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PubMed2025

Deep Characterisation of Circulating Torque Teno Virus DNA Load in Crohn's Disease Patients.

Torque teno virus (TTV) DNA load in plasma is suggested as a marker for immunosuppression post-transplantation. Crohn's disease (CD) arises from genetic susceptibility, environmental factors, and dysbiosis, causing immune responses. This study examines TTV DNA load in CD patients in remission and its correlation with relapse. Using quantitative real-time polymerase chain reaction (PCR) and metagenomic analysis, the dynamic of plasma TTV DNA load was analyzed from a cohort of CD patients (n = 39) over 1 year and compared with controls (n = 49). At inclusion, TTV DNA was significantly higher in CD patients compare to control (Median [IQR]: 3.27 [2.43-3.67] and 2.05 [1.28-2.80] Log copies/mL, p = 0.0004). Plasma TTV DNA load failed to predict disease relapse in CD patients. Augmented plasma TTV DNA levels in CD patients correlated with diminished circulating CD3 + T cells and especially CD4 + T cells. No preferential representation of TTV subspecies or Anelloviridae genera was detected in CD patients' plasma. This study revealed elevated TTV DNA levels in CD patients' plasma compared to healthy controls, underscoring the intriguing potential of TTV blood sampling as a biomarker in CD.

Humans↗

PubMed2026

Evaluating Associations Between Ankylosing Spondylitis, Torque Teno Virus and Polymorphisms in Interleukin 6 and Vitamin D Receptor Genes.

The etiology of ankylosing spondylitis (AS) is complex and not yet fully understood. Interleukin-6 (IL-6), vitamin D and the vitamin D receptor (VDR) play an important role in modulating immune response, and Torque teno virus is considered a marker of immune status. This case-control study aimed to investigate the predisposition to AS. A total of 85 patients with AS and 100 clinically healthy individuals were included. VDR polymorphisms (rs2228570, rs1544410, rs7975232, rs731236) were genotyped using the PCR-RFLP technique, while for the IL-6 -174 G>C (rs1800795) polymorphism the tetra-primer ARMS-PCR technique was used. The presence of TTV was detected using the hemi-nested PCR technique. Our findings indicate a statistically significant association between TTV and AS (p = 0.035). C allele of both rs1800795 polymorphism in main groups (p = 0.027) and rs731236 polymorphism in women subgroups (p = 0.036) may be linked to an increased susceptibility to AS. However, none of these associations reach statistical significance after Bonferroni correction. Furthermore, within female subgroups, a significant association was found between the T allele of rs1544410 polymorphism and AS (p = 0.000038, corrected p = 0.00076). A significant association was also observed between the TT genotype of rs2228570 polymorphism, TTV and AS (p = 0.029). Haplotype analysis revealed that certain VDR haplotypes may confer either a protective effect against AS or an increased risk of developing the condition. Notably, rs1544410 polymorphism or a linked polymorphism may influence AS susceptibility. In conclusion, our data suggest that TTV and VDR polymorphisms may be associated with an increased risk of developing AS, indicating that these markers could potentially be used in the future for earlier diagnosis and more targeted treatment of the disease.

Torque teno virus↗

PubMed2026

Effects of passive blood flow restriction on muscle function following exercise-induced muscle damage in recreationally active males.

