BACKGROUND Diabetic retinopathy(DR)is the primary cause of visual problems in patients with diabetes.The Heyingwuzi formulation(HYWZF)is effective against DR.AIM To determine the HYWZF prevention mechanisms,especially...BACKGROUND Diabetic retinopathy(DR)is the primary cause of visual problems in patients with diabetes.The Heyingwuzi formulation(HYWZF)is effective against DR.AIM To determine the HYWZF prevention mechanisms,especially those underlying mitophagy.METHODS Human retinal capillary endothelial cells(HRCECs)were treated with high glucose(hg),HYWZF serum,PX-478,or Mdivi-1 in vitro.Then,cell counting kit-8,transwell,and tube formation assays were used to evaluate HRCEC proliferation,invasion,and tube formation,respectively.Transmission electron microscopy was used to assess mitochondrial morphology,and Western blotting was used to determine the protein levels.Flow cytometry was used to assess cell apoptosis,reactive oxygen species(ROS)production,and mitochondrial membrane potential.Moreover,C57BL/6 mice were established in vivo using streptozotocin and treated with HYWZF for four weeks.Blood glucose levels and body weight were monitored continuously.Changes in retinal characteristics were evaluated using hematoxylin and eosin,tar violet,and periodic acid-Schiff staining.Protein levels in retinal tissues were determined via Western blotting,immunohistochemistry,and immunostaining.RESULTS HYWZF inhibited excessive ROS production,apoptosis,tube formation,and invasion in hg-induced HRCECs via mitochondrial autophagy in vitro.It increased the mRNA expression levels of BCL2-interacting protein 3(BNIP3),FUN14 domain-containing 1,BNIP3-like(BNIP3L,also known as NIX),PARKIN,PTEN-induced kinase 1,and hypoxia-inducible factor(HIF)-1α.Moreover,it downregulated the protein levels of vascular endothelial cell growth factor and increased the light chain 3-II/I ratio.However,PX-478 and Mdivi-1 reversed these effects.Additionally,PX-478 and Mdivi-1 rescued the effects of HYWZF by decreasing oxidative stress and apoptosis and increasing mitophagy.HYWZF intervention improved the symptoms of diabetes,tissue damage,number of acellular capillaries,and oxidative stress in vivo.Furthermore,in vivo experiments confirmed the results of in vitro experiments.CONCLUSION HYWZF alleviated DR and associated damage by promoting mitophagy via the HIF-1α/BNIP3/NIX axis.展开更多
Refractory high-entropy alloys are considered as potential structural materials for elevated temperature applications.To obtain refractory high-entropy alloys with high strength,different amounts of Si were added into...Refractory high-entropy alloys are considered as potential structural materials for elevated temperature applications.To obtain refractory high-entropy alloys with high strength,different amounts of Si were added into the NbMoTiVW refractory high-entropy alloys.The effects of Si on the phase constitution,microstructure characteristics and mechanical properties of NbMoTiVWSi_(x) alloys were investigated.Results show that when the addition of Si is 0,0.025 and 0.05(molar ratio),the alloys are consisted of primary BCC and secondary BCC in the intergranular area.When the addition of Si is increased to 0.075 and 0.1,eutectic structure including silicide phase and secondary BCC phase is formed.The primary BCC phase shows dendritic morphology,and is refined by adding Si.The volume fraction of intergranular area is increased from 12.22%to 18.13%when the addition of Si increases from 0 to 0.1.The ultimate compressive strength of the NbMoTiVW alloy is improved from 2,242 MPa to 2,532 MPa.Its yield strength is also improved by the addition of Si,and the yield strength of NbMoTiVWSi_(0.1) reaches maximum of 2,298 MPa.However,the fracture strain of the alloy is decreased from 15.31%to 12.02%.The fracture mechanism of the alloys is changed from mixed fracture of ductile and quasi-cleavage to cleavage fracture with increasing of Si.The strengthening of alloys is attributed to the refinement of primary BCC phase,volume fraction increment of secondary BCC phase,and formation of eutectic structure by addition of Si.展开更多
