Search Results (313)

Toxoplasma gondii is an Apicomplexan parasite that possesses a well-developed system of scavengers of reactive oxygen species (ROS). Among its components, T. gondii mitochondrial superoxide dismutase (TgSOD2) is essential, as predicted by the CRISPR phenotype index and evidenced by the non-viability of its constitutive knockouts. As an obligate intracellular parasite, TgSOD2 is upregulated during extracellular stages. Herein, we generated a viable TgSOD2 knockdown mutant using an inducible auxin–degron system to explore the biological role of TgSOD2 in T. gondii. Depletion of TgSOD2 led to impaired parasite growth and replication, reduced mitochondrial membrane potential (MMP), abnormalities in the distribution of ATP synthase within its mitochondrial electron transport chain (mETC), and increased susceptibility to mETC inhibitors. Through a proximal biotinylation approach, we identified the interactions of TgSOD2 with complexes IV and V of its mETC, suggesting that these sites are sensitive to ROS. Our study provides the first insights into the role of TgSOD2 in maintaining its mitochondrial redox homeostasis and subsequent parasite replication fitness. Significance: Toxoplasma gondii infects nearly a third of the world population and can cause fetal miscarriages or life-threatening complications in vulnerable patients. Current therapies do not eradicate the parasite from the human hosts, rendering them at risk of recurrence during their lifetimes. T. gondii has a single mitochondrion, which is well-known for its susceptibility to oxidative damage that leads to T. gondii’s death. Therefore, targeting T. gondii mitochondrion remains an attractive therapeutic strategy for drug development. T. gondii’s mitochondrial superoxide dismutase is an antioxidant protein in the parasite mitochondrion and is essential for its survival. Understanding its biological role could reveal mitochondrial vulnerabilities in T. gondii and provide new leads for the development of effective treatments for T. gondii infections. Full article

(1) Background: As a prominent zoonotic parasitic disease, fascioliasis threatens the sustainable development of animal husbandry and public health. Current research focuses mainly on individual species (parasite or intermediate host), neglecting systematic evaluation of the transmission chain and exposure risks to animal husbandry. Thus, comprehensive studies are urgently needed, especially in the ecologically fragile alpine region of the Qinghai-Tibet Plateau; (2) Methods: Distribution data of Radix spp. and Fasciola hepatica in the Qinghai-Tibet Plateau and adjacent areas were gathered to establish a potential distribution model, which was overlaid on a map of livestock farming in the region; (3) Results: The key environmental factors influencing Radix spp. distribution were temperature seasonality (21.4%), elevation (16.4%), and mean temperature of the driest quarter (14.7%). For F. hepatica, the main factors were elevation (41.3%), human footprint index (30.5%), and Precipitation of the driest month (12.1%), with all AUC values exceeding 0.9. Both species exhibited extensive suitable habitats in Qinghai and Tibet, with higher F. hepatica transmission risk in Qinghai than Tibet; (4) Conclusions: The significant transmission risk and its impacts on the livestock industry in the Qinghai-Tibet Plateau highlight the need for proactive prevention and control measures. This study provides a scientific foundation for targeted alpine diseases control, establishes an interdisciplinary risk assessment framework, fills gaps in high-altitude eco-epidemiology, and offers insights for ecological conservation of the plateau. Full article

Estimating the human impact on parasites in wildlife is essential to create efficient strategies to control diseases and improve public health. This study assessed the human influence on the parasite burden of the two commonest canine mesocarnivores, the red fox (N = 194) and the golden jackal (N = 151), in Europe. We compared the infracommunity crowding index, parasite diversity, prevalence, and abundance of different parasite taxa, and the presence of Echinococcus multilocularis between groups of hosts, such as jackals and foxes hunted at different distances from human settlements. The analysis of hosts’ distribution ascertained that 61.2% of the investigated wild canids were hunted in a 500–1750 m ring around the human settlements. Ancylostomatidae proved the most prevalent taxon (>60%), while Echinococcus multilocularis and Dipylidium caninum occurred least frequently. The two taxa that mostly contributed to the crowding of infracommunities were Ancylostomatidae and Toxocaridae, with a negative correlation between their abundances (Spearman’s ρ = −0.445, p < 0.001). Parasite infracommunities were more crowded in Echinococcus multilocularis infected foxes (p = 0.02) and jackals (p = 0.001). Our study highlighted that human modification of landscapes worsened the parasite burden of wild mesocarnivores, which could increase the public health risk of zoonotic parasites. Full article

