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PubMed2026

Immunomodulatory effects of palm-derived tocotrienol-rich fraction in healthy volunteers following influenza vaccination: A randomised clinical trial.

Most studies on vitamin E and immunity have focused on tocopherols, but the tocotrienol-rich fraction (TRF) from palm oil may exert stronger immunomodulatory effects. This study investigated the effect of various TRF doses on the immune response to influenza immunisation in healthy adults. We hypothesized daily supplementation with lower doses of TRF can boost immune response to the influenza vaccine in healthy Individuals. In a double-blind placebo-controlled trial, 150 participants (≥18 years) were randomised to receive placebo or TRF (50, 100, 200, or 400 mg) daily for 2 months, with vaccination on day 28. Blood samples collected on days 0, 28, and 56 were analyzed for humoral and cellular immunity, antioxidant status, and plasma concentrations of vitamin E. TRF significantly augmented anti-influenza antibody production across all doses, with the 400 mg group exhibiting the highest titers. A selective Th1-type immune response was observed, characterized by significant IFN-γ production upon restimulation in all TRF-supplemented groups compared with placebo. Plasma IL-12 was elevated in the highest dose, whereas the amount of EBI3 produced increased across a broader range of doses compared to placebo. TRF supplementation was associated with increased antioxidant enzyme activities and stable malondialdehyde activity. Elevated α-tocopherol concentrations observed, primarily at higher doses. Supplementation with TRF can enhance immune response to influenza immunisation by modulating humoral, Th1 responses and improving antioxidant status. Critically, antibody production increased similarly across all TRF doses, suggesting that lower doses may offer a cost-effective strategy for supporting humoral immunity, while higher doses provide broader immunomodulatory benefits.

Humans↗

PubMed2026

Serotypic and Genomic Diversity of Vibrio anguillarum in Rainbow Trout Farms in Turkey: Implications for Vibriosis Control and Vaccine Candidate Selection.

Outbreaks of vibriosis caused by Vibrio anguillarum are a persistent constraint on rainbow trout (Oncorhynchus mykiss) aquaculture. However, information on the population structure of field strains in Turkey has been lacking. Here, we report the first systematic serotypic, proteomic, and genomic characterization of 23 V. anguillarum isolates collected over 10 years from rainbow trout farms located in six major aquaculture regions of Turkey. Serological analyses based on microagglutination, supported by ELISA characterization of hyperimmune sera, identified a clear predominance of serotype O1, whereas isolate V12 exhibited a non-agglutinating, atypical O-antigen profile. Protein profiling (SDS-PAGE) and immunoblotting showed largely conserved whole-cell protein patterns among the isolates, but distinct immunogenic bands at 14, 18, and 40 kDa were detected in isolates V18 and V21. Long-read whole-genome sequencing revealed that most Turkish isolates grouped within the global O1 clade, while V12, V25, and V28 isolates occupied more distant branches. Comparative genomics demonstrated a conserved core virulence gene set (RTX toxins, siderophore and iron-uptake systems, motility and adhesion factors, Type VI secretion system), with strain-dependent variation in accessory loci such as anguibactin and T6SS-I. Experimental infections of rainbow trout demonstrated significant differences in virulence among isolates (p < 0.05), with the V18 isolate showing high, the V15 intermediate, and the V12 low-mortality rates. By elucidating the relationship among the serotype, immunogenic protein profiles, virulence gene repertoires, and in vivo pathogenicity, this study provides a comprehensive overview of the antigenic and genomic diversity of Vibrio anguillarum isolates from Turkey. Notably, the identification of V18 and V21 as promising candidate strains for further vaccine evaluation, characterized by high virulence and unique immunogenic features, provides a scientific foundation for the development of serotype-specific vaccination strategies to mitigate vibriosis-associated losses in aquaculture.

Animals↗

PubMed2026

Exploring sex differences in endocannabinoid system biomarkers and their relationship with antidepressant treatment outcomes in major depressive disorder: a CAN-BIND 1 secondary analysis.

