In this article,we present recent findings from a Nature Chemical Biology paper that elucidate the mechanism of crucial biosynthetic steps involved in the synthesis of steroidal glycoalkaloids(SGAs),an important defen...In this article,we present recent findings from a Nature Chemical Biology paper that elucidate the mechanism of crucial biosynthetic steps involved in the synthesis of steroidal glycoalkaloids(SGAs),an important defense substance in a variety of Solanum plants.The enzyme GAME12,identified in Solanum lycopersicum,has evolved from the ancestral GABA enzyme through gene duplication events.Notably,GAME12 has acquired a neofunctional capability,undergoing modifications in both active site specificity and subcellular localization.This shift allows for a transition from its foundational role in core metabolism to its involvement in specialized metabolic pathways.The distinctive function of transamination enables the incorporation of nitrogen atoms into the backbones of steroidal specialized metabolites during the later stages of SGA biosynthesis,resulting in the production of nitrogen-containing antinutrients.This research underscores the significance of hijacking shunt enzymes from core metabolic pathways to facilitate the biosynthesis of nitrogen-containing steroidal glycoalkaloids,thereby enhancing the defensive mechanisms of Solanum species against pests and diseases.展开更多
A new pyridoxal-5-phosphate （PLP） derivative FHMDP was developed for the transamination of different pep- tides with three most hindered amino acid residues （Leu, Ile, Val） as their N-terminus. Compared to the pre...A new pyridoxal-5-phosphate （PLP） derivative FHMDP was developed for the transamination of different pep- tides with three most hindered amino acid residues （Leu, Ile, Val） as their N-terminus. Compared to the previously reported reactions of PLP derivatives, the N-terminus transamination could be accomplished efficiently with the new compound.展开更多
In this paper, we report a novel approach to the heteroaryl-condensed nuclei of natural furo[3,2- a]carbazole alkaloids. Our synthetic studies use N-phthaloyl tryptophan methyl ester as starting material and zinc ion ...In this paper, we report a novel approach to the heteroaryl-condensed nuclei of natural furo[3,2- a]carbazole alkaloids. Our synthetic studies use N-phthaloyl tryptophan methyl ester as starting material and zinc ion mediated transamination reaction as the key step. This work also implicated a novel strategy to assemble other [a]-fused carbazoles.展开更多
Rationale:Fever with myositis and rhabdomyolysis is a medical emergency requiring prompt diagnosis and management.Scrub typhus associated myositis with rhabdomyolysis is rare.Patient concerns:A 36-year-old female pres...Rationale:Fever with myositis and rhabdomyolysis is a medical emergency requiring prompt diagnosis and management.Scrub typhus associated myositis with rhabdomyolysis is rare.Patient concerns:A 36-year-old female presented with intermittent fever up to 38.6℃,jaundice and progressive weakness of all four limbs.Diagnosis:Scrub typhus associated myositis and rhabdomyolysis.Intervention:Doxycycline 100 mg twice daily and injection of ceftriaxone 1 gm twice daily along with continuous intravenous fluids.Outcome:Fever resolved with normalization of liver function and recovery of muscle power.Lessons:Presence of myositis and rhabdomyolysis is uncommon in scrub typhus;high clinical suspicion should be kept in patients with atypical manifestations of scrub typhus.展开更多
Dengue virus infection continues to be major public health problem in large part of world.The epidemiology of dengue viral infection is becoming increasingly complex and has substantially changed over almost past six ...Dengue virus infection continues to be major public health problem in large part of world.The epidemiology of dengue viral infection is becoming increasingly complex and has substantially changed over almost past six decades not only in terms of prevalent strains and geographical locations but also in terms of disease severity and atypical presentations.Though liver is the most common organ affected but is generally asymptomatic.We present a case of infant with severe dengue who died of fulminant hepatic failure and showed pan lobular necrosis on post mortem liver biopsy.The case is being presented to highlight life threatening complication of dengue in young children,and dengue viral infection as a cause of acute liver failure in endemic areas.Thus dengue fever should also be considered as one of the differential diagnosis in children presenting with fever and fulminant hepatic failure in endemic regions.展开更多
Slaughterhouse workers(SHW) are at increased risk of hepatitis which can occur due to different organisms and should be investigated for viral, bacterial, and parasitic organisms. Slaughter house personnel including b...Slaughterhouse workers(SHW) are at increased risk of hepatitis which can occur due to different organisms and should be investigated for viral, bacterial, and parasitic organisms. Slaughter house personnel including butchers are at a higher risk of infections from cuts and blood-letting, with the possible risk of the transmission of blood-borne pathogens to their colleagues. The objective of this review is to evaluate the common etiologies of hepatitis in SHW which will assist in the assessment of these patients presenting with transaminitis. Types of Microorganisms causing hepatitis with their reservoirs, routes of transmission,laboratory diagnosis, clinical features, treatment options and preventive strategies are included in this review. Proper investigation and awareness is of utmost importance as it causes significant financial constraints derived from workers health cost and from livestock production losses when the disease is confirmed. The work up is essential because infected workers might be a source of infections to other colleagues, family and the consumers.展开更多
