Autophagy is an important factor in reducing the efficacy of tumor phototherapy(including PTT and PDT).Accurate regulation of autophagy in tumor cells is a new strategy to improve the anti-tumor efficiency of PTT/PDT....Autophagy is an important factor in reducing the efficacy of tumor phototherapy(including PTT and PDT).Accurate regulation of autophagy in tumor cells is a new strategy to improve the anti-tumor efficiency of PTT/PDT.This project intended to construct a tumor-activated autophagy regulator to efficiently block PTT/PDT-induced autophagy and realize synergistic sensitization to tumor phototherapy.To achieve this goal,we first synthesized TRANSFERRIN(Tf)biomimetic mineralized nano-tellurium(Tf-Te)as photosensitizer and then used disulfide bond reconstruction technology to induce Tf-Te self-assembly.The autophagy inhibitor hydroxychloroquine(HCQ)and iron ions carried by Tf were simultaneously loaded to prepare a tumor-responsive drug reservoir Tf-Te/HCQ.After entering breast cancer cells through the“self-guidance system”,Tf-Te/HCQ can generate hyperpyrexia and ROS under NIR laser irradiation,to efficiently induce PTT/PDT effect.Meanwhile,the disulfide bond broke down in response to GSH,and the nanoparticles disintegrated to release Fe2+and HCQ at fixed points.They simultaneously induce lysosomal alkalinization and increased osmotic pressure,effectively inhibit autophagy,and synergistically enhance the therapeutic effect of phototherapy.In vivo anti-tumor results have proved that the tumor inhibition rate of Tf-Te/HCQ can be as high as 88.6%on 4T1 tumor-bearing mice.This multifunctional drug delivery system might provide a new alternative for more precise and effective tumor phototherapy.展开更多
Organofluorine compounds are widely used in the realm of drug discovery and material science.Herein,we developed palladium catalyzed intermolecular aminofluorination and oxy-aminofluorination of gem‑difluoroalkenes wi...Organofluorine compounds are widely used in the realm of drug discovery and material science.Herein,we developed palladium catalyzed intermolecular aminofluorination and oxy-aminofluorination of gem‑difluoroalkenes with N-fluorobenzenesulfonimide(NFSI),in which NFSI was used as the nitrogen source and oxidant.The reaction provides an efficient and straightforward synthesis route of a series ofα-trifluoromethyl benzylic amines.Notably,three/four components oxy-aminofluorination processes were realized to giveα-trifluoromethyl benzylic ether with a terminal amino group,which proceed through C(sp^(3))-O bond cleavage of easily available ether and simultaneous introduced a fluorine,an amino and an oxy substituent in one pot with excellent regioselectivity.The divergent reactivity not only included the incorporation of one ether molecular,but also much more challenged two ether insertion with excellent selectivity through succession C(sp^(3))-O bonds cleavage.This protocol allows for concise synthesis of high value amines with fluoroalkyl-substituents and selectively transformation of easily available ethers by high-valent palladium catalysis.展开更多
The typical hallmark of tumor evolution is metabolic dysregulation.In addition to secreting immunoregulatory metabolites,tumor cells and various immune cells display different metabolic pathways and plasticity.Harness...The typical hallmark of tumor evolution is metabolic dysregulation.In addition to secreting immunoregulatory metabolites,tumor cells and various immune cells display different metabolic pathways and plasticity.Harnessing the metabolic differences to reduce the tumor and immunosuppressive cells while enhancing the activity of positive immunoregulatory cells is a promising strategy.We develop a nanoplatform(CLCeMOF)based on cerium metal-organic framework(CeMOF)by lactate oxidase(LOX)modification and glutaminase inhibitor(CB839)loading.The cascade catalytic reactions induced by CLCeMOF generate reactive oxygen species“storm”to elicit immune responses.Meanwhile,LOX-mediated metabolite lactate exhaustion relieves the immunosuppressive tumor microenvironment,preparing the ground for intracellular regulation.Most noticeably,the immunometabolic checkpoint blockade