Activation of the RIG-I/MAVS Signaling Pathway during Human Adenovirus Type 3 Infection Impairs the Pro-Inflammatory Response Induced by Secondary Infection with Staphylococcus aureus.

The exacerbation of pneumonia in children with human adenovirus type 3 (HAdV-3E) is secondary to a Staphylococcus aureus (S. aureus) infection. The influence of host-pathogen interactions on disease progression remains unclear. It is important to note that S. aureus infections following an HAdV-3E infection are frequently observed in clinical settings, yet the underlying susceptibility mechanisms are not fully understood. This study utilized an A549 cell model to investigate secondary infection with S. aureus following an HAdV-3E infection. The findings suggest that HAdV-3E exacerbates the S. aureus infection by intensifying lung epithelial cell damage. The results highlight the role of HAdV-3E in enhancing the interferon signaling pathway through RIG-I (DDX58), resulting in the increased expression of interferon-stimulating factors like MX1, RSAD2, and USP18. The increase in interferon-stimulating factors inhibits the NF-κB and MAPK/P38 pro-inflammatory signaling pathways. These findings reveal new mechanisms of action for HAdV-3E and S. aureus in secondary infections, enhancing our comprehension of pathogenesis.

Expression of RNA-m6A-related genes correlates with the HIV latent reservoir level and the CD4+ and CD8+T cell profiles of patients with AIDS.

The HIV latent reservoir is the main obstacle to the eradication of AIDS. Recent studies have shown that the RNA m6A is involved in the regulation of HIV-1 replication. However, no relevant study has reported the relationship between RNA m6A and HIV latent reservoir. For this purpose, peripheral blood mononuclear cell (PBMC) was collected from 36 HIV-infected patients at 1, 24, and 48 weeks after treatment initiation. The number of CD4+ and CD8+ T cells was detected by flow cytometry. Amount of HIV DNA in the PBMC samples one week after treatment initiation was detected by Q-PCR. The expression levels of 23 RNA-m6A-related genes were detected by Q-PCR and Pearson's correlation analysis was performed. Results showed that there was a negative correlation between HIV DNA concentration and the number of CD4+ T cells (r=-0.32, p=0.05; r=-0.32, p=0.06) and a positive correlation with the number of CD8+ T cells (r=0.48, p=0.003; r=0.37, p=0.03). Furthermore, a negative correlation was observed between HIV DNA concentration and the CD4+/CD8+ T cell ratio (r=-0.53, p=0.001; r=-0.51, p=0.001). RNAm6A related genes which correlated with HIV DNA concentration includedALKBH5 (r=-0.45, p=-0.006), METTL3 (r=0.73, p=2.76e-7), METTL16 (r=0.71, p=1.21e2.76e-06), YTHDF1 (r=0.47, p=0.004). Moreover, they have different degrees of correlation with numbers ofCD4+ and CD8+ T cell subsets, and the CD4+/CD8+T cell ratio. In addition, the expression of RBM15 was not correlated with HIV DNA concentration but was significantly negatively correlated with the number of CD4+T cells (r=-0.40, p=0.02). In conclusion, the expression of ALKBH5, METTL3, and METTL16 is correlated with the HIV DNA level, the levels of CD4+ and CD8+ T cell counts, and the CD4+/CD8+ T cell ratio. RBM15 is independent of HIV DNA level and negatively correlated with the number of CD4+T cells.

ZnO-Doped Metal-Organic Frameworks Nanoparticles: Antibacterial Activity and Mechanisms.

Metal-Organic Frameworks (MOFs) offer new ideas for the design of antibacterial materials because of their antibacterial properties, high porosity and specific surface area, low toxicity and good biocompatibility compared with other nanomaterials. Herein, a novel antimicrobial nanomaterial, MIL-101(Fe)@ZnO, has been synthesized by hydrothermal synthesis and characterized by FTIR, UV-vis, ICP-OES, XRD, SEM, EDS and BET to show that the zinc ions are doped into the crystal lattice of MIL-101(Fe) to form a Fe-Zn bimetallic structure. MIL-101(Fe)@ZnO was found to be effective against a wide range of antibacterial materials including Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, Acinetobacter junii and Staphylococcus epidermidis. It has a significant antibacterial effect, weak cytotoxicity, high safety performance and good biocompatibility. Meanwhile, MIL-101(Fe)@ZnO was able to achieve antibacterial effects by causing cells to produce ROS, disrupting the cell membrane structure, and causing protein leakage and lipid preoxidation mechanisms. In conclusion, MIL-101(Fe)@ZnO is an easy-to-prepare antimicrobial nanomaterial with broad-spectrum bactericidal activity and low toxicity.

Glucose oxidase-encapsulated liposomes for amplified autofluorescence-free immunoassay of a prostate-specific antigen with photoluminescence of CePO4:Tb nanocrystals.

