This study was designed to evaluate the immune protective efficacy of the novel Streptococcus pneumoniae (S. pneumoniae) protein vaccine PiuA-PlyD4 through immunoinformatics prediction and in vitro and in vivo experiments.In this study, we conducted immunoinformatics prediction and protection analysis on the fusion protein PiuA-PlyD4. The epitope composition of the vaccine was analyzed based on the prediction of B-cell and helper T-cell epitopes. Meanwhile, the molecular docking of PiuA and TLR2/4 was simulated. After immunizing C57BL/6 mice with the prepared vaccine, the biological safety, immunogenicity and conservation were evaluated. By constructing different infection models and from the aspects of adhesion inhibition and cytokines, the protective effect of the fusion protein vaccine PiuA-PlyD4 on S. pneumoniae infection was explored.PiuA-PlyD4 has abundant B-cell and helper T-cell epitopes and shows a high antigenicity score and structural stability. Molecular docking analysis suggested the potential interaction between PiuA and TLR2/4. The specific antibody titer of fusion protein antiserum was as high as (7.81±2.32) ×105. The protective effect of the immunized mice on nasal and lung colonization was significantly better than that of the control group, and the survival rate against S. pneumoniae infection of serotype 3 reached 50%. Cytokine detection showed that the humoral immune response, Th1, Th2 and Th17 cellular immune pathways were all involved in the process.The study indicates that PiuA-PlyD4, whether the results are predicted by immunoinformatics or experimentally validated in vivo and in vitro, has good immunogenicity and immunoreactivity and can provide effective protection against S. pneumoniae infection. Therefore, it can be considered a promising prophylactic vaccine candidate for S. pneumoniae.
The development of high-performance photothermal nanomaterials is essential for advancing clinical diagnostics, biosensing, and energy conservation technologies. In this study, the potential of multilayered nanostructures to enhance light trapping and improve photothermal efficiency was investigated. We successfully synthesized innovative triple-layer Prussian blue nanocubes (tl-Pt@PBNCs) with a multilevel core-shell architecture, optimizing them for both structural stability and exceptional photothermal performance. The optical wave and laser simulations revealed that the unique architecture of the tl-Pt@PBNCs facilitated multiple internal reflections and refractions of incident light within their cavities. This design greatly increased the effective path length, thereby enhancing light absorption and heat generation. Additionally, density functional theory calculations indicated that the incorporation of Pt atoms disrupted the crystal lattice symmetry, leading to the splitting of the d-orbits in Mn and Fe atoms. This disruption narrowed the band gap, resulting in a red shift of the absorption wavelength and finally improved photothermal conversion efficiency. Leveraging the unique properties of tl-Pt@PBNCs, a portable and sensitive immunoassay was designed for the detection of the illegal additive, rosiglitazone. By investigating the relationship between morphology and photothermal properties, this work deepens our understanding of the photothermal conversion mechanism and expands the potential applications of tl-Pt@PBNCs in point-of-care testing.
To explore the impact of chronic heat stress on commercial echinoderms, the present study assessed the effects of chronic high temperature on the growth, survival, feeding, and differential gene expression in the sea urchin Strongylocentrotus intermedius cultured in northern Yellow Sea in China. One suitable seawater condition (20°C) and one laboratory-controlled high temperature condition (25°C) were set up. After 28 days incubation, our results showed that: (1) The specific growth, survival, and ingestion rates of S. intermedius reared under high temperature (25°C) decreased compared to those reared under optimal temperature (20°C) conditions; (2) comparative transcriptome analysis identified 2,125 differentially expressed genes (DEGs) in S. intermedius reared under high temperature (25°C) compared to those subjected to optimal temperature condition (20°C), which included 1,015 upregulated and 1,100 downregulated genes. The accuracy of the transcriptome profiles was verified by quantitative real-time PCR (qRT-PCR). Further Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analyses revealed that these DEGs mainly enriched the functional categories of ribosome, protein processing in endoplasmic reticulum, and prion diseases. A total of 732 temperature-induced expressed genes, such as ATP5, heat shock protein 70, and heat shock protein 90, were identified as candidates that were closely correlated with heat resistance in S. intermedius. Differentially expressed transcription factors (TFs), such as AP-1, Fos, CREB, and ZNF, were also identified as potential regulators that regulate the molecular network that was associated with responses to heat stress in sea urchins. Observations in the present study provide additional information that improves our understanding of the molecular mechanism of temperate echinoid species in response to heat stress, as well as theoretical basis for the molecular-assisted breeding of heat-resistant sea urchins.