therapy,as a result of glutamine antagonism,is exploited for overall cell mobilization.It is found that CLCeMOF inhibited glutamine metabolism-dependent cells(tumor cells,immunosuppressive cells,etc.),increased infiltration of dendritic cells,and especially reprogrammed CD8^(+)T lymphocytes with considerable metabolic flexibility toward a highly activated,long-lived,and memory-like phenotype.Such an idea intervenes both metabolite(lactate)and cellular metabolic pathway,which essentially alters overall cell fates toward the desired situation.Collectively,the metabolic intervention strategy is bound to break the evolutionary adaptability of tumors for reinforced immunotherapy.展开更多
A Rh(III)-catalyzed,transmetalation triggered C—H activation/annulation of 2-biphenylboronic acids with diazo compounds fromβ-keto esters or 1,3-dicarboxylates has been developed,leading to the synthesis of two kind...A Rh(III)-catalyzed,transmetalation triggered C—H activation/annulation of 2-biphenylboronic acids with diazo compounds fromβ-keto esters or 1,3-dicarboxylates has been developed,leading to the synthesis of two kinds of 9,10-phenanthrenes.Notably,a rhodacyle was synthesized by treating the rhodium catalyst with stoichiometric amounts of 2-biphenylboronic acids and pyridine,which was further verified to be active for the catalytic system.The reactions proceeded under redox-neutral and air-tolerant conditions to produce a series of all-carbon six-membered rings with high efficiency.展开更多
Modified nucleosides,particularly those with 4'-modifications,are significant nucleosides used in antiviral treatments.The drug discovery campaign of Azvudine starts from 2′-deoxynucleoside,followed by extensive ...Modified nucleosides,particularly those with 4'-modifications,are significant nucleosides used in antiviral treatments.The drug discovery campaign of Azvudine starts from 2′-deoxynucleoside,followed by extensive modifications,such as introducing the 4’-position substitutions,a 2’-β-fluoro atom,and changing the nucleobases.Azvudine acts potently toward various HIV-1 strains by inhibiting HIV-1 reverse transcription and preventing Vif-induced A3G degradation,representing the first-in-class dual-acting antiviral agent.In July 2021,the NMPA conditionally approved Azvudine as an adjunct therapy for adult patients with high levels of HIV-1 virus load when combined with NRTIs or NNRTIs.Azvudine is capable of inhibiting SARS-CoV-2,as well as its variants,including Alpha,Beta,Delta,and Omicron.Clinical trials have revealed its real-world effectiveness among hospitalized severely or critically ill COVID-19 patients or those with pre-existing conditions.On July 25th,2022,the NMPA granted conditional authorization approving Azvudine as China's first domestic oral anti-COVID-19 agent.Generally,Azvudine at therapeutic doses is safe and well-tolerated in clinical settings.Azvudine got approval from the National Health Commission and National Administration of Traditional Chinese Medicine on August 9th to be used in the"Diagnosis and Treatment Program for Novel Coronavirus Pneumonia(Ninth Edition)"for treating common COVID-19 adult patients.On August 12th,2022,it was also approved by the National Healthcare Security Administration to be added to the list of medical reimbursements.Of note,the achievements related to Azvudine were indexed in the China Basic Research Development Report in Thirty-Five of 2022.Azvudine was also approved on January 5th,2023,to be used in the"Diagnosis and Treatment Program for Novel Coronavirus Pneumonia(Tenth Edition)"for treating COVID-19 patients.In February 2023,the Ministry of Health of the Russian Federation approved the usage of Azvudine among individuals infected with SARS-CoV-2.What is the most favorite and original chemistry developed in your research group?My favorite chemistries are always those that enable efficient access to drug molecules.How do you get into this specific field?Could you please share some experiences with our readers?The virus uses nucleosides as raw materials for replication.Learned from this biological process,I have been devoted to,for decades,synthesizing nucleoside mimics.Once attached to