(1) Background: We combined physiological and morphological data of the European rabbit (Oryctolagus cuniculus) to provide insights into the question of how urbanization affects the health of urban wildlife populations. (2) Methods: We dissected 39 urban and 34 rural wild rabbits in order to compare organ weights, as well as stomach contents. Furthermore, we collected blood and fecal samples. (3) Results: Rural rabbits had a significantly longer body and a higher body weight as well as more fat tissue around their kidneys compared to urban rabbits. In contrast, the stomach, the intestines, the liver, the lung, and the brain of urban rabbits were significantly heavier. The amount of hematocrit, hemoglobin, and the mean corpuscular volume was significantly higher in urban rabbits. The caloric energy content of the stomach was comparable between rural and urban rabbits and was merely influenced by the season being higher in autumn. Rural rabbits had an overall higher mean parasite index compared to urban rabbits. (4) Conclusions: The results of our study allow for a deeper understanding of how density-dependent (e.g., transmission of diseases) and density-independent factors (e.g., food quality) influence the health status and life history traits of urban wildlife populations compared to their rural counterparts. Full article

Background/Objectives: Rhodesain is a cysteine protease crucial for the life cycle of Trypanosoma brucei rhodesiense, a parasite that causes the lethal form of human African trypanosomiasis. For these reasons, rhodesain is considered an important target for the drug discovery process of novel antitrypanosomal agents. Methods: In the present work, we carried out a combination study of two novel synthetic nitriles, Nitrile 1 and Nitrile 2, with curcumin, the golden multitarget nutraceutical obtained from Curcuma longa L., which we demonstrated to inhibit rhodesain in a non-competitive manner. We calculated the combination index (CI) in both the combination studies by using the Chou and Talalay method. Results: Comparing the CI values of the combinations Nitrile 1 + curcumin and Nitrile 2 + curcumin, we assessed that the inhibitory effect of the combination Nitrile 2 + curcumin against rhodesain was much more potent than that of the other combination. At the IC₅₀ value, in the case of the combination Nitrile 1 + curcumin an additive effect occurred, while in the case of Nitrile 2 + curcumin, we observed a moderate synergism: at 99% of the effect, the synergism induced by the combination Nitrile 2 + curcumin was much stronger than the synergism promoted by the combination Nitrile 1 + curcumin (CI = 0.3843 vs 0.6622, respectively). Conclusions: The co-administration of dipeptide nitriles with curcumin enhances rhodesain inhibition through synergistic effects. Notably, Nitrile 2 + curcumin exhibits a stronger synergy at higher inhibition levels, indicating a greater therapeutic potential. Full article

Visceral leishmaniasis (VL) is a severe parasitic disease caused by Leishmania spp., with a significant impact on pediatric populations, particularly in endemic regions. The diagnosis of VL in children requires a high index of suspicion, as clinical manifestations—such as prolonged fever, hepatosplenomegaly, and pancytopenia—overlap with other infectious and hematologic diseases. While serological and molecular tests aid in detection, bone marrow aspiration remains the gold standard for definitive diagnosis. In this case series, we describe five pediatric patients diagnosed with VL in Italy, emphasizing the importance of a timely and accurate diagnostic approach. Liposomal amphotericin B (LAmB) is the first-line treatment in Southern Europe due to its high efficacy and reduced toxicity. Our patients received a standard regimen of 3 mg/kg daily for five days, plus an additional dose on day 10, leading to rapid clinical improvement. However, some cases required supportive care, such as red blood cell transfusions, particularly in patients with co-infections. Despite being a neglected disease, VL is re-emerging in Europe, influenced by climate change, increased pet ownership, and migration from endemic regions. Prevention strategies focus on vector control, canine vaccination, and public health awareness. The global rise in pediatric VL highlights the need for improved surveillance, access to affordable treatments, and the development of effective vaccines to mitigate the disease burden in both endemic and non-endemic areas. Full article

