Implications of C1q/TNF-related protein superfamily in patients with coronary artery disease.

The C1q complement/TNF-related protein superfamily (CTRPs) displays differential effects on the regulation of metabolic homeostasis, governing cardiovascular function. However, whether and how they may serve as predictor/pro-diagnosis factors for assessing the risks of coronary artery disease (CAD) remains controversial. Therefore, we performed a clinical study to elaborate on the implication of CTRPs (CTRP1, CTRP5, CTRP7, and CTRP15) in CAD. CTRP1 were significantly increased, whereas CTRP7 and CTRP15 levels were decreased in CAD patients compared to the non-CAD group. Significant differences in CTRP1 levels were discovered between the single- and triple-vascular-vessel lesion groups. ROC analysis revealed that CTRP7 and CTRP15 may serve as CAD markers, while CTRP1 may serve as a marker for the single-vessel lesion of CAD. CTRP1 and CTRP5 can serve as markers for the triple-vessel lesion. CTRP1 may serve as an independent risk predictor for triple-vessel lesion, whereas CTRP15 alteration may serve for a single-vessel lesion of CAD. CTRP1 may serve as a novel superior biomarker for diagnosis of severity of vessel-lesion of CAD patients. CTRP7, CTRP15 may serve as more suitable biomarker for the diagnosis of CAD patients, whereas CTRP5 may serve as an independent predictor for CAD. These findings suggest CTRPs may be the superior predictive factors for the vascular lesion of CAD and represent novel therapeutic targets against CAD

Comparisons of three polyethyleneimine-derived nanoparticles as a gene therapy delivery system for renal cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Polyethyleneimine (PEI), which can interact with negatively charged DNA through electrostatic interaction to form nanocomplexes, has been widely attempted to use as a gene delivery system. However, PEI has some defects that are not fit for keeping on gene expression. Therefore, some modifications against PEI properties have been done to improve their application value in gene delivery. In this study, three modified PEI derivatives, including poly(ε-caprolactone)-pluronic-poly(ε-caprolactone) grafted PEI (PCFC-g-PEI), folic acid-PCFC-isophorone diidocyanate-PEI (FA-PEAs) and heparin-PEI (HPEI), were evaluated in terms of their cytotoxicity and transfection efficiency <it>in vitro </it>and <it>in vivo </it>in order to ascertain their potential application in gene therapy.</p> <p>Methods</p> <p>MTT assay and a marker GFP gene, encoding green fluorescent protein, were used to evaluate cell toxicity and transfection activity of the three modified PEI <it>in vitro</it>. Renal cell carcinoma (RCC) models were established in BALB/c nude mice inoculated with OS-RC-2 cells to detect the gene therapy effects using the three PEI-derived nanoparticles as gene delivery vehicles. The expression status of a target gene Von Hippel-Lindau (VHL) in treated tumor tissues was analyzed by semiquantitative RT-PCR and immunohistochemistry.</p> <p>Results</p> <p>Each of three modified PEI-derived biomaterials had an increased transfection efficiency and a lower cytotoxicity compared with its precursor PEI with 25-kD or 2-kD molecule weight <it>in vitro</it>. And the mean tumor volume was obviously decreased 30% by using FA-PEAs to transfer VHL plasmids to treat mice RCC models. The VHL gene expression was greatly improved in the VHL-treated group. While there was no obvious tumor inhibition treated by PCFC-g-PEI:VHL and HPEI:VHL complexes.</p> <p>Conclusions</p> <p>The three modified PEI-derived biomaterials, including PCFC-g-PEI, FA-PEAs and HPEI, had an increased transfection efficiency <it>in vitro </it>and obviously lower toxicities compared with their precursor PEI molecules. The FA-PEAs probably provide a potential gene delivery system to treat RCC even other cancers in future.</p

Nonlinear dynamic analysis of composite piezoelectric plates with graphene skin

This paper studies the nonlinear dynamical characteristic of a composite plate made of new three-phase materials which include the graphene (GP) combined with macro fiber composite (MFC) in the polymer. The GP is supposed to be uniformly dispersed in the upper and lower surfaces of the composite laminated plate with 1–3 mode of macro fiber. The cross-ply MFC composite laminated plate is subjected to transversal excitations. The constitutive laws for the MFC-GP composite material are obtained based on the rule of mixture for multi-components of composite material. The nonlinear governing equations of motion of the MFC-GP plate are derived by Hamilton's principle and the von Kármán geometrical kinematics. Galerkin's approach is employed to discretize the partial differential governing equations into a two-degree-of-freedom nonlinear system. Then, stability analysis is conducted to investigate the influences of various parameters on natural frequencies of the MFC-GP plate, with a particular focus on the effects of GP volume fraction, initial conditions and damping coefficients on nonlinear vibration behaviours of the composite plate

Role of the tumor microenvironment in PD-L1/PD-1-mediated tumor immune escape

Tumor immune escape is an important strategy of tumor survival. There are many mechanisms of tumor immune escape, including immunosuppression, which has become a research hotspot in recent years. The programmed death ligand-1/programmed death-1 (PD-L1/PD-1) signaling pathway is an important component of tumor immunosuppression, which can inhibit the activation of T lymphocytes and enhance the immune tolerance of tumor cells, thereby achieving tumor immune escape. Therefore, targeting the PD-L1/PD-1 pathway is an attractive strategy for cancer treatment; however, the therapeutic effectiveness of PD-L1/PD-1 remains poor. This situation requires gaining a deeper understanding of the complex and varied molecular mechanisms and factors driving the expression and activation of the PD-L1/PD-1 signaling pathway. In this review, we summarize the regulation mechanisms of the PD-L1/PD-1 signaling pathway in the tumor microenvironment and their roles in mediating tumor escape. Overall, the evidence accumulated to date suggests that induction of PD-L1 by inflammatory factors in the tumor microenvironment may be one of the most important factors affecting the therapeutic efficiency of PD-L1/PD-1 blocking

