Abstract

The association between DNA repair gene polymorphisms and bladder cancer risk has been widely studied. However, only few studies have examined the correlation between bladder cancer and instillation agent sensitivity. The aim of this study was to examine the association between polymorphisms of DNA repair genes, namely X-ray repair cross-complementing group I (XRCC1) rs2854509 and rs3213255, and bladder cancer recurrence risk. We recruited 244 patients (130 treated with epirubicin and 114 treated with mitomycin C). Genomic DNA was used to examine the XRCC1 rs2854509 and rs3213255 genotypes by Taqman PCR analysis. Combination analysis of XRCC1 rs2854509 and rs3213255 and examination of XRCC1 diplotypes were performed to reveal possible correlations. The rs2854509 CC and rs3213255 TT genotypes conferred shorter survival times than the rs2854509 AC/AA and rs3213255 CC/CT genotypes in patients treated with epirubicin, but not in those treated with mitomycin C (MMC) in adjusted models [hazard ratio (HR) = 0.23, 95 % confidence interval (CI) = 0.10–0.53 for rs2854509 AC + AA compared with CC; HR = 0.17, 95 % CI = 0.06–0.46 for rs3213255 CC + CT compared with TT]. Combination analysis showed significantly increased recurrence-free survival (RFS) among patients simultaneously carrying the rs2854509 AC/AA and rs3213255 CC/CT genotypes with an HR of 0.15 (95 % CI = 0.05–0.45) compared to those carrying other genotypes. Diplotype analysis demonstrated that the A-C/C-T diplotype is associated with a lower risk of recurrence compared with the common wild C-T/C-T diplotype (HR = 0.17, 95 % CI = 0.06–0.51). Our results suggest that the rs2854509 CC and rs3213255 TT genotypes confer higher sensitivity to epirubicin instillation. Moreover, the A-C/C-T diplotype presents significantly lower recurrence risk than other diplotypes.

Abstract

The metadynamic recrystallizaton behavior of a V-N microalloyed steel was studied by performing a two-pass isothermal compression test at 900 °C–1050 °C at a strain rate of 0.1 s⁻¹ to 7 s⁻¹ with the inter-pass time of 0.2–2 s on a Gleeble-3800 thermo-mechanical simulator. The effects of the processing parameters on the metadynamic recrystallizaton behavior of the tested steel were analyzed. The activation energy of the tested steel was determined by regression method and the kinetic models were constructed. Our results showed that the metadynamic recrystallizaton of the tested steel can easily occur due to low activation energy. The effects of the processing parameters are marked and higher deformation temperature, strain rate, or longer time interval contributes to an increase in the metadynamic recrystallized volume fraction. However, it is difficult to observe work hardening in the second pass at a time interval of 0.2 s and stress tends to be steady. Finally, the kinetic models were confirmed by comparing the experimental and the predicted results.

Abstract

Brain activity is a cooperative process among neurons and involves the coupling relationship, which is crucial to perform operational tasks in various specialized areas of the nervous system. A finite signal transmission speed along the axons results in a space-dependent time delay. The central pattern generator (CPG) can in principle produce basic locomotor rhythm in the absence of inputs from higher brain centers and peripheral sensory feedback. To study the dynamic performance of CPG with time delay and its coupling relationship with the cerebral cortex, a new CPG model with time delay and a model of the neural mass model (NMM) and the CPG are developed. The coupling model is based on biological experimental results. Bifurcation theories and maximal Lyapunov exponent are used to analyze the dynamic performance. From the results, some CPGs are suggested to be embedded in limbs and composed of the parameters space which corresponds to the one of the cerebral cortex. This embodiment of humans can reduce the burden of the brain and simplify the control of the locomotion. The results also show that the phase diagram of the CPG cannot keep the limit cycle, and that the state of the NMM becomes increasingly chaotic as time delay increases. This finding implies that a person with slow reaction can easily lose the stability of his or her locomotion.