Plant-parasitic nematodes and insect pests critically threaten agricultural productivity, but chemical pesticides face limitations due to resistance and environmental concerns, necessitating eco-friendly biopesticides targeting both pests and nematodes. Here, we developed a high-throughput screening platform using Caenorhabditis elegans to identify entomopathogenic fungi exhibiting nematocidal activity against Meloidogyne incognita. Among 32 tested strains, nine Metarhizium spp. and one Beauveria strain demonstrated dual efficacy against C. elegans and M. incognita. Metarhizium anisopliae CQMa421 showed the highest virulence, suppressing nematode reproduction by 42.7% and inducing >80% mortality. Pot experiments revealed a 50% reduction in the root galling index and 50.3% fewer root galls in Solanum lycopersicum. The CQMa421 filtrate caused irreversible locomotor deficits and reduced egg hatching rates by 28%. Concurrently, intestinal damage, elevated oxidative stress and autophagy were observed in C. elegans. This was accompanied by a transcriptome-wide modulation of genes involved in detoxification and immune defense pathways. These findings demonstrate the efficacy of our C. elegans-based screening method for identifying fungi with nematocidal potential. CQMa421’s virulence against M. incognita suggests its promise for pest management, while molecular insights highlight pathways that may contribute to the future design of future nematicides. This study advances fungal biocontrol agents and offers a sustainable strategy for agriculture. Full article

This study explored how potted treatments (with and without Scleroderma bovista inoculation) shape rhizosphere microbial diversity in hazel across five soils using split-root cultivation. Three treatments (control, split-root, split-root with S. bovista) were analyzed for root growth and microbial dynamics. S. bovista inoculation consistently enhanced root parameters (number, tips) in all soils. Potted treatments (with and without S. bovista inoculation) altered microbial features (OTU/ASV), with only 0.9–3.3% of features remaining unchanged. At the class level, potting increased Agaricomycetes abundance while reducing Sordariomycetes, a trend amplified by S. bovista. Potting decreased species richness estimates (ACE and Chao1), while both treatments lowered diversity index (Shannon index). Potted treatments without S. bovista inoculation drove stronger shifts in species composition than inoculation. Findings reveal potting and S. bovista synergistically recruit symbiotic fungi via root exudates, establishing disease-suppressive communities that selectively inhibit pathotrophic fungi (particularly plant pathogen Coniothyrium and fungal parasite Cladobotryum) while roughly maintaining non-pathogenic saprotrophic microbes essential for organic matter decomposition. This work provides insights for optimizing hazel orchard management and ectomycorrhizal agent development. Full article

Our understanding of the molecular mechanisms undergirding artemisinin (ART) resistance in Plasmodium falciparum is currently based on two organizing principles: reduced hemoglobin trafficking into the digestive food vacuole, resulting in lower levels of activated ART, and increased tolerance to ART-induced oxidative stress in the infected erythrocyte. We had previously proposed an extracellular vesicle (EV) export model of ART resistance in P. falciparum. This model predicts that EV abundance will be altered by ART exposure and that the peptide cargo of EVs from the ART-exposed condition will be enriched with aggregation-prone peptides. We tested the predictions of the EV export hypothesis in this study using in vitro culture assays of an ART-resistant transgenic line engineered on a 3D7 background (R561H) and a 3D7 knock-out line (PfVps60KO) with deficient EV production phenotype. EV enrichment was obtained from in vitro parasite culture supernatants via a series of ultracentrifugation and filtration steps, followed by size exclusion chromatography. A quality check on EVs was performed using dynamic light scattering. Liquid chromatography with tandem mass spectrometry was used to determine the proteome cargo from extracted EVs, and parasite peptides were queried for aggregation-prone tendency using open-access software. We report that dihydroartemisinin (DHA) exposure was positively correlated with EV abundance (coefficient estimate = 1038.58, confidence interval of 194.86–1882.30, and p-value = 0.018) and suggests that EV biogenesis is part of the parasite’s response to DHA/ART. Furthermore, our findings suggest the expression of a non-constitutive DHA-induced alternate EV biogenesis pathway as the PfVps60KO was observed to produce the highest number of EVs under DHA exposure. Finally, we show that EVs from both ART-susceptible and resistant parasites under DHA exposure carry a cargo of Chorein N-terminal domain-containing protein (PF3D7_1021700) with a high aggregation-prone index (prion-like domain [PrLD] score = 26.5) out of nine identified parasite peptides. The former of these findings is in concordance with the EV export hypothesis, which posits that the removal of DHA/ART-induced aggregated and/or misfolded peptides is critical to the parasite’s survival under DHA/ART exposure. This observation further implicates EVs in the development of the ART-resistant phenotype. However, the finding of one aggregation-prone peptide out of the nine parasite proteins in the EV cargo does not sufficiently support the EV export hypothesis. Future replicates of this study and further interrogations of the EV export hypothesis are needed. Full article