This investigation examined the effects of passive blood flow restriction (pBFR) on indices of exercise-induced muscle damage (EIMD) in recreationally active males. Fifteen males completed six consecutive visits (±2 hours). Participants completed 3 × 25 maximal, unilateral, isokinetic (60°·s-1), concentric-eccentric leg extensions on both legs. Each leg was randomly assigned to receive pBFR (80% arterial occlusion pressure) or sham (20 mmHg) at 0, 24, 48, 72, and 96 hours post-EIMD. Perceived muscle soreness, range of motion (ROM), pain pressure threshold (PPT), concentric peak torque (CPT), and maximal voluntary isometric contraction (MVIC) torque were assessed and analyzed using separate linear mixed-effects models. Perceived muscle soreness increased at 24 hours (mean difference [meandiff] = 4.9 au; p < 0.001) and recovered by 96 hours (p = 0.482), with no differences between conditions (p = 0.450). ROM (meandiff = -3.1°; p = 0.040), PPT (meandiff = -1.63 kgf; p < 0.001), CPT (meandiff = -27.7 Nm; p < 0.001), and MVIC torque (meandiff = -30.8 Nm; p < 0.001) decreased at 24 hours, with recovery occurring between 48-96 hours. Condition-specific differences were observed for ROM (meandiff = 2.5°; p < 0.001), PPT (meandiff = 0.49 kgf; p = 0.005), CPT (meandiff = 6.2 Nm; p = 0.020), and MVIC torque (meandiff = 7.1 Nm; p = 0.044), which were greater in pBFR than sham. These findings suggested that pBFR may reduce impairments in ROM, PPT, CPT, and MVIC torque following EIMD, despite a similar recovery trajectory between conditions.

Humans↗

PubMed2026

Acute pre-exercise oral intake of cacao polyphenols attenuates central fatigue development during sustained low-intensity ankle dorsiflexion exercise in healthy young male adults.

This double-blind, randomized, crossover study investigated whether acute cacao polyphenol (CP) ingestion attenuates neuromuscular fatigue in 19 healthy young male adults. After consuming CP or placebo, participants performed sustained isometric ankle dorsiflexion at 25% of maximal voluntary isometric contraction (MVIC) torque until task failure. Neuromuscular function (MVIC torque, voluntary activation [VA%], doublet torque) and electromyographic activity were assessed before, immediately after, and during recovery (1 and 5 min). Salivary chromogranin A and α-amylase were measured at baseline and 1 min post-task. Only VA% and chromogranin A showed significant condition × time interactions (p = 0.027-0.039). VA% significantly decreased from before to immediately after the task and 1 min post-task in both conditions (p ≤ 0.002), with significantly higher values in the CP condition than in placebo immediately after and 1 min post-task (p ≤ 0.037). Chromogranin A significantly increased from baseline to 1 min post-task in the placebo condition (p < 0.001) but not in the CP condition (p = 0.083). These findings suggest that acute CP ingestion attenuates the decline in central motor drive and autonomic stress responses following strenuous exercise, without altering performance or peripheral recovery, supporting its potential as a nutritional strategy for modulating central fatigue.

Humans↗

PubMed2026

Effects of free-weight resistance training based on hexagonal barbell deadlift in older women: A 24-week randomized controlled trial.

PURPOSE: This randomized controlled trial examined effects of a 24-week hexagonal barbell deadlift (HBDL)-based free-weight resistance training program on body composition, trunk muscle function, and functional performance in older women. METHODS: Thirty-two women (67.6 ± 6.3 years) were randomly assigned to an HBDL group (DG, n = 16) or control group (CG, n = 16). DG trained twice weekly for 24 weeks under supervision. Primary outcomes were body composition and isokinetic trunk peak torque and average power at 60°/s and 120°/s. Secondary outcomes were isokinetic knee function, mobility, and maximal isotonic strength. Between-group differences after the intervention were examined by analysis of covariance (α = 0.05). RESULTS: After intervention, DG showed greater trunk lean mass (+0.4 kg vs. -0.2 kg, p = 0.006) than CG, and reductions in body fat percentage (-1.4% vs. +0.3%, p = 0.003), total fat mass (-1.1 kg vs. +0.3 kg, p = 0.013), and regional fat mass (trunk, gluteal, thigh; all p < 0.05). Trunk extensor peak torque at 60°/s (+26.0% vs. -6.3%, p < 0.001) and average power at 60°/s (+38.1% vs. -7.6%, p < 0.001) and 120°/s (+33.2% vs. +0.1%, p = 0.002) improved significantly. DG also showed better eyes-closed static balance and 6-min walk performance (both p < 0.05). Whole-body lean mass and lower-limb isokinetic strength did not differ between groups. Attendance was 89.6% with no adverse events. CONCLUSION: HBDL-based free-weight resistance training is a safe, feasible, and effective strategy to improve body composition, trunk extensor function, and mobility in older women.

