The Unexpected and Exceptionally Facile Chemical Modification of the Phenolic Hydroxyl Group of Tyrosine by Polyhalogenated Quinones under Physiological Conditions

The phenolic hydroxyl group of tyrosine residue plays a crucial role in the structure and function of many proteins. However, little study has been reported about its modification by chemical agents under physiological conditions. In this study, we found, unexpectedly, that the phenolic hydroxyl group of tyrosine can be rapidly and efficiently modified by tetrafluoro-1,4-benzoquinone and other polyhalogenated quinones, which are the major genotoxic and carcinogenic quinoid metabolites of polyhalogenated aromatic compounds. The modification was found to be mainly due to the formation of a variety of fluoroquinone–<i>O</i>-tyrosine conjugates and their hydroxylated derivatives via nucleophilic substitution pathway. Analogous modifications were observed for tyrosine-containing peptides. Further studies showed that the blockade of the reactive phenolic hydroxyl group of tyrosine in the substrate peptide, even by very low concentration of tetrafluoro-1,4-benzoquinone, can prevent the kinase catalyzed tyrosine phosphorylation. This is the first report showing the exceptionally facile chemical modification of the phenolic hydroxyl group of tyrosine by polyhalogenated quinones under normal physiological conditions, which may have potential biological and toxicological implications

Image_3_Global Burden of cardiomyopathy and myocarditis in the older adults from 1990 to 2019.TIF

BackgroundCardiomyopathy and myocarditis (CM-MC) are common chronic diseases causing heart failure in older adults. We aimed to analyze the burden of CM-MC in older adults aged 60–89 years at the global, regional, and national levels in 204 countries from 1990 to 2019.MethodsDetailed data on CM-MC from 1990 to 2019 were analyzed from the Global Burden of Diseases Study 2019, including incidence, mortality, disability-adjusted life years (DALYs) and the proportion of deaths caused by different risks factors. All results are presented as numbers, age-standardized rates per 100,000 person-years and estimated annual percentage change (EAPC) with an uncertainty interval of 95%.ResultsGlobally, there were 475,458 (339,942–638,363) incidence cases from CM-MC in 2019; with an age-standardized incidence rate (ASIR) of 16 (13–19.3) per 100,000 person-years. And there were 185,308 (154,610–200,448) deaths, with the age-standardized mortality rate (ASMR) being 4.4 (3.7–4.8). CM-MC resulted in 3,372,716 (2,931,247–3,693,622) DALYs, with an age-standardized DALYs rate (ASDR) of 114.8 (98.7–126.1). Estimated annual percentage change (EAPCs) for ARIS, ARMS, and ARDS has decreased. At the national level, the United States of America had the highest mortality [21,372 (18,924–24,241)] and disability-adjusted life years [407,712 (370,234–470,165)]. And China had the highest number of incident cases [122, 266 (85,925–166,095)]. Globally, high systolic blood pressure and alcohol consumption were the top two risk factors for the proportion of CM-MC deaths.ConclusionCM-MC is still an important cause of early death and chronic disability in older adults. Based on this study, public health agencies should seek more effective methods to prevent and treat CM-MC.</p

Image_5_Global Burden of cardiomyopathy and myocarditis in the older adults from 1990 to 2019.TIF

