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Purpose: C-X-C chemokine receptor type 4 (CXCR4) is known to be involved in both developmental and adult angiogenesis; however, its role in tumor angiogenesis remains largely unknown. Here, the role of vascular CXCR4 in regulating vascular structure in hepatocellular carcinoma (HCC) was assessd, and the clinical value of CXCR4 was explored.Experimental Design: The expression of CXCR4 in HCC was determined by IHC and immunofluorescence. Characteristics of CXCR4+ cells were determined by in vitro and mice experiments. Kaplan–Meier survival analysis was used to determine the correlation of CXCR4 expression with prognosis.Results: We found that CXCR4 is selectively expressed on a fraction of tumor endothelial cells (TECs) in HCC tissues, but not on the hepatic endothelium in peritumoral area. High levels of CXCR4 on TECs tended to develop a sinusoidal vasculature in tumors and predicted poor prognosis for patients with HCC. CXCR4+ endothelial cells (EC) displayed the functional features of tip cells, with increased expression of tip cell–related markers. Functional studies revealed that CXCR4 could directly promote vessel sprouting in vitro and in vivo. Interestingly, sorafenib treatment reduced the frequency of CXCR4+ ECs in culture and inhibited the formation of sinusoidal vasculature and growth of CXCR4High xenograft tumors. Moreover, high CXCR4 vascular density in resected tumor tissues before sorafenib treatment was associated with prolonged survival in patients with advanced HCC treated with sorafenib.Conclusions: These data revealed that CXCR4 is a novel HCC vascular marker for vessel sprouting and could serve as a potential therapeutic target and a predictive factor for sorafenib treatment in patients with HCC. Clin Cancer Res; 23(15); 4482–92. ©2017 AACR.

Background: The complex tumor microenvironment of hepatocellular carcinoma (HCC) has led to a low response to immune checkpoints inhibitors (ICIs) and a poor prognosis. PD-L1, as one of the indications for ICIs, is rich in glycosylation modifications, which result in untimely ICIs. Our study constructed a prognostic model based on N-linked glycosylation related genes for predicting the prognosis and the response to ICIs. Methods: The patients in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts were enrolled. The Cox regression was performed to develop a prognostic model and patients were divided into a low-and high-risk subgroup. 21 recurrent HCC patients who received postoperative adjuvant ICIs were recruited and evaluated the response to ICIs. siRNA was used for in vitro validation. Results: 59 N-linked glycosylation related differentially expressed genes were screened from of HCC and normal tissues in the TCGA cohort. The prognostic model was developed with DDOST, STT3A and TMEM165. The risk score could be an independent prognostic factor. Patients in high-risk subgroup showed worse prognosis than patients in low-risk. ssGSEA showed that patients in the low-risk subgroup were more tend to be immune-activated state. Immunohistochemistry studies showed that DDOST, STT3A and TMEM165 are highly expressed in tumor tissues and patients with high risk score correlated with poor progression free survival and worse immunotherapeutic response. Knockdown of the three genes significantly reduce the proliferation of HCC cell lines. Conclusion: In this study, we establish that the risk model based on N-linked glycosylation related genes could efficiently predict the prognosis and tumor microenvironment immune state of HCC patients, and the risk score could serve as an indicator of ICIs.

As China is implementingquot;Healthy Chinaquot; strategy, medicinal and edible food has attracted unprecedented attention due to the dual attributes of food and medicine. However, there is a lack of the quality control standard and the existing quality control research cannot fully reflect the dual attributes of medicinal and edible food, which consequently restrict the development of medicinal and edible food industry. This study reviewed the research status and proposed the strategy of quality control in line with the dual attribu-tes of medicinal and edible food, and clarified the research contents of quality control of medicinal and edible food of different types to provide references for the follow-up quality control of medicinal and edible food.

Retinopathy of prematurity (ROP) is a vision-threatening ocular disease that occurs in premature infants, but the underlying mechanism is still unclear. Since oxidative stress has been well documented in the ROP development, we aimed to investigate whether ferroptosis, a new type of cell death characterized by lipid peroxidation and iron overload, is also involved in ROP. We detected the lipid peroxidation, oxidative stress and the expression of ferroptosis markers in the retina of mouse model of oxygen-induced retinopathy. After ferroptosis inhibitor, ferrostatin-1, was administered by intravitreal injection, ferroptosis marker, lipid peroxidation, retinal vasculature and glial cell activation were examined. We found decreased expression of SLC7A11 and GPX4, increased expression of FTH1 and TFRC, as well as increase of lipid peroxidation in the retina of OIR mice. Ferrostatin-1 administration significantly reduced lipid peroxidation, and also reversed the change of ferroptosis marker. Neovascular area and avascular area were suppressed and the pathological vasculature changes including acellular vessels and ghost pericytes were decreased. Microglial cell and Müller cell activation was not evidently influenced by ferrostatin-1 treatment. Our findings suggest that ferroptosis is involved in the pathological angiogenesis and might be a promising target for ROP therapy.

