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Coronavirus Disease 2019 (COVID-19) caused by a novel betacoronavirus SARS-CoV-2 has been an ongoing global pandemic. Several vaccines have been developed to control the COVID-19, but the potential effectiveness of the mucosal vaccine remains to be documented. In this study, we constructed a recombinant L. plantarum LP18:RBD expressing the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein via the surface anchoring route. The amount of the RBD protein was maximally expressed under the culture condition with 200 ng/mL of inducer at 33 °C for 6 h. Further, we evaluated the immune response in mice via the intranasal administration of LP18:RBD. The results showed that the LP18:RBD significantly elicited RBD-specific mucosal IgA antibodies in respiratory tract and intestinal tract. The percentages of CD3 + CD4+ T cells in spleens of mice administrated with the LP18:RBD were also significantly increased. This indicated that LP18:RBD could induce a humoral immune response at the mucosa, and it could be used as a mucosal vaccine candidate against the SARS-CoV-2 infection. We provided the first experimental evidence that the recombinant L. plantarum LP18:RBD could initiate immune response in vivo, which implies that the mucosal immunization using recombinant LAB system could be a promising vaccination strategy to prevent the COVID-19 pandemic.

Apoptin is derived from the chicken anemia virus and exhibits specific cytotoxic effects against tumor cells. Herein, we found that Apoptin induced a strong and lasting endoplasmic reticulum (ER) stress response, CaThe intracellular levels of calcium (CaThis study showed that Apoptin induced a strong and long- lasting ER stress and injury, which subsequently led to an imbalance of cellular CaIn summary, Apoptin induced apoptosis in HepG-2 cells via Ca

In this study, we compared the inhibitory effects of recombinant oncolytic adenovirus (Ad-apoptin-hTERTp-E1a, Ad-VT) with that of doxorubicin (DOX), a first-line chemotherapy drug, and tamoxifen (TAM), an endocrine therapy drug, on the proliferation of breast cancer cells. We found that Ad-VT could effectively inhibit the proliferation of breast cancer cells (p 0.01); the inhibition rate of Ad-VT on normal mammary epithelial MCF-10A cells was less than 20%. DOX can effectively inhibit the proliferation of breast cancer cells and also has a strong inhibitory effect on MCF-10A cells (p 0.01). TAM also has a strong inhibitory effect on breast cancer cells, among which the oestrogen-dependent MCF-7 cell inhibition was stronger (p 0.01), At higher concentrations, TAM also had a high rate of inhibition (70%) on the proliferation of MCF-10A cells. We also found that both recombinant adenovirus and both drugs could successfully induce tumour cell apoptosis. Further Western blot results showed that the recombinant adenovirus killed breast cancer cells through the endogenous apoptotic pathway. Analysis of the nude mouse subcutaneous breast cancer model showed that Ad-VT significantly inhibited tumour growth (the luminescence rate of cancer cells was reduced by more than 90%) and improved the survival rate of tumour-bearing mice (p 0.01). Compared with DOX and TAM, Ad-VT has a significant inhibitory effect on breast cancer cells, but almost no inhibitory effect on normal breast epithelial cells, and this inhibitory effect is mainly through the endogenous apoptotic pathway. These results indicate that Ad-VT has significant potential as a drug for the treatment of breast cancer.

Apoptin is derived from the chicken anemia virus and exhibits specific cytotoxic effects against tumor cells. Herein, we found that Apoptin induced a strong and lasting endoplasmic reticulum (ER) stress response and Ca2+ imbalance, and triggered the mitochondrial apoptotic pathway. The aim of this study was to explore the mechanisms by which Apoptin exhibited anti-tumor effects on the HepG-2 cells. The intracellular level of calcium (Ca2+) was induced by ER stress and determined by electron microscopy, flow cytometry and fluorescence staining. Mitochondrial injury was determined by mitochondrial membrane potential, electron microscopy. Western blotting was used to investigate the levels of key proteins in the ER stress and the apoptotic pathway in the mitochondria. The relationship between Ca2+ level and apoptosis on Apoptin-treating cells was analyzed using Ca2+ chelator (BAPTA-AM), flow cytometry and fluorescence staining. We also investigated the in vivo effects of Ca2+ imbalance on the mitochondrial apoptotic pathway using the tumor tissues xenografted on nude mice. In vitro and in vivo experiments showed that Apoptin caused an imbalance in Ca2+, and increased the expression levels of Smac/Diablo and Cyto-C. In summary, Apoptin induced apoptosis in HepG-2 cells via Ca2+ imbalance-triggered mitochondrial apoptotic pathway. This study provided a new direction for antitumor research in Apoptin.

