Quinoxalin-2(1H)-ones are unique nitrogen-containing organic compounds with wide applications in the agrochemical,pharmaceutical,and chemical industries as well as in material science.During the last decades,visible-l...Quinoxalin-2(1H)-ones are unique nitrogen-containing organic compounds with wide applications in the agrochemical,pharmaceutical,and chemical industries as well as in material science.During the last decades,visible-light-promoted photoredox catalysis has emerged as a versatile platform for constructing quinoxalin-2(1H)-one scaffolds under exceptionally mild conditions.In this review,we provide an overview of recent advances in photocatalytic direct C(3)–H functionalization of quinoxaline-2(1H)-ones,including the construction of C(3)–C bonds and C(3)–R_(F)/C/O/N/Cl/S/D bonds,as well as the related reaction mechanisms.We aim to enhance the methods for the reaction of quinoxalin-2(1H)-ones at the C-3 position,which have extensive applications in organic synthesis and medicinal chemistry.展开更多
2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) is a stoichiometric oxidant that is frequently used in traditional organic synthesis. Recently, the rapid development of organic electrochemistry has led to new advancem...2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) is a stoichiometric oxidant that is frequently used in traditional organic synthesis. Recently, the rapid development of organic electrochemistry has led to new advancements in DDQ-catalyzed C—H bonds functionalization. Moreover, the challenging C—H functionalization of electron-deficient arenes has been achieved through the merger of electrochemical DDQ catalysis and photoirradiation. In addition, the synthetic utility of electrophotochemical DDQ catalysis was further demonstrated by the nucleophilic aromatic substitution (SNAr) reaction of unactivated aryl fluorides. The recent developments in electro- and electrophotochemical DDQ-catalyzed C—H/C—F func- tionalizations with attention to their strategies and mechanistic insights are summarized. It is hoped that this not only deepens the understanding of this field, but also helps relevant researchers expand the application scope of DDQ catalysis.展开更多
目的基于核苷酸结合寡聚化结构域样受体3/半胱氨酸蛋白酶-1(NLRP3/caspase-1)信号通路探究二甲双胍对2型糖尿病(T2DM)合并脑卒中患者认知功能的改善作用。方法选取2021年2月至2022年5月就诊于邯郸市中心医院的63例T2DM,按照随机数字表...目的基于核苷酸结合寡聚化结构域样受体3/半胱氨酸蛋白酶-1(NLRP3/caspase-1)信号通路探究二甲双胍对2型糖尿病(T2DM)合并脑卒中患者认知功能的改善作用。方法选取2021年2月至2022年5月就诊于邯郸市中心医院的63例T2DM,按照随机数字表法将其分为对照组(n=32)与试验组(n=31),对照组给予钠-葡萄糖共转运蛋白2抑制剂(SGLT-2i)类药物治疗,试验组在对照组基础上给予二甲双胍治疗,两组患者均连续治疗12周。收集患者临床资料,对比治疗前后两组简易精神量表(MMSE)得分、蒙特利尔认知评估量表(MoCA)得分、空腹血糖(FBG)、糖化血红蛋白(HbA1c)、餐后2小时血糖(2 hPBG)、外周单核细胞中NLRP3炎性小体蛋白表达水平、caspase-1蛋白表达水平及血清IL-8、IL-1β水平;采用Pearson线性相关分析治疗后NLRP3、caspase-1、IL-18、IL-1β与FBG的相关性。结果治疗后,试验组MMSE、MoCA得分均增高,且明显高于对照组(P<0.05),试验组FBG、HbA1c、2 h PBG水平低于对照组(P<0.05),试验组NLRP3、caspase-1蛋白水平和IL-18、IL-1β水平较对照组明显更低(P<0.05);经Pearson线性相关分析显示,治疗后NLRP3、caspase-1、IL-18、IL-1β与FBG呈正相关(P<0.05)。结论二甲双胍治疗能够改善T2DM合并脑卒中患者的认知功能,降低血糖水平和炎症反应,这可能与其对NLRP3/caspase-1信号通路的调节作用有关。展开更多
Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0...Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.展开更多
The activation of the sirtuin1(SIRT1)/nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)pathway has been shown to mitigate oxidative stress-induced apoptosis and mitochondrial damage by reducing ...The activation of the sirtuin1(SIRT1)/nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)pathway has been shown to mitigate oxidative stress-induced apoptosis and mitochondrial damage by reducing reactive oxygen species(ROS)levels.Clinical trials have demonstrated that Zhongfeng Xingnao Liquid(ZFXN)ameliorates post-stroke cognitive impairment(PSCI).However,the underlying mechanism,particularly whether it involves protecting mitochondria and inhibiting apoptosis through the SIRT1/Nrf2/HO-1 pathway,remains unclear.This study employed an oxygen-glucose deprivation(OGD)cell model using SHSY5Y cells and induced PSCI in rats through modified bilateral carotid artery ligation(2VO).The effects of ZFXN on learning and