Search Results (5,297)

Klebsiella pneumoniae (K. pneumoniae) is an opportunistic bacteria that can result in severe liver abscesses, pulmonary damage, and potentially fatal outcomes. Research has demonstrated that the outer membrane vesicles (OMVs) released by it can provide significant protection to infected animals and may serve as a promising candidate antigen for the development of a novel vaccine. Nevertheless, the specific mechanisms through which OMVs mitigate the detrimental effects of K. pneumoniae infection by promoting the polarization pathways of macrophages and T helper cells (Th cells) remain poorly understood. In this study, we first confirmed that Klebsiella pneumoniae outer membrane vesicles (K. pneumoniae_OMVs) were protective in K. pneumoniae-infected mice, and then we investigated the protective mechanisms by transcriptome data analysis. Then, we constructed a model of in vitro macrophage polarization, an in vivo model for Th differentiation, and a K. pneumoniae infection model in K. pneumoniae_OMVs-immunized mice. qRT-PCR, IHC, Western blotting, and ELISA were used to confirm the polarization indicators. The results showed that K. pneumoniae_OMVs were able to provide specific protection for mice with a maximum protection rate of 80%. In addition, the results of a transcriptome analysis suggested that the protective mechanism might be related to Th cells and macrophage polarization. Mice immunized with K. pneumoniae_OMVs were able to achieve rapid bacterial clearance after K. pneumoniae infection through an M1/Th1 immune response. Subsequently, tissue repair was accomplished through Th2/M2 immune response in the late stage of K. pneumoniae infection to avoid causing inflammatory damage. This study offers a theoretical foundation for the K. pneumoniae_OMVs vaccine’s actual application. Full article

Background: Rabies is among the oldest known zoonotic viral diseases and is caused by members of the Lyssavirus genus. The prototype species, Lyssavirus rabies, effectively evades the host immune response, allowing the infection to progress unnoticed until the onset of clinical signs. At this stage, the disease is irreversible and invariably fatal, with definitive diagnosis possible only post-mortem. Given the advances in modern proteomics, this study aimed to identify potential protein biomarkers for antemortem diagnosis of rabies in dogs, which are the principal reservoir hosts of the rabies virus. Methods: Two hundred and thirty-one samples (brain tissues (BT), cerebrospinal fluids (CSF), and serum (SR) samples) were collected from apparently healthy dogs brought for slaughter for human consumption in South-East and North-Central Nigeria. All the BT were subjected to a direct fluorescent antibody test to confirm the presence of lyssavirus antigen, and 8.7% (n = 20) were positive. Protein extraction, quantification, reduction, and alkylation were followed by on-bead (HILIC) cleanup and tryptic digestion. The resulting peptides from each sample were injected into the Evosep One LC system, coupled to the timsTOF HT MS, using the standard dia-PASEF short gradient data acquisition method. Data was processed using Spectronaut^TM (v19). An unpaired t-test was performed to compare identified protein groups (proteins and their isoforms) between the rabies-infected and uninfected BT, CSF, and SR samples. Results: The study yielded 54 significantly differentially abundant proteins for the BT group, 299 for the CSF group, and 280 for the SR group. Forty-five overlapping differentially abundant proteins were identified between CSF and SR, one between BT and CSF, and two between BT and SR; none were found that overlapped all three groups. Within the BT group, 33 proteins showed increased abundance, while 21 showed decreased abundance in the rabies-positive samples. In the CSF group, 159 proteins had increased abundance and 140 had decreased abundance in the rabies-positive samples. For the SR group, 215 proteins showed increased abundance, and 65 showed decreased abundance in the rabies-positive samples. Functional enrichment analysis revealed that pathways associated with CSF, spinocerebellar ataxia, and neurodegeneration were among the significant findings. Conclusion: This study identified canonical proteins in CSF and SR that serve as candidate biomarkers for rabies infection, offering insights into neuronal dysfunction and potential tools for early diagnosis. Full article

