OBJECTIVE:To discuss the influence of Sailuotong(塞络通,SLT)on the Neurovascular Unit(NVUs)of amyloid precursor protein(APP)/presenilin-1(PS1)mice and evaluate the role of gas supplementation in activating blood circu...OBJECTIVE:To discuss the influence of Sailuotong(塞络通,SLT)on the Neurovascular Unit(NVUs)of amyloid precursor protein(APP)/presenilin-1(PS1)mice and evaluate the role of gas supplementation in activating blood circulation during the progression of Alzheimer's disease(AD).METHODS:The mice were allocated into the following nine groups:(a)the C57 Black(C57BL)sham-operated group(control group),(b)ischaemic treatment in C57BL mice(the C57 ischaemic group),(c)the APP/PS1 sham surgery group(APP/PS1 model group),(d)ischaemic treatment in APP/PS1 mice(APP/PS1 ischaemic group),(e)C57BL mice treated with aspirin following ischaemic treatment(C57BL ischaemic+aspirin group),(f)C57BL mice treated with SLT following ischaemic treatment(C57BL ischaemic+SLT group),(g)APP/PS1 mice treated with SLT(APP/PS1+SLT group),(h)APP/PS1 mice treated with donepezil hydrochloride following ischaemic treatment(APP/PS1 ischaemic+donepezil hydrochloride group)and(i)APP/PS1 mice treated with SLT following ischaemic treatment(APP/PS1 ischaemic+SLT group).The ischaemic model was established by operating on the bilateral common carotid arteries and creating a microembolism.The Morris water maze and step-down tests were used to detect the spatial behaviour and memory ability of mice.The hippocampus of each mouse was observed by haematoxylin and eosin(HE)and Congo red staining.The ultrastructure of NVUs in each group was observed by electron microscopy,and various biochemical indicators were detected by enzymelinked immunosorbent assay(ELISA).The protein expression level was detected by Western blot.The mRNA expression was detected by quantitative real-time polymerase chain reaction(qRT-PCR).RESULTS:The results of the Morris water maze and step-down tests showed that ischemia reduced learning and memory in the mice,which were restored by SLT.The results of HE staining showed that SLT restored the pathological changes of the NVUs.The Congo red staining results revealed that SLT also improved the scattered orange-red sediments in the upper cortex a展开更多
Despite exciting achievements with some malignancies,immunotherapy for hypoimmunogenic cancers,especially glioblastoma(GBM),remains a formidable clinical challenge.Poor immunogenicity and deficient immune infiltrates ...Despite exciting achievements with some malignancies,immunotherapy for hypoimmunogenic cancers,especially glioblastoma(GBM),remains a formidable clinical challenge.Poor immunogenicity and deficient immune infiltrates are two major limitations to an effective cancer-specific immune response.Herein,we propose that an injectable signal-amplifying nanocomposite/hydrogel system consisting of granulocyte-macrophage colony-stimulating factor and imiquimod-loaded antigen-capturing nanoparticles can simultaneously amplify the chemotactic signal of antigen-presenting cells and the"danger"signal of GBM.We demonstrated the feasibility of this strategy in two scenarios of GBM.In the first scenario,we showed that this simultaneous amplification system,in conjunction with local chemotherapy,enhanced both the immunogenicity and immune infiltrates in a recurrent GBM model;thus,ultimately making a cold GBM hot and suppressing postoperative relapse.Encouraged by excellent efficacy,we further exploited this signal-amplifying system to improve the efficiency of vaccine lysate in the treatment of refractory multiple GBM,a disease with limited clinical treatment options.In general,this biomaterial-based immune signal amplification system represents a unique approach to restore GBM-specific immunity and may provide a beneficial preliminary treatment for other clinically refractorymalignancies.展开更多
With the development of ocean engineering, it is one of the most important factors which determine the structural safety, cost and suitable forms of engineerings to select the ocean environmental design criteria. Owin...With the development of ocean engineering, it is one of the most important factors which determine the structural safety, cost and suitable forms of engineerings to select the ocean environmental design criteria. Owing to the complexity , variation and randomness of ocean environmental conditions, the commonly used methods for determining design criteria cannot consider the joint occurring probabilities of several environmental factors ,therefore, lead to overestimate design criteria of them and result in an unnecessary overspend invest in engineering. On the basis of the measured and hindcasting data and the multi-demension joint probability theory, this paper presented the study of the joint loads of wind , wave and current on the offshore structures and its responsible joint probability level with the application of random simulation techniques, and presented the joint design criteria of environmental loads for the realistic design of engineerings.展开更多
We report an efficient mid-infrared extracavity optical parametric oscillator(OPO)based on the nonlinear crystal BaGa4Se7 pumped by a diode-side-pumped Q-switched Nd:Y3 Al5O12(Nd:YAG)laser.The maximum pulse energy of ...We report an efficient mid-infrared extracavity optical parametric oscillator(OPO)based on the nonlinear crystal BaGa4Se7 pumped by a diode-side-pumped Q-switched Nd:Y3 Al5O12(Nd:YAG)laser.The maximum pulse energy of 1.03mJ at 4.25μm is obtained with the repetition rate of 10 Hz and pulse width of 12.6 ns when the pump energy was 13.5mJ,corresponding to an optical-to-optical conversion efficiency of 7.6% from 1.064μm to 4.25μm.The idler wave slope conversion efficiency was 12%.To the best of our knowledge,it is the highest reported conversion efficiency for the compact BaGa4Se7 OPO driven by the Nd:YAG laser.展开更多