BACKGROUND: Sex differences in major depressive disorder (MDD) are well documented, but it remains unclear whether sex-related variation in peripheral endocannabinoid system (ECS)-related biomarkers is detectable in MDD. OBJECTIVES: To examine baseline sex differences in ECS-related mRNA expression, DNA methylation, and single nucleotide polymorphisms (SNPs) in MDD, and associations between baseline ECS markers and antidepressant outcomes in sex-stratified analyses. METHODS: Among 178 participants with MDD from CAN-BIND-1, all received escitalopram for 8 weeks; non-responders then received adjunctive aripiprazole from Weeks 8-16.Response was defined as ≥ 50% reduction in MADRS score, and remission as MADRS ≤ 10. ANCOVAs examined baseline sex differences and sex-stratified biomarker associations with percent MADRS reduction at Weeks 8 and 16, as well as categorical response and remission outcomes. Covariates included site, baseline MADRS, age, and ethnicity. False discovery rate correction was applied. RESULTS: Baseline sex differences in methylation were observed for CACNA1H, GABRB2, MAGL, and GABRR2, though none survived correction. No baseline sex differences in mRNA expression or SNPs were detected after correction. Lower baseline DAGLA mRNA in males was associated with greater Week 8 symptom improvement (FDR corrected). This association was not observed in females. No associations with response or remission at Weeks 8 or 16 survived correction. IMPLICATIONS: Baseline sex differences in peripheral ECS-related markers were not detected in this sample. Larger studies are needed to verify whether ECS-related biomarkers, particularly DAGLA, contribute to antidepressant outcomes in a sex-specific manner.

Humans↗

PubMed2026

A Multimethod Evaluation to Assess Feasibility, Acceptability, and Preliminary Efficacy of HPVVaxFacts, a Tailored Mobile Web App, for Parents With Unvaccinated Children: Pilot 2-Arm Randomized Controlled Trial.

BACKGROUND: Mobile health (mHealth) interventions may improve provider-parent communication on human papillomavirus (HPV) vaccination to reduce concerns, and increase intention and uptake. HPVVaxFacts (233 Analytics) is a novel, mobile web app delivering tailored education based on the Health Belief Model and Theory of Reasoned Action, addressing parental concerns preclinic visit. OBJECTIVE: This study aimed to assess the feasibility, acceptability, and preliminary efficacy of HPVVaxFacts among parents of adolescents aged 9-17 years. METHODS: We conducted a pilot, randomized controlled trial in 2 urban Tennessee clinics from June to September 2023 comparing 2 groups: tailored education via HPVVaxFacts mobile web app (intervention, n=27), and nutrition education (attention control, n=30). Eligible parents had or were caregivers to a child aged 9 to 17 years unvaccinated against HPV, had a mobile phone, had an upcoming clinic visit, and spoke English. The recruitment strategy was patient intake software-Phreesia (Phreesia, Inc) and eClinicalWorks (eClinicalWorks). Although unblinded, parents could deduce their study arm assignment. Providers were blinded. Feasibility, acceptability, and preliminary efficacy (HPV vaccine knowledge, concerns, intentions, and vaccination rates) were assessed using multimethod evaluation. Parents were assessed at baseline and immediately post intervention via surveys. Vaccination rates were assessed at 12 months post intervention via electronic health records. Nineteen parent interviews were conducted up to 9 months post intervention. A clinic staff consultation (n=6) was 1 month post intervention. RESULTS: Of 57 enrolled parents, most were female (52/57, 91%), non-Hispanic White (44/57, 77%), had ≤US $80,000 household income (32/57, 56%), and had some college or less (27/57, 47%). In total, 81% (29/36) of parents viewed HPVVaxFacts. Post intervention, HPV vaccine initiation was higher in the intervention group compared to the attention control group (48% vs 17%; difference 0.24; 95% CI 0.03-0.46; P=.01). Parents in the HPVVaxFacts arm demonstrated a greater reduction in knowledge (ie, knowledge increase; mean change: -0.6 vs 0.1) and concern scores (mean change: -3.4 vs -1.4) than those in the nutrition education arm. However, between-arm differences were not statistically significant (P=.13 and P=.14, respectively). The majority found the study protocol and HPVVaxFacts acceptable. Benefits of HPVVaxFacts include confirming their decision to vaccinate, supporting parent-child discussion on the vaccine, and answering questions preclinic visit or offering questions for the provider. Study protocol delivery and mobile web app instructions were suggested areas for improvement. Barriers for HPVVaxFacts use include content in English only and digital format. CONCLUSIONS: Our study suggests HPVVaxFacts was feasible and acceptable among parents to provide previsit, tailored information on HPV vaccination. Outcomes offer a positive trajectory but need more exploration. Next steps include a well-powered efficacy trial to determine the impact of HPVVaxFacts on initiation vaccine rates and parental hesitancy factors, as well as to explore an interaction, effect modification, and mediation among different variables.

