Objective To analyze the interactions between different structural types of volatile oil compo-nents(VOCs)and skin lipid molecules;and investigate the mechanism of volatile oil in Chi-nese materia medica(VOCMM)as pene...Objective To analyze the interactions between different structural types of volatile oil compo-nents(VOCs)and skin lipid molecules;and investigate the mechanism of volatile oil in Chi-nese materia medica(VOCMM)as penetration enhancers.Methods In this study;210 different structural types of VOCs were selected from the VOCMM penetration enhancer database;and the molecular docking experiments were conducted with three main lipid molecules of skin:ceramide 2(CER2);cholesterol(CHL);and free fatty acid(FFA).Each VOC was docked individually with each lipid molecule.Cluster analysis was used to explore the relationship between the binding energy of VOCs and their molecular struc-tures.Nine specific pathogen-free(SPF)Sprague Dawley(SD)rats were randomly divided in-to Control;Nootkatone;and 3-Butylidenephthalide groups for in vitro percutaneous experi-ments;with three rats in each group.The donor pool solutions were 3%gastrodin;3%gas-trodin+3%nootkatone;and 3%gastrodin+3%3-butylidenephthalide;respectively.The pen-etration enhancing effects of VOCs with higher binding energy were evaluated by comparing the 12-hour cumulative percutaneous absorption of gastrodin(Q12;µg/cm²).Results(i)Most of the VOCs were non-hydrogen bonded to the hydrophobic parts of CHL and FFA;and hydrogen bonded to the head group of CER2.Among them;sesquiterpene ox-ides showed the most pronounced binding affinity to CER2.The VOCs with 2-4 rings(in-cluding carbon rings;benzene rings;and heterocycles)demonstrated stronger binding affini-ty for three skin lipid molecules compared with the VOCs without intramolecular rings(P<0.01).(ii)According to the cluster analysis;most of the VOCs that bond well to CER2 had 2-3 intramolecular rings.The non-oxygenated VOCs were bonded to CER2 in a hydrophobic manner.The oxygenated VOCs were mostly bonded to CER2 by hydrogen bonding.(iii)The results of Franz diffusion cell experiment showed that the Q12 of Control group was 260.60±25.09µg/cm2;and the transdermal absorption of gastrodin was significantly increased in Nootkatone group(Q12=5503.00±1080.00µg/cm²;P<0.01).The transdermal absorption of gastrodin was also increased in 3-Butylidenephthalide group(Q12=495.40±56.98µg/cm²;P>0.05).(iv)The type of oxygen-containing functional groups in VOCs was also an influencing factor of binding affinity to CER2.Conclusion The interactions between different types of VOCs with different structures in the VOCMM and three skin lipid molecules in the stratum corneum were investigated at the molecular level in this paper.This research provided theoretical guidance and data support for the screening of volatile oil-based penetration enhancers;and a simple and rapid method for studying the penetration-enhancing mechanism of volatile oils.展开更多
Objective:Inflammation in the central nervous system plays a crucial role in the occurrence and development of sepsis-associated encephalopathy.This study aims to explore the effects of maresin 1(MaR1),an anti-inflamm...Objective:Inflammation in the central nervous system plays a crucial role in the occurrence and development of sepsis-associated encephalopathy.This study aims to explore the effects of maresin 1(MaR1),an anti-inflammatory and pro-resolving lipid mediator,on sepsis-induced neuroinflammation and cognitive impairment.Methods:Mice were randomly assigned to 4 groups:A sham group(sham operation+vehicle),a cecal ligation and puncture(CLP)group(CLP operation+vehicle),a MaR1-LD group(CLP operation+1 ng MaR1),and a MaR1-HD group(CLP operation+10 ng MaR1).MaR1 or vehicle was intraperitoneally administered starting 1 h before CLP operation,then every other day for 7 days.Survival rates were monitored,and serum inflammatory cytokines[tumor necrosis factor alpha(TNF-α),interleukin(IL)-1β,and IL-6]were measured 24 h after operation using enzyme-linked immunosorbent assay(ELISA).Cognitive function was assessed 7 days after operation using the Morris water maze(MWM)test and novel object recognition(NOR)task.The mRNA expression of TNF-α,IL-1β,IL-6,inducible nitric oxide synthase(iNOS),IL-4,IL-10,and arginase 1(Arg1)in cortical and hippocampal tissues was determined by real-time reverse transcription PCR(RT-PCR).Western blotting was used to determine the protein expression of iNOS,Arg1,signal transducer and activator of transcription 6(STAT6),peroxisome proliferator-activated receptor gamma(PPARγ),and phosphorylated STAT6(p-STAT6)in hippocampal tissue.Microglia activation was visualized via immunofluorescence.Mice were also treated with the PPARγantagonist GW9662 to confirm the involvement of this pathway in MaR1’s effects.Results:CLP increased serum levels of TNF-α,IL-1β,and IL-6,and reduced body weight and survival rates(all P<0.05).Both 1 ng and 10 ng doses of MaR1 significantly reduced serum TNF-α,IL-1β,and IL-6 levels,improved body weight,and increased survival rates(all P<0.05).No significant difference in efficacy was observed between the 2 doses(all P>0.05).MWM test and NOR task indicated that CLP impaired spatial learning,which MaR1 mitigated.However,GW9662 partially reversed MaR1’s protective effects.Real-time RTPCR results demonstrated that,compared to the sham group,mRNA expression of TNF-α,IL-1β,and iNOS significantly increased in hippocampal tissues following CLP(all P<0.05),while IL-4,IL-10,and Arg1 showed a slight decrease,though the differences were not statistically significant(all P>0.05).Compared to the CLP group,both 1 ng and 10 ng MaR1 decreased TNF-α,IL-1β,and iNOS mRNA expression in hippocampal tissues and increased IL-4,IL-10,and Arg1 mRNA expression(all P<0.05).Immunofluorescence results indicated a significant increase in Iba1-positive microglia in the hippocampus after CLP compared to the sham group(P<0.05).Administration of 1 ng and 10 ng MaR1 reduced the percentage area of Iba1-positive cells in the hippocampus compared to the CLP group(both P<0.05).Western blotting results showed that,compared to the CLP group,both 1 ng and 10 ng MaR1 down-regulated the iNOS expression,while up-regulated the expression of Arg1,PPARγ,and p-STAT6(all P<0.05).However,the inclusion of GW9662 counteracted the MaR1-induced upregulation of Arg1 and PPARγcompared to the MaR1-LD group(all P<0.05).Conclusion:MaR1 inhibits the classical activation of hippocampal microglia,promotes alternative activation,reduces sepsis-induced neuroinflammation,and improves cognitive decline.展开更多