BackgroundCardiomyopathy and myocarditis (CM-MC) are common chronic diseases causing heart failure in older adults. We aimed to analyze the burden of CM-MC in older adults aged 60–89 years at the global, regional, and national levels in 204 countries from 1990 to 2019.MethodsDetailed data on CM-MC from 1990 to 2019 were analyzed from the Global Burden of Diseases Study 2019, including incidence, mortality, disability-adjusted life years (DALYs) and the proportion of deaths caused by different risks factors. All results are presented as numbers, age-standardized rates per 100,000 person-years and estimated annual percentage change (EAPC) with an uncertainty interval of 95%.ResultsGlobally, there were 475,458 (339,942–638,363) incidence cases from CM-MC in 2019; with an age-standardized incidence rate (ASIR) of 16 (13–19.3) per 100,000 person-years. And there were 185,308 (154,610–200,448) deaths, with the age-standardized mortality rate (ASMR) being 4.4 (3.7–4.8). CM-MC resulted in 3,372,716 (2,931,247–3,693,622) DALYs, with an age-standardized DALYs rate (ASDR) of 114.8 (98.7–126.1). Estimated annual percentage change (EAPCs) for ARIS, ARMS, and ARDS has decreased. At the national level, the United States of America had the highest mortality [21,372 (18,924–24,241)] and disability-adjusted life years [407,712 (370,234–470,165)]. And China had the highest number of incident cases [122, 266 (85,925–166,095)]. Globally, high systolic blood pressure and alcohol consumption were the top two risk factors for the proportion of CM-MC deaths.ConclusionCM-MC is still an important cause of early death and chronic disability in older adults. Based on this study, public health agencies should seek more effective methods to prevent and treat CM-MC.</p

Table_1_Global Burden of cardiomyopathy and myocarditis in the older adults from 1990 to 2019.docx

BackgroundCardiomyopathy and myocarditis (CM-MC) are common chronic diseases causing heart failure in older adults. We aimed to analyze the burden of CM-MC in older adults aged 60–89 years at the global, regional, and national levels in 204 countries from 1990 to 2019.MethodsDetailed data on CM-MC from 1990 to 2019 were analyzed from the Global Burden of Diseases Study 2019, including incidence, mortality, disability-adjusted life years (DALYs) and the proportion of deaths caused by different risks factors. All results are presented as numbers, age-standardized rates per 100,000 person-years and estimated annual percentage change (EAPC) with an uncertainty interval of 95%.ResultsGlobally, there were 475,458 (339,942–638,363) incidence cases from CM-MC in 2019; with an age-standardized incidence rate (ASIR) of 16 (13–19.3) per 100,000 person-years. And there were 185,308 (154,610–200,448) deaths, with the age-standardized mortality rate (ASMR) being 4.4 (3.7–4.8). CM-MC resulted in 3,372,716 (2,931,247–3,693,622) DALYs, with an age-standardized DALYs rate (ASDR) of 114.8 (98.7–126.1). Estimated annual percentage change (EAPCs) for ARIS, ARMS, and ARDS has decreased. At the national level, the United States of America had the highest mortality [21,372 (18,924–24,241)] and disability-adjusted life years [407,712 (370,234–470,165)]. And China had the highest number of incident cases [122, 266 (85,925–166,095)]. Globally, high systolic blood pressure and alcohol consumption were the top two risk factors for the proportion of CM-MC deaths.ConclusionCM-MC is still an important cause of early death and chronic disability in older adults. Based on this study, public health agencies should seek more effective methods to prevent and treat CM-MC.</p

Image_1_Global Burden of cardiomyopathy and myocarditis in the older adults from 1990 to 2019.TIF

BackgroundCardiomyopathy and myocarditis (CM-MC) are common chronic diseases causing heart failure in older adults. We aimed to analyze the burden of CM-MC in older adults aged 60–89 years at the global, regional, and national levels in 204 countries from 1990 to 2019.MethodsDetailed data on CM-MC from 1990 to 2019 were analyzed from the Global Burden of Diseases Study 2019, including incidence, mortality, disability-adjusted life years (DALYs) and the proportion of deaths caused by different risks factors. All results are presented as numbers, age-standardized rates per 100,000 person-years and estimated annual percentage change (EAPC) with an uncertainty interval of 95%.ResultsGlobally, there were 475,458 (339,942–638,363) incidence cases from CM-MC in 2019; with an age-standardized incidence rate (ASIR) of 16 (13–19.3) per 100,000 person-years. And there were 185,308 (154,610–200,448) deaths, with the age-standardized mortality rate (ASMR) being 4.4 (3.7–4.8). CM-MC resulted in 3,372,716 (2,931,247–3,693,622) DALYs, with an age-standardized DALYs rate (ASDR) of 114.8 (98.7–126.1). Estimated annual percentage change (EAPCs) for ARIS, ARMS, and ARDS has decreased. At the national level, the United States of America had the highest mortality [21,372 (18,924–24,241)] and disability-adjusted life years [407,712 (370,234–470,165)]. And China had the highest number of incident cases [122, 266 (85,925–166,095)]. Globally, high systolic blood pressure and alcohol consumption were the top two risk factors for the proportion of CM-MC deaths.ConclusionCM-MC is still an important cause of early death and chronic disability in older adults. Based on this study, public health agencies should seek more effective methods to prevent and treat CM-MC.</p

