Background:Despite highly effective vaccines against SARS-CoV-2,COVID-19 vaccine hesitancy persisted in some populations in England during the pandemic,with rates and motivations for hesitancy varying by demographic g...Background:Despite highly effective vaccines against SARS-CoV-2,COVID-19 vaccine hesitancy persisted in some populations in England during the pandemic,with rates and motivations for hesitancy varying by demographic group.Addressing the drivers of vaccine hesitancy through targeted interventions in hesitant groups is a public health priority for better and more rapid control of disease spread.We aimed to characterise the determinants and subtypes of vaccine hesitancy and identify more persistent forms of hesitancy via analysis of vaccine uptake in a large cross-sectional cohort with linked National Health Service(NHS)data.展开更多
Coronaviruses are single-stranded,positive-sense RNA enveloped viruses that have posed a significant threat to human health over the past few decades,particularly severe acute respiratory syndrome coronavirus(SARS-CoV...Coronaviruses are single-stranded,positive-sense RNA enveloped viruses that have posed a significant threat to human health over the past few decades,particularly severe acute respiratory syndrome coronavirus(SARS-CoV),Middle East respiratory syndrome coronavirus(MERS-CoV),and SARS-CoV-2.These viruses have caused widespread infections and fatalities,with profound impacts on global economies,social life,and public health systems.Due to their broad host range in natural settings and the consequent high potential for zoonotic spillover events,a thorough investigation of the common viral mechanisms and the identification of druggable targets for pan-coronavirus antiviral development are of utmost importance.展开更多
Dear Editor,The COVID-19 pandemic,caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has resulted in millions of deaths worldwide.It poses significant challenges in the management of immunocompr...Dear Editor,The COVID-19 pandemic,caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has resulted in millions of deaths worldwide.It poses significant challenges in the management of immunocompromised patients,particularly people with HIV(PWH).Whether PWH are more vulnerable to COVID with more adverse outcomes has been extensively studied,but the findings are inconsistent.Many cohort studies and meta-analyses support that PWH have a higher risk of SARSCoV-2 infection and more severe COVID-19 outcomes(Bertagnolio et al.,2022;Ssentongo et al.,2021).展开更多
Dear Editor,Historically,dipeptidyl peptidase 4(DPP4),found in alveolar regions,has been recognized as the primary receptor for several merbecoviruses like MERS-CoV(Meyerholz et al.,2016).However,angiotensin-convertin...Dear Editor,Historically,dipeptidyl peptidase 4(DPP4),found in alveolar regions,has been recognized as the primary receptor for several merbecoviruses like MERS-CoV(Meyerholz et al.,2016).However,angiotensin-converting enzyme 2(ACE2),highly expressed in the motile cilia of human airway epithelial cells(Sungnak et al.,2020),has been identified as the functional receptor for sarbecoviruses(e.g.,SARS-CoV-2,SARS-CoV)and setracoviruses(e.g.,HCoV-NL63).Recent studies have shown that some bat-circulating MERS-related coronaviruses(MERSr-CoVs),such as MOW15-22,PnNL2018B and HKU5,can use ACE2 to enter cells(Ma et al.,2025;Park et al.,2025).Even more worrying is that one novel bat-infecting merbecovirus HKU5-CoV lineage 2(BtHKU5-CoV-2)has been reported to use human ACE2 as a cell entry receptor(Chen et al.,2025).These ACE2-utilizing merbecoviruses expand the diversity,geographic distribution,and transmission potential of coronaviruses,posing a significant threat of spillover to humans.If an ACE2-utilizing MERSr-CoV acquire the high lethality of MERS-CoV and the high transmissibility of SARS-CoV-2 using ACE2 as a receptor,it could trigger a global pandemic with catastrophic consequences for humanity.Therefore,it is essential to evaluate serological cross-reactivity in sera from SARS-CoV-2-infected individuals against ACE2-using MERSr-CoVs,and urgent to develop preventive vaccines and pan-coronavirus antivirals confront the potential threat(Jiang and Wu,2025).展开更多