Humans↗

PubMed2026

Muscle mechanical and architectural adaptations in response to different endurance training modalities in older adults.

INTRODUCTION: This study examined the effects of various cycling endurance training modalities, matched for total workload, on muscle mechanical and architectural characteristics in older adults. METHODS: Fifty healthy participants (25 females, 59-79 yrs) were randomly assigned to five age and sex matched groups: one control and four workload-matched training groups (moderate-intensity continuous, heavy-intensity continuous, high-intensity interval, and heavy-intensity continuous in eccentric cycling). Training consisted of three weekly sessions over 8 weeks, with evaluations conducted at the beginning and end of the intervention with maximal voluntary isometric contractions at five different knee angles (90, 75, 60, 45, 30°) and maximal concentric and eccentric isokinetic contractions at five different knee angular velocities (45, 90, 150, 210, 250°/s). Maximum voluntary isometric torque (Tmax) and optimal knee angle (KAopt) were obtained from the isometric contractions; eccentric torque (Tecc) and maximum concentric knee angular velocity (Vmax) were obtained from the isokinetic contractions. The muscle architecture of vastus lateralis (VL) at rest (muscle thickness, pennation angle, and fascicle length) was investigated as well. RESULTS: No statistical differences were detected between groups or time points in VL architecture, in KAopt and in Vmax. A main effect of time was observed for Tmax (p < 0.001, η2p = 0.458) and Tecc (p = 0.002, η2p = 0.191) in all the investigated training groups. The within-group comparisons indicate significant increases in Tmax in the training groups, but not in the control group. CONCLUSIONS: Commonly applied endurance exercises improve muscle mechanical capacity (Tmax and Tecc) in older adults, with no structural (architectural) muscle remodelling, when matched for workload.

Humans↗

PubMed2026

Comparing the Effects of Push and Hold Isometric Training on Strength and Musculotendinous Adaptations: A Within-Subject Randomized Controlled Trial.

Lum, D, Oranchuk, DJ, Chen, SE, and Kong, PW. Comparing the effects of push and hold isometric training on strength and musculotendinous adaptations: A within-subject randomized controlled trial. J Strength Cond Res 40(9): 1050-1058, 2026-Despite recent interest in delineating pushing (PIMA) and holding (HIMA) isometric muscle actions, training-induced adaptations have not been examined. As such, we compared the strength and morphological adaptations between PIMA and HIMA training. Twenty limbs across 10 adults (5 men, 5 women, age: 31.4 ± 6.5 years) were randomly assigned to PIMA or HIMA conditions and underwent 12 training sessions over 6 weeks. PIMA required subjects to exert force against a fixed lever while the HIMA limb maintained a set joint angle while resisting an isotonic lever. During each contraction, subjects had to exert force at 70% of maximal voluntary contraction for 20 seconds at an 80° knee angle, for 4-6 repetitions. Subjects completed isometric, concentric, and eccentric knee extension assessments for both limbs before and after the intervention. Pre- and postintervention ultrasound scans were performed to determine quadriceps muscle architecture and patellar tendon thickness. Increased isometric torque was found following both conditions (p < 0.05, g = 0.30-0.36), while concentric (p < 0.05, g = 0.31) and eccentric (p < 0.01, g = 0.50) torque only increased following PIMA. Both conditions increased muscle thickness (p < 0.05, g = 0.27-0.88) and vastus lateralis fascicle length (p < 0.05, g = 0.20-0.31). Only HIMA increased patellar tendon thickness (p < 0.05, g = 0.12). The increase in total quadriceps (p < 0.05, g = 0.46) and especially rectus femoris (p < 0.05, g = 1.44) thickness was greater in HIMA. The results suggest that PIMA may be more effective at improving strength, while HIMA may be superior for inducing morphological adaptations. Larger sample sizes and more ecologically valid training programs are warranted to further elucidate potential differences between different isometric types.

Humans↗

PubMed2026

Six weeks of isometric resistance training led to evidence of corticospinal but not reticulospinal adaptation in previously untrained adult males.

