Search Results (204)

T. remus is an important egg parasitoid of S. frugiperda, serving as a significant role in its biological control. This study systematically examined the host discrimination behavior of T. remus. The parasitic process comprises several distinct behavioral stages: host searching, antennal tapping and examination, ovipositor probing, “8”-shaped marking, and grooming. Following successful oviposition, females perform a characteristic “8”-shaped marking on the host egg surface with their ovipositor, which deters conspecific females from parasitizing the same host. T. remus exhibited a pronounced ability to discriminate parasitized hosts, utilizing both antennae and ovipositor to avoid superparasitism. As host density increased, the searching time of T. remus decreased while the parasitism rate increased, eventually stabilizing. Parasitic discrimination was significantly influenced by oviposition experience: experienced females effectively recognized marked host eggs across a temperature range of 16 to 36 °C and time intervals of 0 to 12 h post oviposition. In contrast, naive females exhibited discrimination ability only at lower temperature (16 °C) and immediately following oviposition (0 h). These findings deepen the understanding of the behavioral ecology of T. remus and provide a crucial theoretical basis for its efficient application in the biological control of S. frugiperda. Full article

Biodiversity knowledge is fundamental to conservation planning and sustainable environmental decision-making; however, general-purpose Large Language Models (LLMs) frequently produce hallucinations when responding to biodiversity-related queries. To address this challenge, we propose BioChat, a domain-specific question-answering system that integrates a Retrieval-Augmented Generation (RAG) framework with a Re-Ranker–based retrieval and routing mechanism. The system is built upon a verified biodiversity dataset curated by the National Institute of Biological Resources (NIBR), comprising 25,593 species and approximately 970,000 structured data points. We systematically evaluate the effects of embedding selection, routing strategy, and generative model choice on factual accuracy and hallucination mitigation. Experimental results show that the proposed Re-Ranker-based routing strategy significantly improves system reliability, increasing factual accuracy from 47.9% to 71.3% and reducing hallucination rate from 34.0% to 24.4% compared with Naive RAG baseline. Among the evaluated LLMs, Qwen2-7B-Instruct achieves the highest factual accuracy, while Gemma-2-9B-Instruct demonstrates superior hallucination control. By delivering transparent, verifiable, and context-grounded biodiversity information, BioChat supports environmental education, citizen science, and evidence-based conservation policy development. This work demonstrates how trustworthy AI systems can serve as sustainability-enabling infrastructure, facilitating reliable access to biodiversity knowledge for long-term ecological conservation and informed public decision-making. Full article

Background/Objectives: This study aimed to evaluate the pharmacokinetics (PK), effectiveness, and safety of the direct interleukin-6 (IL-6) inhibitor olokizumab (OKZ) in adolescent patients with active polyarticular juvenile idiopathic arthritis (pJIA) who had an inadequate response or intolerance to methotrexate (MTX). Methods: We analyzed results from an open-label, single-arm trial of OKZ therapy at a dose of 64 mg every 4 weeks for 24 weeks. We evaluated pharmacokinetic (PK) parameters, clinical effectiveness, serum C-reactive protein (CRP) dynamics, and adverse events (AEs). Results: Sixteen patients were included in the study, of whom 13 (81.2%) received OKZ through Week 24. The PK profile was consistent with observations in adults with rheumatoid arthritis (RA). By Week 16, 12 (80%) patients achieved an ACRpedi30 response, 11 (73.3%) achieved an ACRpedi50 response, and 2 (13.3%) reached inactive disease status. This response was sustained through Week 24, and no disease flares were observed. A trend toward a better response was noted among patients with baseline CRP > 10 mg/L, higher baseline IL-6, and those naïve to biologic DMARDs. Twelve patients (75.0%) experienced twenty-three mild or moderate AEs. Infections were the most frequent AEs (in 6 patients, 37.5%). No serious AEs or deaths occurred. Conclusions: OKZ treatment reduced pJIA disease activity and was well tolerated. The safety profile was consistent with that of other IL-6 inhibitors, and the PK profile matched that seen in adult RA patients. Full article

