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PubMed2026

Randomized controlled trial comparing 7-day fexuprazan-based and 14-day rabeprazole-based triple therapies for Helicobacter pylori eradication.

BACKGROUND: Fexuprazan is a newly developed potassium-competitive acid blocker used for the treatment of acid-related gastrointestinal diseases; however, clinical data regarding its efficacy in Helicobacter pylori eradication are lacking. This study evaluated the efficacy and safety of a 7-day fexuprazan-based triple therapy regimen compared with a 14-day rabeprazole-based triple therapy regimen for H. pylori infection in Korean patients. METHODS: A randomized controlled single-center study was conducted to compare the eradication rates between 7-day fexuprazan (40 mg)-based triple therapy (with 1 g amoxicillin and clarithromycin 500 mg administered twice daily) and 14-day rabeprazole (20 mg)-based triple therapy for H. pylori eradication. The primary endpoint was the success rate of H. pylori eradication, determined using the 13C-urea breath test. Safety outcomes were also evaluated. RESULTS: A total of 79 patients were randomly assigned to the fexuprazan and rabeprazole groups. In the full analysis set, eradication rates were 80.00% (32/40) in the fexuprazan group and 82.05% (32/39) in the rabeprazole group. In the per-protocol set, eradication rates were 83.78% (31/37) and 88.89% (32/36), respectively (P = 1.000 and P =.737). The overall incidence of treatment-emergent adverse events was 70.00% (28/40) in the fexuprazan group and 66.67% (26/39) in the rabeprazole group, with no significant difference between groups (P =.812); both regimens were well tolerated. Among patients with clarithromycin-susceptible strains in full analysis set, eradication rates were 93.10% (27/29) in the fexuprazan group and 87.09% (27/31) in the rabeprazole group (P =.672). In the per-protocol set, eradication rates for susceptible strains were 96.42% (27/28) in the fexuprazan group and 93.10% (27/29) in the rabeprazole group (P = 1.000). CONCLUSION: Seven-day fexuprazan-based triple therapy demonstrated eradication efficacy comparable with that of 14-day rabeprazole-based therapy in treatment-naïve Korean patients with H. pylori infection. The fexuprazan-based regimen showed a similar safety profile and comparable incidence of adverse events with that of the rabeprazole-based regimen.

Humans↗

PubMed2026

Optimizing physical activity bouts to interrupt sedentary behaviour for cardiometabolic health: a systematic review and meta-analyses of randomized controlled trials.

AIMS: Chronic diseases such as type 2 diabetes mellitus and cardiovascular diseases are leading causes of mortality worldwide, with sedentary behaviour (SB) and physical inactivity recognized as major interrelated risk factors. Prolonged SB, particularly when combined with insufficient physical activity, adversely affects cardiometabolic health. This systematic review aimed to evaluate which characteristics of physical activity (PA) bouts, in terms of frequency, duration, and intensity, are associated with improvements in cardiometabolic outcomes. METHODS AND RESULTS: Studies assessing physical activity interventions compared with sedentary control conditions were included. Eligible studies involved adults aged 18-65 years, with or without cardiometabolic conditions. PubMed, Cochrane Central, Embase, and Web of Science were searched to February 2025. Random-effects models were used to calculate pooled standardized mean differences (SMD) with 95% confidence interval (CI). Subgroup and meta-regression analyses explored potential moderators. A total of 144 studies (247 intervention arms; 2216 participants) were included. Frequent PA bouts reduced blood glucose [SMD -0.22 (95% CI -0.27 to -0.16)]. Longer and/or more intense PA bouts decreased triglycerides [SMD -0.27 (-0.34 to -0.19)], with significant duration × intensity interactions for glucose (P = 0.032) and triglycerides (P < 0.001). Moderate-to-vigorous PA bouts improved endothelial function [flow-mediated dilation SMD 0.88 (0.47-2.24); shear rate SMD 0.54 (0.31-0.78)]. PA bouts also lowered insulin [SMD -0.26 (-0.32 to -0.19)], systolic BP [SMD -0.29 (-0.39 to -0.19)], and diastolic BP [SMD -0.16 (-0.26 to -0.05)]. CONCLUSION: In acute experimental settings, glucose regulation appears to benefit more from frequent PA bouts, while triglyceride responses are more closely related to greater duration and/or intensity. Blood pressure shows favourable acute responses across PA types, whereas higher PA intensity is associated with improved endothelial function. Tailoring strategies to interrupt SB with PA bouts may help inform approaches to improve cardiometabolic health.

