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VG21306 is a novel oncolytic virus (OV) that encodes a secretable bispecific T-cell engager targeting Carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6)-expressing tumors. Delivering a T-cell engager locally to a tumor mass will circumvent physical barriers that prevent antibodies from penetrating the tumor, and will mitigate the off-tumor, on-target toxicity risk. Both in vitro and in vivo testing demonstrated the expression of a functional T-cell engager capable of binding both targets. The efficacy of the engager was demonstrated in vitro, where addition of the engager payload to the OV enhanced anti-tumor efficacy against tumor cells overexpressing CEACAM6. Moreover, we have demonstrated the engager’s ability to induce bystander killing in cells lacking CEACAM6 expression, as well as engaging exhausted T cells and inducing tumor cell death. The safety of the engager was demonstrated by the lack of binding to normal human tissue or normal tissue adjacent to tumors, as well as the absence of any measurable leakage of the expressed engager into the blood of mice treated by intratumoral OV injection.

Background Pulmonary arterial smooth muscle cell (PASMC) proliferation plays a crucial role in hypoxia-induced pulmonary hypertension (HPH). Previous studies have found that resistin-like molecule β (RELM-β) is upregulated de novo in response to hypoxia in cultured human PASMCs (hPASMCs). RELM-β has been reported to promote hPASMC proliferation and is involved in pulmonary vascular remodeling in patients with PAH. However, the expression pattern, effects, and mechanisms of action of RELM-β in HPH remain unclear. Methods We assessed the expression pattern, mitogenetic effect, and mechanism of action of RELM-β in a rat HPH model and in hPASMCs. Results Overexpression of RELM-β caused hemodynamic changes in a rat model of HPH similar to those induced by chronic hypoxia, including increased mean right ventricular systolic pressure (mRVSP), right ventricular hypertrophy index (RVHI) and thickening of small pulmonary arterioles. Knockdown of RELM-β partially blocked the increases in mRVSP, RVHI, and vascular remodeling induced by hypoxia. The phosphorylation levels of the PI3K, Akt, mTOR, PKC, and MAPK proteins were significantly up- or downregulated by RELM-β gene overexpression or silencing, respectively. Recombinant RELM-β protein increased the intracellular Ca2+ concentration in primary cultured hPASMCs and promoted hPASMC proliferation. The mitogenic effects of RELM-β on hPASMCs and the phosphorylation of PI3K, Akt, mTOR, PKC, and MAPK were suppressed by a Ca2+ inhibitor. Conclusions Our findings suggest that RELM-β acts as a cytokine-like growth factor in the development of HPH and that the effects of RELM-β are likely to be mediated by the Ca2+-dependent PI3K/Akt/mTOR and PKC/MAPK pathways.

WRINKLED1 (WRI1), an

In recent years, with the rapid economic development, the scale of highway construction has continued to expand, and the lack of scientific design and construction has led to roadbed settlement problems. The paper first expounds the principle of subgrade settlement, and then discusses the influence of pavement expansion technology on subgrade settlement with an example, hoping to play a certain role in the development of similar projects.

Heat stress substantially reduces the yield potential of wheat (Triticum aestivum L.), one of the most widely cultivated staple crops, and greatly threatens global food security in the context of global warming. However, few studies have explored the heat stress tolerance (HST)-related genetic resources in wheat. Here, we identified and fine-mapped a wheat HST locus, TaHST2, which is indispensable for HST in both the vegetative and reproductive stages of the wheat life cycle. The studied pair of near isogenic lines (NILs) exhibited diverse morphologies under heat stress, based on which we mapped TaHST2 to a 485 kb interval on chromosome arm 4DS. Under heat stress, TaHST2 confers a superior conversion rate from soluble sugars to starch in wheat grains, resulting in faster grain filling and a higher yield potential. A further exploration of genetic resources indicated that TaHST2 underwent strong artificial selection during wheat domestication, suggesting it is an essential locus for basal HST in wheat. Our findings provide deeper insights into the genetic basis of wheat HST and might be useful for global efforts to breed heat-stress-tolerant cultivars.

A surface insulating coating for wind turbines is prepared to study its electrically insulating properties. The effects of different resin base materials, different fillers, and curing processes on the electrical properties of coatings were studied. The results show that when an epoxy resin containing hydroxyl active functional groups and benzene rings is selected as the base material for the coating, the coating shows good electrical insulation performance. Its volume resistivity achieves 17.689×1012Ω∙m, electric strength 45.8 kV/mm, and arc resistance 130s. Mica powder and aluminum tripolyphosphate, as good anticorrosive media, have good electrical insulation performance. Other application indexes and economies should be considered in engineering applications. When the curing agent content is 25%, the coating has the best electrical properties. The longer the curing time, the better the electrical properties of the coating. However, the marginal effect of curing time is diminishing. When curing time exceeds 48h, curing time has little effect on electrical properties. The objective of this paper is to promote the development of surface insulating coatings for wind turbines.

