Prediction and Identification of Potential Immunodominant Epitopes in Glycoproteins B, C, E, G, and I of Herpes Simplex Virus Type 2

Twenty B candidate epitopes of glycoproteins B (gB2), C (gC2), E (gE2), G (gG2), and I (gI2) of herpes simplex virus type 2 (HSV-2) were predicted using DNAstar, Biosun, and Antheprot methods combined with the polynomial method. Subsequently, the biological functions of the peptides were tested via experiments in vitro. Among the 20 epitope peptides, 17 could react with the antisera to the corresponding parent proteins in the EIA tests. In particular, five peptides, namely, gB2466–473 (EQDRKPRN), gC2216–223 (GRTDRPSA), gE2483–491 (DPPERPDSP), gG2572–579 (EPPDDDDS), and gI2286-295 (CRRRYRRPRG) had strong reaction with the antisera. All conjugates of the five peptides with the carrier protein BSA could stimulate mice into producing antibodies. The antisera to these peptides reacted strongly with the corresponding parent glycoproteins during the Western Blot tests, and the peptides reacted strongly with the antibodies against the parent glycoproteins during the EIA tests. The antisera against the five peptides could neutralize HSV-2 infection in vitro, which has not been reported until now. These results suggest that the immunodominant epitopes screened using software algorithms may be used for virus diagnosis and vaccine design against HSV-2

Serum Containing Tao-Hong-Si-Wu Decoction Induces Human Endothelial Cell VEGF Production via PI3K/Akt-eNOS Signaling

Tao-Hong-Si-Wu decoction (TSD) is a famous traditional Chinese medicine (TCM) and widely used for ischemic disease in China. TSD medicated serum was prepared after oral administration of TSD (1.6 g/kg) twice a day for 3 days in rats. TSD medicated serum induced human umbilical vein endothelial cells (HUVECs) proliferation, VEGF secretion, and nitric oxide (NO) production. These promoted effects of TSD were partly inhibited by treatment with PI3K inhibitor (LY294002) or eNOS inhibitor (L-NAME), respectively, and completely inhibited by treatment with LY294002 and L-NAME simultaneously. Western blot analysis findings further indicated that TSD medicated serum upregulated p-Akt and p-eNOS expressions, which were significantly inhibited by LY294002 or L-NAME and completely inhibited by both LY294002 and L-NAME; these results indicated that TSD medicated serum induced HUVECs VEGF expression via PI3K/Akt-eNOS signaling. TSD medicated serum contains hydroxysafflor yellow A, ferulic acid, and ligustilide detected by UPLC with standards, so these effect of TSD medicated serum may be associated with these three active compounds absorbed in serum

Optimization of hole spacing for cut-top blasting based on new hole-sealing technology

In order to solve the problem of stress concentration on the roof of the mining trench, reduce the risk of sudden collapse of the roof overburden and disturbance, improve the control effect of the surrounding rock of the roof cutting and retaining roadway, and reduce the construction cost of mining tunnels, a new type of pouch sealing technology has been developed. By using on-site testing methods, the optimal sealing material ratio was optimized, and the crack propagation law and roof cutting effect of the 11503 W working face in Zhaizhen Coal Mine, Shandong Province were studied under hole spacing of 0.7, 1.0, and 1.1 meters and different sealing methods. The results show that using 1.5 m single pouch sealing technology in the blasting test, when the water cement ratio of the sealing material is 1:1, the required sealing strength and sealing temperature can be achieved, and there will be no punching phenomenon. When the spacing between holes is 1 m, the blasting effect is optimal, with a single hole effectively reaching a cutting seam length of about 0.5 m. There are obvious through cracks in the cave, with a total length of about 7 meters. After using the new pouch sealing technology for blasting, the displacement and bottom drum volume on both sides of the tunnel are lower than those of the traditional yellow mud sealing method, and the bottom drum volume is reduced by 37% and 53%, respectively. Based on comprehensive theoretical analysis and on-site experiments, the optimal hole spacing is determined to be 1 m, and the pouch sealing effect is good

From oncolytic peptides to oncolytic polymers: A new paradigm for oncotherapy

Traditional cancer therapy methods, especially those directed against specific intracellular targets or signaling pathways, are not powerful enough to overcome tumor heterogeneity and therapeutic resistance. Oncolytic peptides that can induce membrane lysis-mediated cancer cell death and subsequent anticancer immune responses, has provided a new paradigm for cancer therapy. However, the clinical application of oncolytic peptides is always limited by some factors such as unsatisfactory bio-distribution, poor stability, and off-target toxicity. To overcome these limitations, oncolytic polymers stand out as prospective therapeutic materials owing to their high stability, chemical versatility, and scalable production capacity, which has the potential to drive a revolution in cancer treatment. This review provides an overview of the mechanism and structure-activity relationship of oncolytic peptides. Then the oncolytic peptides-mediated combination therapy and the nano-delivery strategies for oncolytic peptides are summarized. Emphatically, the current research progress of oncolytic polymers has been highlighted. Lastly, the challenges and prospects in the development of oncolytic polymers are discussed

Design and evaluation of a multi-epitope assembly Peptide (MEAP) against herpes simplex virus type 2 infection in BALB/c mice