Aim To investigate the synergistic effect of the combination of pinellia total alkaloid (PTA) and uncaria total alkaloid (UTA), and explore the mechanism of anticonvulsant action. Methods Anticonvulsant and toxic ...Aim To investigate the synergistic effect of the combination of pinellia total alkaloid (PTA) and uncaria total alkaloid (UTA), and explore the mechanism of anticonvulsant action. Methods Anticonvulsant and toxic effect profiles of combinations of PTA with UTA, alone and at three fixed ratios of 1:4, 1 :1, 4:1, were evaluated in maximal electroshock (MES)-induced seizures and acute toxicity test in mice. Respective ED50 and LD50 were calculated with Bliss's method. Their synergistic effect were evaluated by isobolographic analysis and allowed the determination of benefit indices (BI) for respective combinations. The model of convulsive rats kindled by penicillin topically injected into cortex was used to investigated the content of Glu, Asp, Gly and GABA in hippocampus using high performance liquid chromatography (HPLC). Results Combinations of PTA and UTA at the ratio of 4:1 were synergistic in MES test and antagonistic in acute toxicity test, showing the best profile for combinations of PTA with UTA. In contrast, the ratios of 1 :4 and 1 : 1, despite synergistic in MES test, were additive in acute toxicity test. The 4:1 combination and two drugs alone significantly decreased Glu level and increased GABA level in the hippocampus, but the GABA level in the 4:1 combination group was higher than that in the two drugs alone groups. They did not have significant influence on the levels of ASp and Gly. Conclusion Combinations of PTA and UTA at 4:1 ratio demonstrated synergistic effect in anticonvulsant action and antagonistic effect in toxicity. The anticonvulsant mechanism might be related to decreasing the excitability of Glutamatergic neurons and increasing the inhibition of GABAergic neurons.展开更多
Objective: To investigate the inhibitory effects of combination chemotherapy of Carboplatin (CBP), Teniposide (Vm-26), Methasquin (MTX), and Nimodipine (NIM) on glioma, and to explore the sensitivity of gliom...Objective: To investigate the inhibitory effects of combination chemotherapy of Carboplatin (CBP), Teniposide (Vm-26), Methasquin (MTX), and Nimodipine (NIM) on glioma, and to explore the sensitivity of glioma cells to different treatment regimens so as to provide some clues for clinical usage of interstitial combination chemotherapy. Methods: MTT assay and 3H-TdR incorporation assay were performed to evaluate the inhibitory effects upon the proliferation of glioma cells, and to compare the sen- sitivity of glioma cells to administration of CBP, Vm-26, MTX, and NIM with that of the administration of CBP+NIM, Vm-26+NIM, MTX+NIM, CBP+Vm-26+MTX, or CBP+Vm-26+MTX+NIM, respectively. Results: The inhibition rate of CBP+Vm-26+MTX+NIM combination administration against glioma cells was 96.64%, higher than that of CBP+NIM (69.03%), Vm-26+NIM (71.53%), MTX+NIM (52.75%), CBP+Vm-26+MTX (78.59%) (P〈0.01), and the dosage of CBP, Vm-26, and MTX was declined to 1/10- 1/100 that of respective use of CBP, Vm-26, and MTX. Conclusion: The curative effect of combination administration of CBP, Vm-26, MTX, and NIM was much better than that of respective administration, suggesting a higher inhibition rate and a lower dosage use.展开更多
Objective Neuroinflammation with microglial activation has been implicated to have a strong association with the progressive dopaminergic neuronal loss in Parkinson's disease (PD). The present study was undertaken ...Objective Neuroinflammation with microglial activation has been implicated to have a strong association with the progressive dopaminergic neuronal loss in Parkinson's disease (PD). The present study was undertaken to evaluate the activation profile of microglia in 1-methyl-4-phenyl pyridinium (MPP^+)-induced hemiparkinsonian rats. Triptolide, a potent immunosuppressant and microglia inhibitor, was then examined for its efficacy in protecting dopaminergic neurons from injury and ameliorating behavioral disabilities induced by MPP^+. Methods The rat model of PD was established by intranigral microinjection of MPP^+. At baseline and on day 1, 3, 7, 14, 21 following MPP^+ injection, the degree of microglial activation was examined by detecting the immunodensity of OX-42 (microglia marker) in the substantia nigra (SN). The number of viable dopaminergic neurons was determined by measuring tyrosine hydroxylase (TH) positive neurons in the SN. Behavioral performances were evaluated by counting the number of rotations induced by apomorphine, calculating scores of forelimb akinesia and vibrissae-elicited forelimb placing asymmetry. Results Intranigral injection of MPP^+ resulted in robust activa- tion of microglia, progressive depletion of dopaminergic neurons, and ongoing aggravation of behavioral disabilities in rats. Triptolide significantly inhibited microglial activation, partially prevented dopaminergic cells from death and improved behavioral performances. Conclusion These data demonstrated for the first time a neuroprotective effect of triptolide on dopaminergic neurons in MPP^+ induced hemiparkinsonian rats. The protective effect of triptolide may, at least partially, be related to the inhibition of MPP^+-induced microglial activation. Our results lend strong support to the use of immunosuppressive agents in the management of PD.展开更多
Objective: To investigate the treatment effectiveness and side effects of stereotactic radiotherapy for brain glioma. Methods: From Jun. 1995 to Dec. 1998, 389 cases of brain gliomas were treated by stereotactic rad...Objective: To investigate the treatment effectiveness and side effects of stereotactic radiotherapy for brain glioma. Methods: From Jun. 1995 to Dec. 1998, 389 cases of brain gliomas were treated by stereotactic radiotherapy, among which 151 cases were treated by stereotactic radiosurgery (SRS) and the other 238 cases, by fractionated stereotactic radiotherapy (FSRT). In the SRS group, the marginal tumor dose was 20 to 30 Gy (median, 2.6 Gy). One to 6 isocenters (median, 2.48) and 5 to 21 irradiation arcs (median, 8.45) were applied. In the FSRT group, the per-fraction marginal tumor dose was 8 to 12 Gy with 1 to 6 isocenters (median, 2.53), 6 to 20 irradiation arcs (median, 8.25) and 2-5 fractions delivered everyday or every other day. Results: Three months after treatment, the complete and partial response rates were 13.9% and 45.7% in SRS group respectively. The stable disease rate was 17.2%. The total effective rate was 76.8%. In FSRT group, the complete and partial remission rates were 19.7% and 47.9% respectively. The stable disease rate was 20.6%. The total effective rate was 88.2%. The total effective rate of FSRT group was higher than that in SRS group (X^2=9.874, P=0.020). The 1-year, 3-year and 5-year survival rate of all patients was 54.3%, 29.3%, 16.5% respectively. The 1-year, 3-year and 5-year survival rate in SRS group and FSRT group was 52.3% vs 26.5%, 11.9% vs 55.5%, and 31.1 vs 19.3% respectively. There was no significant difference between the two groups (X^2=2.16, P=0.1417). The brain edema caused by the main radiation was more severe in the SRS group than in FSRT group (X^2=4.916, P=0.027). Conclusion: It is effective for brain glioma to be treated by stereotactic radiotherapy. Compared with SRS, the FSRT has the advantage of good effect and less side response.展开更多