the 3'-hydroxy group of the virus RNA chain,these nucleoside analogs can effectively inhibit virus replication.Hard work pays off!We have developed a series of novel 4’-modified nucleosides,among which Azvudine has been officially approved for treating HIV in China and COVID-19 in both China and Russia.Notably,Azvudine is the first Chinese oral anti-COVID-19 agent.The experiences I would like to share with the readers are many,but emphases are placed on thinking critically and working enthusiastically.How do you supervise your students?I generally supervise students differently according to their aptitudes.For those keen on scientific work,I always suggest them learn from the literature,and practice makes perfect,think critically,and work with passion.What is the most important personality for scientific research?The personalities such as curiosity,creativity,persistence,and the ability to think critically and solve problems matter most for scientific research.Furthermore,what sets successful scientists apart is their passion for their work and their ability to persevere in facing challenges and setbacks.Who influences you mostly in your life?My Ph.D.supervisor profoundly fuels my passion for academia and,to some extent,reshapes my personality.展开更多
A very recent work published in Advanced Science by our group reveals that 2′-deoxy-2′-β-fluoro-4′-azidocytidine(Azvudine,FNC),a clinical candidate originally developed for HIV treatment,has entered clinical trial...A very recent work published in Advanced Science by our group reveals that 2′-deoxy-2′-β-fluoro-4′-azidocytidine(Azvudine,FNC),a clinical candidate originally developed for HIV treatment,has entered clinical trial in China for evaluating its efficacy and safety(ChiCTR2000029853),showing promise for treating novel coronavirus disease 2019(COVID-19).1 This work suggests that nucleoside-based antivirus agents could be repurposed for COVID-19 treatment.展开更多
Since the emergence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)at the end of 2019,thousands of SARS-CoV-2 mutations have been increasingly observed.The virus epidemic has posed unprecedented challen...Since the emergence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)at the end of 2019,thousands of SARS-CoV-2 mutations have been increasingly observed.The virus epidemic has posed unprecedented challenges to global public health.As of September 19,2022,over 609 million confirmed cases and about 6.50 million deaths worldwide have been reported to the World Health Organization.The development of novel antivirals capable of treating SARS-CoV-2 infections has been a central focus of current research.To cope with the current novel coronavirus pneumonia(coronavirus disease 2019[COVID-19])epidemic.展开更多
SARS-CoV-2 infection-induced hyper-inflammation links to the acute lung injury and COVID-19 severity.Identifying the primary mediators that initiate the uncontrolled hypercytokinemia is essential for treatments.Mast c...SARS-CoV-2 infection-induced hyper-inflammation links to the acute lung injury and COVID-19 severity.Identifying the primary mediators that initiate the uncontrolled hypercytokinemia is essential for treatments.Mast cells(MCs)are strategically located at the mucosa and beneficially or detrimentally regulate immune inflammations.In this study,we showed that SARS-CoV-2-triggered MC degranulation initiated alveolar epithelial inflammation and lung injury.SARS-CoV-2 challenge induced MC degranulation in ACE-2 humanized mice and rhesus macaques,and a rapid MC degranulation could be recapitulated with Spike-RBD binding to ACE2 in cells;MC degranulation altered various signaling pathways in alveolar epithelial cells,particularly,the induction of pro-inflammatory factors and consequential disruption of tight junctions.Importantly,the administration of clinical MC stabilizers for blocking degranulation dampened SARS-CoV-2-induced production of pro-inflammatory factors and prevented lung injury.These findings uncover a novel mechanism for SARS-CoV-2 initiating lung inflammation,and suggest an off-label use of MC stabilizer as immunomodulators for COVID-19 treatments.展开更多