<p>Abstract</p> <p>Background</p> <p>Human herpes simplex virus (HSV) 1 and 2 causes oral, ocular, or genital infections, which remains a significant health problem worldwide. HSV-1 and -2 infections in humans range from localized skin infections of the oral, ocular, and genital regions to severe and often disseminated infections in immunocompromised hosts. Epitope based vaccination is a promising mean to achieve protective immunity and to avoid infections with Human herpes simplex virus type 2 (HSV-2).</p> <p>Methods</p> <p>The twelve selected epitopes, six B cell epitopes from different glycoprotein of HSV-2 (amino acid residues 466-473 (EQDRKPRN) from envelope glycoprotein B, 216-223 (GRTDRPSA) from C, 6-18 (DPSLKMADPNRFR) from D, 483-491 (DPPERPDSP) from E, 572-579 (EPPDDDDS) from G and 286-295 (CRRRYRRPRG) from I glycoprotein of HSV-2), four CD4⁺T cell epitopes (amino acid residues 21-28 (NLPVLDQL) from D, 162-177 (KDVTVSQVWFGHRYSQ) from B, 205-224 (KAYQQGVTVDSIGMLPRFIP) from D and 245-259 (KPPYTSTLLPPELSD) from D) and two CD8⁺T cell epitopes (amino acid residues 10-20 (KMADPNRFRGK) from D and 268-276 (ALLEDPAGT) from D), are responsible for the elicitation of the neutralizing antibodies and cytotoxic T lymphocytes (CTLs) that impart protective immunity to the host. In this study, all above epitopes were inserted into the extracellular fragment (amino acid residues 1-290) of HSV-2 glycoprotein D to construct multi-epitope assembly peptides (MEAPs) by replacing some non-epitope amino acid sequences. The epitope independency of the MEAPs was predicted by three-dimensional software algorithms. The gene of the selected MEAP was expressed in <it>E.coli </it>BL21(DE3), and its protective efficacy against HSV-2 infection was assessed in BALB/c mice.</p> <p>Results</p> <p>The MEAP, with each inserted epitopes independently displayed on the molecule surface, was selected as candidate proteins. The results showed that the MEAP was highly immunogenic and could elicit high titer neutralizing antibodies and cell-mediated immune responses.</p> <p>Conclusions</p> <p>The MEAP provided complete protection against infection with HSV-2 in mice, which indicates that it might be a potential candidate vaccine against HSV-2.</p

Dynamic Response and Service Life of Tunnel Bottom Structure Considering Hydro-Mechanical Coupling Effect under the Condition of Bedrock Softening

Due to the long-term coupling effect of a train load and groundwater, the surrounding rock at the tunnel bottom will soften in a certain range and the mechanical parameters of the surrounding rock will decrease, causing the uneven distribution of the confining pressure at the tunnel bottom and affecting the base concrete structure service life. In this research, the method of combining field tests and numerical simulation is adopted, and the vertical displacement, vertical acceleration, and maximum and minimum principal stresses are used as evaluation indicators. The dynamic response law of the base structure with the softened surrounding rock of the heavy-duty train is analyzed, and the Miner linear cumulative damage theory is introduced to obtain the service life of the tunnel bottom structure under different softening conditions. The results show that with the decrease in the softening coefficient and the increase in the softening thickness of the bedrock, the displacement, acceleration, and principal stress response indexes of the structure increase by varying degrees, and the service life of the base structure decreases almost linearly. The maximum vertical displacement, acceleration, and tensile stress are located directly below the track, and the maximum compressive stress is located at the connection between the inverted arch and the side wall. According to the predicted value of the service life, the reliability of the base structure is divided into four levels: safety, warning, danger, and serious danger

Structure and ecological function of the soil microbiome associated with ‘Sanghuang’ mushrooms suffering from fungal diseases

Abstract Background The most serious challenges in medicinal ‘Sanghuang’ mushroom production are the fungal diseases caused by various molds. Application of biological agents has been regarded as a potential crop disease management strategy. Here, the soil microbiome associated with ‘Sanghuang’ mushroom affected by fungal diseases grown under field cultivation (FC) and hanging cultivation (HC) was characterized using culture-dependent and culture-independent methods. Results A total of 12,525 operational taxonomic units (OTUs) and 168 pure cultures were obtained using high-throughput sequencing and a culture-dependent method, respectively. From high-throughput sequencing, we found that HC samples had more OTUs, higher α-diversity, and greater microbial community complexity than FC samples. Analysis of β-diversity divided the soil microbes into two groups according to cultivation mode. Basidiomycota (48.6%) and Ascomycota (46.5%) were the two dominant fungal phyla in FC samples, with the representative genera Trichoderma (56.3%), Coprinellus (29.4%) and Discosia (4.8%), while only the phylum Ascomycota (84.5%) was predominant in HC samples, with the representative genera Discosia (34.0%), Trichoderma (30.2%), Penicillium (14.9%), and Aspergillus (7.8%). Notably, Trichoderma was predominant in both the culture-independent and culture-dependent analyses, with Trichoderma sp. FZ0005 showing high host pathogenicity. Among the 87 culturable bacteria, 15 exhibited varying extents of antifungal activity against Trichoderma sp. FZ0005, with three strains of Bacillus spp. (HX0037, HX0016, and HX0039) showing outstanding antifungal capacity. Conclusions Overall, our results suggest that Trichoderma is the major causal agent of ‘Sanghuang’ fungal diseases and that Bacillus strains may be used as biocontrol agents in ‘Sanghuang’ cultivation