Understanding the dynamic control of supramolecular chirality is essential for the development of advanced chiral materials.This study presents a system where solvent-induced self-assembly of ortho-pyridine-azo-choles...Understanding the dynamic control of supramolecular chirality is essential for the development of advanced chiral materials.This study presents a system where solvent-induced self-assembly of ortho-pyridine-azo-cholesterol(o-PAzPCC)and temperature-regulated co-assembly with Cu2+exhibit dynamic supramolecular chirality inversion.Dimethylsulfoxide(DMSO)and alcohol solvents induce the reverse assembly of o-PAzPCC monomers,leading to circular dichroism(CD)signal inversion.Notably,the chloro-bridged Cu^(2+)/o-PAzPCC co-assembly system demonstrates temperature-regulated chirality inversion within a narrow range(283 to 293 K).At 283 K,van der Waals forces drive the formation of non-equilibrium nanosheet structures(Agg I)with positive CD absorption at 390 nm.At 293 K,π-πstacking interactions promote equilibrium nanoribbon structures(Agg III)with negative CD absorption at 440 nm wavelength.Increasing the temperature from 283 K can induce a transformation of the nanosheet structures to nanoflower structures(Agg II),characterized by positive CD absorption at 440 nm.The chirality inversion can be finely tuned by adjusting the concentrations and ultrasonication time.This work enhances our understanding of chiral assembly processes and their chirality transmission mechanisms,advancing the development of chiral supramolecular materials for applications in biological systems.展开更多
The pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has resulted in more than 230 million cases and over four million deaths worldwide.Furthermore,multiple emerging SARS-CoV-2 variants ha...The pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has resulted in more than 230 million cases and over four million deaths worldwide.Furthermore,multiple emerging SARS-CoV-2 variants have shown enhanced infectivity,transmissibility,pathogenicity and ability to escape neutralization by vaccine-induced humoral immunity[1].The antibody resistance of SARS-CoV-2 variants constitutes a challenge for current vaccines and therapeutic antibodies.No specific antiviral is currently available for coronavirus in humans[2].Although remdesivir was approved by the FDA for the treatment of SARS-CoV-2 infection,the therapeutic effect is limited,particularly for critical cases with severe pneumonia.展开更多
The new predominant circulating SARS-CoV-2 variant,Omicron,can robustly escape current vaccines and neutralizing antibodies.Although Omicron has been reported to have milder replication and disease manifestations than...The new predominant circulating SARS-CoV-2 variant,Omicron,can robustly escape current vaccines and neutralizing antibodies.Although Omicron has been reported to have milder replication and disease manifestations than some earlier variants,its pathogenicity in different age groups has not been well elucidated.Here,we report that the SARS-CoV-2 Omicron BA.1 sublineage causes elevated infection and lung pathogenesis in juvenile and aged hamsters,with more body weight loss,respiratory tract viral burden,and lung injury in these hamsters than in adult hamsters.Juvenile hamsters show a reduced interferon response against Omicron BA.1 infection,whereas aged hamsters show excessive proinflammatory cytokine expression,delayed viral clearance,and aggravated lung injury.Early inhaled IFN-α2b treatment suppresses Omicron BA.1 infection and lung pathogenesis in juvenile and adult hamsters.Overall,the data suggest that the diverse patterns of the innate immune response affect the disease outcomes of Omicron BA.1 infection in different age groups.展开更多
Glioblastoma(GBM)is an aggressive and lethal type of brain tumor in human adults.The standard of care offers minimal clinical benefit,and most GBM patients experience tumor recurrence after treatment.In recent years,s...Glioblastoma(GBM)is an aggressive and lethal type of brain tumor in human adults.The standard of care offers minimal clinical benefit,and most GBM patients experience tumor recurrence after treatment.In recent years,significant advancements have been made in the development of novel immunotherapies or other therapeutic strategies that can overcome immunotherapy resistance in many advanced cancers.However,the benefit of immune-based treatments in GBM is limited because of the unique brain immune profiles,GBM cell heterogeneity,and immunosuppressive tumor microenvironment.In this review,we present a detailed overview of current immunotherapeutic strategies and discuss the challenges and potential molecular mechanisms underlying immunotherapy resistance in GBM.Furthermore,we provide an in-depth discussion regarding the strategies that can overcome immunotherapy resistance in GBM,which will likely require combination therapies.展开更多
基金supported by the National Natural Science Foundation of China(Nos.22471198 and 22101208)the Fundamental Research Funds for the Central Universitiesthe Program for Professors of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning.