Main observation and conclusion The efficient cleavage of carbon-oxygen(C—O)bond is highly important for the transformation of oxygen-rich biomass and industry chemicals.Herein,an efficient[3+3]annulation ofβ-ketoet...Main observation and conclusion The efficient cleavage of carbon-oxygen(C—O)bond is highly important for the transformation of oxygen-rich biomass and industry chemicals.Herein,an efficient[3+3]annulation ofβ-ketoethers with cyclopropenones in the presence of catalytic base has been developed,which proceeds through the C(sp^(3))—O bonds cleavage inβ-ketoethers and C—C bond cleavage in cyclopropenones under transition-metal free conditions.The cleavage of C(sp^(3))—O bonds in alkyl alkyl ethers and aryl alkyl ethers was realized.The reaction featured excellent functional group compatibility and chemoselectivity,affording various 2-pyrones in good to excellent yields under mild conditions and simple operation.展开更多
A synthetic strategy for catalytic asymmetric conjugate addition-protonation and diastereoselective switch between 5H-oxazol-4-ones and 5-methylene 1,3-oxazolidine-2,4-diones was established.An array of chiral conjuga...A synthetic strategy for catalytic asymmetric conjugate addition-protonation and diastereoselective switch between 5H-oxazol-4-ones and 5-methylene 1,3-oxazolidine-2,4-diones was established.An array of chiral conjugate addition-protonation products bearing 1,3-O-heterotertiary-O-heteroquarternary nonadjacent stereocenters were obtained in excellent yields,moderate to good diastereoselectivities,and excellent enantioselectivities (up to 97% yield,11:1 dr,and 98% ee).Induction by 2,2'-biphenol could effectively promote the production of the corresponding diastereoisomers via cycloaddition intermedia.展开更多
An efficient metal-free intramolecular hydroarylation reaction of alkynes is described here.A series of aryl and N-group attached alkynes generated the intramolecular hydroarylation products in high yields.
基金This work was supported by the National Natural Science Foundation of China(Nos.82102918,81972893 and 82172719)the Key Program for Science and Technology Research in Henan Province(No.232102311093,China)the Training Plan for Young Backbone Teachers in Higher Education Institutions of Henan Province(No.2021ZDGGJS054,China).
文摘Autophagy is an important factor in reducing the efficacy of tumor phototherapy(including PTT and PDT).Accurate regulation of autophagy in tumor cells is a new strategy to improve the anti-tumor efficiency of PTT/PDT.This project intended to construct a tumor-activated autophagy regulator to efficiently block PTT/PDT-induced autophagy and realize synergistic sensitization to tumor phototherapy.To achieve this goal,we first synthesized TRANSFERRIN(Tf)biomimetic mineralized nano-tellurium(Tf-Te)as photosensitizer and then used disulfide bond reconstruction technology to induce Tf-Te self-assembly.The autophagy inhibitor hydroxychloroquine(HCQ)and iron ions carried by Tf were simultaneously loaded to prepare a tumor-responsive drug reservoir Tf-Te/HCQ.After entering breast cancer cells through the“self-guidance system”,Tf-Te/HCQ can generate hyperpyrexia and ROS under NIR laser irradiation,to efficiently induce PTT/PDT effect.Meanwhile,the disulfide bond broke down in response to GSH,and the nanoparticles disintegrated to release Fe2+and HCQ at fixed points.They simultaneously induce lysosomal alkalinization and increased osmotic pressure,effectively inhibit autophagy,and synergistically enhance the therapeutic effect of phototherapy.In vivo anti-tumor results have proved that the tumor inhibition rate of Tf-Te/HCQ can be as high as 88.6%on 4T1 tumor-bearing mice.This multifunctional drug delivery system might provide a new alternative for more precise and effective tumor phototherapy.
基金supported by the National Natural Science Foundation of China(Nos.82130103,U1804283,21801067)the Central Plains Scholars and Scientists Studio Fund(No.2018002)+2 种基金the Project funded by the Natural Science Foundation of Henan Province(Nos.202300410225,222102310562)Henan Postdoctoral Science Foundation(No.202103087)the financial support from Henan Key Laboratory of Organic Functional Molecules and Drug Innovation.
