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Pleckstrin homology-like domain family A, member 3 (PHLDA3) is a novel tumor-related protein that mediates carcinogenesis of multiple cancers. However, the relevance of PHLDA3 in prostate cancer has not been explored. The purpose of this work was to illustrate the possible roles and mechanisms of PHLDA3 in prostate cancer. Our data showed strikingly lower abundance of PHLDA3 in prostate cancer, and that low levels of PHLDA3 in prostate cancer patients was associated with reduced survival. PHLDA3 was also weakly expressed in prostate cancer cells, and demethylation treatment dramatically up-regulated the expression level of PHLDA3. Up-regulation of PHLDA3 restrained proliferation, induced G1 cell cycle arrest, suppressed epithelial-mesenchymal transition of prostate cancer cells. In addition, up-regulation of PHLDA3 increased the sensitivity of prostate cancer cells to docetaxel In-depth research into the mechanism elucidated that PHLDA3 overexpression decreased the phosphorylation of Akt and suppressed the activation of Wnt/β-catenin signaling. Overexpression of constitutively active Akt strikingly abolished PHLDA3-mediated inactivation of Wnt/β-catenin pathway. A xenograft assay revealed that prostate cancer cells with PHLDA3 overexpression displayed reduced tumorigenicity in vivo. Collectively, these data document that PHLDA3 exerts an outstanding cancer-inhibiting role in prostate cancer by down-regulating Wnt/β-catenin pathway via the inhibition of Akt. This work highlights PHLDA3 as a novel anticancer target for prostate cancer.

TIGIT is an emerging novel checkpoint target that is expressed on both tumor-infiltrating T cells and NK cells. Some current investigational antibodies targeting TIGIT have also achieved dramatic antitumor efficacy in late clinical research. Most recently, the relevance of NK cell–associated TIGIT signaling pathway to tumors’ evasion of the immune system has been clearly revealed, which endows NK cells with a pivotal role in the therapeutic effects of TIGIT blockade. In this article, we describe a novel anti-TIGIT monoclonal antibody, AET2010, which was acquired from a phage-displayed human single-chain antibody library through a cell panning strategy. With emphasis on its regulation of NK cells, we confirmed the excellent ex vivo and in vivo antitumor immunity of AET2010 mediated by the NK-92MI cells. Intriguingly, our work also revealed that AET2010 displays a lower affinity but parallel avidity and activity relative to MK7684, an investigational monoclonal antibody from MSD, implying a reasonable balance of potency and potential side effects for AET2010. Together, these results are promising and warrant further development of AET2010.

Prostate specific membrane antigen positron emission tomography (PSMA PET) is an excellent molecular imaging technique for prostate cancer. Currently, PSMA PET for patients with primary prostate cancer is supplementary to conventional imaging techniques, according to guidelines. This supplementary function of PSMA PET is due to a lack of systematic review of its strengths, limitations, and potential development direction. Thus, we review PSMA ligands, detection, T, N, and M staging, treatment management, and false results of PSMA PET in clinical studies. We also discuss the strengths and challenges of PSMA PET. PSMA PET can greatly increase the detection rate of prostate cancer and accuracy of T/N/M staging, which facilitates more appropriate treatment for primary prostate cancer. Lastly, we propose that PSMA PET could become the first-line imaging modality for primary prostate cancer, and we describe its potential expanded application.

Background: Immune-related genes (IRGs) are key contributors to bladder cancer (BLCA) development. Whether IRGs-based prognostic signature can predict the prognosis of BLCA patients deserves to be investigated. Methods: Data were downloaded from the Cancer Genome Atlas (TCGA) and gene expression omnibus (GEO) database. The differentially expressed IRGs (DEIRGs) were analyzed through Wilcoxon test. Univariate Cox regression analysis was used to identify the prognostic DEIRGs (PDEIRGs), and multivariate Cox regression analysis was employed to construct a prognostic model. The predictive accuracy and independent forecasting ability were evaluated. Tumor-infiltrating immune cells (TIICs) were obtained through Tumor Immune Estimation Resource (TIMER) website and CIBERSORT method. The correlations between present prognostic signature and clinical variables or TIICs were explored. Furthermore, a transcription factors (TFs)-based regulatory network and enrichment analysis were performed to explore the underlying mechanism. Findings: 3126 DEGs, 261 DEIRGs and 24 PDEIRGs were identified. Ten optimal PDEIRGs were adopted to construct a prognostic model, which can serve as an independent prognostic predictor with excellent predictive accuracy. This model could reflect the clinical variables and TIICs, which further verified its reliability in BLCA prognosis prediction. Besides, several immune-related GO terms and KEGG pathways were significantly enriched, and TFs might involve with PDEIRGs regulating. Interpretation: We find a valuable PDEIRGs-based prognostic signature for BLCA patients and reveal the potential regulatory mechanism. Funding Statement: This study was supported by grants from the National Key Basic Research Development Program (973 Program) (No. 2013CB530500), the National Natural Science Foundation of China (No. 81372225, 81372771, 81772734, 81802935) and the Innovation Capability Support Plan of Shaanxi Province (2020PT-021). Declaration of Interests: The authors declare that they have no competing interests.