In order to study the degradation of organic matter and the change of maturity in the process of agricultural plant enzyme composting, two groups of composting experiments were set up, including adding enzyme composting agent and no adding enzyme composting agent. The dynamic changes of organic carbon, total nitrogen and C / N ratio were measured, and the maturity indexes such as temperature, pH, electrical conductivity, E4 / E6 and germination rate index were analyzed Research. The results showed that: 1. The addition of enzyme decomposing agent could promote the degradation of organic matter and the accumulation of total nitrogen, which were 29% and 3.9% higher than the blank group, respectively. The accumulated temperature of > 50 °C and 50 °C - 40 °C was 23% and 26% higher than that of blank group respectively. Accelerate and improve the germination rate of seeds, and reach the basic non-toxic standard 10 days before the blank group. 2. The overall trend of fermentation in the two groups was basically the same. The temperature increased first and then decreased. The pH, electrical conductivity (EC), E4 / E6 and seed germination rate (GI) increased gradually with the composting process. Except that E4 / E6 value was higher than the maturity standard and further composting was needed, the other indexes met the maturity standard.

Pulmonary hypertension（PH）is a kind of hemodynamic and pathophysiological state, in which the pulmonary artery pressure (PAP) rises above a certain threshold. The main pathological manifestation is pulmonary vasoconstriction and remodelling progressively. More and more studies have found that ions play a major role in the pathogenesis of PH. Many vasoactive substances, inflammatory mediators, transcription-inducing factors, apoptosis mediators, redox substances and translation modifiers can control the concentration of ions inside and outside the cell by regulating the activity of ion channels, which can regulate vascular contraction, cell proliferation, migration, apoptosis, inflammation and other functions. We all know that there are no effective drugs to treat PH. Ions are involved in the occurrence and development of PH, so it is necessary to clarify the mechanism of ions in PH as a therapeutic target for PH. The main ions involved in PH are calcium ion (Ca 2+ ), potassium ion (K + ), sodium ion (Na + ) and chloride ion (Cl – ). Here, we mainly discuss the distribution of these ions and their channels in pulmonary arteries and their role in the pathogenesis of PH.

To investigate the variation of rotten degree of a composting process applied with agricultural plant enzyme, and instruct the farmers to make innoxious, stable and environment-friendly compost, we conducted two sets of compost applied with and without agricultural plant enzyme. The tests were conducted under the condition of high-temperature aerobic compost, in which variables including temperature, PH value, electric conductivity (EC), E4/E6, rate of seed germination (SG) and physical sense of the compost were measured to assess its rotten degree. The results showed: 1. The measured variables followed the similar trends in the compost processes applied with and without the agricultural plant enzyme. The temperature increased at first and then decreased, while the PH value, EC, E4/E6. SG kept increasing as the compost proceeded. 2. Applying bacteria helped to lift and maintain the temperature of the compost, accelerated and improved the SG, facilitated the process of calcification and humification, while had limited effect on PH values, EC and E4/E6. 3. Though the materials were covered with hypha when the main fermentation completed, SG has not reached the expected rotten degree. Currently, farmers generally think that "materials covering with hypha" indicates the competition of humification.

