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Antitumor and off-target effects of cholesterol-conjugated let-7a mimics in an orthotopic hepatocellular carcinoma xenograft nude mouse model
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作者 Jian Guan Mingyang Liu +9 位作者 Xin Li Liangrui Zhou Xueyu Dong Wei Dai Yu Xia Tao Yang Shaojuan Guo Xingqi Li Yehua Han Yufeng Luo 《Journal of Bio-X Research》 2022年第4期181-196,共16页
Objective: To explore the antitumor and potential off-target effects of systemically delivered cholesterol-conjugatedlet-7a mimics(Chol-let-7a) and control mimics(Chol-miRCtrl) on hepatocellular carcinomain vivo.Metho... Objective: To explore the antitumor and potential off-target effects of systemically delivered cholesterol-conjugatedlet-7a mimics(Chol-let-7a) and control mimics(Chol-miRCtrl) on hepatocellular carcinomain vivo.Methods: The antitumor effects of two intravenous dosing regimens ofChol-let-7a on heptocellular carcinoma growth were compared using an orthotopic xenograft mouse model. Off-targets were analyzed with histopathological and ultrapathological features of heparenal tissue and cells in theChol-let-7a-, Chol-miRCtrl-, and saline-treated (blank) xenograft mice and normal control mice. Then,let-7a abundance in orthotopic tumors, corresponding paracancerous hepatic tissue, and normal liver tissue from healthy nude mice was examined by reverse transcription-polymerase chain reaction. The distribution ofChol-let-7a andChol-miRCtrl in vivo was examined by whole-animal imaging and frozen-sections observation. The experiments were approved by the Institutional Research Board of Peking Union Medical College Hospital.Results: Continuous treatment withChol-let-7a resulted in tumors that were 35.86% and 40.02% the size of those in theChol-miRCtrl and blank xenograft group (P < 0.01 andP < 0.01, respectively), while intermittent dosing withChol-let-7a resulted in tumors that were 65.42% and 56.66% the size of those in theChol-miRCtrl and the blank control group, respectively (P < 0.05 andP < 0.05). In addition, some histopathological and ultrapathological features were only observed after treatment with the two cholesterol-conjugated molecules, however mild with intermittent dosingChol-let-7a treatment, such as diffuse sinusoidal dilation and edema, primarily around the centrolobular vein in heptic tissues;mild hypercellularity with dilated capillary lumens in the renal tissue;and some organelle abnormalities found in heptic and renal cells. Furthermore, whole-animal imaging showed thatChol-let-7a andChol-miRCtrl were predominantly distributed in the liver, kidney, and bladder regions after injection, and that the concentration ofChol-let-7a andChol-miRCtrl in the kidney and the bladder decreased much slowly in the xenograft animals, especially in theChol-miRCtrl group. Finally, RT-PCR analysis showed thatlet-7a levels were significantly increased in Chol-let-7a-treated xenografts compared withChol-miRCtrl group (P=0.003) and blank xenograft group (P=0.001);however, the level was only equivalent to 50.6% and 40.7% of that in paracancerous hepatic tissue and hepatic tissue in normal mice, respectively.Conclusions: Chol-let-7a, administered either continuously or intermittently, showed effective antitumor efficacy.Chol-let-7a had some off-target effects, such as mild acute hepatitis-like inflammation and non-specific drug-induced kidney injury. The intermittent dosing regimen resulted in less damage than the continuous regimen, while maintaining relatively satisfactory antitumor efficacy, which could be useful for the investigation and possible clinical use of miRNA treatment regimens in the future. 展开更多
关键词 drug-induced renal injury hepatic toxicity in vivo off target effects let-7 mimics nonviral delivery vector
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Engineering guide RNA to reduce the off-target effects of CRISPR 被引量:4
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作者 Jing Wu Hao Yin 《Journal of Genetics and Genomics》 SCIE CAS CSCD 2019年第11期523-529,共7页
As versatile and robust genome editing tools,clustered regularly interspaced short palindromic repeats(CRISPR)technologies have been broadly used in basic research,biotechnology,and therapeutic development.Off-target ... As versatile and robust genome editing tools,clustered regularly interspaced short palindromic repeats(CRISPR)technologies have been broadly used in basic research,biotechnology,and therapeutic development.Off-target mutagenesis by CRISPR systems has been demonstrated,and various methods have been developed to markedly increase their specificity.In this review,we highlight the efforts of producing and modifying guide RNA(gRNA)to minimize off-target activities,including sequence and structure design,tuning expression and chemical modification.The modalities of gRNA engineering can be applied across CRISPR systems.In conjunction with CRISPR protein effectors,the engineered gRNA enables efficient and precise genome editing. 展开更多