文摘Understanding the dynamic control of supramolecular chirality is essential for the development of advanced chiral materials.This study presents a system where solvent-induced self-assembly of ortho-pyridine-azo-cholesterol(o-PAzPCC)and temperature-regulated co-assembly with Cu2+exhibit dynamic supramolecular chirality inversion.Dimethylsulfoxide(DMSO)and alcohol solvents induce the reverse assembly of o-PAzPCC monomers,leading to circular dichroism(CD)signal inversion.Notably,the chloro-bridged Cu^(2+)/o-PAzPCC co-assembly system demonstrates temperature-regulated chirality inversion within a narrow range(283 to 293 K).At 283 K,van der Waals forces drive the formation of non-equilibrium nanosheet structures(Agg I)with positive CD absorption at 390 nm.At 293 K,π-πstacking interactions promote equilibrium nanoribbon structures(Agg III)with negative CD absorption at 440 nm wavelength.Increasing the temperature from 283 K can induce a transformation of the nanosheet structures to nanoflower structures(Agg II),characterized by positive CD absorption at 440 nm.The chirality inversion can be finely tuned by adjusting the concentrations and ultrasonication time.This work enhances our understanding of chiral assembly processes and their chirality transmission mechanisms,advancing the development of chiral supramolecular materials for applications in biological systems.
基金supported by grants from the National Science Key Research and Development Project(No.2020YFC0842600)National Natural Science Foundation of China(No.82002139)+1 种基金China Postdoctoral Science Foundation(No.2020T130362,No.2020M682092)the CAMS Innovation Fund for Medical Sciences(No.2019RU022).
文摘The pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has resulted in more than 230 million cases and over four million deaths worldwide.Furthermore,multiple emerging SARS-CoV-2 variants have shown enhanced infectivity,transmissibility,pathogenicity and ability to escape neutralization by vaccine-induced humoral immunity[1].The antibody resistance of SARS-CoV-2 variants constitutes a challenge for current vaccines and therapeutic antibodies.No specific antiviral is currently available for coronavirus in humans[2].Although remdesivir was approved by the FDA for the treatment of SARS-CoV-2 infection,the therapeutic effect is limited,particularly for critical cases with severe pneumonia.
基金supported by grants from the National Science Key Research and Development Project (2020YFC0842600)the National Natural Science Foundation of China (82002139)+2 种基金the Guangdong Natural Science Foundation (2019B121205009/HZQB-KCZYZ-2021014/200109155890863/190830095586328/190824215544727)the China Postdoctoral Science Foundation (2020T130362/2020M682092)the CAMS Innovation Fund for Medical Sciences (No.2019RU022).
文摘The new predominant circulating SARS-CoV-2 variant,Omicron,can robustly escape current vaccines and neutralizing antibodies.Although Omicron has been reported to have milder replication and disease manifestations than some earlier variants,its pathogenicity in different age groups has not been well elucidated.Here,we report that the SARS-CoV-2 Omicron BA.1 sublineage causes elevated infection and lung pathogenesis in juvenile and aged hamsters,with more body weight loss,respiratory tract viral burden,and lung injury in these hamsters than in adult hamsters.Juvenile hamsters show a reduced interferon response against Omicron BA.1 infection,whereas aged hamsters show excessive proinflammatory cytokine expression,delayed viral clearance,and aggravated lung injury.Early inhaled IFN-α2b treatment suppresses Omicron BA.1 infection and lung pathogenesis in juvenile and adult hamsters.Overall,the data suggest that the diverse patterns of the innate immune response affect the disease outcomes of Omicron BA.1 infection in different age groups.
基金supported in part by National Institutes of Health(NIH)R01 NS127824(PC),NIH R01 NS124594(PC),NIH P01 CA245705(JDL),R35 NS127083(JDL)the Department of Defense(DoD)Career Development Award W81XWH-21-1-0380(P.C.),as well as the Lerner Research Institute and Case Comprehensive Cancer Center.
文摘Glioblastoma(GBM)is an aggressive and lethal type of brain tumor in human adults.The standard of care offers minimal clinical benefit,and most GBM patients experience tumor recurrence after treatment.In recent years,significant advancements have been made in the development of novel immunotherapies or other therapeutic strategies that can overcome immunotherapy resistance in many advanced cancers.However,the benefit of immune-based treatments in GBM is limited because of the unique brain immune profiles,GBM cell heterogeneity,and immunosuppressive tumor microenvironment.In this review,we present a detailed overview of current immunotherapeutic strategies and discuss the challenges and potential molecular mechanisms underlying immunotherapy resistance in GBM.Furthermore,we provide an in-depth discussion regarding the strategies that can overcome immunotherapy resistance in GBM,which will likely require combination therapies.
