What exactly does the PfK13 C580Y mutation in Plasmodium falciparum influence?

BACKGROUND: The emergence and spread of artemisinin resistance threaten global malaria control and elimination goals, and encourage research on the mechanisms of drug resistance in malaria parasites. Mutations in Plasmodium falciparum Kelch 13 (PfK13) protein are associated with artemisinin resistance, but the unique or common mechanism which results in this resistance is unclear. METHODS: We analyzed the effects of the PfK13 mutation on the transcriptome and proteome of P. falciparum at different developmental stages. Additionally, the number of merozoites, hemozoin amount, and growth of P. falciparum 3D7C580Y and P. falciparum 3D7WT were compared. The impact of iron supplementation on the number of merozoites of P. falciparum 3D7C580Y was also examined. RESULTS: We found that the PfK13 mutation did not significantly change glycolysis, TCA, pentose phosphate pathway, or oxidative phosphorylation, but did reduce the expression of reproduction- and DNA synthesis-related genes. The reduced number of merozoites, decreased level of hemozoin, and slowed growth of P. falciparum 3D7C580Y were consistent with these changes. Furthermore, adding iron supply could increase the number of the merozoites of P. falciparum 3D7C580Y. CONCLUSIONS: These results revealed that the PfK13 mutation reduced hemoglobin ingestion, leading to artemisinin resistance, likely by decreasing the parasites' requirement for haem and iron. This study helps elucidate the mechanism of artemisinin resistance due to PfK13 mutations.

Antibacterial actions of Ag nanoparticles synthesized from Cimicifuga dahurica (Turcz.) Maxim. and their application in constructing a hydrogel spray for healing skin wounds.

Cimicifuga dahurica (Turcz.) Maxim. is an edible natural food and a type of traditional herbal medicine with antipyretic and analgesic properties. In this study, we found that Cimicifuga dahurica (Turcz.) Maxim. extract (CME) has good skin wound healing qualities due to its antibacterial effects on both wound inflammation-related Gram positive (Staphylococcus aureus and Staphylococcus epidermidis) and Gram negative (Escherichia coli and Klebsiella pneumoniae) strains. Using CME as a reducing agent, CME-based Ag nanoparticles (CME-AgNPs) with an average particle size of 7 nm were synthesized. The minimum bactericidal concentration (MBC) of CME-AgNPs against the investigated bacterial species varied from 0.08 to 1.25 mg/mL, indicating much higher antibacterial activity than the pure CME. Additionally, a novel network-like thermosensitive hydrogel spray (CME-AgNPs-F127/F68) was developed and shown a skin wound healing rate of 98.40% in 14 days, demonstrating the spray's potential as a novel wound dressing that accelerates wound healing.

The association of perioperative autologous blood transfusion with the early postoperative cognitive dysfunction in aged patients following lumbar surgery.

PURPOSE: Intraoperation autologous blood transfusion is an effective method that is used in surgeries with an important blood loss. Several studies suggest that massive blood transfusion is one of the independent risks for postoperative cognitive dysfunction (POCD). Whether the autologous blood is one of the risk factor for POCD or not, we retrospectively examined the incidence of POCD and the probable risk factors in patients undergoing lumbar surgery in our hospital, with the same aged non-POCD patients as controls. METHODS: Eighty-one patients who underwent lumbar surgery were included. Perioperative data were examined for association with POCD on the 7 postoperative days by a Mini-Mental State Test. Multivariable logistic regression analysis was conducted to determine the probable risks associated with POCD. RESULTS: POCD was found in 21 patients. Participants who developed POCD were more likely to had a lower eduction level, more likely to had more blood loss, higher incidence of preoperative anemia, and perioperative allogeneic blood transfusion of more than 3 units as independent risk factors for POCD 7 d postoperatively (P < 0.05). Otherwise, there is no significant difference of the patients received autologous blood or not (P > 0.05). CONCLUSION: Autologous blood transfusion is not a risk factor for POCD in aged patients following lumbar surgery. Autologous blood is likely to be a better method of intraoperative blood transfusion during lumbar spine surgery.