Objective: To study p27/Kipl expression in gliomas and its application value. Methods: Imo munohistochemical technique was used to detect the exprssion of p27/Kipl gene in 48 different malignant grade human brain gl...Objective: To study p27/Kipl expression in gliomas and its application value. Methods: Imo munohistochemical technique was used to detect the exprssion of p27/Kipl gene in 48 different malignant grade human brain glioma tissues categorized according to WHO classification and 12 normal human brain tissues,which were analyzed quantitatively by using the image system and compared retrospectively with the patients' clinical characteristics. Results: In this series, the immunohistochemical reaction for p27/Kipl was confined to the nuclei. The abnormal positive expression rate of p27/Kipl in gliomas was found to be higher than that in normal tissues (P〈0.05). The positive nuclei expression of p27/Kipl decreased in number and staining intensity with the increasing degree of histological malignancy (P〈0.05). Lower expression of p27/Kipl was associated with poor prognosis (P〈0.05). P27/Kipl expression could be regarded as an independent prognostic factor. Conclusion: The abnormal expression of p27/Kipl may be closely related to the occurrence and development of gliomas, and also can be used to evaluate the prognosis independently.展开更多
The results of the previous studies seem to show the crustaceans can secrete growth hormone,which regulate their growth.However,more evidences are needed to determine it.So the following research was conducted.The ext...The results of the previous studies seem to show the crustaceans can secrete growth hormone,which regulate their growth.However,more evidences are needed to determine it.So the following research was conducted.The extract of thoracic ganglia (TGE) of adult Macrobrachium rosenbergii was applied to a Sephadex G-50 column,the resulting second peak was further isolated by HPLC,and 9 fractions were obtained.Among the fractions only the second fraction significantly increased the protein synthesis of the abdomen muscle of the juvenile M.rosenbergii that was injected TGE.The increasing effects were related to the protein concentration of the injecting fractions.The molecular weight of the substance in the second fraction isolated by HPLC was below 3.4?kDa.The results indicate that the thoracic ganglia of M.rosenbergii could secrete a peptide hormone,which stimulates the muscle protein synthesis of prawn,and the hormone might be the growth hormone of the prawn.展开更多
The research analyzed social and economic development around Chao Lake as well as changes of water quality in Chao Lake and explored the relation- ships of local population and GDP with water chemical oxygen demand (...The research analyzed social and economic development around Chao Lake as well as changes of water quality in Chao Lake and explored the relation- ships of local population and GDP with water chemical oxygen demand (COD), total phosphorus (TP), total nitrogen (TN), chlorophyll and eutrophication index. The re- sults showed that population around Chao Lake and GDP kept growing from 2001 to 2013, and water quality was improving. In addition, correlation analysis indicated that except of water eutrophication, GDP and population showed inverse correlation with other indices, demonstrating that water quality has been effectively controlled in Chao Lake recently.展开更多
[Objective] This study aimed to provide a theoretical basis for the further development of bag culture in production of facility vegetables. [Method] The effects of different previous crops and bag colors on the growt...[Objective] This study aimed to provide a theoretical basis for the further development of bag culture in production of facility vegetables. [Method] The effects of different previous crops and bag colors on the growth and development, yield and quality of tomato were investigated under the condition of substrate bag culture. [Result] The plant growth of tomato cultivated in bag was close to that of the tomato growing in soil. Under the condition of substrate bag culture, the yield of tomato was increased by as high as 4%, the irrigation water was saved by 39.6%, the fertilizer for drip irrigation was saved by 77.5%, the vitamin C content and the flavor of tomato were improved, and the content of nitrate in tomato was reduced compared with soil cultivation. [Conclusion] Substrate bag culture of tomato could achieve better economic benefits.展开更多
In order to carry out an integrated assessment of sea water quality objectively, this paper based on the concept and principle of artificial neural network, generated appropriate training samples for BP artificial neu...In order to carry out an integrated assessment of sea water quality objectively, this paper based on the concept and principle of artificial neural network, generated appropriate training samples for BP artificial neural network model through the method of producing samples to the concentration of various pollution index of sea water quality from the viewpoint of threshold, established the BP artificial neural network model of sea water quality assessment using multi-layer neural network with error back-propagation algorithm. This model was used to assess water environment and obtain sea water quality categories of offshore area in Bohai Bay through calculating. The calculations shown that pollution index in river's wet season was higher than that in dry season from 2004 to 2007, and the pollution was particularly serious in 2005 and 2006, but a little better in 2007. The assessed results of cases shown that the model was reasonable in design and higher in generalization, meanwhile, it was common, objective and practical to sea water quality assessment.展开更多
Given the great strides that China's education sector has made in recent decades, it can be expected that the overall workforce quality of exiting China's labor market in coming one or two decades will be relatively...Given the great strides that China's education sector has made in recent decades, it can be expected that the overall workforce quality of exiting China's labor market in coming one or two decades will be relatively low, while the overall quality of workforce newly entering into China's labor market will be high. As the new, bettereducated generation takes over, China's workforce quality will be vastly improved. This in turn will promote economic growth. We refer to economic growth arising from improved workforce quality as qualitative demographic dividend. Using the computable general equilibrium (CGE) model, this paper investigates the relationship between workforce quality improvements and economic growth. According to the model's results, an improvement in workforce quality will raise the economic growth rate by about two percentage points per annum between 2016 and 2020 and by 10 percentage points cumulatively by 2020. In other words, GDP will be 1.1 times the level of baseline GDP by 2020 due to the improved education levels. Given different production functions across sectors, the improvement of workforce quality will affect different sectors in different ways. On the whole, the improvement of workforce quality is more favorable to the development of capital-intensive sectors and sectors with rapid technology progress. According to this paper, considering the improvement of workforce quality, we cannot conclude that China's potential economic growth rate has already begun to decline. Despite diminishing conventional quantitative demographic dividends, China "s qualitative demographic dividends will keep rising. Qualitative demographic dividends will further push forward China's industrial restructuring and the strategic transition of industrial competitiveness from quantitative to qualitative and from an extensive to an intensive pattern of development.展开更多
