Objective:Histone modification has a significant effect on gene expression.Enhancer of zeste homolog 2(EZH2)contributes to the epigenetic silencing of target chromatin through its roles as a histone-lysine N-methyltra...Objective:Histone modification has a significant effect on gene expression.Enhancer of zeste homolog 2(EZH2)contributes to the epigenetic silencing of target chromatin through its roles as a histone-lysine N-methyltransferase enzyme.The development of anoikis resistance in tumor cells is considered to be a critical step in the metastatic process of primary malignant tumors.The purpose of this study was to investigate the effect and mechanism of anoikis resistance in ovarian adenocarcinoma peritoneal metastasis.Methods:In addition to examining EZH2 protein expression in ovarian cancer omental metastatic tissues,we established a model of ovarian cancer cell anoikis and a xenograft tumor model in nude mice.Anoikis resistance and ovarian cancer progression were tested after EZH2 and N6-methyladenosine(m6A)levels were modified.Results:EZH2 expression was significantly higher in ovarian cancer omental metastatic tissues than in normal ovarian tissues.Reducing the level of EZH2 decreased the level of m6A and ovarian cancer cell anoikis resistance in vitro and inhibited ovarian cancer progression in vivo.M6a regulation altered the effect of EZH2 on anoikis resistance.Conclusion:Our results indicate that EZH2 contributes to anoikis resistance and promotes ovarian adenocarcinoma abdominal metastasis by m6A modification.Our findings imply the potential of the clinical application of m6A and EZH2 for patients with ovarian cancer.展开更多
Background: To study the influence of blood lipid levels on hemorrhagic transformation(HT) and prognosis after acute cerebral infarction(ACI).Methods: Patients with ACI within 72 h of symptoms onset between January 1 ...Background: To study the influence of blood lipid levels on hemorrhagic transformation(HT) and prognosis after acute cerebral infarction(ACI).Methods: Patients with ACI within 72 h of symptoms onset between January 1 st, 2015, and December 31 st, 2016, were retrospectively analyzed. Patients were divided into group A(without HT) and group B(HT). The outcomes were assessed after 3 months of disease onset using the modified Rankin Scale(m RS). An m RS score of 0–2 points indicated excellent prognosis, and an m RS score of 3–6 points indicated poor prognosis.Results: A total of 732 patients conformed to the inclusion criteria, including 628 in group A and 104 in group B. The incidence of HT was 14.2%, and the median onset time was 2 d(interquartile range, 1–7 d). The percentages of patients with large infarct size and cortex involvement in group B were 80.8% and 79.8%, respectively, which were both significantly higher than those in group A(28.7 and 33.4%, respectively). The incidence rate of atrial fibrillation(AF) in group B was significantly higher than that in group A(39.4% vs. 13.9%, P<0.001). The adjusted multivariate analysis results showed that large infarct size, cortex involvement and AF were independent risk factors of HT, while total cholesterol(TC) was a protective factor of HT(OR=0.359, 95% CI 0.136–0.944, P=0.038). With every 1 mmol/L reduction in normal TC levels, the risk of HT increased by 64.1%. The mortality and morbidity at 3 months in group B(21.2% and 76.7%, respectively) were both significantly higher than those in group A(8.0% and 42.8%, respectively). The adjusted multivariate analysis results showed that large infarct size(OR=12.178, 95% CI 5.390–27.516, P<0.001) was an independent risk factor of long-term unfavorable outcomes, whereas low-density lipoprotein cholesterol(LDL-C) was a protective factor(OR=0.538, 95% CI 0.300–0.964, P=0.037). With every 1 mmol/L reduction in normal LDL-C levels, the risk of an unfavorable outcome increased by 46.2%. Major therapies, including intravenous recombinant human tissue plasminogen activator(r TPA), intensive lipid-lowering statins and anti-platelets, were not significantly related to either HT or long-term, post-ACI poor prognosis.Conclusions: For patients with large infarct sizes, especially those with cortex involvement, AF, or lower levels of TC, the risk of HT might increase after ACI. The risk of a long-term unfavorable outcome in these patients might increase with a reduction in LDL-C.展开更多
Gastrodin, an active component of tall gastrodia tuber, is widely used in the treatment of dizziness, paralysis, epilepsy, stroke and dementia, and exhibits a neuroprotective effect. A rat model of spinal cord injury ...Gastrodin, an active component of tall gastrodia tuber, is widely used in the treatment of dizziness, paralysis, epilepsy, stroke and dementia, and exhibits a neuroprotective effect. A rat model of spinal cord injury was established using Allen's method, and gastrodin was administered via the subarachnoid cavity and by intraperitoneal injection for 7 days. Results show that gastrodin promoted the secretion of brain-derived neurotrophic factor in rats with spinal cord injury. After gastrodin treatment, the maximum angle of the inclined plane test, and the Basso, Beattie and Bresnahan scores increased. Moreover, gastrodin improved neural tissue recovery in the injured spinal cord. These results demonstrate that gastrodin promotes the secretion of brain-derived neurotrophic factor, contributes to the recovery of neurological function, and protects neural cells against injury.展开更多