Abstract

Solid phosphoric acid (SPA) catalysts with different carriers were prepared and used for catalytic fast pyrolysis of poplar wood to produce levoglucosenone (LGO), a valuable anhydrosugar derivative that can be used in various organic synthesis applications. Pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) experiments were performed to evaluate the catalytic capabilities of these catalysts under different reaction conditions. The results indicated that SPA catalyst prepared with the SBA-15 carrier exhibited the best catalytic capability for selectively producing LGO. Both the catalytic pyrolysis temperature and catalyst-to-biomass ratio affected the pyrolytic products greatly. The maximal LGO yield reached as high as 8.2 wt% from poplar wood, obtained at the pyrolysis temperature of 300 °C and the catalyst-to-biomass ratio of 1. The by-products during the catalytic pyrolysis process were mainly acetic acid (AA) and furfural (FF). In addition, the SPA catalyst possessed better catalytic capability than the liquid phosphoric acid (H₃PO₄) catalyst to produce LGO.

Abstract

Hypertriglyceridemic waist (HW) phenotype was associated with an atherogenic lipid profile in adolescents. But unlike adults, the cutoffs of waist circumference are age- and gender-specific standards and are less feasible for non-professional use. The present study tested the hypothesis that simple variables, such as waist-to-height ratio (WHtR) and serum triacylglycerol (TG) concentrations, could be used as screening tools for the identification of adolescents characterized by atherogenic lipid profile. In 2006, anthropometric and biochemical measurements were assessed in a cross-sectional population-based study of 3136 Han adolescents, aged 13–17 years. The hypertriglyceridemic waist-to-height ratio (HWHtR) phenotype was defined as serum TG concentrations ≥1.47 mmol/L and WHtR ≥0.48 for boys and ≥0.46 for girls. Hypercholesterolemia (total cholesterol ≥5.18 mmol/L), high low-density lipoprotein cholesterol (LDL-C ≥3.37 mmol/L), low high-density lipoprotein cholesterol (HDL-C <1.03 mmol/L), and high non-HDL-C (≥3.76 mmol/L) were considered as atherogenic lipid profiles. After control for age and sex, adolescents with the HWHtR phenotype were more likely to have hypercholesterolemia (odds ratio (OR) = 7.8, 95 % confidence interval (CI) = 3.5–17.3, P < 0.001), high LDL-C (OR = 9.4, 95 % CI = 2.8–31.2, P < 0.001), low HDL-C (OR = 10.8, 95 % CI = 6.9–17.0, P < 0.001), and high non-HDL-C (OR = 22.9, 95 % CI = 10.0–52.2, P < 0.001) than those adolescents with normal WHtR and normal serum TG concentrations.

Conclusion: The present study demonstrates that HWHtR phenotype is a simple marker for identifying adolescents with atherogenic lipid profile. Compared with HW phenotype, HWHtR phenotype is a non-age-dependent index with higher applicability to screen for cardiovascular risk factors in adolescents.

Abstract

To find potential serum biomarkers for upper tract urothelial carcinomas (UTUCs) via ¹H nuclear magnetic resonance (¹H NMR)-based metabolomic analysis. Serum specimens collected from 34 healthy individuals and 39 patients with UTUCs were subjected to ¹H NMR-based metabolomic analysis. Principal component and orthogonal partial least squares discriminant analyses were used to analyse the data. Compared with serum samples from healthy subjects, samples from UTUC patients showed elevated levels of lactate and creatinine as well as decreased levels of glucose, glutamine and taurine. Serum low-density lipoprotein/very low-density lipoprotein, valine and glycoprotein levels showed decreasing trends whereas serum polyunsaturated fatty acids and 3,7-dimethyluric acid level presented increasing trends in UTUC patients. ¹H NMR-based metabolomic analysis of serum enhances the current understanding of the mechanisms involved in UTUC development. The present analysis may be a valuable tool for UTUC detection.