Background: Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease that requires regular monitoring. The University of Alberta IBD Unit piloted a proactive outreach protocol for biologic-naïve UC patients, including clinical and biochemical variables, and assessed its impact on UC care. Methods: Biologic-naïve UC patients without follow-up for ≥6 months were recruited by phone and completed Partial Mayo, modified Sutherland Index, and MARS-5 questionnaires, as well as blood work and fecal calprotectin (FCP). Results were sent to each patient’s gastroenterologist, who then completed a survey about intended UC management changes. Results: 81 patients completed the protocol. UC management was changed in 45 (55.6%) cases, with 82.2% of changes being expedited follow-up or management escalation. Six patients had active flares, and 17 with asymptomatic inflammation were identified. 23 patients underwent endoscopy, with 10 (43.4%) showing active disease. Six patients started biologic therapies based on protocol and endoscopic findings. UC management escalations were significantly predicted by FCP and Sutherland Index scores on logistic regression analysis. 86.4% of gastroenterologists rated the protocol helpful. Conclusions: Patient care can be improved by a one-time, proactive outreach program for biologic-naïve UC. Outreach and monitoring in biologic-naïve UC should include assessment of both FCP and clinical markers to improve UC management. Full article

Background: Filgotinib is an emerging Janus kinase 1 (JAK1) inhibitor being investigated for inflammatory bowel disease. This systematic review and network meta-analysis (NMA) evaluated the efficacy and safety of filgotinib in adult patients with moderate-to-severe crohn’s disease. Methods: We systematically searched PubMed, EMBASE, and Scopus through April 2025. Randomized controlled trials evaluating filgotinib versus placebo in adults with moderate-to-severe Crohn’s disease were included. Primary outcomes were clinical remission and endoscopic response. Study quality was assessed using the Cochrane Risk of Bias 2.0 tool. A network meta-analysis was performed to integrate direct and indirect evidence, reporting risk ratios (RRs) with 95% confidence intervals (CIs). Results: Five randomized controlled trials (from 4 publications) met the inclusion criteria. Filgotinib 200 mg significantly improved clinical remission compared with placebo (RR: 1.75 [1.40–2.19]) and 100 mg (RR: 1.38 [1.11–1.71]), while 100 mg showed no significant difference versus placebo (RR: 1.27 [0.99–1.63]). For endoscopic response, both 200 mg (RR: 1.72 [1.09–2.69]) and 100 mg (RR: 1.65 [1.02–2.69]) demonstrated significant benefit over placebo, though no difference was observed between active doses (RR: 1.04 [0.64–1.68]; I² = 57%). In the two-item patient-reported outcome, 200 mg showed significant improvement versus placebo (RR: 1.47 [1.20–1.80]) and 100 mg (RR: 1.26 [1.02–1.55]), while 100 mg remained insignificant versus placebo (RR: 1.17 [0.93–1.46]). Neither dose increased the risk of treatment-emergent adverse events, serious adverse events, or infections compared with placebo, with consistent homogeneity across analyses. Conclusions: Filgotinib 200 mg demonstrated superior efficacy across clinical, endoscopic, and patient-reported outcomes compared with 100 mg and placebo, with a favorable safety profile. The 100 mg dose showed limited efficacy and no advantage over placebo. Filgotinib represents a promising oral therapeutic option, particularly for biologic-naïve patients and in maintenance therapy, while also showing potential benefit in perianal fistulising crohn’s disease. Future trials should explore long-term safety and head-to-head comparisons with established biologics. Full article

Background: Severe asthma is a complex chronic airway disease. Biologic therapies are targeted monoclonal antibody treatments used in patients with uncontrolled, severe asthma, but real-world data from long-term registries and on patients who remain biologic-naïve are limited. This study compared severe asthma patients with and without biologic therapy and identified predictors of key clinical remission components. Methods: In this cross-sectional analysis of adult patients from the Swiss Severe Asthma Registry (SSAR), we compared patients treated with a biologic for ≥6 months to biologic-naïve patients (never exposed to biologics). Baseline characteristics were summarized descriptively. Multivariable logistic regression was used to identify predictors of four remission components: good asthma control (ACT ≥ 20), absence of exacerbations, no maintenance oral corticosteroid (OCS) use, and preserved lung function (FEV₁ > 80% predicted). Results: Of 394 patients, 298 (75.6%) were biologic-treated and 96 (24.4%) were biologic-naïve. Biologic-treated patients more often had allergic asthma and type-2–related comorbidities, and showed better outcomes, including fewer exacerbations (0.49 vs. 1.09/year; p < 0.001) and higher ACT scores (20.0 vs. 17.2; p < 0.001). Biologic therapy was independently associated with higher odds of asthma control (OR 3.96; p = 0.006), no exacerbations (OR 5.11; p = 0.001), no OCS use (OR 6.27; p = 0.002), and FEV₁ > 80% predicted (OR 4.42; p = 0.011). Overall, 24.2% of biologic-treated patients and 6.2% of biologic-naïve patients fulfilled all four remission components. Conclusions: In this real-world registry cohort, biologic-treated patients were more likely to meet individual and composite remission criteria than biologic-naïve patients. The relatively low proportion of patients achieving all four stringent criteria highlights the need to revisit current remission definitions and to adopt individualized, multidimensional treatment goals in severe asthma. Full article