Humans↗

PubMed2026

Reduced FOXP3 expression and its association with genetic ancestry in neuromyelitis Optica spectrum disorder: a Colombian cohort.

BACKGROUND: Autoimmune disorders are characterized by impaired immune tolerance, largely mediated by CD4⁺ regulatory T cells (Tregs), whose function depends on the transcription factor FOXP3. OBJECTIVES: To compare FOXP3 expression levels between patients with neuromyelitis optica spectrum disorder (NMOSD) and healthy controls from Bogotá, Colombia, and to explore their association with genetic ancestry. METHODS: FOXP3 expression was quantified from peripheral blood mononuclear cells using RNA-based analysis. Genomic ancestry proportions were estimated using ancestry-informative markers. RESULTS: FOXP3 mRNA expression was significantly reduced in NMOSD patients compared with controls (∼2.4-fold decrease in median expression; p = 0.027). Lower FOXP3 mRNA expression was associated with optic neuritis (p = 0.0059), but not with historical or current AQP4-IgG seropositivity. In a sensitivity analysis restricted to patients with documented historical AQP4-IgG seropositivity, the direction of reduced FOXP3 mRNA expression was preserved but did not reach statistical significance. In pre-specified exploratory ancestry-related analyses, African (p = 0.035) and Amerindian ancestry (p = 0.012) were associated with FOXP3 mRNA expression levels. CONCLUSIONS: Reduced FOXP3 mRNA expression in Peripheral Blood Mononuclear Cells (PBMCs) suggests an altered immune regulatory profile in NMOSD, potentially involving mechanisms beyond antibody-mediated immunity. The association between genetic ancestry and FOXP3 mRNA expression suggests that population-specific genetic background may influence immune regulatory pathways. These findings should be interpreted as exploratory and require validation in larger, clinically homogeneous cohorts.

Adolescent↗

PubMed2026

CRISPR-Cas and Infectious Diseases: A Decade of Translational Advances in Molecular Biotechnology.

CRISPR-Cas systems have emerged as a versatile tool for diagnosing, treating, and preventing infectious diseases. This review highlights translational advancements in CRISPR-Cas-based applications, concentrating on the past decades in diagnostics, therapeutic genome editing, and vaccine development. The article highlights key platforms like DETECTR and SHERLOCK, which enable rapid, sensitive pathogen detection, and explores CRISPR-Cas9 systems in therapeutic strategies for directly targeting viral genomes and combating antimicrobial resistance. It also examines the role of CRISPR-Cas9 in engineering live-attenuated and personalized neoantigen vaccines. Principal findings demonstrate a clear progression from experimental proof-of-concept to preclinical applications primarily in CRISPR-based diagnostics and the engineering of live-attenuated vaccine candidates, whereas translation in CRISPR-based therapeutics and personalized neoantigen vaccines for infectious diseases remains at earlier, more exploratory stages. CRISPR-based diagnostics have progressed further toward clinical evaluation than therapeutics due to delivery and safety constraints, while personalized neoantigen vaccines are included mainly as an emerging, comparative concept for infectious diseases rather than a mature application. This review uniquely integrates CRISPR-based diagnostics, therapeutics, and vaccine development within a single infectious disease framework, critically assesses their current maturity, and systematically highlights technical, regulatory, and ethical barriers alongside realistic future priorities. The review concludes that while CRISPR-Cas holds transformative potential for infectious disease management, significant challenges in delivery efficiency, off-target effects, and ethical regulation must be addressed to ensure safe and equitable clinical translation.