Changes in mitochondrial morphology and function play an important role in secondary damage after acute spinal cord injury. We recorded the time representation of mitochondrial morphology and function in rats with acu...Changes in mitochondrial morphology and function play an important role in secondary damage after acute spinal cord injury. We recorded the time representation of mitochondrial morphology and function in rats with acute spinal cord injury. Results showed that mitochondria had an irregular shape, and increased in size. Mitochondrial cristae were disordered and mitochondrial membrane rupture was visible at 2–24 hours after injury. Fusion protein mitofusin 1 expression gradually increased, peaked at 8 hours after injury, and then decreased to its lowest level at 24 hours. Expression of dynamin-related protein 1, amitochondrial fission protein, showed the opposite kinetics. At 2–24 hours after acute spinal cord injury, malondialdehyde content, cytochrome c levels and caspase-3 expression were increased, but glutathione content, adenosine triphosphate content, Na+-K+-ATPase activity and mitochondrial membrane potential were gradually reduced. Furthermore, mitochondrial morphology altered during the acute stage of spinal cord injury. Fusion was important within the first 8 hours, but fission played a key role at 24 hours. Oxidative stress was inhibited, biological productivity was diminished, and mitochondrial membrane potential and permeability were reduced in the acute stage of injury. In summary, mitochondrial apoptosis is activated when the time of spinal cord injury is prolonged.展开更多
In this study, we constructed tissue-engineered nerves with acellular nerve allografts in Sprague-Dawley rats, which were prepared using chemical detergents-enzymatic digestion and mechanical methods, in combination w...In this study, we constructed tissue-engineered nerves with acellular nerve allografts in Sprague-Dawley rats, which were prepared using chemical detergents-enzymatic digestion and mechanical methods, in combination with bone marrow mesenchymal stem cells of Wistar rats cultured in vitro, to repair 15 mm sciatic bone defects in Wistar rats. At postoperative 12 weeks, electrophysiological detection results showed that the conduction velocity of regenerated nerve after repair with tissue-engineered nerves was similar to that after autologous nerve grafting, and was higher than that after repair with acellular nerve allografts. Immunohistochemical staining revealed that motor endplates with acetylcholinesterase-positive nerve fibers were orderly arranged in the middle and superior parts of the gastrocnemius muscle; regenerated nerve tracts and sprouted branches were connected with motor endplates, as shown by acetylcholinesterase histochemistry combined with silver staining. The wet weight ratio of the tibialis anterior muscle at the affected contralateral hind limb was similar to the sciatic nerve after repair with autologous nerve grafts, and higher than that after repair with acellular nerve allografts. The hind limb motor function at the affected side was significantly improved, indicating that acellular nerve allografts combined with bone marrow mesenchymal stem cell bridging could promote functional recovery of rats with sciatic nerve defects.展开更多
【正】Objective:To search and analyze nitric oxide synthase(NOS) and similar proteins from Plasmodium berghei(Pb).Methods:The structure and function of nitric oxide synthase and similar proteins from Plasmodium berghe...【正】Objective:To search and analyze nitric oxide synthase(NOS) and similar proteins from Plasmodium berghei(Pb).Methods:The structure and function of nitric oxide synthase and similar proteins from Plasmodium berghei were analyzed and predicted by bioinformatics. Results:P6NOS were not available,but nicotinamide adenine dinucleotide 2’-phosphate reduced tetrasodium(NADPH)-cytochrome p450 reductase(CPR) were gained.PiCPR was in the nucleus of Plasmodium berghei,while 134aa-229aa domain was localize in nucleolar organizer. The amino acids sequence of P6CPR had the closest genetic relationship with Plasmodium vivax showing a 73%homology.The tertiary structure of PbCPR displayed the forcep-shape with wings,but no wings existed in the tertiary structure of its’ host,Mus musculus(Mm).137aa-200aa, 201aa-218aa,220aa-230aa,232aa-248,269aa-323aa,478aa-501aa and 592aa-606aa domains of P6CPR showed no homology with MmCPRs’,and all domains were exposed on the surface of the protein.Conclusions:NOS can’t be found in Plasmodium berghei and other Plasmodium species.PbCPR may be a possible resistance site of antimalarial drug,and the targets of antimalarial drug and vaccine.It may be also one of the mechanisms of immune evasion.This study on Plasmodium berghei may be more suitable to Plasmodium vivax.And137aa-200aa, 201aa-218aa,220aa-230aa,232aa-248,269aa-323aa,478aa-501aa and 592aa-606aa domains of PbCPR are more ideal targets of antimalarial drug and vaccine.展开更多