BACKGROUND Since its discovery in Wuhan,China in December of 2019,the novel coronavirus has progressed to become one of the worst pandemics seen in the last 100 years.Recently,there has been an increased interest in t...BACKGROUND Since its discovery in Wuhan,China in December of 2019,the novel coronavirus has progressed to become one of the worst pandemics seen in the last 100 years.Recently,there has been an increased interest in the hepatic manifestations of coronavirus disease 19(COVID-19).AIM To describe the demographic and clinical characteristics of COVID-19 positive patients and study the association between transaminitis and all-cause mortality.METHODS This is a descriptive retrospective cohort study of 130 consecutive patients with a positive COVID PCR test admitted between March 16,2020 to May 14,2020 at a tertiary care University-based medical center.The Wilcoxon-rank sum test and paired t-test were used for comparing non-parametric and parametric continuous variables respectively and a multivariable logistic regression models to study the association between transaminitis and mortality using SAS version 9.4(SAS Institute,Cary,NC,United States).RESULTS Out of the 130 patients,73(56%)patients were found to have transaminitis and 57(44%)did not.When compared to patients without transaminitis,the transaminitis group was found to have a higher median body mass index(30.2 kg/m2 vs 27.3 kg/m2,P=0.04).In the multivariate analysis those with transaminitis were found to have 3.4 times higher odds of dying as compared to those without transaminitis adjusting for gender,the Age-adjusted Charlson Comorbidity Index and admission to the intensive care unit(P=0.03).CONCLUSION Our study showed that transaminitis on admission was associated with severe clinical outcomes such as admission to the intensive care unit,need for mechanical ventilation,and mortality.展开更多
Within a year of its emergence,coronavirus disease-2019(COVID-19)has evolved into a pandemic.What has emerged during the past 1 year is that,apart from its potentially fatal respiratory presentation from which the sev...Within a year of its emergence,coronavirus disease-2019(COVID-19)has evolved into a pandemic.What has emerged during the past 1 year is that,apart from its potentially fatal respiratory presentation from which the severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2)derives its name,it presents with a myriad of gastrointestinal(GI)and liver manifestations.Expression of the angiotensinconverting enzyme-2(ACE-2)receptor throughout the GI tract and liver,which is the receptor for the SARS-CoV-2,may be responsible for the GI and liver manifestations.Besides acting directly via the ACE-2 receptor,the virus triggers a potent immune response,which might have a role in pathogenesis.The virus leads to derangement in liver function tests in close to 50%of the patients.The impact of these derangements in patients with a normal underlying liver seems to be innocuous.Severe clinical presentations include acute decompensation and acute-on-chronic liver failure in a patient with chronic liver disease,leading to high mortality.Evolving data suggests that,contrary to intuition,liver transplant recipients and patients with autoimmune liver disease on immunosuppression do not have increased mortality.The exact mechanism underlying why immunosuppressed patients fare well as compared to other patients remains to be deciphered.With newer variants of COVID-19,which can spread faster than the original strain,the data on hepatic manifestations needs to be updated to keep a step ahead of the virus.展开更多
Duchenne muscular dystrophy (DMD) is a fatal X-linked genetic disease of the neuromuscular system and is the most serious type of muscular dystrophy in humans. The disease is characterized by progressive muscular atro...Duchenne muscular dystrophy (DMD) is a fatal X-linked genetic disease of the neuromuscular system and is the most serious type of muscular dystrophy in humans. The disease is characterized by progressive muscular atrophy and a poor prognosis. The incidence rate is 1/3500, and symptoms appear at age of 5 years-old. Some patients present with abnormal aminotransferases as the first symptom. In addi-tion to the clinical characteristics and genetic history, electro-myography examination, muscle biopsy, serum enzyme examination, and measures of creatine kinase (CK), CK isoenzyme, and serum lactate dehydrogenase are important features of auxiliary examination. Clinicians who encounter unknown causes of transaminitis should consider the possi-bility of DMD. We describe here a 3 year-old pediatric patient with increased aminotransferases who had elevated CK and a family genetic history but without liver damage on computed tomography. He was suspected as having inherited the disorder and was finally diagnosed as having DMD by next-generation sequencing.展开更多
基金support from the National Key Research and Development Program of China(2021YFD1700100)Excellent Youth Program of Anhui Province(2022AH030095).