Image_2_Global Burden of cardiomyopathy and myocarditis in the older adults from 1990 to 2019.TIF

BackgroundCardiomyopathy and myocarditis (CM-MC) are common chronic diseases causing heart failure in older adults. We aimed to analyze the burden of CM-MC in older adults aged 60–89 years at the global, regional, and national levels in 204 countries from 1990 to 2019.MethodsDetailed data on CM-MC from 1990 to 2019 were analyzed from the Global Burden of Diseases Study 2019, including incidence, mortality, disability-adjusted life years (DALYs) and the proportion of deaths caused by different risks factors. All results are presented as numbers, age-standardized rates per 100,000 person-years and estimated annual percentage change (EAPC) with an uncertainty interval of 95%.ResultsGlobally, there were 475,458 (339,942–638,363) incidence cases from CM-MC in 2019; with an age-standardized incidence rate (ASIR) of 16 (13–19.3) per 100,000 person-years. And there were 185,308 (154,610–200,448) deaths, with the age-standardized mortality rate (ASMR) being 4.4 (3.7–4.8). CM-MC resulted in 3,372,716 (2,931,247–3,693,622) DALYs, with an age-standardized DALYs rate (ASDR) of 114.8 (98.7–126.1). Estimated annual percentage change (EAPCs) for ARIS, ARMS, and ARDS has decreased. At the national level, the United States of America had the highest mortality [21,372 (18,924–24,241)] and disability-adjusted life years [407,712 (370,234–470,165)]. And China had the highest number of incident cases [122, 266 (85,925–166,095)]. Globally, high systolic blood pressure and alcohol consumption were the top two risk factors for the proportion of CM-MC deaths.ConclusionCM-MC is still an important cause of early death and chronic disability in older adults. Based on this study, public health agencies should seek more effective methods to prevent and treat CM-MC.</p

Image_4_Global Burden of cardiomyopathy and myocarditis in the older adults from 1990 to 2019.TIF

BackgroundCardiomyopathy and myocarditis (CM-MC) are common chronic diseases causing heart failure in older adults. We aimed to analyze the burden of CM-MC in older adults aged 60–89 years at the global, regional, and national levels in 204 countries from 1990 to 2019.MethodsDetailed data on CM-MC from 1990 to 2019 were analyzed from the Global Burden of Diseases Study 2019, including incidence, mortality, disability-adjusted life years (DALYs) and the proportion of deaths caused by different risks factors. All results are presented as numbers, age-standardized rates per 100,000 person-years and estimated annual percentage change (EAPC) with an uncertainty interval of 95%.ResultsGlobally, there were 475,458 (339,942–638,363) incidence cases from CM-MC in 2019; with an age-standardized incidence rate (ASIR) of 16 (13–19.3) per 100,000 person-years. And there were 185,308 (154,610–200,448) deaths, with the age-standardized mortality rate (ASMR) being 4.4 (3.7–4.8). CM-MC resulted in 3,372,716 (2,931,247–3,693,622) DALYs, with an age-standardized DALYs rate (ASDR) of 114.8 (98.7–126.1). Estimated annual percentage change (EAPCs) for ARIS, ARMS, and ARDS has decreased. At the national level, the United States of America had the highest mortality [21,372 (18,924–24,241)] and disability-adjusted life years [407,712 (370,234–470,165)]. And China had the highest number of incident cases [122, 266 (85,925–166,095)]. Globally, high systolic blood pressure and alcohol consumption were the top two risk factors for the proportion of CM-MC deaths.ConclusionCM-MC is still an important cause of early death and chronic disability in older adults. Based on this study, public health agencies should seek more effective methods to prevent and treat CM-MC.</p