关键词 CRISPR GENOME EDITING Engineered guide RNA Off-target effects
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Leaf surface factors of transgenic Bt cotton associated with the feeding behaviors of cotton aphids:A case study on non-target effects 被引量:7
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作者 XUE Kun, DENG Su, WANG RongJiang, YAN FengMing, XU ChongRen College of Life Sciences, Peking University, Beijing 100871, China 《Science China(Life Sciences)》 SCIE CAS 2008年第2期145-156,共12页
The present paper reports case study results of the risk assessment of transgenic Bt cotton on a non-target pest, cotton aphid, Aphis gossypii. Several types of techniques, i.e., electrical penetration graph (EPG), li... The present paper reports case study results of the risk assessment of transgenic Bt cotton on a non-target pest, cotton aphid, Aphis gossypii. Several types of techniques, i.e., electrical penetration graph (EPG), light and electron microscopy, bioassays and chemical analysis, were applied to investigate physical and chemical leaf factors of 2 transgenic Bt cotton lines (GK12 and GK19) and their pa-rental non-Bt cotton line (Simian3) associated with searching and feeding behaviors of cotton aphids on leaves or leaf extracts of cotton plants. EPG results showed that there were some differences among behaviors of cotton aphids on 2 Bt cotton and 1 non-Bt cotton lines. Cotton aphids performed similarly to leaf surface extracts from 3 cotton lines; and leaf surface chemicals, mainly volatiles and waxes, were almost identical in the components and concentrations among the cotton lines. However, three cotton lines were quite different from each other in the densities of certain kinds of covering trichomes. Therefore, the relationships between the physical characteristics and the searching behaviors of cotton aphids on the three cotton lines were constructed as the regression equations. Glandular trichomes and covering trichomes with 5 branches influenced the cotton aphids' searching behaviors effectively; and other trichomes with other branches affected aphids in varying ways. These results demonstrated that leaf surface physical factors of transgenic Bt cotton lines different from their parental non-Bt line could affect the penetration behaviors of non-target cotton aphids. Cotton aphids penetrate and feed more easily on two Bt cotton lines than on the non-Bt cotton line. 展开更多
关键词 Bt cotton TRICHOME LEAF surface chemicals APHIS GOSSYPII SEARCHING behavior EPG electrical penetration graph non-target effect
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Design and operation strategies of the system for destroying time-sensitive target based on system effectiveness 被引量:2
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作者 Chen Jun Gao Xiaoguang Ding Lin 《Journal of Systems Engineering and Electronics》 SCIE EI CSCD 2008年第6期1151-1156,共6页
To improve the effect of destroying time-sensitive target (TST), a method of operational effectiveness evaluation is presented and some influential factors are analyzed based on the combat flow of system for destroy... To improve the effect of destroying time-sensitive target (TST), a method of operational effectiveness evaluation is presented and some influential factors are analyzed based on the combat flow of system for destroying TST. Considering the possible operation modes of the system, a waved operation mode and a continuous operation mode are put forward at first. At the same time, some relative formulas are modified. In examples, the influential factors and operation modes are analyzed based on the system effectiveness. From simulation results, some design and operation strategies of the system for destroying time sensitive targets are concluded, which benefit to the improvement of the system effectiveness. 展开更多
关键词 effectiveness evaluation time-sensitive target waved operation mode continuous operation mode
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采用蛋白组学技术分析质粒介导siRNA的“Off-target”效应 被引量:1