文摘Organofluorine compounds are widely used in the realm of drug discovery and material science.Herein,we developed palladium catalyzed intermolecular aminofluorination and oxy-aminofluorination of gem‑difluoroalkenes with N-fluorobenzenesulfonimide(NFSI),in which NFSI was used as the nitrogen source and oxidant.The reaction provides an efficient and straightforward synthesis route of a series ofα-trifluoromethyl benzylic amines.Notably,three/four components oxy-aminofluorination processes were realized to giveα-trifluoromethyl benzylic ether with a terminal amino group,which proceed through C(sp^(3))-O bond cleavage of easily available ether and simultaneous introduced a fluorine,an amino and an oxy substituent in one pot with excellent regioselectivity.The divergent reactivity not only included the incorporation of one ether molecular,but also much more challenged two ether insertion with excellent selectivity through succession C(sp^(3))-O bonds cleavage.This protocol allows for concise synthesis of high value amines with fluoroalkyl-substituents and selectively transformation of easily available ethers by high-valent palladium catalysis.
基金financially supported by the National Natural Science Foundation of China(81901878,China)China Postdoctoral Science Foundation(2020T130611 and 2019M662553,China)+4 种基金Key Scientific Research Project(Education Department of Henan Province)(20HASTIT049,China)Youth Talent Promotion Project in Henan Province(2021HYTP010,China)Central Plains Talents Program(ZYYCYU202012176,China)Henan Medical Science and technology research plan project(LHGJ20200455,China)Youth talent innovation team support plan of Zhengzhou University。
文摘The typical hallmark of tumor evolution is metabolic dysregulation.In addition to secreting immunoregulatory metabolites,tumor cells and various immune cells display different metabolic pathways and plasticity.Harnessing the metabolic differences to reduce the tumor and immunosuppressive cells while enhancing the activity of positive immunoregulatory cells is a promising strategy.We develop a nanoplatform(CLCeMOF)based on cerium metal-organic framework(CeMOF)by lactate oxidase(LOX)modification and glutaminase inhibitor(CB839)loading.The cascade catalytic reactions induced by CLCeMOF generate reactive oxygen species“storm”to elicit immune responses.Meanwhile,LOX-mediated metabolite lactate exhaustion relieves the immunosuppressive tumor microenvironment,preparing the ground for intracellular regulation.Most noticeably,the immunometabolic checkpoint blockade therapy,as a result of glutamine antagonism,is exploited for overall cell mobilization.It is found that CLCeMOF inhibited glutamine metabolism-dependent cells(tumor cells,immunosuppressive cells,etc.),increased infiltration of dendritic cells,and especially reprogrammed CD8^(+)T lymphocytes with considerable metabolic flexibility toward a highly activated,long-lived,and memory-like phenotype.Such an idea intervenes both metabolite(lactate)and cellular metabolic pathway,which essentially alters overall cell fates toward the desired situation.Collectively,the metabolic intervention strategy is bound to break the evolutionary adaptability of tumors for reinforced immunotherapy.
基金the financial support for this work from the National Key R&D Program of China(2021YFC0864700)the NSFC(Nos.21801066,U1804283 and 82130103)+2 种基金the Central Plains Scholars and Scientists Studio Fund(2018002)the project funded by the Natural Science Foundation of Henan Province(222300420056,222300420204)the China Postdoctoral Science Foundation(2020M682307,2021T140183).
文摘A Rh(III)-catalyzed,transmetalation triggered C—H activation/annulation of 2-biphenylboronic acids with diazo compounds fromβ-keto esters or 1,3-dicarboxylates has been developed,leading to the synthesis of two kinds of 9,10-phenanthrenes.Notably,a rhodacyle was synthesized by treating the rhodium catalyst with stoichiometric amounts of 2-biphenylboronic acids and pyridine,which was further verified to be active for the catalytic system.The reactions proceeded under redox-neutral and air-tolerant conditions to produce a series of all-carbon six-membered rings with high efficiency.
基金supported by the National Natural Science Foundation of China(Nos.82130103 and U1804283)the National Key R&D Program of China(Nos.2021YFC0864700 and 2022YFE0202700).
