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The clinical outcomes of cancer nanovaccine have been largely impeded owing to the low antigen-specific T cell response rate and acquired resistance caused by the immunosuppressive tumor microenvironment (TME). Here, we reported a tumor acidity-responsive nanovaccine to remodel the immunosuppressive TME and expand the recruitment of tumor infiltrating lymphocytes (TILs) using hybrid micelles (HM), which encapsulated colony stimulating factor 1 receptor (CSF1-R) inhibitor BLZ-945 and indoleamine 2,3-dioxygenase (IDO) inhibitor NLG-919 in its core and displayed a model antigen ovalbumin (OVA) on its surface (denoted as BN@HM-OVA). The bioactive nanovaccine is coated with a polyethylene glycol (PEG) shell for extending nanoparticle circulation. The shell can be shed in response to the weakly acidic tumor microenvironment. The decrease in size and the increase in positive charge may cause the deep tumor penetration of drugs. We demonstrated that the bioactive nanovaccine dramatically enhance antigen presentation by dendritic cells (DCs) and drugs transportation into M1-like tumor-associated macrophages (TAMs) and tumor cells via size reduction and increasing positive charge caused by the weakly acidic TME. Such bioactive nanovaccine could remodel the immunosuppressive TME into an effector T cells favorable environment, leading to tumor growth inhibition in prophylactic and therapeutic E.G7-OVA tumor models. Furthermore, combining the bioactive nanovaccine with simultaneous anti-PD-1 antibody treatment leads to a long-term tumor inhibition, based on the optimal timing and sequence of PD-1 blockade against T cell receptor. This research provides a new strategy for the development of efficient cancer immunotherapy.

Tumor microenvironment (TME)-oriented nanomedicine emerges as an efficient routine to greatly improve the efficiency of cancer treatment. The typical feature of hypoxia in TME remains as the main obstacle of many therapeutics like photodynamic therapy. Herein, a specific two-dimensional (2D) phototheranostics (GO-MnO

ContextHemichorea associated with nonketotic hyperglycemia (HC-NH) is a rare diabetic complication for which the pathogenesis remains unclear.ObjectiveThis study reported 16 cases of HC-NH to improve the understanding of the disease and avoid misdiagnosis and missed diagnosis.MethodsData of 16 patients with HC-NH in a single center from 2000 to 2021 were analyzed retrospectively, and the relevant literature was reviewed.ResultsThe participants (8 men and 8 women) had a mean age of 67.6 ± 16.4 years. Bilateral limbs were involved in 2 cases, and the others had hemichorea (6 in the left side and 8 in the right side). The average random blood glucose level was 17.51 ± 7.67 mmol/L, and the glycated hemoglobin A1c level was 11.9%±3.1% at admission. Eleven patients had a history of diabetes, and the other 5 patients were diagnosed with new-onset diabetes mellitus, but no remarkable differences were observed in the presentation or treatment of chorea. Ketonuria was detected in 7 patients. The basal ganglia (putamen, globus pallidus, and caudate nucleus) of 9 cases had typical hyperdensity on computed tomography and/or hyperintensity signals from magnetic resonance imaging. The chorea symptoms of 15 patients improved within 5.0 ± 1.9 days after treatment.ConclusionThis study provides additional valuable information about the clinical and neuroimaging features of HC-NH. We hypothesize that chronic ischemia of the basal ganglia due to cerebral atherosclerosis combined with hyperglycemia is associated with HC-NH.

3D soma detection in whole brain images is a critical step for neuron reconstruction. However, existing soma detection methods are not suitable for whole mouse brain images with large amounts of data and complex structure. In this paper, we propose a two-stage deep neural network to achieve fast and accurate soma detection in large-scale and high-resolution whole mouse brain images (more than 1TB). For the first stage, a lightweight Multi-level Cross Classification Network (MCC-Net) is proposed to filter out images without somas and generate coarse candidate images by combining the advantages of the multi convolution layer's feature extraction ability. It can speed up the detection of somas and reduce the computational complexity. For the second stage, to further obtain the accurate locations of somas in the whole mouse brain images, the Scale Fusion Segmentation Network (SFS-Net) is developed to segment soma regions from candidate images. Specifically, the SFS-Net captures multi-scale context information and establishes a complementary relationship between encoder and decoder by combining the encoder-decoder structure and a 3D Scale-Aware Pyramid Fusion (SAPF) module for better segmentation performance. The experimental results on three whole mouse brain images verify that the proposed method can achieve excellent performance and provide the reconstruction of neurons with beneficial information. Additionally, we have established a public dataset named WBMSD, including 798 high-resolution and representative images (256 × 256 × 256 voxels) from three whole mouse brain images, dedicated to the research of soma detection, which will be released along with this paper.

Nanomedicine enabled cancer combination immunotherapy not only sufficiently activates the host immune system, but also reprograms the immunosuppressive microenvironment, representing a new generation approach to treat cancer. Herein, we demonstrated a targeted photo- and immune-active nanoplatform termed NLG919@HA-Ce6 to simultaneously elicit efficient immunogenic cell death (ICD) using the photosensitizer Ce6 and modulate the tryptophan metabolic pathway using an indoleamine 2,3-dioxygenase (IDO) inhibitor NLG919 for the combined photodynamic therapy (PDT) and checkpoint blockade immunotherapy. Against the triple-negative and poorly immunogenic 4T1 breast cancer model, the stable spherical nanomicelle NLG919@HA-Ce6 selectively killed tumour cells via the toxic singlet oxygen upon laser excitation, thus in situ triggering a potent antitumor immune response, as seen via the obvious CRT exposure, ATP release, dendritic cell maturation, etc. Meanwhile, the IDO1-mediated immunosuppression was effectively reprogrammed to an immunostimulatory phenotype, which was accompanied by an enhanced cytotoxic T cell response as well as reduced Treg infiltration in tumour bed. Ultimately, the 4T1 tumour was synergistically suppressed by NLG919@HA-Ce6 due to the outcome of focused PDT, obvious ICD post PDT and IDO1 blockade. This study suggests the promise of NLG919@HA-Ce6 as an alternative simple, stimulative and targeted nanoagent to enable the whole-body photo-immune therapy against "immune cold" cancer.