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作者 周昌华 章崇杰 +2 位作者 彭晓东 魏大鹏 王光迪 《中国生物化学与分子生物学报》 CAS CSCD 北大核心 2010年第2期170-180,共11页
siRNA的"脱靶效应"(off-target effects)是RNA干扰应用研究领域的热点问题.采用蛋白组学技术对质粒介导的siRNA稳定沉默原癌基因c-myc可能存在的"off-target"效应进行初步研究,为siRNA靶向特异性的系统评价奠定理... siRNA的"脱靶效应"(off-target effects)是RNA干扰应用研究领域的热点问题.采用蛋白组学技术对质粒介导的siRNA稳定沉默原癌基因c-myc可能存在的"off-target"效应进行初步研究,为siRNA靶向特异性的系统评价奠定理论与实验基础.构建靶向c-myc的siRNA真核表达质粒p-Mat01-1及其错配质粒p-Mis09-1,空质粒pEGFP-C1为对照,并稳定转染MCF-7人乳腺癌细胞.通过RT-PCR和Western印迹分析结果显示p-Mat01-1稳定转染克隆中c-myc/c-MYC的表达降低.采用2-DE及LC-ESI-MS/MS等方法,研究了p-Mat01-1与pEGFP-C1稳定转染克隆的蛋白组表达差异.结果显示,p-Mat01-1稳定转染克隆中有47个c-myc非调控蛋白点表达升高或降低,约占423个随机检测蛋白点的11.1%.这些蛋白涉及细胞骨架、代谢、增殖、信号传导、分子伴侣、氧化还原等多条途径.实验结果表明,质粒介导靶向c-myc的siRNA在MCF-7细胞中存在明显的"off-target"效应,提示在设计siRNA实验及应用研究时应系统考察其靶向特异性. 展开更多
关键词 C-MYC RNA干扰 小干扰RNA 脱靶效应 蛋白组学
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Impact Assessments of Transgenic cry1Ab Rice on the Population Dynamics of Five Non-Target Thrips Species and Their General Predatory Flower Bug in Bt and Non-Bt Rice Fields Using Color Sticky Card Traps 被引量:9
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作者 Akhtar Zunnu Raen YE Gong-yin +4 位作者 LU Zeng-bin CHANG Xue SHEN Xiao-jing PENG Yu-fa HU Cui 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2013年第10期1807-1815,共9页
A 2-yr field study was conducted to assess the effects of transgenic japonica rice(KMD1 and KMD2) with a synthetic cry1 Ab gene from Bacillus thuingiensis Berliner on population dynamics and seasonal average densiti... A 2-yr field study was conducted to assess the effects of transgenic japonica rice(KMD1 and KMD2) with a synthetic cry1 Ab gene from Bacillus thuingiensis Berliner on population dynamics and seasonal average densities of five thrips species including Stenchaetothrips biformis(Bagnall),Frankliniella intonsa(Trybom),F.tenuicornis(Uzel),Haplothrips aculeatus(Fabricius),Haplothrips tritici(Kurd) and their general predatory flower bug,Orius similis Zheng as compared to the parental control rice line using the white,blue and yellow sticky card traps.Population dynamics and seasonal average densities of these five thrips species and their general predatory flower bug were not significantly affected by rice type.Additionally,the white sticky card trap was suggested to be the most suitable for monitoring the population of these five thrips species and their general predator.These results show that our tested Bt rice lines do not interrupt the population of non-target thrips species and their general predatory flower bug in the field,and also cannot result in more occurrence of these thrips species in the rice ecosystem. 展开更多
关键词 rice thrips predatory flower bug non-target effects Bt rice risk assessment
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Electroacupuncture pretreatment exhibits antidepressive effects by regulating hippocampal proteomics in rats with chronic restraint stress 被引量:8
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作者 Zhuo Guo Ya Tu +7 位作者 Tian-wei Guo Yun-chu Wu Xue-qin Yang Lan Sun Xin-jing Yang Wen-yue Zhang Yu Wang Xu-hui Zhang 《Neural Regeneration Research》 SCIE CAS CSCD 2015年第8期1298-1304,共7页
The clinical effect of electroacupuncture on depression is widely recognized. However, the signal transduction pathways and target proteins involved remain unclear. In the present study, rat models of chronic restrain... The clinical effect of electroacupuncture on depression is widely recognized. However, the signal transduction pathways and target proteins involved remain unclear. In the present study, rat models of chronic restraint stress were used to explore the mechanism by which electroacupuncture alleviates depression. Rats were randomly divided into control, model, and electroacupuncture groups. Chronic restraint stress was induced in the model and electroacupuncture groups by restraining rats for 28 days. In the electroacupuncture group, electroacupuncture pretreatment at Baihui(GV20) and Yintang(GV29) acupoints was performed daily(1 m A, 2 Hz, discontinuous wave, 20 minutes) prior to restraint for 28 days. Open field tests and body weight measurements were carried out to evaluate the depressive symptoms at specific time points. On day 28, the crossing number, rearing number, and body weights of the model group were significantly lower than those in the control group. Behavior test results indicated that rat models of depressive-like symptoms were successfully established by chronic restraint stress combined with solitary raising. On day 28, an isobaric tag for a relative and absolute quantitation-based