Introduction: Infectious diseases significantly impact pulmonary vascular disorders, particularly in developing countries where parasitic infections remain prevalent. These infections constitute a substantial yet frequently overlooked contributor to pulmonary hypertension. Discussion: This review examines the prevalence of parasitic lung diseases in regions where communicable infections are endemic and highlights their pathophysiological links to pulmonary hypertension. Schistosomiasis and HIV notably increase pulmonary hypertension risk in these areas. While other infectious diseases may also cause pulmonary vascular lesions, most remain insufficiently studied. The review addresses global epidemiological trends, diagnostic challenges, and recent advancements in understanding the multifaceted origins of pulmonary hypertension. Conclusion: The association between parasitic infections and pulmonary hypertension is significant, necessitating a high index of suspicion for pulmonary hypertension in patients with a history of parasitic diseases, especially in endemic regions. More research is needed to understand infection-related pulmonary hypertension mechanisms and reduce its global impact. Full article

To explore the spatiotemporal niche characteristics and changing regularities of insect communities under lamps in a semi-arid region, this paper analyzed Levins’ niche breadth index and the Pianka niche overlap index of 10 orders and 19 selected common families or superfamilies of insect communities under lamps from April to September 2018 at six vegetation sites in the Habahu National Nature Reserve, a rare desert grassland–wetland reserve in China. The results indicated the following: (1) Different taxa possess varying spatiotemporal, temporal, and spatial niche breadths, suggesting that insects effectively utilized resources in the Habahu Nature Reserve. (2) Among these groups, in terms of the orders aspect, Lepidoptera had the largest temporal niche breadth, the Hemiptera had the largest spatial niche breadth, and Lepidoptera, Coleoptera, and Hemiptera had relatively large spatiotemporal niche breadths, while Odonata had the smallest niche breadth in all three aspects. The orders of Coleoptera and Lepidoptera had the largest spatiotemporal niche overlap value, while Odonata and Diptera had the smallest. (3) In terms of the common families (superfamilies) aspect, Noctuidae had the largest temporal niche breadth and spatiotemporal niche breadth, while Hydrophilidae had the smallest. The spatial niche breadth of Sphingidae was the largest, while Corixidae was the smallest. Noctuidae and Pyraloidea had the largest spatiotemporal niche overlap value among these herbivore groups, Miridae and Chrysopidae, among the herbivore to predatory groups, and Noctuidae and Braconidae, among the herbivore to parasitic groups. This lays a theoretical foundation for developing Chrysopidae and Braconidae as biological control taxa in the Habahu Nature Reserve. Full article

Leishmaniasis and Chagas disease are parasitic diseases considered to be among the most important neglected diseases, with implications for both developed and developing countries. Currently, there are no effective therapeutic treatments for these diseases due to challenges in drug administration, high toxicity, high costs, and drug resistance. In this study, a series of eleven thymol derivatives were designed, synthesized, and evaluated for their in vitro kinetoplastid activity against Leishmania amazonensis and Trypanosoma cruzi, as well as their cytotoxicity against a murine macrophage cell line. The most active compounds, thymol anysoate (9) and thymol picolinate (10), displayed the highest kinetoplastid activity with IC₅₀ values of 22.87 and 25.16 µM against L. amazonensis and T. cruzi, respectively. Notably, both compounds demonstrated an excellent selectivity index against the mammal cell line. Structure–activity relationship studies revealed that the ester group plays a crucial role in activity. The most promising derivatives, 9 and 10, activate autophagy and apoptosis-like processes in the treated cells. Atomic force microscopy observations showed that derivative 9 induces the formation of cytoplasmic vacuoles, indicating an autophagic process, and drug-likeness analysis revealed that it meets all the pharmacokinetic criteria. Overall, these results highlight derivative 9 as a potential lead compound for the development of new drugs for the treatment of Trypanosomatidae infections and warrants further studies to elucidate the cell death cascade involved. Full article

