BACKGROUND:Parkinson's disease is a multifactorial neurological disorder characterized by progressive loss of dopaminergic neurons,and dimethyl fumarate(DMF)has potent neuroprotective and immunomodulatory effects in neurodegenerative diseases. OBJECTIVE:To explore the neuroprotective mechanism of DMF in a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease. METHODS:Twenty-four C57BL/6 mice were selected and randomly divided into control group,model group,low-dose DMF,and high-dose DMF groups.An animal model of Parkinson's disease was established in the latter three groups by intraperitoneal injection of 30 mg/kg MPTP,once a day for 5 consecutive days.Intragastric administration was given 30 minutes after each injection of MPTP.Mice in the low-dose DMF group(30 mg/kg)and high-dose DMF group(50 mg/kg)were intragastrically administered once a day for 7 consecutive days.The control and model groups were initially administered the same dose of normal saline.Behavioral testing,western blot,oxidative stress marker detection,and immunohistochemical staining were used to analyze the regulatory effects of DMF on oxidative stress and Keap1/Nrf2 signaling pathway in MPTP-induced Parkinson's disease mice,as well as the protective mechanism of DMF on degeneration of dopamine neurons. RESULTS AND CONCLUSION:Compared with the model group,mice in the low-dose DMF group exhibited significant improvements in motor retardation and postural imbalance(P<0.01),with even more remarkable improvements observed in the high-dose DMF group(P<0.01).Compared with the control group,the model group showed a significant increase in the oxidative stress marker malondialdehyde and a decrease in superoxide dismutase expression(P<0.01).Compared with the model group,the low-dose DMF group reduced malondialdehyde production and increased superoxide dismutase expression(P<0.01),and similar improvements were observed in the high-dose DMF group(P<0.01).Immunohistochemical and western blot assays demonstrated a significant decrease in the number of dopaminergic neurons and tyrosine hydroxylase protein expression in the substantia nigra of mice in the model group compared with the control group(P<0.01).However,in the low-dose DMF group,there was an increase in the number of dopaminergic neurons and tyrosine hydroxylase protein expression in the substantia nigra(P<0.01),with even more significant improvements in the high-dose DMF group(P<0.01).Western blot results revealed that the model group exhibited elevated Keap1 protein expression and decreased Nrf2 protein expression.In contrast,the DMF groups showed reduced Keap1 protein expression and increased Nrf2 protein expression compared to the model group(P<0.01).To conclude,DMF regulates the Keap1/Nrf2 pathway in the substantia nigra of mice with Parkinson's disease,and this regulatory effect is positively correlated with the dose of DMF(P<0.01).Therefore,we infer that DMF exerts neuroprotective effects through the Keap1/Nrf2 signaling pathway.

Palliative care is recognized as an effective measure to improve the quality of life for patients with end-stage diseases， and the significance and role of such patients participating in clinical trials to conquer major diseases has also become a broad consensus. However， due to the special physical， psychological， and social conditions of terminal trial participants， the ethical problems encountered in the trial process are more serious and complex. Drawing on ethical practice experience， these seemingly common phenomena and issues were deeply analyzed. Combined with the palliative care philosophy for end-stage patients， this paper proposed a series of improvement suggestions throughout the entire life cycle of clinical trials， hoping to promote the quality improvement of clinical research in which end-stage patients participate as subjects， while effectively protecting the safety and rights of the subjects and ensuring they receive appropriate palliative care during their participation in clinical trials or clinical-related scientific research.

Sesquiterpenes are natural terpenes containing 15 carbon atoms. They are widely used in the perfume, pharmaceutical, and biofuel industries due to their remarkable biological activities. The traditional production of sesquiterpenes relies on chemical synthesis or plant extraction, which has the disadvantages of low yields and waste of resources. The construction of microbial cell factories for the efficient synthesis of sesquiterpenes by means of synthetic biology provides a new option. In recent years, with the development of metabolic engineering and synthetic biology, the heterologous synthesis of a variety of sesquiterpenes has been successfully achieved by metabolic engineering of the oleaginous yeast, Yarrowia lipolytica. In this paper, we review the research progress in the heterologous synthesis of different sesquiterpenes by Y. lipolytica, discuss the synthetic biology strategies commonly used in this field, and make an outlook on the research directions and engineering approaches to further enhance the sesquiterpene yield in this host. This paper provides a reference for strategies such as synergistic optimization of synthetic biology and metabolic engineering, enhanced precursors, and opens up new directions for the application of synthetic biology in green chemistry and sustainable production.
Yarrowia/genetics* ; Sesquiterpenes/metabolism* ; Metabolic Engineering/methods* ; Synthetic Biology/methods*

【Objective】 To investigate the prevalence of Hepatitis E virus (HEV) among blood donors in Wuhan urban agglomeration, aimed at providing data support for the development of HEV screening strategies for blood donors. 【Methods】 A total of 3 329 blood samples were collected from four centralized testing areas (Ezhou, Tianmen, Xiantao and Qianjiang) and screened at Wuhan Blood Center from January to December 2021. Among them, 2 737 were eligible blood samples with normal ALT (ALT normal group) and 592 were with elevated ALT (ALT elevated group). Enzyme linked immunosorbent assay (ELISA) was used to detect anti-HEV IgG, anti-HEV IgM and HEV-Ag, and Real-time PCR was used to perform single HEV RNA detection on blood samples with elevated ALT and normal ALT anti-HEV IgM+ blood samples. A two-sided Pearson’s chi-squared test or Fisher's exact test was used to evaluate the differences in the positive rates of anti-HEV IgG and anti-HEV IgM in different regions and ALT groups. 【Results】 The overall positive rates of anti-HEV IgG, anti-HEV IgM, and HEV-Ag in 3 329 blood samples from four regions were 21.63%, 1.29%, and 0%, respectively. There was a significant difference in the positive rates of anti-HEV IgG among blood donors in different regions (P<0.05). The highest positive rate of anti-HEV IgG was found in Tianmen 29.44% (136/462), followed by Qianjiang 22.69% (236/1 040), Xiantao 22.66% (230/1 015), and Ezhou 14.53% (118/812). The positive rates of anti-HEV IgG and anti-HEV IgM in blood samples with elevated ALT were significantly higher than that in normal ALT samples (25.68% vs 20.75%, 2.53% vs 1.02%, both P<0.05). However, none of the samples was HEV RNA positive. 【Conclusion】 HEV is prevalent among blood donors in Wuhan urban agglomeration with extremely low current infection rates, and the prevalence of anti-HEV IgG serum varies among different regions. The prevalence of anti-HEV antibodies in blood donors with elevated ALT is significantly higher than that in normal ALT donors.