The localization of four neuropeptidelike substances during embryonic development in amphibian was studied by using immuno cytochemical technique. The cells with positive reaction appeared firstly in the endoderm ce...The localization of four neuropeptidelike substances during embryonic development in amphibian was studied by using immuno cytochemical technique. The cells with positive reaction appeared firstly in the endoderm cells during early tailbud stage, and then were detected in connective tissue at the outer portion of gastrointestinal tract during tadpole stage. In the nervous system, the cells with positive reaction were observed in cranial ganglion and glial cells at the outer margin of the brain and in the inner wall of ventricles. They were also frequently observed in the epidermis during late tailbud stage. The relationship between the appearance of neuropeptides in timespatial sequences and the development of nervous system, the neural crest origin of the cells with positive reaction, and the role of epidermal conductivity in neuropeptidelike cells in epiderms were discussed.展开更多
Objective To identify new genes required for neurosecretory control of aging in C. elegans. Methods In view of the importance of nervous system in aging regulation, we performed the screen for genes involved in the ag...Objective To identify new genes required for neurosecretory control of aging in C. elegans. Methods In view of the importance of nervous system in aging regulation, we performed the screen for genes involved in the aging regulation from genetic loci encoding synaptic proteins by lifespan assay and accumulation of lipofuscin autofluorescence. We further investigated the dauer formation phenotypes of their corresponding mutants and whether they were possibly up-regulated by the insulin-like signaling pathway. Results The genetic loci of unc-10, syd-2, hlb-1, dlk-1, mkk-4, scd- 2, snb-1, ric-4, nrx-1, unc-13, sbt-1 and unc-64 might be involved in the aging control. In addition, functions of unc-10, syd-2, hlb-1, dlk-1, mkk-4, scd-2, snb-1, ric-4 and nrx-1 in regulating aging may be opposite to those of unc-13, sbt-1 and unc-64. The intestinal autofluorescence assay further indicated that the identified long-lived and short-lived mutants were actually due to the suppressed or accelerated aging. Among the identified genes, syd-2, hlb-1, mkk-4, scd-2, snb-1, ric-4 and unc-64 were also involved in the control of dauer formation. Moreover, daf-2 mutation positively regulated the expression of syd-2 and hlb-1, and negatively regulated the expression of mkk-4, nrx-1, ric-4, sbt-1, rpm-1, unc-10, dlk- 1 and unc-13. The daf-16 mutation positively regulated the expression of syd-2 and hlb-1, and negatively regulated the expression of mkk-4, nrx-1, sbt-1, rpm-1, unc-10, dlk-1 and unc-13. Conclusion These data suggest the possibly important status of the synaptic transmission to the animal' s life-span control machinery, as well as the dauer formation control.展开更多
Objective To investigate the cell proliferation and differentiation in the developing brain of mouse. Methods C57/BL6 mice were divided into 3 groups at random. Bromodeoxyuridine (BrdU) was injected into the brains ...Objective To investigate the cell proliferation and differentiation in the developing brain of mouse. Methods C57/BL6 mice were divided into 3 groups at random. Bromodeoxyuridine (BrdU) was injected into the brains in different development periods once a day for 7 d. The brains were retrieved 4 weeks after the last BrdU injection. Immunohistochemical and immunofluorescent studies were carried out for detecting cell proliferation (BrdU) and cell differentiation (NeuN, APC, lbal, and S 100β), respectively. Results The number of BrdU labeled cells decreased significantly with the development of the brain. Cell proliferation was prominent in the cortex and striatum. A small portion of BrdU and NeuN double labeled cells could be detected in the cortex at the early stage of development, and in the striatum and CA of the hippocampus in all groups. The majority of BrdU labeled cells were neuroglia, and the number of neuroglia cells decreased dramatically with brain maturation. Neurogenesis is the major cytogenesis in the dentate gyrus. Conclusion These results demonstrated that cell proliferation, differentiation and survival were age and brain region related.展开更多
Objective To evaluate the role of thrombin-activated microglia in the neurodegeneration of nigral dopaminergic neurons in the rat substantia nigra (SN) in vivo. Methods After stereotaxic thrombin injection into unil...Objective To evaluate the role of thrombin-activated microglia in the neurodegeneration of nigral dopaminergic neurons in the rat substantia nigra (SN) in vivo. Methods After stereotaxic thrombin injection into unilateral SN of rats, immunostaining, reverse transcription polymerase chain reaction (RT-PCR) and biochemical methods were used to observe tyrosine hydroxylase (TH) irnmunoreactive positive cells, microglia activation, nitric oxide (NO) amount and inducible nitricoxide synthase (iNOS) expression. Results (1) Selective damage to dopaminergic neurons was produced after thrombin injection, which was evidenced by loss of TH imrnunostaining in time-dependent manner; (2) Strong microglial activation was observed in the SN; (3) RT-PCR demonstrated the early and transient expression of neurotoxic factors iNOS mRNA in the SN. Immunofluorescence results found that thrombin induced expression of iNOS in microglia. The NO production in the thrombininjected rats was significantly higher than that of controls (P 〈 0.05). Conclusion Thrombin intranigral injection can injure the dopaminergic neurons in the SN. Thrombin-induced microglia activation precedes dopaminergic neuron degeneration, which suggest that activation of microglia and release of NO may play important roles in dopaminergic neuronal death in the SN.展开更多
A new type of recurrent neural network is discussed, which provides the potential for modelling unknown nonlinear systems. The proposed network is a generalization of the network described by Elman, which has three la...A new type of recurrent neural network is discussed, which provides the potential for modelling unknown nonlinear systems. The proposed network is a generalization of the network described by Elman, which has three layers including the input layer, the hidden layer and the output layer. The input layer is composed of two different groups of neurons, the group of external input neurons and the group of the internal context neurons. Since arbitrary connections can be allowed from the hidden layer to the context layer, the modified Elman network has more memory space to represent dynamic systems than the Elman network. In addition, it is proved that the proposed network with appropriate neurons in the context layer can approximate the trajectory of a given dynamical system for any fixed finite length of time. The dynamic backpropagation algorithm is used to estimate the weights of both the feedforward and feedback connections. The methods have been successfully applied to the modelling of nonlinear plants.展开更多
基金National Science Foundation of China(82174093)Fundamental Research Funds for the Central Universities(BUCM-2019-JYB-JS-016).
