Background:Hyperglycemia is a characteristic feature of diabetes that often results in neuropsychological complications such as depression.Diabetic individuals are more vulnerable to experience depression compared to ...Background:Hyperglycemia is a characteristic feature of diabetes that often results in neuropsychological complications such as depression.Diabetic individuals are more vulnerable to experience depression compared to the normal population.Thus,novel treatment approaches are required to reduce depressive symptoms among diabetic individuals.Traditional Chinese medicines(TCMs)such as Shengmai San(SMS)and Radix puerariae(R)are usually widely used to treat ailments such as neurological com-plications since ancient time.Methods:In this study,SMS was combined with R to prepare an R-SMS formulation and screened for their antidepressant activity in diabetic rats.The antidepressant po-tential of the prepared combination was evaluated behaviorally using open field test,novelty-induced hypophagia,and forced swim test in diabetic rats with biochemical and protein expression(PI3K,BDNF[brain-derived neurotrophic factor],and SYN[pr-esynaptic vesicle protein])analysis.Results:Diabetic rats(streptozotocin,45 mg/kg)showed elevated fasting blood glu-cose(FBG)>12 mM with depressive symptoms throughout the study.Treatment with R-SMS(0.5,1.5,and 4.5 g/kg)significantly reverted depressive symptoms in diabetic rats as evinced by significantly(p<0.05)reduced immobility time with an increased tendency to eat food in a novel environment.Treatment with R-SMS also significantly increased the protein expression of PI3K,BDNF,and SYN protein,which play a crucial role in depression.Conclusion:This study showed that R-SMS formulation antagonized depressive symptoms in diabetic rats;thus,this formulation might be studied further to develop as an antidepressant.展开更多
Picea crassifolia and P.wilsonii,commonly used for afforestation in northern China,are increasingly likely to be subjected to high temperatures and soil drought stress as a result of global warming.However,little is k...Picea crassifolia and P.wilsonii,commonly used for afforestation in northern China,are increasingly likely to be subjected to high temperatures and soil drought stress as a result of global warming.However,little is known about the effects of these stresses on foliar photosynthesis in the two species.To investigate how photosynthetic characteristics and sensitivity respond to prolonged high temperatures and soil drought,foliar gas exchange and other closely related parameters were recorded from four-year-old seedlings of both species.Seedlings were grown under two temperature treatments(25/15 and 35/25 °C) and four soil water regimes [80,60,40 and 20% of maximum field capacity(FC)] for 4 months.Although all treatments significantly reduced photosynthetic rates(Pn) of both species,P.crassifolia exhibited greater photosynthetic acclimation than P.wilsonii.Differences in photosynthetic acclimation were mainly related to variations in stomatal conductance(Cond) and the maximum quantum yield of PSII(Fv/Fm) between treatments.Indeed,higher Cond and Fv/Fmin all treatments were shown for P.crassifolia than for P.wilsonii.Moreover,photosynthesis in P.crassifolia exhibited inherently lower temperature sensitivities(broader span for the temperature response curves; lower b) and higher thermostability(invariable b between treatments).Further,severe drought stress(20% FC) limited the survival of P.wilsonii.Our results indicate that P.wilsonii is more susceptible to high temperatures and soil drought stress.Planting P.crassifolia would be more expected to survive these conditions and hence be of greater benefit to forest stability if predicted increases in drought and temperature in northern China occur.展开更多
