Human Cytomegalovirus Encoded miR-US25-1-5p Attenuates CD147/EMMPRIN-Mediated Early Antiviral Response.

Cellular receptor-mediated signaling pathways play critical roles during the initial immune response to Human Cytomegalovirus (HCMV) infection. However, the involvement of type-I transmembrane glycoprotein CD147/EMMPRIN (extracellular matrix metalloproteinase inducer) in the antiviral response to HCMV infection is still unknown. Here, we demonstrated the specific knockdown of CD147 significantly decreased HCMV-induced activation of NF-κB and Interferon-beta (IFN-β), which contribute to the cellular antiviral responses. Next, we confirmed that HCMV-encoded miR-US25-1-5p could target the 3 UTR (Untranslated Region) of CD147 mRNA, and thus facilitate HCMV lytic propagation at a low multiplicity of infection (MOI). The expression and secretion of Cyclophilin A (sCyPA), as a ligand for CD147 and a proinflammatory cytokine, were up-regulated in response to HCMV stimuli. Finally, we confirmed that CD147 mediated HCMV-triggered antiviral signaling via the sCyPA-CD147-ERK (extracellular regulated protein kinases)/NF-κB axis signaling pathway. These findings reveal an important HCMV mechanism for evading antiviral innate immunity through its encoded microRNA by targeting transmembrane glycoprotein CD147, and a potential cause of HCMV inflammatory disorders due to the secretion of proinflammatory cytokine CyPA

Genome-Wide Identification and Salt Stress Response Analysis of the bZIP Transcription Factor Family in Sugar Beet

As one of the largest transcription factor families in plants, bZIP transcription factors play important regulatory roles in different biological processes, especially in the process of stress response. Salt stress inhibits the growth and yield of sugar beet. However, bZIP-related studies in sugar beet (Beta vulgaris L.) have not been reported. This study aimed to identify the bZIP transcription factors in sugar beet and analyze their biological functions and response patterns to salt stress. Using bioinformatics, 48 BvbZIP genes were identified in the genome of sugar beet, encoding 77 proteins with large structural differences. Collinearity analysis showed that three pairs of BvbZIP genes were fragment replication genes. The BvbZIP genes were grouped according to the phylogenetic tree topology and conserved structures, and the results are consistent with those reported in Arabidopsis. Under salt stress, the expression levels of most BvbZIP genes were decreased, and only eight genes were up-regulated. GO analysis showed that the BvbZIP genes were mainly negatively regulated in stress response. Protein interaction prediction showed that the BvbZIP genes were mainly involved in light signaling and ABA signal transduction, and also played a certain role in stress responses. In this study, the structures and biological functions of the BvbZIP genes were analyzed to provide foundational data for further mechanistic studies and for facilitating the efforts toward the molecular breeding of stress-resilient sugar beet

Determinants of HPV vaccine uptake intentions in Chinese clinical interns: an extended theory of planned behavior approach

BackgroundThis study aims to utilize the extended Theory of Planned Behavior (TPB) model to examine the intentions of clinical interns in China towards Human papillomaviruses (HPV) vaccination. It also fills a significant gap in the literature concerning vaccine acceptance in this specific population.MethodsThis cross-sectional study was carried out with clinical interns in Shandong Province, China, with a total of 1,619 participants. Data were collected through self-reported questionnaires, including demographic characteristics, TPB variables, and HPV-related health knowledge. Hierarchical regression analysis was employed to identify key factors influencing vaccination intentions, and Structural Equation Modeling (SEM) was used to analyze the interrelationships between these factors.ResultsThis study initially identified key predictors affecting clinical interns’ intentions to receive the HPV vaccine through hierarchical regression analysis. The preliminary model, which accounted for demographic factors, revealed foundational impacts of household income and HPV-related clinical experience on intentions. After integrating TPB variables—attitude, subjective norm, perceived behavioral control, and HPV-related health knowledge—the model’s explanatory power was enhanced to 37.30%. SEM analysis focused on the interplay among TPB constructs and extended variables, confirming their significance in forming vaccination intentions, with subjective norm having the most substantial impact (β = 0.375, p < 0.001). The extended TPB model explained over half of the variance in vaccination intentions, substantiating the hypotheses and revealing the psychological determinants behind clinical interns’ decision-making for HPV vaccination.ConclusionThe extended TPB model from this study effectively explains the vaccination intentions among clinical interns for HPV, offering theoretical support for public health strategies and educational interventions targeting this group. These findings are of significant importance for public health practice and future health promotion strategies

Isolation of Low-Abundant Bacteroidales in the Human Intestine and the Analysis of Their Differential Utilization Based on Plant-Derived Polysaccharides