Objective:In the context of the"dual-channel"management of national medicine,it analyzes the drug purchase selection and influencing factors of local employees in retail pharmacies,and puts forward policy suggestions for optimizing the"dual-channel"of national negotiation drugs.Methods:Using the fsQCA method,it analyzes the combination of individual factors(economic level,health status,et al.)and policy factors(policy promotion efforts,policy implementation degree)on patients'retail pharmacy purchasing selects.Results:Three combinations of conditions were obtained,namely"the type of individual and policy factors working together","the type of policy promotion and implementation driving together",and"the type of policy implementation leading".Conclusion:Firstly,improving the ability of prescription circulation and drug supply in designated retail pharmacies;secondly,strengthening the information release of the"dual-channel"management policy;thirdly,building a collaborative management system centered on insured individuals.

Objective:In the context of the"dual-channel"management of national medicine,it analyzes the drug purchase selection and influencing factors of local employees in retail pharmacies,and puts forward policy suggestions for optimizing the"dual-channel"of national negotiation drugs.Methods:Using the fsQCA method,it analyzes the combination of individual factors(economic level,health status,et al.)and policy factors(policy promotion efforts,policy implementation degree)on patients'retail pharmacy purchasing selects.Results:Three combinations of conditions were obtained,namely"the type of individual and policy factors working together","the type of policy promotion and implementation driving together",and"the type of policy implementation leading".Conclusion:Firstly,improving the ability of prescription circulation and drug supply in designated retail pharmacies;secondly,strengthening the information release of the"dual-channel"management policy;thirdly,building a collaborative management system centered on insured individuals.

Objective:In the context of the"dual-channel"management of national medicine,it analyzes the drug purchase selection and influencing factors of local employees in retail pharmacies,and puts forward policy suggestions for optimizing the"dual-channel"of national negotiation drugs.Methods:Using the fsQCA method,it analyzes the combination of individual factors(economic level,health status,et al.)and policy factors(policy promotion efforts,policy implementation degree)on patients'retail pharmacy purchasing selects.Results:Three combinations of conditions were obtained,namely"the type of individual and policy factors working together","the type of policy promotion and implementation driving together",and"the type of policy implementation leading".Conclusion:Firstly,improving the ability of prescription circulation and drug supply in designated retail pharmacies;secondly,strengthening the information release of the"dual-channel"management policy;thirdly,building a collaborative management system centered on insured individuals.

Objective:In the context of the"dual-channel"management of national medicine,it analyzes the drug purchase selection and influencing factors of local employees in retail pharmacies,and puts forward policy suggestions for optimizing the"dual-channel"of national negotiation drugs.Methods:Using the fsQCA method,it analyzes the combination of individual factors(economic level,health status,et al.)and policy factors(policy promotion efforts,policy implementation degree)on patients'retail pharmacy purchasing selects.Results:Three combinations of conditions were obtained,namely"the type of individual and policy factors working together","the type of policy promotion and implementation driving together",and"the type of policy implementation leading".Conclusion:Firstly,improving the ability of prescription circulation and drug supply in designated retail pharmacies;secondly,strengthening the information release of the"dual-channel"management policy;thirdly,building a collaborative management system centered on insured individuals.

Objective:In the context of the"dual-channel"management of national medicine,it analyzes the drug purchase selection and influencing factors of local employees in retail pharmacies,and puts forward policy suggestions for optimizing the"dual-channel"of national negotiation drugs.Methods:Using the fsQCA method,it analyzes the combination of individual factors(economic level,health status,et al.)and policy factors(policy promotion efforts,policy implementation degree)on patients'retail pharmacy purchasing selects.Results:Three combinations of conditions were obtained,namely"the type of individual and policy factors working together","the type of policy promotion and implementation driving together",and"the type of policy implementation leading".Conclusion:Firstly,improving the ability of prescription circulation and drug supply in designated retail pharmacies;secondly,strengthening the information release of the"dual-channel"management policy;thirdly,building a collaborative management system centered on insured individuals.

Objective:In the context of the"dual-channel"management of national medicine,it analyzes the drug purchase selection and influencing factors of local employees in retail pharmacies,and puts forward policy suggestions for optimizing the"dual-channel"of national negotiation drugs.Methods:Using the fsQCA method,it analyzes the combination of individual factors(economic level,health status,et al.)and policy factors(policy promotion efforts,policy implementation degree)on patients'retail pharmacy purchasing selects.Results:Three combinations of conditions were obtained,namely"the type of individual and policy factors working together","the type of policy promotion and implementation driving together",and"the type of policy implementation leading".Conclusion:Firstly,improving the ability of prescription circulation and drug supply in designated retail pharmacies;secondly,strengthening the information release of the"dual-channel"management policy;thirdly,building a collaborative management system centered on insured individuals.