In the past few years, we have witnessed great development and application potential of various up-conversion luminescent nanoparticles (UCNPs) in the nanomedicine field. Based on the unique luminescent mechanism of UCNPs and the distinguishable features of cancer biomarkers and the microenvironment, an increasing number of smart UCNPs nanoprobes have been designed and widely applied to molecular imaging, cancer diagnosis, and treatment. Considerable technological success has been achieved, but the main obstacles to oncology nanomedicine is becoming an incomplete understanding of nano-bio interactions, the challenges regarding chemistry manufacturing and controls required for clinical translation and so on. This review highlights the progress of the design principles, synthesis and surface functionalization preparation, underlying applications and challenges of UCNPs-based probes for cancer bioimaging, diagnosis and treatment that capitalize on our growing understanding of tumor biology and smart nano-devices for accelerating the commercialization of UCNPs.

The combination of magnetic hyperthermia and chemotherapy within a nanosystem is thought to be a promising approach for cancer therapies. However, the nonspecific accumulation and fast clearance of magnetic nanoparticles in the physiological environment limited their further biomedical applications. Herein, we report a highly selective theranostic nanocomplex, ZIPP-Apt:DOX/siHSPs, built with superparamagnetic zinc-doped iron oxide nano-octahedral core, cationic PAMAM dendrimer, and functional surface modifications such as PEG, AS1411 aptamer, and fluorescent tags (FITC or Cy5.5), together with the loading of hydrophobic anticancer drug doxorubicin (DOX) and HSP70/HSP90 siRNAs. Our results demonstrate that the cellular uptake and the tumor-specific accumulation of ZIPP-Apt:DOX/siHSPs were significantly increased due to the AS1411-nucleolin affinity and further confirmed that the simultaneous depletion of HSP70 and HSP90 sensitized magnetic hyperthermia and chemotherapy-induced cell death both in vitro and in vivo. Altogether, our study provides a theranostic nanoplatform for aptamer-targeted, NIR/MR dual-modality imaging guided, and HSP70/HSP90 silencing sensitized magnetochemotherapy, which has the potential to advance versatile magnetic nanosystems toward clinical applications.

The combination of photothermal therapy (PTT) and chemotherapy is considered a promising tumor treatment modality, nevertheless, cellular resistance induced by heat shock proteins (HSPs) overexpressed in tumor cells will restrict the therapeutic effect. Herein, a multifunctional nanobeacon DOX/HCuS@PDA-MB (D/CP-MB) with a scout function for HSP90 mRNA fluorescence detection and near-infrared (NIR) triggered drug release for sensitizing chemo-photothermal therapy, is proposed. In the theranostic nanobeacons, HSP90MBs not only enable fluorescence detection of intracellular HSP90 mRNAs, but also downregulate the expression of HSP90 to reduce cell resistance. With the assistance of NIR and guidance of fluorescence imaging, spatiotemporal doxorubicin release can be achieved by the trigger of the photothermal effect, allowing for combined chemotherapy and photothermal treatment. Furthermore, the dual photothermal effect of hollow mesoporous CuS (HCuS) and polydopamine will lead to a better photothermal effect. Moreover, compared with other control groups, D/CP-MB nanobeacons exhibit effective boost therapeutic efficacy by inducing significant suppression of tumor proliferation and enhancement of apoptosis both in vitro and in vivo. In summary, this work provides novel theranostic nanobeacons that integrate imaging and therapy in a single nanoparticle, this strategy of imaging-guided therapy can enable precise tumor treatment and effectively improve tumor treatment efficacy.

T cell stimulatory and inhibitory molecules are critical for the regulation of immune responses. In this study, we identify a novel T cell co‐inhibitory molecule TAPBPL, whose amino acid sequence shares homology with known B7 family members. TAPBPL protein is expressed on resting and activated T cells, B cells, monocytes, and dendritic cells (DCs), as well as on some tumor tissues. The putative TAPBPL receptor is expressed on activated CD4 and CD8 T cells. A soluble recombinant human TAPBPL‐IgG Fc (hTAPBPL‐Ig) fusion protein inhibits the proliferation, activation, and cytokine production of both mouse and human T cells in vitro. In vivo administration of hTAPBPL‐Ig protein attenuates experimental autoimmune encephalomyelitis (EAE) in mice. Furthermore, an anti‐TAPBPL monoclonal antibody neutralizes the inhibitory activity of hTAPBPL‐Ig on T cells, enhances antitumor immunity, and inhibits tumor growth in animal models. Our results suggest that therapeutic intervention of the TAPBPL inhibitory pathway may represent a new strategy to modulate T cell‐mediated immunity for the treatment of cancer, infections, autoimmune diseases, and transplant rejection., T cells play a critical role in immune response. This study identifies a novel B7 family‐related T cell inhibitory molecule TAPBPL. Targeting the TAPBPL pathway may represent a new strategy to modulate T cell‐mediated immunity to treat autoimmune disease and cancer.