The present study investigated the effect of extract of Poria cocos polysaccharides(PCP) on cytochrome P450 2 E1(CYP2 E1) and nuclear factor κB(NF-κB) inflammatory signaling pathways in alcoholic liver disease(ALD) mice and explored its protective effect and mechanism. Sixty male C57 BL/6 N mice of SPF grade were randomly divided into a control group, a model group, a positive drug group(bifendate, 200 mg·kg~(-1)), and high-(200 mg·kg~(-1)) and low-dose(50 mg·kg~(-1)) PCP groups. Gao-binge mo-del was induced and the mice in each group were treated correspondingly. Liver morphological and pathological changes were observed and organ index was calculated. Serum levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were detected. Malondialdehyde(MDA) and superoxide dismutase(SOD) in liver tissues were detected by assay kits. The levels of interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) were detected by ELISA. The activation of macrophages was observed by immunofluorescence staining and protein expression of CYP2 E1, Toll-like receptor 4(TLR4), NF-κB p65, and phosphorylated NF-κB p65(p-NF-κB p65) were analyzed by Western blot. The ALD model was properly induced. Compared with the model group, the PCP groups significantly improved the pathological injury of liver tissues. Immunofluorescence staining revealed that compared with the model group, the groups with drug intervention showed decreased macrophages in liver tissues. Additionally, the PCP groups showed reduced ALT, AST, MDA, IL-6, and TNF-α(Plt;0.05), and potentiated activity of SOD(Plt;0.01). PCP extract has the protective effect against alcoholic liver injury in mice, and the underlying mechanism may be related to the regulation of the expression of CYP2 E1 and inhibition of TLR4/NF-κB inflammatory signaling pathway to reduce oxidative stress and inflammatory injury, thereby inhibiting the development of ALD.

Parabens are widely used as preservatives, which have been found to affect thyroid function in toxicological studies. However, population studies on whether they are associated with thyroid tumor remain unclear. This study aims to investigate the relationship between environmental paraben exposure and thyroid cancer and benign nodules. The detectable percentages of methyl paraben, ethyl paraben, and propyl paraben in the urinary samples of 425 study subjects were 99.06%, 95.29% and 92.00%, respectively. In the single pollutant model, we found statistically significant difference between certain parabens and thyroid cancer/ benign nodules. Further, we found the mixture effect of parabens on increased risk of thyroid cancer (OR = 0.24, 95% CI: 0.18, 0.31) and benign nodule (OR =1.33, 95% CI: 0.86, 1.80). The significant gender-associated effects were found in associations with certain parabens and thyroid cancer and benign nodules (Both P for interactions < 0.05). Overall, our results showed that individual exposure of paraben mixtures may be associated with the risk of thyroid cancer and benign nodules, and there were gender differences.

BACKGROUND Hepatocellular carcinoma (HCC) is a common cancer with a poor prognosis. Previous studies revealed that the tumor microenvironment (TME) plays an important role in HCC progression, recurrence, and metastasis, leading to poor prognosis. However, the effects of genes involved in TME on the prognosis of HCC patients remain unclear. Here, we investigated the HCC microenvironment to identify prognostic genes for HCC. AIM To identify a robust gene signature associated with the HCC microenvironment to improve prognosis prediction of HCC. METHODS We computed the immune/stromal scores of HCC patients obtained from The Cancer Genome Atlas based on the ESTIMATE algorithm. Additionally, a risk score model was established based on Differentially Expressed Genes (DEGs) between high‐ and low‐immune/stromal score patients. RESULTS The risk score model consisting of eight genes was constructed and validated in the HCC patients. The patients were divided into high- or low-risk groups. The genes (Disabled homolog 2, Musculin, C-X-C motif chemokine ligand 8, Galectin 3, B-cell-activating transcription factor, Killer cell lectin like receptor B1, Endoglin and adenomatosis polyposis coli tumor suppressor) involved in our risk score model were considered to be potential immunotherapy targets, and they may provide better performance in combination. Functional enrichment analysis showed that the immune response and T cell receptor signaling pathway represented the major function and pathway, respectively, related to the immune-related genes in the DEGs between high- and low-risk groups. The receiver operating characteristic (ROC) curve analysis confirmed the good potency of the risk score prognostic model. Moreover, we validated the risk score model using the International Cancer Genome Consortium and the Gene Expression Omnibus database. A nomogram was established to predict the overall survival of HCC patients. CONCLUSION The risk score model and the nomogram will benefit HCC patients through personalized immunotherapy.

