The effects of toxic substance D1,extracted from burn eschars,on the hepatic mitochondrial respiratory function and its damages to the respirtatory chain were observed in the rat.It was found that the rate of stste 3r...The effects of toxic substance D1,extracted from burn eschars,on the hepatic mitochondrial respiratory function and its damages to the respirtatory chain were observed in the rat.It was found that the rate of stste 3respiration was inhibited and that of state 4 respiration stimulated by D1.There was an obvious dosage-effect relationship between D1 dosage and the rate of oxygen consumption, that is,the changes of the rate was slow in the range of low dosage and fast in the range of high dosage. The point of change was at 1 mg/ml of D1 concentration.The ratio of FCCP-stimulated respiration rate/state 4 respiration rate was decreased when D1 dosage was increased.The results of experiments were similar whether glutamate+malate or succinate were used as the substrate. The point of change was also at 1 mg/ml of D1 concentration. The decrease of FCCP-stimulated rate/state 4rate implied that the respiratory chain was damaged.But complex Ⅳ-the terminal segment of the chain-remained intact. Thus, the site of damage must be somewhere in complexesⅠ￣Ⅲ and/or complexes Ⅱ￣Ⅲ. Since NADH dehydrogenase and succinate dehydrogenase-the main enzymes in complexesⅠand Ⅱ-were not affected by D1 but NADH: cytochrome c reductase and succinate:cytochrome c reductase markedly inhibited, the site of damage was most likely located in complex Ⅲ-the bc1 complex.展开更多
Mitochondria,the powerhouse of a cell,are closely linked to the pathophysiology of various common as well as not so uncommon disorders of the liver and beyond.Evolution supports a prokaryotic descent,and,unsurprisingl...Mitochondria,the powerhouse of a cell,are closely linked to the pathophysiology of various common as well as not so uncommon disorders of the liver and beyond.Evolution supports a prokaryotic descent,and,unsurprisingly,the organelle is worthy of being labeled an organism in itself.Since highly metabolically active organs require a continuous feed of energy,any dysfunction in the structure and function of mitochondria can have variable impact,with the worse end of the spectrum producing catastrophic consequences with a multisystem predisposition.Though categorized a hepatopathy,mitochondrial respiratory chain defects are not limited to the liver in time and space.The liver involvement is also variable in clinical presentation as well as in age of onset,from acute liver failure,cholestasis,or chronic liver disease.Other organs like eye,muscle,central and peripheral nervous system,gastrointestinal tract,hematological,endocrine,and renal systems are also variably involved.Diagnosis hinges on recognition of subtle clinical clues,screening metabolic investigations,evaluation of the extrahepatic involvement,and role of genetics and tissue diagnosis.Treatment is aimed at both circumventing the acute metabolic crisis and long-term management including nutritional rehabilitation.This review lists and discusses the burden of mitochondrial respiratory chain defects,including various settings when to suspect,their evolution with time,including certain specific disorders,their tiered evaluation with diagnostic algorithms,management dilemmas,role of liver transplantation,and the future research tools.展开更多
Objective To evaluate the infectivity of severe acute respiratory syndrome （SARS） during its incubation period by investigating chains of transmission and individuals isolated for medical observation with a view to ...Objective To evaluate the infectivity of severe acute respiratory syndrome （SARS） during its incubation period by investigating chains of transmission and individuals isolated for medical observation with a view to providing scientific evidence for updating protocols of medical isolation. Methods Individuals related with the two SARS chains of transmission in Beijing in 2003 and a group of individuals isolated for medical observation in Haidian district of Beijing during the SARS outbreak were selected as subjects of study. Contactors with SARS patients and those with symptom development following the contacts were investigated via questionnaire. Serum samples were collected from super transmitters and tested for SARS-CoV antibody by neutralization test and enzyme linked immunosorbent assay （ELISA）. Results A total of 1 112 contactors were investigated in three surveys. Of them, 669 had a history of close contact with symptomatic SARS patients, 101 developed symptoms with a rate of 15.1%, 363 had a history of close contact with patients in their incubation period, none of whom developed symptoms （0%）. Serum samples were collected fi＇om 32 highly-exposed individuals, of whom 13 developing SARS symptoms atter contact had serum samples positive for SARS-CoV antibody. Samples collected from the asymptomatic contactors were all negative for SARS-CoV antibody. Conclusion SARS cases are infectious only during their symptomatic period and are non-infectious during the incubation period. Isolation for medical observation should be placed for individuals who are in close contact with symptomatic SARS patients. The results of our study are of decisive significance for the Ministry of Health to the definition of SARS close contactor.展开更多