The gradual improvement of global navigation satellite systems in recent decades and their combination greatly increase the visible satellite number for positioning and integrity monitoring process. This enhances the positioning accuracy and availability of the navigation system but at the cost of the large growth in computation load and function failure rate. Satellite selection is a useful way to relieve the side effect of superabundant measurements in use and has been developed for geometric dilution of precision (GDOP) optimization, but it has scarcely been studied in the integrity monitoring field. This paper proposes a slope-based fast satellite selection algorithm with the motivation to optimize the horizontal protection level (HPL) of subset while maintaining an acceptable positioning accuracy. The basis of this algorithm is a cost function which illustrates the relationship between satellite geometry and the slope effect. While the principle is to find the max slope satellite in the subset and introduce a new satellite which can significantly reduce the max slope by the cost function so the HPL decreases. Comparison simulations show the effectiveness of the proposed algorithm in HPL reduction, positioning accuracy maintenance and computation load mitigation, which means it is more suitable for real-time multi-constellation navigation applications.

Therapeutic approaches of combining conventional photodynamic therapy (PDT) with other adjuvant treatments to sensitize PDT represent an appealing strategy. Herein, a novel synergetic "nanobomb" strategy based on glutathione (GSH)-responsive biodegradation was proposed to effectively destroy tumors expeditiously and accurately. This "nanobomb" was rationally constructed via the simultaneous encapsulation of methylene blue (MB) and l-arginine (L-Arg) into polyethylene glycol (PEG) modified mesoporous organosilicon nanoparticles (MON). The resulting L-Arg/MB@MP initially exhibited prolonged blood circulation, improved bioavailability, and enhanced tumor accumulation in mice after tail vein injection according to the pharmacokinetic investigations, before the nanoparticles were entirely excreted. Under laser irradiation, L-Arg/MB@MP produced remarkable reactive oxygen species (ROS) directly for PDT therapy, while a portion of ROS may oxidize L-Arg to generate nitric oxide (NO) not only for gas therapy (GT) but also serve as a biological messenger to regulate vasodilation to alleviate the tumor hypoxia. Subsequently, the rapidly released NO was further oxidized to reactive nitrogen species, which together with ROS promote immunogenic cell death by inducing G2/M cell-cycle arrest and apoptosis in cancer cells, and eventually resulting in enhanced anti-tumor immune responses. Moreover, the GSH depletion in tumor tissues induced by L-Arg/MB@MP biodegradation can cooperate with GT to amplify the therapeutic effect of PDT. These results demonstrate that this "nanobomb" provides new ideas for clinical translation to treat tumor patients in terms of synergistic PDT-GT nanotherapy in hypoxic-solid tumors.

We study the global stability of endemic equilibrium of a SIQRS epidemic model on complex networks. This model was proposed by Li et al. (2014). The local asymptotic stability of disease-free equilibrium and the permanence of the disease were proved by them. By use of a combination of Lyapunov function method and a monotone iterative technique, we prove that the endemic equilibrium is globally asymptotically stable. Numerical simulations indicate that quarantine strategy is an effective measure in preventing and controlling epidemic spreading.

Transgenic adenocarcinoma of the mouse prostate (TRAMP) mice is a widely used transgenic animal model of prostate cancer (PCa). We performed a label-free quantitative proteomics analysis combined with a bioinformatics analysis on the entire prostate protein extraction from TRAMP mice and compared it with WT littermates. From 2379 total identified proteins, we presented a modest mice prostate reference proteome containing 919 proteins. 61 proteins presented a significant expression difference between two groups. The integrative bioinformatics analysis predicted the overexpression of platelet-derived growth factor B (PDGF-B) in tumor tissues and supports the hypothesis of the PDGF-B signaling network as a key upstream regulator in PCa progression. Furthermore, we demonstrated that Crenolanib, a novel PDGF receptor inhibitor, inhibited PCa cell proliferation in a dose-dependent manner. Finally, we revealed the importance of PDGF-B regulatory network in PCa progression, which will assist us in understanding the role and mechanisms of PDGF-B in promoting cancer growth and provide valuable knowledge for future research on anti-PDGF therapy.

We study global stability of endemic equilibrium of an epidemic model with birth and death on complex networks. Under some conditions, the local asymptotic stability of the endemic equilibrium was established by Zhang and Jin (2011) for correlated networks, and the global asymptotic stability was obtained by Chen and Sun (2014) for uncorrelated networks. In this work, we remove those conditions, and prove by constructing a Lyapunov function that the endemic equilibrium is globally asymptotically stable. Numerical simulations are also presented to illustrate the feasibility of the result.

The moment-curvature skeleton curve of a cross-section, and the force-displacement skeleton curve of shear walls, are both simplified to four lines represented by four reference points: the crackin...