Lanthanide-doped inorganic nanocrystals have attracted extensive attention due to their long luminescence lifetime and large Stokes shift. In this work, an immunosensing platform based on CePO4:Tb (CPOT) was successfully constructed, which could avoid the autofluorescence interference of complex biological matrices. Specifically, CPOT was synthesized by a solvothermal method, which exhibited H2O2-responsive luminescence behavior. Taking advantage of this feature, an autofluorescence-free immunosensor with CPOT as the probe and H2O2 as the quencher was developed to detect prostate-specific antigen (PSA). Functionalized liposomes were used to encapsulate glucose oxidase (GOD) and labeled on detection antibodies to improve the sensitivity of the probe. Under the proven optimal experimental conditions, the developed autofluorescence-free immunosensor exhibited a linear luminescence response to the logarithm of PSA concentration (0.005-25 ng mL-1) with a limit of detection (LOD) of 3.25 pg mL-1. The performance shows that the autofluorescence-free immunosensor based on this strategy opens up a new field of vision for clinical PSA detection.

Research Progress on Synthesis and Application of Cyclodextrin Polymers.

Cyclodextrins (CDs) are a series of cyclic oligosaccharides formed by amylose under the action of CD glucosyltransferase that is produced by Bacillus. After being modified by polymerization, substitution and grafting, high molecular weight cyclodextrin polymers (pCDs) containing multiple CD units can be obtained. pCDs retain the internal hydrophobic-external hydrophilic cavity structure characteristic of CDs, while also possessing the stability of polymer. They are a class of functional polymer materials with strong development potential and have been applied in many fields. This review introduces the research progress of pCDs, including the synthesis of pCDs and their applications in analytical separation science, materials science, and biomedicine.

The Structural Characteristics of Seaweed Polysaccharides and Their Application in Gel Drug Delivery Systems.

In recent years, researchers across various fields have shown a keen interest in the exploitation of biocompatible natural polymer materials, especially the development and application of seaweed polysaccharides. Seaweed polysaccharides are a multi-component mixture composed of one or more monosaccharides, which have the functions of being anti-virus, anti-tumor, anti-mutation, anti-radiation and enhancing immunity. These biological activities allow them to be applied in various controllable and sustained anti-inflammatory and anticancer drug delivery systems, such as seaweed polysaccharide-based nanoparticles, microspheres and gels, etc. This review summarizes the advantages of alginic acid, carrageenan and other seaweed polysaccharides, and focuses on their application in gel drug delivery systems (such as nanogels, microgels and hydrogels). In addition, recent literature reports and applications of seaweed polysaccharides are also discussed.

The Application of Prussian Blue Nanoparticles in Tumor Diagnosis and Treatment.

Prussian blue nanoparticles (PBNPs) have attracted increasing research interest in immunosensors, bioimaging, drug delivery, and application as therapeutic agents due to their large internal pore volume, tunable size, easy synthesis and surface modification, good thermal stability, and favorable biocompatibility. This review first outlines the effect of tumor markers using PBNPs-based immunosensors which have a sandwich-type architecture and competitive-type structure. Metal ion doped PBNPs which were used as T1-weight magnetic resonance and photoacoustic imaging agents to improve image quality and surface modified PBNPs which were used as drug carriers to decrease side effects via passive or active targeting to tumor sites are also summarized. Moreover, the PBNPs with high photothermal efficiency and excellent catalase-like activity were promising for photothermal therapy and O2 self-supplied photodynamic therapy of tumors. Hence, PBNPs-based multimodal imaging-guided combinational tumor therapies (such as chemo, photothermal, and photodynamic therapies) were finally reviewed. This review aims to inspire broad interest in the rational design and application of PBNPs for detecting and treating tumors in clinical research.

Photoelectrochemical immunoassay for thyroglobulin on nanogold-functionalized BiVO4 photoanode coupling with enzymatic biocatalytic precipitation.

Methods derived from photoelectrochemical (PEC) have been constructed for immunoassays, but most involve the split-type immunoreaction modes, and thus easily cause unpredictable intermediate precision. Herein, we innovatively designed an integrated PEC immunosensing platform for the quantitative monitoring of thyroglobulin (TG) on the gold nanoparticles (AuNPs)-functionalized BiVO4 photoanode coupling with enzymatic biocatalytic precipitation (EBCP). This sensing system could simultaneously implement the immunoreaction and photocurrent measurement. Anti-TG capture antibodies were modified onto AuNPs-decorated BiVO4 photoelectrode. A sandwich-type immunoreaction was carried out in the presence of target TG using horseradish peroxidase (HRP)-conjugated anti-TG detection antibody. The carried HRP molecules catalyzed 4-chloro-1-naphthol (4-CN) to generate an insoluble benzo-4-chlorohexadienone product on the photoanode in the presence of peroxide hydrogen, thereby decreasing the photocurrent. Under optimal conditions, the PEC immunosensors gave good photocurrent responses toward target TG within the dynamic range of 0.01-10 ng mL-1 at a detection limit of 7.6 pg mL-1. Good repeatability and precision, high specificity and acceptable storage stability were acquired during the measurement. No significant differences were encountered for screening 15 human serum specimens between the developed PEC immunoassay and commercially available enzyme-linked immunosorbent assay (ELISA) method for the detection of target TG. Significantly, PEC immunosensing system offers promise for simple and cost-effective analysis of disease-related biomarkers.