Background: Acute respiratory infection (ARI) is a leading cause of morbidity and mortality in children under five years of age in developing countries with viruses contributing significantly to this problem. The rece...Background: Acute respiratory infection (ARI) is a leading cause of morbidity and mortality in children under five years of age in developing countries with viruses contributing significantly to this problem. The recently identified parvovirus, Human Bocavirus (HBoV), has also been associated with ARI. Objective: To determine the frequency of HBoV in patients with ARI. Materials and Methods: Samples from 125 consenting patients with influenza like illness signs and symptoms were collected. DNA was extracted from these samples using the QIAamp DNA blood mini kit (Qiagen, Germany). Conventional PCR was carried out and the amplicons were examined in 2% agarose gels stained with ethidium bromide. This was followed by sequencing of the HBoV positive samples. Results: Twenty one (16.8%) patients were found to have HBoV infection. Males (n = 61.9%) were mainly infected with HBoV. Local HBoV strains had 98.9% - 100% similarities and were found to cluster together with other strains obtained elsewhere. Conclusion: These findings suggest that HBoV plays a role in respiratory tract infections in children in Kenya just like it has been found elsewhere. It also sheds light on multiple infections associated with HBoV infections in Kenya.展开更多
The pattern of clinical forms of respiratory tuberculosis in children shows a preponderance of intrathoracic lymph node tuberculosis （89.4%） that is characterized by a complicated process in every third child under ...The pattern of clinical forms of respiratory tuberculosis in children shows a preponderance of intrathoracic lymph node tuberculosis （89.4%） that is characterized by a complicated process in every third child under present-day conditions. Positive result of PCR closely correlates with the severity and extent of the specific process in children. Real-time PCR （RT-PCR） was ascertain to exhibit the highest sensitivity in detecting Mycobacterium tuberculosis DNA in children with primary generalized tuberculosis （62.5%） and in those with a disseminated specific process （55.6%）, which was much higher than conventional bacteriological study of diagnostic materials. By taking into account the findings, the RT-PCR detection of M. tuberculosis was considered as a substantial criterion for evaluating the magnitude of specific changes and the degree of tuberculosis infection activity in children.展开更多
Background Military recruits are at a higher risk of acute respiratory disease(ARD) and the causative agents might change over time, which needs to be investigated. Methods The nasopharyngeal swabs and blood samples w...Background Military recruits are at a higher risk of acute respiratory disease(ARD) and the causative agents might change over time, which needs to be investigated. Methods The nasopharyngeal swabs and blood samples were consecutively collected from conscripts for three years in a military training center. The real-time fluorescent quantitative PCR assays were conducted for 15 species of common respiratory pathogens; the serum anti-Legionella pneumophila antibodies were detected by indirect immunofluorescence(IIF) assay, and serum anti-Microplasma pneumoniae antibodies, serum anti-influenza B virus and anti-influenza A virus-Ig M and Ig G were detected by ELISA. Results The prevalences of ARD were 59.3%(108/182) in 2008, 23.3%(50/215) in 2009,and 19.6%(40/204) in 2010. Among the patients with ARD from 2008 to 2010, the influenza B virus infection accounted for 45.4%, 30.0% and 55.0%, and seasonal influenza A virus infection for 8.3%, 8.0% and 5.0%, respectively; the positive rates of serum anti-Legionella pneumophila and anti-Microplasma pneumoniae antibodies in recruits was lower than 10% each year respectively in the three years without diagnostic significance. Conclusion The early appropriate diagnosis and treatment of ARD in military personnel will ensure the power strength of armed forces.展开更多
Mammalian mitochondrial electron transport chain complexes are the most important and complicated protein machinery in mitochondria.Although this system has been studied for more than a century,its composition and mol...Mammalian mitochondrial electron transport chain complexes are the most important and complicated protein machinery in mitochondria.Although this system has been studied for more than a century,its composition and molecular mechanism are still largely unknown.Here we report the high-resolution cryo-electron microscopy(Cryo-EM)structures of porcine respiratory chain megacomplex-Ⅰ_(2)Ⅲ_(2)Ⅳ_(2)(MCⅠ_(2)Ⅲ_(2)Ⅳ_(2))in five different conformations,including State 1,State 2,Mid 1,Mid 2,and Mid 3.High-resolution Cryo-EM imaging,combined with super-resolution gated stimulated emission depletion microscopy(gSTED),strongly supports the formation of MCⅠ_(2)Ⅲ_(2)Ⅳ_(2)in live cells.Each MCⅠ_(2)Ⅲ_(2)Ⅳ_(2)structure contains 141 subunits(70 different kinds of peptides,2.9 MDa)in total with 240 transmembrane helices.The mutual influence among CⅠ,CⅢ,and CⅣshown in the MCⅠ_(2)Ⅲ_(2)Ⅳ_(2)structure suggests this megacomplex could act as an integral unit in electron transfer and proton pumping.The conformational changes from different states suggest a plausible regulatory mechanism for the MCⅠ_(2)Ⅲ_(2)Ⅳ_(2)activation/deactivation process.展开更多