Pediatric kidney transplantation (KTx) offers the best outcomes for children with end-stage renal disease (ESRD), offering dramatic improvements in survival, quality of life, growth, and developmental outcomes compared to dialysis. Modern regimens centered on tacrolimus, mycophenolate mofetil, and risk-adapted induction have substantially reduced acute rejection and improved graft survival. This viewpoint summarizes the evolution of pediatric immunosuppression, current practice trends, and emerging strategies aimed at minimizing toxicity while preserving long-term graft function. Recent data show increasing use of T-cell-depleting induction, selective application of IL-2 receptor antagonists, and gradual adoption of steroid-sparing and mTOR-based protocols. Nevertheless, progress is limited by a scarcity of pediatric randomized trials, continued reliance on extrapolated adult evidence, infection risk, long-term metabolic complications, and adherence challenges during adolescence. Insights from recent trials including steroid minimization, everolimus-based regimens, and selective Belatacept use highlight opportunities for more individualized, risk-adapted therapy. Future efforts must prioritize precision approaches supported by biomarkers, multicenter collaboration, and long-term follow-up. Overall, contemporary trends support a shift toward tailored immunosuppression that balances efficacy with safety to optimize outcomes in pediatric KTx recipients. Full article

N⁶-methyladenosine (m⁶A), the most prevalent internal mRNA modification in eukaryotes, is also present in plants and is known to influence plant–virus interactions. However, its specific role in regulating Potato virus Y (PVY; Potyvirus yituberosi) infection, a major pathogen of potatoes, remains unclear. This study identified 16 potential m⁶A regulator genes in Nicotiana benthamiana through homology screening of Arabidopsis thaliana AlkB family members. Based on expression profiles in leaves at various developmental stages and following PVY infection, NbALKBH1L was selected for further analysis. Enzyme assays confirmed its m⁶A demethylase activity. Experiments with NbALKBH1L mutants, using RT-qPCR and m⁶A-IP-qPCR, demonstrated that it regulates PVY infection via the m⁶A pathway. Further investigation revealed that NbALKBH1L interacts with the PVY-encoded cylindrical inclusion (CI) protein. An interaction network constructed through immunoprecipitation–mass spectrometry (IP-MS) and RNA sequencing (RNA-seq) suggested that NbALKBH1L may serve as a central node in plant antiviral immunity, potentially linking metabolic processes with the regulation of viral infection. In summary, this study advances our understanding of plant m⁶A modifications in antiviral defense and provides valuable insights for future antiviral breeding strategies. Full article

Chemical defenses help insects resist pathogen infection. The volatile compositions, emission patterns, and external immune functions of the red palm weevil (RPW), a major invasive pest now established in numerous countries including the Mediterranean Basin, North Africa, Middle East, and parts of Latin America and the Caribbean, are largely unknown. In this study, we examined RPW larval volatiles, analyzing their emission patterns across developmental stages and under pathogen stress from feeding Metarhizium anisopliae. RPW larvae shared a number of volatile components across stages, but the emission dynamics were significantly different. These volatile chemicals were primarily alcohols, phenols and aromatic hydrocarbons, and styrene was the predominant volatile. Furthermore, pathogen stress induced distinct volatile profiles: phenylacetaldehyde unidirectionally decreased, whereas n-nonanol, 4-ethylguaiacol, 2-phenylethanol, hexanal, and benzophenone levels increased. Antimicrobial analysis showed that these upregulated compounds broadly inhibited fungal and bacterial growth. Therefore, our results illustrated the immune defense role of RPW larval volatiles and their potential bioactive compounds, including n-nonanol, 4-ethylguaiacol, 2-phenylethanol, hexanal, and benzophenone. Full article

Legionella pneumophila, a waterborne pathogen naturally present in freshwater and capable of colonizing artificial water systems, is responsible for Legionnaires’ disease (LD), a severe form of pneumonia transmitted through inhalation of contaminated aerosols. Virulence of Legionella strains is affected by the plasticity of their genome, shaped by horizontal gene transfer and recombination events. Thus, contaminated water systems can host diverse Legionella populations with a distinct virulence potential. Here, we compare the genomic diversity of Legionella pneumophila strains isolated in water systems of academic buildings, together with their cytotoxicity and intracellular replication in THP-1-like macrophages. A six-year environmental surveillance revealed Legionella pneumophila contamination in 20 out of the 50 monitored sites, identifying five serogroups (sg) and 13 Sequence Types (STs). Phylogenetic investigations based on core genome multilocus sequence typing (cgMLST) and comparative genomics of representative isolates of each ST showed a broad diversity and a heterogeneous virulence repertoire, especially within the Dot/Icm and Lvh secretion systems. Following macrophage infection, a strain-dependent cytotoxicity and intracellular replication was observed, underlying significant pathogenic diversity within the same species and stage-dependent infection dynamics. Together, these results showed strain-specific genetic and phenotypic virulence traits to be considered during risk assessment in environmental surveillance. Full article