The frost heave of soil has a significant influence on the stability and durability of various infrastructures. It is necessary to investigate the occurrence mechanism and development law of soil frost heaving. In this research, a triaxial frost heave experimental setup was developed, and a series of frost heave experiments were carried out by considering different confining pressures, deviator stresses, temperature gradients, and water supply conditions. The research found that the temperature gradient was the core driving force of soil frost heave. The increase of deviator stress and confining pressure would limit the development of frost heave by inhibiting water absorption. The growth of warm end temperature would increase the temperature of both water supply and soil near the warm end, which restrained the development of soil frost heaving. Finally, an improved prediction model for saturated clay soil's frost heave ratio was developed based on Takashi's one-dimensional frost heave ratio model, considering the effects of stress level and temperature gradient.

The overuse of resources and environmental destruction has led to the development of renewable research. Research on reclaimed asphalt pavement (RAP) has received widespread attention. In this study, reclaimed milling material from China’s Changyu Highway, which has been in operation for 15 years, was used to study the influence of aged asphalt content on the rheological properties, high-temperature performance, low-temperature performance and microscopic performance of blended asphalt and the impact of RAP content on the high-temperature stability, low-temperature crack resistance, water stability and resilience performance of recycled asphalt mixtures. The results show that the impact of aged asphalt content on the performance of base asphalt shares the same trend with the influence of RAP content on the performance of recycled asphalt mixture. With the admixing of aged asphalt, the blended asphalt is harder, increases in elasticity, and decreases in viscosity. The high-temperature performance improves, but the low-temperature performance worsens. With the addition of RAP, the water stability of the recycled asphalt mixtures improves, the high-temperature stability improves, and the low-temperature crack resistance worsens. This result is consistent with dynamic modulus test results. Overall, based on the micro and macro properties of blended asphalt and asphalt mixtures, a reasonable RAP content of 30% for road performance is given when the gradation is ATB-25.

Representational State Transfer (REST), as a promising software architecture style, has been used in large scale since proposed. But considerable confusions about REST exist and many examples of supposedly RESTful applications violate key REST constraints. In this paper, we focus on the most important constraints of REST, stateless property and hypertext-driven property. First we establish a formal model for REST on HTTP in CSP. In the model, components in RESTful systems communicate with each other using standard HTTP methods and are modeled as CSP processes. From the model we can find the effects of HTTP methods on resources. Then we give formal descriptions for failure cases of stateless, hypertext-driven constraints of REST, and safe, idempotent properties of HTTP methods, within which whether a system breaks REST constraints or basic HTTP requirements can be checked. Furthermore, we use model checker PAT to prove all the constraints hold in our model. In the end, a case study about the process of buying food is mapped to our model to better illustrate the REST concepts and our approach.

To the aim of efficient utilization of both of xylose and cellulose, a laboratory xylose/cellulose fractionation and separate fermentation (XCFSF) bioethanol process was performed. Three xylose/cellulose fractionation strategies: (A) dilute sulfur acid hydrolysis and detoxification, (B) lime pretreatment and xylanase hydrolysis, (C) bio-treatment with Phanerochaete chrysosporium and xylanase hydrolysis were applied to corn cobs. As a result, the maximum xylose yields obtained from A, B and C fractionation methods were 78.47%, 57.84% and 42.54%, respectively, and 96.81%, 92.14% and 80.34% of cellulose were preserved in the corresponding solid residues. The xylose dissolved in acid and enzymatic hydrolysates was fermented to ethanol by Candida shahatae and the cellulose remaining in solid residues was converted to ethanol by simultaneous saccharification and fermentation (SSF) with Saccharomyces cerevisiae. Finally, for A, B, C fractionation methods, 70.40%, 52.87%, 39.22% of hemicellulose and 89.77%, 84.30%, 71.90% of cellulose in corn cobs was converted to ethanol, respectively.