文摘The effects of toxic substance D1,extracted from burn eschars,on the hepatic mitochondrial respiratory function and its damages to the respirtatory chain were observed in the rat.It was found that the rate of stste 3respiration was inhibited and that of state 4 respiration stimulated by D1.There was an obvious dosage-effect relationship between D1 dosage and the rate of oxygen consumption, that is,the changes of the rate was slow in the range of low dosage and fast in the range of high dosage. The point of change was at 1 mg/ml of D1 concentration.The ratio of FCCP-stimulated respiration rate/state 4 respiration rate was decreased when D1 dosage was increased.The results of experiments were similar whether glutamate+malate or succinate were used as the substrate. The point of change was also at 1 mg/ml of D1 concentration. The decrease of FCCP-stimulated rate/state 4rate implied that the respiratory chain was damaged.But complex Ⅳ-the terminal segment of the chain-remained intact. Thus, the site of damage must be somewhere in complexesⅠ￣Ⅲ and/or complexes Ⅱ￣Ⅲ. Since NADH dehydrogenase and succinate dehydrogenase-the main enzymes in complexesⅠand Ⅱ-were not affected by D1 but NADH: cytochrome c reductase and succinate:cytochrome c reductase markedly inhibited, the site of damage was most likely located in complex Ⅲ-the bc1 complex.
文摘Mitochondria,the powerhouse of a cell,are closely linked to the pathophysiology of various common as well as not so uncommon disorders of the liver and beyond.Evolution supports a prokaryotic descent,and,unsurprisingly,the organelle is worthy of being labeled an organism in itself.Since highly metabolically active organs require a continuous feed of energy,any dysfunction in the structure and function of mitochondria can have variable impact,with the worse end of the spectrum producing catastrophic consequences with a multisystem predisposition.Though categorized a hepatopathy,mitochondrial respiratory chain defects are not limited to the liver in time and space.The liver involvement is also variable in clinical presentation as well as in age of onset,from acute liver failure,cholestasis,or chronic liver disease.Other organs like eye,muscle,central and peripheral nervous system,gastrointestinal tract,hematological,endocrine,and renal systems are also variably involved.Diagnosis hinges on recognition of subtle clinical clues,screening metabolic investigations,evaluation of the extrahepatic involvement,and role of genetics and tissue diagnosis.Treatment is aimed at both circumventing the acute metabolic crisis and long-term management including nutritional rehabilitation.This review lists and discusses the burden of mitochondrial respiratory chain defects,including various settings when to suspect,their evolution with time,including certain specific disorders,their tiered evaluation with diagnostic algorithms,management dilemmas,role of liver transplantation,and the future research tools.
文摘Objective To evaluate the infectivity of severe acute respiratory syndrome （SARS） during its incubation period by investigating chains of transmission and individuals isolated for medical observation with a view to providing scientific evidence for updating protocols of medical isolation. Methods Individuals related with the two SARS chains of transmission in Beijing in 2003 and a group of individuals isolated for medical observation in Haidian district of Beijing during the SARS outbreak were selected as subjects of study. Contactors with SARS patients and those with symptom development following the contacts were investigated via questionnaire. Serum samples were collected from super transmitters and tested for SARS-CoV antibody by neutralization test and enzyme linked immunosorbent assay （ELISA）. Results A total of 1 112 contactors were investigated in three surveys. Of them, 669 had a history of close contact with symptomatic SARS patients, 101 developed symptoms with a rate of 15.1%, 363 had a history of close contact with patients in their incubation period, none of whom developed symptoms （0%）. Serum samples were collected fi＇om 32 highly-exposed individuals, of whom 13 developing SARS symptoms atter contact had serum samples positive for SARS-CoV antibody. Samples collected from the asymptomatic contactors were all negative for SARS-CoV antibody. Conclusion SARS cases are infectious only during their symptomatic period and are non-infectious during the incubation period. Isolation for medical observation should be placed for individuals who are in close contact with symptomatic SARS patients. The results of our study are of decisive significance for the Ministry of Health to the definition of SARS close contactor.