文摘In this article,we present recent findings from a Nature Chemical Biology paper that elucidate the mechanism of crucial biosynthetic steps involved in the synthesis of steroidal glycoalkaloids(SGAs),an important defense substance in a variety of Solanum plants.The enzyme GAME12,identified in Solanum lycopersicum,has evolved from the ancestral GABA enzyme through gene duplication events.Notably,GAME12 has acquired a neofunctional capability,undergoing modifications in both active site specificity and subcellular localization.This shift allows for a transition from its foundational role in core metabolism to its involvement in specialized metabolic pathways.The distinctive function of transamination enables the incorporation of nitrogen atoms into the backbones of steroidal specialized metabolites during the later stages of SGA biosynthesis,resulting in the production of nitrogen-containing antinutrients.This research underscores the significance of hijacking shunt enzymes from core metabolic pathways to facilitate the biosynthesis of nitrogen-containing steroidal glycoalkaloids,thereby enhancing the defensive mechanisms of Solanum species against pests and diseases.
基金Project supported by the National Natural Science Foundation of China （Nos. 20932006 and 21002056）.
文摘A new pyridoxal-5-phosphate （PLP） derivative FHMDP was developed for the transamination of different pep- tides with three most hindered amino acid residues （Leu, Ile, Val） as their N-terminus. Compared to the previously reported reactions of PLP derivatives, the N-terminus transamination could be accomplished efficiently with the new compound.
基金supported by NSFC (No.21102026)Qiankehe [2011] 3002West Light Foundation of the Chinese Academy of Sciences
文摘In this paper, we report a novel approach to the heteroaryl-condensed nuclei of natural furo[3,2- a]carbazole alkaloids. Our synthetic studies use N-phthaloyl tryptophan methyl ester as starting material and zinc ion mediated transamination reaction as the key step. This work also implicated a novel strategy to assemble other [a]-fused carbazoles.
文摘Rationale:Fever with myositis and rhabdomyolysis is a medical emergency requiring prompt diagnosis and management.Scrub typhus associated myositis with rhabdomyolysis is rare.Patient concerns:A 36-year-old female presented with intermittent fever up to 38.6℃,jaundice and progressive weakness of all four limbs.Diagnosis:Scrub typhus associated myositis and rhabdomyolysis.Intervention:Doxycycline 100 mg twice daily and injection of ceftriaxone 1 gm twice daily along with continuous intravenous fluids.Outcome:Fever resolved with normalization of liver function and recovery of muscle power.Lessons:Presence of myositis and rhabdomyolysis is uncommon in scrub typhus;high clinical suspicion should be kept in patients with atypical manifestations of scrub typhus.
文摘Dengue virus infection continues to be major public health problem in large part of world.The epidemiology of dengue viral infection is becoming increasingly complex and has substantially changed over almost past six decades not only in terms of prevalent strains and geographical locations but also in terms of disease severity and atypical presentations.Though liver is the most common organ affected but is generally asymptomatic.We present a case of infant with severe dengue who died of fulminant hepatic failure and showed pan lobular necrosis on post mortem liver biopsy.The case is being presented to highlight life threatening complication of dengue in young children,and dengue viral infection as a cause of acute liver failure in endemic areas.Thus dengue fever should also be considered as one of the differential diagnosis in children presenting with fever and fulminant hepatic failure in endemic regions.