Humans↗

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

Deimplementation of inappropriate feeding practices in early care and education: a Hybrid Type 3 cluster-randomized trial.

BACKGROUND: The science of deimplementation-reducing harmful or ineffective practices-has focused almost exclusively on clinical prescribing, with no studies conducted in community or educational settings. Early care and education (ECE) settings offer a strategic venue for shaping eating behaviors, with children consuming up to 500 meals annually in these environments. However, ECE educators routinely use feeding practices that undermine self-regulation, including pressuring children to eat, rushing mealtimes, and offering food as reward. These practices contribute to food aversions, diminished self-regulation, and obesity risk. METHODS: We will conduct a Hybrid Type 3 cluster-randomized trial evaluating a co-designed deimplementation strategy package (WISE Words) across 88 ECE sites in Arkansas and Louisiana. Sites will be randomized 1:1 to WISE Words or usual practice, with usual practice sites receiving the intervention after two years (waitlist design). WISE Words includes six strategies: dynamic training using improvisation methods, peer learning collaboratives with goal setting, external facilitation, audit and feedback, environmental reminders, and tailored educational materials. The primary outcome is de-adoption of inappropriate feeding practices measured via direct mealtime observation (Table Talk). Secondary outcomes include adoption of evidence-based practices, acceptability, appropriateness, and sustainability at 12- and 24-months post-intervention. Child outcomes include Body Mass Index, skin carotenoid levels (Veggie Meter) willingness to try new foods (observed) and food neophobia (teacher and caregiver report). An explanatory sequential mixed methods design will test mechanisms of change derived from the Implementation Trust Building Theory of Change examining whether trust mediates strategy effects on outcomes. DISCUSSION: This trial extends deimplementation science into community settings by targeting culturally embedded behavioral practices rather than clinical prescribing behaviors. Results will inform approaches to shifting entrenched practices in ECE and similar settings while testing trust as a deimplementation mechanism. Sustainability assessments will address a notable gap, as few studies have examined whether deimplementation effects persist. TRIAL REGISTRATION: NCT07101321, July 20, 2025.

Humans↗

PubMed2026

O'nyong-nyong virus adaptive mutations in non-structural protein 1 and 3 enhance RNA replication and overcome FHL1 requirement.

Arthritogenic alphaviruses, like o'nyong-nyong virus (ONNV), cause debilitating musculoskeletal diseases and are geographically expanding. To predict their emergence, we seek to better understand evolutionary mechanisms that enable changes in virus tropism. Here, we identify adaptive mutations in the ONNV non-structural proteins (nsPs) that arose during cellular serial passaging and enabled ONNV to infect non-permissive Lunet cells. Using shotgun proteomics, we show that this human hepatoma cell line lacks the four-and-a-half-LIM domain protein 1 (FHL1), an essential host factor in ONNV RNA replication. Individual single nucleotide mutations in the nsP1 ring-aperture membrane-binding and oligomerization domain, the nsP3 macrodomain, and the nsP3 opal stop codon overcome FHL1 deficiency in Lunet cells by enhanced RNA replication. These findings demonstrate how subtle genomic changes in nsPs can profoundly influence alphavirus replication and tropism.

LIM Domain Proteins↗

PubMed2026

Parallel evolutionary trajectories rewire enteropathogenic Escherichia coli adhesion to restore host attachment.

