Pyrrolizidine alkaloids(PAs)are natural toxins generated as secondarymetabolites in plants,predominantly consisting of unsaturated PAs with diverse toxicities,such as hepatotoxicity.Echimidine,a prominent PA,is believ...Pyrrolizidine alkaloids(PAs)are natural toxins generated as secondarymetabolites in plants,predominantly consisting of unsaturated PAs with diverse toxicities,such as hepatotoxicity.Echimidine,a prominent PA,is believed to exert various toxicological effects,including survival inhibition and induction of apoptosis of hepatocytes.However,the effects of echimidine on development remain unclear.We selected three concentrations of 0.02,0.2,and 2 mg/L to investigate the developmental toxicity of echimidine on zebrafish embryos.After a 7-day exposure,we observed hyperactivity and anxiety-like behavior in zebrafish larvae.Furthermore,we found that echimidine exposure significantly promoted embryonic motor neurodevelopment in geneticallymodified zebrafish.Next,we detected that echimidine exposure significantly increased the content of the excitatory neurotransmitter acetylcholine(ACh),accompanied by a significant decrease in acetylcholinesterase(AChE)activity.Conversely,echimidine led to a significant reduction in the content of the sedative neurotransmitterγ-aminobutyric acid(GABA),accompanied by abnormal gene expression of enzymes related to GABA synthesis.Moreover,we elucidated the strong direct binding of echimidine to zebrafish and human AChE protein through molecular docking.In summary,our study found that echimidine induced ACh accumulation possibly by inhibiting AChE activity,leading to motor neurodevelopmental abnormalities and hyperactivity in zebrafish larvae.This work provides important scientific knowledge on the effects and mechanisms of PAs on neural development,which is helpful for controlling the risk of PAs in food and protecting public health.展开更多
This study aimed to investigate the clinical characteristics of elderly-onset rheumatoid arthritis(EORA)patients with COVID-19.We ret-rospectively enrolled EORA patients diagnosed with COVID-19 from December 2022 thro...This study aimed to investigate the clinical characteristics of elderly-onset rheumatoid arthritis(EORA)patients with COVID-19.We ret-rospectively enrolled EORA patients diagnosed with COVID-19 from December 2022 through February 2023 and followed them up.Demographic characteristics of the patients and clinical data on COVID-19 were collected,and EORA-related data at the onset of rheu-matoid arthritis and during COVID-19 episodes were evaluated.A total of 102 EORA outpatients were enrolled and stratified into the COVID-19 group(n=60)and the non–COVID-19 group(n=42).In the COVID-19 group,56(93.3%)had symptoms,8(13.3%)had viral pneumonia,and 4(6.7%)developed severe COVID-19.Multivariate logistic regression analysis showed that lack of COVID-19 vac-cination(P=0.016 and P=0.030,respectively)and having interstitial lung disease(P=0.013 and P=0.001,respectively)were inde-pendent risk factors for viral pneumonia and severe COVID-19.Compared with the general population,EORA patients did not show significantly higher susceptibility to COVID-19 or a higher risk of severe COVID-19.However,EORA patients with interstitial lung disease require special consideration during COVID-19 episodes.展开更多
基金supported by the Key Project at the Central Government Level:the ability establishment of sustainable use for valuable Chinese medicine resources(No.2060302)the National Natural Science Foundation of China(No.82104389)+2 种基金the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(No.CI2023E002)the High-level Key Discipline Program of National Administration of Traditional Chinese Medicine(No.ZYYZDXK-2023244)China Agricultural Research System of MOF and MARA(No.CARS-21).
文摘Pyrrolizidine alkaloids(PAs)are natural toxins generated as secondarymetabolites in plants,predominantly consisting of unsaturated PAs with diverse toxicities,such as hepatotoxicity.Echimidine,a prominent PA,is believed to exert various toxicological effects,including survival inhibition and induction of apoptosis of hepatocytes.However,the effects of echimidine on development remain unclear.We selected three concentrations of 0.02,0.2,and 2 mg/L to investigate the developmental toxicity of echimidine on zebrafish embryos.After a 7-day exposure,we observed hyperactivity and anxiety-like behavior in zebrafish larvae.Furthermore,we found that echimidine exposure significantly promoted embryonic motor neurodevelopment in geneticallymodified zebrafish.Next,we detected that echimidine exposure significantly increased the content of the excitatory neurotransmitter acetylcholine(ACh),accompanied by a significant decrease in acetylcholinesterase(AChE)activity.Conversely,echimidine led to a significant reduction in the content of the sedative neurotransmitterγ-aminobutyric acid(GABA),accompanied by abnormal gene expression of enzymes related to GABA synthesis.Moreover,we elucidated the strong direct binding of echimidine to zebrafish and human AChE protein through molecular docking.In summary,our study found that echimidine induced ACh accumulation possibly by inhibiting AChE activity,leading to motor neurodevelopmental abnormalities and hyperactivity in zebrafish larvae.This work provides important scientific knowledge on the effects and mechanisms of PAs on neural development,which is helpful for controlling the risk of PAs in food and protecting public health.
基金supported by the National Key Research and Development Program of China(2022YFC360200).
文摘This study aimed to investigate the clinical characteristics of elderly-onset rheumatoid arthritis(EORA)patients with COVID-19.We ret-rospectively enrolled EORA patients diagnosed with COVID-19 from December 2022 through February 2023 and followed them up.Demographic characteristics of the patients and clinical data on COVID-19 were collected,and EORA-related data at the onset of rheu-matoid arthritis and during COVID-19 episodes were evaluated.A total of 102 EORA outpatients were enrolled and stratified into the COVID-19 group(n=60)and the non–COVID-19 group(n=42).In the COVID-19 group,56(93.3%)had symptoms,8(13.3%)had viral pneumonia,and 4(6.7%)developed severe COVID-19.Multivariate logistic regression analysis showed that lack of COVID-19 vac-cination(P=0.016 and P=0.030,respectively)and having interstitial lung disease(P=0.013 and P=0.001,respectively)were inde-pendent risk factors for viral pneumonia and severe COVID-19.Compared with the general population,EORA patients did not show significantly higher susceptibility to COVID-19 or a higher risk of severe COVID-19.However,EORA patients with interstitial lung disease require special consideration during COVID-19 episodes.