VG2025 is a genetically modified HSV-1 oncolytic virus (OV) wherein the transcription and translation of critical viral genes are regulated to enhance virus safety and promote tumor specific virus replication without attenuating the virus. The TTDR design is based on transcriptional control of the essential HSV-1 immediate-early protein ICP27 using a tumor specific CEA promoter, coupled with translational control of the key neurovirulence factor ICP34.5 accomplished by introducing multiple tandem copies of miRNA binding sites for miR-124 and miR-143 which are downregulated in tumors but abundantly expressed in normal brain tissues. The anti-tumor and immune stimulatory properties of VG2025 are also enhanced by expressing a pair of cytokines (IL-12 and IL-15/IL-15Rα complex) that are linked by 2A cleavage peptides and controlled by the tumor specific promoter CXCR4. The dual regulation strategy was verified in vitro and shown to be highly selective. Growth of VG2025 virus correlated with CEA expression in a panel of cell lines including normal cells and a selection of tumor cells with varying CEA levels. miRNA-mediated regulation of ICP34.5 expression was validated by transfecting HEK293t cells with miR-124 and miR-143 precursors, followed by infection with VG2025. RT-qPCR testing revealed a significant decrease in the levels of viral ICP34.5 mRNA when the miRNA was present. VG2025 virus replication was evaluated in a variety of human tumor cell lines, and two cell lines representing NSCLC and pancreatic cancer (A549 and BxPC3, respectively) were selected for testing in a humanized mouse model, where VG2025 displayed strong in vivo anti-tumor efficacy. The immune stimulatory characteristics of VG2025, and the bioactivity of expressed cytokines, were demonstrated in a syngeneic mouse colorectal tumor model (CT26) and lymphoma model (A20) using VG2026, which is an identical mouse specific variant of VG2025 that expresses murine IL-12 in place of human IL-12. In addition to a significant reduction in the growth of injected tumors, we observed a clear abscopal effect on contralateral tumors, indicating a robust anti-tumor immune response with an immune memory effect. Due to the tendency of HSV-1 to establish latency which may lead to neurotoxicity and potential safety concerns, we performed a safety pharmacology study by subcutaneously inoculating immunocompetent DBA mice with VG2025. Absence of neurotoxicity was further verified by more aggressive routes of administration, including via the nose and by corneal scarification. The risk of VG2025 reactivation from a latent state was evaluated in a two-step study: latent infection in the CNS was first established and confirmed, then the trigeminal ganglia were removed and co-cultured with Vero cells to detect reactivation-related cytopathic effects. All studies showed that VG2025 was safe with no reactivation events detected. Citation Format: Yanal Murad, Guoyu Liu, I-Fang Lee, Zahid Delwar, Dmitry Chouljenko, Will Liu, Jun Ding, Luke Bu, Ronghua Zhao, William Jia. VG2025: Transcriptional and translational dually regulated (TTDR) oncolytic virus for cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5205.

Oncolytic virotherapy is a promising new tool for cancer treatment, but direct lytic destruction of tumor cells is not sufficient and must be accompanied by strong immune activation to elicit anti-tumor immunity. We report here the creation of a novel replication-competent recombinant oncolytic herpes simplex virus type 1 (VG161) that carries genes coding for IL-12, IL-15, and IL-15 receptor alpha subunit, along with a peptide fusion protein capable of disrupting PD-1/PD-L1 interactions. The VG161 virus replicates efficiently and exhibits robust cytotoxicity in multiple tumor cell lines. Moreover, the encoded cytokines and the PD-L1 blocking peptide work cooperatively to boost immune cell function. In vivo testing in syngeneic CT26 and A20 tumor models reveals superior efficacy when compared to a backbone virus that does not express exogenous genes. Intratumoral injection of VG161 induces abscopal responses in non-injected distal tumors and grants resistance to tumor re-challenge. The robust anti-tumor effect of VG161 is associated with T cell and NK cell tumor infiltration, expression of Th1 associated genes in the injection site, and increased frequency of splenic tumor-specific T cells. VG161 also displayed a superb safety profile in GLP acute and repeated injection toxicity studies performed using cynomolgus monkeys. Overall, we demonstrate that VG161 can induce robust oncolysis and stimulate a robust anti-tumor immune response without sacrificing safety.

BACKGROUND: Pulmonary arterial smooth muscle cells(PASMCs) proliferation plays a crucial role in Hypoxia-induced pulmonary hypertension(HPH). Previous studies have found that Resistin-like molecule β(RELM-β) up-regulated de novo in response to hypoxia in cultured primary human PASMCs(HASMCs). RELM-β has been proved to promote PASMCs proliferation and involved in pulmonary vascular remodeling of patients with PAH. However, the expression pattern, the effects, and the mechanisms of RELM-β in HPH keep unknown. METHODS: We assessed the expression pattern, mitogenetic effect, and underlying mechanism of RELM-β in the rat HPH model and HASMCs. RESULTS: Overexpression of RELM-β alone caused the hemodynamic change in the rat model of HPH, similar to that caused by chronic hypoxia, with increased mean pulmonary arterial pressure(mPAP), right ventricle hypertrophy(RVSP), and thickening of small pulmonary arterioles. Knocking down of RELM-β partially blocked the increased mPAP, RVSP, and vascular remodeling induced by hypoxia. Phosphorylated PI3K/Akt/mTOR and PKC/MAPKs proteins were significantly up- or down-regulated by RELM-β gene overexpression or silencing. Recombinant RELM-β protein increase primary cultured human PASMCs intracellular Ca 2+ concentration and promote HASMCs proliferation. The mitogenic effect of RELM-β on HASMCs and phosphorylated PI3K/Akt/mTOR and PKC/MAPKs was suppressed by Ca 2+ inhibitor. CONCLUSIONS: Our findings suggested that RELM-β acts as a cytokine-like growth factor in the development of HPH and that this process is likely mediated by the Ca 2+ dependent PI3K/Akt/mTOR and PKC/MAPKs pathway. Keywords : hypoxic pulmonary arterial hypertension; resistin-like molecule β; Ca 2+ ; pulmonary vascular remodeling; signaling pathway