Humans↗

PubMed2026

Genetic diversity and recombination of NA-PRRSV field strains in Vietnam: Implications for vaccine efficacy.

Porcine reproductive and respiratory syndrome (PRRS) causes severe reproductive losses in pregnant sows and piglets, resulting in substantial economic impact on the swine industry worldwide. However, due to the significant genetic diversity and rapid evolutionary changes of the pathogen, continuous surveillance and detailed genetic analysis of circulating strains are essential. The current study aimed to evaluate the genetic diversity of the hypervariable (HV) region of non-structural protein 2 (nsp2) among North American PRRSV strains isolated from swine farms in Vietnam. Phylogenetic analysis and multiple sequence alignment were conducted to determine subtype classification and assess genetic variability. A total of 48 field isolates were obtained, of which 12.5% belonged to classical NA-PRRSV, 16.6% to NADC30-like and 70.9% to HP-PRRSV, primarily distributed across sublineages 1.4, 5.1, 8.7 and 8.9. Amino acid comparisons found multiple insertions, deletions and substitutions at various positions within the hypervariable region of nsp2. The study revealed substantial genetic variation in the HV region of nsp2 among NA-PRRSV field strains, largely associated with recombination and immune escape. These findings highlight epidemiological risks to vaccine efficacy and underscore the need for continuous molecular surveillance to support effective PRRSV control in Vietnam.

PRRSV↗

PubMed2026

A randomized trial of viral vector and adjuvanted protein HBV therapeutic vaccine in people with chronic hepatitis B on nucleos(t)ide analogs.

BACKGROUND: This study assessed the safety, efficacy, and immunogenicity of a therapeutic immunization strategy aimed at reaching a functional cure for chronic hepatitis B (CHB), relying on a heterologous prime-boost with viral vectors ChAd155-hIi-HBV and MVA-HBV, combined with sequential or concomitant administration of adjuvanted recombinant HBV proteins (HBc-HBs/AS01B). METHODS: This single-blind, randomized, controlled, first-in-human, phase 1/2 trial enrolled adults aged 18-65 years with HBeAg-negative CHB, virally suppressed on nucleos(t)ide analogs (NAs), with HBsAg >50 IU/mL. Participants received NAs and the following regimens of 4 doses (8-week intervals): sequential administration of ChAd155-hIi-HBV, MVA-HBV, and 2 HBc-HBs/AS01B doses; co-administration of ChAd155-hIi-HBV+HBc-HBs/AS01B, followed by 3 co-administered MVA-HBV+HBc-HBs/AS01B doses; 4 HBc-HBs/AS01B doses; 2 placebo doses followed by ChAd155-hIi-HBV and MVA-HBV administered alone or with HBc-HBs/AS01B; or 4 placebo doses. Safety, efficacy (≥1-log decrease in quantitative (q)HBsAg or HBsAg loss 24 weeks post-dose 4 [day (D)337]), antibody, and T-cell responses were evaluated. RESULTS: In all, 134 participants were vaccinated. Grade 3 solicited adverse events (AEs) (median duration: 2-3 days) were more frequent after co-administration (systemic: 59.3%; administration-site: 33.3%) than sequential administration (systemic: 10.3%; administration-site: 12.8%) of high-dose viral vectors and proteins. No vaccine-related or fatal serious AEs were reported. After 4 doses, no participant had HBsAg loss or ≥1-log decrease in qHBsAg (D337 vs. D1). Co-administration induced the strongest anti-HBs response (73.7% achieved anti-HBs ≥10 mIU/mL 2 weeks post-dose 4 vs. 40.0% after sequential administration). Both sequential and co-administration induced HBc-specific CD4+ and CD8+ T-cell responses, with a prime-boost effect of the viral vectors. CONCLUSIONS: Heterologous prime-boost with ChAd155-hIi-HBV and MVA-HBV, combined with sequential or co-administration of HBc-HBs/AS01B, had an acceptable safety profile, were moderately immunogenic, but no participants showed the expected efficacy outcome.

