BACKGROUND Primary sclerosing cholangitis(PSC)is characterized by chronic inflammation and it predisposes to cholangiocarcinoma due to lack of effective treatment options.Recombinant adeno-associated virus(rAAV)provid...BACKGROUND Primary sclerosing cholangitis(PSC)is characterized by chronic inflammation and it predisposes to cholangiocarcinoma due to lack of effective treatment options.Recombinant adeno-associated virus(rAAV)provides a promising platform for gene therapy on such kinds of diseases.A microRNA(miRNA)let-7a has been reported to be associated with the progress of PSC but the potential therapeutic implication of inhibition of let-7a on PSC has not been evaluated.AIM To investigate the therapeutic effects of inhibition of a miRNA let-7a transferred by recombinant adeno-associated virus 8(rAAV8)on a xenobiotic-induced mouse model of sclerosing cholangitis.METHODS A xenobiotic-induced mouse model of sclerosing cholangitis was induced by 0.1% 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine(DDC)feeding for 2 wk or 6 wk.A single dose of rAAV8-mediated anti-let-7a-5p sponges or scramble control was injected in vivo into mice onset of DDC feeding.Upon sacrifice,the liver and the serum were collected from each mouse.The hepatobiliary injuries,hepatic inflammation and fibrosis were evaluated.The targets of let-7a-5p and downstream molecule NF-κB were detected using Western blot.RESULTS rAAV8-mediated anti-let-7a-5p sponges can depress the expression of let-7a-5p in mice after DDC feeding for 2 wk or 6 wk.The reduced expression of let-7a-5p can alleviate hepato-biliary injuries indicated by serum markers,and prevent the proliferation of cholangiocytes and biliary fibrosis.Furthermore,inhibition of let-7a mediated by rAAV8 can increase the expression of potential target molecules such as suppressor of cytokine signaling 1 and Dectin1,which consequently inhibit of NF-κB-mediated hepatic inflammation.CONCLUSION Our study demonstrates that a rAAV8 vector designed for liver-specific inhibition of let-7a-5p can potently ameliorate symptoms in a xenobiotic-induced mouse model of sclerosing cholangitis,which provides a possible clinical translation of PSC of human.展开更多
1,7β- Dimethyl-7α- hydroxy-8aα-carboxymethyl-9β-carbomethoxy-4bα, 5, 6, 7, 8, 8α-hexahydrofluorene lactone(2) is converted to 8, 12-epoxyallogibberic acid methyl ester(4) by the action of diisobutyl aluminum hyd...1,7β- Dimethyl-7α- hydroxy-8aα-carboxymethyl-9β-carbomethoxy-4bα, 5, 6, 7, 8, 8α-hexahydrofluorene lactone(2) is converted to 8, 12-epoxyallogibberic acid methyl ester(4) by the action of diisobutyl aluminum hydride (DIBAL-H) with a novel rearrangement reaction.展开更多
Organic electrodes are advantageous for rechargeable lithium-ion batteries owing to their high theoretical capacities, diverse functionalities, and environmental compatibility. Understanding the working mechanism of o...Organic electrodes are advantageous for rechargeable lithium-ion batteries owing to their high theoretical capacities, diverse functionalities, and environmental compatibility. Understanding the working mechanism of organic electrodes is vital to strategic materials design. However, due to lack of suitable characterization tools, it has been challenging to probe the reaction processes of organic electrodes in real-time. Here, non-destructive in situ electron paramagnetic resonance(EPR) was performed on a model organic electrode, 7,7,8,8-tetracyanoquinodimethane(TCNQ) used in rechargeable lithium-ion batteries,to directly follow the redox reactions in real-time. In order to minimize interfering signals from other parts of the batteries than the TCNQ electrode of interest, two sets of batteries are fabricated and studied with in situ EPR:(1) a Li CoO_(2)//Li_(4)Ti_5O_(12) full-cell battery to determine the EPR signal evolution of additives and electrolytes;(2) a Li CoO_(2)//TCNQ battery, and the difference in the observed EPR signals reflects purely the redox reactions of TCNQ upon lithiation and delithiation. A two-electron reversible redox reaction is delineated for TCNQ. TCNQ dimers form during the first electron injection upon lithiation and followed by the break-down of the dimers and associated electron coupling to produce massive delocalized electrons, resulting in increased EPR signal during the 2 nd electron injection. Reversible trends are observed during electron ejection upon delithiation. In situ EPR is very sensitive to electron activities,thus is a powerful tool to follow redox reactions of organic electrodes, allowing for improved fundamental understanding of how organic electrodes work and for informed design of high-performance organic materials for energy storage.展开更多