quantitative proteomic approach was performed to identify differentially expressed proteins in hippocampal samples obtained from the model and electroacupuncture groups. The potential function of these differential proteins was predicted through the use of the Cluster of Orthologous Groups of proteins(COG) database. Twenty-seven differential proteins(uncharacteristic proteins expected) were selected from the model and electroacupuncture groups. In addition to unknown protein functions, COG are mainly concentrated in general prediction function, mechanism of signal transduction, amino acid transport and metabolism groups. This suggests that electroacupuncture improved depressive-like symptoms by regulating differential proteins, and most of these related proteins exist in nerve cells. 展开更多
关键词 nerve regeneration traditional Chinese medicine electroacupuncture depression chronic restraint stress i TRAQ differential protein proteomics multi-target effect neural regeneration
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Thrips-mediated impacts from transgenic rice expressing Cry1Ab on ecological fitness of non-target predator Orius tantilus(Hemiptera:Anthocoridae)
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作者 Akhtar Zunnu Raen DANG Cong +2 位作者 WANG Fang PENG Yu-fa YE Gong-yin 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2016年第9期2059-2069,共11页
Various rice lines have been genetically modified with genes from Bacillus thuringiensis(Bt) to continuously produce Bt insecticidal proteins against lepidopteran larvae. The Bt insecticidal protein constantly expre... Various rice lines have been genetically modified with genes from Bacillus thuringiensis(Bt) to continuously produce Bt insecticidal proteins against lepidopteran larvae. The Bt insecticidal protein constantly expresses in the plants to create an opportunity for non-target herbivores to acquire and convey the protein to their predators or parasitoids across trophic levels. This paper evaluates the effects of Bt rice(namely, Kemindao 1(KMD1) and Kemindao 2(KMD2)) expressing Cry1 Ab as compared to its non-Bt control line, Xiushui 11 on non-target predator Orius tantilus(a generalist predatory anthocorid of thrips) under laboratory and field conditions. To measure several biological parameters such as total nymphal duration and fecundity of this bug, it was reared on thrips and pollens of KMD1 and KMD2 as compared to their control under laboratory conditions. By comparison with the control, Bt rice did not significantly affect main life-history characteristics(total nymphal duration, female adult longevity, oviposition period and fecundity) of this anthocorid preying on Bt rice-fed thrips along with Bt rice pollens, except that the fecundity of this predator for KMD1 was distinctly lower as compared with KMD2 or the control. Enzyme-linked immunosorbent assay(ELISA) results showed that no Cry1 Ab protein was detected in this predator fed on thrips or rice pollen from Bt rice but was in Bt rice pollens. With the beat plate, plastic bag and color trap sampling methods, two-year field monitoring of O. tantilus abundance demonstrated that Bt rice had no significant detrimental effects on the population dynamics and seasonal average densities of this predatory anthocorid as compared with the control. Thus, it is suggested that growing our tested Bt rice(KMD1 and KMD2) producing Cry1 Ab will pose a negligible risk to the anthocorid, O. tantilus. 展开更多
关键词 Orius tantilus Btrice Cry1Ab risk assessment non-target effects
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Long-term acupuncture treatment has a multitargeting regulation on multiple brain regions in rats with Alzheimer's disease:a positron emission tomography study 被引量:3
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作者 Yang-jia Lu Xiao-wen Cai +9 位作者 Gui-feng Zhang Yong Huang Chun-zhi Tang Bao-ci Shan Shao-yang Cui Jun-qi Chen Shan-shan Qu Zheng Zhong Xin-sheng Lai Genevieve Zara Steiner 《Neural Regeneration Research》 SCIE CAS CSCD 2017年第7期1159-1165,共7页