Child maltreatment (MALT) is a devastating form of early-life adversity (ELA) and a primary risk for mental and physical illness. It is difficult to disentangle postnatal caregiving effects from heritable factors. Here we investigated the long-term effects of maternal care using a cross-fostering design to control for biological/heritable factors on immune function and inflammation during adolescence in a translational and naturalistic macaque model of MALT. We studied the impact of MALT on the immunophenotype of peripheral blood mononuclear cells (PBMCs) and assessed glucocorticoid receptor expression and function during adolescence. MALT was associated with elevated expression of NR3C1, the gene that encodes for the glucocorticoid receptor, in PBMCs. Glucocorticoid receptor function was not altered by MALT when examined for response to dexamethasone (DEX). In addition, MALT led to a reduction in the percentage of naïve CD4⁺ T cells and an increase in the percentage of central memory (Tcm) CD4⁺ T cells. These results suggest that MALT-exposed adolescents show residual effects of MALT on CD4⁺ T cells and increased expression of NR3C1 without demonstration of increased function of the glucocorticoid receptor. Taken together, these results suggest that ELA has enduring implications for cellular glucocorticoid receptor biology and CD4⁺ T cells. Full article

Streptococcus agalactiae (GBS) has emerged as one of the most prevalent bacterial pathogens causing severe economic losses in tilapia aquaculture due to its highly contagious and lethal nature. Nanobodies (Nbs), characterized by their small molecular size, enhanced tissue penetration, high tolerance, and exceptional antigen-binding affinity, represent a promising green alternative to conventional antibiotics. In the present study, the objective was to explore the potential of specific Nbs in the treatment of tilapia GBS disease. We first screened specific Nbs targeting the surface immunogenic (Sip) protein of GBS from a naïve phage display library, and a novel nanobody Nb30 was obtained. Nb30 was expressed in Escherichia coli and purified using the Ni-NTA Agarose column. Indirect ELISA showed that Nb30 had a high affinity against Sip and GBS in vitro. Moreover, Nb30 significantly reduced GBS colonization in the liver, spleen, and brain of GBS-infected tilapia. The survival rate in the control groups was 53%, whereas it was increased to 86% after treatment with 100 mg/kg Nb30. Transcriptome profiling revealed that Nb30 could modulate critical biological processes, including antioxidant defense, immune regulation, amino acid/protein synthesis, and energy metabolism in the liver tissues of GBS-infection tilapia. Notably, the expression levels of antioxidant enzymes (cat and gpx) were significantly up-regulated, and the TLR/MyD88/NF-κB pathway-related genes (tlr5, myd88, irak4, traf6, Rela, and NF-κB2) were significantly down-regulated after treatment with Nb30. Collectively, these findings establish a novel therapeutic strategy for controlling GBS infection in tilapia and provide evidence supporting the application of nanobodies as sustainable alternatives to antibiotics in aquaculture disease management. Full article

Background: Arterial hypertension is highly prevalent among patients with chronic kidney disease (CKD), acting both as a cause and consequence of declining kidney function, and significantly increasing cardiovascular risk. Among modifiable risk factors, diet—particularly excessive sodium intake—plays a central role in the prevention and personalized management of CKD. Methods: This study aimed to develop an innovative, digitally accessible tool to estimate sodium intake in stages 3 to 5 CKD patients, using 24-h urinary sodium excretion as the reference standard. Results: Twenty-five clinical, biological, therapeutic, and dietary variables were collected from 493 patients followed across 6 French centers. A probabilistic Tree-Augmented Naive Bayes model was used to develop the tool based on the 15 most informative variables. The model demonstrated an internal accuracy of 71%, indicating that predicted and observed sodium intake categories matched in 71% of cases. Conclusions: This AI-based prediction model offers a promising clinical tool to estimate daily sodium intake in patients with stages 3 to 5 CKD. However, external validation using independent national and international datasets is essential to establish its robustness and generalizability prior to implementation in routine clinical practice. Full article