As an important form of informal finance,commercial credit is widely used among enterprises.Does commercial credit promote the total factor productivity of enterprises?According to the theoretical literature and the r...As an important form of informal finance,commercial credit is widely used among enterprises.Does commercial credit promote the total factor productivity of enterprises?According to the theoretical literature and the reality,using the large sample data of Chinese industrial enterprises,the paper empirically tests the impact of commercial credit on the productivity of enterprises from three aspects:the provision and acquisition of commercial credit and the net commercial credit.The study finds that the provision of commercial credit reduces the productivity level of enterprises;the acquisition of commercial credit fails to promote productivity;while the net commercial credit as a short-term financial buffer for enterprises can alleviate the financing constraints,faced by enterprises,especially private enterprises,which help to increase their productivity levels.In addition,the study found that the higher the marketization process in the region,the more favorable the commercial credit is to the improvement of the production efficiency of private enterprises.展开更多
The main purpose of this paper is to test the production efficiency of different Chinese property industrial enterprises.Based on the large sample panel data of industrial enterprises of the National Bureau of Statist...The main purpose of this paper is to test the production efficiency of different Chinese property industrial enterprises.Based on the large sample panel data of industrial enterprises of the National Bureau of Statistics,we found that although the production efficiency of China-funded enterprises is generally weaker than foreign-funded enterprises,some China-funded enterprises have better learning ability.On the one hand,dynamic analysis found that private enterprises have significant learning ability.On the other hand,the results of convergence analysis show that China’s private enterprises have the potential to gradually catch up with the frontier level of world production efficiency and have better learning ability to catch up potential.And state-owned enterprises tend to be more efficient at the beginning of their establishment,but their productivity is fairly slow to improve,especially for state-owned enterprises with high efficiency sub-samples,so that it’s hard for them to continue improving their efficiency.Institutional analysis found that the marketization process helped the China enterprises to improve their learning ability and China should continue to strengthen the reform of property rights and promote the marketization process.展开更多
BACKGROUND : Parkinson disease is neurodegenerative disorders, characterized by a progressive and selective degeneration of nigrostdatal dopaminergic pathway. Its main clinical symptoms include bradykinesia, dgidity,...BACKGROUND : Parkinson disease is neurodegenerative disorders, characterized by a progressive and selective degeneration of nigrostdatal dopaminergic pathway. Its main clinical symptoms include bradykinesia, dgidity, rest tremor and disturbances in balance. Levodopa (L-DOPA) is the "gold standard" for the symptomatic treatment of Parkinson disease, but L-DOPA is toxic to dopaminergic neurons and the chronic administration of L-DOPA often causes the side effects of motor such as "on-off ", etc., and its mechanism still has not been completely clarified. OBJECTIVE : To observe the changes of the content of glutathione (GSH), activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) and content of malondialdehyde (MDA) in gila-containing mesencephalic culture fluid after L-DOPA of different concentrations were added. DESIGN: A comparative observation. SETTINGS : Department of Neurology, Affiliated Hospital of Taishan Medical University; Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. MATERIALS : The experiment was carried out in the Basic Research Institute, Taishan Medical University from December 2003 to September 2004. Ten postnatal newborn SD rats (within 2 days) were selected, either male or female. Fetal bovine serum (DMEM/F12) was from Gibco Company; L-DOPA and glial fibrillary acidic protein (GFAP) from Sigma Company. Kits for determination of GSH, GSH-Px, SOD and MDA were purchased from Nanjing Jiancheng Bioengineering Research Institute. METHODS : Gila-containing mesencephalic culture fluid were placed in 24-well culture plate, and L-DOPA of 50, 100 and 500 μmot/L was added to each group, the blank control group was also set. The glia-containing mesencephalic culture fluid selected at 4, 24, 48 and 72 hours respectively to determine the GSH content with colorimetdc quantitative technique, GSH-Px activity with colorimetdc method, SOD activity with xanthine oxidase method and MDA content with thiol-barbituric