The acute effect of acupuncture on Alzheimer's disease,i.e.,on brain activation during treatment,has been reported.However,the effect of long-term acupuncture on brain activation in Alzheimer's disease is unclear.Th... The acute effect of acupuncture on Alzheimer's disease,i.e.,on brain activation during treatment,has been reported.However,the effect of long-term acupuncture on brain activation in Alzheimer's disease is unclear.Therefore,in this study,we performed long-term needling at Zusanli(ST36)or a sham point(1.5 mm lateral to ST36)in a rat Alzheimer's disease model,for 30 minutes,once per day,for 30 days.The rats underwent 18F-fluorodeoxyglucose positron emission tomography scanning.Positron emission tomography images were processed with SPM2.The brain areas activated after needling at ST36 included the left hippocampus,the left orbital cortex,the left infralimbic cortex,the left olfactory cortex,the left cerebellum and the left pons.In the sham-point group,the activated regions were similar to those in the ST36 group.However,the ST36 group showed greater activation in the cerebellum and pons than the sham-point group.These findings suggest that long-term acupuncture treatment has targeted regulatory effects on multiple brain regions in rats with Alzheimer's disease. 展开更多
关键词 nerve regeneration NEURODEGENERATION ACUPUNCTURE Zusanli (ST36) Alzheimer's disease long-term treatment positron emissiontomography rat mechanism targeting effect compensation multi-target regulation neural regeneration
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An Air Defense Weapon Target Assignment Method Based on Multi-Objective Artificial Bee Colony Algorithm 被引量:2
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作者 Huaixi Xing Qinghua Xing 《Computers, Materials & Continua》 SCIE EI 2023年第9期2685-2705,共21页
With the advancement of combat equipment technology and combat concepts,new requirements have been put forward for air defense operations during a group target attack.To achieve high-efficiency and lowloss defensive o... With the advancement of combat equipment technology and combat concepts,new requirements have been put forward for air defense operations during a group target attack.To achieve high-efficiency and lowloss defensive operations,a reasonable air defense weapon assignment strategy is a key step.In this paper,a multi-objective and multi-constraints weapon target assignment(WTA)model is established that aims to minimize the defensive resource loss,minimize total weapon consumption,and minimize the target residual effectiveness.An optimization framework of air defense weapon mission scheduling based on the multiobjective artificial bee colony(MOABC)algorithm is proposed.The solution for point-to-point saturated attack targets at different operational scales is achieved by encoding the nectar with real numbers.Simulations are performed for an imagined air defense scenario,where air defense weapons are saturated.The non-dominated solution sets are obtained by the MOABC algorithm to meet the operational demand.In the case where there are more weapons than targets,more diverse assignment schemes can be selected.According to the inverse generation distance(IGD)index,the convergence and diversity for the solutions of the non-dominated sorting genetic algorithm III(NSGA-III)algorithm and the MOABC algorithm are compared and analyzed.The results prove that the MOABC algorithm has better convergence and the solutions are more evenly distributed among the solution space. 展开更多
关键词 Weapon target assignment multi-objective artificial bee colony air defense defensive resource loss total weapon consumption target residual effectiveness
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No detrimental effect of Bt maize pollen containing Cry1Ab/2Aj or Cry1Ac on adult green lacewings Chrysoperla sinica Tjeder 被引量:1
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作者 LIU Yan-min LI Yun-he +3 位作者 CHEN Xiu-ping SONG Xin-yuan SHEN Ping PENG Yu-fa 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2019年第4期893-899,共7页
Adult Chrysoperla sinica Tjeder is a common pollen feeder in maize fields. They are thus directly exposed to insecticidal proteins by consumption of genetically engineered maize pollen containing Bacillus thuringiensi... Adult Chrysoperla sinica Tjeder is a common pollen feeder in maize fields. They are thus directly exposed to insecticidal proteins by consumption of genetically engineered maize pollen containing Bacillus thuringiensis(Bt) proteins. Here we assessed the potential effects of Cry1 Ab/2 Aj-or Cry1 Ac-containing Bt maize pollen on the fitness of adult C. sinica via a dietary-exposure assay under laboratory conditions. Survival, pre-oviposition, fecundity and adult dry weight did not differ between adult C. sinica consuming Bt or the corresponding non-Bt maize pollen. The stability of the Cry protein in the food sources and uptake of the Cry protein by adult C. sinica during the feeding experiment were confirmed by ELISA. These results demonstrate that adult C. sinica are not affected by the consumption of Cry1 Ab/2 Aj-or Cry1 Ac-containing maize pollen, suggesting that production of Bt maize expressing cry1 Ab/2 Aj or cry1 Ac genes will pose a negligible risk to adult C. sinica. 展开更多