// Tingting Men 1, * , Cuicui Yu 2, * , Dan Wang 3 , Fang Liu 3 , Jingjing Li 3 , Xiaoying Qi 3 , Chunhua Yang 3 , Wenguo Jiang 3 , Xiaodan Wei 3 , Xuri Li 3 , Bin Wang 4 , Jia Mi 3 and Geng Tian 3 1 School of Nursing, Binzhou Medical University, Yantai, Shandong, China 2 Department of Anesthesiology, Yantai Yu Huang Ding Hospital, Yantai, Shandong, China 3 Medicine and Pharmacy Research Center, Binzhou Medical University, Yantai, Shandong, China 4 Institute of Molecular Imaging, Binzhou Medical University, Yantai, Shandong, China * These authors have contributed equally to this work Correspondence to: Geng Tian, email: tiangengshandong@yeah.net Jia Mi, email: Jia.mi@kemi.uu.se Bin Wang, email: binwang001@aliyun.com Keywords: prostate cancer, interleukin-10, polymorphism, peripheral blood interleukin-10, meta-analysis Received: December 16, 2016 Accepted: April 11, 2017 Published: April 29, 2017 ABSTRACT This study purported to investigate the impact of interleukin-10 (IL-10) gene 4 polymorphisms (-1082G>A, -819T>C, -592A>C and 210T>C) on peripheral blood IL-10 variation and prostate cancer (PCa) risk, with a special consideration given to various origins of between-study heterogeneity. 2 researchers independently fulfilled literature retrieval, quality assessment and information collection. Sub-grouped analyses per ethnicity, continent, design type, control source, genotyping procedure, genotype validation, age-matched status, study sample size, quality score and controls’ mean age were conducted, respectively. Total 17 unduplicated studies (patients/controls: 7561/8101) were assessable for PCa risk, and 4 unduplicated studies (1189 subjects) for peripheral blood IL-10 variation. Pooling all assessable studies identified a marginally significant association between the -1082A allele and increased PCa risk (odds ratio (OR)=1.10, 95% confidence interval [CI]: 1.00 to 1.21) (Heterogeneity I 2 =64.3%), and no significance was detected in sub-grouped analyses of this polymorphism. Contrastingly, the -592C allele was significantly associated with reduced PCa risk in both prospective (OR=0.85, 95% CI: 0.77 to 0.95) and population-based (OR=0.92, 95% CI: 0.84 to 1.00) studies (Heterogeneity I 2 =0.0% and 18.1%). Moreover, carriers of combined -592CA/CC genotypes had a significant higher level of peripheral blood IL-10 than the -592AA genotype carriers (weighted mean difference=0.45 and 0.54 mg/dL, 95% CI: 0.23 to 0.67 and 0.30 to 0.39). The above comparisons possessed a low probability of publication bias. In sum, our findings suggested that IL-10 gene -592A>C polymorphism may represent a promising candidate locus for the occurrence of PCa, and further signified a contributing role of this polymorphism in prostate carcinogenesis.

// Fang Liu 1, 2, * , Yuan Zhang 1, * , Tingting Men 1 , Xingyue Jiang 2 , Chunhua Yang 1 , He Li 4 , Xiaodan Wei 1 , Dong Yan 1 , Gangming Feng 5 , Jianke Yang 1 , Jonas Bergquist 3 , Bin Wang 2 , Wenguo Jiang 1 , Jia Mi 1, 3 , Geng Tian 1 1 Medicine and Pharmacy Research Center, Binzhou Medical University, Yantai, Shandong Province, 264003 China 2 Department of Radiology, Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong Province, 256603 China 3 Department of Chemistry – BMC, Uppsala University, Uppsala, 75124, Sweden 4 Department of Gastric and Intestine, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong Province, 264003 China 5 Yantai Institute, China Agriculture University, Yantai, Shandong Province, 264670 China * Shared first author Correspondence to: Geng Tian, email: Tiangeng@live.se Wenguo Jiang, email: jiangwg@foxmail.com Jia Mi, email: jia.mi@kemi.uu.se Keywords: proteomic, PDGF-B, gastric cancer, PRDX5, pathway Received: December 02, 2016 Accepted: February 07, 2017 Published: March 06, 2017 ABSTRACT Gastric cancer is one of the most common cancers in Asian countries. Searching for reliable biomarkers involving the development of gastric cancer is important for clinical practice. Quantitative proteomics has become an important method contributed to the discovery of novel diagnostic or therapeutic targets for the management of cancer. Here, we identified differently expressed proteins in gastric cancer and normal gastric tissues by using the high resolution mass spectrometer. Among the total of 2280 identified proteins, 87 were differentially expressed between gastric cancer and normal gastric tissues. Notably, several significant proteins are in the PDGF-B signaling pathway, including peroxiredoxin5 (PRDX5), S100A6, calreticulin (CALR) and cathepsin D (CTSD), which were validated by western blot. Furthermore, upstream regulators including PDGF-B, PDGFR-β, Akt, eIF4E and p70s6K were found significantly increased in the gastric cancer tissues. In addition, silencing of PRDX5 and PDGF-B suppressed the proliferation of gastric cancer cells in vitro . The administration of exogenous PDGF-BB recovered the reduced expression of PDGF-B signaling pathway in PDGF-B knockdown cells. Taken together, our findings suggested that PDGF-B signaling pathway plays an important role in the regulation of gastric cancer proliferation and the inhibition of this pathway may be a potential approach for treatment of gastric cancer.

In this paper, we study the global stability and attractivity of the endemic equilibrium for a network-based SIS epidemic model with nonmonotone incidence rate. The model was introduced in Li (2015). We prove that the endemic equilibrium is globally asymptotically stable if α (a parameter of this model) is sufficiently large, and is globally attractive if the transmission rate λ satisfies λ λ c ∈ ( 1 , 2 ] , where λ c is the epidemic threshold. Some numerical experiments are also presented to illustrate the theoretical results.