Muscle-derived stem cells(MDSCs) can come from a number of different sources,which are easy to isolate and culture,and are also useful in the transformation and expression of exogenous genes.Therefore,MDSCs could poss...Muscle-derived stem cells(MDSCs) can come from a number of different sources,which are easy to isolate and culture,and are also useful in the transformation and expression of exogenous genes.Therefore,MDSCs could possibly be used for gene therapy in the treatment of neurological diseases.However,research on MDSCs has focused on identifying phenotypes and induced differentiation,with few in vivo animal experiments conducted.In this study,MDSCs were selected as seed cells and implanted into the rat spinal cord injury area.Results demonstrated that the MDSCs survived,migrated,and were distributed along the spinal nerves.Moreover,the motor function of rat lower limbs improved significantly,suggesting that MDSCs could be used as seed cells to repair spinal cord injury.展开更多
Different from the traditional railway trains,the combined levitation and guidance EDS maglev train is more likely to rotate after being disturbed.Therefore,the rotational electromagnetic stiffnesses are significant o...Different from the traditional railway trains,the combined levitation and guidance EDS maglev train is more likely to rotate after being disturbed.Therefore,the rotational electromagnetic stiffnesses are significant operating parameters for the train.In this paper,the different effects of each translational offset generated in the rotational motion on the corresponding rotational electromagnetic stiffnesses in the EDS maglev train are analyzed and calculated.Firstly,a three-dimensional model of the maglev train is established.Then,based on the space harmonic method and the equivalent circuit of the levitation and guidance circuits,the formulas of rolling,pitching and yawing stiffness are presented.Finally,by comparing with the three-dimensional finite element simulation results,the key translational displacements in the rotational motion which has a great impact on the stiffness are obtained.Hence,the three-dimensional analytical formula can be simplified and the computation can be reduced.In addition,the accuracy of the calculation results is verified by comparing with the experimental data of Yamanashi test line.展开更多
Dynamic stability analysis of superconducting electro-dynamic maglev train under lateral and yawing motion condition is the key research content.The novel three-dimensional electromagnetic model of integrated linear s...Dynamic stability analysis of superconducting electro-dynamic maglev train under lateral and yawing motion condition is the key research content.The novel three-dimensional electromagnetic model of integrated linear synchronous motor in electro-dynamic maglev train with yawing operation condition is proposed,which can not only simultaneously achieve the propulsion,levitation and guidance performances of maglev vehicle,but also analyze the dynamic stability performance of train with yawing condition.The three-dimensional analytical method is introduced for analyzing the electromagnetic force characteristics of the linear synchronous motor with the yawing operation condition.Firstly,the topology structure and operation principle of the linear synchronous motor with yawing attitude are proposed.Secondly,the three-dimensional analytical model and expressions of electromagnetic characteristics are obtained by equivalent circuit method and Fourier decomposition method,such as levitation force,guidance force,propulsion force and yawing torque,etc.Finally,the three-dimensional electromagnetic characteristics of the linear synchronous motor are calculated under yawing operation conditions of maglev train,and the correctness of the analytical theory is verified by the finite element analysis and measured data on the test line.展开更多
Cryptosporidium is an emerging single-cell zoonotic pathogen.By invading human and animal small intestinal epithelial cells,the host produces a variety of clinical symptoms,mainly diarrhea.Spores of Cryptosporidium ca...Cryptosporidium is an emerging single-cell zoonotic pathogen.By invading human and animal small intestinal epithelial cells,the host produces a variety of clinical symptoms,mainly diarrhea.Spores of Cryptosporidium can be transmitted through water-borne,food-borne,and mutual transmission between hosts,which has important public health significance.Studies have shown that non-human primates can be infected with multiple Cryptosporidium genotypes.Moreover,this species has a high genetic similarity with humans,so it needs to be taken seriously.This article reviews the infection rates,genotypes,and zoonotic risk of Cryptosporidium in non-human primates.展开更多