The dityrosine layer is a unique structure present in the spore wall of the budding yeast Saccharomyces cerevisiae. The primary constituent of this layer is bisformyl dityrosine. A sporulation-specific protein, Dit1 is localized in the spore cytosol and produces a precursor of bisformyl dityrosine. Although Dit1 is similar to isocyanide synthases, the loss of Dit1 is not rescued by heterologous expression of the Pseudomonas aeruginosa isocyanide synthase, PvcA, indicating that Dit1 does not mediate isocyanidation. The product of Dit1 is most likely formyl tyrosine. Dit1 can produce its product when it is expressed in vegetative cells, however, formyl tyrosine was not detected in the crude cell lysate. We reasoned that formyl tyrosine is unstable and reacts with some molecule to form formyl tyrosine-containing molecules in the cell lysate. In support of this hypothesis, formyl tyrosine was detected when the lysate was hydrolyzed with a mild acid. The same property was also found for bisformyl dityrosine. Bisformyl dityrosine molecules assemble to form the dityrosine layer by an unknown mechanism. Given that bisformyl dityrosine can be released from the spore wall by mild hydrolysis, the process of formyl tyrosine-containing molecule formation may resemble the assembly of the dityrosine layer.

In the budding yeast Saccharomyces cerevisiae, Svl3 and Pam1 proteins work as functional homologues. Loss of their function causes increased levels of chitin deposition in the cell wall and temperature sensitivity, suggesting their involvement in cell wall formation. We found that the N- and C-termini of these proteins have distinctive and critical functions. They contain an N-terminal part that has a probable 2-dehydropantoate 2-reductase domain. In Svl3, this part can be replaced with the yeast 2-dehydropantoate 2-reductase, Pan5, suggesting that Svl3 and its homologues may be able to mediate 2-dehydropantoate 2-reductase function. On the other hand, Svl3 is recruited to the bud tip and bud neck via multiple localization signals in the C-terminal part. One of such signals is the lysine-rich region located in the C-terminal end. The function and localization of Svl3 are significantly disrupted by the loss of this lysine-rich region; however, its localization is not completely abolished by the mutation because another localization signal enables appropriate transport. Svl3 and Pam1 orthologues are found in cells across fungal species. The Svl3 orthologues of Candida glabrata can complement the loss of Svl3 and Pam1 in S. cerevisiae. C. glabrata cells lacking the SVL3 and PAM1 orthologue genes exhibit phenotypes similar to those observed in svl3∆pam1∆ S. cerevisiae cells. Thus, Svl3 homologues may be generally required for the assembly of the cell wall in fungal cells.

A common issue encountered when drilling in the Permian Basin involves the twist-off of a bottomhole assembly (BHA) component. A twist-off incident can result in significant costs incurred due to nonproductive time (NPT) as well as lost-in-hole (LIH) charges if retrieval of the fish is unsuccessful. The paper will present several case studies to illustrate the primary cause of the failures. An innovative thread connection for BHA components was designed in 2016 to reduce risk of twist-off. The paper will demonstrate its effect on reducing twist-off risk as well as the enablement of improved drilling performance in 2019. The paper will illustrate statistical analysis of data gathered from 2016 through 2019 comparing the performance of the conventional thread connection versus the new thread design. The goal of the analysis is to evaluate whether the thread design is effective in reducing the frequency of twist-off incidents. The bending moment of each connection within the BHA will be analyzed using modeling software to understand the stress-loading profile. Memory data from the rotary steerable system (RSS), including near-bit attitude measurements and downhole drilling dynamics, will be analyzed in conjunction with data acquired from the rig's surface sensors to identify if any abnormal drilling events are observed prior to the twist off. The BHA bending moment study concludes that connections between the measurements-while-drilling (MWD) tool and the RSS suffer higher stress loading compared to other connections in the BHA. Empirically, field statistics confirm that the connections between RSS and MWD exhibit the highest frequency of twist-off incidents. However, further analysis is required to understand the root cause of the connection failure. The memory data retrieved from the RSS enables the visualization of hole curvature and vibration at the time of the incident. Investigation into several field cases concluded that, immediately prior to connection twist off, there is sudden change in borehole curvature and/or emergence of shock and vibration (S&V) which can dramatically reduce the expected fatigue life of the connection. Based on the statistical analysis, it can be concluded that the new connection design is effective in reducing the twist-off failure rate of the BHA. Consequently, the implementation of the new thread design enabled a step-change in drilling performance through use of a more powerful positive displacement motor (PDM) to drive the RSS system.