文摘Modified nucleosides,particularly those with 4'-modifications,are significant nucleosides used in antiviral treatments.The drug discovery campaign of Azvudine starts from 2′-deoxynucleoside,followed by extensive modifications,such as introducing the 4’-position substitutions,a 2’-β-fluoro atom,and changing the nucleobases.Azvudine acts potently toward various HIV-1 strains by inhibiting HIV-1 reverse transcription and preventing Vif-induced A3G degradation,representing the first-in-class dual-acting antiviral agent.In July 2021,the NMPA conditionally approved Azvudine as an adjunct therapy for adult patients with high levels of HIV-1 virus load when combined with NRTIs or NNRTIs.Azvudine is capable of inhibiting SARS-CoV-2,as well as its variants,including Alpha,Beta,Delta,and Omicron.Clinical trials have revealed its real-world effectiveness among hospitalized severely or critically ill COVID-19 patients or those with pre-existing conditions.On July 25th,2022,the NMPA granted conditional authorization approving Azvudine as China's first domestic oral anti-COVID-19 agent.Generally,Azvudine at therapeutic doses is safe and well-tolerated in clinical settings.Azvudine got approval from the National Health Commission and National Administration of Traditional Chinese Medicine on August 9th to be used in the"Diagnosis and Treatment Program for Novel Coronavirus Pneumonia(Ninth Edition)"for treating common COVID-19 adult patients.On August 12th,2022,it was also approved by the National Healthcare Security Administration to be added to the list of medical reimbursements.Of note,the achievements related to Azvudine were indexed in the China Basic Research Development Report in Thirty-Five of 2022.Azvudine was also approved on January 5th,2023,to be used in the"Diagnosis and Treatment Program for Novel Coronavirus Pneumonia(Tenth Edition)"for treating COVID-19 patients.In February 2023,the Ministry of Health of the Russian Federation approved the usage of Azvudine among individuals infected with SARS-CoV-2.What is the most favorite and original chemistry developed in your research group?My favorite chemistries are always those that enable efficient access to drug molecules.How do you get into this specific field?Could you please share some experiences with our readers?The virus uses nucleosides as raw materials for replication.Learned from this biological process,I have been devoted to,for decades,synthesizing nucleoside mimics.Once attached to the 3'-hydroxy group of the virus RNA chain,these nucleoside analogs can effectively inhibit virus replication.Hard work pays off!We have developed a series of novel 4’-modified nucleosides,among which Azvudine has been officially approved for treating HIV in China and COVID-19 in both China and Russia.Notably,Azvudine is the first Chinese oral anti-COVID-19 agent.The experiences I would like to share with the readers are many,but emphases are placed on thinking critically and working enthusiastically.How do you supervise your students?I generally supervise students differently according to their aptitudes.For those keen on scientific work,I always suggest them learn from the literature,and practice makes perfect,think critically,and work with passion.What is the most important personality for scientific research?The personalities such as curiosity,creativity,persistence,and the ability to think critically and solve problems matter most for scientific research.Furthermore,what sets successful scientists apart is their passion for their work and their ability to persevere in facing challenges and setbacks.Who influences you mostly in your life?My Ph.D.supervisor profoundly fuels my passion for academia and,to some extent,reshapes my personality.
基金financially supported by the National Natural Science Foundation of China(21905253,51973200)the China Postdoctoral Science Foundation(2018M640681,2019T120632)。
基金supported by Henan Province Novel Coronavirus Control and Prevention Emergency Science and Technology Tackling Key Project(No.201100311500)National Natural Science Foundation of China(No.U1804283).
文摘A very recent work published in Advanced Science by our group reveals that 2′-deoxy-2′-β-fluoro-4′-azidocytidine(Azvudine,FNC),a clinical candidate originally developed for HIV treatment,has entered clinical trial in China for evaluating its efficacy and safety(ChiCTR2000029853),showing promise for treating novel coronavirus disease 2019(COVID-19).1 This work suggests that nucleoside-based antivirus agents could be repurposed for COVID-19 treatment.
基金supported by the National Natural Science Foundation of China(nos.82130103 and U1804283)National Key R&D Program Emergency Response Project for Novel Coronavirus Pneumonia(no.2021YFC0864700)and Henan Province Novel Coronavirus Control and Prevention Emergency Science and Technology Tackling Key Project(no.201100311500).