The three-dimensional(3D)analytical model of the magnetic field in an Axial Flux Permanent Magnets Maglev Motor(AFPMMM)is proposed and investigated the influence of the structural parameters on electromagnetic charact...The three-dimensional(3D)analytical model of the magnetic field in an Axial Flux Permanent Magnets Maglev Motor(AFPMMM)is proposed and investigated the influence of the structural parameters on electromagnetic characteristics.Firstly,the topology and working principle of the AFPMMM is introduced,and the model is transferred into a mathematical model in 3D cartesian coordinate.Then,the volume integral method and equivalent current sheets model is applied to find the 3D magnetic field distribution function of Halbach rotor.A unified form expression can be obtained by two dimensional discrete fourier transform(2-D DFT)is applied on the 3D magnetic field distribution function.Thirdly,the conductive and nonconductive regions of AFPMMM will be formulated by the second order vector potential(SOVP)to built the 3D analytic model.The expression of the lift force,torque and power losses was derived.Besides,the relationship between electromagnetic characteristics and structural parameters of the AFPMMM were analyzed based on 3D analytic model and validated using the 3D finite element analysis(FEA).Finally,the experiments based on a small scale prototype are carried out to verify the analytical results.展开更多
Evolutionary testing (ET) is an effective test case generation technique which uses some meta-heuristic search algorithm, especially genetic algorithm, to generate test case automatically. However, the population prem...Evolutionary testing (ET) is an effective test case generation technique which uses some meta-heuristic search algorithm, especially genetic algorithm, to generate test case automatically. However, the population prematurity problem may decrease the performance of ET. In this paper, a hybrid optimization strategy is proposed based on extended cataclysm which integrates both static configuration strategies and dynamic optimization strategy. Dynamic optimization strategy included the optimization of initial population and the dynamic population optimization based on extended cataclysm, where the diversity of population was monitored during the evolution process of ET, and once the population prematurity was detected, extended cataclysm operation was used to renew the diversity of the population. Experimental results show that the hybrid optimization strategy can improve the performance of ET.展开更多
Background:Heterogeneity of leukemia-initiating cells(LICs)is a major obstacle in acute myeloid leukemia(AML)therapy.Accumulated evidence indicates that the coexistence of multiple types of LICs with different pathoge...Background:Heterogeneity of leukemia-initiating cells(LICs)is a major obstacle in acute myeloid leukemia(AML)therapy.Accumulated evidence indicates that the coexistence of multiple types of LICs with different pathogenicity in the same individual is a common feature in AML.However,the functional heterogeneity including the drug response of coexistent LICs remains unclear.Therefore,this study aimed to clarify the intra-heterogeneity in LICs that can help predict leukemia behavior and develop more effective treatments.Methods:Spleen cells from the primary Setd2^(-/-)-AML mouse were transplanted into C57BL/6 recipient mice to generate a transplantable model.Flow cytometry was used to analyze the immunophenotype of the leukemic mice.Whole-genome sequencing was conducted to detect secondary hits responsible for leukemia transformation.A serial transplantation assay was used to determine the self-renewal potential of Setd2^(-/-)-AML cells.A limiting-dilution assay was performed to identify the LIC frequency in different subsets of leukemia cells.Bulk and single-cell RNA sequencing were performed to analyze the transcriptional heterogeneity of LICs.Small molecular inhibitor screening and in vivo drug treatment were employed to clarify the difference in drug response between the different subsets of LICs.Results:In this study,we observed an aged Setd2^(-/-)mouse developing AML with co-mutation of Nras^(G12S) and Braf^(K520E).Further investigation identified two types of LICs residing in the c-Kit^(+)B220^(+)Mac-1^(-)and c-Kit^(+)B220^(+)Mac-1^(+)subsets,respectively.In vivo transplantation assay disclosed the heterogeneity in differentiation between the coexistent LICs.Besides,an intrinsic doxorubicinresistant transcriptional signature was uncovered in c-Kit^(+)B220^(+)Mac-1^(+)cells.Indeed,doxorubicin plus cytarabine(DA),the standard chemotherapeutic regimen used in AML treatment,could specifically kill c-Kit^(+)B220^(+)Mac-1^(−)cells,but it hardly affected c-Kit^(+)B220^(+)Mac-1^(+)cells.Transcriptome analysis unveiled a higher activation of RAS downstream signaling pathways in c-Kit^(+)B220^(+)Mac-1^(+)cells than in c-Kit^(+)B220^(+)Mac-1^(-)cells.Combined treatmentwithDAand RAS pathway inhibitors killed both c-Kit^(+)B220^(+)Mac-1^(−)and c-Kit^(+)B220^(+)Mac-1^(+)cells and attenuated disease progression.Conclusions:This study identified two cell subsets enriched for LICs inmurine Setd2^(-/-)-AML and disclosed the transcriptional and functional heterogeneity of LICs,revealing that the coexistence of different types of LICs in thismodel brings about diverse drug response.展开更多