Bacteroidales are the most abundant Gram-negative bacteria flourished in the human intestine with great underlying benefits to be discovered and developed as the next-generation probiotics. However, the traditional isolation method limits the mining of low-abundant species. In this study, modified selective medium was established using xylan as the sole carbohydrate source to enrich low-abundant species such as Prevotella copri and Bacteroides xylanisolvens from healthy human fecal samples. The growth rate, transcriptomics, and metabolomics profiles of the enriched low-abundant species were then evaluated. The considerable upregulated genes encoding xylan-associated hydrolysis and transportation, along with the increased xylose production detected in the culture of the enriched Bacteroidales strains based on xylan, were considered as positive proof of the feasibility of the modified methodology

Pilot Safety Evaluation of a Novel Strain of Bacteroides ovatus

Bacteroides ovatus ELH-B2 is considered as a potential next-generation probiotic due to its preventive effects on lipopolysaccharides-associated inflammation and intestinal microbiota disorders in mice. To study safety issues associated with B. ovatus ELH-B2, we conducted comprehensive and systematic experiments, including in vitro genetic assessments of potential virulence and antimicrobial resistance genes, and an in vivo acute toxicity study of both immunocompetent and immunosuppressed mice via cyclophosphamide treatment. The results indicated that this novel strain is non-toxigenic, fragilysin is not expressed, and most of potential virulence genes are correlated with cellular structures such as capsular polysaccharide and polysaccharide utilizations. The antibiotic resistance features are unlikely be transferred to other intestinal microorganisms as no plasmids nor related genomic islands were identified. Side effects were not observed in mice. B. ovatus ELH-B2 also alleviated the damages caused by cyclophosphamide injection

Associations between Interleukin-31 Gene Polymorphisms and Dilated Cardiomyopathy in a Chinese Population

To explore the role of Interkeulin-31 (IL-31) in dilated cardiomyopathy (DCM), in our study, two SNPs of IL-31, rs4758680 (C/A) and rs7977932 (C/G), were analyzed in 331 DCM patients and 493 controls in a Chinese Han population. The frequencies of C allele and CC genotype of rs4758680 were significantly increased in DCM patients (P = 0 005, P = 0 001, resp.). Compared to CC genotype of rs4758680, the A carriers (CA/AA genotypes) were the protect factors in DCM susceptibility while the frequencies of CA/AA genotypes were decreased in the dominant model for DCM group (P < 0 001, OR = 0.56, 95%CI = 0.39-0.79). Moreover, IL-31 mRNA expression level of white blood cells was increased in DCM patients (0.072 (0.044-0.144) versus 0.036 (0.020-0.052), P < 0 001). In survival analysis of 159 DCM patients, Kaplan-Meier curve revealed the correlation between CC homozygote of rs4758680 and worse prognosis for DCM group (P = 0 005). Compared to CC genotype, the CA/AA genotypes were the independent factors in both univariate (HR = 0.530, 95%CI = 0.337-0.834, P = 0 006) and multivariate analyses after age, gender, left ventricular end-diastolic diameter, and left ventricular ejection fraction adjusted (HR = 0.548, 95%CI = 0.345-0.869, P = 0 011). Thus, we concluded that IL-31 gene polymorphisms were tightly associated with DCM susceptibility and contributed to worse prognosis in DCM patients

Cumulative live birth rates and birth outcomes after IVF/ICSI treatment cycles in young POSEIDON patients: A real-world study

ObjectiveThe aim of this study was to describe the cumulative live birth rates (CLBRs) of young women with or without low prognosis according to the POSEIDON criteria after IVF/ICSI cycles and to investigate whether the diagnosis of low prognosis increases the risk of abnormal birth outcomes.DesignRetrospective study.SettingA single reproductive medicine center.PopulationFrom January 2016 to October 2020, there were 17,893 patients (<35 years) involved. After screening, 4,105 women were included in POSEIDON group 1, 1,375 women were included in POSEIDON group 3, and 11,876 women were defined as non-POSEIDON.Intervention(s)Baseline serum AMH level was measured on the D2–D3 of menstrual cycle before IVF/ICSI treatment.Main outcome measure(s)Cumulative live birth rate (CLBR), birth outcomes.Result(s)After four stimulation cycles, the CLBRs in POSEIDON group 1, POSEIDON group 3, and non-POSEIDON group reached 67.9% (95% CI, 66.5%–69.3%), 51.9% (95% CI, 49.2%–54.5%), and 79.6% (95% CI, 78.9%–80.3%), respectively. There was no difference in gestational age, preterm delivery, cesarean delivery, and low birth weight infants between the three groups, but macrosomia was significantly higher in non-POSEIDON group, after adjusting for maternal age and BMI.Conclusion(s)The POSEIDON group shows lower CLBRs than the non-POSEIDON group in young women, while the risk of abnormal birth outcomes in the POSEIDON group will not increase

Chronic Hepatitis B Virus Infection and Risk of Stroke Types: A Prospective Cohort Study of 500 000 Chinese Adults