Enteropathogenic Escherichia coli (EPEC) causes disease in children, presenting as chronic diarrhea that can impair physical and cognitive development. The attachment of typical EPEC (tEPEC) to the gut epithelium via bundle-forming pili (BFP) is a key factor in its virulence. Yet, infections by atypical EPEC (aEPEC), which lack BFP, have become increasingly common. To investigate how aEPEC recover host-attachment in the absence of BFP, we performed experimental evolution using a non-adherent E. coli, constructed to mimic the ancestor of aEPEC, and selected adherent progeny. Highly adherent variants evolved through phase-variable activation of type I fimbriae (T1F), followed by two alternative trajectories: bacterial filamentation, which increases T1F avidity, or point mutations in the T1F adhesin FimH that enhance ligand affinity. Extending our analysis to the genomes of 327 aEPEC strains isolated from infected patients revealed that similar FimH mutations are common. We further demonstrated experimentally that these naturally occurring variants often increase epithelial-attachment. Our findings implicate T1F in aEPEC pathogenesis and suggest it may be clinically relevant for anti-adhesion therapy. More broadly, these results indicate that impaired host-attachment can be rapidly compensated by upregulating and optimizing an alternative adhesin, and that combining experimental evolution with comparative genomics can reveal evolutionary trajectories occurring in nature.

Bacterial Adhesion↗

PubMed2026

Proteomics-based analysis of the defense mechanisms of disease-resistant grass carp against Aeromonas veronii.

Sustainable aquaculture of grass carp (Ctenopharyngodon idella, GC) is consistently threatened by bacterial diseases, particularly those caused by Aeromonas veronii. A disease-resistant grass carp (DR-GC) has been developed by backcrossing female gynogenetic GC with normal male GC, exhibiting improved resistance. However, the systemic molecular mechanisms of DR-GC defending against Aeromonas veronii infection remain largely unexplored. Here, a label-free quantitative proteomics approach was employed to systematically compare proteomic profiles across five tissues (intestine, liver, muscle, skin, and kidney) in DR-GC and GC under healthy and infected conditions. The intestine was identified as the central defense tissue, exhibiting the highest number of differentially abundant proteins (DAPs). In DR-GC, A0A3N0YEK7 (small ribosomal subunit protein eS28), A0A3N0YGT8 (ATP synthase-coupling factor 6) and A0A3N0YNS7 (apolipoprotein A-I) were significantly upregulated in intestine, while D5KZW6 (GCHV-induced protein), A0A3N0Z0A1 and Q8JH84 (hemoglobin subunit alpha) were significantly dysregulated across multiple tissues, which playing the critical roles in defense mechanisms at the protein level. Furthermore, cytochrome P450-associated pathways, cytosolic DNA-sensing and RIG-I-like receptor signaling pathways were identified as crucial coordinators mediating immune and metabolic responses. This study provides the first comprehensive proteomic view of multi-tissue defense mechanisms in DR-GC, and identifies key DAPs and pathways for subsequent functional validation.

Animals↗

PubMed2028

Parental son preference in childhood and sex differences in the risk of cardiovascular disease in middle-aged and older adults.