The DD33 superalloy with ultra-low nitrogen (N) content was prepared by vacuum induced melting, and the effect of N on micro-pores in the DD33 single crystal nickel-base superalloy during solidification and homogeniza...The DD33 superalloy with ultra-low nitrogen (N) content was prepared by vacuum induced melting, and the effect of N on micro-pores in the DD33 single crystal nickel-base superalloy during solidification and homogenization was investigated by in-situ X-ray computed tomography (XCT). Results indicate that the volume fraction of micro-pores, including shrinkage pores and gas pores, increases from 0.08% to 0.11% with increasing N content from 5 ppm to 45 ppm during solidification. Correspondingly, the level of micro-pores in the sample with high N content is higher than that in the sample with low N content during homogenization at 1,330 °C for different time periods. However, the evolution behaviors of gas pores is different from that of shrinkage pores during solidification and homogenization. The number of gas pores is obviously larger in the high N sample during solidification, while the number of shrinkage pores and gas pores is almost the same in both samples after 1 h homogenization. Quantitative results show that the annihilation of micro-pores is associated with bubble diffusion, while the growth behavior of micro-pores during further exposure is dominated by Kirkendall-Frenkel effect.展开更多
To improve the microstructure and microhardness,Ti-48Al(at.%)alloy was rapidly solidified by melt spinning under different cooling rates.The microstructure and microhardness of rapidly solidified Ti-48Al alloy were sy...To improve the microstructure and microhardness,Ti-48Al(at.%)alloy was rapidly solidified by melt spinning under different cooling rates.The microstructure and microhardness of rapidly solidified Ti-48Al alloy were systematically investigated.Results show that the average lamellar colony size of the alloy reduces from 60.6μm to 11μm as the cooling rate increases from 2.3×105 to 5.1×105 K·s-1,caused by the increase of nucleation rate at a higher cooling rate.At the high cooling rate of(4.3-5.1)×105 K·s-1,theαphase is the primary phase,and a few metastableαphases are reserved,which then transform intoα2 phase and subsequently lead to the formation ofα2 equiaxed grain.The lamellar spacing also decreases with the increase of cooling rate.The relationship between lamellar spacing(d)and cooling rate(v)is d=33.6v-1.34.The microhardness increases with the increase of cooling rate because the refined lamellar spacing and grain size can improve the microhardness.展开更多
Traditional Chinese medicine(TCM)was developed from and is rooted in traditional Chinese culture.Nowadays,the Chinese state attaches great importance to the development of TCM and has implemented a series of policies ...Traditional Chinese medicine(TCM)was developed from and is rooted in traditional Chinese culture.Nowadays,the Chinese state attaches great importance to the development of TCM and has implemented a series of policies and measures.This paper first demonstrates the rationality of the view that"traditional culture plays a fundamental role in the development of TCM",and analyzes the influence of traditional culture on the development of TCM from the perspective of philosophy and religion,in order to have a deeper understanding of the formation and development process of TCM.Finally,taking ophthalmology of TCM as an example,this paper discusses the importance of the continual inheritance of traditional culture and development of TCM.展开更多
Tetrabromobisphenol A-bis(2,3-dibromopropyl ether)(TBBPA-BDBPE),a widely used flame retardant,has been frequently detected in various environmental compartments,but its health hazard remains largely unknown.Here,we in...Tetrabromobisphenol A-bis(2,3-dibromopropyl ether)(TBBPA-BDBPE),a widely used flame retardant,has been frequently detected in various environmental compartments,but its health hazard remains largely unknown.Here,we investigated the adverse effects of TBBPA-BDBPE(50 and 1000μg/kg/day)on postnatal testis development in CD-1 mice and the underlying mechanism.Following the first week of maternal exposure,neonatal mice in the high-dose group exhibited reduced seminiferous tubule area,fewer Sertoli cells and germ cells,and damaged microtubules in Sertoli cells;even microtubule damage was also observed in the low-dose group.When exposure extended to adulthood,male offspring in the high-dose group presented more remarkable alterations in reproductive parameters,including reduced sperm count;in the low-dose group,microtubule damage was also observable,along with blood−testis barrier impairment.Further molecular docking analysis and tubulin polymerization assay indicated that TBBPA-BDBPE could interact with tubulin and disrupt its polymerization.Moreover,we observed attenuated microtubules in mouse Sertoli cells in vitro(TM4)following TBBPABDBPE treatment,suggesting that TBBPA-BDBPE impaired testis development possibly by interfering with tubulin dynamics.This study not only highlights the male reproductive hazard of TBBPA-BDBPE but also greatly improved the understanding of the molecular mechanism for male reproductive toxicity of chemicals.展开更多
基金Supported by the National Key Research and Development Project of China,No.2019YFC1711605National Natural Science Foundation of China,No.81904257Medical Innovation Research Project of Science and Technology Commission of Shanghai Municipality,No.21Y11923100.