BACKGROUND: Stroke is a leading cause of mortality and permanent disability in China, with large and unexplained geographic variations in rates of different stroke types. Chronic hepatitis B virus infection is prevalent among Chinese adults and may play a role in stroke cause. // METHODS: The prospective China Kadoorie Biobank included >500 000 adults aged 30 to 79 years who were recruited from 10 (5 urban and 5 rural) geographically diverse areas of China from 2004 to 2008, with determination of hepatitis B surface antigen (HBsAg) positivity at baseline. During 11 years of follow-up, a total of 59 117 incident stroke cases occurred, including 11 318 intracerebral hemorrhage (ICH), 49 971 ischemic stroke, 995 subarachnoid hemorrhage, and 3036 other/unspecified stroke. Cox regression models were used to estimate adjusted hazard ratios (HRs) for risk of stroke types associated with HBsAg positivity. In a subset of 17 833 participants, liver enzymes and lipids levels were measured and compared by HBsAg status. // RESULTS: Overall, 3.0% of participants were positive for HBsAg. HBsAg positivity was associated with an increased risk of ICH (adjusted HR, 1.29 [95% CI, 1.16–1.44]), similarly for fatal (n=5982; adjusted HR, 1.36 [95% CI, 1.16–1.59]) and nonfatal (n=5336; adjusted HR, 1.23 [95% CI, 1.06–1.44]) ICH. There were no significant associations of HBsAg positivity with risks of ischemic stroke (adjusted HR, 0.97 [95% CI, 0.92–1.03]), subarachnoid hemorrhage (adjusted HR, 0.87 [95% CI, 0.57–1.33]), or other/unspecified stroke (adjusted HR, 1.12 [95% CI, 0.89–1.42]). Compared with HBsAg-negative counterparts, HBsAg-positive individuals had lower lipid and albumin levels and higher liver enzyme levels. After adjustment for liver enzymes and albumin, the association with ICH from HBsAg positivity attenuated to 1.15 (0.90–1.48), suggesting possible mediation by abnormal liver function. // CONCLUSIONS: Among Chinese adults, chronic hepatitis B virus infection is associated with an increased risk of ICH but not other stroke types, which may be mediated through liver dysfunction and altered lipid metabolism

Tumor-penetrating peptide fused EGFR single-domain antibody enhances cancer drug penetration into 3D multicellular spheroids and facilitates effective gastric cancer therapy

Human tumors, including gastric cancer, frequently express high levels of epidermal growth factor receptors (EGFRs), which are associated with a poor prognosis. Targeted delivery of anticancer drugs to cancerous tissues shows potential in sparing unaffected tissues. However, it has been a major challenge for drug penetration in solid tumor tissues due to the complicated tumor microenvironment. We have constructed a recombinant protein named anti-EGFR-iRGD consisting of an anti-EGFR VHH (the variable domain from the heavy chain of the antibody) fused to iRGD, a tumor-specific binding peptide with high permeability. Anti-EGFR-iRGD, which targets EGFR and αvβ3, spreads extensively throughout both the multicellular spheroids and the tumor mass. The recombinant protein anti-EGFR-iRGD also exhibited antitumor activity in tumor cell lines, multicellular spheroids, and mice. Moreover, anti-EGFR-iRGD could improve anticancer drugs, such as doxorubicin (DOX), bevacizumab, nanoparticle permeability and efficacy in multicellular spheroids. This study draws attention to the importance of iRGD peptide in the therapeutic approach of anti-EGFR-iRGD. As a consequence, anti-EGFR-iRGD could be a drug candidate for cancer treatment and a useful adjunct of other anticancer drugs

Vortex Generation and Auroral Response to a Solar Wind Dynamic Pressure Increase: Event Analyses

In this study, we investigate ionospheric responses, including currents and aurorae, to solar wind dynamic pressure (SW Pdyn) sudden increases, which are critical for understanding solar wind‐magnetosphere‐ionosphere coupling. We focus on two similar SW Pdyn pulse events that occurred on 24 January 2012 and 12 November 2010. In both cases, equivalent ionospheric currents (EIC) vortices were generated within about ten minutes after the pressure pulse arrival, with a counter‐clockwise rotating vortex (viewed from above) observed on the dusk side in the former case, and a clockwise vortex observed on the dawn side in the latter. Simultaneous ground‐based All‐Sky Imager (ASI) observations in the vicinity of the observed EIC vortex in each case showed that aurorae intensified on the dusk side, and diminished on the dawn side. These observations provide direct evidence of the scenario proposed byShi et al. (2014) that magnetospheric flow vortices generated by a solar wind pressure pulse carry field‐aligned currents into the ionosphere and thereby modulate auroral activity. The dawn/dusk asymmetry in the auroral intensification is a direct result of the opposite sense of vortex rotation on the dawn and dusk sides, which generate oppositely directed field‐aligned currents into/out of the ionosphere