INTRODUCTION: Sex differences in cardiovascular disease (CVD) risk are examined through biological and clinical factors, with less attention to early-life social exposures. This study examined associations of childhood parental son preference with CVD risk, sex differences, and mediation by modifiable risk factors. METHODS: This cohort analysis included China Health and Retirement Longitudinal Study participants aged ≥45 years without baseline CVD. Parental son preference was assessed retrospectively in 2014; incident CVD was self-reported physician-diagnosed heart disease or stroke through 2020. Sampling-weighted, community-clustered Cox models estimated adjusted hazard ratios (aHRs) and 95% CIs. Sex was prespecified as an effect modifier; mediation by 13 risk factors used inverse-odds-ratio weighting. Data were collected from 2011 to 2020 and analyzed from 2025 to 2026. RESULTS: Among 8,079 participants (mean age, 57.5 years; 4,216 women [52.2%]), 1,820 (22.5%) reported parental son preference. Son preference was associated with higher CVD risk overall (aHR 1.23 [95% CI 1.04, 1.46]) and among women (aHR 1.25 [95% CI 1.03, 1.53]); among men, the estimate was 1.16 (95% CI 0.87, 1.56), with limited heterogeneity by sex (ratio of aHRs 1.06 [95% CI 0.72, 1.58]). Among women, risk was concentrated in the highest paternal (aHR 1.47 [95% CI 1.14, 1.90]) and maternal (aHR 1.50 [95% CI 1.12, 1.99]) preference categories. Modifiable risk factors mediated 5.8% (95% CI 1.9%, 9.7%) of the association among women, mainly through socioeconomic and psychosocial factors. CVD risk was highest with both son preference and high risk-factor burden overall (aHR 1.97 [95% CI 1.43, 2.73]) and among women (aHR 2.23 [95% CI 1.61, 3.10]). CONCLUSIONS: Parental son preference was associated with higher incident CVD risk, with the largest estimates in the highest paternal or maternal categories among women. Modifiable risk factors explained a modest proportion, supporting life-course cardiovascular prevention that considers sex-differentiated childhood environments alongside risk-factor modification.

cardiovascular disease↗

PubMed2026

Extragenital testing for gonorrhea and chlamydia in health department clinics in Virginia, 2018-2023.

BACKGROUND: Extragenital testing for chlamydia and gonorrhea infections is now routine in many settings. We assessed temporal and demographic trends in extragenital testing and positivity in public health department clinics in Virginia. METHODS: We analyzed urogenital and extragenital chlamydia/gonorrhea laboratory results for clients aged 15 years or older who attended 116 health department clinics from 2018 to 2023. Test volume and positivity was stratified by anatomic site, year, sex, and age. RESULTS: There were 181,471 client visits with valid test results. The proportion of visits with any extragenital testing increased from 19% to 46% during this time. Male clients were twice as likely as females to receive pharyngeal testing (46% vs. 22%) and five times as likely to be tested rectally (15% vs. 3%). Rectal specimen positivity surpassed urogenital positivity for chlamydia (females and males) and gonorrhea (males only). Overall, one-quarter of clients diagnosed with gonorrhea infections were identified exclusively through extragenital testing, as were 9% of clients with positive chlamydia tests. These proportions increased over time and were greater for younger clients and for males relative to females. Two-thirds of extragenital infections would have been missed by urogenital testing alone, including 40% and 49% of females and 86% and 73% of males with extragenital chlamydia and gonorrhea infections respectively. CONCLUSIONS: The proportion of clients who received extragenital chlamydia/gonorrhea testing increased over time, extragenital test positivity was high, and it identified infections that would have been missed otherwise. The impact on sexually transmitted infection sequelae and transmission remains unclear.

NAAT↗

PubMed2026

Tuberculosis in children who are HIV-exposed uninfected.

OBJECTIVES: 1.3 million children are born each year to mothers with HIV but remain HIV-uninfected; more than 70% of these children live in settings with high tuberculosis (TB) burden. Whether children who are HIV-exposed uninfected (cHEU) are at increased risk of TB infection and disease is debated. DESIGN: We performed a systematic review and meta-analysis of TB infection and disease in cHEU versus children who are HIV-unexposed uninfected (cHUU) and children with HIV (CWH). METHODS: We searched PubMed, Embase, Web of Science, the Cumulative Index to Nursing and Allied Health Literature, and publication bibliographies through October 2025, using terms related to gestational HIV exposure and TB. We performed a qualitative synthesis and a meta-analysis of TST/IGRA positivity prevalence and disease cumulative incidence in cHEU versus cHUU, and cHEU versus CWH. RESULTS: : We included 26 studies in a systematic review and 18 studies in meta-analyses; 21/26 (81%) studies were restricted to children less than 2 years of age. Prevalence of TST/IGRA positivity [RR 1.26; 95% confidence interval (CI) 0.92-1.72, I2  = 0.0%] and cumulative disease incidence (RR 0.72; 95% CI 0.48-1.08, I2  = 0.0%) were similar between cHEU and cHUU. Prevalence of TST/IGRA positivity (RR 0.24; 95% CI 0.02-3.91, I2  = 93.2%) was not significantly different between cHEU and CWH. cHEU had lower risk of TB disease cumulative incidence than CWH (RR 0.29; 95% CI 0.16-0.51, I2  = 71.5%). CONCLUSION: cHEU and cHUU experience similar risk of TB infection and disease, while cHEU experience lower risk of disease than CWH. Findings were limited by a lack of studies after infancy and a small number of studies.