基金funded by the National Natural Science Foundation of China(No.81672573)Natural Science Foundation of Xinjiang Uygur Autonomous Region(No.2021D01F21)Natural Science Foundation of Hubei Province(No.2021CFB474)。
文摘Objective:Histone modification has a significant effect on gene expression.Enhancer of zeste homolog 2(EZH2)contributes to the epigenetic silencing of target chromatin through its roles as a histone-lysine N-methyltransferase enzyme.The development of anoikis resistance in tumor cells is considered to be a critical step in the metastatic process of primary malignant tumors.The purpose of this study was to investigate the effect and mechanism of anoikis resistance in ovarian adenocarcinoma peritoneal metastasis.Methods:In addition to examining EZH2 protein expression in ovarian cancer omental metastatic tissues,we established a model of ovarian cancer cell anoikis and a xenograft tumor model in nude mice.Anoikis resistance and ovarian cancer progression were tested after EZH2 and N6-methyladenosine(m6A)levels were modified.Results:EZH2 expression was significantly higher in ovarian cancer omental metastatic tissues than in normal ovarian tissues.Reducing the level of EZH2 decreased the level of m6A and ovarian cancer cell anoikis resistance in vitro and inhibited ovarian cancer progression in vivo.M6a regulation altered the effect of EZH2 on anoikis resistance.Conclusion:Our results indicate that EZH2 contributes to anoikis resistance and promotes ovarian adenocarcinoma abdominal metastasis by m6A modification.Our findings imply the potential of the clinical application of m6A and EZH2 for patients with ovarian cancer.
文摘Background: To study the influence of blood lipid levels on hemorrhagic transformation(HT) and prognosis after acute cerebral infarction(ACI).Methods: Patients with ACI within 72 h of symptoms onset between January 1 st, 2015, and December 31 st, 2016, were retrospectively analyzed. Patients were divided into group A(without HT) and group B(HT). The outcomes were assessed after 3 months of disease onset using the modified Rankin Scale(m RS). An m RS score of 0–2 points indicated excellent prognosis, and an m RS score of 3–6 points indicated poor prognosis.Results: A total of 732 patients conformed to the inclusion criteria, including 628 in group A and 104 in group B. The incidence of HT was 14.2%, and the median onset time was 2 d(interquartile range, 1–7 d). The percentages of patients with large infarct size and cortex involvement in group B were 80.8% and 79.8%, respectively, which were both significantly higher than those in group A(28.7 and 33.4%, respectively). The incidence rate of atrial fibrillation(AF) in group B was significantly higher than that in group A(39.4% vs. 13.9%, P<0.001). The adjusted multivariate analysis results showed that large infarct size, cortex involvement and AF were independent risk factors of HT, while total cholesterol(TC) was a protective factor of HT(OR=0.359, 95% CI 0.136–0.944, P=0.038). With every 1 mmol/L reduction in normal TC levels, the risk of HT increased by 64.1%. The mortality and morbidity at 3 months in group B(21.2% and 76.7%, respectively) were both significantly higher than those in group A(8.0% and 42.8%, respectively). The adjusted multivariate analysis results showed that large infarct size(OR=12.178, 95% CI 5.390–27.516, P<0.001) was an independent risk factor of long-term unfavorable outcomes, whereas low-density lipoprotein cholesterol(LDL-C) was a protective factor(OR=0.538, 95% CI 0.300–0.964, P=0.037). With every 1 mmol/L reduction in normal LDL-C levels, the risk of an unfavorable outcome increased by 46.2%. Major therapies, including intravenous recombinant human tissue plasminogen activator(r TPA), intensive lipid-lowering statins and anti-platelets, were not significantly related to either HT or long-term, post-ACI poor prognosis.Conclusions: For patients with large infarct sizes, especially those with cortex involvement, AF, or lower levels of TC, the risk of HT might increase after ACI. The risk of a long-term unfavorable outcome in these patients might increase with a reduction in LDL-C.
基金financially supported by the National Natural Science Foundation of China, No. 81171799
文摘Gastrodin, an active component of tall gastrodia tuber, is widely used in the treatment of dizziness, paralysis, epilepsy, stroke and dementia, and exhibits a neuroprotective effect. A rat model of spinal cord injury was established using Allen's method, and gastrodin was administered via the subarachnoid cavity and by intraperitoneal injection for 7 days. Results show that gastrodin promoted the secretion of brain-derived neurotrophic factor in rats with spinal cord injury. After gastrodin treatment, the maximum angle of the inclined plane test, and the Basso, Beattie and Bresnahan scores increased. Moreover, gastrodin improved neural tissue recovery in the injured spinal cord. These results demonstrate that gastrodin promotes the secretion of brain-derived neurotrophic factor, contributes to the recovery of neurological function, and protects neural cells against injury.