关键词 non-target effect environmental risk assessment ELISA DIETARY exposure ASSAY
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EPR Effect of Amphiphilic Copolymer Micelles Observed by Fluorescent Imaging 被引量:4
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作者 LIU Tong-jun LIU Shi +3 位作者 HU Xiu-li SHENG Shi-hou HUANG Yu-bin JING Xia-bin 《Chemical Research in Chinese Universities》 SCIE CAS CSCD 2011年第4期628-634,共7页
Enhanced permeation and retention(EPR) targeting effect of rhodamine B labeled PEG-b-P(LA-co-DHP) [PEG:poly(ethylene glycol);LA:L-lactide;DHP:2,2-dihydroxylmethyl-propylene carbonate] micelles(RhB-micelles)... Enhanced permeation and retention(EPR) targeting effect of rhodamine B labeled PEG-b-P(LA-co-DHP) [PEG:poly(ethylene glycol);LA:L-lactide;DHP:2,2-dihydroxylmethyl-propylene carbonate] micelles(RhB-micelles) was observed in H22 liver cancer bearing mice.The RhB-micelles were prepared by conjugating rhodamine B with the DHP units of amphiphilic block copolymer PEG-b-P(LA-co-DHP) followed by subsequent self-assembling of the conjugate.The parent copolymer PEG-b-P(LA-co-DHP) was synthesized by ring-opening copolymerization of LA and DHP with PEG as macroinitiator and diethyl zinc(ZnEt2) as catalyst.The micelles have a spherical shape and the average diameter is ca.50 nm by TEM(transmission electron microscope) or 80 nm by DLS(dynamic light scattering).Their in vitro cell uptake experiment by CLSM(confocal laser scanning microscopy) and flow cytometry showed preferential internalization of micelles by MCF-7 human breast cancer cells to free RhB.The in vivo tests by live animal imaging and ex vivo excised organ imaging showed that after vena tail injection,free RhB molecules were distributed in the whole body through the circulation system and then gradually metabolized and excreted and there was no preferential partition in tumor bed from the beginning to the end.But the RhB-micelles were preferentially distributed to the tumor bed so that their concentration(fluorescent intensity) in tumor bed got the level of the liver at a certain time point between 1 and 6 h and reached a maximum relative intensity at around 12 h,indicating an obvious EPR effect of RhB-micelles in H22 liver cancer. 展开更多
关键词 Enhanced permeability and retention(EPR) effect Fluorescent imaging MICELLE Passive targeting
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Novel antidepressants targeting TREK1 channel
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作者 LUO Qi-chao CHEN Li-ping +5 位作者 CHENG Xi MA Yu-qin LI Xiao-na ZHANG Shi-lei LI Yang YANG Huai-yu 《中国药理学与毒理学杂志》 CAS CSCD 北大核心 2018年第9期729-730,共2页
OBJECTIVE To find that the extracellular cap of a K2P channel can act as a new allosteric site and may serve as a direct drug target.METHODS Molecular biology and cell transfection,electrophysiology,molecular docking,... OBJECTIVE To find that the extracellular cap of a K2P channel can act as a new allosteric site and may serve as a direct drug target.METHODS Molecular biology and cell transfection,electrophysiology,molecular docking,molecular dynamics simulations,virtual screening for TREK1,and depressive-related behavior tests.RESULTS Extracellular domain of TREK1 channel existed a dynamic cavity in the extracellular domain by the method of computations,mutagenesis and electrophysiology.Molecular dynamics simulations suggested that ligand-induced allosteric conformational transitions lead to blockage of the ion conductive pathway.Using virtual screening approach,we identified other inhibitors targeting the extracellular allosteric ligand-binding site of these channels.Overall,our results suggested that the allosteric site at the extracellular cap of the K2P channels might be a promising drug target for these membrane proteins.The TREK1 inhibitor TKDC had significantly faster onset than that of fluoxetine in chronic administration trials,and the study confirms that TREK1 was an important target for the development of rapid antidepressants.CONCLUSION The study is a significant step forward for understanding the function of TREK and for identifying specific inhibitors,which should be of interest to others in the field. 展开更多
关键词 POTASSIUM CHANNELS target identification TREK1 INHIBITOR ANTIDEPRESSANT effect