This paper focuses on the modeling challenges of a multi-cell heterojunction bipolar transistor (HBT) used in radio frequency (RF) power amplifiers and proposes an innovative linear small-signal modeling method. Based on devices with an emitter size of 3 μm × 40 μm × 2–6 (emitter width × emitter length × emitter index-cell number), an equivalent circuit model including peripheral parasitic parameters is constructed by analyzing device layout characteristics in response to additional parasitic effects introduced by the multi-cell structure. A step-by-step parameter extraction method is used, with particular attention paid to the correction of saturated current parameters, temperature coefficients, thermal resistance correction, and the optimization of junction capacitance parameters based on the capacitance ratio relationship. After the extraction of parasitic parameters, the input and output reflection coefficient errors of the model under zero-bias conditions are below 1.66% in the 0.7–25 GHz frequency band. The accuracy of this model is significantly improved compared to the directly parallel single-cell model. The power simulation results match the measured results very well at frequencies of 2.6 GHz and 3.5 GHz. This modeling method significantly improves the model accuracy of multi-cell HBT devices in RF circuit design and provides an effective tool for high-power amplifier optimization. Full article

Background/Objectives: The increasing pressure from pathogens and parasites on Apis mellifera populations is resulting in significant colony losses. It is desirable to identify resistance-associated single-nucleotide polymorphisms (SNPs) and their variability for the purpose of breeding resilient honeybee lines. This study examined the genetic diversity of 13 SNPs previously studied for associations with various resistance-providing traits, including six linked to Varroa-specific hygiene, five linked to suppressed mite reproduction, one linked to immune response, and one linked to chalkbrood resistance. Methods: Genotyping was performed using a novel SNaPshot genotyping panel designed for this study. The sample pool consisted of 308 honeybee samples in total, covering all 77 administrative districts of the Czech Republic. Results: All examined loci were polymorphic. The frequency of positive alleles in our population is medium to low, depending on the specific SNP. An analysis of genotype frequencies revealed that most loci exhibited the Hardy–Weinberg equilibrium. A comparison of the allele and genotype frequencies of the same locus between samples from hives and samples from flowers revealed no significant differences. The genetic diversity, as indicated by the heterozygosity values, ranged from 0.05 to 0.50. The fixation index (F) was, on average, close to zero, indicating minimal influence of inbreeding or non-random mating on the genetic structure of the analyzed samples. Conclusions: The obtained results provide further insights into the genetic variation of SNPs associated with the immune response and resistance to pathogens in honeybee populations in the Czech Republic. This research provides a valuable foundation for future studies of honeybee diversity and breeding. Full article

Trypanosoma brucei rhodesiense (Tbr) and Plasmodium falciparum (Pf) are protozoan parasites that cause severe diseases, namely, Human African Trypanosomiasis (HAT) and Malaria. Due to limited treatment options, there is an urgent need for new antiprotozoal drugs. Pachysandra terminalis (P. terminalis), a plant belonging to the family Buxaceae, is known as a rich source of aminosteroid alkaloids, and a previous study of our working group already showed that the alkaloid-enriched fraction of P. terminalis aerial parts showed promising activity against protozoan parasites. In the present study, the alkaloid-enriched fraction obtained from a 75% ethanol extract of aerial parts was separated to isolate a chemically diverse array of Pachysandra alkaloids for assessment of their antiprotozoal activity and later structure–activity studies. This work yielded a new megastigmane alkaloid (1), 7 new aminosteroids (2, 7, 16, 17, 18, 19, 20), along with 10 known aminosteroids (3–5, 8, 10–15) and 2 artifacts (6, 9) that were formed during the isolation process. The structures were elucidated by UHPLC/+ESI-QqTOF-MS/MS, as well as extensive 1- and 2D-NMR measurements. The extract and its fractions, as well as the isolated compounds, were tested in vitro against Tbr and Pf, as well as cytotoxicity against mammalian cells (L6 cell line). The activity (IC₅₀ values) of the isolated alkaloids ranged between 0.11 and 26 µM (Tbr) and 0.39 and 80 µM (Pf). 3α,4α-diapachysanaximine A (7) showed the highest activity against Tbr (IC₅₀ = 0.11 µM) with a selectivity index (SI) of 133 and was also quite active against Pf with IC₅₀ = 0.63 µM (SI = 23). This compound is, therefore, a promising new antiprotozoal target for further investigations. Full article