Introduction: Primary Cytomegalovirus (CMV) infection occurs in 0.7–4.1% of all pregnancies. Our study aims to analyze the incidence rate of ultrasound anomalies, as well as CMV PCR analysis of the amniotic fluid sample obtained from amniocentesis in CMV-infected pregnancies, as well as the outcome of the pregnancies and neonatal follow-up. Methods: We analyzed cases of recent maternal CMV infections confirmed by serological testing at the Department of Obstetrics and Gynecology, Semmelweis University, between 2001 and 2023. In cases of primary CMV infection confirmed by serological testing during pregnancy, we offered amniocentesis at the genetic counseling, which was performed at the 20–21 weeks stage of the pregnancy. Results: In 130 cases of recent maternal CMV infection confirmed by serological testing, amniocentesis was performed, and a total of 11 cases (8.46%) were found to have CMV DNA in the amniotic fluid. Based on the neonatological follow-up examinations in 116 deliveries, 18 newborns had complications (15.52%); however, some cases were associated with multiple complications, resulting in a total of 33 types of complications being identified (28.45%). Among the 11 neurological complications (9.48%), we found 1 case each (0.86%) of severe inoperable intracranial space occupation, hydrocephalus, balance disorder, sleep disorder–sleep apnea, and speech development disorder. Two cases (1.72%) were found to have rigid muscles, epilepsy, and hypotonic muscles. Ophthalmological complications occurred in five cases (4.31%), such as enophthalmos, cataract, and retinopathy of prematurity (ROP), one case each, and two cases of strabism. Other complications were detected in 17 cases (14.66%). Conclusions: Because of the high incidence rate of recent CMV infection, serological testing is recommended following fetal abnormality detected by ultrasound. If a serologically confirmed new infection is diagnosed, the affected couple should be offered amniocentesis. Full article

The outbreaks of large-scale epidemics, such as COVID-19 in 2019–2022, challenge modelers. Beside the effect of the incubation period of the virus, the delay property of detection should be also stressed. This kind of memory effect affects the entire change rate, which cannot be reflected by the conventional instantaneous derivative. The fractional derivative (FD) meets this request to some extent. Yet the shortcoming of it limits its usage. Through a strict modeling approach, a new susceptible–infective–removed (SIR) model with the memory-dependent derivative (MDD) has been constructed. The numerical simulations indicate that (1) the neglecting of the incubation period may underestimate the number of susceptible individuals and overestimate the infected ones; (2) the neglecting of the treatment period may badly overestimate the removed individuals; (3) the consequence of tardy detection intervention may be very serious, and the infectious rate may increase rapidly with a postponed peak time; and (4) the SIR model with the FD yields bad estimations, not only in the primary stage but also in the subsequent evolution. Due to the reasonability of the new SIR model with the MDD, it is suggested to epidemic researchers. Full article

Background/Objectives: Women carry two-thirds of the global anal cancer burden. Persistent genital (vulval, vaginal and cervical) high-risk Human Papillomavirus (hrHPV) infection and the resultant genital high-grade squamous intraepithelial lesions (HSILs) and genital cancers are now acknowledged as independent risk factor for anal dysplasia in women. Patients with both genital and anal hrHPV-related diseases, however, are poorly researched. Methods: National Cancer Registration and Analysis Service (NCRAS) data was requested via the NHS Digital data access request service (DARS). Women in England over the age of 25 years diagnosed with anal HSIL/cancer between 2001 and 2020 who also had a vulval and/or vaginal and/or cervical cancer HSIL/cancer diagnosis within the 20-year period before or 1-year period after their anal cancer/HSIL were studied. The burden of genital disease in women with anal cancer, their sociodemographic risk factors and timelines between acquisition of genital and anal pathology were assessed. Results: A total of 8% (n = 1297/16,301) of all women with anal HSIL/cancer also had metachronous or synchronous genital HSIL/cancer diagnoses. Women who were first diagnosed with cervical HSIL had a lower burden of recurrent anogenital lesions over time (p = 0.04) but a significantly higher risk of presenting with late-stage anal cancer than women first presenting with vulval pathology (p = 0.02). Women who had disease in more than one anatomical site developed disease features 10–20 years earlier compared to other published datasets on women with single site disease. Conclusions: These findings support the current IANS screening recommendation guidelines and suggest that the current anal cancer risk for women with cervical dysplasia may be underestimated. Full article