Humans↗

PubMed2026

Characteristics of children with ureteroceles presenting for urological evaluation in the modern medical era.

INTRODUCTION: Historically, children with ureteroceles presented symptomatically and were managed surgically. It is unclear if this changed in the modern medical era of prenatal imaging and shared decision making. We aimed to describe the presentation and management of ureteroceles during initial urological evaluation of children in the era of widespread prenatal ultrasonography. PATIENTS AND METHODS: We retrospectively reviewed records of children (<18 years old [yo]) initially evaluated at our center with a ureterocele (2011-2020). We analyzed demographics, renal anatomy, initial presentation for evaluation, and initial management with non-parametric statistics. Febrile urinary tract infections (fUTIs, ≥ 38 °C) were classified as 1) urosepsis (positive urine culture admitted to pediatric intensive care), 2) documented (positive urine culture) or 3) family-reported. RESULTS: We identified 188 children (65% female). Median age at presentation was 1.2 months old (mo) (IQR 18 days-4.4 mo). Antenatally-detected congenital anomalies of the kidney and urinary tract (aCAKUT) were noted in 143 (76%) children with a confirmed postnatal diagnosis of ureterocele. Overall, 129/188 (69%) children presented without symptoms and 59 (31%) presented with symptoms. fUTI was the most common symptomatic presentation (46/188, 24%): urosepsis (6 children), documented (30), and family-reported (10). Children with aCAKUT presented earlier than those without aCAKUT (27 days vs. 1.6 yo, p < 0.0001). They were also less likely to present with symptoms (11% vs. 96%, p < 0.0001), including fUTIs (7% vs. 78%, p < 0.0001). In total, 108 children (57%) were initially managed with transurethral incision, 73 (39%) were observed, and 7 (4%) had reconstructive surgery. Asymptomatic children with aCAKUT (42%) and symptomatic children without aCAKUT (37%) were more likely to be observed than symptomatic children with aCAKUT (7%, p = 0.02). Among 143 children with aCAKUT, those on antibiotic prophylaxis were less likely to present with a history of a fUTI compared to those not on prophylaxis (4/106 vs. 6/37, 4% vs. 16%, p = 0.02). COMMENT: We present a large observational study describing clinical and anatomical characteristics of children presenting with ureteroceles in a medical era of ubiquitous prenatal ultrasonography. Our retrospective study was limited by incomplete documentation of all antenatal ultrasonography and adherence with antibiotic prophylaxis. Long-term clinical outcomes will be the focus of future work. CONCLUSION: In contrast to historical cohorts, most children presented to urologists with asymptomatic ureteroceles diagnosed with aCAKUT. Most children without aCAKUT presented with a fUTI. Overall, 39% of children were initially observed, indicating an increased use of observation in the modern medical era.

Humans↗

PubMed2026

Flexible ureteroscopy with a flexible and negative suction ureteral access sheath versus traditional sheath for treatment of infectious upper urinary tract stones: A prospective, randomized controlled study.