In order to solve the problem of information extraction from Sentinel-2A satellite remote sensing images, four scene images of mountainous landscape with complex forests, flat cultivated rural landscape suburban coastal landscape and complex urban landscape were selected as experimental objects, and three algorithms of KNN, CART and SVM of object-oriented method are used to extract the main feature information, so as to compare the extraction accuracy of different methods in different scenes. The experimental results show that the overall accuracy of object-oriented feature classification of Sentinel-2A image in four scenes is greater than 75.47%, and the kappa coefficient is greater than 0.72 except that the overall accuracy of KNN in Scenes 4 is 0.66. Through the comprehensive comparative analysis of the four scenes, it can be seen that the average overall accuracy of rural landscape of Sentinel-2A image is 84.65%, the average kappa coefficient is 0.79, which is better than the average overall accuracy of urban landscape classification of 78.1%, the average kappa coefficient is 0.7, and the flat terrain scene is better than the mountainous area with large topographic elevation difference. In terms of classification methods, SVM algorithm has better classification accuracy than CART algorithm, and CART has better classification accuracy than KNN.

Strong physical unclonable function (PUF) transcends the limitations of legacy secure key storage methods as emerging security primitive for cryptography and device identification/authentication. In this paper, a new low power and reliable mono-stable strong PUF is proposed. Its primary entropy is derived from the process variations of the parallel diode-clamped single inverter ring working in the subthreshold region. Due to manufacturing process variations, the mono-stable state of the output voltage of single inverter ring is Gaussian distributed around the half $V_{\text {dd}}$ point. The spread of the Gaussian is broadened by mixing it with another Gaussian distributed trip point obtained from a diode-clamped parallel inverter stage. As the main entropy of the raw response bits is derived from a mono-stable circuit, it has greater immunity to perturbances introduced by operating environments. In addition, as the mono-stable state for the output voltage is a non-linear combination of individual inverter rings, the resilience against machine learning attacks can be improved. The prototype chip was fabricated using a commercial 40-nm CMOS technology. The measurement results show that the power consumption of the 64-bit mono-stable PUF is merely $3.85~\mu \text{W}$ . The native bit error rate is $36{\times}$ and $75{\times}$ , respectively, over that of arbiter PUF.

Background Recent clinical studies have suggested that programmed death ligand 1 (PD-L1) expression in a tumour could be a potential biomarker for PD-L1/PD-1 blockade therapies. Methods To better characterise PD-L1 expression in hepatocellular carcinoma (HCC), we analysed its expression patterns in 453 HCC patients by double staining for CD68 and PD-L1 using the Tyramide Signal Amplification Systems combined with immunohistochemistry. We also investigated its correlation with clinical features, prognosis and immune status. Results The results showed that PD-L1 expression on tumour cells (TCs) was negatively associated with patients’ overall survival (OS; P = 0.001) and relapse-free survival (RFS; P = 0.006); however, PD-L1 expression on macrophages (Mφs) was positively correlated with OS (P = 0.017). Multivariate analysis revealed that PD-L1 expression on TCs and Mφs were both independent prognostic factors for OS (hazard ratio (HR) = 1.168, P = 0.004 for TC-PD-L1; HR = 0.708, P = 0.003 for Mφ-PD-L1). Further studies showed that Mφ-PD-L1+ tumours exhibited an activated immune microenvironment, with high levels of CD8+ T-cell infiltration and immune-related gene expression. Conclusion Our study provided a novel methodology to evaluate PD-L1 expression in the tumour microenvironment, which might help to select patients who would benefit from anti-PD-1/PD-L1 immunotherapies.

Background Exposure to per- and polyfluoroalkyl substances (PFAS) during pregnancy has been suggested to be associated with adverse pregnancy and birth outcomes; however, the findings have been inconsistent. We aimed to conduct a systematic review and meta-analysis to provide an overview of these associations. Methods The online databases PubMed, EMBASE and Web of Science were searched comprehensively for eligible studies from inception to February 2021. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled using random- or fixed-effects models, and dose-response meta-analyses were also conducted when possible. Findings A total of 29 studies (32,905 participants) were included. The pooled results demonstrated that perfluorooctane sulfonate (PFOS) exposure during pregnancy was linearly associated with increased preterm birth risk (pooled OR per 1-ng/ml increase: 1.01, 95% CIs: 1.00–1.02, P = 0.009) and perfluorononanoate (PFNA) and perfluorooctanoate (PFOA) exposure showed inverted U-shaped associations with preterm birth risk (P values for the nonlinear trend: 0.025 and 0.030). Positive associations were also observed for exposure to perfluorodecanoate (PFDA) and miscarriage (pooled OR per 1-ng/ml increase: 1.87, 95% CIs: 1.15–3.03) and PFOS and preeclampsia (pooled OR per 1-log increase: 1.27, 95% CIs: 1.06–1.51), whereas exposure to perfluoroundecanoate (PFUnDA) was inversely associated with preeclampsia risk (pooled OR per 1-log increase: 0.81, 95% CIs: 0.71–0.93). Based on individual evidence, detrimental effects were observed between PFDA exposure and small for gestational age and between PFOA and PFOS and intrauterine growth restriction. No significant associations were found between pregnancy PFAS exposure and other adverse pregnancy outcomes (i.e., gestational diabetes mellitus, pregnancy-induced hypertension, low birth weight, and large and small for gestational age). Interpretation Our findings indicated that PFOS, PFOA and PFNA exposure during pregnancy might be associated with increased preterm birth risk and that PFAS exposure might be associated with the risk of miscarriage and preeclampsia. Due to the limited evidence obtained for most associations, additional studies are required to confirm these findings.