Apoptin is derived from the chicken anemia virus and exhibits specific cytotoxic effects against tumor cells. In our previous study, we demonstrated that Apoptin induced significant changes in the expression levels of endoplasmic reticulum stress (ERS) related proteins and caused a strong and lasting ERS response. The aim of this study was to explore the effects of ERS injury induced by Apoptin on the endoplasmic reticulum (ER) and the apoptotic pathway in mitochondria. ERS injury induced the intracellular levels of calcium (Ca2+) were determined by electron microscopy, flow cytometry and fluorescence staining. Mitochondrial injury was determined by mitochondrial membrane potential and electron microscopy. The relationship between Ca2+ level and mitochondrial injury on Apoptin-treating cells was analyzed using Ca2+ chelator, flow cytometry and fluorescence staining. Western blotting was used to investigate the levels of key proteins in the ER and the apoptotic pathway in mitochondria. We also investigated the in vivo effects of ERS injury on the ER and the mitochondrial apoptotic pathway via the immunohistochemical analysis of tumor tissues from HepG-2 cells acquired from nude mice undergoing xenografts. In vitro and in vivo experiments showed that Apoptin caused ERS injury and an imbalance in Ca2+, damaged the structure of the mitochondria, and increased the expression levels of Caspase-12, CHOP, AIF, HtrA2, Smac/Diablo, and Cyto-C. In summary, Apoptin induced apoptosis in HepG-2 cells via ERS and the mitochondrial apoptotic pathway. This study showed that Apoptin induced apoptosis in HepG-2 cells via ERS injury.

In this study, we investigated the effects of Apoptin-induced endoplasmic reticulum (ER) stress on lipid metabolism, migration and invasion of HepG-2 cells, and preliminarily explored the relationship between endoplasmic reticulum stress, lipid metabolism, migration, and invasion. The effects of Apoptin on ER function and structure in HepG-2 cells were determined by flow cytometry, fluorescence staining and western blotting by assessing the expression levels of ER stress related proteins. The effects of Apoptin on HepG-2 cells’ lipid metabolism were determined by western blot analysis of the expression levels of triglyceride, cholesterol, and lipid metabolism related enzymes. The effects of Apoptin on HepG-2 cells’ migration and invasion were studied using migration and invasion assays and by Western-blot analysis of the expression of proteins involved in migration and invasion. The in vivo effects of endoplasmic reticulum stress on lipid metabolism, migration and invasion of HepG-2 cells were also investigated by immunohistochemistry analysis of tumor tissues from HepG2 cells xenografted nude mice models. Both in vitro and in vivo experiments showed that Apoptin can cause a strong and lasting ER stress response, damage ER functional structure, significantly change the expression levels of lipid metabolism related enzymes and reduce the migration and invasion abilities of HepG-2 cells. Apoptin can also affect HepG-2 cells’ lipid metabolism through endoplasmic reticulum stress and the abnormal expression of enzymes closely related to tumor migration and invasion. These results also showed that lipid metabolism may be one of the main inducements that reduce HepG-2 cells’ migration and invasion abilities.