The latest hypothesis regarding the source of enhanced neural activation from resistance training is the reticulospinal rather than the corticospinal tract, based on invasive animal and emerging human data. The present study employed a six-week isometric resistance training intervention in a randomized controlled design to address this knowledge gap. Thirty-nine healthy, untrained males (age ~23 y, sustained contraction group n = 13, explosive contraction group n = 9, control group n = 17) underwent neuromuscular and electrophysiological testing and completed all study requirements. Maximal isometric torque (MVC) and rate of torque development (RTD) were measured during a familiarization session as well as before and after the six-week period. Transcranial magnetic stimulation was used to assess motor-evoked potential (MEP) area and silent period duration while subjects contracted to 10% of MVC. Loud sound (120 dB) was used to modulate MEP area and reaction time to visual stimuli during the StartReact test. Only the intervention groups demonstrated significant improvements in MVC (27%) and RTD (60%) (both P < 0.01), along with reduced MEP area (- 21%) and silent period duration (- 23%) (both P < 0.01). The sustained contraction group showed reduced modulation of reaction time and increased MEP suppression due to loud sound. Short-term resistance training seemed to reduce cortical inhibition and corticospinal excitability in both training groups. The study showed conflicting changes in measures purported to evaluate reticulospinal functioning. It is recommended to examine different forms of resistance training and longer training exposure in future.

Humans↗

PubMed2026

Effects of blood flow restriction training combined with plyometric training on lower limb muscle strength and motor unit recruitment in basketball players: An experimental study.

OBJECTIVE: Previous studies have shown that plyometric training (PT) improves neuromuscular function and explosive power but not maximal strength. Blood flow restriction training (BFR) combined with low-intensity resistance training (RT) increases muscle mass and strength. This study investigated the effects of PT, and BFR combined with PT on lower-limb muscle function. METHODS: Twenty elite basketball players were randomly assigned to two groups: PT-alone group (PT, n = 10) and BFR combine with PT group (PT-BFR, n = 10). All participants underwent bodyweight-based plyometric training three times per week for eight weeks. Peak torque values for hip and knee flexion and extension, as well as root mean square (RMS) values derived from electromyography, were measured before and after the intervention. RESULTS: After the 8-week intervention, both groups showed significant improvements in knee flexion and extension peak torque at 180°/s (all p < 0.01). Between-group comparisons revealed greater gains in the PT-BFR group for hip extension and flexion at 60°/s (p = 0.036-0.002; ηp2 = 0.225-0.233). RMS of the rectus femoris increased significantly more in the PT-BFR group than in the PT group (right: p = 0.004, ηp2 = 0.385; left: p = 0.020, ηp2 = 0.266), whereas no significant changes were observed in the gastrocnemius, tibialis anterior, or biceps femoris (all p > 0.05). CMJ height also improved more in the PT-BFR group, with a significant group × time interaction (p = 0.042, ηp2 = 0.210). CONCLUSION: Both training protocols enhanced bilateral lower-limb strength, with notable gains in the non-dominant leg; however, the magnitude did not differ substantially between groups. In contrast, compared with PT alone, BFR combined with PT produced superior enhancements in lower-limb muscle strength and neuromuscular recruitment. These findings suggest that when PT is employed to improve explosive power, it may be effectively combined with BFR to further augment muscular strength.

Humans↗

PubMed2025

Methylation patterns associated with TTV load in geriatric hospitalized patients: an exploratory functional analysis.