Malaria remains one of the devastating illnesses, and drug-resistant malaria has incurred enormous societal costs. A few host kinases are vital for the liver stage malaria and might be promising drug targets against drug-resistant malaria. STK35L1 is one of the host kinases that is highly upregulated during the liver stage of malaria, and the knockdown of STK35L1 significantly suppresses Plasmodium sporozoite infection. In this study, we retrieved the promoter region of STK35L1 based on 5′ complete transcripts, transcription start sites, and cap analysis of gene expression tags. Furthermore, we identify transcriptionally active regions by analyzing CpG islands, histone acetylation (H3K27ac), and histone methylation (H3K4me3). It suggests that the identified promoter region is active and has cis-regulatory elements and enhancer regions. We identified various putative transcription factors (TFs) from the various high-throughput ChIP data that might bind to the promoter region of STK35L1. These TFs were differentially regulated during the infection of Plasmodium sporozoites in HepG2 cells. Our molecular modeling study suggests that, except for SMAD3, the identified TFs may be directly bound to the promoter. Together, the data suggest that these TFs may play a role in sporozoite infection and in regulating STK35L1 expression during the liver stage of malaria. Full article

The production and quality of wheat and maize grain can be significantly affected by various pests and pathogens, with phytoplasmas posing a particular threat due to their rapid spread and potential to cause severe damage to cultivated crops. The objective of this investigation was to evaluate the risk associated with these wall-less bacteria in wheat and maize crops. To achieve this, a survey was conducted in commercial fields located in southwestern Poland. Samples of winter wheat and fodder maize were collected at two distinct developmental stages, including both symptomatic and asymptomatic plants. Symptoms observed in wheat included yellowing, stunting, and excessive tillering, while maize plants showed yellow leaf striping, red discoloration, and stunted growth. Polymerase chain reaction (PCR) assays using phytoplasma-specific primers, followed by Sanger sequencing and sequence analysis, confirmed phytoplasma infections in 2% of wheat and 1.5% of maize samples. Virtual restriction fragment length polymorphism (RFLP) analysis identified the wheat-infecting phytoplasmas as belonging to subgroup 16SrI-C (‘Candidatus Phytoplasma tritici’-related strain)—a pathogen of major concern for wheat, while maize-infecting phytoplasmas were classified into subgroups 16SrI-B and 16SrV-C. Additionally, wheat plants collected during the early elongation phase were tested for Mastrevirus hordei (former wheat dwarf virus, WDV) using double antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA), which confirmed the presence of WDV in all tested samples. Preliminary screening of field-collected leafhoppers revealed that 7.5% of Psammotettix alienus, the predominant species in wheat fields, carried 16SrI-C phytoplasmas. In maize fields, Zyginidia scutellaris was the most prevalent species, with 1.7% of individuals carrying 16SrV-C phytoplasma. These findings suggest that these insect species may contribute to the transmission of phytoplasmas in wheat and maize. This study provides the first documented evidence of 16SrI-C phytoplasma infecting wheat in Poland, and of 16SrV-C and 16SrI-B phytoplasmas infecting maize, expanding the known host range of these subgroups in the country and highlighting their potential phytosanitary importance. Full article