Background Chitin is an important component of the insect exoskeleton and peritrophic membrane. Chitin synthase 1 (CHS1) is a key enzyme in the chitin synthesis pathway, and has a role in insect molting and growth. Plant-mediated RNA interference (RNAi) has been used as a more target-specific and environmentally safe approach to prevent and control agricultural insects. The aims of this study were to use grain aphid (Sitobion avanae) CHS1 as the target gene and to produce transgenic wheat lines for aphid control via plant-mediated RNAi. Results Expression levels of CHS1 changed at different developmental stages. After feeding on the representative T3 transgenic lines Tb5-2 and Tb10-3, CHS1 expression levels in grain aphid decreased by 50.29% and 45.32%, respectively; and total and molting aphid numbers reduced significantly, compared with controls. Consistent with this, aphid numbers in mixed natural populations reduced significantly in the respective T4 and T5 transgenic lines under field conditions, and T5 transgenic lines had higher grain weight compared with the unsprayed insecticide wild-type and insecticide-sprayed wild-type. Conclusion These results indicate that plant-mediated RNAi of the grain aphid CHS1 gene confers common wheat resistance against aphids. © 2018 Society of Chemical Industry.

Potassium (K+) is the most abundant inorganic cation in plants, and molecular dissection of K+ deficiency has received considerable interest in order to minimize K+ fertilizer input and develop high quality K+-efficient crops. However, the molecular mechanism of plant responses to K+ deficiency is still poorly understood. In this study, 2-week-old bread wheat seedlings grown hydroponically in Hoagland solution were transferred to K+-free conditions for 8 d, and their root and leaf proteome profiles were assessed using the iTRAQ proteome method. Over 4000 unique proteins were identified, and 818 K+-responsive protein species showed significant differences in abundance. The differentially expressed protein species were associated with diverse functions and exhibited organ-specific differences. Most of the differentially expressed protein species related to hormone synthesis were involved in jasmonic acid (JA) synthesis and the upregulated abundance of JA synthesis-related enzymes could result in the increased JA concentrations. Abundance of allene oxide synthase (AOS), one key JA synthesis-related enzyme, was significantly increased in K+-deficient wheat seedlings, and its overexpression markedly increased concentrations of K+ and JA, altered the transcription levels of some genes encoding K+-responsive protein species, as well as enhanced the tolerance of rice plants to low K+ or K+ deficiency. Moreover, rice AOS mutant (osaos) exhibited more sensitivity to low K+ or K+ deficiency. Our findings could highlight the importance of JA in K+ deficiency, and imply a network of molecular processes underlying plant responses to K+ deficiency.

Poly(lactic acid) (PLA)/poly(ϵ-caprolactone) (PCL)/nano-silica composite degradable films were prepared by a solvent casting method. SEM results showed that the nano-silica particles were dispersed...

Herein we demonstrate that ultraviolet light-inactivated Herpes Simplex Virus-1 (UV-HSV-1) stimulates peripheral blood mononuclear cells (PBMCs) to lyse both androgen-sensitive and androgen-independent prostate cancer (PrCA) cell lines, but not the benign prostatic hyperplastic epithelial cell line, BPH-1, and is 1000-10,000-fold more potent at stimulating this killing than ultraviolet light-inactivated Vesicular Stomatitis Virus, adenovirus, reovirus or cytomegalovirus. Among PBMCs, natural killer (NK) cells appear to be a major cell type involved in this killing and UV-HSV-1 appears to directly and potently stimulate NK cell expression of CD69, degranulation, cytokine production, and migration to IL-8 in PC3 conditioned medium. We also found that UV-HSV-1 stimulates glycolysis in PBMCs and NK cells, and that 2-deoxyglucose and the protein kinase C inhibitor, Go6976, and the NFκB inhibitor, Bay 11-7082, all abrogate UV-HSV-1 activated killing of PC3 cells by PBMCs and NK cells. Using neutralizing anti-Toll-like receptor 2 (TLR2) we found that UV-HSV-1, like HSV-1, activates NK cells via TLR2. Taken together, these results are consistent with Toll-like receptor 2 ligands on UV-HSV-1 stimulating TLR2 on NK cells to activate protein kinase C, leading to enhanced glycolysis and NFκB activation, both of which play a critical role in this anti-PrCA innate immune response. Importantly, UV-HSV-1 synergizes with IL-15 to increase the cytolytic activity of PBMCs against PC3 cells and there was considerable donor-to-donor variation in killing ability. These results support the preclinical development of UV-HSV-1 as an adjuvant, in combination with IL-15, for cell infusions of healthy, preselected NK cells to treat PrCA.