基金supported by the National Natural Science Foundation of China,No.81272074the Scientific Research Foundation Project for Doctors in Liaoning Province of China,No.20121094+1 种基金Aohongboze Graduate Sci-tech Innovation Foundationthe President Fund of Liaoning Medical University of China,No.2013003
文摘Changes in mitochondrial morphology and function play an important role in secondary damage after acute spinal cord injury. We recorded the time representation of mitochondrial morphology and function in rats with acute spinal cord injury. Results showed that mitochondria had an irregular shape, and increased in size. Mitochondrial cristae were disordered and mitochondrial membrane rupture was visible at 2–24 hours after injury. Fusion protein mitofusin 1 expression gradually increased, peaked at 8 hours after injury, and then decreased to its lowest level at 24 hours. Expression of dynamin-related protein 1, amitochondrial fission protein, showed the opposite kinetics. At 2–24 hours after acute spinal cord injury, malondialdehyde content, cytochrome c levels and caspase-3 expression were increased, but glutathione content, adenosine triphosphate content, Na+-K+-ATPase activity and mitochondrial membrane potential were gradually reduced. Furthermore, mitochondrial morphology altered during the acute stage of spinal cord injury. Fusion was important within the first 8 hours, but fission played a key role at 24 hours. Oxidative stress was inhibited, biological productivity was diminished, and mitochondrial membrane potential and permeability were reduced in the acute stage of injury. In summary, mitochondrial apoptosis is activated when the time of spinal cord injury is prolonged.
基金financially sponsored by the Natural Science Foundation of Liaoning Province,No.201102135
文摘In this study, we constructed tissue-engineered nerves with acellular nerve allografts in Sprague-Dawley rats, which were prepared using chemical detergents-enzymatic digestion and mechanical methods, in combination with bone marrow mesenchymal stem cells of Wistar rats cultured in vitro, to repair 15 mm sciatic bone defects in Wistar rats. At postoperative 12 weeks, electrophysiological detection results showed that the conduction velocity of regenerated nerve after repair with tissue-engineered nerves was similar to that after autologous nerve grafting, and was higher than that after repair with acellular nerve allografts. Immunohistochemical staining revealed that motor endplates with acetylcholinesterase-positive nerve fibers were orderly arranged in the middle and superior parts of the gastrocnemius muscle; regenerated nerve tracts and sprouted branches were connected with motor endplates, as shown by acetylcholinesterase histochemistry combined with silver staining. The wet weight ratio of the tibialis anterior muscle at the affected contralateral hind limb was similar to the sciatic nerve after repair with autologous nerve grafts, and higher than that after repair with acellular nerve allografts. The hind limb motor function at the affected side was significantly improved, indicating that acellular nerve allografts combined with bone marrow mesenchymal stem cell bridging could promote functional recovery of rats with sciatic nerve defects.
基金Supported in part by the Research Program in Higher Educational Institutes of the Education Department in Hainan(No.Hjkj2009-50)Scientific Research Funds of Hainan Medical University in 2011(No.2010-014)
文摘【正】Objective:To search and analyze nitric oxide synthase(NOS) and similar proteins from Plasmodium berghei(Pb).Methods:The structure and function of nitric oxide synthase and similar proteins from Plasmodium berghei were analyzed and predicted by bioinformatics. Results:P6NOS were not available,but nicotinamide adenine dinucleotide 2’-phosphate reduced tetrasodium(NADPH)-cytochrome p450 reductase(CPR) were gained.PiCPR was in the nucleus of Plasmodium berghei,while 134aa-229aa domain was localize in nucleolar organizer. The amino acids sequence of P6CPR had the closest genetic relationship with Plasmodium vivax showing a 73%homology.The tertiary structure of PbCPR displayed the forcep-shape with wings,but no wings existed in the tertiary structure of its’ host,Mus musculus(Mm).137aa-200aa, 201aa-218aa,220aa-230aa,232aa-248,269aa-323aa,478aa-501aa and 592aa-606aa domains of P6CPR showed no homology with MmCPRs’,and all domains were exposed on the surface of the protein.Conclusions:NOS can’t be found in Plasmodium berghei and other Plasmodium species.PbCPR may be a possible resistance site of antimalarial drug,and the targets of antimalarial drug and vaccine.It may be also one of the mechanisms of immune evasion.This study on Plasmodium berghei may be more suitable to Plasmodium vivax.And137aa-200aa, 201aa-218aa,220aa-230aa,232aa-248,269aa-323aa,478aa-501aa and 592aa-606aa domains of PbCPR are more ideal targets of antimalarial drug and vaccine.