To evaluate the efficacy and safety of the flexible ureteroscopy (fURS) with a flexible and negative suction ureteral access sheath (FANS) versus traditional sheath for patients with infectious upper urinary tract stones (IUUTS). A total of 185 patients were enrolled, with 93 assigned to the FANS group and 92 to the traditional UAS group. The primary outcome was the stone-free rate (SFR) at the first postoperative day. Secondary outcomes included the SFR at 30 days postoperatively, operative time, hemoglobin reduction, length of hospital stay, quality of life (QoL) improvement, incidence of ureteral stricture at 3 months, and surgery-related complications. No significant differences were observed between the two groups in baseline demographics or preoperative clinical characteristics (P > 0.05). The FANS group had significantly lower white blood cell count, C-reactive protein, and procalcitonin levels at 6 and 24 h postoperatively (all P < 0.05). Mean operative time was significantly shorter (P < 0.001), QoL improvement was obviously greater (P < 0.001), and average hospital stay was shorter in the FANS group (P < 0.001). The SFRs on postoperative day 1 and at 30 days were both significantly higher in the FANS group (both P < 0.05). At 3 months, ureteral strictures occurred in three patients in the traditional UAS group and one in the FANS group, a difference that was not statistically significant (P > 0.05). The overall complication rate was significantly lower in the FANS group (P < 0.05). For patients with IUUTS, fURS combined with FANS effectively improves stone clearance efficiency and reduces the risk of postoperative infection.

Humans↗

PubMed2026

Hypoxaemia and mortality in children with lower respiratory infection in low-income and middle-income countries: systematic review and meta-analysis.

BACKGROUND: Hypoxaemic lower respiratory infections (LRIs) are a leading cause of childhood mortality, with the highest burden in low-income and middle-income countries (LMICs). Hypoxaemia-low peripheral capillary oxyhaemoglobin saturation (SpO2)-is a marker of severity, and WHO recommends hospitalisation and oxygen administration for patients with SpO2 <90%. We aimed to update estimates from a 2015 systematic review and meta-analysis examining the association between hypoxaemia and mortality among children with LRIs in LMICs by incorporating studies published over the subsequent decade and evaluating mortality risk across multiple SpO2 thresholds. METHODS: We conducted a systematic review with meta-analysis by searching PubMed, Embase, LILACS, Global Index Medicus, Web of Science, and Scopus for peer-reviewed studies published between Jan 1, 2015, and June 18, 2025, with combined terms related to pneumonia, children, mortality, and LMICs. We also included selected earlier studies through citation checking. Eligible studies reported associations between hypoxaemia and mortality in children younger than 5 years with LRIs in LMICs. We excluded case reports and case series with fewer than five deaths, studies focused exclusively on the neonatal period, and those limited to children with specific comorbidities or to postoperative patients, for consistency with the original review. Two reviewers independently screened studies, extracted data, and assessed quality. Eligible studies were combined with those from the original review and analysed using random-effects models to estimate odds ratios (ORs) by hypoxaemia threshold subgroup. The protocol was registered on PROSPERO (CRD42023433946). FINDINGS: We identified 7734 records; 26 new studies met inclusion criteria and were combined with 18 from the original review. The 44 studies were published between 1993 and 2024 and were primarily from Africa (25 [57%] of 44) or Asia (19 [43%]); some studies spanned multiple locations. Data from 33 studies including 155 633 participants were included in the primary meta-analysis. Hypoxaemia of any threshold was associated with higher odds of LRI mortality (OR 4·36 [95% CI 3·52-5·39]) compared with no hypoxaemia. For SpO2 <90% versus 90-100%, OR for death was 4·75 (95% CI 3·42-6·58). For SpO2 90-94% versus 95-100%, mortality risk was more than twice as high (OR 2·27 [95% CI 1·22-4·25]). Heterogeneity was substantial (I2 64-85% across analyses), and eight (24%) of 33 studies in the primary meta-analysis had a high overall risk of bias; however, a sensitivity analysis restricted to studies with low or moderate risk of bias yielded similar results. INTERPRETATION: SpO2 <90% strongly predicts mortality in children with LRIs in LMICs. Children with SpO2 90-94% also have elevated risk, suggesting that paediatric LRI and pneumonia treatment algorithms should consider management at this hypoxaemia threshold. FUNDING: None.