Purpose: C-X-C chemokine receptor type 4 (CXCR4) is known to be involved in both developmental and adult angiogenesis; however, its role in tumor angiogenesis remains largely unknown. Here, the role of vascular CXCR4 in regulating vascular structure in hepatocellular carcinoma (HCC) was assessd, and the clinical value of CXCR4 was explored. Experimental Design: The expression of CXCR4 in HCC was determined by IHC and immunofluorescence. Characteristics of CXCR4+ cells were determined by in vitro and mice experiments. Kaplan–Meier survival analysis was used to determine the correlation of CXCR4 expression with prognosis. Results: We found that CXCR4 is selectively expressed on a fraction of tumor endothelial cells (TECs) in HCC tissues, but not on the hepatic endothelium in peritumoral area. High levels of CXCR4 on TECs tended to develop a sinusoidal vasculature in tumors and predicted poor prognosis for patients with HCC. CXCR4+ endothelial cells (EC) displayed the functional features of tip cells, with increased expression of tip cell–related markers. Functional studies revealed that CXCR4 could directly promote vessel sprouting in vitro and in vivo. Interestingly, sorafenib treatment reduced the frequency of CXCR4+ ECs in culture and inhibited the formation of sinusoidal vasculature and growth of CXCR4High xenograft tumors. Moreover, high CXCR4 vascular density in resected tumor tissues before sorafenib treatment was associated with prolonged survival in patients with advanced HCC treated with sorafenib. Conclusions: These data revealed that CXCR4 is a novel HCC vascular marker for vessel sprouting and could serve as a potential therapeutic target and a predictive factor for sorafenib treatment in patients with HCC. Clin Cancer Res; 23(15); 4482–92. ©2017 AACR.

EZH2, a histone methyltransferase, has been shown to involve in cancer development and progression via epigenetic regulation of tumor suppressor microRNAs, whereas BMI1, a driver of hepatocellular carcinoma (HCC), is a downstream target of these microRNAs. However, it remains unclear whether EZH2 can epigenetically regulate microRNA expression to modulate BMI1-dependent hepatocarcinogenesis. Here, we established that high EZH2 expression correlated with enhanced tumor size, elevated metastasis, increased relapse, and poor prognosis in HCC patients. Further clinical studies revealed that EZH2 overexpression was positively correlated to its gene copy number gain/amplification in HCC. Mechanistically, EZH2 epigenetically suppressed miR-200c expression both in vitro and in vivo, and more importantly, miR-200c post-transcriptionally regulated BMI1 expression by binding to the 3′-UTR region of its mRNA. Furthermore, miR-200c overexpression inhibits the growth of HCC cells in vivo. Silencing miR-200c rescued the tumorigenicity of EZH2-depleted HCC cells, whereas knocking down BMI1 reduced the promoting effect of miR-200c depletion on HCC cell migration. Finally, combination treatment of EZH2 and BMI1 inhibitors further inhibited the viability of HCC cells compared with the cells treated with EZH2 or BMI1 inhibitor alone. Our findings demonstrated that alteration of EZH2 gene copy number status induced BMI1-mediated hepatocarcinogenesis via epigenetically silencing miR-200c, providing novel therapeutic targets for HCC treatment.

