暂无摘要。

Malaria remains one of the most perilous vector-borne infectious diseases for humans globally. Sexual gametocyte represents the exclusive stage at which malaria parasites are transmitted from the vertebrate to the Anopheles host. The feasible and effective approach to prevent malaria transmission is by addressing the sexual developmental processes, that is, gametocytogenesis and gametogenesis. Thus, this review will comprehensively cover advances in the regulation of gene expression surrounding the transmissible stages, including epigenetic, transcriptional, and post-transcriptional control.

Malaria continues to be a major barrier to socioeconomic development in Africa, where its death rate is over 90%. The predictive power of many machine learning models-such as multi-linear regression (MLR), artificial neural networks (ANN), adaptive neuro-fuzzy inference systems (ANFISs) and Random Forest classifier-is investigated in this study using data from 2207 patients. The dataset was reduced from the initial dataset of thirty-two criteria samples to fifteen. Assessment measures such as the root mean square error (RMSE), mean square error (MSE), coefficient of determination (R2), and adjusted correlation coefficient R were used. ANFIS, Random Forest, MLR, and ANN are among the models. After training, ANN outperforms ANFIS (97%), MLR (92%), and Random Forest (68%) with the greatest R (99%) and R2 (99%), respectively. The testing stage confirms the superiority of ANN. The paper also presents a statistical forecasting sheet with few errors and excellent accuracy for MLR models. When the models are assessed with Random Forest, the latter shows the least results, thus broadening the modeling techniques and offering significant insights into the prediction of malaria and healthcare decision making. The outcomes of using machine learning models for precise and efficient illness prediction add to an expanding body of knowledge, assisting healthcare systems in making better decisions and allocating resources more effectively.

Plasmodium species adapt a complex lifecycle with multiple phenotypes to survive inside various cell types of humans and mosquitoes. Stage-specific gene expression in the developmental stages of parasites is tightly controlled in Plasmodium species; however, the underlying mechanisms have yet to be explored. Genome organization and gene expression for each stage of the malaria parasite need to be better characterized. Recent studies indicated that epigenetic modifications of histone proteins play a vital role in chromatin plasticity. Like other eukaryotes, Plasmodium species N-terminal tail modifications form a distinct \"histone code,\" which creates the docking sites for histone reader proteins, including gene activator/repressor complexes, to regulate gene expression. The emerging research findings shed light on various unconventional epigenetic changes in histone proteins\' core/globular domain regions, which might contribute to the chromatin organization in different developmental stages of the malaria parasite. The malaria parasite lost many transcription factors during evolution, and it is proposed that the nature of local chromatin structure essentially regulates the stage-specific gene expression. This review highlights recent discoveries of unconventional histone globular domain epigenetic modifications and their functions in regulating chromatin structure dynamics in various developmental stages of malaria parasites.

UNASSIGNED: Scarcity of annotated image data sets of thin blood smears makes expert-level differentiation among Plasmodium species challenging. Here, we aimed to establish a deep learning algorithm for identifying and classifying malaria parasites in thin blood smears and evaluate its performance and clinical prospect.
UNASSIGNED: You Only Look Once v7 was used as the backbone network for training the artificial intelligence algorithm model. The training, validation, and test sets for each malaria parasite category were randomly selected. A comprehensive analysis was performed on 12 708 thin blood smear images of various infective stages of 12 546 malaria parasites, including P falciparum, P vivax, P malariae, P ovale, P knowlesi, and P cynomolgi. Peripheral blood samples were obtained from 380 patients diagnosed with malaria. Additionally, blood samples from monkeys diagnosed with malaria were used to analyze P cynomolgi. The accuracy for detecting Plasmodium-infected blood cells was assessed through various evaluation metrics.
UNASSIGNED: The total time to identify 1116 malaria parasites was 13 seconds, with an average analysis time of 0.01 seconds for each parasite in the test set. The average precision was 0.902, with a recall and precision of infected erythrocytes of 96.0% and 94.9%, respectively. Sensitivity and specificity exceeded 96.8% and 99.3%, with an area under the receiver operating characteristic curve >0.999. The highest sensitivity (97.8%) and specificity (99.8%) were observed for trophozoites and merozoites.
UNASSIGNED: The algorithm can help facilitate the clinical and morphologic examination of malaria parasites.

Romanowsky staining was an important methodological breakthrough in diagnostic hematology and cytopathology during the late 19th and early 20th centuries; it has facilitated for decades the work of biologists, hematologists and pathologists working with blood cells. Despite more than a century of studying Romanowsky staining, no systematic review has been published that explains the chemical processes that produce the \"Romanowsky effect\" or \"Romanowsky-Giemsa effect\" (RGE), i.e., a purple coloration arising from the interaction of an azure dye with eosin and not due merely to their simultaneous presence. Our review is an attempt to build a bridge between chemists and biomedical scientists and to summarize the available data on methylene blue (MB) demethylation as well as the related reduction and decomposition of MB to simpler compounds by both light and enzyme systems and microorganisms. To do this, we analyze modern data on the mechanisms of MB demethylation both in the presence of acids and bases and by disproportionation due to the action of light. We also offer an explanation for why the RGE occurs only when azure B, or to a lesser extent, azure A is present by applying experimental and calculated physicochemical parameters including dye-DNA binding constants and electron density distributions in the molecules of these ligands. Finally, we discuss modern techniques for obtaining new varieties of Romanowsky dyes by modifying previously known ones. We hope that our critical literature study will help scientists understand better the chemical and physicochemical processes and mechanisms of cell staining with such dyes.