Based on virtual assembly simulation technique for installing cables on biaxial drive mechanism, this paper describes the process of building flexible virtual assembly environment and simulating installation of cables. First of all, the basic element of cable-laying is simulated, such as wires, thermistors, heat plates, etc. Then the process of cable laying is simulated and analyzed by step level in detail. The laying path of each wire is carefully planned in the complex space surface of biaxial drive mechanism. The feasibility of the path is validated in view of overall laying course. The length of each wire can be determined. So it can get the specific process parameters. The project application results indicate that the virtual simulation technique can optimize the process of the spacecraft assembly and integration design, avoid faults by mistake, extend the process expression technique, insure the reliability of irreversible operations, and enhance the level of process design.

Oncolytic viruses (OVs) are the wild-type or genomic modified viruses, which can specifically replicate in cancer cells but not in normal cells. They cause cancer cell lysis and more importantly, their replication in tumor cells induces an antitumor immune response from the host. As synergistic stimulation of antitumor immune response requires multiple immune-regulatory factors, OVs armed with multiple immune-modulating factors are of high potential in cancer immunotherapy. We have constructed a novel herpes simplex virus type-1 virus (HSV-1), VG161, that is armed with IL12, IL15, and a unique PDL-1 peptide blocker. The aim of this study is to investigate the anticancer efficacy of VG161 in gastrointestinal (GI) cancers including gastric, hepatic, and colorectal cancers. The immune-stimulating activities in tumor-bearing immune competent mice were also demonstrated. VG161 was given to the tumor-bearing animals by intratumor injection (5 × 106-5 × 107 PFU/animal, once a day for 3-5 days). Antitumor activity of VG161 was tested in both immune-deficient mice as well as in immune-competent mice. Oncolytic activity of VG161 was demonstrated in human gastric (SGC-7901), hepatic (patient-derived xenograft, PDX), and colorectal (LS174T) cancer-bearing nude mice as the human tumors are susceptible to HSV infection and the immune system is compromised in those models. To determine the antitumor immune response activated by VG161, colorectal cancer (CT26) syngeneic model was used in immune competent animals and T cell subpopulation analysis, ELISPOT, and tumor rechallenge assay was applied to measure specific antitumor immunity. VG161 caused complete tumor eradication in PDX and CT26 tumor models and significantly inhibited tumor growth in SGC-7901 and LS174T models. All animals treated with VG161 survived for many months till sacrificed. In the CT26 model, no tumor could be found after rechallenging with the same tumor cells. The number of CD8+ tumor infiltrated T cells was significantly increased, and systemic specific anticancer immunity was confirmed by ELISPOT assay on T cells isolated from spleen. VG161 is a novel oncolytic virus that is both strong in oncolysis and stimulating antitumor immunity for GI cancers. Intratumorally expressing multiple immune-regulatory factors by an oncolytic virus may significantly change the GI tumor immune microenvironment and stimulate anticancer immunity, to further enhance the efficacy of the oncolytic virus. Citation Format: Ronghua Zhao, Jun Ding, Tianchi Liu, Shuyun Liu, Dmitry Chouljenko, Yanal Murad, Erica Lee, Guoyu Liu, Luke Bu, William Jia. Anticancer efficacy of a novel immune-stimulating oncolytic virus: VG161 in gastrointestinal cancers [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr B85.

Chitin is an important component of the insect exoskeleton and peritrophic membrane. Chitin synthase 1 (CHS1) is a key enzyme in the chitin synthesis pathway, and has a role in insect molting and growth. Plant-mediated RNA interference (RNAi) has been used as a more target-specific and environmentally safe approach to prevent and control agricultural insects. The aims of this study were to use grain aphid (Sitobion avanae) CHS1 as the target gene and to produce transgenic wheat lines for aphid control via plant-mediated RNAi.Expression levels of CHS1 changed at different developmental stages. After feeding on the representative TThese results indicate that plant-mediated RNAi of the grain aphid CHS1 gene confers common wheat resistance against aphids. © 2018 Society of Chemical Industry.