acid method. MAIN OUTCOME MEASURES : GSH and MDA contents, GSH-Px and SOD activities in the glia-containing mesencephalic culture fluid at 4, 24, 48 and 72 hours after L-DOPA of different concentrations were added. RESULTS : In the glia-containing mesencephalic culture fluid after 100 μmol/L L-DOPA was added for 24, 48 and 72 hours, the GSH contents were lower than those in the blank control group [(174.14±39.28), (161.55± 40.79), (144.97±57.59) mg/L; (220.66±32.61), (221.10±32.98), (220.43±31.98) mg/L, P 〈 0.05]; The GSH-Px activities were lower than those in the blank control group [(4.03±1.05), (3.99±1.12), (3.47±1.00) μmol/L; (5.45±1.14), (5.69±1.21), (5.49±1.28) μmol/L, P 〈 0.05]; The SOD activities were also lower than those in the blank control group [(42.02±5.08), (39.38±5.34), (38.87±5.75)kNU/L; (51.35±8.87), (51.78±8.96), (50.99± 9.09) kNU/L, P 〈 0.05]; Whereas the MDA contents were higher than those in the blank control group [(3.51 ± 1.05), (3.99±1.03), (4.45±1.58) μmol/L; (2.09±1.13), (2.18±1.29), (2.01±1.05) μmol/L, P〈 0.05]. In the gli- a-containing mesencephalic culture fluid after 100 μmol/L L-DOPA was added for 4, 24, 48 and 72 hours, the GSH contents were (172.27±26.07), (140.15±61.44), (137.30±50.87), (121.09±66.07) mg/L, the GSH-Px activities were (3.89±1.20), (3.56±1.23), (3.38±1.18), (3.01±1.09) μmol/L, the SOD activities were (38.18±6.75), (35.23±7.85), (4.59±1.24), (31.42±7.01) kNU/L, which were all lower than those in the blank control group (P 〈 0.05-0.01 ); The MDA contents were (3.65±0.86), (3.87±1.14), (4.59±1.24), (4.79±1.32) μmol/L, which were higher than those in the blank control group (P 〈 0.05-0.01). In the gila-containing mesencephalic culture fluid added by 50 μmol/L L-DOPA, the GSH and MDA contents, GSH-Px and SOD activities at each time point were all close to those in the blank control group (P〉 0.05). CONCLUSION : L-DOPA of certain concentration can destroy the dynamical balance of free radicals in glia-containing mesencephalic culture fluid, and accelerate the degeneration of neurons, which are in concentration- and time-dependent manners.展开更多
CDK4/6 inhibitors are the standard treatment in advanced HR+/HER2-breast cancer patients.Nevertheless,the resistance to CDK4/6 inhibitors is inevitable and the strategies to overcome resistance are of great interest.H...CDK4/6 inhibitors are the standard treatment in advanced HR+/HER2-breast cancer patients.Nevertheless,the resistance to CDK4/6 inhibitors is inevitable and the strategies to overcome resistance are of great interest.Here,we show that the palbociclibresistant breast cancer cells expressed significantly higher levels of Cyclin D1 and CDK4 proteins because of upregulated protein synthesis.Silencing Cyclin D1 or CDK4 led to cell cycle arrest while silencing Cyclin E1 or CDK2 restored the sensitivity to palbociclib.Furthermore,PI3K/mTOR pathway was hyper-activated in palbociclib-resistant cells,leading to more phosphorylated 4E-BP1 and higher levels of Cyclin D1 and CDK4 translation.Targeting PI3K/mTOR pathway with a specific PI3Kαinhibitor(BYL719)or an mTOR inhibitor(everolimus)reduced the protein levels of Cyclin D1 and CDK4,and restored the sensitivity to palbociclib.The tumor samples expressed significantly higher levels of Cyclin D1,CDK4,p-AKT and p-4E-BP1 after progression on palbociclib treatment.In conclusion,our findings suggest that overexpressed Cyclin D1 and CDK4 proteins lead to the resistance to CDK4/6 inhibitor and PI3K/mTOR inhibitors are able to restore the sensitivity to CDK4/6 inhibitors,which provides the biomarker and rationale for the combinational use of CDK4/6 inhibitors and PI3K/mTOR inhibitors after CDK4/6 inhibitor resistance in breast cancer.展开更多