文摘Objective To analyze the interactions between different structural types of volatile oil compo-nents(VOCs)and skin lipid molecules;and investigate the mechanism of volatile oil in Chi-nese materia medica(VOCMM)as penetration enhancers.Methods In this study;210 different structural types of VOCs were selected from the VOCMM penetration enhancer database;and the molecular docking experiments were conducted with three main lipid molecules of skin:ceramide 2(CER2);cholesterol(CHL);and free fatty acid(FFA).Each VOC was docked individually with each lipid molecule.Cluster analysis was used to explore the relationship between the binding energy of VOCs and their molecular struc-tures.Nine specific pathogen-free(SPF)Sprague Dawley(SD)rats were randomly divided in-to Control;Nootkatone;and 3-Butylidenephthalide groups for in vitro percutaneous experi-ments;with three rats in each group.The donor pool solutions were 3%gastrodin;3%gas-trodin+3%nootkatone;and 3%gastrodin+3%3-butylidenephthalide;respectively.The pen-etration enhancing effects of VOCs with higher binding energy were evaluated by comparing the 12-hour cumulative percutaneous absorption of gastrodin(Q12;µg/cm²).Results(i)Most of the VOCs were non-hydrogen bonded to the hydrophobic parts of CHL and FFA;and hydrogen bonded to the head group of CER2.Among them;sesquiterpene ox-ides showed the most pronounced binding affinity to CER2.The VOCs with 2-4 rings(in-cluding carbon rings;benzene rings;and heterocycles)demonstrated stronger binding affini-ty for three skin lipid molecules compared with the VOCs without intramolecular rings(P<0.01).(ii)According to the cluster analysis;most of the VOCs that bond well to CER2 had 2-3 intramolecular rings.The non-oxygenated VOCs were bonded to CER2 in a hydrophobic manner.The oxygenated VOCs were mostly bonded to CER2 by hydrogen bonding.(iii)The results of Franz diffusion cell experiment showed that the Q12 of Control group was 260.60±25.09µg/cm2;and the transdermal absorption of gastrodin was significantly increased in Nootkatone group(Q12=5503.00±1080.00µg/cm²;P<0.01).The transdermal absorption of gastrodin was also increased in 3-Butylidenephthalide group(Q12=495.40±56.98µg/cm²;P>0.05).(iv)The type of oxygen-containing functional groups in VOCs was also an influencing factor of binding affinity to CER2.Conclusion The interactions between different types of VOCs with different structures in the VOCMM and three skin lipid molecules in the stratum corneum were investigated at the molecular level in this paper.This research provided theoretical guidance and data support for the screening of volatile oil-based penetration enhancers;and a simple and rapid method for studying the penetration-enhancing mechanism of volatile oils.
基金supported by the National Natural Science Foundation (81601728,31500726)the Natural Science Foundation of Hunan Province (2021JJ41002),China。
文摘Objective:Inflammation in the central nervous system plays a crucial role in the occurrence and development of sepsis-associated encephalopathy.This study aims to explore the effects of maresin 1(MaR1),an anti-inflammatory and pro-resolving lipid mediator,on sepsis-induced neuroinflammation and cognitive impairment.Methods:Mice were randomly assigned to 4 groups:A sham group(sham operation+vehicle),a cecal ligation and puncture(CLP)group(CLP operation+vehicle),a MaR1-LD group(CLP operation+1 ng MaR1),and a MaR1-HD group(CLP operation+10 ng MaR1).MaR1 or vehicle was intraperitoneally administered starting 1 h before CLP operation,then every other day for 7 days.Survival rates were monitored,and serum inflammatory cytokines[tumor necrosis factor alpha(TNF-α),interleukin(IL)-1β,and IL-6]were measured 24 h after operation using enzyme-linked immunosorbent assay(ELISA).Cognitive function was assessed 7 days after operation using the Morris water maze(MWM)test and novel object recognition(NOR)task.The mRNA expression of TNF-α,IL-1β,IL-6,inducible nitric oxide synthase(iNOS),IL-4,IL-10,and arginase 1(Arg1)in cortical and hippocampal tissues was determined by real-time reverse transcription PCR(RT-PCR).Western blotting was used to determine the protein expression of iNOS,Arg1,signal transducer and activator of transcription 6(STAT6),peroxisome proliferator-activated receptor gamma(PPARγ),and phosphorylated STAT6(p-STAT6)in hippocampal tissue.Microglia activation was visualized via immunofluorescence.Mice were also treated with the PPARγantagonist GW9662 to confirm the involvement of this pathway in MaR1’s effects.Results:CLP increased serum levels of TNF-α,IL-1β,and IL-6,and reduced body weight and survival rates(all P<0.05).Both 1 ng and 10 ng doses of MaR1 significantly reduced serum TNF-α,IL-1β,and IL-6 levels,improved body weight,and increased survival rates(all P<0.05).No significant difference in efficacy was observed between the 2 doses(all P>0.05).MWM test and NOR task indicated that CLP impaired spatial learning,which MaR1 mitigated.However,GW9662 partially reversed MaR1’s protective effects.Real-time RTPCR results demonstrated that,compared to the sham group,mRNA expression of TNF-α,IL-1β,and iNOS significantly increased in hippocampal tissues following CLP(all P<0.05),while IL-4,IL-10,and Arg1 showed a slight decrease,though the differences were not statistically significant(all P>0.05).Compared to the CLP group,both 1 ng and 10 ng MaR1 decreased TNF-α,IL-1β,and iNOS mRNA expression in hippocampal tissues and increased IL-4,IL-10,and Arg1 mRNA expression(all P<0.05).Immunofluorescence results indicated a significant increase in Iba1-positive microglia in the hippocampus after CLP compared to the sham group(P<0.05).Administration of 1 ng and 10 ng MaR1 reduced the percentage area of Iba1-positive cells in the hippocampus compared to the CLP group(both P<0.05).Western blotting results showed that,compared to the CLP group,both 1 ng and 10 ng MaR1 down-regulated the iNOS expression,while up-regulated the expression of Arg1,PPARγ,and p-STAT6(all P<0.05).However,the inclusion of GW9662 counteracted the MaR1-induced upregulation of Arg1 and PPARγcompared to the MaR1-LD group(all P<0.05).Conclusion:MaR1 inhibits the classical activation of hippocampal microglia,promotes alternative activation,reduces sepsis-induced neuroinflammation,and improves cognitive decline.