Torque Teno Virus (TTV) is a widespread commensal virus within the human virome, characterized by a high prevalence in human population and an unclear pathogenic role. Over the past three decades, TTV has garnered increasing attention due to its ability to establish lifelong chronic viremia, which intriguingly fluctuates among individuals in relation to immune competence status, with a typical peak after an organ transplantation, followed by a plateau and a slow decrease. The regulatory mechanisms underlying TTV infection remain elusive, and factors influencing its interactions with the immune system have yet to be identified. To explore this complex interplay, we analyzed DNA methylation patterns associated with TTV load in older adult hospitalized patients (mean age: 83.15 ± 7.49) from the PROMOTERA cohort. In this study, we present for the first time the identification of differentially methylated probes (DMPs) correlated to TTV load in our cohort. The statistically significant DMPs were located in genes involved in immune regulation and lipid metabolism. To further characterize these findings, we performed an exploratory enrichment analysis by applying several p-value thresholds, which yielded multiple gene lists derived from the sets of significant probes. Genes associated with this epigenetic signature were found to enrich functional pathways related to immune activation, leukocyte differentiation, and cytokine production, while additional significantly enriched gene sets were involved in cell-cell adhesion and cell migration processes. Since our analysis followed an exploratory approach, these results should be interpreted as hypothesis-generating and warrant further investigation.

Humans↗

PubMed2024

Characterization of the brain virome in human immunodeficiency virus infection and substance use disorder.

Viruses can infect the brain in individuals with and without HIV-infection: however, the brain virome is poorly characterized. Metabolic alterations have been identified which predispose people to substance use disorder (SUD), but whether these could be triggered by viral infection of the brain is unknown. We used a target-enrichment, deep sequencing platform and bioinformatic pipeline named "ViroFind", for the unbiased characterization of DNA and RNA viruses in brain samples obtained from the National Neuro-AIDS Tissue Consortium. We analyzed fresh frozen post-mortem prefrontal cortex from 72 individuals without known viral infection of the brain, including 16 HIV+/SUD+, 20 HIV+/SUD-, 16 HIV-/SUD+, and 20 HIV-/SUD-. The average age was 52.3 y and 62.5% were males. We identified sequences from 26 viruses belonging to 11 viral taxa. These included viruses with and without known pathogenic potential or tropism to the nervous system, with sequence coverage ranging from 0.03 to 99.73% of the viral genomes. In SUD+ people, HIV-infection was associated with a higher total number of viruses, and HIV+/SUD+ compared to HIV-/SUD+ individuals had an increased frequency of Adenovirus (68.8 vs 0%; p<0.001) and Epstein-Barr virus (EBV) (43.8 vs 6.3%; p=0.037) as well as an increase in Torque Teno virus (TTV) burden. Conversely, in HIV+ people, SUD was associated with an increase in frequency of Hepatitis C virus, (25 in HIV+/SUD+ vs 0% in HIV+/SUD-; p=0.031). Finally, HIV+/SUD- compared to HIV-/SUD- individuals had an increased frequency of EBV (50 vs 0%; p<0.001) and an increase in TTV viral burden, but a decreased Adenovirus viral burden. These data demonstrate an unexpectedly high variety in the human brain virome, identifying targets for future research into the impact of these taxa on the central nervous system. ViroFind could become a valuable tool for monitoring viral dynamics in various compartments, monitoring outbreaks, and informing vaccine development.

Male↗

PubMed2026

Genomic and structural insights into the atpB L173I substitution: modulation of the F₀ rotor architecture in Mycobacterium tuberculosis ATP synthase and altered Bedaquiline binding dynamics.

The F₀F₁ ATP synthase of Mycobacterium tuberculosis (M. tuberculosis) is an essential membrane-embedded rotary motor responsible for ATP synthesis and maintenance of the proton motive force in bacteria. The transmembrane F₀ domain comprises the c-subunit (atpE) and the a-subunit (atpB). Their coordinated interactions are needed for proton translocation and torque generation. Bedaquiline (BDQ), FDA-approved diarylquinoline for the treatment of multidrug-resistant tuberculosis (MDR-TB), targets the F₀ motor by binding at the a-c interface and inhibiting rotary catalysis. To the best of our knowledge, this study represents the first attempt to analyze the effects of mutations in the atpB protein on its structural stability in the F₀ domain, thereby highlighting the novelty of this work. In this study, we integrated Indian whole-genome sequencing (WGS) datasets (PRJNA37907) with long-timescale (1000 ns) membrane-embedded molecular dynamics (MD) simulations. Among 57 atpB mutations identified from WGS analysis, L173I was selected for structural and MD analysis. L173I is located at the atpB-atpE interface near the BDQ-binding region, despite V177L and S184A showing higher prevalence. Comparative MD simulations encompassed four systems: wild-type apo, wild-type with BDQ, L173I apo, and L173I with BDQ. Structural interrogation revealed that the L173I substitution induces subtle destabilization of the global fold of the atpB-atpE complex relative to the apo state, while more critically attenuating inter-subunit contacts between the a-subunit and the c-ring. These perturbations provide a mechanistic rationale for reduced BDQ susceptibility, arising from altered interfacial dynamics rather than complete abrogation of drug binding. This integrative genomic-structural framework advances our understanding of ATP synthase-mediated resistance in M. tuberculosis.