Human cytomegalovirus (HCMV), a herpesvirus, is an important human pathogen that causes asymptomatic infections in healthy or immunocompetent individuals but can lead to severe and potentially life-threatening complications in immune-immature individuals such as neonates or immune-compromised patients such as organ-transplant recipients and HIV-positive individuals. Congenital HCMV infection represents a significant public health issue and poses substantial healthcare and economic burden to society. This virus causes the most common viral congenital infection worldwide, and is the leading non-genetic cause of sensorineural hearing loss in children in developed countries. Congenital HCMV infection is believed to fulfill the criteria of the American College of Medical Genetics to be considered as a condition targeted for a newborn screening program. This is because congenital HCMV infection can be identified during a time (within 2 days after birth) at which it would not ordinarily be detected clinically, and there are demonstrated benefits of early detection, timely intervention, and efficacious treatment of the condition. Recent progresses in developing polymerase chain reaction-based approaches to detect HCMV in samples obtained from newborns have generated much excitement in the field. In this review, we highlight the recent progress in diagnostic techniques that could potentially be used for the detection of HCMV infection in neonates and its direct implications in public health settings for diagnosing congenital HCMV infection.

Oncolytic viruses (OVs) are among the most powerful approaches in cancer immunotherapy. OVs not only cause cancer cell lysis but more importantly, their infection in tumors induces anti-tumor immune response from the host, resulting in lasting anti-tumor immunity. It has been recognized that anti-tumor immune response requires multiple immune regulatory factors that act synergistically and tumor microenvironment is critical for tumor to grow. Herpes simplex virus type-1 (HSV-1) has been approved by FDA as an oncolytic viral drug to treat melanoma. One advantage of HSV-1 is its large genomic capacity for carrying multiple exogenous genes.A HSV-1 oncolytic viral vector (VG161) was constructed to simultaneously express IL12, IL15 with its receptor alpha unit and a PDL-1 blocking peptide. Antitumor activity of VG161 was tested in both immune competent mice (CT26 and A20 tumor models) and nude mice for human tumor models (LNCaP and U87). Since CT26 and A20 are poorly permissive for HSV-1 replication, the mouse tumor models were able to demonstrate the antitumor immune response induced by VG161 while oncolytic activity of VG161 was demonstrated in LNCaP and U87 models since the immune system is compromised in those models.VG161 completely inhibited tumors in all the models tested and the animals survived tumor-free for many months till sacrificed. VG161 induced tumor oncolysis in both LNCaP and U87 tumors. In the CT26 model, animals were protected from the second challenging with CT26 cells following previous virally induced tumor regression. Furthermore, in a A20 double tumor model, intratumoral injection into the tumor on one side caused tumor regression on both sides. Transcriptome analysis showed significant change in tumor microenvironment. Finally, tumor specific memory T-cells were evident in the treated animals. The anti-tumor immune response by VG161 was significantly stronger than similar viruses that did not express any immune stimulating gene or only express GM-CSF. These results showed that intratumorally expressed multiple immune regulatory factors by an oncolytic virus may significantly change the tumor immune microenvironment to enhance efficacy of the oncolytic virus. Citation Format: Ronghua Zhao, Jun Ding, Dmitry Choujenko, Yanal Murad, Erica Lee, Guoyu Liu, Luke Bu, William Jia. Synergistic activation of antitumor immunity by an oncolytic virus VG161 armed with multiple immune-stimulating genes [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B059.

The thermodynamics properties of novel branched gemini imidazolium surfactants (BGIS) with different numbers of carbon atoms in the hydrophobic group or hydroxyl numbers of the spacer are studied by the free energy perturbation (FEP) model. In the FEP model, the Gibbs free energy contributions to the driving force for micelle formation are computed using hydration data obtained from molecular dynamics simulations. The thermodynamic properties of micellization in aqueous solutions for BGIS were discussed according to the pseudo-phase separation model. The results show that the micellization of BGIS in aqueous solutions is a spontaneous and entropy-driven process. It is linearly enthalpy-entropy compensated. The compensation temperature of BGIS was lower for BGIS with hydroxyl group than without it at 297 ± 3 versus 307 ± 3 K. The contribution of entropy change to the micellization tends to decrease, while the contribution of enthalpy change tends to increase. In particular, as the number of hydroxyl groups in spacer is increased, the thermodynamic favorability and stability of the micelles of BGIS with hydroxyl group improve significantly.