Humans↗

PubMed2026

A Duty to Act.

Explore the source record for details and available documents.

healthcare↗

PubMed2026

A User-Friendly Protocol for Microinjection into Teleost Embryos to Study Gene Function.

Zebrafish (Danio rerio) and medaka (Oryzias latipes) are popular teleost models used in developmental biology and functional genomics. To achieve high-quality and reproducible microinjections, it is essential to have robust protocols for breeding, egg collection, and the precise delivery of genetic material. In this protocol, we present a comprehensive and optimized methodology for setting up breeding tanks under controlled photoperiod conditions to maximize egg yield while minimizing contamination. We provide detailed procedures for sex identification, pair selection, the use of grated breeding inserts, and methods to increase egg collection efficiency. We outline procedures for making injection gel beds, pulling needles, and calibration using one-microliter microcapillaries to achieve consistent nanoliter-scale injections. Our protocol outlines settings for the pico-liter injector that are optimized to deliver a precise amount per pulse with minimal variability. Finally, we demonstrate the application of these methods for gene knockdown using morpholino antisense oligonucleotides, gene knockout using CRISPR-Cas9, and gain-of-function mRNA overexpression experiments. Phenotypic assessments conducted at various developmental stages to evaluate gene-specific effects reveal consistent phenotypic outcomes between the morpholino and CRISPR-Cas9 approaches. This easy and comprehensive protocol enables efficient, precise, and scalable genetic manipulation of zebrafish and medaka embryos, thereby supporting advanced functional studies in developmental biology and disease modeling. To our knowledge, this is the first unified protocol for both zebrafish and medaka microinjection systems achieving 97.7% phenotype penetrance in CRISPR-Cas9 knockouts with precision together with a triple validation approach that confirms gene function across multiple techniques.

Animals↗

PubMed2026

A Duty to Act.

Explore the source record for details and available documents.

healthcare↗

PubMed2026

Systematic review of the mutations in the active antigenic site Ø of the prefusion F protein of the Respiratory Syncytial Virus (RSV) following the implementation of monoclonal antibody prophylaxis.

BACKGROUND: Monoclonal antibody (mAb) nirsevimab, which targets the antigenic site Ø of the prefusion F protein (pre-F) of RSV, was introduced for RSV prophylaxis in several countries. METHODS: A systematic search was conducted between January 1, 2022, and July 31, 2026 for studies analyzing substitutions within the epitope of pre-F RSV protein, which is the target of nirsevimab, after the implementation of the mAb. We searched across PubMed, Scopus, Web of Science and ClinicalTrial.gov for studies involving children with confirmed RSV infection, that conducted genomic analysis. RESULTS: Seven studies (five observational and two randomized controlled trials) including 2156 RSV-positive samples (RSV-A: 1347, RSV-B: 809) were analyzed. RSV-A strains showed limited variability within antigenic site Ø, with K65R being the most common substitution and K209E being the only intermediate-resistance RSV-A substitution. RSV-B strains demonstrated substantially higher substitution frequencies, particularly involving I206M, Q209R, and S211N. Most identified substitutions appeared to represent naturally occurring polymorphisms and retained susceptibility to nirsevimab, while multiple RSV-B substitutions and combinations involving residues 64-68 and 204-208 demonstrated reduced susceptibility or high-level resistance. Resistance-associated variants were detected in 28 of 2156 (1.3%) RSV-positive samples and exclusively among nirsevimab breakthrough infections. In a sub-analysis restricted to nirsevimab-treated individuals, resistance-associated variants were significantly more frequent among RSV-B than RSV-A (9.8% vs 0.5%; p < 0.001). CONCLUSION: Most substitutions that were detected within the nirsevimab antigenic site reflect ongoing natural RSV evolution and do not significantly affect nirsevimab susceptibility. However, detection of resistance-associated variants highlights the importance of continuous genomic and phenotypic surveillance.