The exploration of an intelligent multifunctional imaging-guided therapeutic platform is of great significance because of its ideal delivery efficiency and controlled release. In this work, a tumor microenvironment (TME)-responsive nanocarrier (denoted as MB@MSP) is designed for on-demand, sequentially release of a short D-peptide antagonist of programmed cell death-ligand 1 (named as PDPPA-1) and a photosensitizer methylene blue (MB). Fe3O4-Au located in the core of MB@MSP is used as a magnetic resonance imaging and micro-computed tomography imaging contrast agent for noninvasive diagnosis of solid tumors and simultaneous monitoring of drug delivery. The PDPPA-1 coated on MB@MSP can be shed due to the cleavage of the peptide substrate by matrix metalloproteinase-2 (MMP-2) that is highly expressed in the tumor stroma, and disulfide bonding is further broken when it encounters high levels of glutathione (GSH) in TME, which finally leads to significant size reduction and charge-reversal. These transitions facilitate penetration and uptake of nanocarriers against tumors. Noticeably, the released PDPPA-1 can block the immune checkpoint to create an environment that favors the activation of cytotoxic T lymphocytes and augment the antitumor immune response elicited by photodynamic therapy, thus significantly improving therapeutic outcomes. Studies of the underlying mechanisms suggest that the designed MMP-2 and GSH-sensitive delivery system not only induce apoptosis of tumor cells but also modulate the immunosuppressive tumor microenvironment to eventually augment the suppression tumor metastasis effect of CD8+ cytotoxic T cells. Overall, the visualization of the therapeutic processes with comprehensive information renders MB@MSP an intriguing platform to realize the combined treatment of metastatic tumors.

Nanoscaled metal organic frameworks have emerged as a novel type of organic-inorganic hybrid coordination polymeric nanomaterials and showed great promise in biomedical area in recent decades. As a special subclass, zeolitic imidazolate frameworks (ZIFs), constructing with metal ions and imidazolate linkers, own unique advantages of high porosity, large surface area, good biocompatibility, pH sensitivity and etc. These render ZIFs as attractive and promising platforms to delivery various cargos of drugs, imaging probes and biomacromolecules for cancer diagnosis and therapy. And this review specially summaries the state-of-the-art research on ZIFs for biosensing, cancer imaging and phototheranostics within the latest 5 years. The multiply strategies of synthesis, characterization and functionalization of ZIFs-based nanosystems are firstly discussed. The vital roles of ZIFs in biosensors, including electrochemical, fluorescent and colorimetric sensors are analyzed. Then, the monomodal and/or multimodal cancer imaging techniques mediated by ZIFs are addressed. Particular emphasis is placed on the ZIFs-based cancer phototheranostics which provide a potential alternative avenue to greatly improve the therapeutic index of cancer. Finally, the future opportunities and challenges of ZIFs are tentatively proposed and discussed from the point of translational medicine.

// Min Li 1,* , Peiyuan Wang 2,* , Chunhua Yang 1 , Wenguo Jiang 1 , Xiaodan Wei 1 , Xinbo Mu 3 , Xuri Li 1 , Jia Mi 1 and Geng Tian 1 1 Medicine and Pharmacy Research Center, Binzhou Medical University, Yantai, Shandong, China 2 Institute of Imaging, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, China 3 Personnel Department, Binzhou Medical University, Yantai, Shandong, China * These authors have contributed equally to this work Correspondence to: Geng Tian, email: // Jia Mi, email: // Xuri Li, email: // Keywords : hepatitis C virus; chronic kidney disease; meta-analysis; effect estimate Received : August 19, 2016 Accepted : October 14, 2016 Published : October 25, 2016 Abstract We aimed to meta-analytically assess the predisposition of hepatitis C virus (HCV) infection to the occurrence and severity of chronic kidney disease (CKD). Two authors independently searched articles and abstracted information. Odds ratio (OR) or hazard ratio (HR) along with 95% confidence interval (CI) was converged separately in 12 longitudinal (1,972,044 subjects) and 15 cross-sectional (937,607 subjects) studies. Overall effect estimate was remarkably significant in longitudinal studies (HR, 95% CI, P : 1.45, 1.23-1.71, 95%). HCV infection was also associated with an 1.54-fold (95% CI, P : 1.27-1.87, < 0.001) increased risk of having prevalent proteinuria. In longitudinal studies with estimated glomerular filtration rate (eGFR) < 60, < 30 and < 15 ml/min/1.73m 2 , the corresponding HR was 1.39 (95% CI, P : 1.14-1.69, 0.001), 1.79 (0.91-3.51, 0.091) and 2.30 (1.26-4.19, 0.007). Further grouping the longitudinal studies by median follow-up time at 5 years revealed that the effect estimate was reinforced in long-term studies (HR, 95% CI, P : 1.86, 1.19-2.89, 0.006; I 2 =98.1%) relative to that in short-term studies (1.21, 1.03-1.43, 0.024; 92.0%). In conclusion, our findings demonstrate the significant risk of experiencing incident CKD after HCV infection, with the lower eGFR and longer HCV exposure time entailing a greater risk.