Background: Hepatitis B virus (HBV) infection is considered as an independent risk factor for poor prognosis in hepatocellular carcinoma (HCC) patients, but the molecular mechanisms have not been fully elucidated. Ectonucleotide pyrophosphatase-phosphodiesterase 2 (ENPP2) hydrolyzes lysophosphatidylcholine (LPC) to produce lysophosphatidic acid (LPA) and participates in virus replication and tumor progress. This study aimed to elucidate whether HBV infection inducing HCC progression via LPC/ENPP2/LPA axis. Methods: The clinical data for HCC patients were collected and prognosis was analyzed. The in vitro and in vivo experiments were used to investigate the influences of HBV, ENPP2 and activated hepatic stellate cell (HSC) on HCC progression. Findings: We found that ENPP2 expression was positively related to HBV infection and poor prognosis. HBV-induced HCC progression via ENPP2 was enhanced by LPC which was secreted by activated HSC. HCC patients with high ENPP2 combined with cirrhosis had worse prognosis than non-cirrhotic patients. In cirrhotic HCC patients, high ENPP2 expression cohort also had worse prognosis than low expression cohort. Interpretation: In HBV positive cirrhotic HCC patients, HBV enhanced host cell secretion of ENPP2, combined with LPC secreted by fibroblast to promote tumor progression via LPC/ENPP2/LPA. These findings may provide insights into novel approaches to HBV associated HCC therapy. Funding Statement: This study was supported by the National Natural Science Foundation of China (81801999, 81772597, 81672412, 81972255), the Guangdong Science and Technology Foundation (2017A030311002), the Science Foundation of Jiangxi (20181BAB214002), the Education Department Science and Technology Foundation of Jiangxi (GJJ170936) and grant from Guangdong Science and Technology Department (2017B030314026). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The clinicopathologic information of HCC patient (n = 774) and tumor tissues (n = 158) were obtained from Sun Yat-sen Memorial Hospital after approval by the hospital Ethical Committee. Animal studies were carried out in the South China University of Technology and approved by the Laboratory Animal Welfare and Ethics Committee of the South China University of Technology. All animal experiments conformed to the approved guidelines of Animal Care and Use Committee of South China University of Technology.

BACKGROUND: Despite an increasing appreciation of the roles that myeloid cells play in tumor progression and therapy, challenges remain in interpreting the tumor-associated myeloid response balance and its translational value. We aimed to construct a simple and reliable myeloid signature for hepatocellular carcinoma (HCC). METHODS: Using in situ immunohistochemistry, we assessed the distribution of major myeloid subtypes in both peri- and intratumoral regions of HCC. A 2-feature-based, myeloid-specific prognostic signature, named the myeloid response score (MRS), was constructed using an L1-penalized Cox regression model based on data from a training subset (n = 244), a test subset (n = 244), and an independent internal (n = 341) and 2 external (n = 94; n = 254) cohorts. RESULTS: The MRS and the MRS-based nomograms displayed remarkable discriminatory power, accuracy, and clinical usefulness for predicting recurrence and patient survival, superior to current staging algorithms. Moreover, an increase in MRS was associated with a shift in the myeloid response balance from antitumor to protumor activities, accompanied by enhanced CD8(+) T cell exhaustion patterns. Additionally, we provide evidence that the MRS was associated with the efficacy of sorafenib treatment for recurrent HCC. CONCLUSION: We identified and validated a simple myeloid signature for HCC that showed remarkable prognostic potential and may serve as a basis for the stratification of HCC immune subtypes. FUNDING: This work was supported by the National Science and Technology Major Project of China, the National Natural Science Foundation of China, the Science and Information Technology of Guangzhou, the Fundamental Research Funds for the Central Universities, the Guangdong Basic and Applied Basic Research Foundation, and the China Postdoctoral Science Foundation.

Additional file 1: Figure S1. The expression of EZH2 in HCC tissue microarray. Figure S2. Knockdown of EZH2 upregulates PD-L1 expression induced by IFNγ at different time points. Figure S3. EZH2 inhibitors promotes the IFNγ-induced PD-L1 expression.. Figure S4. The IFNγ-STAT1 signaling is not regulated by EZH2. Figure S5. The EZH2/H3K27me3 axis regulates the expression of IRF1. Figure S6. Transcriptome profiling and gene ontology biological analysis of immune-suppressed and immune-activated HCC tissues. Figure S7. Effect of IL-6 and TNFα on the expression of PD-L1 in hepatoma cells. Figure S8. EZH2 did not effect the protein stability of PD-L1.

The increasing evidences suggest that Immunoscore(IS), a combinatorial density analysis of CD8+ and CD3+ cells in the centre and invasive margin of tumour (CT and IM), has an advantage over the currently used tumour staging methods in a variety of tumours; however, IS in hepatocellular carcinoma remains unreported. In this study, IS was performed on serial sections from two HCC cohorts (total 449) and compared with current tumour staging systems. Kaplan–Meier curves illustrate a positive association between a higher IS (IS≥2) and longer survival of HCC patients. Although the IS was highly related to the outcome of patients, however, IS seems not to be the optimal prognostic factor when compared with the CD8CT. As noted, among CD8CT, CD8IM, CD3CT, CD3IM and IS, CD8CT, as an independent indicator, demonstrated the highest prognostic impact on both DFS and OS in our Cox multivariate regression analysis (P< 0.0001). In our study, the minimum cut-off value was 93 CD8CT cells per mm2, to be used to divide the patients into CD8CTHi group and CD8CTLo group in clinical settings. Our results suggest that CD8CT densities analysis notably improved the accuracy of survival prediction with convenience of clinical manipulation in HCC.