文摘Slaughterhouse workers(SHW) are at increased risk of hepatitis which can occur due to different organisms and should be investigated for viral, bacterial, and parasitic organisms. Slaughter house personnel including butchers are at a higher risk of infections from cuts and blood-letting, with the possible risk of the transmission of blood-borne pathogens to their colleagues. The objective of this review is to evaluate the common etiologies of hepatitis in SHW which will assist in the assessment of these patients presenting with transaminitis. Types of Microorganisms causing hepatitis with their reservoirs, routes of transmission,laboratory diagnosis, clinical features, treatment options and preventive strategies are included in this review. Proper investigation and awareness is of utmost importance as it causes significant financial constraints derived from workers health cost and from livestock production losses when the disease is confirmed. The work up is essential because infected workers might be a source of infections to other colleagues, family and the consumers.
文摘BACKGROUND Since its discovery in Wuhan,China in December of 2019,the novel coronavirus has progressed to become one of the worst pandemics seen in the last 100 years.Recently,there has been an increased interest in the hepatic manifestations of coronavirus disease 19(COVID-19).AIM To describe the demographic and clinical characteristics of COVID-19 positive patients and study the association between transaminitis and all-cause mortality.METHODS This is a descriptive retrospective cohort study of 130 consecutive patients with a positive COVID PCR test admitted between March 16,2020 to May 14,2020 at a tertiary care University-based medical center.The Wilcoxon-rank sum test and paired t-test were used for comparing non-parametric and parametric continuous variables respectively and a multivariable logistic regression models to study the association between transaminitis and mortality using SAS version 9.4(SAS Institute,Cary,NC,United States).RESULTS Out of the 130 patients,73(56%)patients were found to have transaminitis and 57(44%)did not.When compared to patients without transaminitis,the transaminitis group was found to have a higher median body mass index(30.2 kg/m2 vs 27.3 kg/m2,P=0.04).In the multivariate analysis those with transaminitis were found to have 3.4 times higher odds of dying as compared to those without transaminitis adjusting for gender,the Age-adjusted Charlson Comorbidity Index and admission to the intensive care unit(P=0.03).CONCLUSION Our study showed that transaminitis on admission was associated with severe clinical outcomes such as admission to the intensive care unit,need for mechanical ventilation,and mortality.
文摘Within a year of its emergence,coronavirus disease-2019(COVID-19)has evolved into a pandemic.What has emerged during the past 1 year is that,apart from its potentially fatal respiratory presentation from which the severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2)derives its name,it presents with a myriad of gastrointestinal(GI)and liver manifestations.Expression of the angiotensinconverting enzyme-2(ACE-2)receptor throughout the GI tract and liver,which is the receptor for the SARS-CoV-2,may be responsible for the GI and liver manifestations.Besides acting directly via the ACE-2 receptor,the virus triggers a potent immune response,which might have a role in pathogenesis.The virus leads to derangement in liver function tests in close to 50%of the patients.The impact of these derangements in patients with a normal underlying liver seems to be innocuous.Severe clinical presentations include acute decompensation and acute-on-chronic liver failure in a patient with chronic liver disease,leading to high mortality.Evolving data suggests that,contrary to intuition,liver transplant recipients and patients with autoimmune liver disease on immunosuppression do not have increased mortality.The exact mechanism underlying why immunosuppressed patients fare well as compared to other patients remains to be deciphered.With newer variants of COVID-19,which can spread faster than the original strain,the data on hepatic manifestations needs to be updated to keep a step ahead of the virus.
基金This study was supported by the Medical Scientific Research Project of Foshan Health Bureau(No.20200225 to JD).
文摘Duchenne muscular dystrophy (DMD) is a fatal X-linked genetic disease of the neuromuscular system and is the most serious type of muscular dystrophy in humans. The disease is characterized by progressive muscular atrophy and a poor prognosis. The incidence rate is 1/3500, and symptoms appear at age of 5 years-old. Some patients present with abnormal aminotransferases as the first symptom. In addi-tion to the clinical characteristics and genetic history, electro-myography examination, muscle biopsy, serum enzyme examination, and measures of creatine kinase (CK), CK isoenzyme, and serum lactate dehydrogenase are important features of auxiliary examination. Clinicians who encounter unknown causes of transaminitis should consider the possi-bility of DMD. We describe here a 3 year-old pediatric patient with increased aminotransferases who had elevated CK and a family genetic history but without liver damage on computed tomography. He was suspected as having inherited the disorder and was finally diagnosed as having DMD by next-generation sequencing.
