To the Editor:Obesity is a pivotal risk factor for type 2 diabetes mellitus(T2DM),and its frequent co-occurrence has contributed to increased morbidity and mortality worldwide.Bariatric surgery represents an effective...To the Editor:Obesity is a pivotal risk factor for type 2 diabetes mellitus(T2DM),and its frequent co-occurrence has contributed to increased morbidity and mortality worldwide.Bariatric surgery represents an effective intervention for obese patients with diabetes.However,the extent of postoperative diabetes remission varies considerably across individuals.Current predictive scoring models are derived from variables identified through univariate analyses,which may insufficiently capture the heterogeneity of T2DM and are limited in their ability to discriminate among distinct diabetes subgroups.In contrast,clustering-based approaches offer a more integrative,phenotype-driven classification system that may better inform surgical outcomes.A well-established clustering framework classifies T2DM into four subtypes:severe insulin-resistant diabetes(SIRD),mild age-related diabetes(MARD),severe insulin-deficient diabetes(SIDD),and mild obesity-related diabetes(MOD).These subtypes differ in clinical presentation,complication risks,and response to pharmacologic treatments,suggesting their potential for guiding individualized treatment.While this classification has been initially investigated in European populations undergoing bariatric surgery,its relevance and applicability in Chinese diabetic patients undergoing surgery remain unexplored.Ethnic differences are known to influence diabetes phenotypes and treatment response.In the Chinese population,T2DM develops at a lower body mass index(BMI),often accompanied by intrinsic β-cell dysfunction,increased visceral adiposity,and heightened insulin resistance.展开更多
Major outbreaks of severe acute respiratory syndrome(SARS)and coronavirus disease 2019(COVID-19),together with the continuous risk of zoonotic spillover of animal sarbecoviruses,underscore the urgent need for vaccines...Major outbreaks of severe acute respiratory syndrome(SARS)and coronavirus disease 2019(COVID-19),together with the continuous risk of zoonotic spillover of animal sarbecoviruses,underscore the urgent need for vaccines that confer broad protection across the sarbecovirus subgenus.Current immunogen selection strategies for pansarbecovirus vaccine development predominantly rely on phylogenetic or spike sequence conservation analyses,which often fail to accurately predict the breadth of cross-neutralization.To overcome this limitation,we systematically evaluated cross-neutralization profiles among 25 representative sarbecoviruses from clades 1 and 3 via guinea pig antisera individually raised against full-length spike proteins in pseudovirus neutralization assays while excluding clade 2 viruses lacking known receptor usage.Neutralization profiling revealed four distinct immunogenic clusters that diverged from traditional phylogenetic relationships.Antisera induced by the palm civet-derived SARS-CoV-1 strain SZ1 broadly neutralized all clade 1a viruses,whereas full coverage of clade 1b viruses required at least two distinct immunogens.Remarkably,sera elicited by multiple clade 1 immunogens also neutralized clade 3 viruses despite no prior exposure to clade 3 antigens.Guided by these findings,we proposed a minimal trivalent immunogen combination—SZ1,SARS-CoV-2,and PCoV-GX—that elicited broad neutralization against both clade 1 and clade 3.This rational approach eliminates the need for additional clade 3-specific antigens and provides a preclinical framework for developing next-generation pansarbecovirus vaccines.展开更多
基金supported by grants from the National Key Research and Development Program of China(No.2022YFC2505204)Noncommunicable Chronic Diseases-National Science and Technology Major Project(No.2024ZD0531700)the National Natural Science Foundation of China(Nos.82370871,and 32241011).
文摘To the Editor:Obesity is a pivotal risk factor for type 2 diabetes mellitus(T2DM),and its frequent co-occurrence has contributed to increased morbidity and mortality worldwide.Bariatric surgery represents an effective intervention for obese patients with diabetes.However,the extent of postoperative diabetes remission varies considerably across individuals.Current predictive scoring models are derived from variables identified through univariate analyses,which may insufficiently capture the heterogeneity of T2DM and are limited in their ability to discriminate among distinct diabetes subgroups.In contrast,clustering-based approaches offer a more integrative,phenotype-driven classification system that may better inform surgical outcomes.A well-established clustering framework classifies T2DM into four subtypes:severe insulin-resistant diabetes(SIRD),mild age-related diabetes(MARD),severe insulin-deficient diabetes(SIDD),and mild obesity-related diabetes(MOD).These subtypes differ in clinical presentation,complication risks,and response to pharmacologic treatments,suggesting their potential for guiding individualized treatment.While this classification has been initially investigated in European populations undergoing bariatric surgery,its relevance and applicability in Chinese diabetic patients undergoing surgery remain unexplored.Ethnic differences are known to influence diabetes phenotypes and treatment response.In the Chinese population,T2DM develops at a lower body mass index(BMI),often accompanied by intrinsic β-cell dysfunction,increased visceral adiposity,and heightened insulin resistance.
基金supported by the Natural Science Foundation of China(grant no.82172244)the Major Project of Guangzhou National Laboratory(GZNL2024A01019).
文摘Major outbreaks of severe acute respiratory syndrome(SARS)and coronavirus disease 2019(COVID-19),together with the continuous risk of zoonotic spillover of animal sarbecoviruses,underscore the urgent need for vaccines that confer broad protection across the sarbecovirus subgenus.Current immunogen selection strategies for pansarbecovirus vaccine development predominantly rely on phylogenetic or spike sequence conservation analyses,which often fail to accurately predict the breadth of cross-neutralization.To overcome this limitation,we systematically evaluated cross-neutralization profiles among 25 representative sarbecoviruses from clades 1 and 3 via guinea pig antisera individually raised against full-length spike proteins in pseudovirus neutralization assays while excluding clade 2 viruses lacking known receptor usage.Neutralization profiling revealed four distinct immunogenic clusters that diverged from traditional phylogenetic relationships.Antisera induced by the palm civet-derived SARS-CoV-1 strain SZ1 broadly neutralized all clade 1a viruses,whereas full coverage of clade 1b viruses required at least two distinct immunogens.Remarkably,sera elicited by multiple clade 1 immunogens also neutralized clade 3 viruses despite no prior exposure to clade 3 antigens.Guided by these findings,we proposed a minimal trivalent immunogen combination—SZ1,SARS-CoV-2,and PCoV-GX—that elicited broad neutralization against both clade 1 and clade 3.This rational approach eliminates the need for additional clade 3-specific antigens and provides a preclinical framework for developing next-generation pansarbecovirus vaccines.