Packet classification is a key function for software defined networking switches. We study the method of packet classification in network protocol, and our goal is to match forwarding rules according to several fields in the head of packets and the rule database. On the basis of the existing string matching model, a Key-Position Vector (KPV) algorithm is put forward, which aims to find some key positions for partitioning all the rules into evenly subsets. Some mathematical background of this problem is provided first, and then the joint and conditional entropy theory is applied to determine the KPV positions step by step in order to achieve an approximately optimized KPV for reducing the searching subsets' size. Moreover, this model possesses important significance in improving search efficiency, and an example is given to illustrate it at the end of this paper.

Using power-up reset to reuse Static Random Access Memory (SRAM) as physical unclonable function (PUF) suffers from two major constraints. First, it has limited entropy of only one response bit per cell. Second, as power-up reset has a global effect, extra storage is needed to temporarily buffer the original SRAM content before switching to PUF mode. This process has introduced extra area-power overhead as well as potential security leakage. The emerging dual-port (DP) SRAM cell offers attractive multiple access capability for low-power and high-speed memory transfer. By levering the forbidden contention state in one of its four multiple access modes, a new DP-SRAM based PUF is proposed to generate two independent response bits per cell and limit data buffering to only those cell content addressed by the challenge. Simulation results based on PTM 22nm LP CMOS model has corroborated its superior reliability, uniqueness and randomness over and above these meritorious advantages.

According to the available geological data and monitoring data, the completely weathered phyllite slope dilates and softens under the condition of continuous rainfall, which is then prone to instability failure. The indoor artificial rainfall test was carried out through the construction of the slope model, and the soil moisture sensor, pore water pressure sensor and matric suction sensor were used to study the variation laws of moisture content, pore water pressure and infiltration line at the back edge, slope body and the foot of the slope under continuous heavy rainfall. According to the sensor data and recorded information, with the influence of heavy rainfall over a long period of time, the water content and pore water pressure increased firstly, then decreased, and finally stabilized. The infiltration line moved from the top, the surface and the foot of the slope to the slope body, and shallow slip failure occurred in the shallow layer of the slope body.

Based on a tunnel through slope of Yongji highway project, relying on ABAQUS geotechnical numerical analysis software, using the appearance of plastic penetration area for instablilty criterion, choosing 11 typical influential factors as independent variables to tunnel stability, the orthogonal test array L50(511) is used to analyze sensitivity of influence factors under evaluating indexes of safety factor to the tunnel stability and the maximum principal tensile on the inner surface of surrounding rock. Research results show that: there are some certain differences between calculation results of safety factor and maximum principal tensile, but overall presentation represents favorable consistency, and the sensitivity of influence factors to the stability of tunnel through unfavorable geological slope can be preferably annlyzed by orthogonal test. The influence of the cohesion of rock c, the horizontal distance d between tunnel centerline and slope toe, the inclination angle of slope α are significant. Comprehensive consideration of safety factor and maximum principal tensile of tunnel circumference is more perfect than one-sided safety factor when performing the analysis of tunnel stability. The research results of this paper can provide reference to design, construction of similar tunnels.

Background Macrophages (Mφs) constitute a major component of the leukocyte infiltrate and perform distinct roles in different tumor microenvironments. This study aimed to characterize the distribution, composition and prognostic value of Mφs in hepatocellular carcinoma (HCC) and gastric cancer (GC). Methods Immunohistochemistry and immunofluorescence were used to identify Mφ subsets in HCC and GC tissues. Kaplan–Meier analysis and Cox regression models were applied to estimate the overall survival (OS) for HCC and GC patients. Results The results showed that the density of Mφs decreased in the intra-tumor region (IT) of HCC, but remarkably increased in the IT of GC, as compared with their non-tumor regions (NT). In HCC, most CD68+ Mφs were CD204+ and CD169+ cells in the NT region; however, there was a significant decrease in the percentage of CD169+ Mφ in the IT region. In contrast, CD68+ Mφs comprised a smaller percentage of CD204+ than the CD169+ subpopulation in the NT region, while more CD204+ but fewer CD169+ cells were present in the IT region of GC. The density of CD204+ Mφs correlated with poor prognosis in HCC, and CD169+ Mφs were associated with good survival in both HCC and GC. Moreover, the combination of low numbers of CD204+ and high numbers of CD169+ Mφs was associated with improved OS in both GC and HCC. Conclusions Mφs display tissue-specific distributions and distinct composition patterns in HCC and GC tissues. Our results suggested that different types of tumors might use diverse strategies to reconstitute Mφ patterns to promote tumor progression. Electronic supplementary material The online version of this article (doi:10.1186/s12967-017-1139-2) contains supplementary material, which is available to authorized users.

