Artemisinin is an endoperoxide sesquiterpene lactone isolated from Artemisia annua and is often used to treat malaria. Artemisinin’s peroxide bridge is the key structure behind its antimalarial action. Scientists have created dihydroartemisinin, artemether, artesunate, and other derivatives preserving artemisinin’s peroxide bridge to increase its clinical utility value. Artemisinin compounds exhibit excellent efficacy, quick action, and minimal toxicity in malaria treatment and have greatly contributed to malaria control. With the wide and unreasonable application of artemisinin-based medicines, malaria parasites have developed artemisinin resistance, making malaria prevention and control increasingly challenging. Artemisinin-resistant Plasmodium strains have been found in many countries and regions. The mechanisms of antimalarials and artemisinin resistance are not well understood, making malaria prevention and control a serious challenge. Understanding the antimalarial and resistance mechanisms of artemisinin drugs helps develop novel antimalarials and guides the rational application of antimalarials to avoid the spread of resistance, which is conducive to malaria control and elimination efforts. This review will discuss the antimalarial mechanisms and resistance status of artemisinin and its derivatives, which will provide a reference for avoiding drug resistance and the research and development of new antimalarial drugs.

The oncogene DEK is found fused with the NUP214 gene creating oncoprotein DEK-NUP214 that induces acute myeloid leukemia (AML) in patients, and secreted DEK protein functions as a hematopoietic cytokine to regulate hematopoiesis; however, the intrinsic role of nuclear DEK in hematopoietic stem cells (HSCs) remains largely unknown. Here, we show that HSCs lacking DEK display defects in long-term self-renew capacity, eventually resulting in impaired hematopoiesis. DEK deficiency reduces quiescence and accelerates mitochondrial metabolism in HSCs, in part, dependent upon activating mTOR signaling. At the molecular level, DEK recruits the corepressor NCoR1 to repress acetylation of histone 3 at lysine 27 (H3K27ac) and restricts the chromatin accessibility of HSCs, governing the expression of quiescence-associated genes (e.g., Akt1/2, Ccnb2, and p21). Inhibition of mTOR activity largely restores the maintenance and potential of Dek-cKO HSCs. These findings highlight the crucial role of nuclear DEK in preserving HSC potential, uncovering a new link between chromatin remodelers and HSC homeostasis, and have clinical implications.

Despite the significance of n-3 long-chain polyunsaturated fatty acid (n-3 LC-PUFA) in fish oil in promoting the maturation of female broodstocks, the detailed mechanism of the effect on the expression of hepatic reproduction-related genes is still unclear. In this study, transcriptome sequencing was used to analyze the effect of the higher dietary n-3 LC-PUFA level on gene expression in the liver of adult females spotted scat. Two-year-old female spotted scat (average weight, 242.83 ± 50.90 g) were fed with diets containing 8% fish oil (FO) or 8% soybean oil (SO) for 40 days. The fatty acid profile in the serum, liver, and ovary was analyzed, and high proportions of n-3 LC-PUFA were observed in the FO group. The final average fish body weight and gonadosomatic index were similar between the FO and SO groups. The serum vitellogenin (Vtg) and hepatosomatic index (HSI) of the FO group were significantly higher and lower than that of the SO group, respectively. Comparatively, the liver transcriptome analysis showed 497 upregulated and 267 downregulated genes in the FO group. Among them, the expression levels of three estrogen-regulated genes (i.e., Vtga, Vtgb, and Zp4) were significantly higher in the FO than in the SO group. This expression pattern could be related to the upregulation of Hsd17b7 (the key gene for the synthesis of liver steroid hormone) and the downregulation of the Hsp90 (the estrogen receptor chaperone). The expression levels of Foxo1a and Lep, which are involved in the lipid metabolism, decreased significantly in the FO group, which may be related to the lower level of HSI in the FO group. The genes related to liver LC-PUFA absorption and transport, Fabp2 and Mfsd2ab, were significantly upregulated in the FO group, indicating that fish actively adapt to high-fish-oil diets. In brief, high-fish-oil diets can influence the expression of genes related to liver n-3 LC-PUFA metabolism and reproduction, inhibit the accumulation of liver fat, and promote the liver health and gonad development. This study will contribute to clarifying the mechanism of dietary n-3 LC-PUFA on promoting reproductive development in teleost fish.

Malaria poses a serious threat to human health. Existing vector-based interventions have shortcomings, such as environmental pollution, strong resistance to chemical insecticides, and the slow effects of biological insecticides. Therefore, the need to develop novel strategies for controlling malaria, such as reducing mosquito vector competence, is escalating. Human defensin 5 (HD5) has broad-spectrum antimicrobial activity. To determine its effect on Plasmodium development in mosquitoes, HD5 was injected into Anopheles stephensi at various time points. The infection density of Plasmodium yoelii in An. stephensi was substantially reduced by HD5 treatment administered 24 h prior to infection or 6, 12, or 24 h post-infection (hpi). We found that HD5 treatment upregulated the expression of the innate immune effectors TEP1, MyD88, and Rel1 at 24 and 72 hpi. Furthermore, the RNA interference of MyD88, a key upstream molecule in the Toll signaling pathway, decreased the HD5-induced resistance of mosquitoes against Plasmodium infection. These results suggest that HD5 microinjection inhibits the development of malaria parasites in An. stephensi by activating the Toll signaling pathway.

Background: The gut microbiota and plasma metabolites have been shown to contribute to the etiology of post-traumatic stress disorder (PTSD). The relationship between the gut microbiome and plasma metabolome in PTSD is poorly understood. This study aims to integrate the gut microbiome data and plasma metabolome data to elucidate microbial–metabolite associations specific for PTSD in a mouse model. Methods: A PTSD mouse model was induced by single prolonged stress and electric foot shock (SPS&S). We sequenced the gut microbiota composition by 16S rRNA gene sequencing and used ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) for the plasma metabolomic profiling to explore the association between the gut microbiota and the plasma metabolites in mice with PTSD. Results: The PTSD mice exhibited robust anxiety-like behaviors, significantly elevated plasma IL-1β and TNF-α, and profound gut dysbiosis characterized by a marked depletion of Muribaculaceae and Akkermansia and expansion of the Lachnospiraceae_NK4A136_group. The plasma metabolomics identified 24 significantly dysregulated metabolites, including upregulated L-arginine, palmitic acid, and oleic acid, and downregulated uridine. The pathway enrichment analysis revealed coordinated perturbations in arginine biosynthesis, pyrimidine metabolism, unsaturated fatty acid biosynthesis, and glycerophospholipid metabolism. Critically, genus-level correlation analysis uncovered biologically coherent associations. The Muribaculaceae abundance showed strong negative correlations with L-arginine and palmitic acid and positive correlations with L-glutamine and thymidine. Conclusions: This study provides an exploratory investigation into the association network between the gut microbiota and the plasma metabolites in a PTSD mouse model, offering preliminary insights into potential microbe–metabolite interactions in PTSD.