Hair follicle stem cells(HFSCs)reside in the bulge region of the outer root sheath of the hair follicle.They are considered slow-cycling cells that are endowed with multilineage differentiation potential and superior ...Hair follicle stem cells(HFSCs)reside in the bulge region of the outer root sheath of the hair follicle.They are considered slow-cycling cells that are endowed with multilineage differentiation potential and superior proliferative capacity.The normal morphology and periodic growth of HFSCs play a significant role in normal skin functions,wound repair and skin regeneration.The HFSCs involved in these pathophysiological processes are regulated by a series of cell signal transduction pathways,such as lymphoid enhancer factor/T-cell factor,Wnt/β-catenin,transforming growth factor-β/bone morphogenetic protein,Notch and Hedgehog.The mechanisms of the interactions among these signaling pathways and their regulatory effects on HFSCs have been previously studied,but many mechanisms are still unclear.This article reviews the regulation of hair follicles,HFSCs and related signaling pathways,with the aims of summarizing previous research results,revealing the regulatory mechanisms of HFSC proliferation and differentiation and providing important references and new ideas for treating clinical diseases.展开更多
De novo variants(DNVs)are one of the most significant contributors to severe earlyonset genetic disorders such as autism spectrum disorder,intellectual disability,and other developmental and neuropsychiatric(DNP)disor...De novo variants(DNVs)are one of the most significant contributors to severe earlyonset genetic disorders such as autism spectrum disorder,intellectual disability,and other developmental and neuropsychiatric(DNP)disorders.Presently,a plethora of DNVs have been identified using next-generation sequencing,and many efforts have been made to understand their impact at the gene level.However,there has been little exploration of the effects at the isoform level.The brain contains a high level of alternative splicing and regulation,and exhibits a more divergent splicing program than other tissues.Therefore,it is crucial to explore variants at the transcriptional regulation level to better interpret the mechanisms underlying DNP disorders.To facilitate a better usage and improve the isoform-level interpretation of variants,we developed NeuroPsychiatric Mutation Knowledge Base(PsyMuKB).It contains a comprehensive,carefully curated list of DNVs with transcriptional and translational annotations to enable identification of isoformspecific mutations.PsyMuKB allows a flexible search of genes or variants and provides both table-based descriptions and associated visualizations,such as expression,transcript genomic structures,protein interactions,and the mutation sites mapped on the protein structures.It also provides an easy-to-use web interface,allowing users to rapidly visualize the locations and characteristics of mutations and the expression patterns of the impacted genes and isoforms.PsyMuKB thus constitutes a valuable resource for identifying tissue-specific DNVs for further functional studies of related disorders.PsyMuKB is freely accessible at http://psymukb.net.展开更多
Communication tower(CT)and its accessory equipment(AE)such as radio frequency equipment(RFE)and antenna,are essential in providing highspeed and stable mobile network services.It is necessary to routinely monitor the ...Communication tower(CT)and its accessory equipment(AE)such as radio frequency equipment(RFE)and antenna,are essential in providing highspeed and stable mobile network services.It is necessary to routinely monitor the security and stability of CT and AE for seamless communication.There is limited research on fine segmentation of communication base station objects.This paper proposes a method for accurately segmenting the point cloud of the CT and AE from Terrestrial Laser Scanning(TLS)data.At first,the CT point cloud is accurately segmented based on region growing and Random Sample Consensus(RANSAC).Then,the point cloud of pole-shaped apart is extended to a certain distance to obtain the buffer point cloud containing AE.Normal Differential(ND)clustering is employed to obtain several groups of clusters containing planes,and calculate each plane's filling rate and size.Finally,the cluster type(such as antenna,RFE,or other)is distinguished.The experimental results demonstrate that the point-based average F1-score of CTs is 98.70%,the point-based and object-based average F1-scores of antennas are 96.09%and 97.93%,and the corresponding values for the RFE are 89.89%and 90.00%,respectively,indicating the optimal performance of the proposed method.展开更多
基金We thank the National High-End Foreign Experts Recruitment Plan(G2022051012L)National Key Research and Development Program of China(2016YFE0131800)+1 种基金Science and Technology Department of Sichuan Province(2019YFH0023)the High-End Talents Recruitment Program(Liu Xinmin group)of Luzhou Municipal People's Government.