文摘BACKGROUND Diabetic retinopathy(DR)is the primary cause of visual problems in patients with diabetes.The Heyingwuzi formulation(HYWZF)is effective against DR.AIM To determine the HYWZF prevention mechanisms,especially those underlying mitophagy.METHODS Human retinal capillary endothelial cells(HRCECs)were treated with high glucose(hg),HYWZF serum,PX-478,or Mdivi-1 in vitro.Then,cell counting kit-8,transwell,and tube formation assays were used to evaluate HRCEC proliferation,invasion,and tube formation,respectively.Transmission electron microscopy was used to assess mitochondrial morphology,and Western blotting was used to determine the protein levels.Flow cytometry was used to assess cell apoptosis,reactive oxygen species(ROS)production,and mitochondrial membrane potential.Moreover,C57BL/6 mice were established in vivo using streptozotocin and treated with HYWZF for four weeks.Blood glucose levels and body weight were monitored continuously.Changes in retinal characteristics were evaluated using hematoxylin and eosin,tar violet,and periodic acid-Schiff staining.Protein levels in retinal tissues were determined via Western blotting,immunohistochemistry,and immunostaining.RESULTS HYWZF inhibited excessive ROS production,apoptosis,tube formation,and invasion in hg-induced HRCECs via mitochondrial autophagy in vitro.It increased the mRNA expression levels of BCL2-interacting protein 3(BNIP3),FUN14 domain-containing 1,BNIP3-like(BNIP3L,also known as NIX),PARKIN,PTEN-induced kinase 1,and hypoxia-inducible factor(HIF)-1α.Moreover,it downregulated the protein levels of vascular endothelial cell growth factor and increased the light chain 3-II/I ratio.However,PX-478 and Mdivi-1 reversed these effects.Additionally,PX-478 and Mdivi-1 rescued the effects of HYWZF by decreasing oxidative stress and apoptosis and increasing mitophagy.HYWZF intervention improved the symptoms of diabetes,tissue damage,number of acellular capillaries,and oxidative stress in vivo.Furthermore,in vivo experiments confirmed the results of in vitro experiments.CONCLUSION HYWZF alleviated DR and associated damage by promoting mitophagy via the HIF-1α/BNIP3/NIX axis.
基金The authors are grateful for the financial supports from the National Natural Science Foundation of China(51825401 and 52001114)the State Key Laboratory of Materials Processing and Die&Mould Technology(P2020-023)the Guangdong Introducing Innovative and Entrepreneurial Teams,China(2016ZT06G025).
基金supported by the National Natural Science Foundation of China(Grant Nos.52001114,51825401)Cultivation Program for Outstanding Young Teacher in Henan Province(Grant Nos.21420152,2021GGJS064)+2 种基金Scientific Research Fund of State Key Laboratory of Materials Processing and Die&Mould Technology(Grant No.P2020-023)Program for Guangdong Introducing Innovative and Entrepreneurial Teams(Grant No.2016ZT06G025)the Project of Science and Technology in Henan Province(Grant No.192102210011).
文摘Refractory high-entropy alloys are considered as potential structural materials for elevated temperature applications.To obtain refractory high-entropy alloys with high strength,different amounts of Si were added into the NbMoTiVW refractory high-entropy alloys.The effects of Si on the phase constitution,microstructure characteristics and mechanical properties of NbMoTiVWSi_(x) alloys were investigated.Results show that when the addition of Si is 0,0.025 and 0.05(molar ratio),the alloys are consisted of primary BCC and secondary BCC in the intergranular area.When the addition of Si is increased to 0.075 and 0.1,eutectic structure including silicide phase and secondary BCC phase is formed.The primary BCC phase shows dendritic morphology,and is refined by adding Si.The volume fraction of intergranular area is increased from 12.22%to 18.13%when the addition of Si increases from 0 to 0.1.The ultimate compressive strength of the NbMoTiVW alloy is improved from 2,242 MPa to 2,532 MPa.Its yield strength is also improved by the addition of Si,and the yield strength of NbMoTiVWSi_(0.1) reaches maximum of 2,298 MPa.However,the fracture strain of the alloy is decreased from 15.31%to 12.02%.The fracture mechanism of the alloys is changed from mixed fracture of ductile and quasi-cleavage to cleavage fracture with increasing of Si.The strengthening of alloys is attributed to the refinement of primary BCC phase,volume fraction increment of secondary BCC phase,and formation of eutectic structure by addition of Si.