Journal Article↗

PubMed2026

Whole-transcriptome RNA sequencing and ceRNA network analyses provide novel insights into the antibacterial immune response of Hippocampus abdominalis against Vibrio harveyi.

Long non-coding RNAs (lncRNAs) stand as newly-arisen molecular types that exert regulatory effects, able to operate as competitive endogenous RNAs (ceRNAs) to engage microRNAs (miRNAs) in interaction, resulting in the recovery of target mRNA expression and activity. Increasing evidences indicate that the ceRNA network affects various biological processes in mammals, including development, cellular differentiation, metabolism, immune response, and disease pathogenesis. In teleost fish, the lncRNA-miRNA-mRNA regulatory networks have been reported occasionally. However, up to now, the roles of lncRNAs in the big-belly seahorse (Hippocampus abdominalis) remains unclear. In this study, we reported for the first time, via whole-transcriptome RNA sequencing, the lncRNA mediated ceRNA regulatory network in Vibrio harveyi-infected H. abdominalis. A total of 4197 differentially expressed mRNAs (DE-mRNAs), 1317 DE-lncRNAs, and 183 DE-miRNAs were identified. Furthermore, the crosstalk between miRNAs and lncRNAs as well as between miRNAs and mRNAs was inferred based on the negative correlations between miRNAs and their target lncRNAs/mRNAs. A core immune associated lncRNA-miRNA-mRNA putative regulatory network was thus constructed, comprising 211 lncRNA-miRNA and 224 mRNA-miRNA pairs. In conclusion, our findings provide an integrative overview of the ceRNA regulatory networks on the underlying immune responses to V. harveyi infection in the big-belly seahorse, and offer a solid theoretical foundation for the comparative immunological research of teleost fish.

Animals↗

PubMed2026

Suppression of HIV-1 replication in CEM-A cell cultures by trans-splicing group I introns targeting PAS/PBS sequences and conditionally expressing ΔN-Bax.

Anti-HIV group I introns containing antisense guide sequences directed against the HIV-1 primer activation signal and primer-binding site (PAS/PBS) were designed and evaluated. Because PAS/PBS sequences are present in the viral RNA species examined, these RNAs can serve as trans-splicing substrates. The introns were active against both artificial target RNAs and viral RNA generated during infection. Cleavage and degradation of targeted viral RNA may have contributed to suppression, whereas inclusion of a 3' exon encoding the proapoptotic protein ΔN-Bax was associated with increased programmed cell death and may have augmented suppression of viral replication. In cultured CEM-A cells, transgene expression of these introns markedly suppressed HIV-1 replication, with p24 levels falling below the assay detection limit in selected clones. RESULTS: RT-PCR and sequence analysis detected splice products containing the expected PAS/PBS junctions. In the dual-luciferase assay, intron expression reduced normalized Gaussia luciferase signal by approximately 70% relative to the negative control. Qualitative Annexin V imaging and caspase-3 assays were consistent with infection-dependent apoptosis after ΔN-Bax splice-product formation. Transient expression of each intron in HEK293T cells followed by infection with VSV-G-pseudotyped HIV-1NL4-3 at an MOI of 2 reduced p24 levels by approximately 50% at 4 days post-infection. Construct 128L produced the strongest RT-PCR band under the tested conditions and was selected for subsequent experiments. A canonical splice product and a low-abundance noncanonical splice product were detected; both involved the intended HIV-derived target RNA, although transcriptome-wide off-target splicing was not assessed. Heterogeneous transformed HEK293T populations showed an approximately 2-log10 reduction in p24. In selected clonal HEK293T and CEM-A lines, p24 was below the assay detection limit at the measured endpoints, including up to 90 days after infection in some CEM-A clones. CONCLUSIONS: PAS/PBS-targeting group I introns suppressed HIV-1-associated p24 production in the tested cell-culture models. Linking the introns to a ΔN-Bax 3' exon was associated with infection-dependent apoptosis and may further limit viral replication and spread. The use of highly conserved, functionally constrained target sequences may reduce the likelihood of escape, but viral evolution and transcriptome-wide off-target effects were not assessed. This conditional death-upon-infection strategy warrants further evaluation in primary-cell and in vivo models.