We study an ocean related system with a small viscosity parameter, which is the linearized version of the modified Primitive Equations. As the parameter goes to zero, a $L^\infty$ convergence result is obtained together with the estimation on the thickness of the boundary layer., Comment: 7 pages

BACKGROUND An ozonation catalyst needs to be recycled easily and to exhibit high activity in view of its practical application in wastewater treatment. In this study, magnetic mesoporous MgFe2O4 was successfully prepared and used as a new ozonation catalyst for degradation of Acid Orange II (AOII). The role of Mg in MgFe2O4 was revealed to explain the high activity by catalytic experiments and XPS analysis. RESULTS The degradation efficiency of AOII in the MgFe2O4/O3 process exceeds 90% over a wide pH range of 4.6–9.6, slightly affected by the solution pH. The catalytic activity of MgFe2O4 is much higher than that of MgO, Fe2O3 and also their mixture (MgO+Fe2O3) with identical molar ratio of Mg2+ to Fe3+, indicating the first role of Mg, i.e. coupling with Fe to present a synergistically catalytic effect. Furthermore, MgFe2O4 possesses a reaction rate constant at least 2.3 times that of NiFe2O4, MnFe2O4, and CuFe2O4. It illustrates the second role of Mg, i.e. causing the high electron density on lattice oxygen in MgFe2O4 indicated by XPS and thus favoring activation of the electrophilic ozone. CONCLUSIONS This study demonstrated the easy recycling and high activity of MgFe2O4 in catalytic ozonation, and revealed the role of Mg in MgFe2O4. © 2015 Society of Chemical Industry

This paper studies the dynamics of a network-based SIRS epidemic model with vaccination and a nonmonotone incidence rate. This type of nonlinear incidence can be used to describe the psychological or inhibitory effect from the behavioral change of the susceptible individuals when the number of infective individuals on heterogeneous networks is getting larger. Using the analytical method, epidemic threshold $R_0$ is obtained. When $R_0$ is less than one, we prove the disease-free equilibrium is globally asymptotically stable and the disease dies out, while $R_0$ is greater than one, there exists a unique endemic equilibrium. By constructing a suitable Lyapunov function, we also prove the endemic equilibrium is globally asymptotically stable if the inhibitory factor $\alpha$ is sufficiently large. Numerical experiments are also given to support the theoretical results. It is shown both theoretically and numerically a larger $\alpha$ can accelerate the extinction of the disease and reduce the level of disease., Comment: 19 pages, 7 figures

Background Apurinic/apyrimidinic endonuclease-1 (APE1) is a rate-limiting enzyme in DNA base excision repair and has been implicated in carcinogenesis. In this study, we summarize available data to examine the susceptibility of APE1 gene Asp148Glu variant to digestive cancer via a meta-analysis. Material/Methods Study selection and data abstraction were conducted independently by 2 authors. Random-effects model was utilized to pool effect estimates. Heterogeneity and publication bias were addressed. Results Sixteen articles involving 4916 digestive cancer patients and 7748 controls were qualified for this meta-analysis. Overall association showed an indicative association between Asp148Glu variant and digestive cancer under allelic (odds ratio or OR=1.11; 95% confidence interval or CI: 0.99–1.25; P=0.074) and dominant (OR=1.18; 95% CI: 1.00–1.40; P=0.056) models, with strong evidence of heterogeneity. Deviation from Hardy-Weinberg equilibrium was an obvious source of heterogeneity. In subgroup analyses by cancer sites, this variant was significantly associated with the increased risk for hepatocellular cancer under allelic (OR=1.50; 95% CI: 1.25–1.80; P

This paper is concerned with the existence, nonexistence, uniqueness, and non-uniqueness of solutions for a singular parabolic equation in one dimension case. For different cases of some constant m of the equation, we study the uniqueness of solutions for m > − 1, the nonexistence of solutions for m ≤ − p, and the existence and non-uniqueness of solutions for − p

Longitudinal displacement of cross section of T-shaped shortlegshear wall was simplified to three parts: shear lag warpingdisplacement, plane section bending displacement and axialdisplacement. Shear lag warping deformation was assumed ascubic parabola distribution along flange, and based on minimumpotential energy principle, differential equations were deduced;with boundary conditions, a calculation theory for shear lageffect was established. With two T-shaped short-leg shear wallmodels, vertical stresses of flanges were obtained by calculationtheory and finite element calculation respectively, and comparisonbetween theoretical analysis results and numerical calculationresults was made. At last, parameter analysis was carriedout, and the influence of shear force, shear span ratio andheight-thickness ratio on shear lag coefficient was obtained.Research shows that numerical calculation results are in goodagreement with theoretical analysis results, and each parameterhas different influence on shear lag coefficient.

In this paper, we are concerned with the existence of positive steady states for a diffusive predator-prey model in a spatially heterogeneous environment. We completely determine the intervals of certain parameter of the model in which a positive steady state exists.