基金the National Nature Science Foundation of China (No.30772890)the Collaborative Education,Research and Development Project of Beijing Municipal Commission of Education and the Key Project of Chinese Ministry of Education (No.108132).
基金the Natural Science Foundation of Liaoning Province,No.20072204
文摘Muscle-derived stem cells(MDSCs) can come from a number of different sources,which are easy to isolate and culture,and are also useful in the transformation and expression of exogenous genes.Therefore,MDSCs could possibly be used for gene therapy in the treatment of neurological diseases.However,research on MDSCs has focused on identifying phenotypes and induced differentiation,with few in vivo animal experiments conducted.In this study,MDSCs were selected as seed cells and implanted into the rat spinal cord injury area.Results demonstrated that the MDSCs survived,migrated,and were distributed along the spinal nerves.Moreover,the motor function of rat lower limbs improved significantly,suggesting that MDSCs could be used as seed cells to repair spinal cord injury.
基金supported in part by the National Natural Science Foundation of China under Grant(52077003 and 51777009)。
文摘Different from the traditional railway trains,the combined levitation and guidance EDS maglev train is more likely to rotate after being disturbed.Therefore,the rotational electromagnetic stiffnesses are significant operating parameters for the train.In this paper,the different effects of each translational offset generated in the rotational motion on the corresponding rotational electromagnetic stiffnesses in the EDS maglev train are analyzed and calculated.Firstly,a three-dimensional model of the maglev train is established.Then,based on the space harmonic method and the equivalent circuit of the levitation and guidance circuits,the formulas of rolling,pitching and yawing stiffness are presented.Finally,by comparing with the three-dimensional finite element simulation results,the key translational displacements in the rotational motion which has a great impact on the stiffness are obtained.Hence,the three-dimensional analytical formula can be simplified and the computation can be reduced.In addition,the accuracy of the calculation results is verified by comparing with the experimental data of Yamanashi test line.
基金supported in part by the National Natural Science Foundation of China under Grant 52077003 and 51777009。
文摘Dynamic stability analysis of superconducting electro-dynamic maglev train under lateral and yawing motion condition is the key research content.The novel three-dimensional electromagnetic model of integrated linear synchronous motor in electro-dynamic maglev train with yawing operation condition is proposed,which can not only simultaneously achieve the propulsion,levitation and guidance performances of maglev vehicle,but also analyze the dynamic stability performance of train with yawing condition.The three-dimensional analytical method is introduced for analyzing the electromagnetic force characteristics of the linear synchronous motor with the yawing operation condition.Firstly,the topology structure and operation principle of the linear synchronous motor with yawing attitude are proposed.Secondly,the three-dimensional analytical model and expressions of electromagnetic characteristics are obtained by equivalent circuit method and Fourier decomposition method,such as levitation force,guidance force,propulsion force and yawing torque,etc.Finally,the three-dimensional electromagnetic characteristics of the linear synchronous motor are calculated under yawing operation conditions of maglev train,and the correctness of the analytical theory is verified by the finite element analysis and measured data on the test line.
基金Innovation Research Team Project of Natural Science Foundation of Hainan Province(No.2018CXTD340)National Natural Science Foundation of China(No.81760378)National Natural Science Foundation of China(No.82060375)。
文摘Cryptosporidium is an emerging single-cell zoonotic pathogen.By invading human and animal small intestinal epithelial cells,the host produces a variety of clinical symptoms,mainly diarrhea.Spores of Cryptosporidium can be transmitted through water-borne,food-borne,and mutual transmission between hosts,which has important public health significance.Studies have shown that non-human primates can be infected with multiple Cryptosporidium genotypes.Moreover,this species has a high genetic similarity with humans,so it needs to be taken seriously.This article reviews the infection rates,genotypes,and zoonotic risk of Cryptosporidium in non-human primates.
基金supported in part by the Fundamental Research Funds for the Central Universities of China under Grant No.2022JBMC050。
文摘The three-dimensional(3D)analytical model of the magnetic field in an Axial Flux Permanent Magnets Maglev Motor(AFPMMM)is proposed and investigated the influence of the structural parameters on electromagnetic characteristics.Firstly,the topology and working principle of the AFPMMM is introduced,and the model is transferred into a mathematical model in 3D cartesian coordinate.Then,the volume integral method and equivalent current sheets model is applied to find the 3D magnetic field distribution function of Halbach rotor.A unified form expression can be obtained by two dimensional discrete fourier transform(2-D DFT)is applied on the 3D magnetic field distribution function.Thirdly,the conductive and nonconductive regions of AFPMMM will be formulated by the second order vector potential(SOVP)to built the 3D analytic model.The expression of the lift force,torque and power losses was derived.Besides,the relationship between electromagnetic characteristics and structural parameters of the AFPMMM were analyzed based on 3D analytic model and validated using the 3D finite element analysis(FEA).Finally,the experiments based on a small scale prototype are carried out to verify the analytical results.