Zheng Liu,1,* Ronghai Wang,2,* Guangze Zhu3 1Department of Traditional Chinese Medicine and Acupuncture, Central Hospital of Baoji, Baoji City, Shaanxi Province, People’s Republic of China; 2Department of Urology, Linzi District People’s Hospital, Zibo City, Shandong Province, People’s Republic of China; 3Department of Clinical Laboratory Medicine, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun City, Jilin Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guangze ZhuDepartment of Clinical Laboratory Medicine, The Affiliated Hospital to Changchun University of Chinese Medicine, No. 1478 Gongnong Road, Chaoyang District, Changchun, Jilin Province 130021, People’s Republic of ChinaTel/Fax +86 431-86177939Email zhugz0820@126.comBackground: Renal cell carcinoma (RCC) that originates from the proximal renal tubules is the most common cancer of the human kidney. Increasing circRNA/miRNA/mRNA networks have been found in RCC regulation. This study will explore the regulatory relation of circular RNA (circRNA) circ_0035483, microRNA-31-5p (miR-31-5p) and high mobility group A1 (HMGA1).Methods: The levels of circ_0035483, miR-31-5p and HMGA1 were measured by real-time polymerase chain reaction (qRT-PCR) or Western blot. Cell proliferation was determined using Cell Counting Kit-8 (CCK-8) and colony formation assays. Cell migration and invasion were assessed by transwell assay. HMGA1 and epithelial–mesenchymal transition (EMT)-related protein levels were quantified using Western blot. Glycolytic metabolism was evaluated by glucose consumption and lactate production. The interaction between targets was confirmed via dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays. In vivo experiment was performed through the establishment of xenograft models in mice.Results: Circ_0035483 expression was upregulated in RCC tissues and cells. The inhibitory effects on RCC cell proliferation, migration, invasion, EMT and glycolysis were induced after circ_0035483 was downregulated. MiR-31-5p was identified as a target of circ_0035483 and miR-31-5p upregulation was related to the function of circ_0035483 knockdown in RCC cells. Additionally, miR-31-5p targeted HMGA1 and inhibited the malignant behaviors of RCC cells by negatively regulating HMGA1. Moreover, HMGA1 expression was regulated by circ_0035483 via targeting miR-31-5p. Circ_0035483 also affected tumor growth in vivo by relying on the miR-31-5p/HMGA1 axis.Conclusion: These findings clarified that the tumor-promoting function of circ_0035483 in RCC was partly achieved by regulating the miR-31-5p/HMGA1 axis.Keywords: circ_0035483, renal cell carcinoma; RCC, miR-31-5p, HMGA1

As the scale of the power grid grows and develops, the problem of power quality is becoming more and more serious. Only by effectively monitoring and analyzing various power quality problems can it be improved and managed in a targeted manner. This paper uses HHT to detect and analyze power quality disturbance signals and harmonics. The method consists of two parts: Empirical Mode Decomposition (EMD) and Hilbert Transform (HT). After obtaining the intrinsic mode function (IMF) by EMD, Then perform a Hilbert transform, The instantaneous frequency and amplitude of the corresponding moment can be accurately characterized. Design a monitoring system combining dsp and Labview on the hardware to effectively analyze and real-time monitoring various parameters of power quality.

Since few-mode fibers (FMFs) have great potential as the new transmission media for optical communications, the ability to distinguish different fiber modes is essential. Most of the traditional schemes do not yield phase information, or are limited by beam size and mechanical requirements. Here, a method is presented to analyze the mode distribution of FMFs. The fiber modes are mapped to different frequencies by using dynamic spatial phase masks. The complex amplitudes at these frequencies indicate the amplitudes and phases of the fiber modes. The method can extract not only the amplitude distribution, but also the phase distribution of the fiber modes, and no other assisted light is needed.