A hyperdiverse class of pathogens of humans and wildlife, including the malaria parasite Plasmodium falciparum, relies on multigene families to encode antigenic variation. As a result, high (asymptomatic) prevalence is observed despite high immunity in local populations under high-transmission settings. The vast diversity of \"strains\" and genes encoding this variation challenges the application of established models for the population dynamics of such infectious diseases. Agent-based models have been formulated to address theory on strain coexistence and structure, but their complexity can limit application to gain insights into population dynamics. Motivated by P. falciparum malaria, we develop an alternative formulation in the form of a structured susceptible-infected-susceptible population model in continuous time, where individuals are classified not only by age, as is standard, but also by the diversity of parasites they have been exposed to and retain in their specific immune memory. We analyze the population dynamics and bifurcation structure of this system of partial-differential equations, showing the existence of alternative steady states and an associated tipping point with transmission intensity. We attribute the critical transition to the positive feedback between parasite genetic diversity and force of infection. Basins of attraction show that intervention must drastically reduce diversity to prevent a rebound to high infection levels. Results emphasize the importance of explicitly considering pathogen diversity and associated specific immune memory in the population dynamics of hyperdiverse epidemiological systems. This statement is discussed in a more general context for ecological competition systems with hyperdiverse trait spaces.

Malaria remains a devastating disease and, with current measures failing to control its transmission, there is a need for novel interventions. A family of proteins that have long been pursued as potential intervention targets are aquaporins, which are channels facilitating the movement of water and other solutes across membranes. We identify an aquaporin in malaria parasites and demonstrate that it is important for completion of Plasmodium development in the mosquito vector. Disruption of AQP2 in the human parasite Plasmodium falciparum and the rodent parasite Plasmodium berghei blocks sporozoite production inside oocysts established on mosquito midguts, greatly limiting parasite infection of salivary glands and transmission to a new host. In vivo epitope tagging of AQP2 in P. berghei, combined with immunofluorescence assays, reveals that the protein is localized in vesicle-like organelles found in the cytoplasm of gametocytes, ookinetes, and sporozoites. The number of these organelles varies between individual parasites and lifecycle stages suggesting that they are likely part of a dynamic endomembrane system. Phylogenetic analysis confirms that AQP2 is unique to malaria and closely related parasites and most closely resembles intracellular aquaporins. Structure prediction analyses identify several unusual features, including a large accessory extracellular loop and an arginine-to-phenylalanine substitution in the selectivity filter principally determining pore function, a unique feature among known aquaporins. This in conjunction with the importance of AQP2 for malaria transmission suggests that AQP2 may be a fruitful target of antimalarial interventions.

The human malaria parasite Plasmodium falciparum represses transcription of the gene encoding AP2-G, which is the master regulator of germ cell differentiation, via heterochromatin condensation following histone H3 lysine 9 trimethylation (H3K9me3). Although H3K9me3-marked heterochromatin is typically constitutive and its establishment depends on the RNA interference (RNAi) pathway in fission yeast centromeres, malaria parasites lack molecular members essential for RNAi. We developed a strategy to assess heterochromatin establishment on artificial chromosomes introduced into P. falciparum. We show that a particular DNA sequence in the AP2-G promoter is able to induce de novo H3K9me3 nucleosome deposition. In addition, we also found that the AP2-G promoter contains a distinct element required in maintenance of the repression memory. Thus, we speculate that malaria parasites have evolutionarily acquired a sequence-dependent establishment system of non-constitutive, i.e. facultative, H3K9me3-marked heterochromatin.

Green nanotechnology has recently attracted a lot of attention as a potential technique for drug development. In the present study, silver nanoparticles were synthesised by using Sargassum tenerrimum, a marine seaweed crude extract (Ag-ST), and evaluated for antimalarial activity in both in vitro and in vivo models. The results showed that Ag-ST nanoparticles exhibited good antiplasmodial activity with IC50 values 7.71±0.39 µg/ml and 23.93±2.27 µg/ml against P. falciparum and P. berghei respectively. These nanoparticles also showed less haemolysis activity suggesting their possible use in therapeutics. Further, P. berghei infected C57BL/6 mice were used for the four-day suppressive, curative and prophylactic assays where it was noticed that the Ag-ST nanoparticles significantly reduced the parasitaemia and there were no toxic effects observed in the biochemical and haematological parameters. Further to understand its possible toxic effects, both in vitro and in vivo genotoxicological studies were performed which revealed that these nanoparticles are non-genotoxic in nature. The possible antimalarial activity of Ag-ST may be due to the presence of bioactive phytochemicals and silver ions. Moreover, the phytochemicals prevent the nonspecific release of ions responsible for low genotoxicity. Together, the bio-efficacy and toxicology outcomes demonstrated that the green synthesized silver nanoparticles (Ag-ST) could be a cutting-edge alternative for therapeutic applications.