基金National Natural Science Foundation of China under Grant No. 61806068, 61672204by Visiting Scholar at Home and Aboard Funded Project of Universities of Anhui Province under Grant gxfxZD2016209+3 种基金by Key Technologies R&D Program of Anhui Province under Grant 1804a09020058by the Major Program for Scientific and Technological of Anhui Province under Grant 17030901026by Talent Research Foundation Project of Hefei University under Grant 16-17RC23by Humanities and Social Science Research Project of Universities of Anhui Province under Grant SK2018A0605.
文摘Evolutionary testing (ET) is an effective test case generation technique which uses some meta-heuristic search algorithm, especially genetic algorithm, to generate test case automatically. However, the population prematurity problem may decrease the performance of ET. In this paper, a hybrid optimization strategy is proposed based on extended cataclysm which integrates both static configuration strategies and dynamic optimization strategy. Dynamic optimization strategy included the optimization of initial population and the dynamic population optimization based on extended cataclysm, where the diversity of population was monitored during the evolution process of ET, and once the population prematurity was detected, extended cataclysm operation was used to renew the diversity of the population. Experimental results show that the hybrid optimization strategy can improve the performance of ET.
基金National Natural Science Foundation of China,Grant/Award Numbers:81670149,81870102Samuel Waxman Cancer Research FoundationFoundation of Key Laboratory of Veterinary Biotechnology,Grant/Award Number:shklab202008。
文摘Background:Heterogeneity of leukemia-initiating cells(LICs)is a major obstacle in acute myeloid leukemia(AML)therapy.Accumulated evidence indicates that the coexistence of multiple types of LICs with different pathogenicity in the same individual is a common feature in AML.However,the functional heterogeneity including the drug response of coexistent LICs remains unclear.Therefore,this study aimed to clarify the intra-heterogeneity in LICs that can help predict leukemia behavior and develop more effective treatments.Methods:Spleen cells from the primary Setd2^(-/-)-AML mouse were transplanted into C57BL/6 recipient mice to generate a transplantable model.Flow cytometry was used to analyze the immunophenotype of the leukemic mice.Whole-genome sequencing was conducted to detect secondary hits responsible for leukemia transformation.A serial transplantation assay was used to determine the self-renewal potential of Setd2^(-/-)-AML cells.A limiting-dilution assay was performed to identify the LIC frequency in different subsets of leukemia cells.Bulk and single-cell RNA sequencing were performed to analyze the transcriptional heterogeneity of LICs.Small molecular inhibitor screening and in vivo drug treatment were employed to clarify the difference in drug response between the different subsets of LICs.Results:In this study,we observed an aged Setd2^(-/-)mouse developing AML with co-mutation of Nras^(G12S) and Braf^(K520E).Further investigation identified two types of LICs residing in the c-Kit^(+)B220^(+)Mac-1^(-)and c-Kit^(+)B220^(+)Mac-1^(+)subsets,respectively.In vivo transplantation assay disclosed the heterogeneity in differentiation between the coexistent LICs.Besides,an intrinsic doxorubicinresistant transcriptional signature was uncovered in c-Kit^(+)B220^(+)Mac-1^(+)cells.Indeed,doxorubicin plus cytarabine(DA),the standard chemotherapeutic regimen used in AML treatment,could specifically kill c-Kit^(+)B220^(+)Mac-1^(−)cells,but it hardly affected c-Kit^(+)B220^(+)Mac-1^(+)cells.Transcriptome analysis unveiled a higher activation of RAS downstream signaling pathways in c-Kit^(+)B220^(+)Mac-1^(+)cells than in c-Kit^(+)B220^(+)Mac-1^(-)cells.Combined treatmentwithDAand RAS pathway inhibitors killed both c-Kit^(+)B220^(+)Mac-1^(−)and c-Kit^(+)B220^(+)Mac-1^(+)cells and attenuated disease progression.Conclusions:This study identified two cell subsets enriched for LICs inmurine Setd2^(-/-)-AML and disclosed the transcriptional and functional heterogeneity of LICs,revealing that the coexistence of different types of LICs in thismodel brings about diverse drug response.