Abstract

MicroRNAs (miRNAs) are recognized as important molecules and have emerged as important gene regulators in tumorigenesis. Growing evidence suggested that miR-218 was a tumor suppressor in many human cancers. However, its underlying role in bladder cancer (BCa) remains unclear. The aim of this study was to explore the effect of miR-218 on the proliferation, migration, and invasion of BCa cells. We found that miR-218 was frequently downregulated in BCa tissues compared with normal adjacent tissues. In vitro and in vivo assays demonstrated that miR-218 overexpression in the BCa cells inhibited cell proliferation, migration, and invasion. Luciferase reporter assay showed that BMI-1 was a direct target of miR-218. In addition, we found that miR-218 regulated the expression of BMI-1 and its downstream target (PTEN) and participated in the phosphorylation of AKT. Our findings indicate that miR-218 functions as tumor suppressor in BCa, and the miR-218/BMI-1 axis may provide novel diagnostic and therapeutic strategies for the treatment of BCa.

Abstract

Computational protein-ligand docking is of great importance in drug discovery and design. Conformational changes greatly affect the results of protein-ligand docking, especially when water molecules take part in mediating protein ligand interactions or when large conformational changes are observed in the receptor backbone interface. We have developed an improved protocol, SWRosettaLigand, based on the RosettaLigand protocol. This approach incorporates the flexibility of interfacial water molecules and modeling of the interface of the receptor into the original RosettaLigand. In a coarse sampling step, SWRosettaLigand pre-optimizes the initial position of the water molecules, docks the ligand to the receptor with explicit water molecules, and minimizes the predicted structure with water molecules. The receptor backbone interface is treated as a loop and perturbed and refined by kinematic closure, or cyclic coordinate descent algorithm, with the presence of the ligand. In two cross-docking test sets, it was identified that for 8 out of 14, and 16 out of 22, test instances, the top-ranked structures by SWRosettaLigand achieved better accuracy than other protocols.

Abstract

Silk materials with different nanostructures have been developed without the understanding of the inherent transformation mechanism. Here we attempt to reveal the conversion road of the various nanostructures and determine the critical regulating factors. The regulating conversion processes influenced by a hierarchical charge distribution were investigated, showing different transformations between molecules, nanoparticles and nanofibers. Various repulsion and compressive forces existed among silk fibroin molecules and aggregates due to the exterior and interior distribution of charge, which further controlled their aggregating and deaggregating behaviors and finally formed nanofibers with different sizes. Synergistic action derived from molecular mobility and concentrations could also tune the assembly process and final nanostructures. It is suggested that the complicated silk fibroin assembly processes comply a same rule based on charge distribution, offering a promising way to develop silk-based materials with designed nanostructures.

Abstract

The outstanding compliance and adaptability of invertebrate limbs have motivated a recent surge of research activity in continuum robots. In previous studies, the dynamical model of the continuum robot is constructed by using the Lagrange method and the analytic method for the kinematics and dynamics of a continuum robot are shown. In this paper, we focus on the development of the kinematic models of the continuum robot and the energy optimal planning for the continuum robot. A multilayer neural network is used for solving the non-linearity of the rigid parallel mechanism. Based on Bishop frames, an optimal curve is used to generate the continuous backbone curve. The optimality criteria are used to choose the curve that satisfies task constraints while optimizing energy consumption. Kinematic models are validated through experiments done with the continuum robot. The results demonstrate that the proposed method for the continuum robot is feasible.