Diarylquinolines↗

PubMed2026

Gut Microbiome Composition Is Associated With Response to CD38 Antibody (Daratumumab) Treatment Among Relapsed Multiple Myeloma Patients.

INTRODUCTION: Growing data support interactions between host-gut microbes and treatment responses in multiple myeloma (MM), where a higher abundance of Eubacterium hallii in stool samples has been found among MM patients with negative minimal residual disease after induction therapy. Here, we evaluated changes in the gut microbiome associated with daratumumab (dara) based therapy in 40 MM patients, before and after therapy. PATIENTS AND METHODS: Patients with relapsed MM and prior autologous transplantation who had received 1 to 4 prior lines of therapy were eligible. Two stool samples were collected, one within 1 week prior to dara (predara) and one immediately after 4 doses of dara (postdara). Metagenomics sequencing was conducted. Microbiome taxonomic analyses were performed using MetaPhlAn4, and microbial functional pathway analyses were conducted using HUMAnN3.6. QIIME2 was used for compositional and statistical analyses. RESULTS: Of 40 participants enrolled, there were 5 nonresponders; 35 patients achieved partial response (PR) or better (responders). Among responders, 10 patients achieved complete remission (CR), and 25 patients achieved either very good partial response (VGPR) or PR. There were no statistically significant differences between overall pre and postdara gut microbiomes. Differential abundance analysis (ANCOM-BC) showed statistically significant (q ≤ 0.05) overgrowth of Alistipes finegoldii and Acidaminococcus intestini species in responders and Ruminococcus torques, Sellimonas intestinalis and Clostridium symbiosum in nonresponders. Compared to non-CR, CR samples showed enrichment of Faecalibacterium prausnitzii; non-CR samples were enriched in Segatella copri and Faecalimonas umbilicata. DISCUSSION/CONCLUSION: Our results suggest differences in species between clinical responders and nonresponders, but larger prospective studies are needed to confirm these results.

Clinical response↗

PubMed2026

Effects of exercise on muscle strength and characteristics in rheumatic diseases and sarcopenia: Protocol for the Care for Muscle (C4M) Study.

OBJECTIVE: Muscle weakness is prevalent in rheumatoid arthritis (RA), osteoarthritis (OA) and sarcopenia (SARC). Endurance exercises may improve mitochondrial function and oxidative capacity, while strength exercises are thought to stimulate myofibrillar protein synthesis. This study aims to compare the effects of strength and endurance exercise and explore the association between muscle characteristics and exercise outcomes in patients with RA, OA and SARC. We hypothesize that responses to endurance and strength exercises in patients with muscle weakness are influenced by intramuscular pathology including muscle morphology, mitochondrial function, and systemic inflammation, based on their disease pathology, potentially requiring personalized training schedules. METHODS: This two-arm, parallel-group exploratory trial will enroll 69 patients (23 RA, 23 OA, 23 SARC), randomized to endurance (n = 35) or muscle strength exercises (n = 34), using minimization to balance disease type and gender. The 8-week intervention includes two supervised sessions per week using a controlled cable pulley device (Reforter™) and fitness equipment, plus one weekly home-based session. The primary outcome is isokinetic muscle strength (peak torque), measured with the Biodex system®. Secondary outcomes include muscle morphology, mitochondrial function, systemic inflammation and muscle endurance (by Biodex and 6 Minute Walk test). Muscle morphology will be assessed via 3D ultrasound imaging of the vastus lateralis. Mitochondrial function will be analyzed using high-resolution respirometry on muscle biopsies. Systemic inflammation will be measured using multiplex assays or ELISA on serum samples. DISCUSSION: This study will explore differential responses to muscle endurance and muscle strength exercises in patients with RA, OA, and SARC, offering novel insights into the molecular mechanisms of muscle weakness. The findings may help identify potential mechanisms underlying variability in exercise response and provide effect size estimates to guide future confirmatory studies and more targeted exercise interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT06480643 (date of registration28-06-24).