基金This work was financially supported by the Guangdong Major Project of Basic and Applied Basic Research(No.2020B0301030001)the Program for Guangdong Introducing Innovative and Entrepreneurial Teams(No.2016ZT06G025).
文摘The DD33 superalloy with ultra-low nitrogen (N) content was prepared by vacuum induced melting, and the effect of N on micro-pores in the DD33 single crystal nickel-base superalloy during solidification and homogenization was investigated by in-situ X-ray computed tomography (XCT). Results indicate that the volume fraction of micro-pores, including shrinkage pores and gas pores, increases from 0.08% to 0.11% with increasing N content from 5 ppm to 45 ppm during solidification. Correspondingly, the level of micro-pores in the sample with high N content is higher than that in the sample with low N content during homogenization at 1,330 °C for different time periods. However, the evolution behaviors of gas pores is different from that of shrinkage pores during solidification and homogenization. The number of gas pores is obviously larger in the high N sample during solidification, while the number of shrinkage pores and gas pores is almost the same in both samples after 1 h homogenization. Quantitative results show that the annihilation of micro-pores is associated with bubble diffusion, while the growth behavior of micro-pores during further exposure is dominated by Kirkendall-Frenkel effect.
基金the National Natural Science Foundation of China(Grant No.51825401)the China Postdoctoral Science Foundation(Grant No.2019TQ0076)the Program for Guangdong Introducing Innovative and Entrepreneurial Teams(Grant No.2016ZT06G025)。
文摘To improve the microstructure and microhardness,Ti-48Al(at.%)alloy was rapidly solidified by melt spinning under different cooling rates.The microstructure and microhardness of rapidly solidified Ti-48Al alloy were systematically investigated.Results show that the average lamellar colony size of the alloy reduces from 60.6μm to 11μm as the cooling rate increases from 2.3×105 to 5.1×105 K·s-1,caused by the increase of nucleation rate at a higher cooling rate.At the high cooling rate of(4.3-5.1)×105 K·s-1,theαphase is the primary phase,and a few metastableαphases are reserved,which then transform intoα2 phase and subsequently lead to the formation ofα2 equiaxed grain.The lamellar spacing also decreases with the increase of cooling rate.The relationship between lamellar spacing(d)and cooling rate(v)is d=33.6v-1.34.The microhardness increases with the increase of cooling rate because the refined lamellar spacing and grain size can improve the microhardness.
文摘Traditional Chinese medicine(TCM)was developed from and is rooted in traditional Chinese culture.Nowadays,the Chinese state attaches great importance to the development of TCM and has implemented a series of policies and measures.This paper first demonstrates the rationality of the view that"traditional culture plays a fundamental role in the development of TCM",and analyzes the influence of traditional culture on the development of TCM from the perspective of philosophy and religion,in order to have a deeper understanding of the formation and development process of TCM.Finally,taking ophthalmology of TCM as an example,this paper discusses the importance of the continual inheritance of traditional culture and development of TCM.
基金supported by the National Key Research and Development Program of China(2018YFA0901103)the National Natural Science Foundation of China(21876196).
文摘Tetrabromobisphenol A-bis(2,3-dibromopropyl ether)(TBBPA-BDBPE),a widely used flame retardant,has been frequently detected in various environmental compartments,but its health hazard remains largely unknown.Here,we investigated the adverse effects of TBBPA-BDBPE(50 and 1000μg/kg/day)on postnatal testis development in CD-1 mice and the underlying mechanism.Following the first week of maternal exposure,neonatal mice in the high-dose group exhibited reduced seminiferous tubule area,fewer Sertoli cells and germ cells,and damaged microtubules in Sertoli cells;even microtubule damage was also observed in the low-dose group.When exposure extended to adulthood,male offspring in the high-dose group presented more remarkable alterations in reproductive parameters,including reduced sperm count;in the low-dose group,microtubule damage was also observable,along with blood−testis barrier impairment.Further molecular docking analysis and tubulin polymerization assay indicated that TBBPA-BDBPE could interact with tubulin and disrupt its polymerization.Moreover,we observed attenuated microtubules in mouse Sertoli cells in vitro(TM4)following TBBPABDBPE treatment,suggesting that TBBPA-BDBPE impaired testis development possibly by interfering with tubulin dynamics.This study not only highlights the male reproductive hazard of TBBPA-BDBPE but also greatly improved the understanding of the molecular mechanism for male reproductive toxicity of chemicals.