High levels of heat shock protein 70 (HSP70) in tumors are commonly associated with poor prognosis, enhanced doxorubicin (DOX)-induced cardiotoxicity, and even drug resistance in DOX-related cancer chemotherapy. Several peptides possess remarkable protein inhibition and chemosensitization effects, which are attributed to their specific targeting ability against HSP70. However, the inherent poor cell penetration capacity considerably restricts the biomedical applications of these peptides. We herein describe the design and development of anti-MUC1 aptamer-peptide conjugates (ApPCs) as targeted chemosensitizers to overcome the above-mentioned issues. Moreover, DOX could be loaded on the ApPC to deliver the DOX-enclosed agent ApPC-DOX, which simultaneously acts as a targeted chemosensitizer and anticancer agent for combating drug resistance in breast cancer therapy. This innovative, engineered biocompatible conjugate not only enhances the sensitivity of DOX-resistant cells but also alleviates cardiotoxicity of DOX in vivo, highlighting the success of this targeted chemosensitizer strategy.
We report that preexisting (old) and newly synthesized (new) histones H3 and H4 are asymmetrically partitioned during the division of Drosophila intestinal stem cells (ISCs). Furthermore, the inheritance patterns of old and new H3 and H4 in postmitotic cell pairs correlate with distinct expression patterns of Delta, an important cell fate gene. To understand the biological significance of this phenomenon, we expressed a mutant H3T3A to compromise asymmetric histone inheritance. Under this condition, we observe an increase in Delta-symmetric cell pairs and overpopulated ISC-like, Delta-positive cells. Single-cell RNA-seq assays further indicate that H3T3A expression compromises ISC differentiation. Together, our results indicate that asymmetric histone inheritance potentially contributes to establishing distinct cell identities in a somatic stem cell lineage, consistent with previous findings in Drosophila male germline stem cells.
Phosgene is a very dangerous but important industrial intermediate and is a significant threat to public health. There is, therefore, an urgent need to develop a rapid, visual, and on-site detection method for phosgene. Sensitive and selective phosgene responsive carbon dots (CDs) were synthesized by employing 2-nitro-4-aminodiphenylamine as precursors. The amine group of the CDs can interact selectively with phosgene to effect acylation reactions, which cause color changes from yellow to amaranth and remarkable changes in fluorescence from bright yellow to orange-red due to modification of the CDs’ intramolecular charge transfer (ICT) process. The CDs exhibited fast response (< 2 s) for detection of phosgene with an ultralow detection limit (0.63 nM). Furthermore, a portable CD/polystyrene droplet system was developed for rapid and on-site visualization of phosgene. Specifically, the droplet system can realize rapid on-spot visual inspection of gaseous phosgene in the liquid phase with the naked eye and also long-term visualization in the solid phase via a polystyrene membrane after solvent volatilization. This study has expanded the scope for application of CDs in sensing field, and as such the CD technique can serve as a flexible tool for real-time detection of phosgene leakage in industrial and public safety applications.
Objective
To determine the effect of Xinjikang on signaling pathway and apoptosis of Toll-like receptors 4 (TLR4) -nuclear factor-κB (TLR4-NF-κB) in rats with viral myocarditis (VMC) .
Methods
Eighty 3-month-old male rats were randomly divided into the model group (n=30) , Xinjikang group (n=30) and normal control group (n=20) . The model group receieved intraperitoneal injection of Coxsackievirus B3 (CVB3) . In addition, the Xinjikang group was injected with Xinjikang decoction (15 g/kg) . The normal group was inoculated intraperitoneally with 0.2 ml virus-free Eagle’s solution. The cardiac index (body weight/cardiac weight) in each group was statistically analyzed. The pathological changes of heart tissues were examined by HE staining. The expression levels of TLR-4 and NF-κB in myocardial tissues were determined by immunohistochemistry. The protein expression levels of TLR-4 and NF-κB in myocardial tissues were determined by Western Blotting. The myocardial cell apoptosis index (AI) was examined by in situ end labeling (TUNEL) method.
Results
(1) The mortality in the Xinjikang group was significantly lower than that in the model group, whereas the median survival time was significantly longer than that in the model group (P Xinjikang group>normal control group (P Xinjikang group>normal control group (P<0.05) .
Conclusion
Xinjikang may reduce the mortality of VMC rats, prolong the median survival time, inhibit the expression of TLR4 and NF-κB, and improve the myocardial cell apoptosis.
Key words:
Myocarditis; TLR4; NF-κB; Apoptosis
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