memory,neuroprotective activity,mitochondrial function,oxidative stress,and the SIRT1/Nrf2/HO-1 pathway were evaluated both in vivo and in vitro.Results indicated that ZFXN significantly increased the B-cell lymphoma 2(Bcl2)/Bcl2-associated X(Bax)ratio,reduced terminal deoxynucleotidyl transferase-mediated d UTP nickend-labeling(TUNEL)+cells,and markedly improved cognition,synaptic plasticity,and neuronal function in the hippocampus and cortex.Furthermore,ZFXN exhibited potent antioxidant activity,evidenced by decreased ROS and malondialdehyde(MDA)content and increased superoxide dismutase(SOD),catalase(CAT),and glutathione(GSH)levels.ZFXN also demonstrated considerable enhancement of mitochondrial membrane potential(MMP),Tom 20 fluorescence intensity,adenosine triphosphate(ATP)and energy charge(EC)levels,and mitochondrial complexⅠandⅢactivity,thereby inhibiting mitochondrial damage.Additionally,ZFXN significantly increased SIRT1 activity and elevated SIRT1,nuclear Nrf2,and HO-1 levels.Notably,these effects were substantially counteracted when SIRT1 was suppressed by the inhibitor EX-527 in vitro.In conclusion,ZFXN alleviates PSCI by activating the SIRT1/Nrf2/HO-1 pathway and preventing mitochondrial damage.展开更多
The photo-/electrocatalytic functionalization of quinoxalin-2(1H)-ones has emerged as a promising and powerful approach for post-synthetic modification of quinoxalin-2(1H)-ones.This review provides an overview of rece...The photo-/electrocatalytic functionalization of quinoxalin-2(1H)-ones has emerged as a promising and powerful approach for post-synthetic modification of quinoxalin-2(1H)-ones.This review provides an overview of recent developments in photo-/electrocatalytic functionalization of quinoxalin-2(1H)-ones including arylation,alkylation,fluoroalkylation,amination,phosphorylation,acylation,alkoxylation,thiolation,silylation,and annulation.The reaction scope and the related mechanism are also well discussed.展开更多
基金support from the National Natural Science Foundation of China(No.22101267)the China Postdoctoral Science Foundation(Nos.2021M692905 and 2024T170832)+2 种基金Natural Science Foundation of Henan Province,China(No.242300421123)Scientific Research Project of Hubei Provincial Education Department,China(No.Q20233104)Hubei Provincial Natural Science Foundation,China(No.2024AFB946).
文摘Quinoxalin-2(1H)-ones are unique nitrogen-containing organic compounds with wide applications in the agrochemical,pharmaceutical,and chemical industries as well as in material science.During the last decades,visible-light-promoted photoredox catalysis has emerged as a versatile platform for constructing quinoxalin-2(1H)-one scaffolds under exceptionally mild conditions.In this review,we provide an overview of recent advances in photocatalytic direct C(3)–H functionalization of quinoxaline-2(1H)-ones,including the construction of C(3)–C bonds and C(3)–R_(F)/C/O/N/Cl/S/D bonds,as well as the related reaction mechanisms.We aim to enhance the methods for the reaction of quinoxalin-2(1H)-ones at the C-3 position,which have extensive applications in organic synthesis and medicinal chemistry.
文摘2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) is a stoichiometric oxidant that is frequently used in traditional organic synthesis. Recently, the rapid development of organic electrochemistry has led to new advancements in DDQ-catalyzed C—H bonds functionalization. Moreover, the challenging C—H functionalization of electron-deficient arenes has been achieved through the merger of electrochemical DDQ catalysis and photoirradiation. In addition, the synthetic utility of electrophotochemical DDQ catalysis was further demonstrated by the nucleophilic aromatic substitution (SNAr) reaction of unactivated aryl fluorides. The recent developments in electro- and electrophotochemical DDQ-catalyzed C—H/C—F func- tionalizations with attention to their strategies and mechanistic insights are summarized. It is hoped that this not only deepens the understanding of this field, but also helps relevant researchers expand the application scope of DDQ catalysis.