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基于高分辨一维距离像及其特征的空间目标识别效果分析 被引量:1
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作者 王放 韩晓磊 张延鑫 《电讯技术》 北大核心 2024年第3期465-469,共5页
目标高分辨一维距离像(High Resolution Range Profile,HRRP)中包含了丰富的目标尺寸、结构等目标特征,是进行空间目标身份识别的有效途径。但由于卫星宽带雷达实测数据获取难度大,前期相关研究多集中于基于HRRP的目标识别算法,结论也... 目标高分辨一维距离像(High Resolution Range Profile,HRRP)中包含了丰富的目标尺寸、结构等目标特征,是进行空间目标身份识别的有效途径。但由于卫星宽带雷达实测数据获取难度大,前期相关研究多集中于基于HRRP的目标识别算法,结论也多是基于仿真数据和少量类别(几类)的前提下得到的,与工程应用实际情况有较大差距,工程指导意义有限。为解决这一问题,基于地基雷达获取的30类卫星目标的大量一维距离像实测数据,从识别正确率的角度对目标HRRP及其特征(组合)的可分性和在空间目标个体识别中的应用效果进行了量化分析,分析结果可为后续基于HRRP的空间目标个体识别技术研究和工程应用提供可靠依据。 展开更多
关键词 空间目标 高分辨率一维距离像(HRRP) 目标识别 识别效果分析
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Contribution of mammalian target of rapamycin in the pathophysiology of cirrhotic cardiomyopathy
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作者 Seyed Soheil Saeedi Saravi Mahmoud Ghazi-Khansari +3 位作者 Shahram Ejtemaei Mehr Maliheh Nobakht Seyyedeh Elaheh Mousavi Ahmad Reza Dehpour 《World Journal of Gastroenterology》 SCIE CAS 2016年第19期4685-4694,共10页
AIM: To explore the role of mammalian target of rapamycin(m TOR) in the pathogenesis of cirrhotic cardiomyopathy and the potential of rapamycin to improve this pathologic condition.METHODS: Male albino Wistar rats wei... AIM: To explore the role of mammalian target of rapamycin(m TOR) in the pathogenesis of cirrhotic cardiomyopathy and the potential of rapamycin to improve this pathologic condition.METHODS: Male albino Wistar rats weighing 100-120 g were treated with tetrachloride carbon(CCl_4) for 8 wk to induce cirrhosis. Subsequently, animals were administered rapamycin(2 mg/kg per day). The QT_c intervals were calculated in a 5-min electrocardiogram. Then, the left ventricular papillary muscles wereisolated to examine inotropic responsiveness to β-adrenergic stimulation using a standard organ bath equipped by Powerlab system. Phosphorylated-m TOR localization in left ventricles was immunohistochemically assessed, and ventricular tumor necrosis factor(TNF)-α was measured. Western blot was used to measure levels of ventricular phosphorylated-m TOR protein.RESULTS: Cirrhosis was confirmed by hematoxylin and eosin staining of liver tissues, visual observation of lethargy, weight loss, jaundice, brown urine, ascites, liver stiffness, and a significant increase of spleen weight(P < 0.001). A significant prolongation in QTc intervals occurred in cirrhotic rats exposed to CCl_4(P < 0.001), while this prolongation was decreased with rapamycin treatment(P < 0.01). CCl_4-induced cirrhosis caused a significant decrease of contractile responsiveness to isoproterenol stimulation and a significant increase in cardiac TNF-α. These findings were correlated with data from western blot and immunohistochemical studies on phosphorylated-m TOR expression in left ventricles. Phosphorylated-m TOR was significantly enhanced in cirrhotic rats, especially in the endothelium, compared to controls. Rapamycin treatment significantly increased contractile force and myocardial localization of phosphorylated-m TOR and decreased cardiac TNF-α concentration compared to cirrhotic rats with no treatment. CONCLUSION: In this study, we demonstrated a potential role for cardiac m TOR in the pathophysiology of cirrhotic cardiomyopathy. Rapamycin normalized the inotropic effect and altered phosphorylated-m TOR expression and myocardial localization in cirrhotic rats. 展开更多
关键词 Cirrhotic CARDIOMYOPATHY Rat MAMMALIAN target of RAPAMYCIN RAPAMYCIN INOTROPIC effect
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糖尿病中医治疗切入点的探讨与思考
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作者 牟新 刘超 《实用医学杂志》 CAS 北大核心 2024年第16期2211-2218,共8页
本文对中医学在糖尿病治疗领域的切入点进行探讨,提出了从中医对糖尿病及其并发症病因病机的独到认识、糖尿病前期的治疗、改善糖尿病患者的临床症状、糖尿病并发症的治疗、改善药物不良反应、历代经典方剂和治疗有效的药物挖掘、中医... 本文对中医学在糖尿病治疗领域的切入点进行探讨,提出了从中医对糖尿病及其并发症病因病机的独到认识、糖尿病前期的治疗、改善糖尿病患者的临床症状、糖尿病并发症的治疗、改善药物不良反应、历代经典方剂和治疗有效的药物挖掘、中医药治疗手段的多样性等几个方向作为切入点。与现代医学既可以优势互补,又能扬长避短。中医药有着整体调节、多靶点作用的特点,在改善症状、治疗并发症和伴发疾病方面的优势更加明显。 展开更多
关键词 糖尿病 中医药 多靶点作用 伴发疾病
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Numerical study of size effect in concrete penetration with LDPM 被引量:2
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作者 Jun Feng Wei-wei Sun Bao-ming Li 《Defence Technology(防务技术)》 SCIE EI CAS CSCD 2018年第5期560-569,共10页