During the first week of T. b. brucei infection, pro-inflammatory IFN-γ production drives acute anaemia by promoting red blood cell clearance by activated macrophages in concert with insufficient bone marrow compensation. The latter is followed by a partial recovery phase, which later progresses to chronic anaemia. To compensate for acute anaemia, stress-induced extramedullary erythropoiesis occurs in the spleen. However, the role of IL-10, a key anti-inflammatory cytokine in regulating stress-induced acute anaemia during African trypanosomosis (AT), remains unclear. Using both genetic and pharmacological approaches, we show that IL-10 is essential to limit acute anaemia by dampening inflammation and promoting splenic erythropoiesis, enabling recovery. More specifically, IL-10 blockade impairs erythropoiesis in both bone marrow and spleen, particularly at early erythroid differentiation stages, and associates with reduced central macrophage (CM) numbers in the bone marrow. In contrast, the co-inhibition of IL-10 and IFN-γ reduces inflammation and partially restores splenic CM numbers and erythropoiesis, highlighting IFN-γ’s suppressive role in erythropoiesis. Overall, these findings underscore IL-10’s key role in regulating stress-induced erythropoiesis during AT by modulating erythroid differentiation and CM abundance, thereby limiting immune-mediated acute anaemia. Consequently, timely adjustment of the IL-10/IFN-γ balance may enhance erythropoiesis and offer a potential therapeutic strategy to mitigate anaemia development. Full article

Paragonimus westermani is a food-borne zoonotic trematode transmitted to humans through the consumption of undercooked crustaceans. Freshwater crabs act as the second intermediate host for the encysted metacercariae stage. However, accurate identification of intermediate hosts remains a challenge. Here, we aimed to detect and identify P. westermani in randomly collected freshwater crabs and determine the species of infected crabs in Davao Oriental through molecular methods. Specifically, Sanger and next-generation sequencing were conducted for species identification through BLASTn, followed by phylogenetic analyses to understand geographic and taxonomic relationships. Results showed P. westermani DNA was detected in five out of eleven crab samples and these sequences were closely grouped to the Philippine reference sequence. Through a similar approach, the infected crabs showed high sequence similarity and formed tight clustering to Isolapotamon sp. Overall, the results provided evidence that P. westermani DNA was detected in Isolapotamon sp., a genus endemic to Mindanao, and can be a potential intermediate host. This expands our current understanding of transmission ecology beyond the only known intermediate host in the Philippines, Sundathelphusa philippina. Full article

This study explores the use of remote sensing and machine learning (ML) for early detection of Pyricularia oryzae (rice blast) in ‘Bomba’ rice. Conducted in Spain’s Albufera Natural Park over four seasons (2021–2024), 94 fields were monitored using Sentinel-2 imagery and Topcon Yield Trakk data. Principal Component Analysis (PCA) identified key spectral bands (B03, B04, B05, B07, B08, B11) at early stages (35 and 55 DAS). Three ML classifiers—K-Nearest Neighbors (KNN), Random Forest (RF) and Support Vector Machines (SVMs)—were tested to categorize fields by yield-based infection levels. RF achieved the best performance (up to 94% Accuracy), showing high robustness across band combinations and dates. KNN was more input-sensitive, and SVM performed weakest. Integrating multispectral and multitemporal data enhanced accuracy. Overall, RF and remote sensing proved reliable tools for early disease detection, supporting Precision Agriculture and real-time pest management. Full article

This study aims to elucidate the physiological and biochemical alterations induced by parasitic Cuscuta sp. (dodder) in lucerne (Medicago sativa L.), a key forage crop. Comparative analyses between infected and healthy plants revealed that significant reductions in chlorophyll a, b, and total chlorophyll, and protein levels in the leaf and stem tissues of Cuscuta-infested plants were evident. The parasitic infection led to increased activities in antioxidant enzymes such as catalase (CAT) and peroxidase (POX) in stems, but not in leaves. Phenolic compounds were significantly lower both in leaves and stems of dodder-infected lucerne plants. No statistically significant changes were detected in jasmonic acid (JA) and salicylic acid (SA) levels in both plant parts, suggesting that classical defense signaling pathways may not be predominantly activated under Cuscuta-mediated stress. Possibly, host defense might be impaired. Histological examinations demonstrated active structural defense responses, including localized tissue remodeling and the formation of callose-like structures at haustorial penetration sites. DNA fragmentations showed that Cuscuta-infected M. sativa plants exhibited slightly higher instability. Collectively, these findings provide novel insights into the molecular and biochemical basis of the Cuscuta-lucerne interactions and highlight the need for further investigation into host defense mechanisms. We assume that active defense structural parts at early growth stages of lucerne or hypersensitive-type responses occurring in the early penetration phase might fend off the invading holoparasite. The results also offer a valuable foundation for the development of Cuscuta-resistant lucerne cultivars and support the design of integrated, sustainable weed management strategies to mitigate the detrimental effects of parasitic plants on forage production systems. Full article