Abstract

To help understand the pyrolysis mechanism of lignin, a non-phenolic lignin dimer model compound with β-O-4 linkage, namely 1-methoxy-2-(4-methoxyphenethoxy)benzene, was prepared. Its pyrolysis mechanism was investigated by density functional theory calculations and confirmed by the analytical pyrolysis–gas chromatography/mass spectrometry experiments. Possible pyrolytic pathways were proposed and analyzed based on three initial pyrolysis mechanisms of the model compound, including the C_β–O homolytic mechanism, the C_α–C_β homolytic mechanism and the C_β–O concerted decomposition mechanism. The results indicate that the lignin dimer model compound is thermally stable at low pyrolysis temperature (300 °C), whereas at moderate pyrolysis temperature (500 °C), four major pyrolytic products will be generated via the initial C_β–O concerted decomposition and C_β–O homolysis, including the 1-methoxy-4-vinylbenzene, 2-hydroxybenzaldehyde, 1-ethyl-4-methoxybenzene and 2-methoxyphenol. Products from the C_α–C_β homolysis can hardly be formed, due to the high-energy barriers and limitation of the available free hydrogen atoms. Secondary cracking of the primary pyrolytic products will take place to form some light compounds, which will be enhanced with the increase in pyrolysis temperature.

Abstract

Abstract

Abstract

Abstract

Recent progress in chimeric antigen receptor-modified T-cell (CAR-T cell) technology in cancer therapy is extremely promising, especially in the treatment of patients with B-cell acute lymphoblastic leukemia. In contrast, due to the hostile immunosuppressive microenvironment of a solid tumor, CAR T-cell accessibility and survival continue to pose a considerable challenge, which leads to their limited therapeutic efficacy. In this study, we constructed two anti-MUC1 CAR-T cell lines. One set of CAR-T cells contained SM3 single chain variable fragment (scFv) sequence specifically targeting the MUC1 antigen and co-expressing interleukin (IL) 12 (named SM3-CAR). The other CAR-T cell line carried the SM3 scFv sequence modified to improve its binding to MUC1 antigen (named pSM3-CAR) but did not co-express IL-12. When those two types of CAR-T cells were injected intratumorally into two independent metastatic lesions of the same MUC1⁺ seminal vesicle cancer patient as part of an interventional treatment strategy, the initial results indicated no side-effects of the MUC1 targeting CAR-T cell approach, and patient serum cytokines responses were positive. Further evaluation showed that pSM3-CAR effectively caused tumor necrosis, providing new options for improved CAR-T therapy in solid tumors.

Abstract

Abstract

Abstract

Epithelioid angiomyolipoma is considered to be a rare variant of angiomyolipoma and potentially malignant. Reported cases of renal epithelioid angiomyolipoma with extension into the renal vein and inferior vena cava are even rarer. Once it occurs, it is difficult to differentiate from renal cell carcinoma on imaging. In addition, very few of the reported cases presented contrast-enhanced ultrasound images. Here, we report a case of a renal epithelioid angiomyolipoma extending into the renal vein and inferior vena cava along with its contrast-enhanced ultrasonic information. Contrast-enhanced ultrasound provided valuable information for diagnosis in this case.

Abstract

Although amazing progress has been made in machine learning to achieve high generalization accuracy and efficiency, there is still very limited work on deriving meaningful decision-making actions from the resulting models. However, in many applications such as advertisement, recommendation systems, social networks, customer relationship management, and clinical prediction, the users need not only accurate prediction, but also suggestions on actions to achieve a desirable goal (e.g., high ads hit rates) or avert an undesirable predicted result (e.g., clinical deterioration). Existing works for extracting such actionability are few and limited to simple models such as a decision tree. The dilemma is that those models with high accuracy are often more complex and harder to extract actionability from.

In this paper, we propose an effective method to extract actionable knowledge from additive tree models (ATMs), one of the most widely used and best off-the-shelf classifiers. We rigorously formulate the optimal actionable planning (OAP) problem for a given ATM, which is to extract an actionable plan for a given input so that it can achieve a desirable output while maximizing the net profit. Based on a state space graph formulation, we first propose an optimal heuristic search method which intends to find an optimal solution. Then, we also present a sub-optimal heuristic search with an admissible and consistent heuristic function which can remarkably improve the efficiency of the algorithm. Our experimental results demonstrate the effectiveness and efficiency of the proposed algorithms on several real datasets in the application domain of personal credit and banking.

Abstract