Humans↗

PubMed2026

Whole cell inactivated poly-bacterial preparation MV130 effect on nasal mucosal immunity and experimental human pneumococcal carriage: double-blind randomised controlled trial with controlled human infection model.

BACKGROUND: Bacterial mucosal immunotherapy has shown protection of children and adults from both viral and bacterial respiratory infections, offering the potential to reduce antimicrobial use, and hence also control antimicrobial resistance (AMR). Pneumococcal carriage of vaccine type Streptococcus pneumoniae remains high in Malawi despite infant conjugate vaccination and AMR is increasing. We compared nasal inflammation following sublingual bacterial immunotherapy including S. pneumoniae (MV130, Inmunotek, Spain) or placebo and determined the effect in an experimental human pneumococcal carriage model. METHODS: A double-blind, randomised, placebo-controlled trial in healthy adult volunteers was conducted at Queen Elizabeth Central Hospital in Blantyre, Malawi. Participants were randomly allocated to receive MV130 or placebo sublingually once daily for 42 days. Mucosal inflammation (neutrophil to T cell ratio, NTR) was measured in nasal micro-biopsies. Post-treatment, participants were challenged with 160,000 CFU/naris S. pneumoniae 6B (Spn6b). Experimental pneumococcal carriage rates post inoculation were compared between the two arms. All participants completing the study were included in the analysis. Prospective trial registration: PACTR202403820001276. FINDINGS: 107 participants were enrolled and randomised to MV130/placebo between May and December 2024. There were no serious adverse events, complete compliance was good (72%) and all adverse events were mild. 96 participants (53 male, 43 female) completed the study with 52 participants randomised to MV130 and 44 to placebo. There was no difference in mucosal inflammation (neutrophil to T cell ratio) at day 14 of the intervention MV130 NTR median = 0.737 (IQR 0.294, 2.059) and placebo NTR = 0.831 (IQR 0.450, 2.073), p = 0.64. Secondary analyses showed a rise in mucosal neutrophils after MV130 treatment and after experimental pneumococcal inoculation. There was no difference in nasal or serum anti-pneumococcal immunoglobulin or in experimental pneumococcal carriage proportion between MV130 (12/52, 23%) and placebo (10/44, 23%) groups (unadjusted risk ratio 1.02 (CI 0.49-2.12) p = 1.0). INTERPRETATION: MV130 induced non-specific mild neutrophil inflammation of the nasal mucosa but had no protective effect against experimental human pneumococcal carriage. FUNDING: Wellcome Trust.

Humans↗

PubMed2026

Comparative transcriptome analysis reveals ncRNA-mediated regulatory networks associated with muscle crispiness in grass carp.

Non-coding RNAs (ncRNAs) have been demonstrated to be involved in muscle development and to function as key regulators. However, the molecular mechanism underlying muscle crispiness in grass carp (GC) remains poorly understood, and whether these ncRNAs are involved in its regulation is still unknown. In the current investigation, differentially expressed (DE) RNAs (including lncRNAs, circRNAs, miRNAs, and mRNAs) were identified; concomitantly, target genes prediction was conducted, and functional and signaling pathway enrichment analyses were performed. Pathways related to muscle crispiness were identified, and the competitive endogenous RNA (ceRNA) (lncRNA/circRNA-miRNA-mRNA) regulatory network was further constructed. The results showed that a total of 126 DE-lncRNAs, 17 DE-circRNAs, 329 DE-miRNAs, and 442 DE-mRNAs were identified in muscle tissues of both the GC and crisp grass carp (CGC). GO and KEGG enrichment analyses revealed that target genes of DE-ncRNAs were significantly enriched in signaling pathways, including structural constituents of muscle, apoptosis, oxidative phosphorylation, and regulation of actin cytoskeleton, suggesting that these pathways may be involved in muscle texture remodeling. Subsequently, DE-RNAs enriched in related pathways were identified, and a core ceRNA regulation network comprising 3 lncRNAs, 4 circRNAs, 3 miRNAs, and 17 mRNAs was constructed. Additionally, 10 DE-RNAs from randomly selected groups were validated by qRT-PCR. Our findings not only provide scientific evidence elucidating the molecular mechanisms underlying muscle crispiness in GC but also establish a foundation for studying changes in muscle textural qualities across other fish species.