Additional file 1: Figure S1. Coexistence of CD169, CD204 and CD68 in intra-tumor (IT) of HCC and GC tissues. Figure S2. Composition patterns of CD204+ MĎ s and CD169+ MĎ s subpopulations in CD68+ MĎ s of HCC and GC non-tumor (NT) tissues. Table S1. Univariate and multivariate analyses of variables associated with overall survival.

Ring oscillator (RO) based physical uncloanble function (PUF) is an emerging hardware security primitive but its response is susceptible to changes in operating conditions. Current solutions either incur large hardware overhead or require sophisticated RO selection algorithms to increase its reliability. This is the first paper that exploits the temperature invariant biasing of three different types of current staved inverter for the design of RO PUFs with high temperature stability. The reliability is further improved by a simple proximity detector circuit and the generation of internal challenges is made more secure by an irregular clocking scheme for linear feedback shift register. The results show that the proposed method increases the reliability of regular inverter based RO PUF by more than 12% with only less than 9% of hardware overhead.

Static Random Access Memory (SRAM) has recently been developed into a physical unclonable function (PUF) for generating chip-unique signatures for hardware cryptography. The most compelling issue in designing a good SRAM-based PUF (SPUF) is that while maximizing the mismatches between the transistors in the cross-coupled inverters improves the quality of the SPUF, this ironically also gives rise to increased memory read/write failures. For this reason, the memory cells of existing SPUFs cannot be reused as storage elements, which increases the overheads of cryptographic system where long signatures and high-density storage are both required. This paper presents a novel design methodology for dual-mode SRAM cell optimization. The design conflicts are resolved by using word-line voltage modulation, dynamic voltage scaling, negative bit-line and adaptive body bias techniques to compensate for reliability degradation due to transistor downsizing. The augmented circuit-level techniques expand the design space to achieve a good solution to fulfill several otherwise contradicting key design qualities for both modes of operation, as evinced by our statistical analysis and simulation results based on complementary metal–oxide–semiconductor (CMOS) 45 nm bulk Predictive Technology Model.

This paper presents the design of a novel shape memory alloys (SMAs) damper, and its application in the vibration control of transmission towers. Firstly, based on a brief introduction for the essential properties of SMAs, a kind of constitutive model, i.e., the Brinson model is established to describe the unique behaviors of the material, combined with the experiments results. And then, a novel SMA damper, with the functions of displacement amplification and re-centering, is specifically designed by utilizing SMAs’ damping capacity. To verify and evaluate the device’s performance, the FEM model of an actual transmission tower is subsequently built in ANSYS, and by embedding the theoretical model of the damper into its analysis process, the responses of the tower subjected to the natural wind are numerically calculated. The results show that under the reasonable installations, the proposed SMA damper has a good effect on the wind-induced response control of the transmission tower.

Background & aims Inflammation is a hallmark of cancer, yet the mechanisms that regulate immune cell infiltration into tumors remain poorly characterized. This study attempted to characterize the composition, distribution, and prognostic value of CXCR2+ cells in hepatocellular carcinoma (HCC) and to examine the CXCR2 ligands that are responsible for local immune infiltration in different areas of HCC tumors. Methods Immunohistochemistry and immunofluorescene were used to identify CXCR2+ cells in HCC tissues. Kaplan–Meier analysis and Cox regression models were applied to estimate recurrence-free survival (RFS) and overall survival (OS) for 259 HCC patients. The expression levels of CXCR2 ligands (CXCL-1, −2, −5, and −8) were measured by real-time PCR and compared with local immune cell density. The combined prognostic value of the CXCR2–CXCL1 axis was further evaluated. Results In HCC tissues, CXCR2+ cells were mainly neutrophils that were enriched in the peri-tumoral stroma (PS) region. Kaplan–Meier survival analysis showed that increased CXCR2+PS cells were associated with reduced RFS and OS (P = 0.015 for RFS; P = 0.002 for OS). Multivariate Cox proportional hazards analysis identified CXCR2+PS cell density as an independent prognostic factor for OS (hazard ratio [HR] = 1.737, 95 % confidence interval [CI] = 1.167–2.585, P = 0.006). Furthermore, we detected a positive correlation between the density of CD15+ neutrophils and CXCL1 levels in both the peri-tumoral stroma and intra-tumoral regions. The combination of CXCR2 and CXCL1 expression levels represented a powerful predictor of a poor prognosis for patients with HCC. Conclusions Our data showed that the CXCR2+ cell density was an independent prognostic factor for predicting OS for HCC patients. The CXCR2–CXCL1 axis can regulate neutrophil infiltration into HCC tumor tissues and might represent a useful target for anti-HCC therapies. Electronic supplementary material The online version of this article (doi:10.1186/s13046-015-0247-1) contains supplementary material, which is available to authorized users.