Background: Chronic lymphocytic leukemia (CLL) is characterized by malignant B lymphocyte accumulation and progressive immune dysfunction. The immune checkpoint molecule TIM-3 and its ligand galectin-9 (Gal-9) contribute to T cell exhaustion, impairing anti-tumour immunity. Interleukin-27 (IL-27) has pleiotropic immunomodulatory properties, but its impact on TIM-3 and Gal-9 expression in CLL remains unclear. Methods: Peripheral blood mononuclear cells (PBMCs) from 20 treatment-naive CLL patients were cultured with or without IL-27 (100 ng/mL) for 72 h. Flow cytometry assessed TIM-3 and Gal-9 expression on CD4⁺, CD8⁺, and CD19⁺ cells. Results: IL-27 stimulation significantly increased TIM-3 expression on CD8⁺ T cells (2.18 ± 0.32% vs. 3.09 ± 0.49%, p = 0.009), a hallmark of T cell exhaustion. IL-27 also modestly increased intracellular Gal-9 levels in total lymphocytes (93.91 ± 1.17% vs. 96.55 ± 0.67%, p = 0.005). Additionally, IL-27 reduced CD4⁺ T cell proportions (26.71 ± 4.19% vs. 22.01 ± 3.23%, p = 0.010). Although numerically modest, these changes may be biologically pertinent in the context of checkpoint-mediated CD8⁺ T-cell exhaustion. Conclusions: IL-27 may enhance immunosuppressive mechanisms in CLL by modulating immune checkpoint expression, potentially contributing to disease progression. These ex vivo findings in PBMCs from CLL patients indicate the IL-27-associated modulation of checkpoint expression under the conditions tested. In the absence of parallel healthy-donor controls, CLL specificity cannot be established in this study. Full article

Background/Objectives: Surgery remains the mainstay of treatment for retroperitoneal sarcoma (RPS); however, definitive therapeutic strategies for patients with insufficient surgical margins and unresectable disease owing to locally advanced RPS remain unclear. Carbon ion radiotherapy (CIRT) has been employed in patients with unresectable RPS. This study aimed to evaluate the effectiveness of CIRT in this patient population. Methods: A retrospective analysis was conducted in 76 patients with unresectable RPS treated with CIRT. Of these, 95% had a confirmed prognosis until 2022. In 74 patients, the prescribed relative biological effectiveness dose was 70.4 Gy, delivered in 16 fractions over 4 weeks. Respiratory gating was used, and spot scanning irradiation has been performed in all patients since 2016. Results: The 3- and 5-year overall survival rates for the entire cohort were 68.3% and 49.4%, respectively, with a median overall survival time of 58.1 months. The 3- and 5-year local control rates were 79.0% and 72.0%, respectively. Among 47 naïve patients with treatment-naïve tumors, the 3- and 5-year abdominal recurrence-free survival rates were 51.1% and 29.1%, respectively. Late adverse events of grade 3 or higher occurred in 4 (5.2%) patients. Conclusions: CIRT represents a definitive treatment option for patients with unresectable RPS. In the future, multicenter studies should be conducted to evaluate the effectiveness of CIRT for RPS in larger patient cohorts. Full article

Men with high-risk localized prostate cancer (PCa) often have poor long-term outcomes, underscoring the need for improved neoadjuvant strategies beyond the current standard of care. Radioligand therapy with ¹⁷⁷Lutetium-PSMA-617 (¹⁷⁷Lu-PSMA-617) has emerged as a promising method to eliminate occult micrometastases while enhancing immune-mediated clearance of the primary tumor. Initial trials have affirmed the treatment’s feasibility and safety; however, they have consistently reported a lack of pathological complete response. This absence of profound initial tumor reduction necessitates further therapeutic advancements. The underlying rationale for future strategies is clear, as ¹⁷⁷Lu-PSMA-617 promotes immunogenic cell death, potentially sensitizing immunologically “cold” tumors to checkpoint inhibitors. However, caution is warranted. The synergy observed between these therapies in advanced, metastatic castration-resistant PCa stems from a different biological context, and similar outcomes cannot be presumed in treatment-naïve, localized disease without rigorous validation. Continued progress hinges on developing improved metrics for success and patient selection. Simple prostate-specific antigen reductions have demonstrated minimal correlation with significant pathological outcomes in this setting, underscoring the critical need for validated surrogate endpoints and predictive biomarkers. Ultimately, large-scale randomized trials are essential to determine whether this investigational approach impacts key clinical outcomes—namely, metastasis-free and overall survival. While the strategy is theoretically sound, its capacity to enhance cure rates for high-risk localized PCa remains unverified. Full article

