Japanese encephalitis virus (JEV) infection triggers endoplasmic reticulum (ER) stress and neuron apoptosis. ER stress sensor protein kinase R-like endoplasmic reticulum kinase (PERK) has been reported to induce apoptosis under acute or prolonged ER stress. However, whether the PERK pathway of ER stress response plays important roles in JEV-induced apoptosis and encephalitis remains unknown. Here, we found that JEV infection activates ER stress sensor PERK in neuronal cells and mouse brains. PERK activation induces apoptosis via the PERK-ATF4-CHOP apoptosis pathway upon JEV infection. Among the JEV proteins prM, E, NS1, NS2A, NS2B, and NS4B, only NS4B activates PERK. Moreover, activated PERK participates in apoptosis and encephalitis induced by JEV and NS4B. These findings provide a novel therapeutic approach for JEV-caused encephalitis.
The whole-complete genome sequence of a strain of duck tembusu virus (DTMUV), DTMUV/CH/2014, affecting layer ducks in China, was determined and characterized. Compared with DTMUV sequences available in GenBank, DTMUV/CH/2014 has 3 amino acid mutations located in the capsid, prM, and NS3 genes of DTMUV/CH/2014.
e14250 Background: Systemic administration of checkpoint inhibitors alone and especially concurrent with intratumoral administration of oncolytic herpes simplex viruses (oHSV) have a major impact on cancer therapy marred by rare failures of healthy organs. Methods: We constructed 3 families of recombinant oHSVs expressing no immunomodulatory genes (T1 series), murine or human IL-12 (T2 series) and murine or human IL-12 and anti-PD-1 antibody (T3 series). We compared the oncolytic effects of a single or multiple intratumoral injection(s) of T1, T2 and T3 series oHSVs. We also compared the effectiveness of intratumoral injection of T3 oHSV with systemic administration of anti PD-1 ab and IL12 alone or in combinations with T1. Results: Insertion of the gene encoding PD-1 Ab significantly augmented the oncolytic activity of oHSV bereft of immunostimulatory genes (T1 series) or expressing IL-12 alone (T2 series). In syngeneic mice the T3 series oHSV expressing murine IL-12 and PD-1 Ab was effective against a variety of murine tumors. Concurrent with enhanced cytolytic activity the T3 oHSV induced the production and significant intratumoral accumulation of IL-12, PD-1 Ab and IFN-γ. Consistent with an earlier report we noted an inverse correlation between the volume of the tumor and the quantity of retained IFN-γ. The most effective oncolytic effect resulted from the administration of T3855 expressing both IL12 and anti PD-1 antibody or T2850 concurrently with intraperitoneal administration of anti PD-1 antibody alone. The least effective were single intraperitoneal administration of IL12 or PD-1 antibody. Intratumoral injection of T3 oHSV was most effective against murine tumors in comparison of either systemic administration of anti PD-1 ab and IL12 or intratumoral injection of T1 in combinations of systemic administration of anti PD-1 ab and IL12. Conclusions: We report the marriage in a single therapeutic agent of three distinct cancer therapies: the targeting of cancer cells by oncolytic viruses, the stimulation of immune system by IL12, and the production of immunotherapeutic antibodies against PD-1. The significant finding reported in this article is that the anti-tumor responses remain concentrated in the tumor environment.
As the number of cores in a chip multiprocessor increase, the directory area overhead becomes excessive. Current research shows that directory area can be reduced by tracking private entries with coarse-grain region entries. The insight is that contiguous memory blocks are often accessed by a single core. In order to indicate which blocks the region owner has cached, a bit vector format is applied in the dual-grain directory (DGD). However, this limits scalability and is incompatible with the latest scalable directories. In this paper, we propose a scalable short-entry dual-grain coherence directory (SS-DGD). In private region entries, a counter is used instead of the original bit vector. To reduce the directory area, we use a separate short-entry directory to store private block entries with a pointer format and region entries with counters. The detailed simulation-based study in 64-core CMPs shows that our proposal can reduce the area overhead by 29.9% compared with DGD.
