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
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
This study proposes a low-energy pulse current(LEPC)rapid solution treatment method,which can dis-solve more primaryγ'phase in a shorter time and effectively suppress abnormal grain growth,thereby successfully ac...This study proposes a low-energy pulse current(LEPC)rapid solution treatment method,which can dis-solve more primaryγ'phase in a shorter time and effectively suppress abnormal grain growth,thereby successfully achieving microstructure optimization and property enhancement.The microstructure anal-ysis showed that,compared with the 62.5%dissolution rate of the standard traditional solution treat-ment(1100℃/4 h),LEPC achieved an 88.9%dissolution of the primaryγ'phase in just 5 min at the same temperature.Furthermore,due to the rapidity of the LEPC treatment and its“targeted dissolution effect”on theγ'phase,excessivegrain growthwas effectivelysuppressed,resultingingrain sizecom-parable to those obtained with traditional solution treatment.Mechanical property testing indicated that the alloy treated with LEPC had a hardness of 531 HV at room temperature,while the yield strength,Ultimate strength,and maximum strain reached 994 MPa,1030 MPa,and 5.1%at the service tempera-ture(750℃).Compared to the standard traditional solution treatment,these properties were improved by 10.4%,11.1%,10.4%,and 17.5%,respectively.Finally,theoretical calculations revealed that the non-thermal effect of LEPC reduced the dissolution-free energy by approximately 49.4 kJ/mol and increased the diffusion coefficient by about 76 times,which was the fundamental reason for the accelerated disso-lution of the primaryγ’phase.展开更多
A series of drug delivery systems based on a sodium alginate derivative were prepared by mixing glycyrrhetinic acid （GA） and doxorubicin （DOX） conjugates at different ratios. GA （a liver-targeting ligand） and D...A series of drug delivery systems based on a sodium alginate derivative were prepared by mixing glycyrrhetinic acid （GA） and doxorubicin （DOX） conjugates at different ratios. GA （a liver-targeting ligand） and DOX （an antitumor drug） were both conjugated to oligomeric glycol monomethyl ether-modified sodium alginate （ALG-mOEG） for prolonged duration of action. These NP-based delivery systems exhibited active cell uptake and cytotoxicity in vitro and liver-targeted distribution and anti-tumor activity in vivo. In addition, nanoparticles with a 1：1 （W：W） ratio of GA-ALG-mOEG and DOX-ALG-mOEG （NPs-3） showed the highest cellular uptake and cytotoxicity in vitro and liver-targeted distribution and anti-tumor activity in vivo. Specifically, when mixed nanoparticles defined as NPs-3 were injected in mice, liver DOX concentration reached 61.9 μg/g 3 h after injection, and AUC0-∞ and t1/2 of DOX in liver reached 4744.9 μg·h/g and 49.5 h, respectively. In addition, mice receiving a single injection of NPs-3 exhibited much slower tumor growth （88.37% reduction in tumor weight） 16 days after injection compared with placebo. These results indicate that effective cancer treatment may be developed using mixed NP delivery systems with appropriate ratio of targeted ligand and drug.展开更多
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 uncl...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
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
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
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
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
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
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
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
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
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
基金supported by the National Key Research and Development Program of China(2018YFA0801401 and 2019YFA0802801)the National Natural Science Foundation of China 31871345+1 种基金the Young Thousand Talented Program from Wuhan Universitythe startup funding from Wuhan University to H.Y.
文摘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.
基金supported by the National Natural Science Foundation of China (60774064)the Aerospace Science Foundation (05D53022)the Youth for NPU Teachers Scientific and Technological Innovation Foundation (W016210)
文摘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.
基金financially supported by the National Key R&D Program of China(Nos.2020YFA0714901 and 2020YFA0714904).