基金Natural Science Foundation of Shanxi Province(No 20041109).
文摘Aim To investigate the synergistic effect of the combination of pinellia total alkaloid (PTA) and uncaria total alkaloid (UTA), and explore the mechanism of anticonvulsant action. Methods Anticonvulsant and toxic effect profiles of combinations of PTA with UTA, alone and at three fixed ratios of 1:4, 1 :1, 4:1, were evaluated in maximal electroshock (MES)-induced seizures and acute toxicity test in mice. Respective ED50 and LD50 were calculated with Bliss's method. Their synergistic effect were evaluated by isobolographic analysis and allowed the determination of benefit indices (BI) for respective combinations. The model of convulsive rats kindled by penicillin topically injected into cortex was used to investigated the content of Glu, Asp, Gly and GABA in hippocampus using high performance liquid chromatography (HPLC). Results Combinations of PTA and UTA at the ratio of 4:1 were synergistic in MES test and antagonistic in acute toxicity test, showing the best profile for combinations of PTA with UTA. In contrast, the ratios of 1 :4 and 1 : 1, despite synergistic in MES test, were additive in acute toxicity test. The 4:1 combination and two drugs alone significantly decreased Glu level and increased GABA level in the hippocampus, but the GABA level in the 4:1 combination group was higher than that in the two drugs alone groups. They did not have significant influence on the levels of ASp and Gly. Conclusion Combinations of PTA and UTA at 4:1 ratio demonstrated synergistic effect in anticonvulsant action and antagonistic effect in toxicity. The anticonvulsant mechanism might be related to decreasing the excitability of Glutamatergic neurons and increasing the inhibition of GABAergic neurons.
文摘Objective: To investigate the inhibitory effects of combination chemotherapy of Carboplatin (CBP), Teniposide (Vm-26), Methasquin (MTX), and Nimodipine (NIM) on glioma, and to explore the sensitivity of glioma cells to different treatment regimens so as to provide some clues for clinical usage of interstitial combination chemotherapy. Methods: MTT assay and 3H-TdR incorporation assay were performed to evaluate the inhibitory effects upon the proliferation of glioma cells, and to compare the sen- sitivity of glioma cells to administration of CBP, Vm-26, MTX, and NIM with that of the administration of CBP+NIM, Vm-26+NIM, MTX+NIM, CBP+Vm-26+MTX, or CBP+Vm-26+MTX+NIM, respectively. Results: The inhibition rate of CBP+Vm-26+MTX+NIM combination administration against glioma cells was 96.64%, higher than that of CBP+NIM (69.03%), Vm-26+NIM (71.53%), MTX+NIM (52.75%), CBP+Vm-26+MTX (78.59%) (P〈0.01), and the dosage of CBP, Vm-26, and MTX was declined to 1/10- 1/100 that of respective use of CBP, Vm-26, and MTX. Conclusion: The curative effect of combination administration of CBP, Vm-26, MTX, and NIM was much better than that of respective administration, suggesting a higher inhibition rate and a lower dosage use.
文摘Objective Neuroinflammation with microglial activation has been implicated to have a strong association with the progressive dopaminergic neuronal loss in Parkinson's disease (PD). The present study was undertaken to evaluate the activation profile of microglia in 1-methyl-4-phenyl pyridinium (MPP^+)-induced hemiparkinsonian rats. Triptolide, a potent immunosuppressant and microglia inhibitor, was then examined for its efficacy in protecting dopaminergic neurons from injury and ameliorating behavioral disabilities induced by MPP^+. Methods The rat model of PD was established by intranigral microinjection of MPP^+. At baseline and on day 1, 3, 7, 14, 21 following MPP^+ injection, the degree of microglial activation was examined by detecting the immunodensity of OX-42 (microglia marker) in the substantia nigra (SN). The number of viable dopaminergic neurons was determined by measuring tyrosine hydroxylase (TH) positive neurons in the SN. Behavioral performances were evaluated by counting the number of rotations induced by apomorphine, calculating scores of forelimb akinesia and vibrissae-elicited forelimb placing asymmetry. Results Intranigral injection of MPP^+ resulted in robust activa- tion of microglia, progressive depletion of dopaminergic neurons, and ongoing aggravation of behavioral disabilities in rats. Triptolide significantly inhibited microglial activation, partially prevented dopaminergic cells from death and improved behavioral performances. Conclusion These data demonstrated for the first time a neuroprotective effect of triptolide on dopaminergic neurons in MPP^+ induced hemiparkinsonian rats. The protective effect of triptolide may, at least partially, be related to the inhibition of MPP^+-induced microglial activation. Our results lend strong support to the use of immunosuppressive agents in the management of PD.
