Diabetic retinopathy(DR)is a prevalent microvascular complication of diabetes and the leading cause of blindness and severe visual impairment in adults.The high levels of glucose trigger multiple intracellular oxidati...Diabetic retinopathy(DR)is a prevalent microvascular complication of diabetes and the leading cause of blindness and severe visual impairment in adults.The high levels of glucose trigger multiple intracellular oxidative stress pathways,such as POLDIP2,resulting in excessive reactive oxygen species(ROS)production and increased expression of vascular cell adhesion molecule-1(VCAM-1),hypoxia-inducible factor 1a(HIF-1a),and vascular endothelial growth factor(VEGF),causing microvascular dysfunction.Dihydromyricetin(DMY)is a natural flavonoid small molecule antioxidant.However,it exhibits poor solubility in physiological environments,has a short half-life in vivo,and has low oral bioavailability.In this study,we present,for the first time,the synthesis of ultra-small Fe-DMY nano-coordinated polymer particles(Fe-DMY NCPs),formed by combining DMY with low-toxicity iron ions.In vitro and in vivo experiments confirm that Fe-DMY NCPs alleviate oxidative stress-induced damage to vascular endothelial cells by high glucose,scavenge excess ROS,and improve pathological features of DR,such as retinal vascular leakage and neovascularization.Mechanistic validation indicates that Fe-DMY NCPs can inhibit the activation of the Poldip2-Nox4-H_(2)O_(2) signaling pathway and downregulate vital vascular function indicators such as VCAM-1,HIF-1a,and VEGF.These findings suggest that Fe-DMY NCPs could serve as a safe and effective antioxidant and microangio-protective agent,with the potential as a novel multimeric drug for DR therapy.展开更多
Cyclic polymers have attracted more and more attentions in recent years because of their unique topological structures and characteristic properties in both solution and bulk state. There are relatively few reports on...Cyclic polymers have attracted more and more attentions in recent years because of their unique topological structures and characteristic properties in both solution and bulk state. There are relatively few reports on cyclic polymers, partly because of the more demanding synthetic procedures. In recent years, 'click' reaction, especially Cu(I)-catalyzed azide-alkyne cycloaddition(CuAAC), has been widely utilized in the synthesis of cyclic polymer materials because of its high efficiency and low susceptibility to side reactions. In this review, we will focus on three aspects:(1) Constructions of monocyclic polymer using CuAAC 'click' chemistry;(2) Formation of complex cyclic polymer topologies through CuAAC reactions;(3) Using CuAAC 'click' reaction in the precise synthesis of molecularly defined macrocycles. We believe that the CuAAC click reaction is playing an important role in the design and synthesis of functional cyclic polymers.展开更多
The controlled and efficient synthesis of polymers with tailored topologies is challenging but important for exploring structure/property research. Herein, we proposed a concept of macro-latent monomer to achieve the ...The controlled and efficient synthesis of polymers with tailored topologies is challenging but important for exploring structure/property research. Herein, we proposed a concept of macro-latent monomer to achieve the controlled growth of polymer topologies.The macro-latent monomer was installed by a dynamic furan/maleimide covalent bond at the chain terminal. One-shot reversible additionfragmentation chain transfer(RAFT) polymerization of styrene and the macro-latent monomer created controlled growth of polymer topologies.Low temperature such as 40 ℃ could not activate the macro-latent monomer and thus the polymerization created the homo-polystyrene. By contrast, high temperature of ~110 ℃ activated the macro-latent monomer, and a maleimide-terminated macro-monomer was released via the retro-Diels Alder reaction. This macro-monomer immediately joined the cross polymerization with styrene and thus produced the side chains. By delicately manipulating the polymerization temperature, the predetermined placement of the macro-latent monomer-derived polymeric sidechains created controllably growing topologies, including star-, π-shaped, and density-variable grafting copolymers. This work paved a new way for creating on-demand topologies and would greatly enrich the topology synthesis.展开更多
Clinical staging,Gleason score,and prostate-specific antigen(PSA)have been accepted as factors for evaluating the prognosis of prostate cancer(PCa).With the in-depth study of iron metabolism and the development of mul...Clinical staging,Gleason score,and prostate-specific antigen(PSA)have been accepted as factors for evaluating the prognosis of prostate cancer(PCa).With the in-depth study of iron metabolism and the development of multiparametric magnetic resonance imaging technology,we used q-Dixon magnetic resonance imaging(MRI)to measure the iron content of the PCa patients'lesions,and used enzyme-linked immunosorbent assay(ELISA)to measure the iron metabolism indicators in the patients'serum samples,combined with the patients'postoperative clinical data for analysis.We found that the serum indexes were correlated with the T2 star values,International Society of Urological Pathology(ISUP)grade,and pathological classification in PCa patients(all P<O.001)but not in benign prostatic hyperplasia(BPH)patients(all P>O.05).The utilization of q-Dixon-based MRI and serum indexes allows the noninvasive measurement of iron content in prostate lesions and the assessment of differential iron metabolism between PCa and BPH,which may be helpful for evaluating the prognosis of PCa.展开更多