文摘Background: Acute respiratory infection (ARI) is a leading cause of morbidity and mortality in children under five years of age in developing countries with viruses contributing significantly to this problem. The recently identified parvovirus, Human Bocavirus (HBoV), has also been associated with ARI. Objective: To determine the frequency of HBoV in patients with ARI. Materials and Methods: Samples from 125 consenting patients with influenza like illness signs and symptoms were collected. DNA was extracted from these samples using the QIAamp DNA blood mini kit (Qiagen, Germany). Conventional PCR was carried out and the amplicons were examined in 2% agarose gels stained with ethidium bromide. This was followed by sequencing of the HBoV positive samples. Results: Twenty one (16.8%) patients were found to have HBoV infection. Males (n = 61.9%) were mainly infected with HBoV. Local HBoV strains had 98.9% - 100% similarities and were found to cluster together with other strains obtained elsewhere. Conclusion: These findings suggest that HBoV plays a role in respiratory tract infections in children in Kenya just like it has been found elsewhere. It also sheds light on multiple infections associated with HBoV infections in Kenya.
文摘The pattern of clinical forms of respiratory tuberculosis in children shows a preponderance of intrathoracic lymph node tuberculosis （89.4%） that is characterized by a complicated process in every third child under present-day conditions. Positive result of PCR closely correlates with the severity and extent of the specific process in children. Real-time PCR （RT-PCR） was ascertain to exhibit the highest sensitivity in detecting Mycobacterium tuberculosis DNA in children with primary generalized tuberculosis （62.5%） and in those with a disseminated specific process （55.6%）, which was much higher than conventional bacteriological study of diagnostic materials. By taking into account the findings, the RT-PCR detection of M. tuberculosis was considered as a substantial criterion for evaluating the magnitude of specific changes and the degree of tuberculosis infection activity in children.
基金supported for causative pathogen survey of ARD in conscripts as a medical science key project of the People’s Liberation Army(grant number 08G021)The funders had no role in the study design,data collection and analysis,decision to publish,or preparation of the manuscript
文摘Background Military recruits are at a higher risk of acute respiratory disease(ARD) and the causative agents might change over time, which needs to be investigated. Methods The nasopharyngeal swabs and blood samples were consecutively collected from conscripts for three years in a military training center. The real-time fluorescent quantitative PCR assays were conducted for 15 species of common respiratory pathogens; the serum anti-Legionella pneumophila antibodies were detected by indirect immunofluorescence(IIF) assay, and serum anti-Microplasma pneumoniae antibodies, serum anti-influenza B virus and anti-influenza A virus-Ig M and Ig G were detected by ELISA. Results The prevalences of ARD were 59.3%(108/182) in 2008, 23.3%(50/215) in 2009,and 19.6%(40/204) in 2010. Among the patients with ARD from 2008 to 2010, the influenza B virus infection accounted for 45.4%, 30.0% and 55.0%, and seasonal influenza A virus infection for 8.3%, 8.0% and 5.0%, respectively; the positive rates of serum anti-Legionella pneumophila and anti-Microplasma pneumoniae antibodies in recruits was lower than 10% each year respectively in the three years without diagnostic significance. Conclusion The early appropriate diagnosis and treatment of ARD in military personnel will ensure the power strength of armed forces.
基金supported by funds from the National Natural Science Foundation of China(32030056 and 32100962)the Tsinghua University Spring Breeze Fund(20201080572)+4 种基金the National Science Fund for Distinguished Young Scholars(3210110055)the China Postdoctoral Science Foundation(2020TQ0178,2020M680519,and 2020M680521)the Guangdong Basic and Applied Basic Research Foundation(2023B1515020039)the Shenzhen Science and Technology Program(RCYX20221008092904016)the Shenzhen University 2035 Program for Excellent Research(2022C012).
文摘Mammalian mitochondrial electron transport chain complexes are the most important and complicated protein machinery in mitochondria.Although this system has been studied for more than a century,its composition and molecular mechanism are still largely unknown.Here we report the high-resolution cryo-electron microscopy(Cryo-EM)structures of porcine respiratory chain megacomplex-Ⅰ_(2)Ⅲ_(2)Ⅳ_(2)(MCⅠ_(2)Ⅲ_(2)Ⅳ_(2))in five different conformations,including State 1,State 2,Mid 1,Mid 2,and Mid 3.High-resolution Cryo-EM imaging,combined with super-resolution gated stimulated emission depletion microscopy(gSTED),strongly supports the formation of MCⅠ_(2)Ⅲ_(2)Ⅳ_(2)in live cells.Each MCⅠ_(2)Ⅲ_(2)Ⅳ_(2)structure contains 141 subunits(70 different kinds of peptides,2.9 MDa)in total with 240 transmembrane helices.The mutual influence among CⅠ,CⅢ,and CⅣshown in the MCⅠ_(2)Ⅲ_(2)Ⅳ_(2)structure suggests this megacomplex could act as an integral unit in electron transfer and proton pumping.The conformational changes from different states suggest a plausible regulatory mechanism for the MCⅠ_(2)Ⅲ_(2)Ⅳ_(2)activation/deactivation process.