Animals↗

PubMed2026

Proteome-level evidence that tebuconazole, both alone and in interaction with thiacloprid, affects epigenetic events in bumblebee heads.

Tebuconazole, a widely used ergosterol biosynthesis-inhibiting fungicide, can affect nontargets, especially when combined with insecticides. We employed label-free quantitative proteomics to investigate the effects of long-term exposure to sublethal concentrations (100 μg/L) of tebuconazole, either by itself or alongside the neonicotinoid thiacloprid (100 μg/L), on the heads of Bombus terrestris workers. A Bayesian factor power analysis revealed that the experiment produced conclusive proteomic results. Tebuconazole treatment revealed eleven differentially abundant proteins, which increased elevenfold with thiacloprid. The proteins that changed in the same direction in both treatments suggest the occurrence of epigenetic events because they are involved in histone trimethylation (H3K4me3), pre-mRNA processing, and folate (vitamin B9) metabolism. Following co-exposure, the abundance of histone H2A.V and its associated proteins was affected. Two important detoxification-related proteins, CYP6BE1 and CYP6AQ1 (honey bee homologs), were identified, as well as proteins that suggest hormonal and neurotoxic effects. Overall, this study suggests that tebuconazole affects key epigenetic processes in bumblebee heads at the proteome level, though this was not confirmed at the biological level or through orthogonal methods. The tested chemicals were previously found to affect trimethylations, but not H3K4me3. We suggest analyzing the different trimethylations, their interplay, and associated hallmarks, such as folate levels. SIGNIFICANCE: The effects of pesticides and their combinations on organisms can be unexpected until they are examined using modern, complex methods. High-throughput proteomics can provide data on important biochemical processes affected by pesticides, offering a different perspective to that at the expression level. Despite their low acute toxicity, a group of fungicides that inhibit (ergo)sterol biosynthesis (EBI or SBI) are considered dangerous to pollinators, including bumblebees. This is due to the increasing toxicity of insecticides through the inhibition of cytochrome P450 detoxification enzymes. We found that tebuconazole had a similar effect on epigenetic events when used alone or in combination with the insecticide thiacloprid. Key proteins suggest that H3K4 histone trimethylation (H3K4me3) was impacted. To our knowledge, this expands the existing evidence suggesting that tebuconazole/triazole fungicides affect histone trimethylation H3K27me3. Since literature shows that thiacloprid affects H3K9me3, it is possible that thiacloprid and tebuconazole interact in these epigenetic events that affect each other. Overall, our results suggest that tebuconazole affects proteins involved in histone trimethylation, pre-mRNA processing, and folate metabolism. These are all hallmarks of epigenetic processes and were further extended by the co-exposure of tebuconazole and thiacloprid to more differently abundant proteins. Additionally, the results provide data on cytochrome P450s of the CYP6 family, which act as detoxifying proteins, as well as proteins that indicate hormonal and neurotoxic effects in bumblebee heads. Finally, the results of the Bayesian power analysis confirmed the meaningfulness of the proteomic data analyzed in this study. If the new findings obtained at the proteome level are verified by different methods, the full extent of the side effects of tebuconazole can be revealed.

Animals↗

PubMed2026

Emerging techniques of CRISPR/Cas system in antiviral therapy and diagnostics: Applications, limitations, and translational perspectives.