Biological therapies for Crohn’s disease (CD), including infliximab, adalimumab, and vedolizumab, show variable efficacy. While some predictive biomarkers exist, data on regulatory immune cells are limited. This study examined whether baseline levels of circulating T and B cell subsets can predict response to these treatments. We recruited 43 adults with conventional treatment-resistant active CD (CDAI > 330) and 16 healthy controls. Blood samples were analysed by flow cytometry at baseline (week 0) and after induction therapy (week 12 or 14, depending on the received drug) to measure T and B cell subsets and correlate them with disease activity. CD patients at baseline showed a significantly reduced frequency of memory B cells, CD5⁺CD1d⁺ B cells, plasmablasts, and transitional B cells. Additionally, significant negative correlations were identified between transitional B cells and calprotectin/platelets, and between CD5⁺CD1d⁺ B cells and calprotectin. All CD patients responded clinically to biologic therapy. In those treated with infliximab or adalimumab, mature naïve B cells decreased, with a trend toward increased CD24^hiCD27⁺ B cells. Adalimumab responders showed a trend toward higher CD161 expression on Tregs, while vedolizumab-treated patients had a slight increase in plasmablasts. Biologic therapies in CD revealed treatment-specific immune correlations: infliximab/adalimumab responses involved B and T cell changes linked to inflammation, while VDZ response correlated with CD4⁺ and CD5⁺CD1d⁺ B cells. Our study suggests that infliximab/adalimumab induction therapy in CD expands circulating CD24^hiCD27⁺ B cells and reduces mature naïve B cells, while vedolizumab increases plasmablasts. These B-cell changes may reflect distinct mechanisms and serve as potential response biomarkers. Full article

The global unregulated drug supply faces a critical challenge with the emergence of nitazenes, a class of novel synthetic opioids (NSOs) structurally distinct from fentanyl and associated with extreme potency and high risk of fatal overdose. First synthesised in the late 1950s, etonitazene was a target of preclinical research in rats and rhesus monkeys, but it never reached clinical trials due to an unfavourable balance between therapeutic and toxic effects. Nitazenes’ consistent reappearance began in 2019 with isotonitazene, followed by a rapid proliferation of analogues worldwide, many reported to be hundreds to thousands of times more potent than morphine and, in some cases, stronger than fentanyl. This rise is fuelled by their ease of synthesis, low production costs, and evasion of regulatory controls. Nitazenes are frequently mis-sold as counterfeit medications or adulterated into other drugs, resulting in unintentional exposure and overdose, particularly among opioid-naïve users. The primary cause of death is severe and prolonged respiratory depression. Analytical challenges are significant, as traditional screening methods are ineffective, and the low concentration in biological samples requires expensive and highly sensitive liquid chromatography mass spectrometry techniques. This perspective paper highlights critical gaps in detection, clinical management, and regulatory readiness for nitazenes. Urgent efforts are needed to improve surveillance, develop robust analytical methodologies, provide clinical guidance to nitazene intoxications, and strengthen international policy to curb their proliferation. Full article

Extracellular vesicles (EVs) are rapidly gaining recognition as critical mediators of inter-cellular communication during viral infections. To contribute to fill the gap in knowledge regarding the role of EVs in adenovirus infection, we used human adenovirus type 4 of species Mastadenovirus exoticum (HAdV-E4), a prevalent respiratory and ocular pathogen, and characterized the cargo and biological properties of EVs released by HAdV-E4-infected A549 lung epithelial cells at a pre-lytic stage of infection. Using immunocapture-based isolation and multi-omics approaches, we found that infection profoundly alters the EV uploaded proteome and small non-coding RNA repertoire. Mass spectrometry identified 268 proteins unique to EVs purified from infected cells (AdV-EVs), with enrichment in pathways supporting vesicle trafficking and viral protein translation, and importantly also a few virus-encoded proteins. A small RNA transcriptome analysis showed differential uploading in AdV-EVs of various small non-coding RNAs, including snoRNAs, as well as the presence of virus associated RNAs I and II. Notably, AdV-EVs contained viral genomic DNA and could initiate productive infection upon delivery to naïve cells in the absence of detectable viral particles. Our data suggest that EVs released during the HAdV-E4 infection may serve as vehicles for non-lytic viral dissemination and highlight their possible role in intra-host dissemination Full article