CD147/extracellular matrix metalloproteinase inducer (EMMPRIN) expressed by tumor cells stimulates peri-tumorous fibroblasts to produce matrix metalloproteinases (MMPs), thus contributing to tumor invasion and metastasis. To assess its suitability as a potential therapeutic target, as well as its association with the clinicopathologic features and the prognosis of patients, the expression of CD147/EMMPRIN in neoplastic tissues of the genitourinary system were analyzed.CD147/EMMPRIN expression in 52 patients with renal carcinoma, 58 patients with bladder carcinoma, 101 patients with prostate carcinoma, 17 patients of penis carcinoma, and 17 patients of testis carcinoma were examined by immunostaining on paraffin-embedded tumor specimens using monoclonal antibodies. Then, the association of its expression with clinicopathologic characteristics to the patients' prognosis was analyzed. The RNA interference approach was used to silence CD147/EMMPRIN expression in the human prostate carcinoma cell line LNCAP and human bladder carcinoma cell line J82. The in vitro proliferative ability of CD147/EMMPRIN-deficient cells was determined by a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MTT assay.CD147/EMMPRIN was expressed in neoplastic tissues, but not in normal tissues. Positive expression was shown in 42 of 52 (80.77%) of the patients with renal carcinoma, 41 of 58 (70.69%) of the patients with bladder carcinoma, 67 of 101 (66.34%) of the patients with prostate carcinoma, 16 of 17 (94.12%) of the patients with penis carcinoma and testis carcinoma. Positive CD147/EMMPRIN staining was significantly associated with TNM stages and histological subtypes of patients with various urinary carcinomas (P0.05). In all five groups, for different expression levels of CD147/EMMPRIN, the patients with a highly positive expression of CD147/EMMPRIN had the poorest prognosis. The siRNA-treated cells exhibited significantly decreased growth ability compared with control cells in vitro.These results may assist in defining the suitability of CD147/EMMPRIN as a therapeutic target and as a method for predicting a poor outcome in patients with various urinary carcinomas.

Objectives To evaluate the protective effects of inosine on bladder dysfunction, nerve density, and oxidative damage after partial bladder outlet obstruction in rats. Methods A total of 60 adult male Sprague-Dawley rats were divided into 5 groups. Groups 1-4 underwent bladder outlet obstruction. Groups 1-3 were treated with inosine at 100, 150, or 225 mg/kg/d intraperitoneally and group 4 with saline. Group 5 consisted of sham-operated control rats. At 21 days postoperatively, cystometry were performed in 30 rats (6 per group). In the remaining 30 rats (6 per group), the bladders were excised and used for contractile responses to various stimulations, immunohistochemical examination for protein gene product 9.5 (a neuronal marker) and evaluation of superoxide dismutase activity and thiobarbituric acid reductase substance level. Results Inosine administration resulted in dose-dependent protective effects on the contractile responses to both field stimulation and carbachol, although the protective responses to KCl was restricted to a greater dose of inosine. A dose-dependent reduction in residual volume was noted in inosine-treated groups at different dosages compared with the saline-treated group. In addition, the protein gene product 9.5-positive nerve density decreased in the saline-treated group but significantly increased in the inosine-treated (225 mg/kg/d) group. Compared with the saline-treated group, significantly enhanced superoxide dismutase activity and a reduced thiobarbituric acid reductase substance level were observed in the inosine-treated group at 150 and 225 mg/kg/d. Conclusions These results suggest that inosine has a potential protective effect against partial bladder outlet obstruction-induced bladder dysfunction and oxidative injury in rats.

We present a technology to make ultrahigh spacing tissue arrays (USTA) which facilitates screening hybridoma by immunohistochemistry, results in easier performance of staining and image analysis, minimal sample mixed-up and less bookkeeping efforts. 32 array cores are designated a 4 × 8 microarray, leaving 4 mm spacing between two adjacent array elements. After separated each array spot with PAP pen, one USTA is sufficient for testing of supernatants from 32 different hybridomas.

Dendritic cells (DCs) have been widely used as cancer vaccines. However, their functional abilities have often been suppressed by tumor-secreted immunosuppressants such as transforming growth factor-beta (TGF-beta). We developed a new strategy using a TGF-beta insensitive DC as cancer vaccine. The effect of this vaccine was tested in a murine pulmonary metastases model of renal carcinoma (Renca). Tumor lysate-pulsed DCs (TP-DCs) were infected with retrovirus containing gene of dominant negative TGF-beta type II receptor (TbetaRIIDN) and thus made TGF-beta insensitive. Vaccination of the mice bearing Renca pulmonary metastases with the TbetaRIIDN TP-DC induced powerful tumor-specific cytotoxic T lymphocyte (CTL) responses, suppressed pulmonary metastases, and prolonged survival times. These results suggest TGF-beta-insensitive TP-DC vaccine can be used to enhance the antitumor efficacy of DC vaccine.

To develop reagents for early diagnosis and therapeutic drugs against SARS-associated coronavirus (SARS-CoV), a large (3 × 109) immunized human antibody library was constructed from peripheral blood mononuclear cells from six SARS convalescent patients. A single chain variable fragment antibody (N18) with high affinity against N protein of SARS-CoV was isolated. Sequence analysis revealed that the VL gene was composed of VL3 h (V lambda subgroup) and JL2 regions and the VH gene was composed of VH1-69 (VH1 subgroup), D2-15, D3-22 and JH6 regions. Soluble N18 antibody was expressed in Escherichia coli HB2151, purified by Ni–NTA affinity chromatography and verified by SDS-PAGE and Western blot. The potential application for early diagnosis was evaluated using N protein capture ELISA in which N18 antibody demonstrated high sensitive activity in detecting N protein of SARS-CoV. Finally, the potential usefulness of the N18 antibody in prophylaxis, vaccine design and therapy of SARS is discussed.