In the present study, a mouse model of sciatic nerve injury was treated with intraperitoneal injection of 7, 8-dihydroxycoumarin （10, 5, or 2.5 mg/kg per day）. Western blot and real-time PCR results showed that grow...In the present study, a mouse model of sciatic nerve injury was treated with intraperitoneal injection of 7, 8-dihydroxycoumarin （10, 5, or 2.5 mg/kg per day）. Western blot and real-time PCR results showed that growth associated protein 43 expression was significantly increased in the L4-6 segments of the spinal cord. The amplitude and velocity of motor nerve conduction in the sciatic nerve were significantly increased in model mice. In addition, the appearance of the myelin sheath in the injured sciatic nerve was regular, with an even thickness and clear outline, and the surrounding fibroplasia was not obvious. Our results indicate that 7, 8-dihydroxycoumarin can promote the repair of injured nerve by upregulating growth associated protein 43 expression in the corresponding spinal cord segments of mice with sciatic nerve injury.展开更多
The Total Coloring Conjecture (TCC) proposes that every simple graph G is (Δ + 2)-totally-colorable, where Δ is the maximum degree of G. For planar graph, TCC is open only in case Δ = 6. In this paper, we prove tha...The Total Coloring Conjecture (TCC) proposes that every simple graph G is (Δ + 2)-totally-colorable, where Δ is the maximum degree of G. For planar graph, TCC is open only in case Δ = 6. In this paper, we prove that TCC holds for planar graph with Δ = 6 and every 7-cycle contains at most two chords.展开更多
基金Supported by the National Natural Science Foundation of China,No.82172297Natural Science Foundation of Jiangsu Province of China,No.BK20211346 and No.BK20201011+1 种基金Natural Science Foundation of Jiangsu Higher Education Institutions of China,No.22KJA310007Xuzhou Science and Technology Project,No.KC22055.
文摘BACKGROUND Primary sclerosing cholangitis(PSC)is characterized by chronic inflammation and it predisposes to cholangiocarcinoma due to lack of effective treatment options.Recombinant adeno-associated virus(rAAV)provides a promising platform for gene therapy on such kinds of diseases.A microRNA(miRNA)let-7a has been reported to be associated with the progress of PSC but the potential therapeutic implication of inhibition of let-7a on PSC has not been evaluated.AIM To investigate the therapeutic effects of inhibition of a miRNA let-7a transferred by recombinant adeno-associated virus 8(rAAV8)on a xenobiotic-induced mouse model of sclerosing cholangitis.METHODS A xenobiotic-induced mouse model of sclerosing cholangitis was induced by 0.1% 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine(DDC)feeding for 2 wk or 6 wk.A single dose of rAAV8-mediated anti-let-7a-5p sponges or scramble control was injected in vivo into mice onset of DDC feeding.Upon sacrifice,the liver and the serum were collected from each mouse.The hepatobiliary injuries,hepatic inflammation and fibrosis were evaluated.The targets of let-7a-5p and downstream molecule NF-κB were detected using Western blot.RESULTS rAAV8-mediated anti-let-7a-5p sponges can depress the expression of let-7a-5p in mice after DDC feeding for 2 wk or 6 wk.The reduced expression of let-7a-5p can alleviate hepato-biliary injuries indicated by serum markers,and prevent the proliferation of cholangiocytes and biliary fibrosis.Furthermore,inhibition of let-7a mediated by rAAV8 can increase the expression of potential target molecules such as suppressor of cytokine signaling 1 and Dectin1,which consequently inhibit of NF-κB-mediated hepatic inflammation.CONCLUSION Our study demonstrates that a rAAV8 vector designed for liver-specific inhibition of let-7a-5p can potently ameliorate symptoms in a xenobiotic-induced mouse model of sclerosing cholangitis,which provides a possible clinical translation of PSC of human.