Mixed infection with hepatitis E virus (HEV) in patients with chronic hepatitis B virus (HBV) infection is frequent. HEV mixed infection often leads to activation of hepatic pathological changes and worsens the inflammatory activity. However, it is not known clearly how these two types of virus influence each other in human body. Intensive investigation has revealed that HEV mixed infection inhibits HBV replication. We have just encountered a relative rare case. The patient who was a HBV carrier and was infected by HEV. Before he was infected by the HEV, the measurement of his HBV DNA fixed quantity examination on fluorescence was 3 copies/ml; his routine biochemistry was normal; and his anti HEV-IgM and anti-HEV-IgG appeared to be negative reaction. After he was infected by HEV, his routine biochemistry increased, and the measurement of his HBV DNA fixed quantity examination on fluorescence was 8.51 × 105 copies/ml. It indicated that the replication of HBV was activated after the patient infected HEV. Finally, he was dead. This case revealed that HEV mixed infection may activate the replication of HBV, not inhibit HBV replication, and demonstrated the needs for further studies about the mechanism of the interaction of the two viruses.

Goatpox, caused by goatpox virus (GTPV), is an acute feverish and contagious disease in goats often associated with high morbidity and high mortality. To resolve potential safety risks and vaccination side effects of existing live attenuated goatpox vaccine (AV41), two Semliki forest virus (SFV) replicon-based bicistronic expression DNA vaccines (pCSm-AAL and pCSm-BAA) which encode GTPV structural proteins corresponding to the Vaccinia virus proteins A27, L1, A33, and B5, respectively, were constructed. Then, theirs ability to induce humoral and cellular response in mice and goats, and protect goats against virulent virus challenge were evaluated. The results showed that, vaccination with pCSm-AAL and pCSm-BAA in combination could elicit strong humoral and cellular responses in mice and goats, provide partial protection against viral challenge in goats, and reduce disease symptoms. Additionally, priming vaccination with the above-mentioned DNA vaccines could significantly reduce the goats' side reactions from boosting vaccinations with current live vaccine (AV41), which include skin lesions at the inoculation site and fevers. Data obtained in this study could not only facilitate improvement of the current goatpox vaccination strategy, but also provide valuable guidance to suitable candidates for evaluation and development of orthopoxvirus vaccines.

Two recombinant fowlpox viruses (rFPV-P1 and rFPV-IL18-2AP12A) containing foot-and-mouth disease virus (FMDV) capsid polypeptide, 3C coding regions of O/NY00 were evaluated to determine their abilities to induce humoral and cellular responses in the presence or absence of swine IL-18 as genetic adjuvant. The ability to protect swine against homologous virus challenge was examined. All swine were given booster vaccinations at 21 days after the initial inoculation and were challenged 10 days after the booster vaccination. Control groups were inoculated with wild-type fowlpox virus (wtFPV). All animals vaccinated with rFPV-P12A and rFPV-IL18-P12A developed specific anti-FMDV ELISA antibody and neutralizing antibody and T-lymphocyte proliferation was observed. Cellular immune function was evaluated via examination of IFN-gamma production in swine peripheral blood serum. The results demonstrate the potential viability of a fowlpox virus-based recombinant vaccine in the control and prevention of FMDV infections.

Two recombinant fowlpox viruses (rFPV-ORF5-ORF3 and rFPV-IL-18-ORF5-ORF3) containing the ORF5/ORF3 cDNAs of PRRSV (strain Chang Chun) and IL-18 of swine were constructed and evaluated for theirs abilities to induce humoral and cellular responses in piglets. In addition, their abilities to protect piglets against homologous virus challenge were examined. All piglets were given booster vaccinations at 21 days after the initial inoculation, and all piglets were challenged at 60 after the initial inoculation. Control groups were inoculated with wild-type fowlpox virus (wtFPV). All animals vaccinated with rFPV-ORF5-ORF3 and rFPV-IL-18-ORF5-ORF3 developed specific anti-PRRSV ELISA antibody and neutralizing antibody, as well as T-lymphocyte proliferation response. To evaluate the cellular immune function, IFN-gamma production in pigs serum and T-lymphocytes (CD4 and CD8 T cells) in peripheral blood were examined. Following challenge with a pathogenic strain of PRRSV (strain Chang Chun), piglets inoculated with recombinant fowlpox virus (rFPV) showed lower (P