Human cytochrome P4501B1(h CYP1B1),an extrahepatic heme-dependent monooxygenase,has been validated as a key target for overcoming chemotherapy resistance and tumorigenesis.Herein,to discover novel efficacious h CYP1B1...Human cytochrome P4501B1(h CYP1B1),an extrahepatic heme-dependent monooxygenase,has been validated as a key target for overcoming chemotherapy resistance and tumorigenesis.Herein,to discover novel efficacious h CYP1B1 inhibitors,a suite of 1,8-naphthalimide derivatives was designed,synthesized,and biologically evaluated,via integrating structure-based drug design(SBDD)and biochemical assays.After two rounds of structural modifications and structure-activity relationship(SAR)studies,the results suggested that introducing a benzene ring at the north part and a halogen atom at the C-4 site significantly enhanced the anti-h CYP1B1 effects of naphthalimides.Among all tested 1,8-naphthalimides,NB-10showed the most potent anti-h CYP1B1 effect(half maximal inhibitory concentration(IC_(50))=0.41 nmol/L)and excellent specificity,while this agent did not activate Ah R transcription activity in living cells.Further cellular assays and in vivo tests in paclitaxel(PTX)-resistance xenograft mice showed that NB-10could significantly potentiate the anti-cancer effects of PTX both in vitro and in vivo,while this agent also showed high safety profiles in mice.Mechanistically,NB-10 potently inhibited h CYP1B1-catalyzed 7-ethoxyresorufin O-deethylation in a competitive manner,with an estimated Kivalue of 0.15 nmol/L.Docking simulations showed that NB-10 could be well-fitted in the catalytic pocket of h CYP1B1 to form a stable conformation with a high binding affinity.Collectively,several potent 4-halogenated naphthalimides were developed as novel h CYP1B1 inhibitors,while NB-10 showed high safety profiles and impressive efficacy for overcoming h CYP1B1-associated PTX resistance both in vitro and in vivo.展开更多
文摘Background:Despite highly effective vaccines against SARS-CoV-2,COVID-19 vaccine hesitancy persisted in some populations in England during the pandemic,with rates and motivations for hesitancy varying by demographic group.Addressing the drivers of vaccine hesitancy through targeted interventions in hesitant groups is a public health priority for better and more rapid control of disease spread.We aimed to characterise the determinants and subtypes of vaccine hesitancy and identify more persistent forms of hesitancy via analysis of vaccine uptake in a large cross-sectional cohort with linked National Health Service(NHS)data.
基金supported by the Key Research and Development Program,Ministry of Science and Technology of the People’s Republic of China(Nos.2023YFC2606500,2023YFE0206500).
文摘Coronaviruses are single-stranded,positive-sense RNA enveloped viruses that have posed a significant threat to human health over the past few decades,particularly severe acute respiratory syndrome coronavirus(SARS-CoV),Middle East respiratory syndrome coronavirus(MERS-CoV),and SARS-CoV-2.These viruses have caused widespread infections and fatalities,with profound impacts on global economies,social life,and public health systems.Due to their broad host range in natural settings and the consequent high potential for zoonotic spillover events,a thorough investigation of the common viral mechanisms and the identification of druggable targets for pan-coronavirus antiviral development are of utmost importance.
基金National Key Research and Development Project of China(2023YFC2306600)Key Program of the National Natural Science Foundation of China(82430070)+6 种基金Shanghai Pujiang Program(No.23PJ1410800)National Natural Science Foundation of China(82072260,32370168)Eastern Talent Plan Leading Project,Shanghai Hospital Development Center Foundation(SHDC12022121)Shanghai 2020“Science and Technology Innovation Action Plan”Medical Innovation Research Special(20Z11900900)Three-year Action Plan(2023-2025)Key Discipline Program on Public Health System Construction of Shanghai(GWVI-11.1-15)Construction of the Major Infectious Disease Medical Treatment System(GWVI-2.2).
文摘Dear Editor,The COVID-19 pandemic,caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has resulted in millions of deaths worldwide.It poses significant challenges in the management of immunocompromised patients,particularly people with HIV(PWH).Whether PWH are more vulnerable to COVID with more adverse outcomes has been extensively studied,but the findings are inconsistent.Many cohort studies and meta-analyses support that PWH have a higher risk of SARSCoV-2 infection and more severe COVID-19 outcomes(Bertagnolio et al.,2022;Ssentongo et al.,2021).