文摘Objective: To investigate the treatment effectiveness and side effects of stereotactic radiotherapy for brain glioma. Methods: From Jun. 1995 to Dec. 1998, 389 cases of brain gliomas were treated by stereotactic radiotherapy, among which 151 cases were treated by stereotactic radiosurgery (SRS) and the other 238 cases, by fractionated stereotactic radiotherapy (FSRT). In the SRS group, the marginal tumor dose was 20 to 30 Gy (median, 2.6 Gy). One to 6 isocenters (median, 2.48) and 5 to 21 irradiation arcs (median, 8.45) were applied. In the FSRT group, the per-fraction marginal tumor dose was 8 to 12 Gy with 1 to 6 isocenters (median, 2.53), 6 to 20 irradiation arcs (median, 8.25) and 2-5 fractions delivered everyday or every other day. Results: Three months after treatment, the complete and partial response rates were 13.9% and 45.7% in SRS group respectively. The stable disease rate was 17.2%. The total effective rate was 76.8%. In FSRT group, the complete and partial remission rates were 19.7% and 47.9% respectively. The stable disease rate was 20.6%. The total effective rate was 88.2%. The total effective rate of FSRT group was higher than that in SRS group (X^2=9.874, P=0.020). The 1-year, 3-year and 5-year survival rate of all patients was 54.3%, 29.3%, 16.5% respectively. The 1-year, 3-year and 5-year survival rate in SRS group and FSRT group was 52.3% vs 26.5%, 11.9% vs 55.5%, and 31.1 vs 19.3% respectively. There was no significant difference between the two groups (X^2=2.16, P=0.1417). The brain edema caused by the main radiation was more severe in the SRS group than in FSRT group (X^2=4.916, P=0.027). Conclusion: It is effective for brain glioma to be treated by stereotactic radiotherapy. Compared with SRS, the FSRT has the advantage of good effect and less side response.
文摘Objective: To study p27/Kipl expression in gliomas and its application value. Methods: Imo munohistochemical technique was used to detect the exprssion of p27/Kipl gene in 48 different malignant grade human brain glioma tissues categorized according to WHO classification and 12 normal human brain tissues,which were analyzed quantitatively by using the image system and compared retrospectively with the patients' clinical characteristics. Results: In this series, the immunohistochemical reaction for p27/Kipl was confined to the nuclei. The abnormal positive expression rate of p27/Kipl in gliomas was found to be higher than that in normal tissues (P〈0.05). The positive nuclei expression of p27/Kipl decreased in number and staining intensity with the increasing degree of histological malignancy (P〈0.05). Lower expression of p27/Kipl was associated with poor prognosis (P〈0.05). P27/Kipl expression could be regarded as an independent prognostic factor. Conclusion: The abnormal expression of p27/Kipl may be closely related to the occurrence and development of gliomas, and also can be used to evaluate the prognosis independently.
文摘The results of the previous studies seem to show the crustaceans can secrete growth hormone,which regulate their growth.However,more evidences are needed to determine it.So the following research was conducted.The extract of thoracic ganglia (TGE) of adult Macrobrachium rosenbergii was applied to a Sephadex G-50 column,the resulting second peak was further isolated by HPLC,and 9 fractions were obtained.Among the fractions only the second fraction significantly increased the protein synthesis of the abdomen muscle of the juvenile M.rosenbergii that was injected TGE.The increasing effects were related to the protein concentration of the injecting fractions.The molecular weight of the substance in the second fraction isolated by HPLC was below 3.4?kDa.The results indicate that the thoracic ganglia of M.rosenbergii could secrete a peptide hormone,which stimulates the muscle protein synthesis of prawn,and the hormone might be the growth hormone of the prawn.
基金Supported by Anhui Environmental Protection Scientific Research Program(2014-004)~~
文摘The research analyzed social and economic development around Chao Lake as well as changes of water quality in Chao Lake and explored the relation- ships of local population and GDP with water chemical oxygen demand (COD), total phosphorus (TP), total nitrogen (TN), chlorophyll and eutrophication index. The re- sults showed that population around Chao Lake and GDP kept growing from 2001 to 2013, and water quality was improving. In addition, correlation analysis indicated that except of water eutrophication, GDP and population showed inverse correlation with other indices, demonstrating that water quality has been effectively controlled in Chao Lake recently.
文摘[Objective] This study aimed to provide a theoretical basis for the further development of bag culture in production of facility vegetables. [Method] The effects of different previous crops and bag colors on the growth and development, yield and quality of tomato were investigated under the condition of substrate bag culture. [Result] The plant growth of tomato cultivated in bag was close to that of the tomato growing in soil. Under the condition of substrate bag culture, the yield of tomato was increased by as high as 4%, the irrigation water was saved by 39.6%, the fertilizer for drip irrigation was saved by 77.5%, the vitamin C content and the flavor of tomato were improved, and the content of nitrate in tomato was reduced compared with soil cultivation. [Conclusion] Substrate bag culture of tomato could achieve better economic benefits.
文摘In order to carry out an integrated assessment of sea water quality objectively, this paper based on the concept and principle of artificial neural network, generated appropriate training samples for BP artificial neural network model through the method of producing samples to the concentration of various pollution index of sea water quality from the viewpoint of threshold, established the BP artificial neural network model of sea water quality assessment using multi-layer neural network with error back-propagation algorithm. This model was used to assess water environment and obtain sea water quality categories of offshore area in Bohai Bay through calculating. The calculations shown that pollution index in river's wet season was higher than that in dry season from 2004 to 2007, and the pollution was particularly serious in 2005 and 2006, but a little better in 2007. The assessed results of cases shown that the model was reasonable in design and higher in generalization, meanwhile, it was common, objective and practical to sea water quality assessment.