文摘Diabetic retinopathy(DR)is a prevalent microvascular complication of diabetes and the leading cause of blindness and severe visual impairment in adults.The high levels of glucose trigger multiple intracellular oxidative stress pathways,such as POLDIP2,resulting in excessive reactive oxygen species(ROS)production and increased expression of vascular cell adhesion molecule-1(VCAM-1),hypoxia-inducible factor 1a(HIF-1a),and vascular endothelial growth factor(VEGF),causing microvascular dysfunction.Dihydromyricetin(DMY)is a natural flavonoid small molecule antioxidant.However,it exhibits poor solubility in physiological environments,has a short half-life in vivo,and has low oral bioavailability.In this study,we present,for the first time,the synthesis of ultra-small Fe-DMY nano-coordinated polymer particles(Fe-DMY NCPs),formed by combining DMY with low-toxicity iron ions.In vitro and in vivo experiments confirm that Fe-DMY NCPs alleviate oxidative stress-induced damage to vascular endothelial cells by high glucose,scavenge excess ROS,and improve pathological features of DR,such as retinal vascular leakage and neovascularization.Mechanistic validation indicates that Fe-DMY NCPs can inhibit the activation of the Poldip2-Nox4-H_(2)O_(2) signaling pathway and downregulate vital vascular function indicators such as VCAM-1,HIF-1a,and VEGF.These findings suggest that Fe-DMY NCPs could serve as a safe and effective antioxidant and microangio-protective agent,with the potential as a novel multimeric drug for DR therapy.
基金financially supported by the National Natural Science Foundation of China(No.21234005)the State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials,the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)the Program of Innovative Research Team of Soochow University
文摘Cyclic polymers have attracted more and more attentions in recent years because of their unique topological structures and characteristic properties in both solution and bulk state. There are relatively few reports on cyclic polymers, partly because of the more demanding synthetic procedures. In recent years, 'click' reaction, especially Cu(I)-catalyzed azide-alkyne cycloaddition(CuAAC), has been widely utilized in the synthesis of cyclic polymer materials because of its high efficiency and low susceptibility to side reactions. In this review, we will focus on three aspects:(1) Constructions of monocyclic polymer using CuAAC 'click' chemistry;(2) Formation of complex cyclic polymer topologies through CuAAC reactions;(3) Using CuAAC 'click' reaction in the precise synthesis of molecularly defined macrocycles. We believe that the CuAAC click reaction is playing an important role in the design and synthesis of functional cyclic polymers.
基金financially supported by the National Natural Science Foundation of China(Nos.21925107 and 21674072)the Collaborative Innovation Center of Suzhou Nano Science and Technology+1 种基金the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)the Program of Innovative Research Team of Soochow University。
文摘The controlled and efficient synthesis of polymers with tailored topologies is challenging but important for exploring structure/property research. Herein, we proposed a concept of macro-latent monomer to achieve the controlled growth of polymer topologies.The macro-latent monomer was installed by a dynamic furan/maleimide covalent bond at the chain terminal. One-shot reversible additionfragmentation chain transfer(RAFT) polymerization of styrene and the macro-latent monomer created controlled growth of polymer topologies.Low temperature such as 40 ℃ could not activate the macro-latent monomer and thus the polymerization created the homo-polystyrene. By contrast, high temperature of ~110 ℃ activated the macro-latent monomer, and a maleimide-terminated macro-monomer was released via the retro-Diels Alder reaction. This macro-monomer immediately joined the cross polymerization with styrene and thus produced the side chains. By delicately manipulating the polymerization temperature, the predetermined placement of the macro-latent monomer-derived polymeric sidechains created controllably growing topologies, including star-, π-shaped, and density-variable grafting copolymers. This work paved a new way for creating on-demand topologies and would greatly enrich the topology synthesis.
基金supported by grants from the 201816^(th) Science and Technology Development Plan of Suzhou,Suzhou,China(No.SS201863).
文摘Clinical staging,Gleason score,and prostate-specific antigen(PSA)have been accepted as factors for evaluating the prognosis of prostate cancer(PCa).With the in-depth study of iron metabolism and the development of multiparametric magnetic resonance imaging technology,we used q-Dixon magnetic resonance imaging(MRI)to measure the iron content of the PCa patients'lesions,and used enzyme-linked immunosorbent assay(ELISA)to measure the iron metabolism indicators in the patients'serum samples,combined with the patients'postoperative clinical data for analysis.We found that the serum indexes were correlated with the T2 star values,International Society of Urological Pathology(ISUP)grade,and pathological classification in PCa patients(all P<O.001)but not in benign prostatic hyperplasia(BPH)patients(all P>O.05).The utilization of q-Dixon-based MRI and serum indexes allows the noninvasive measurement of iron content in prostate lesions and the assessment of differential iron metabolism between PCa and BPH,which may be helpful for evaluating the prognosis of PCa.
