The study considers the closed-loop supply chain (CLSC) decision using federated learning platform (FL platform), establishes a CLSC game model including one manufacturer, one retailer and one third party, analyzes the influence of FL platform on optimal decisions and revenues of CLSC system from the perspectives of information reliability, information security and investment cost, and establishes a cost-sharing and revenue-sharing contract (CSRS contract) to coordinate CLSC system. Results show that, the greater consumers' recognition of the remanufactured product, the higher its price and revenue; using FL platform can guarantee the degree of consumer information security, which in turn has a constructive effect on the CLSC; when the FL platform is not adopted, the manufacturer will raise more revenue by misrepresenting the manufacturing and remanufacturing costs; the FL platform would provide some incentive for manufacturers to disclose true cost information and improve the CLSC revenue; an increase in investment costs would lead to a reduction in revenue, so CLSC members would need to make investment decisions based on revenue comparisons before and after using the platform; finally, within the feasibility of the contract parameters, the CSRS contract both maximizes optimal revenue of CLSC system and improves revenue per member.
Great progress has been made in the prevention and treatment of human parasitic diseases in China over the past six decades, but parasitic diseases are still one of the most serious public health problems in the world. The specific prevalence of parasitic diseases varies in different provinces due to their geographical environment and the dietary habits of people. In this study, a total of 4,428 patients suspected to have parasitic infection by clinicians or themselves from January 1, 2016, to December 31, 2020 were recommended to our laboratory for further testing. In total, 5,246 samples including fecal, blood, and other body fluids were detected by etiological and immunological methods. Approximately 15.20% (673/4,428) of all suspected patients were infected by at least one species of parasite, and the overall positive rate of suspected patients from Hunan Province was 15.10% (594/3,933). A total of 18 species of parasites, namely, nematodes (4 species), trematodes (5 species), cestodes (4 species), protozoa (2 species), and medical arthropods (3 species), and 3 of them were imported parasites outside of Hunan Province. There are 9 species of foodborne parasites, accounting for 89.92% (464/516) of patients infected by one species of parasite. Common parasites in Hunan Province include plerocercoid, Paragonimus westermani, Clonorchis sinensis, cysticercus, Toxoplasma gondii, and Schistosoma japonicum. In this study, we found that the incidence of soilborne nematode infections has decreased significantly. However, foodborne parasites gradually become the main parasitic infections as well as multiple infections are becoming more common. Therefore, we should not only continue the prevention and control of soil-derived nematodes but also focus on the prevention and control of foodborne parasites in the future.
Conclusions: Appropriate fatty acid modification can improve the serum stability of Lycosin-I and enhance the in vivo anti-Toxoplasma gondii effect of Lycosin-I. These results suggest that the lipopeptide derivative of Lycosin-Ⅰ have the potential as a novel drug candidate of anti- T. gondii. Background: Toxoplasmosis, caused by Toxoplasma gondii (T. gondii), is a serious zoonotic parasitic disease. Due to the side effects and drug resistance of clinical medications for toxoplasmosis, it is urgent to develop new anti-toxoplasmosis drugs. In our previous study, we found that Lycosin-I exhibited anti- T. gondii activity both in vitro and in vivo, but its serum stability in vivo was not good enough. In this study, we aimed to improve the stability and activity of Lycosin-I through fatty acid modification, so as to find a better anti- T. gondii targeting drug candidate. Methods: The α/ε-amino radicals of different lysine residues of Lycosin-Ⅰ were covalently coupled with lauric acid to obtain eight lipopeptides, namely L-C12, L-C12-1, L-C12-2, L-C12-3, L-C12-4, L-C12-5, L-C12-6, L-C12-7. The anti-T. gondii activity of these lipopeptides in vitro was screened using Trypan blue assay. The anti-T. gondii effects of Lycosin-I, L-C12 and L-an were evaluated by invasion assay, proliferation assay and plaque assay in vitro. A mouse model acutely infected with T. gondii was established to evaluate their efficacy in vivo. Results: Among these eight lipopeptides, L-C12 showed the best activity against T. gondii in vitro. We then conjugated a shorter length fatty chain, aminocaproic acid, at the same modification site of L-C12, namely L-an. The serum stability of L-C12 and L-an was improved, and they showed comparable or even better activity than Lycosin-I in inhibiting the invasion, proliferation and migration of T. gondii tachyzoites. L-an effectively prolonged the survival time of mice acutely infected with T. gondii.
Toxoplasma gondii (T. gondii) is a nucleated intracellular parasitic protozoan with a broad host selectivity. It causes toxoplasmosis in immunocompromised or immunodeficient patients. The currently available treatments for toxoplasmosis have significant side effects as well as certain limitations, and the development of vaccines remains to be explored. Animal venoms are considered to be an important source of novel antimicrobial agents. Some peptides from animal venoms have amphipathic alpha-helix structures. They inhibit the growth of pathogens by targeting membranes to produce lethal pores and cause membrane rupture. Venom molecules generally possess immunomodulatory properties and play key roles in the suppression of pathogenic organisms. Here, we summarized literatures of the last 15 years on the interaction of animal venom peptides with T. gondii and attempt to explore the mechanisms of their interaction with parasites that involve membrane and organelle damage, immune response regulation and ion homeostasis. Finally, we analyzed some limitations of venom peptides for drug therapy and some insights into their development in future studies. It is hoped that more research will be stimulated to turn attention to the medical value of animal venoms in toxoplasmosis.
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