文摘目的基于核苷酸结合寡聚化结构域样受体3/半胱氨酸蛋白酶-1(NLRP3/caspase-1)信号通路探究二甲双胍对2型糖尿病(T2DM)合并脑卒中患者认知功能的改善作用。方法选取2021年2月至2022年5月就诊于邯郸市中心医院的63例T2DM,按照随机数字表法将其分为对照组(n=32)与试验组(n=31),对照组给予钠-葡萄糖共转运蛋白2抑制剂(SGLT-2i)类药物治疗,试验组在对照组基础上给予二甲双胍治疗,两组患者均连续治疗12周。收集患者临床资料,对比治疗前后两组简易精神量表(MMSE)得分、蒙特利尔认知评估量表(MoCA)得分、空腹血糖(FBG)、糖化血红蛋白(HbA1c)、餐后2小时血糖(2 hPBG)、外周单核细胞中NLRP3炎性小体蛋白表达水平、caspase-1蛋白表达水平及血清IL-8、IL-1β水平;采用Pearson线性相关分析治疗后NLRP3、caspase-1、IL-18、IL-1β与FBG的相关性。结果治疗后,试验组MMSE、MoCA得分均增高,且明显高于对照组(P<0.05),试验组FBG、HbA1c、2 h PBG水平低于对照组(P<0.05),试验组NLRP3、caspase-1蛋白水平和IL-18、IL-1β水平较对照组明显更低(P<0.05);经Pearson线性相关分析显示,治疗后NLRP3、caspase-1、IL-18、IL-1β与FBG呈正相关(P<0.05)。结论二甲双胍治疗能够改善T2DM合并脑卒中患者的认知功能,降低血糖水平和炎症反应,这可能与其对NLRP3/caspase-1信号通路的调节作用有关。
基金supported by the National Natural Science Foundation of China,Nos.82204360(to HM)and 82270411(to GW)National Science and Technology Innovation 2030 Major Program,No.2021ZD0200900(to YL)。
文摘Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.
基金supported by the Science&Technology Department of Sichuan Province(No.2019YFS0040)the Improvement Plan of“Xinglin Scholar”Scientific Research Talent,Chengdu University of Traditional Chinese Medicine(No.XKTD2022002)。
文摘The activation of the sirtuin1(SIRT1)/nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)pathway has been shown to mitigate oxidative stress-induced apoptosis and mitochondrial damage by reducing reactive oxygen species(ROS)levels.Clinical trials have demonstrated that Zhongfeng Xingnao Liquid(ZFXN)ameliorates post-stroke cognitive impairment(PSCI).However,the underlying mechanism,particularly whether it involves protecting mitochondria and inhibiting apoptosis through the SIRT1/Nrf2/HO-1 pathway,remains unclear.This study employed an oxygen-glucose deprivation(OGD)cell model using SHSY5Y cells and induced PSCI in rats through modified bilateral carotid artery ligation(2VO).The effects of ZFXN on learning and memory,neuroprotective activity,mitochondrial function,oxidative stress,and the SIRT1/Nrf2/HO-1 pathway were evaluated both in vivo and in vitro.Results indicated that ZFXN significantly increased the B-cell lymphoma 2(Bcl2)/Bcl2-associated X(Bax)ratio,reduced terminal deoxynucleotidyl transferase-mediated d UTP nickend-labeling(TUNEL)+cells,and markedly improved cognition,synaptic plasticity,and neuronal function in the hippocampus and cortex.Furthermore,ZFXN exhibited potent antioxidant activity,evidenced by decreased ROS and malondialdehyde(MDA)content and increased superoxide dismutase(SOD),catalase(CAT),and glutathione(GSH)levels.ZFXN also demonstrated considerable enhancement of mitochondrial membrane potential(MMP),Tom 20 fluorescence intensity,adenosine triphosphate(ATP)and energy charge(EC)levels,and mitochondrial complexⅠandⅢactivity,thereby inhibiting mitochondrial damage.Additionally,ZFXN significantly increased SIRT1 activity and elevated SIRT1,nuclear Nrf2,and HO-1 levels.Notably,these effects were substantially counteracted when SIRT1 was suppressed by the inhibitor EX-527 in vitro.In conclusion,ZFXN alleviates PSCI by activating the SIRT1/Nrf2/HO-1 pathway and preventing mitochondrial damage.
文摘The photo-/electrocatalytic functionalization of quinoxalin-2(1H)-ones has emerged as a promising and powerful approach for post-synthetic modification of quinoxalin-2(1H)-ones.This review provides an overview of recent developments in photo-/electrocatalytic functionalization of quinoxalin-2(1H)-ones including arylation,alkylation,fluoroalkylation,amination,phosphorylation,acylation,alkoxylation,thiolation,silylation,and annulation.The reaction scope and the related mechanism are also well discussed.