// Dan Wang 1,* , Xiaoying Qi 1 , Fang Liu 1,* , Chuanhua Yang 1 , Wenguo Jiang 1 , Xiaodan Wei 1 , Xuri Li 1 , Jia Mi 1 and Geng Tian 1 1 Medicine and Pharmacy Research Center, Binzhou Medical University, Yantai, Shandong, China * The first two authors have contributed equally to this work Correspondence to: Geng Tian, email: // Jia Mi, email: // Xuri Li, email: // Keywords : hepatocellular carcinoma; HMGB1/RAGE axis; polymorphism; genetic susceptibility; haplotype Received : December 22, 2016 Accepted : January 25, 2017 Published : February 08, 2017 Abstract Based on 540 hepatocellular carcinoma patients and 540 age- and gender-matched controls, we tested the hypothesis that high mobility group protein box1 ( HMGB1 ) and the receptor for advanced glycation end products ( RAGE ) genes are two potential candidate susceptibility genes for hepatocellular carcinoma in a multicenter hospital-based case-control analysis. The genotypes of seven widely-studied polymorphisms were determined, and their distributions respected the Hardy-Weinberg equilibrium. The mutant alleles of two polymorphisms, rs1045411 in HMGB1 gene and rs2070600 in RAGE gene, had significantly higher frequencies in patients than in controls ( P < 0.001), with the power to detect this significance of being over 99.9%. Moreover, the above two polymorphisms increased the risk of developing hepatocellular carcinoma significantly, particularly for rs2070600 under the additive (odds ratio [OR] = 1.77; 95% confidence interval [CI]: 1.34-2.32; P < 0.001) and dominant (OR = 1.75; 95% CI: 1.23-2.50; P = 0.002) models after adjusting for body mass index, smoking and drinking. Haplotype analysis showed that the T-C-T haplotype (rs1045411-rs2249825-rs1415125) in HMGB1 gene was associated with a 2.47-fold (95% CI: 1.41-4.34; P = 0.002) increased risk of hepatocellular carcinoma compared with the commonest C-C-T haplotype after adjustment. In RAGE gene, the T-T-A-G (rs1800625-rs1800624-rs2070600-rs184003) (adjusted OR; 95% CI; P: 1.75; 1.02-3.03; 0.045) and T-T-A-T (adjusted OR; 95% CI; P: 1.95; 1.01-3.76; 0.048) haplotypes were associated with a marginally increased risk of hepatocellular carcinoma compared with the commonest T-T-G-G haplotype. In summary, we identified two risk-associated polymorphisms (rs1045411 and rs2070600), and more importantly a joint impact of seven polymorphisms from the HMGB1/RAGE axis in susceptibility to hepatocellular carcinoma.

The main purpose of this paper is to estimate the thickness of boundary layer for nonlinear evolution equations with damping and diffusion as the diffusion parameter β goes to zero. We prove that the thickness of layer is of the order $O(\beta^{\gamma})$ with $0

This paper concerns the nonexistence of solutions for singular elliptic equations with a quadratic gradient term. The main results complement and partly extend some works by Arcoya et al. (2009) [1] . As a by-product of the main results, we fill in a gap in one of their works.

In this paper, we are concerned with the existence and nonexistence of positive solutions of boundary value problems for the one-dimensional p -Laplacian with a singular nonlinearity. In the case of the model equation, we give the necessary and sufficient conditions of the existence of positive solutions for both the Dirichlet problem and the periodic problem.

As a new type of high-rise building structure system, diagridtube in tube structure is increasingly applied in high-rise building.Guangzhou West tower is the first high-rise diagrid tube intube structure in China. To study seismic performance of thestructure, elastic time-history analysis and shaking table testwere conducted. The results of elastic time-history analysis andshaking table test were in a good agreement, which verified thevalidity of the elastic time-history analysis. Dynamic characteristicsand responses of the model structure’s acceleration,displacement and strain under different intensity earthquakeaction were obtained through analysis and test. Dynamicresponses of prototype structure were deduced based on similaritylaw and shaking table test results. Research shows thatdiagrid tube structure has a small deformation under earthquakeactions; the main vibration mode is translation, whiletorsional effect is not obvious; whiplash effect has less influenceon the structure; diagrid members, diagrid nodes andshear walls at the bottom of the structure are weak parts.

In this paper, we are interested in the positive solutions to a singular differential equation φ ″ − λ | φ ′ | 2 φ + f ( t ) = 0 , 0 t 1 , subject to the first or all of the following boundary conditions φ ( 1 ) = φ ( 0 ) = 0 , φ ′ ( 1 ) = φ ′ ( 0 ) = 0 , where λ is a positive constant, f ( t ) ∈ C 1 [ 0 , 1 ] , f ( t ) > 0 on [0,1]. By the classical method of elliptic regularization, some existence results of the above BVPs are obtained. Moreover, the uniqueness and the asymptotic behaviors as λ → 0 and as λ → ∞ will also be studied.

Interleukin-6 (IL-6) plays a contributory role in the progression and severity of many forms of cancer; it however remains unclear whether the relevance between circulating IL-6 and cancer is causal. We therefore meta-analyzed published articles in this regard using IL-6 gene -174G/C variant as an instrument. Seventy-eight and six articles were eligible for the association of -174G/C variant with cancer and circulating IL-6, respectively. Overall analyses failed to identify any significance between -174G/C and cancer risk. In Asians, carriers of the -174CC genotype had an 1.95-fold increased cancer risk compared with the -174GG genotype carriers (P = 0.009). By cancer type, significance was only attained for liver cancer with the -174C allele conferring a reduced risk under allelic (odds ratio or OR = 0.74; P = 0.001), homozygous genotypic (OR = 0.59; P = 0.029) and dominant (OR = 0.67; P = 0.004) models. Carriers of the -174CC genotype (weighted mean difference or WMD = −4.23 pg/mL; P

The epitaxial growth of BaTiO 3 (BTO) thin films on LaAlO 3 (0 0 1) substrates by laser molecular beam epitaxy was studied using real-time reflection-high-energy-electron-diffraction (RHEED). Atomic force microscopy (AFM) was employed to investigate the surface topography. When the BTO thin films were directly grown at 320 °C with a thickness of above two monolayers (ML), the RHEED patterns vanished rapidly, indicating the failure of crystallinity. However, the growth of eight ML BTO layers can be controlled by decreasing temperature from 600 °C step-by-step to 300 °C. The evolution of diffraction streaks revealed a scaling behavior with temperature and film thickness, demonstrating the evolution of the quasi-two-dimensional BTO islands growth and distribution. Furthermore, subsequently deposited 30 ML BTO thin films with a good crystallinity were obtained on the eight ML BTO buffer layers at a low temperature of 280 °C. It is found that the nucleation centers formed during decreasing temperature play a key role in determining the subsequent crystallization of BTO thin films at a lower temperature.