文摘Since the emergence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)at the end of 2019,thousands of SARS-CoV-2 mutations have been increasingly observed.The virus epidemic has posed unprecedented challenges to global public health.As of September 19,2022,over 609 million confirmed cases and about 6.50 million deaths worldwide have been reported to the World Health Organization.The development of novel antivirals capable of treating SARS-CoV-2 infections has been a central focus of current research.To cope with the current novel coronavirus pneumonia(coronavirus disease 2019[COVID-19])epidemic.
文摘SARS-CoV-2 infection-induced hyper-inflammation links to the acute lung injury and COVID-19 severity.Identifying the primary mediators that initiate the uncontrolled hypercytokinemia is essential for treatments.Mast cells(MCs)are strategically located at the mucosa and beneficially or detrimentally regulate immune inflammations.In this study,we showed that SARS-CoV-2-triggered MC degranulation initiated alveolar epithelial inflammation and lung injury.SARS-CoV-2 challenge induced MC degranulation in ACE-2 humanized mice and rhesus macaques,and a rapid MC degranulation could be recapitulated with Spike-RBD binding to ACE2 in cells;MC degranulation altered various signaling pathways in alveolar epithelial cells,particularly,the induction of pro-inflammatory factors and consequential disruption of tight junctions.Importantly,the administration of clinical MC stabilizers for blocking degranulation dampened SARS-CoV-2-induced production of pro-inflammatory factors and prevented lung injury.These findings uncover a novel mechanism for SARS-CoV-2 initiating lung inflammation,and suggest an off-label use of MC stabilizer as immunomodulators for COVID-19 treatments.
基金supported by the NSFC(Nos.21801067,U1804283,21801066)the Central Plains scholars and ScientistsStudio Fund(No.2018002)+1 种基金the Project funded by the NaturalScience Foundation of Henan Province(Nos.202300410225,212300410181 and 201901023)the China Postdoctoral Science Foundation(Nos.2020T130176 and 2020M682306)。
文摘Main observation and conclusion The efficient cleavage of carbon-oxygen(C—O)bond is highly important for the transformation of oxygen-rich biomass and industry chemicals.Herein,an efficient[3+3]annulation ofβ-ketoethers with cyclopropenones in the presence of catalytic base has been developed,which proceeds through the C(sp^(3))—O bonds cleavage inβ-ketoethers and C—C bond cleavage in cyclopropenones under transition-metal free conditions.The cleavage of C(sp^(3))—O bonds in alkyl alkyl ethers and aryl alkyl ethers was realized.The reaction featured excellent functional group compatibility and chemoselectivity,affording various 2-pyrones in good to excellent yields under mild conditions and simple operation.
基金This work was supported by the National Natural Science Foundation of China (U1804283)the National Postdoctoral Pro-gram for Innovative Talents (No. BX201700071)+1 种基金a project funded by the China Postdoctoral Science Foundation (No. 2017M622348)the 111 project (D17007).
文摘A synthetic strategy for catalytic asymmetric conjugate addition-protonation and diastereoselective switch between 5H-oxazol-4-ones and 5-methylene 1,3-oxazolidine-2,4-diones was established.An array of chiral conjugate addition-protonation products bearing 1,3-O-heterotertiary-O-heteroquarternary nonadjacent stereocenters were obtained in excellent yields,moderate to good diastereoselectivities,and excellent enantioselectivities (up to 97% yield,11:1 dr,and 98% ee).Induction by 2,2'-biphenol could effectively promote the production of the corresponding diastereoisomers via cycloaddition intermedia.
基金We thank the National Natural Science Foundation of China(no.81803406 and U1804283)the Foundation of Henan Educational Committee(19A150009)for financial support.
文摘An efficient metal-free intramolecular hydroarylation reaction of alkynes is described here.A series of aryl and N-group attached alkynes generated the intramolecular hydroarylation products in high yields.