Humans↗

PubMed2024

Role of the Pseudomonas plecoglossicida fliL gene in immune response of infected hybrid groupers (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂).

Pseudomonas plecoglossicida, a gram-negative bacterium, is the main pathogen of visceral white-point disease in marine fish, responsible for substantial economic losses in the aquaculture industry. The FliL protein, involved in torque production of the bacterial flagella motor, is essential for the pathogenicity of a variety of bacteria. In the current study, the fliL gene deletion strain (ΔfliL), fliL gene complement strain (C-ΔfliL), and wild-type strain (NZBD9) were compared to explore the influence of the fliL gene on P. plecoglossicida pathogenicity and its role in host immune response. Results showed that fliL gene deletion increased the survival rate (50%) and reduced white spot disease progression in the hybrid groupers. Moreover, compared to the NZBD9 strain, the ΔfliL strain was consistently associated with lower bacterial loads in the grouper spleen, head kidney, liver, and intestine, coupled with reduced tissue damage. Transcriptomic analysis identified 2 238 differentially expressed genes (DEGs) in the spleens of fish infected with the ΔfliL strain compared to the NZBD9 strain. Based on Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, the DEGs were significantly enriched in seven immune system-associated pathways and three signaling molecule and interaction pathways. Upon infection with the ΔfliL strain, the toll-like receptor (TLR) signaling pathway was activated in the hybrid groupers, leading to the activation of transcription factors (NF-κB and AP1) and cytokines. The expression levels of proinflammatory cytokine-related genes IL-1β, IL-12B, and IL-6 and chemokine-related genes CXCL9, CXCL10, and CCL4 were significantly up-regulated. In conclusion, the fliL gene markedly influenced the pathogenicity of P. plecoglossicida infection in the hybrid groupers. Notably, deletion of fliL gene in P. plecoglossicida induced a robust immune response in the groupers, promoting defense against and elimination of pathogens via an inflammatory response involving multiple cytokines.

Animals↗

PubMed2026

Transmission of Anellovirus From Kidney-Donor to Pediatric Recipient: An Exploratory Study.

BACKGROUND: Among the most abundant viruses in the human blood virome are anelloviruses, including alpha-, beta-, and gammatorqueviruses (TTV, TTMV, and TTMDV). Whether anelloviruses are transmitted through kidney transplantation at a young age and subsequently persist in their new host is unknown. This study investigates the dynamics and composition of the anellome in the blood of six pediatric donor-recipient pairs, with monitoring beginning before transplantation and continuing until 2 years after transplantation. METHODS: Donors were sampled once, before donation, while recipients were sampled before and multiple times after transplantation (median 6.5 samples). Quantitative PCR, rolling circle amplification, Illumina sequencing, and SCANellome V2 analysis were used to detect, characterize, and compare anellovirus presence in donors and recipients. RESULTS: At baseline, four out of six donors tested positive for TTV by quantitative anellovirus PCR, three of whom had sufficient viral loads to enable genomic comparison with their recipients. All recipients tested positive at baseline, five had a moderate viral load (< 105 copies/mL), and one had > 109 copies of TTV DNA/mL. This recipient was already immunosuppressed before transplantation, and only in this recipient was a donor-derived anellovirus identified. This lineage was detected among 15 other lineages in the recipient and matched one of the four lineages identified in the donor. CONCLUSION: This finding demonstrates that anellovirus transmission from donor to recipient occurs in pediatric kidney transplantation. This may be associated with pre-existing immunosuppression.

Humans↗