Abstract Cereal allergy has a high prevalence and incidence of sensitization worldwide, posing a serious safety risk to cereal-allergic populations. Multiple cereal allergens are often present in foods, and the complex matrix of cereal allergen-containing foods can easily affect identification. At the same time, processed foods are susceptible to contamination with trace amounts of cereal allergens such as wheat and buckwheat. Therefore, it is imperative to accurately identify multiple cereal allergens in foods. It has been shown that next-generation sequencing technologies can identify multiple species components at once and quantify species components relative to each other by relative abundance. In summary, four cereal allergens, including barley, wheat, buckwheat and sweet buckwheat were identified in the study using next-generation sequencing technology. The results showed that: ① this method can simultaneously identify wheat, barley, buckwheat, and sweet buckwheat allergens in the samples and determine the high or low content of the target allergens in the samples; ② the detection limit is as low as 0.1%; ③ is suitable for the detection of commercially available food products contain cereal allergens. In conclusion, this method provides solid and robust technical support for detecting cereal-like allergens in foods, reducing the possibility of exposure to target allergens.
Abstract Background: In China, large-scale outbreaks of severe diarrhea caused by viruses have occurred in pigs since late 2010. To investigate the prevalence and genetic evolution of diarrhea-associated viruses responsible for the outbreaks, a total of 2,987 field diarrheal samples derived from 168 pig farms in five provinces in southern China were collected during 2012-2018 and tested. Results: Porcine epidemic diarrhea virus (PEDV) was the mostly frequently detected virus with prevalence rates between 50.21% and 62.10% in samples, and 96.43% (162/168) in premises, respectively. In addition, porcine deltacoronavirus (PDCoV) was the second prevalent virus with prevalence rates ranging from 19.62% to 29.19%, and 70.24% (118/168) in premises, respectively. Both transmissible gastroenteritis virus (TGEV) and porcine rotavirus (PRoV) were detected at low prevalence rates of < 3% in samples and 10.12% in premises. In the present study, we identified the newly emerged swine acute diarrhea syndrome coronavirus (SADS-CoV) in diarrheal samples of piglets from the Fujian province in southern China, and the prevalence rate of SADS-CoV was 10.29% (7/68). Co-infections of these diarrhea-associated viruses were common. The most frequent co-infection was PEDV with PDCoV, with an average rate of 12.72% (380/2987, ranging from 8.26%-17.33%). Phylogenetic analysis revealed that of PEDV strains circulating in southern China during the last 7 years involved G IIa variant strains. The most frequent mutations were present in the collagenase equivalent (COE) and epitope regions of the spike protein of the PEDVs presently circulating in the field. Genetic characteristics of PDCoVs in this area were closely related with Chinese strains, other than the strains present in the USA, South Korea, Thailand and Lao's public. Conclusion: The findings of this study indicated that PEDV, PDCoV, and SADS-CoV were leading etiologic agents of porcine diarrhea, and severe mono-infections and co-infections of pathogenic enteric CoVs were present in pigs in Southern China during 2012 -2018. Thus, significant attention should be paid to prevent and control porcine viral diarrhea.
During investigations into the outbreak of duck viral infection in 2010 in China, with a severe drop in egg production, a flavivirus was isolated from the affected ducks. It was characterized as a Tembusu virus (TMUV). In this study, we obtained a complete genome sequence of Tembusu virus using RT-PCR and RACE techniques. TMUV genome is a singled-stranded RNA, with 10 990 nucleotides in length, and contains a single open reading frame (3410 amino acids) encoding 11 viral proteins with 5′and 3′non-translated regions (NTRs) of 142 and 618 nt, respectively. We characterized the open reading frame (ORF) with respect to gene sizes, cleavage sites and potential glycosylation sites. The different genomic regions of the virus were also compared with those of six other flaviviruses including Japanese encephalitis virus, West Nile virus (WNV), dengue-2 virus, yellow fever virus, tick-borne encephalitis virus (TBEV) and Bagaza virus. TMUV demonstrated the highest similarity to Bagaza virus. The result of entire ORF scanning shows that TMUV was close to Bagaza viruses in genetic relatedness. These data demonstrate that TMUV is a unique virus among the mosquito-borne flaviviruses and also provide a useful reference for a critically important study to determine why TMUV is a serious pathogen for ducks.
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