文摘1,7β- Dimethyl-7α- hydroxy-8aα-carboxymethyl-9β-carbomethoxy-4bα, 5, 6, 7, 8, 8α-hexahydrofluorene lactone(2) is converted to 8, 12-epoxyallogibberic acid methyl ester(4) by the action of diisobutyl aluminum hydride (DIBAL-H) with a novel rearrangement reaction.
基金supported by the National Science Foundation under Grant No. DMR-1847038supported by the National Science Foundation Cooperative Agreement No. DMR-1644779 and the State of Florida。
文摘Organic electrodes are advantageous for rechargeable lithium-ion batteries owing to their high theoretical capacities, diverse functionalities, and environmental compatibility. Understanding the working mechanism of organic electrodes is vital to strategic materials design. However, due to lack of suitable characterization tools, it has been challenging to probe the reaction processes of organic electrodes in real-time. Here, non-destructive in situ electron paramagnetic resonance(EPR) was performed on a model organic electrode, 7,7,8,8-tetracyanoquinodimethane(TCNQ) used in rechargeable lithium-ion batteries,to directly follow the redox reactions in real-time. In order to minimize interfering signals from other parts of the batteries than the TCNQ electrode of interest, two sets of batteries are fabricated and studied with in situ EPR:(1) a Li CoO_(2)//Li_(4)Ti_5O_(12) full-cell battery to determine the EPR signal evolution of additives and electrolytes;(2) a Li CoO_(2)//TCNQ battery, and the difference in the observed EPR signals reflects purely the redox reactions of TCNQ upon lithiation and delithiation. A two-electron reversible redox reaction is delineated for TCNQ. TCNQ dimers form during the first electron injection upon lithiation and followed by the break-down of the dimers and associated electron coupling to produce massive delocalized electrons, resulting in increased EPR signal during the 2 nd electron injection. Reversible trends are observed during electron ejection upon delithiation. In situ EPR is very sensitive to electron activities,thus is a powerful tool to follow redox reactions of organic electrodes, allowing for improved fundamental understanding of how organic electrodes work and for informed design of high-performance organic materials for energy storage.
基金supported by the Science and Technology Development Foundation of Jilin Province, No.20100751a grant from Jilin Province Science and Technology Division, No. 200505174
文摘In the present study, a mouse model of sciatic nerve injury was treated with intraperitoneal injection of 7, 8-dihydroxycoumarin （10, 5, or 2.5 mg/kg per day）. Western blot and real-time PCR results showed that growth associated protein 43 expression was significantly increased in the L4-6 segments of the spinal cord. The amplitude and velocity of motor nerve conduction in the sciatic nerve were significantly increased in model mice. In addition, the appearance of the myelin sheath in the injured sciatic nerve was regular, with an even thickness and clear outline, and the surrounding fibroplasia was not obvious. Our results indicate that 7, 8-dihydroxycoumarin can promote the repair of injured nerve by upregulating growth associated protein 43 expression in the corresponding spinal cord segments of mice with sciatic nerve injury.
文摘The Total Coloring Conjecture (TCC) proposes that every simple graph G is (Δ + 2)-totally-colorable, where Δ is the maximum degree of G. For planar graph, TCC is open only in case Δ = 6. In this paper, we prove that TCC holds for planar graph with Δ = 6 and every 7-cycle contains at most two chords.