Risk of Obesity Among Children Aged 2-6 Years Who Had Prolonged Screen Time in Taiwan: A Nationwide Cross-Sectional Study.

Objective: To evaluate the risk of obesity in preschool children with prolonged screen time in Taiwan. Methods: Using a nationwide survey with random sampling, we collected information on 8378 preschool children aged 2-6 years among 206 preschools in Taiwan from 2016 to 2019. Socioeconomic data, body mass index, and lifestyle of the preschool children and their caregivers were compared among the groups of preschool children who had moderate and prolonged daily screen time. We used multiple log-binomial regression models to calculate the adjusted prevalence ratios (PRs) and 95% confidence intervals (CIs) of obesity associated with prolonged screen time. Results: The prevalence of obesity in the preschool children was 13.1%, and the average screen time was 104.6 minutes. Children's age, sleep hours, outdoor play time, sugar intake, snack eating before dinner, sleep disturbance, and obesity, as well as caregiver's sex, age, education, screen time, exercise time and parent obesity were factors related to high screen time for preschool children. Compared with children with moderate screen time, children with prolonged screen time had a higher risk of obesity (PR, 1.45; 95% CI, 1.18-1.79). With a 60-minute increase in screen time, the risk of obesity increased, with an PR of 1.10 (95% CI, 1.03-1.17). Conclusion: Preschool children with prolonged screen time had an increased risk of obesity in Taiwan. Interventions may be needed for this very susceptible population.

Clinical diagnostic biomarker "circulating tumor cells" in breast cancer - a meta-analysis.

Objective: Using meta-analysis, we evaluate circulating tumor cells(CTCs) as a potential diagnostic tool for breast cancer. Methods: A document search was conducted using publicly available databases up to May 2021. Specific inclusion and exclusion criteria were formulated and summarize relevant data through literature types, research types, case populations, samples, etc. Subgroup analysis of documents based on regions, enrichment methods, and detection methods. The included research projects were evaluated using DeeKs' bias, and evaluation indicators such as specificity (SPE), sensitivity (SEN), diagnosis odds ratio (DOR) were used as evaluation indicators. Results: 16 studies on the use of circulating tumor cells to diagnose breast cancer were included in our meta-analysis. Overall sensitivity value was 0.50 (95%CI:0.48-0.52), specificity value was 0.93 (95%CI:0.92- 0.95), DOR value was 33.41 (95%CI:12.47-89.51), and AUC value was 0.8129. Conclusion: In meta-regressions and subgroup analysis, potential heterogeneity factors were analyzed, but the source of heterogeneity is still unclear. CTCs, as a novel tumor marker, have a good diagnostic value, but its enrichment and detection methods still need to continue to be developed to improve detection accuracy. Therefore, CTCs can be used as an auxiliary means of early detection, which is helpful to the diagnosis and screening of breast cancer.

3'UTR of SARS-CoV-2 spike gene hijack host miR-296 or miR-520h to disturb cell proliferation and cytokine signaling.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has becoming globally public health threat. Recently studies were focus on SARS-CoV-2 RNA to design vaccine and drugs. It was demonstrated that virus RNA could play as sponge to host noncoding RNAs to regulate cellular processes. Bioinformatic research predicted a series of motif on SARS-CoV-2 genome where are targets of human miRNAs. In this study, we used dual-luciferase reporter assays to validate the interaction between 3'UTR of SARS-CoV-2 S (S-3'UTR) gene and bioinformatic predicted targeting miRNAs. The growth of 293T cells and HUVECs with overexpressed S-3'UTR was determined, while miRNAs and IL6, TNF-α levels were checked in this condition. Then, miR-296 and miR-602 mimic were introduced into 293T cells and HUVECs with overexpressed S-3'UTR, respectively, to reveal the underlying regulation mechanism. In results, we screened 19 miRNAs targeting the S-3'UTR, including miR-296 and miR-602. In 293T cell, S-3'UTR could inhibit 293T cell growth through down-regulation of miR-296. By reducing miR-602, S-3'UTR could induce HUVECs cell proliferation, alter the cell cycle, reduce apoptosis, and enhanced IL6 and TNF-αlevel. In conclusion, SARS-CoV-2 RNA could play as sponge of host miRNA to disturb cell growth and cytokine signaling. It suggests an important clue for designing COVID-19 drug and vaccine.