文摘Background:Hyperglycemia is a characteristic feature of diabetes that often results in neuropsychological complications such as depression.Diabetic individuals are more vulnerable to experience depression compared to the normal population.Thus,novel treatment approaches are required to reduce depressive symptoms among diabetic individuals.Traditional Chinese medicines(TCMs)such as Shengmai San(SMS)and Radix puerariae(R)are usually widely used to treat ailments such as neurological com-plications since ancient time.Methods:In this study,SMS was combined with R to prepare an R-SMS formulation and screened for their antidepressant activity in diabetic rats.The antidepressant po-tential of the prepared combination was evaluated behaviorally using open field test,novelty-induced hypophagia,and forced swim test in diabetic rats with biochemical and protein expression(PI3K,BDNF[brain-derived neurotrophic factor],and SYN[pr-esynaptic vesicle protein])analysis.Results:Diabetic rats(streptozotocin,45 mg/kg)showed elevated fasting blood glu-cose(FBG)>12 mM with depressive symptoms throughout the study.Treatment with R-SMS(0.5,1.5,and 4.5 g/kg)significantly reverted depressive symptoms in diabetic rats as evinced by significantly(p<0.05)reduced immobility time with an increased tendency to eat food in a novel environment.Treatment with R-SMS also significantly increased the protein expression of PI3K,BDNF,and SYN protein,which play a crucial role in depression.Conclusion:This study showed that R-SMS formulation antagonized depressive symptoms in diabetic rats;thus,this formulation might be studied further to develop as an antidepressant.
基金supported by the National Natural Science Foundation of China(Grant Nos.31370603,31170571 and31522013)the Fundamental Research Funds for the Central Universities(lzujbky-2016-ct10)
文摘Picea crassifolia and P.wilsonii,commonly used for afforestation in northern China,are increasingly likely to be subjected to high temperatures and soil drought stress as a result of global warming.However,little is known about the effects of these stresses on foliar photosynthesis in the two species.To investigate how photosynthetic characteristics and sensitivity respond to prolonged high temperatures and soil drought,foliar gas exchange and other closely related parameters were recorded from four-year-old seedlings of both species.Seedlings were grown under two temperature treatments(25/15 and 35/25 °C) and four soil water regimes [80,60,40 and 20% of maximum field capacity(FC)] for 4 months.Although all treatments significantly reduced photosynthetic rates(Pn) of both species,P.crassifolia exhibited greater photosynthetic acclimation than P.wilsonii.Differences in photosynthetic acclimation were mainly related to variations in stomatal conductance(Cond) and the maximum quantum yield of PSII(Fv/Fm) between treatments.Indeed,higher Cond and Fv/Fmin all treatments were shown for P.crassifolia than for P.wilsonii.Moreover,photosynthesis in P.crassifolia exhibited inherently lower temperature sensitivities(broader span for the temperature response curves; lower b) and higher thermostability(invariable b between treatments).Further,severe drought stress(20% FC) limited the survival of P.wilsonii.Our results indicate that P.wilsonii is more susceptible to high temperatures and soil drought stress.Planting P.crassifolia would be more expected to survive these conditions and hence be of greater benefit to forest stability if predicted increases in drought and temperature in northern China occur.
基金the financial support from Chinese National Planning Office of Philosophy and Social Science(Project Title:Research on Trade Credit under Technology Innovation Strategy,Project No.17CJY006)Surface Project of“Social Science Found of Shandong Province”(Project Title:Study on the Mechanism of Informal Finance Promoting Innovation in Shandong Province,Project No.19CJJJ23)Key Project of“Shandong University Humanities and Social Sciences”(Project Title:the Mechanism of Commercial Credit Influencing Technological Innovation:an Empirical Study of Shandong Enterprises,Project No.J17RZ005)。
文摘As an important form of informal finance,commercial credit is widely used among enterprises.Does commercial credit promote the total factor productivity of enterprises?According to the theoretical literature and the reality,using the large sample data of Chinese industrial enterprises,the paper empirically tests the impact of commercial credit on the productivity of enterprises from three aspects:the provision and acquisition of commercial credit and the net commercial credit.The study finds that the provision of commercial credit reduces the productivity level of enterprises;the acquisition of commercial credit fails to promote productivity;while the net commercial credit as a short-term financial buffer for enterprises can alleviate the financing constraints,faced by enterprises,especially private enterprises,which help to increase their productivity levels.In addition,the study found that the higher the marketization process in the region,the more favorable the commercial credit is to the improvement of the production efficiency of private enterprises.