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

Emerging hantavirus risks in mass gatherings: epidemiology, diagnostic challenges, and outbreak preparedness.

Hantaviruses are emerging rodent borne zoonotic pathogens of increasing global public health concern because of their high mortality, expanding ecological distribution, and potential for international dissemination. Although traditionally associated with sporadic rural outbreaks, recent ecological disruption, climate variability, urbanization, and increased global mobility have heightened concerns regarding hantavirus risks in mass gathering settings. This review critically examines the epidemiology, transmission uncertainty, diagnostic and surveillance challenges, and preparedness strategies related to hantavirus infections in the context of mass gatherings, including religious events, refugee settlements, cruise tourism, sporting events, and temporary accommodations. Particular emphasis is placed on the 2026 multinational cruise ship associated outbreak linked to the MV Hondius, which highlighted vulnerabilities related to delayed diagnosis, international passenger dispersal, and uncertainties surrounding possible human to human transmission of Andes virus. Current evidence indicates that hantavirus transmission occurs primarily through inhalation of aerosolized rodent excreta; however, controversies regarding limited interpersonal transmission, environmental persistence, and asymptomatic infections continue to complicate risk assessment and outbreak preparedness. Diagnostic limitations, underreporting, insufficient environmental surveillance, and lack of mass gathering specific preparedness frameworks remain major public health challenges, especially in resource limited settings. Strengthening proactive preparedness through integrated One Health approaches, ecological surveillance, genomic monitoring, AI driven epidemic intelligence, and coordinated international response systems is essential for mitigating future risks. The review emphasizes the urgent need for multidisciplinary research and evidence based policy development to improve global preparedness against emerging hantavirus associated threats in increasingly interconnected mass gathering environments.

Humans↗

PubMed2026

Molecular Diagnostics for WHO Priority Bacterial Pathogens: A Bibliometric Mapping of Diagnostic Platforms, Resistance Markers, and Antimicrobial Resistance Research Trends.

Antimicrobial resistance (AMR) constrains effective treatment and carries implications for infection control, surveillance, and public health. The World Health Organization (WHO) priority bacterial pathogen framework has intensified the need for diagnostic innovation by redefining research priorities around organisms combining high disease burden with complex resistance profiles. Molecular diagnostics have accordingly moved beyond culture-based workflows, integrating rapid pathogen identification, resistance-marker detection, genomic surveillance, and clinical decision support. The present study conducted a bibliometric mapping of the literature on WHO priority pathogens. Rather than addressing resistance at a general level or a single pathogen or technology, it integrates priority pathogens, molecular platforms, and resistance markers within a single framework, tracing their joint thematic and temporal evolution along an explicit pathogen-platform-marker axis. Scopus-indexed articles and reviews (2000-2025) were retrieved, yielding 1746 publications after screening adapted from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Analyses used Bibliometrix/Biblioshiny, R, and VOSviewer. The literature expanded markedly after 2018, led by China and the United States. Methicillin-resistant Staphylococcus aureus (MRSA), Mycobacterium tuberculosis, Enterococcus faecium, and the Enterobacterales-carbapenemase axis constituted the principal thematic cores, whereas conventional polymerase chain reaction (PCR)/nucleic acid amplification testing (NAAT) and whole-genome sequencing were the dominant platforms. Overall, the field has evolved from pathogen detection into an AMR-centered translational domain encompassing resistance prediction, genomic epidemiology, surveillance, and clinical decision support. Diagnostic development, stewardship, and surveillance depend on hybrid workflows coupling rapid marker-targeted assays with genome-based characterization, delivering actionable resistance within clinically meaningful timeframes, and extending coverage to underrepresented pathogens and platforms.

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