Apart from performance and power efficiency, security is another critical concern in the modern memory sub-system design. SRAM, which is routinely used as a data preservation component, has now been developed into an effective primitive known as Physical Unclonable Function (PUF) for cryptographic key generation to protect the sensitive local information. Considering the constraints of hardware resource on the embedded systems, it is highly desirable to have an SRAM used both as a regular memory and a PUF to save the overheads of having these two functions implemented independently on different memory chips. Unfortunately, while process variations are the entropy sources for secure key generation, it impacts failure rates in memory accesses. This paper presents a statistical analysis on SRAM and provides an insight into how the SRAM cell geometry can be optimized to qualify it for both modes of operation simultaneously - a feasibility that has not been conceived before in the literature. Accepted version

Objective To investigate the incidence of functional gastrointestinal disorders (FGIDs) in navy officers and soldiers (OSs) in grass-root units, and analyze their correlation factors. Methods A total of 1931 navy OSs from different regions and different services involved in the present study were selected by a cluster sampling method. The samples were investigated with the Rome III adult functional gastrointestinal disease diagnostic questionnaire (Rome Ⅲ-DQ), and diagnosis was made according to Rome III classification and diagnostic standard of FGIDs, and then the correlation risk factors were analyzed. Results A total of 1882 valid questionnaires were retrieved with validity rate of 97.46%. The overall incidence of FGIDs in navy OSs was 26.62%. Among FGIDs, functional bloating bore the highest incidence (8.66%), followed by functional dyspepsia (6.91%), irritable bowel syndrome (5.79%), functional constipation (4.57%), while the incidence of functional biliary pain was the lowest (0.7%). Comparison between different groups showed that the incidence of FGIDs was higher in 26-35 years group (54.78%) than that in 16-25 and 36-45 years group ( 29.73% and 15.11%, respectively, P

Objective To investigate the effects of progesterone on gastric mucosal inflammatory response, changes in mucosa structure, and cell apoptosis in rats with open abdominal wound and seawater immersion. Methods Thirty male Wistar rats were randomly divided into 3 groups (10 each). The rats in group A were subjected to open abdominal wound + subcutaneous injection of sterile water, and rats in group B to open abdominal wound + seawater immersion + subcutaneous injection of sterile water, and rats in group C to open abdominal wound + seawater immersion + progesterone treatment. The animal model of open abdominal wound and seawater immersion was reproduced, and the rats in groups B and C were given subcutaneous injection of sterile water or progesterone (16mg/kg) at 1, 6 and 12h after immersion. All rats were executed at 16h after immersion. The ulcer index (UI) of gastric mucosa was calculated in the three groups. The pathological changes in gastric mucosa were observed under light microscope. The concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL -6) in gastric mucosa were measured by enzyme-linked immunoassay, the expression of caspase-3 in gastric mucosa was detected by immunohistochemistry, and the cell apoptosis of gastric mucosa was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining. Results The UI, concentrations of TNF-α and IL-6, and injury score of gastric mucosa in group B were all significantly higher than those in group A (P

Primer Sequences. (DOC 58 kb)

Association of CXCR2 with clinicopathological characteristics. (DOC 66 kb)

Univariate and multivariate analyses of factors associated with survival and recurrence. (DOC 40 kb)

In recent years, with the economic development of western China, the influence of Xinjiang CPI on national CPI is increasingly becoming great, so accurately predicting Xinjiang CPI has become very significant for the whole country. Considering this, this paper tentatively uses public attention based on Baidu search index to predict Xinjiang CPI. After clarifying the connections among public attention, Baidu search index, Xinjiang CPI from the theoretical aspect, the Baidu search index obtained from Baidu keywords automate recommendation function was synthesized to well measure public attention by stepwise synthetic method. Then this paper empirical analyzes the relationship between Xinjiang CPI and public attention based on Baidu search synthesis index. From the empirical result, the predicted average absolute error of the prediction model is 4.65%, meaning that public attention could well predict the fluctuation of Xinjiang CPI.

CXC ligand 17 (CXCL17) is a novel CXC chemokine whose clinical significance remains largely unknown. In the present study, we characterized the prognostic value of CXCL17 in patients with hepatocellular carcinoma (HCC) and evaluated the association of CXCL17 with immune infiltration. We examined CXCL17 expression in 227 HCC tissue specimens by immunohistochemical staining, and correlated CXCL17 expression patterns with clinicopathological features, prognosis, and immune infiltrate density (CD4 T cells, CD8 T cells, B cells, natural killer cells, neutrophils, macrophages). Kaplan-Meier survival analysis showed that both increased intratumoral CXCL17 (P = 0.015 for overall survival [OS], P = 0.003 for recurrence-free survival [RFS]) and peritumoral CXCL17 (P = 0.002 for OS, P