基金The financial support from Chinese National Planning Office of Philosophy and Social Science(Project Title:Research on Trade Credit under Technology Innovation Strategy,Project No.:17CJY006)Surface Project of“Social Science Found of Shandong Province”(Project Title:Study on the Mechanism of Informal Finance Promoting Innovation in Shandong Province,Project No.:19CJJJ23)Key Project of“Shandong University Humanities and Social Sciences”(Project Title:the Mechanism of Commercial Credit Influencing Technological Innovation:an Empirical Study of Shandong Enterprises,Project No.:J17RZ005).
文摘The main purpose of this paper is to test the production efficiency of different Chinese property industrial enterprises.Based on the large sample panel data of industrial enterprises of the National Bureau of Statistics,we found that although the production efficiency of China-funded enterprises is generally weaker than foreign-funded enterprises,some China-funded enterprises have better learning ability.On the one hand,dynamic analysis found that private enterprises have significant learning ability.On the other hand,the results of convergence analysis show that China’s private enterprises have the potential to gradually catch up with the frontier level of world production efficiency and have better learning ability to catch up potential.And state-owned enterprises tend to be more efficient at the beginning of their establishment,but their productivity is fairly slow to improve,especially for state-owned enterprises with high efficiency sub-samples,so that it’s hard for them to continue improving their efficiency.Institutional analysis found that the marketization process helped the China enterprises to improve their learning ability and China should continue to strengthen the reform of property rights and promote the marketization process.
文摘BACKGROUND : Parkinson disease is neurodegenerative disorders, characterized by a progressive and selective degeneration of nigrostdatal dopaminergic pathway. Its main clinical symptoms include bradykinesia, dgidity, rest tremor and disturbances in balance. Levodopa (L-DOPA) is the "gold standard" for the symptomatic treatment of Parkinson disease, but L-DOPA is toxic to dopaminergic neurons and the chronic administration of L-DOPA often causes the side effects of motor such as "on-off ", etc., and its mechanism still has not been completely clarified. OBJECTIVE : To observe the changes of the content of glutathione (GSH), activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) and content of malondialdehyde (MDA) in gila-containing mesencephalic culture fluid after L-DOPA of different concentrations were added. DESIGN: A comparative observation. SETTINGS : Department of Neurology, Affiliated Hospital of Taishan Medical University; Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. MATERIALS : The experiment was carried out in the Basic Research Institute, Taishan Medical University from December 2003 to September 2004. Ten postnatal newborn SD rats (within 2 days) were selected, either male or female. Fetal bovine serum (DMEM/F12) was from Gibco Company; L-DOPA and glial fibrillary acidic protein (GFAP) from Sigma Company. Kits for determination of GSH, GSH-Px, SOD and MDA were purchased from Nanjing Jiancheng Bioengineering Research Institute. METHODS : Gila-containing mesencephalic culture fluid were placed in 24-well culture plate, and L-DOPA of 50, 100 and 500 μmot/L was added to each group, the blank control group was also set. The glia-containing mesencephalic culture fluid selected at 4, 24, 48 and 72 hours respectively to determine the GSH content with colorimetdc quantitative technique, GSH-Px activity with colorimetdc method, SOD activity with xanthine oxidase method and MDA content with thiol-barbituric acid method. MAIN OUTCOME MEASURES : GSH and MDA contents, GSH-Px and SOD activities in the glia-containing mesencephalic culture fluid at 4, 24, 48 and 72 hours after L-DOPA of different concentrations were added. RESULTS : In the glia-containing mesencephalic culture fluid after 100 μmol/L L-DOPA was added for 24, 48 and 72 hours, the