文摘Given the great strides that China's education sector has made in recent decades, it can be expected that the overall workforce quality of exiting China's labor market in coming one or two decades will be relatively low, while the overall quality of workforce newly entering into China's labor market will be high. As the new, bettereducated generation takes over, China's workforce quality will be vastly improved. This in turn will promote economic growth. We refer to economic growth arising from improved workforce quality as qualitative demographic dividend. Using the computable general equilibrium (CGE) model, this paper investigates the relationship between workforce quality improvements and economic growth. According to the model's results, an improvement in workforce quality will raise the economic growth rate by about two percentage points per annum between 2016 and 2020 and by 10 percentage points cumulatively by 2020. In other words, GDP will be 1.1 times the level of baseline GDP by 2020 due to the improved education levels. Given different production functions across sectors, the improvement of workforce quality will affect different sectors in different ways. On the whole, the improvement of workforce quality is more favorable to the development of capital-intensive sectors and sectors with rapid technology progress. According to this paper, considering the improvement of workforce quality, we cannot conclude that China's potential economic growth rate has already begun to decline. Despite diminishing conventional quantitative demographic dividends, China "s qualitative demographic dividends will keep rising. Qualitative demographic dividends will further push forward China's industrial restructuring and the strategic transition of industrial competitiveness from quantitative to qualitative and from an extensive to an intensive pattern of development.
文摘The localization of four neuropeptidelike substances during embryonic development in amphibian was studied by using immuno cytochemical technique. The cells with positive reaction appeared firstly in the endoderm cells during early tailbud stage, and then were detected in connective tissue at the outer portion of gastrointestinal tract during tadpole stage. In the nervous system, the cells with positive reaction were observed in cranial ganglion and glial cells at the outer margin of the brain and in the inner wall of ventricles. They were also frequently observed in the epidermis during late tailbud stage. The relationship between the appearance of neuropeptides in timespatial sequences and the development of nervous system, the neural crest origin of the cells with positive reaction, and the role of epidermal conductivity in neuropeptidelike cells in epiderms were discussed.
文摘Objective To identify new genes required for neurosecretory control of aging in C. elegans. Methods In view of the importance of nervous system in aging regulation, we performed the screen for genes involved in the aging regulation from genetic loci encoding synaptic proteins by lifespan assay and accumulation of lipofuscin autofluorescence. We further investigated the dauer formation phenotypes of their corresponding mutants and whether they were possibly up-regulated by the insulin-like signaling pathway. Results The genetic loci of unc-10, syd-2, hlb-1, dlk-1, mkk-4, scd- 2, snb-1, ric-4, nrx-1, unc-13, sbt-1 and unc-64 might be involved in the aging control. In addition, functions of unc-10, syd-2, hlb-1, dlk-1, mkk-4, scd-2, snb-1, ric-4 and nrx-1 in regulating aging may be opposite to those of unc-13, sbt-1 and unc-64. The intestinal autofluorescence assay further indicated that the identified long-lived and short-lived mutants were actually due to the suppressed or accelerated aging. Among the identified genes, syd-2, hlb-1, mkk-4, scd-2, snb-1, ric-4 and unc-64 were also involved in the control of dauer formation. Moreover, daf-2 mutation positively regulated the expression of syd-2 and hlb-1, and negatively regulated the expression of mkk-4, nrx-1, ric-4, sbt-1, rpm-1, unc-10, dlk- 1 and unc-13. The daf-16 mutation positively regulated the expression of syd-2 and hlb-1, and negatively regulated the expression of mkk-4, nrx-1, sbt-1, rpm-1, unc-10, dlk-1 and unc-13. Conclusion These data suggest the possibly important status of the synaptic transmission to the animal' s life-span control machinery, as well as the dauer formation control.
基金This work was supported by the grant of National Natural Science Foundation of China (No. 30470598).
文摘Objective To investigate the cell proliferation and differentiation in the developing brain of mouse. Methods C57/BL6 mice were divided into 3 groups at random. Bromodeoxyuridine (BrdU) was injected into the brains in different development periods once a day for 7 d. The brains were retrieved 4 weeks after the last BrdU injection. Immunohistochemical and immunofluorescent studies were carried out for detecting cell proliferation (BrdU) and cell differentiation (NeuN, APC, lbal, and S 100β), respectively. Results The number of BrdU labeled cells decreased significantly with the development of the brain. Cell proliferation was prominent in the cortex and striatum. A small portion of BrdU and NeuN double labeled cells could be detected in the cortex at the early stage of development, and in the striatum and CA of the hippocampus in all groups. The majority of BrdU labeled cells were neuroglia, and the number of neuroglia cells decreased dramatically with brain maturation. Neurogenesis is the major cytogenesis in the dentate gyrus. Conclusion These results demonstrated that cell proliferation, differentiation and survival were age and brain region related.
文摘Objective To evaluate the role of thrombin-activated microglia in the neurodegeneration of nigral dopaminergic neurons in the rat substantia nigra (SN) in vivo. Methods After stereotaxic thrombin injection into unilateral SN of rats, immunostaining, reverse transcription polymerase chain reaction (RT-PCR) and biochemical methods were used to observe tyrosine hydroxylase (TH) irnmunoreactive positive cells, microglia activation, nitric oxide (NO) amount and inducible nitricoxide synthase (iNOS) expression. Results (1) Selective damage to dopaminergic neurons was produced after thrombin injection, which was evidenced by loss of TH imrnunostaining in time-dependent manner; (2) Strong microglial activation was observed in the SN; (3) RT-PCR demonstrated the early and transient expression of neurotoxic factors iNOS mRNA in the SN. Immunofluorescence results found that thrombin induced expression of iNOS in microglia. The NO production in the thrombininjected rats was significantly higher than that of controls (P 〈 0.05). Conclusion Thrombin intranigral injection can injure the dopaminergic neurons in the SN. Thrombin-induced microglia activation precedes dopaminergic neuron degeneration, which suggest that activation of microglia and release of NO may play important roles in dopaminergic neuronal death in the SN.
文摘A new type of recurrent neural network is discussed, which provides the potential for modelling unknown nonlinear systems. The proposed network is a generalization of the network described by Elman, which has three layers including the input layer, the hidden layer and the output layer. The input layer is composed of two different groups of neurons, the group of external input neurons and the group of the internal context neurons. Since arbitrary connections can be allowed from the hidden layer to the context layer, the modified Elman network has more memory space to represent dynamic systems than the Elman network. In addition, it is proved that the proposed network with appropriate neurons in the context layer can approximate the trajectory of a given dynamical system for any fixed finite length of time. The dynamic backpropagation algorithm is used to estimate the weights of both the feedforward and feedback connections. The methods have been successfully applied to the modelling of nonlinear plants.