文摘Dear Editor,Historically,dipeptidyl peptidase 4(DPP4),found in alveolar regions,has been recognized as the primary receptor for several merbecoviruses like MERS-CoV(Meyerholz et al.,2016).However,angiotensin-converting enzyme 2(ACE2),highly expressed in the motile cilia of human airway epithelial cells(Sungnak et al.,2020),has been identified as the functional receptor for sarbecoviruses(e.g.,SARS-CoV-2,SARS-CoV)and setracoviruses(e.g.,HCoV-NL63).Recent studies have shown that some bat-circulating MERS-related coronaviruses(MERSr-CoVs),such as MOW15-22,PnNL2018B and HKU5,can use ACE2 to enter cells(Ma et al.,2025;Park et al.,2025).Even more worrying is that one novel bat-infecting merbecovirus HKU5-CoV lineage 2(BtHKU5-CoV-2)has been reported to use human ACE2 as a cell entry receptor(Chen et al.,2025).These ACE2-utilizing merbecoviruses expand the diversity,geographic distribution,and transmission potential of coronaviruses,posing a significant threat of spillover to humans.If an ACE2-utilizing MERSr-CoV acquire the high lethality of MERS-CoV and the high transmissibility of SARS-CoV-2 using ACE2 as a receptor,it could trigger a global pandemic with catastrophic consequences for humanity.Therefore,it is essential to evaluate serological cross-reactivity in sera from SARS-CoV-2-infected individuals against ACE2-using MERSr-CoVs,and urgent to develop preventive vaccines and pan-coronavirus antivirals confront the potential threat(Jiang and Wu,2025).
基金supported by the National Natural Science Foundation of China(Nos.82273897,U23A20516,32101202)Organizational Key Research and Development Program of Shanghai University of Traditional Chinese Medicine(No.2023YZZ02)+5 种基金Shanghai Municipal Health Commission’s TCM research project(No.2022CX005)Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(No.ZYYCXTDD-202004)Pudong Institute of Clinical Chinese Medicine(No.YC-2023-0603)The“Fourteenth Five-Year Plan”Traditional Chinese Medicine Specialty Project for the Construction of Andrology Departments in TCM(No.ZYTSZK1-4)the State Key Laboratory of Fine Chemicals,Dalian University of Technology(No.KF2202)the Fundamental Research Funds for the Central Universities(No.G2024KY05106)。
文摘Human cytochrome P4501B1(h CYP1B1),an extrahepatic heme-dependent monooxygenase,has been validated as a key target for overcoming chemotherapy resistance and tumorigenesis.Herein,to discover novel efficacious h CYP1B1 inhibitors,a suite of 1,8-naphthalimide derivatives was designed,synthesized,and biologically evaluated,via integrating structure-based drug design(SBDD)and biochemical assays.After two rounds of structural modifications and structure-activity relationship(SAR)studies,the results suggested that introducing a benzene ring at the north part and a halogen atom at the C-4 site significantly enhanced the anti-h CYP1B1 effects of naphthalimides.Among all tested 1,8-naphthalimides,NB-10showed the most potent anti-h CYP1B1 effect(half maximal inhibitory concentration(IC_(50))=0.41 nmol/L)and excellent specificity,while this agent did not activate Ah R transcription activity in living cells.Further cellular assays and in vivo tests in paclitaxel(PTX)-resistance xenograft mice showed that NB-10could significantly potentiate the anti-cancer effects of PTX both in vitro and in vivo,while this agent also showed high safety profiles in mice.Mechanistically,NB-10 potently inhibited h CYP1B1-catalyzed 7-ethoxyresorufin O-deethylation in a competitive manner,with an estimated Kivalue of 0.15 nmol/L.Docking simulations showed that NB-10 could be well-fitted in the catalytic pocket of h CYP1B1 to form a stable conformation with a high binding affinity.Collectively,several potent 4-halogenated naphthalimides were developed as novel h CYP1B1 inhibitors,while NB-10 showed high safety profiles and impressive efficacy for overcoming h CYP1B1-associated PTX resistance both in vitro and in vivo.