Summary The landslides caused by the 5.12 Wenchuan earthquake resulted in enormous casualties and property losses. Since the earthquake, more than 3,600 landslides have occurred, and 17 of them were catastrophic, each of which has killed more than 30 people. Meanwhile, passive flexible protection has gradually been introduced to resist landslides due to its significant advantages of economy, safety, and environmental protection. To resist landslides effectively, it is necessary to study the load path and design method of passive flexible protection under the action of landslides. In the design of passive flexible protection against landslides, determination of the landslide load is the primary task. In this paper, the formulas of the probability density function and distribution function of the landslide pressure are developed to obtain the value of the accumulated landslide pressure acting on the passive flexible protection, which can be used as the load input parameter in the design of passive flexible protection to resist landslides. Based on the case of the “Shiziliang” potential landslide for the 5.12 earthquake, the pressure data of the landslide are collected, the calculation formulas of the volume, and the pressure of the intercepted landslide are established, and the statistical parameters of the landslide pressure-loading sample are obtained. According to the Kolmogorov–Smirnov test method, the loading sample of the landslide pressure obeys an extreme-value type-I distribution, and then the load model of the landslide pressure is determined. Based on the reliability analysis method, the standard value of the landslide pressure with an over-95% assurance rate is obtained. These results can provide references for load confirmation to design the passive flexible protection to resist landslides.

Concrete and steel are two indispensable important construction materials. As the rapidly economic development and urbanization proceeding, the construction industry is towards to high-end direction development. In high-rise buildings, the advantage of steel structure is obvious, and owns considerable economic and social benefits. This paper clarifies the main characteristic of the steel structure in civil engineering; analysis the basic principle that maintain the stability of steel structure; discusses the construction method of steel structure in civil engineering, and puts forward the development trend of steel structure in civil engineering.

Background The severity of ischemic stroke symptoms varies among patients and is a critical determinant of patient outcome. To date, the association between the number of stenotic intracranial arteries and stroke severity remains unclear. Aims We aimed to investigate the association between the number of stenotic major intracranial arteries (NSMIA) and ischemic stroke severity, as well as the degree of stenosis and common stroke risk factors. Methods We performed a retrospective analysis of patients with digital subtraction angiography (DSA)-confirmed ischemic stroke. Clinical stroke severity was measured using the National Institutes of Health Stroke Scale (NIHSS). The number of stenotic vessels was counted from the internal carotid arteries and vertebral arteries, bilaterally. Results Eighty three patients were recruited from a single center and included in the study. NSMIA was significantly correlated with stroke severity (Pearson Correlation Coefficient = 0.485, P < 0.001), but not with the degree of stenosis (Pearson Correlation Coefficient = 0.01, P = 0.90). Multivariate regression analysis revealed that NSMIA was significantly associated with the NIHSS score after adjusting for stroke risk factors. The adjusted odds ratio (per lateral) was 2.092 (95% CI, 0.865 to 3.308, P = 0.001). The degree of stenosis was also significantly associated with the NIHSS score after adjusting for common risk factors. The odds ratio (per 10%) was 0.712 (95% CI, 0.202 to 1.223, P = 0.007). Conclusions The number of stenotic intracranial major arteries is associated with the severity of ischemic stroke independent of the degree of stenosis and other stroke risk factors. To the best of our knowledge, this has not been previosuly studied in great detail using DSA. Our data highlight the importance of examining all major arteries in stroke patients.

We analyze the transition from slow to fast light upon increasing the modulation frequency based on coherent population oscillation in Cascaded Erbium-doped fiber structure. The change from slow to fast light is more obvious in the Cascaded structure. In this structure, the transition bandwidth is lager and the relative delay difference between the maximum fractional advancement and the maximum fractional delay is greater than that in the single-stage fiber.

Ventricular septal defects (VSDs) are the most common type of congenital heart diseases (CHDs). To date, the genetic causes for sporadic VSDs remain largely unknown. GATA transcription factor 4 (GATA4) is a zinc-finger transcription factor that is expressed in developing heart and adult cardiomyocytes. Mutations in the coding region of the GATA4 gene have been identified in CHD patients, including VSD. As the GATA4 factor is a dosage-sensitive regulator, we hypothesized that the promoter region variants of the GATA4 gene may be genetic causes of VSD. In this study, we analyzed the promoter region of the GATA4 gene by bidirectional sequencing in 172 VSD patients and 171 healthy controls. The results showed that 5 heterozygous sequence variants (NG_008177:g.4071T>C, NG_008177:g.4148C>A, NG_008177:g.4566C>T, NG_008177:g.4653G>T, and NG_008177:g.4690G>deletion) within the promoter region of the GATA gene were identified in 5 VSD patients, but in none of controls. One heterozygous sequence variant (g.4762C>A) was found only in one control, which may have no functional significance. A functional analysis revealed that the transcriptional activity of variant NG_008177:g.4566C>T was reduced significantly, whereas the transcriptional activities of the variants (NG_008177:g.4071T>C, NG_008177:g.4148C>A, NG_008177:g.4653G>T, and NG_008177:g.4690G>deletion) were increased significantly compared with the wild-type GATA4 gene promoter. As GATA4 is a dosage-sensitive regulator during development, our data suggest that these sequence variants within the promoter region of the GATA4 gene may contribute to the VSD etiology by altering its gene expression. Additional studies in experimental animals will deepen our understanding of the genetic basis of VSD and shed light on designing novel molecular therapies for adult VSD patients carrying these variants.