基金National Natural Science Foundation of China(81503450):Experimental study on the treatment of transgenic mice with Alzheimer's disease by protecting neurovascular unit by supplementing Qi and activating blood circulation investigate。
文摘OBJECTIVE:To discuss the influence of Sailuotong(塞络通,SLT)on the Neurovascular Unit(NVUs)of amyloid precursor protein(APP)/presenilin-1(PS1)mice and evaluate the role of gas supplementation in activating blood circulation during the progression of Alzheimer's disease(AD).METHODS:The mice were allocated into the following nine groups:(a)the C57 Black(C57BL)sham-operated group(control group),(b)ischaemic treatment in C57BL mice(the C57 ischaemic group),(c)the APP/PS1 sham surgery group(APP/PS1 model group),(d)ischaemic treatment in APP/PS1 mice(APP/PS1 ischaemic group),(e)C57BL mice treated with aspirin following ischaemic treatment(C57BL ischaemic+aspirin group),(f)C57BL mice treated with SLT following ischaemic treatment(C57BL ischaemic+SLT group),(g)APP/PS1 mice treated with SLT(APP/PS1+SLT group),(h)APP/PS1 mice treated with donepezil hydrochloride following ischaemic treatment(APP/PS1 ischaemic+donepezil hydrochloride group)and(i)APP/PS1 mice treated with SLT following ischaemic treatment(APP/PS1 ischaemic+SLT group).The ischaemic model was established by operating on the bilateral common carotid arteries and creating a microembolism.The Morris water maze and step-down tests were used to detect the spatial behaviour and memory ability of mice.The hippocampus of each mouse was observed by haematoxylin and eosin(HE)and Congo red staining.The ultrastructure of NVUs in each group was observed by electron microscopy,and various biochemical indicators were detected by enzymelinked immunosorbent assay(ELISA).The protein expression level was detected by Western blot.The mRNA expression was detected by quantitative real-time polymerase chain reaction(qRT-PCR).RESULTS:The results of the Morris water maze and step-down tests showed that ischemia reduced learning and memory in the mice,which were restored by SLT.The results of HE staining showed that SLT restored the pathological changes of the NVUs.The Congo red staining results revealed that SLT also improved the scattered orange-red sediments in the upper cortex a
基金supported by the National Natural Science Foundation of China(No.81773911,81690263,and 81573616)the Development Project of Shanghai Peak Disciplines-Integrated Medicine(No.20180101).
文摘Despite exciting achievements with some malignancies,immunotherapy for hypoimmunogenic cancers,especially glioblastoma(GBM),remains a formidable clinical challenge.Poor immunogenicity and deficient immune infiltrates are two major limitations to an effective cancer-specific immune response.Herein,we propose that an injectable signal-amplifying nanocomposite/hydrogel system consisting of granulocyte-macrophage colony-stimulating factor and imiquimod-loaded antigen-capturing nanoparticles can simultaneously amplify the chemotactic signal of antigen-presenting cells and the"danger"signal of GBM.We demonstrated the feasibility of this strategy in two scenarios of GBM.In the first scenario,we showed that this simultaneous amplification system,in conjunction with local chemotherapy,enhanced both the immunogenicity and immune infiltrates in a recurrent GBM model;thus,ultimately making a cold GBM hot and suppressing postoperative relapse.Encouraged by excellent efficacy,we further exploited this signal-amplifying system to improve the efficiency of vaccine lysate in the treatment of refractory multiple GBM,a disease with limited clinical treatment options.In general,this biomaterial-based immune signal amplification system represents a unique approach to restore GBM-specific immunity and may provide a beneficial preliminary treatment for other clinically refractorymalignancies.
文摘With the development of ocean engineering, it is one of the most important factors which determine the structural safety, cost and suitable forms of engineerings to select the ocean environmental design criteria. Owing to the complexity , variation and randomness of ocean environmental conditions, the commonly used methods for determining design criteria cannot consider the joint occurring probabilities of several environmental factors ,therefore, lead to overestimate design criteria of them and result in an unnecessary overspend invest in engineering. On the basis of the measured and hindcasting data and the multi-demension joint probability theory, this paper presented the study of the joint loads of wind , wave and current on the offshore structures and its responsible joint probability level with the application of random simulation techniques, and presented the joint design criteria of environmental loads for the realistic design of engineerings.
基金supported by the Science and Technology on Plasma Physics Laboratory(No.6142A04030403)the Innovation Fund of the Chinese Academy of Sciences(No.CXJJ-17-M164)
文摘We report an efficient mid-infrared extracavity optical parametric oscillator(OPO)based on the nonlinear crystal BaGa4Se7 pumped by a diode-side-pumped Q-switched Nd:Y3 Al5O12(Nd:YAG)laser.The maximum pulse energy of 1.03mJ at 4.25μm is obtained with the repetition rate of 10 Hz and pulse width of 12.6 ns when the pump energy was 13.5mJ,corresponding to an optical-to-optical conversion efficiency of 7.6% from 1.064μm to 4.25μm.The idler wave slope conversion efficiency was 12%.To the best of our knowledge,it is the highest reported conversion efficiency for the compact BaGa4Se7 OPO driven by the Nd:YAG laser.