The function of a wheat starch regulator 1 (TaRSR1) in regulating the synthesis of grain storage starch was determined using the barley stripe mosaic virus—virus induced gene-silencing (BSMV-VIGS) method in field experiments. Chlorotic stripes appeared on the wheat spikes infected with barley stripe mosaic virus-virus induced gene-silencing- wheat starch regulator 1 (BSMV-VIGS-TaRSR1) at 15 days after anthesis, at which time the transcription levels of the TaRSR1 gene significantly decreased. Quantitative real-time PCR was also used to measure the transcription levels of 26 starch synthesis-related enzyme genes in the grains of BSMV-VIGS-TaRSR1-silenced wheat plants at 20, 27, and 31 days after anthesis. The results showed that the transcription levels of some starch synthesis-related enzyme genes were markedly induced at different sampling time points: TaSSI, TaSSIV, TaBEIII, TaISA1, TaISA3, TaPHOL, and TaDPE1 genes were induced at each of the three sampling time points and TaAGPS1-b, TaAGPL1, TaAGPL2, TaSSIIb, TaSSIIc, TaSSIIIb, TaBEI, TaBEIIa, TaBEIIb, TaISA2, TaPHOH, and TaDPE2 genes were induced at one sampling time point. Moreover, both the grain starch contents, one thousand kernel weights, grain length and width of BSMV-VIGS-TaRSR1-infected wheat plants significantly increased. These results suggest that TaRSR1 acts as a negative regulator and plays an important role in starch synthesis in wheat grains by temporally regulating the expression of specific starch synthesis-related enzyme genes.

In recent years, as China's coal mining strength has increased, the accident of coal mine thus happened frequently. It is often caused by the human factors, and there is no doubt that the unsafe behavior of the people and psychological conditions were closely linked together. In the safety production, we should put “people-oriented, pay attention to the human care” into effect. Strengthening the safety psychological education in the coal mine safety management, further training psychological sense of anxiety through the safety education and then improving the staff's psychological quality should go first in reducing safety accidents, which is also one of the best ways to prevent the coal mine accidents. This paper focused on the exploration about some psychological factors in the coal mine accidents, and then gave the methods to evaluate the safety psychological factors in the safety production. The facts proved us that it had caution effect to the coal mine accident, and at the same time the coal mine principal should attach importance to miners’ psychological education.

This study was focused on the experimental investigations about mechanical characteristics and tribological mechanisms of nanometric zirconia dental ceramics. A universal mechanical testing machine was used to test the three- point flexural strength and the fracture toughness. A microhardness tester was used to test the Vickers hardness of the test specimens. An MRH-3 digital-display high-speed ring-on-block tribometer was used for frictional wear experiments. A PGI800 coarseness profiling instrument was used to test the width and the length of the grinding defects on specimen surfaces. An S-3500N SEM was employed in the microscopic observation of the surface morphology after the abrasion. Results indicates that the flexural strength of the test specimens � 890MPa, the fracture toughness � 6Mpa.m 1/2 , the Vickers hardness � 1240MPa, the linear contraction � 21%, and the apparent porosity � 0.32%. Moreover, the frictional factor and the wear rate of nanometric ZrO2 ceramics decreased significantly under identical working and frictional conditions compared with ZrO2. The wear mechanism of nanometric ZrO2 ceramics was micromachining and plastic deformation while the wearing mechanism of ZrO2 ceramics was brittle fracture and abrasive wear.

Molecular dynamics simulations and free energy perturbation (FEP) were performed for studying the enthalpy-entropy compensation with a series of ionic liquid-type Gemini imidazolium surfactants (ILGIS), with different carbon atoms of the hydrophobic group or the spacer chain length, in aqueous solutions. According to the law of mass action, the thermodynamic properties of micellization in aqueous solutions for ILGIS were discussed. The results show that the solvation free energy changes calculated from the free energy perturbation are close to the Gibbs free energy calculated from the surface tension method and can be used to discriminate the tendency for micellization and predict the thermodynamic properties of ILGIS. The micellization of ILGIS in aqueous solutions is a spontaneous and entropy-driven process. It is enthalpy-entropy compensated, and the enthalpy-entropy compensation plots exhibit an excellent linearity. The compensation temperature was found to be (307±2) K. As the number carbon atoms in the alkyl chains is increased, the tendency and stability of micellization both increase. At spacer length S≤6, with the spacer chain length increasing, the thermodynamic favorability and stability of the micelles decrease. However, if S>6, thermodynamic favorability and stability increase with raising the spacer chain length.

A method for the preparation of pentaerythrityl tetraimidazole was reported with pentaerythritol and imidazole as raw material. Pentaerythrityl tetrabromide(PEBr4) was first prepared starting from pentaerythritol via two steps. Pentaerythrityl tetrabromide was then treated with imidazole, which was converted to pentaerythrityl tetraimidazole. The overall yield was 68.6%. The target product was analyzed and characterized by 1H-NMR and 13C-NMR methods, indicating that our route of synthesis is reasonable and feasible.