The CRISPR/Cas (clustered regularly interspaced short palindromic repeats) system is a versatile technology for developing antiviral medicines and editing viral genomes in both diagnostics and vaccine synthesis. Emerging insights into class 2 effectors, such as Cas9, Cas12, and Cas13, which target viral DNA and RNA, have revolutionized vaccines against viruses such as HIV, HPV, HBV, and EBV. Innovative diagnostic techniques such as SHERLOCK, DETECTR, and FELUDA have demonstrated system's diversity and accuracy in detecting the virus markers, supporting clinical decision-making, indicating adaptability and precision of CRISPR. This review critically evaluates CRISPR's role in RNA editing, emphasizing its importance for functional genomics and development of recombinant vaccines. Translational challenges are critically discussed, including off-target effects, delivery limitations, and ethical issues, for which unique approaches such as high-fidelity Cas variants, non-viral delivery systems, and bioethical frameworks are evaluated to address these limitations. This review also covers other social implications, such as accessibility and biosecurity risks, associated with CRISPR technologies Collectively, these advances underscore the transformative potential of CRISPR technologies in shaping next-generation antiviral diagnostics and therapeutics.

CRISPR-Cas Systems↗

PubMed2026

Histidine Supplementation Stabilizes Hearing and Vision and Improves Growth in HARS1-Related Autosomal Recessive Disorder Associated With Usher-Like Symptoms.

Autosomal recessive HARS1-related disorder (originally described as Usher syndrome type 3B) caused by a homozygous Y454S variant in the histidyl-tRNA synthetase gene (HARS1) is characterized by progressive sensorineural hearing and vision loss and respiratory deterioration with risk for sudden death following febrile illnesses. In-vitro studies have previously shown that histidine can rescue a humanized yeast model for pathogenic HARS alleles. Fourteen children homozygous for HARS Y454S were treated with supplemental oral histidine (50 mg/kg BID) and monitored with bloodwork and physical, visual, and audiometry assessments during a 3-year clinical trial, then followed for more than 4 years on histidine in the post-trial period. Patient fibroblasts were assessed for response to histidine. Hearing and vision remained stable, and growth improved significantly. Children remained healthy, with no severe deteriorations despite exposure to bacterial and viral infections, including COVID-19. Gains in growth were maintained in the post-trial period on varying levels of histidine supplementation. Daily oral histidine supplementation in children with autosomal recessive HARS1-related disorder can ameliorate or slow the progression of disease and is safe, inexpensive, and well tolerated. This study adds to the growing list of autosomal recessive ARSopathies (aminoacyl-tRNA synthetase disorders) that are amenable to amino acid supplementation.

Humans↗

PubMed2026

Translational reprogramming of TGF-β signaling via TRMT61A-mediated tRNA m1A drives prostatic fibrosis and hyperplasia.

Dysregulation of the epitranscriptomic landscape is closely linked to pathological proliferation, but its specific role in benign prostatic hyperplasia (BPH) remains unclear. Here, we identify the tRNA methyltransferase TRMT61A as a critical driver of BPH progression. We found that TRMT61A and global N1-methyladenosine (m1A) levels are aberrantly upregulated in human BPH tissues. Functionally, TRMT61A knockdown potently suppresses prostate cell proliferation and reduces stromal fibrosis, inducing G1 cell cycle arrest and reversing pathological remodeling both in vitro and in vivo. By integrating ribosome profiling (Ribo-seq) and tRNA-seq, we observed that TRMT61A drives translational reprogramming. TRMT61A preserves the stability of specific tRNA isoacceptors (e.g., tRNA-Leu-CAA), which is required for the efficient decoding of mRNAs containing m1A-dependent codons. Consequently, TRMT61A selectively promotes the translational elongation of the key receptor TGFβR1. This amplifies downstream TGF-β/SMAD signaling and drives epithelial-mesenchymal transition (EMT) without affecting mRNA transcription. In summary, our study reveals how TRMT61A drives BPH progression through TGFβR1 translation, highlighting the therapeutic potential of targeting epitranscriptomic pathways to reverse prostatic hyperplasia and fibrosis.

Male↗