GSH contents were lower than those in the blank control group [(174.14±39.28), (161.55± 40.79), (144.97±57.59) mg/L; (220.66±32.61), (221.10±32.98), (220.43±31.98) mg/L, P 〈 0.05]; The GSH-Px activities were lower than those in the blank control group [(4.03±1.05), (3.99±1.12), (3.47±1.00) μmol/L; (5.45±1.14), (5.69±1.21), (5.49±1.28) μmol/L, P 〈 0.05]; The SOD activities were also lower than those in the blank control group [(42.02±5.08), (39.38±5.34), (38.87±5.75)kNU/L; (51.35±8.87), (51.78±8.96), (50.99± 9.09) kNU/L, P 〈 0.05]; Whereas the MDA contents were higher than those in the blank control group [(3.51 ± 1.05), (3.99±1.03), (4.45±1.58) μmol/L; (2.09±1.13), (2.18±1.29), (2.01±1.05) μmol/L, P〈 0.05]. In the gli- a-containing mesencephalic culture fluid after 100 μmol/L L-DOPA was added for 4, 24, 48 and 72 hours, the GSH contents were (172.27±26.07), (140.15±61.44), (137.30±50.87), (121.09±66.07) mg/L, the GSH-Px activities were (3.89±1.20), (3.56±1.23), (3.38±1.18), (3.01±1.09) μmol/L, the SOD activities were (38.18±6.75), (35.23±7.85), (4.59±1.24), (31.42±7.01) kNU/L, which were all lower than those in the blank control group (P 〈 0.05-0.01 ); The MDA contents were (3.65±0.86), (3.87±1.14), (4.59±1.24), (4.79±1.32) μmol/L, which were higher than those in the blank control group (P 〈 0.05-0.01). In the gila-containing mesencephalic culture fluid added by 50 μmol/L L-DOPA, the GSH and MDA contents, GSH-Px and SOD activities at each time point were all close to those in the blank control group (P〉 0.05). CONCLUSION : L-DOPA of certain concentration can destroy the dynamical balance of free radicals in glia-containing mesencephalic culture fluid, and accelerate the degeneration of neurons, which are in concentration- and time-dependent manners.
基金supported by the Notional Natural Science Foundation of China(82061148016,81630074,81872141,81702630,81672622)Guangzhou Science and Technology Plan Key Projects(201804020076)+2 种基金Natural Science Foundation of Guangdong(2019A1515010146)Beijing Medical Award Foundation(YXJL-20200941-0760)China Postdoctoral Science Foundation(2021TQ0384,2021M703731)。
文摘CDK4/6 inhibitors are the standard treatment in advanced HR+/HER2-breast cancer patients.Nevertheless,the resistance to CDK4/6 inhibitors is inevitable and the strategies to overcome resistance are of great interest.Here,we show that the palbociclibresistant breast cancer cells expressed significantly higher levels of Cyclin D1 and CDK4 proteins because of upregulated protein synthesis.Silencing Cyclin D1 or CDK4 led to cell cycle arrest while silencing Cyclin E1 or CDK2 restored the sensitivity to palbociclib.Furthermore,PI3K/mTOR pathway was hyper-activated in palbociclib-resistant cells,leading to more phosphorylated 4E-BP1 and higher levels of Cyclin D1 and CDK4 translation.Targeting PI3K/mTOR pathway with a specific PI3Kαinhibitor(BYL719)or an mTOR inhibitor(everolimus)reduced the protein levels of Cyclin D1 and CDK4,and restored the sensitivity to palbociclib.The tumor samples expressed significantly higher levels of Cyclin D1,CDK4,p-AKT and p-4E-BP1 after progression on palbociclib treatment.In conclusion,our findings suggest that overexpressed Cyclin D1 and CDK4 proteins lead to the resistance to CDK4/6 inhibitor and PI3K/mTOR inhibitors are able to restore the sensitivity to CDK4/6 inhibitors,which provides the biomarker and rationale for the combinational use of CDK4/6 inhibitors and PI3K/mTOR inhibitors after CDK4/6 inhibitor resistance in breast cancer.
基金National Natural Science Foundation of China(Grant No.81773646)the National Key Research and Development Program of China(Grant No.2017YFA0205600)the Innovation Team of the Ministry of Education(Grant No.BMU2017TD003)。
基金supported by the National Natural Science Foundation of China(81772136,82172205,81902042)the Medical Scientific Research Foundation of Guangdong Province(A2018113)+2 种基金the Guangdong Basic and Applied Basic Research Foundation(2021A1515011453,2022A1515012160)the Special Fund of Foshan Summit plan(2019C002,2019D008,2019A006 and 2020A015)the Foundation of Foshan City(FS0AA-KJ218-1301-0034,2018AB003411).