Projectile size effect is of great importance since the scaling researches are extensively applied to concrete penetration investigations. This paper numerically deals with the projectile size effect on penetration re... Projectile size effect is of great importance since the scaling researches are extensively applied to concrete penetration investigations. This paper numerically deals with the projectile size effect on penetration resistance via the recently developed Lattice Discrete Particles Model(LDPM) which is featured with mesoscale constitutive laws governing the interaction between adjacent particles to account for cohesive fracture, strain hardening in compression and compaction due to pore collapse. Simulations of two different penetration tests are carried to shed some light on the size effect issue. The penetration numerical model is validated by matching the projectile deceleration curve of and predicting the depth of penetration(DOP). By constant velocity penetration simulations, the target resistance is found to be dependent on the projectile size. By best fitting numerical results of constant velocity penetration, a size effect law for target resistance is proposed and validated against literature data. Moreover, the size effect is numerically obtained in the projectile with longer extended nose part meanwhile the shorter extended nose is found to improve the DOP since the projectile nose is sharpened. 展开更多
关键词 PENETRATION of CONCRETE Size effect LATTICE discrete particle model target resistance ABNORMAL NOSE PROJECTILE
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社会建构、反馈效应与延迟退休年龄政策停滞 被引量:1
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作者 郭磊 白晨 《广西师范大学学报(哲学社会科学版)》 CSSCI 2024年第2期75-88,共14页
党的十八届三中全会以来,我国屡次提出研究和制定“渐进式延迟退休年龄政策”的方针策略,然时至今日,全国性的延迟退休政策尚未出台。以社会建构与政策设计理论为理论基础与分析框架,以1951—2021年54份中央政府文件为样本,考察目标群... 党的十八届三中全会以来,我国屡次提出研究和制定“渐进式延迟退休年龄政策”的方针策略,然时至今日,全国性的延迟退休政策尚未出台。以社会建构与政策设计理论为理论基础与分析框架,以1951—2021年54份中央政府文件为样本,考察目标群体的社会建构如何通过反馈效应影响延迟退休年龄政策进程,研究发现:干部和高级专业技术人员被正面建构且因政策受益,产生正反馈,政策长期仅适用于该群体,普通劳动者被正面建构但因政策受损,产生负反馈,以致全国性政策无法出台,政策陷入停滞;而正反馈效应长期积累促使社会建构转向,社会环境因素改变政策认知,进而推动政策进程。因此,政策制定者坚定决心,不断优化政策设计,回应目标群体的社会建构转向;党和中央政府以积极应对人口老龄化战略吸纳延迟退休年龄政策,塑造公众政策认知;地方政府积极开展政策试验,总结经验教训,这些措施都有助于加快政策进程。 展开更多
关键词 老龄化 延迟退休年龄 社会建构 反馈效应 目标群体 政策进程
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5-Fluorocytosine–Sugar Conjugates for Glucose Transporter-Mediated Tumor Targeting: Synthesis, Cytotoxicity, and Cellular Uptake Mechanism 被引量:1
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作者 Yu Wang Xiaofei Cheng +1 位作者 Hongxia Zhao Qingzhi Gao 《Transactions of Tianjin University》 EI CAS 2019年第6期611-617,共7页
Two novel sugar-conjugated 5-fluorocytosine(5-FC)antineoplastic compounds were designed and synthesized to improve the selective drug uptake by targeting the tumor-specific glucose transporter(GLUT).The antitumor acti... Two novel sugar-conjugated 5-fluorocytosine(5-FC)antineoplastic compounds were designed and synthesized to improve the selective drug uptake by targeting the tumor-specific glucose transporter(GLUT).The antitumor activity of these compounds was evaluated in four different human cancer cell lines:A549(human lung cancer cell line),HT29(human colorectal cancer cell line),H460(human lung cancer cell line),and PC3(human prostate cancer cell line).The sugar conjugates exhibited cytotoxicity similar to or higher than 5-FC and 1-hexylcarbamoyl-5-FC in A549,HT29,H460,and PC3.Furthermore,GLUT-mediated transport of the glycoconjugate was investigated with GLUT inhibitor-mediated cytotoxicity analysis in a GLUT-overexpressing HT29 cell line.The cell-killing potency of 5-FC glycoconjugate was found to depend significantly on the GLUT inhibitor,and the cellular uptake of molecules was regulated by GLUT-mediated transport.All the results demonstrate the potential advantages of glycoconjugation for Warburg effect-targeted drug design. 展开更多
关键词 WARBURG effect Glucose TRANSPORTER overexpressed 5-FLUOROCYTOSINE GLYCOCONJUGATE Tumor targeting
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针对性护理干预在腹腔镜下全子宫切除术中的应用效果 被引量:1
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作者 李思思 《中外医学研究》 2024年第9期76-79,共4页
目的:分析针对性护理干预应用于腹腔镜下全子宫切除术中的效果。方法:选取2022年3月—2023年3月滨州医学院附属医院收治的80例择期行腹腔镜下全子宫切除术患者作为研究对象。随机分为研究组和对照组,各40例。对照组采用常规护理,研究组... 目的:分析针对性护理干预应用于腹腔镜下全子宫切除术中的效果。方法:选取2022年3月—2023年3月滨州医学院附属医院收治的80例择期行腹腔镜下全子宫切除术患者作为研究对象。随机分为研究组和对照组,各40例。对照组采用常规护理,研究组在对照组护理基础上进行针对性护理。比较两组术后恢复情况、护理满意度及并发症发生率等。结果:研究组住院时间短于对照组,首次下床时间早于对照组,差异有统计学意义(P<0.05)。干预后,两组抑郁自评量表(SDS)评分、焦虑自评量表(SAS)评分均低于干预前,且研究组低于对照组,差异有统计学意义(P<0.05)。研究组护理总满意度显著高于对照组,差异有统计学意义(P<0.05)。研究组并发症总发生率低于对照组,差异有统计学意义(P<0.05)。结论:针对性护理干预在腹腔镜下全子宫切除术治疗患者中的应用获得了较为显著的效果,有效促进预后,改善负性情绪,有利于降低并发症发生。 展开更多
关键词 针对性护理干预 腹腔镜 全子宫切除术 应用效果
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