文摘This study proposes a low-energy pulse current(LEPC)rapid solution treatment method,which can dis-solve more primaryγ'phase in a shorter time and effectively suppress abnormal grain growth,thereby successfully achieving microstructure optimization and property enhancement.The microstructure anal-ysis showed that,compared with the 62.5%dissolution rate of the standard traditional solution treat-ment(1100℃/4 h),LEPC achieved an 88.9%dissolution of the primaryγ'phase in just 5 min at the same temperature.Furthermore,due to the rapidity of the LEPC treatment and its“targeted dissolution effect”on theγ'phase,excessivegrain growthwas effectivelysuppressed,resultingingrain sizecom-parable to those obtained with traditional solution treatment.Mechanical property testing indicated that the alloy treated with LEPC had a hardness of 531 HV at room temperature,while the yield strength,Ultimate strength,and maximum strain reached 994 MPa,1030 MPa,and 5.1%at the service tempera-ture(750℃).Compared to the standard traditional solution treatment,these properties were improved by 10.4%,11.1%,10.4%,and 17.5%,respectively.Finally,theoretical calculations revealed that the non-thermal effect of LEPC reduced the dissolution-free energy by approximately 49.4 kJ/mol and increased the diffusion coefficient by about 76 times,which was the fundamental reason for the accelerated disso-lution of the primaryγ’phase.
基金financially supported by the National Natural Science Foundation of China(Nos.51073080 and 51273095)Natural Science Foundation of Tianjin(No.13JCYBJC25100)and PCSIRT(No.IRT1257)
文摘A series of drug delivery systems based on a sodium alginate derivative were prepared by mixing glycyrrhetinic acid （GA） and doxorubicin （DOX） conjugates at different ratios. GA （a liver-targeting ligand） and DOX （an antitumor drug） were both conjugated to oligomeric glycol monomethyl ether-modified sodium alginate （ALG-mOEG） for prolonged duration of action. These NP-based delivery systems exhibited active cell uptake and cytotoxicity in vitro and liver-targeted distribution and anti-tumor activity in vivo. In addition, nanoparticles with a 1：1 （W：W） ratio of GA-ALG-mOEG and DOX-ALG-mOEG （NPs-3） showed the highest cellular uptake and cytotoxicity in vitro and liver-targeted distribution and anti-tumor activity in vivo. Specifically, when mixed nanoparticles defined as NPs-3 were injected in mice, liver DOX concentration reached 61.9 μg/g 3 h after injection, and AUC0-∞ and t1/2 of DOX in liver reached 4744.9 μg·h/g and 49.5 h, respectively. In addition, mice receiving a single injection of NPs-3 exhibited much slower tumor growth （88.37% reduction in tumor weight） 16 days after injection compared with placebo. These results indicate that effective cancer treatment may be developed using mixed NP delivery systems with appropriate ratio of targeted ligand and drug.
基金supported by the National Basic Research Program of China(973 Program),No.2006CB504505,2012CB518504the National Natural Science Foundation of China,No.90709027+1 种基金the Student's Platform for Innovation and Entrepreneurship Training Program of Southern Medical University of China,No.201512121165the Doctoral Foundation of Guangdong Medical University of China,No.2XB13058
文摘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.
基金supported by the National Natural Science Foundation of China(71771216).
文摘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.
基金supported by the National GMO New Variety Breeding Program of China(2015ZX08013-003)
文摘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.
基金Financial supports were provided from the Special Research Projects for Developing Transgenic Plants,China(2013ZX08011-001)the China National Science Fund for Innovative Research Groups of Biological Control(31021003)the National 973 Program of China(2007CB109202)
文摘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.
基金Supported by the National Basic Research Program of China(No.2009CB930102)the National High Technology Research and Development Program of China(No.2007AA03Z535)+3 种基金the National Natural Science Foundation of China(No.21004062)the China-Japan-Korea Foresight Program(No.20621140369)"100 Talents Program" of the Chinese Academy of Sciences(No.KGCX2- YW-802) the Project of Jilin Provincial Science & Technology Department,China(No.200705110)
文摘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.
基金supported by the Natural Science Foundation of Jiangsu Province (No. BK20170824)the Fundamental Research Funds for the Central Universities (No. 30917011343)
文摘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.
基金supported by the National Natural Science Foundation of China,No.81373729
文摘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.
基金Financial supports were provided from the Special Research Projects for Developing Transgenic Plants,China(2014ZX08011-001)the National Natural Science Fundation of China for Innovative Research Group(31321063)the Rice Pests Management Research Group of the Agricultural Science and Technology Innovation Program,China
文摘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.
基金supported by the National Natural Science Foundation of China (No. 21772144 and No. 21801184)Tianjin Municipal Applied Basic and Key Research Scheme, China (No. 18JCQNIC06400)
文摘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.
基金National Natural Science Foundation of China(3120077181030065+5 种基金8127405531371066013117101101)Ministry of Science and Technology(2013CB91060101)National Science Technology Major Project of China (2012ZX09301-001-062014ZX09102001-005).
文摘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.