文摘Hair follicle stem cells(HFSCs)reside in the bulge region of the outer root sheath of the hair follicle.They are considered slow-cycling cells that are endowed with multilineage differentiation potential and superior proliferative capacity.The normal morphology and periodic growth of HFSCs play a significant role in normal skin functions,wound repair and skin regeneration.The HFSCs involved in these pathophysiological processes are regulated by a series of cell signal transduction pathways,such as lymphoid enhancer factor/T-cell factor,Wnt/β-catenin,transforming growth factor-β/bone morphogenetic protein,Notch and Hedgehog.The mechanisms of the interactions among these signaling pathways and their regulatory effects on HFSCs have been previously studied,but many mechanisms are still unclear.This article reviews the regulation of hair follicles,HFSCs and related signaling pathways,with the aims of summarizing previous research results,revealing the regulatory mechanisms of HFSC proliferation and differentiation and providing important references and new ideas for treating clinical diseases.
基金The National Key Research and Development Program of China(Grant No.2017YFA0205600)the National Natural Science Foundation of China(Grant No.81773646)the Innovation Team of the Ministry of Education(Grant No.BMU2017TD003)
基金supported by grants from the National Key R&D Program of China(Grant No.2017YFC0909200)the National Natural Science Foundation of China(Grant Nos.81671328 and 61802057)+3 种基金Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning(Grant No.1610000043)Innovation Research Plan supported by Shanghai Municipal Education Commission(Grant No.ZXWF082101)Science and Technology Development Plan of Jilin Province(Grant Nos.20180414006GH and 20180520028JH)the Fundamental Research Funds for the Central Universities
文摘De novo variants(DNVs)are one of the most significant contributors to severe earlyonset genetic disorders such as autism spectrum disorder,intellectual disability,and other developmental and neuropsychiatric(DNP)disorders.Presently,a plethora of DNVs have been identified using next-generation sequencing,and many efforts have been made to understand their impact at the gene level.However,there has been little exploration of the effects at the isoform level.The brain contains a high level of alternative splicing and regulation,and exhibits a more divergent splicing program than other tissues.Therefore,it is crucial to explore variants at the transcriptional regulation level to better interpret the mechanisms underlying DNP disorders.To facilitate a better usage and improve the isoform-level interpretation of variants,we developed NeuroPsychiatric Mutation Knowledge Base(PsyMuKB).It contains a comprehensive,carefully curated list of DNVs with transcriptional and translational annotations to enable identification of isoformspecific mutations.PsyMuKB allows a flexible search of genes or variants and provides both table-based descriptions and associated visualizations,such as expression,transcript genomic structures,protein interactions,and the mutation sites mapped on the protein structures.It also provides an easy-to-use web interface,allowing users to rapidly visualize the locations and characteristics of mutations and the expression patterns of the impacted genes and isoforms.PsyMuKB thus constitutes a valuable resource for identifying tissue-specific DNVs for further functional studies of related disorders.PsyMuKB is freely accessible at http://psymukb.net.
基金funded by Guangxi Natural Science Fund for Innovation Research Team[grant number 2019GXNSFGA245001]High-Level Talent Aggregation Project in Hunan Province,China-Innovation Team[grant number 2019RS1060].
文摘Communication tower(CT)and its accessory equipment(AE)such as radio frequency equipment(RFE)and antenna,are essential in providing highspeed and stable mobile network services.It is necessary to routinely monitor the security and stability of CT and AE for seamless communication.There is limited research on fine segmentation of communication base station objects.This paper proposes a method for accurately segmenting the point cloud of the CT and AE from Terrestrial Laser Scanning(TLS)data.At first,the CT point cloud is accurately segmented based on region growing and Random Sample Consensus(RANSAC).Then,the point cloud of pole-shaped apart is extended to a certain distance to obtain the buffer point cloud containing AE.Normal Differential(ND)clustering is employed to obtain several groups of clusters containing planes,and calculate each plane's filling rate and size.Finally,the cluster type(such as antenna,RFE,or other)is distinguished.The experimental results demonstrate that the point-based average F1-score of CTs is 98.70%,the point-based and object-based average F1-scores of antennas are 96.09%and 97.93%,and the corresponding values for the RFE are 89.89%and 90.00%,respectively,indicating the optimal performance of the proposed method.