Combination of Anoectochilus roxburghii Polysaccharide and Exercise Ameliorates Diet-Induced Metabolic Disorders in Obese Mice.

Metabolic syndrome is a cluster of metabolic disorders that threatens public health. Nevertheless, its exact mechanism and relative intervention remain largely obscure. Accumulating evidence indicate that tither Anoectochilus roxburghii polysaccharide (ARP) or exercise (EX) exhibited the beneficial effects on metabolic health. However, the synergetic beneficial effects of ARP and EX as a combined intervention on obesity-induced metabolic disorders remain largely obscure. Male C57BL/6 mice were fed a high-fat diet (HFD) and intervened with ARP and EX for 12 continuous weeks. The results indicated that the ARP, EX, and ARP combined with EX treatment group regulated lipogenesis by suppressing the fatty acid pathway, dampening the system oxidative stress by stimulating Nrf2-mediated phase II enzyme system, and promoting the mitochondrial function by activating the mitochondrial complexes and PGC-1α in HFD mice. More importantly, the combination of ARP and EX showed an even greater beneficial effects relative to either ARP or EX alone, especially in decreasing reactive oxygen species (ROS) level and increasing adenosine triphosphate (ATP) content. Taken together, these findings further confirmed that ARP and EX could be effective interventions on obesity-induced metabolic abnormalities, and that the combination of ARP and EX exhibited the beneficial synergetic effects.

Meta-Analysis of Peripheral Blood Transcriptome Datasets Reveals a Biomarker Panel for Tuberculosis in Patients Infected With HIV.

Biomarkers are critical for rapid diagnosis of tuberculosis (TB) and could benefit patients with AIDS where diagnosis of TB co-infection is challenging. Meta-analysis is an approach to combine the results of the studies with standard statistical method by weighting each study with different sample size. This study aimed to use meta-analysis to integrate transcriptome datasets from different studies and screen for TB biomarkers in patients who were HIV-positive. Five datasets were subjected to meta-analysis on whole-blood transcriptomes from 640 patients infected with HIV. A total of 293 differentially expressed genes (DEGs) were identified as significant (P<0.0001) using the random effective model to integrate the statistical results from each study. DEGs were enriched in biological processes related to TB, such as "Type I interferon signaling" and "stimulatory C-type lectin receptor signaling". Eighteen DEGs had at least a two-fold change in expression between patients infected with HIV who were TB-positive and those who were TB-negative. GBP4, SERPING1, ATF3 and CDKBN3 were selected as a biomarker panel to perform multivariable logistic regression analysis on TB status and relative gene expression levels. The biomarker panel showed excellent accuracy (AUC>0.90 for HIV+TB) in clinical trial and suggests that meta-analysis is an efficient method to integrate transcriptome datasets from different studies.

The ethnopharmacology, phytochemistry, pharmacology and toxicology of genus Albizia: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Albizia (Leguminosae) comprises about 150 species and some species have been used for the treatment of rheumatism, stomachache, cough, diarrhea, and wounds in traditional and local medicine. The aim of the review: This review article documents and critically assesses the current status of the traditional uses, phytochemistry, pharmacology, and toxicology of the Albizia species. MATERIALS AND METHODS: All provided literatures on the Albizia species were searched using the electronic databases (e.g. Web of Science, Elsevier, Springer, PubMed, ACS, CNKI, Google Scholar, and Baidu Scholar), books, and theses with keywords of 'Albizia' and 'Albizzia'. RESULTS: Albizia species have been used for melancholia, insomnia, wounds, fever, abscesses, diabetes, headache, stomachache, diarrhea, cough, rheumatism, snake bite, malaria, and parasitic infection in traditional and local medicine. These plants mainly contain triterpenoid saponins, flavonoids, lignanoids, alkaloids, phenolic glycosides, etc. Albizia species have been demonstrated to possess various pharmacological activities. Among them, the antidiabetic, anti-inflammatory, antifertility, antianxiety, antidepressant, and anti-fever properties are consistent with the traditional and local applications of the Albizia species. CONCLUSIONS: The traditional and local uses of Albizia species have been partially demonstrated by the pharmacological investigation. However, some traditional applications have not been assessed scientifically due to incomplete methodologies and ambiguous findings. Moreover, no clinical evidences support the health benefits of these plants. The systematic and comprehensive preclinical studies and clinical trials are still required to verify the pharmacological activities, clinical efficacy, and safety of Albizia species.