphosis. T3 exposure for 2 days induced more dramatic increases of TRβ expression in stage 27 than in stage34 tadpoles but not in stage 42 tadpoles, showing that the responsiveness of R. nigromaculata to TH decreased with development and disappeared at the onset of metamorphic climax.Corresponding to greater changes of TRβ expression in the liver and intestine than in the tail and brain during metamorphosis, the liver and intestine had higher responsiveness to exogenous T3 than the tail and brain. Amiodarone inhibited T3-induced TRβ expression. Our results show that R. nigromaculata can be used as a model species for assaying TH signaling disrupting actions by analyzing TRβ expression, and intestine tissues at stage 27 are ideal test materials due to high responsiveness and easy accessibility. 展开更多
关键词 Rana nigromaculata Thyroid hormone receptor Thyroid hormone signaling Developmental expression pattern responsiveness
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Radiation effects on scientific CMOS image sensor 被引量:2
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作者 赵元富 刘丽艳 +2 位作者 刘晓会 晋孝峰 李想 《Journal of Semiconductors》 EI CAS CSCD 2015年第11期53-57,共5页
A systemic solution for radiation hardened design is presented. Besides, a series of experiments have been carried out on the samples, and then the photoelectric response characteristic and spectral characteristic bef... A systemic solution for radiation hardened design is presented. Besides, a series of experiments have been carried out on the samples, and then the photoelectric response characteristic and spectral characteristic before and after the experiments have been comprehensively analyzed. The performance of the CMOS image sensor with the radiation hardened design technique realized total-dose resilience up to 300 krad(Si) and resilience to singleevent latch up for LET up to110 Me V cm^2/mg. 展开更多
关键词 CMOS image sensor(APS) dark current dark signal response non-uniformity total dose effects single event effects
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Ab-Induced Insulin Resistance and the Effects of Insulin on the Cholesterol Synthesis Pathway and Ab Secretion in Neural Cells 被引量:6
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作者 Dema Najem Michelle Bamji-Mirza +1 位作者 Ze Yang Wandong Zhang 《Neuroscience Bulletin》 SCIE CAS CSCD 2016年第3期227-238,共12页
Alzheimer's disease(AD) is characterized by amyloid-b(Ab) toxicity,tau pathology,insulin resistance,neuroinflammation,and dysregulation of cholesterol homeostasis,all of which play roles in neurodegeneration.Insu... Alzheimer's disease(AD) is characterized by amyloid-b(Ab) toxicity,tau pathology,insulin resistance,neuroinflammation,and dysregulation of cholesterol homeostasis,all of which play roles in neurodegeneration.Insulin has polytrophic effects on neurons and may be at the center of these pathophysiological changes.In this study,we investigated possible relationships among insulin signaling and cholesterol biosynthesis,along with the effects of Ab42 on these pathways in vitro.We found that neuroblastoma 2a(N2a) cells transfected with the human gene encoding amyloid-b protein precursor(Ab PP)(N2aAb PP) produced Ab and exhibited insulin resistance by reduced p-Akt and a suppressed cholesterol-synthesis pathway following insulin treatment,and by increased phosphorylation of insulin receptor subunit-1 at serine 612(p-IRS-S612) as compared to parental N2 a cells.Treatment of human neuroblastoma SH-SY5 Y cells with Ab42 also increased p-IRS-S612,suggesting that Ab42 is responsible for insulin resistance.The insulin resistance was alleviated when N2a-Ab PP cells were treated with higher insulin concentrations.Insulin increased Ab release from N2 aAb PP cells,by which it may promote Ab clearance.Insulin increased cholesterol-synthesis gene expression in SHSY5 Y and N2 a cells,including 24-dehydrocholesterol reductase(DHCR24) and 3-hydroxy-3-methyl-glutaryl-Co A reductase(HMGCR) through sterol-regulatory element-binding protein-2(SREBP2).While Ab42-treated SH-SY5 Y cells exhibited increased HMGCR expression and c-Jun phosphorylation as pro-inflammatory responses,they also showed down-regulation of neuro-protective/antiinflammatory DHCR24.These results suggest that Ab42 may cause insulin resistance,activate JNK for c-Jun phosphorylation,and lead to dysregulation of cholesterol homeostasis,and that enhancing insulin signaling may relieve the insulin-resistant phenotype and the dysregulated cholesterol-synthesis pathway to promote Ab release for clearance from neural cells. 展开更多
关键词 Alzheimer's disease Insulin resistance Ab peptides Insulin signaling Cholesterol synthesis pathway Pro-inflammatory response
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