Nicotine aggravates vascular adiponectin resistance via ubiquitin-mediated adiponectin receptor degradation in diabetic Apolipoprotein E knockout mouse

There is limited and discordant evidence on the role of nicotine in diabetic vascular disease. Exacerbated endothelial cell dysregulation in smokers with diabetes is associated with the disrupted adipose function. Adipokines possess vascular protective, anti-inflammatory, and anti-diabetic properties. However, whether and how nicotine primes and aggravates diabetic vascular disorders remain uncertain. In this study, we evaluated the alteration of adiponectin (APN) level in high-fat diet (HFD) mice with nicotine (NIC) administration. The vascular pathophysiological response was evaluated with vascular ring assay. Confocal and co-immunoprecipitation analysis were applied to identify the signal interaction and transduction. These results indicated that the circulating APN level in nicotine-administrated diabetic Apolipoprotein E-deficient (ApoE−/−) mice was elevated in advance of 2 weeks of diabetic ApoE−/− mice. NIC and NIC addition in HFD groups (NIC + HFD) reduced the vascular relaxation and signaling response to APN at 6 weeks. Mechanistically, APN receptor 1 (AdipoR1) level was decreased in NIC and further significantly reduced in NIC + HFD group at 6 weeks, while elevated suppressor of cytokine signaling 3 (SOCS3) expression was induced by NIC and further augmented in NIC + HFD group. Additionally, nicotine provoked SOCS3, degraded AdipoR1, and attenuated APN-activated ERK1/2 in the presence of high glucose and high lipid (HG/HL) in human umbilical vein endothelial cells (HUVECs). MG132 (proteasome inhibitor) administration manifested that AdipoR1 was ubiquitinated, while inhibited SOCS3 rescued the reduced AdipoR1. In summary, this study demonstrated for the first time that nicotine primed vascular APN resistance via SOCS3-mediated degradation of ubiquitinated AdipoR1, accelerating diabetic endothelial dysfunction. This discovery provides a potential therapeutic target for preventing nicotine-accelerated diabetic vascular dysfunction

The encoding of whiteness and blackness in Japanese manga

This thesis explores the use of black and white space on the manga page to portray characters associated with differential amounts of "blackness/darkness" and " whiteness/lightness" and how manga artists thereby relayed messages about social status, desirability, and Japan’s place within international hierarchies configured by race, ethnicity, and gender in the 1970s. Blackness and whiteness on the manga page were sometimes intended to correlate with perceived racial categories as understood by manga artists at that time, but because manga iconography often lacks explicit differentiation between individuals of different races or nationalities, in many cases that correlation was ambiguous or absent. Nonetheless, relative whiteness/lightness or blackness/darkness still relayed messages about relative merit in fictional situations that referenced postwar social issues in Japan: the Women’s Liberation movement and the concern over the renewal of the United States-Japan Security Treaty. The analysis centers on Ikeda Riyoko’s shōjo manga The Rose of Versailles and Tezuka Osamu’s shōnen manga "Black Jack," both from the 1970s. While the analysis of the former does not primarily address racial issues, it reveals that in shōjo manga, the "White" world of fantasy can represent a liberating realm for female readers. In contrast, shōnen manga uses "Whiteness" and "Blackness" to symbolize strength and weakness in a more realistic context, where race, ethnicity, and nationality are explicitly depicted on the manga page. The thesis further examines how these two manga were adapted for the all-women Takarazuka theatre, analyzing depictions of whiteness/lightness and blackness/darkness as portrayed by bodies that are themselves already gendered and racialized.Arts, Faculty ofAsian Studies, Department ofGraduat

Aerodynamic Characteristics of a Z-Shaped Folding Wing

Z-shaped folding wings have the potential to enhance the flight performance of an aircraft, contingent upon its mission requirements. However, the current scope of research on unmanned aerial vehicles (UAVs) with Z-shaped folding wings primarily focuses on the analysis of their folding structure and aeroelasticity-related vibrations. Computational fluid dynamics methods and dynamic meshing are employed to examine the folding process of Z-shaped folding wings. By comparing the steady aerodynamic characteristics of Z-shaped folding wings with those of conventional wings, this investigation explores the dynamic aerodynamic properties of Z-shaped folding wings at varying upward folding speeds. The numerical findings reveal that the folding of Z-shaped folding wings reduces the lift-to-drag ratio, yet simultaneously diminishes the nose-down pitching moment, thereby augmenting maneuverability. Concerning unsteady aerodynamics, the transient lift and drag coefficients of the folded wing initially increase and subsequently decrease as the folding angle increases at small angles of attack. Likewise, the nose-down pitching moment exhibits the same pattern in response to the folding angle. Additionally, the aerodynamic coefficients experience a slight decrease during the initial half of the folding process with increasing folding speed. Once the wing reaches approximately 40°~45° of folding, there is an abrupt change in the transient aerodynamic coefficients. Notably, this abrupt change is delayed with higher folding speeds, eventually converging to similar values across different folding speeds

Using a stacked-autoencoder neural network model to estimate sea state bias for a radar altimeter.

This paper constructed a stacked-autoencoder neural network model (SAE model) to estimate sea state bias (SSB) based on radar altimeter data. Six cycles of the geophysical data record (GDR) from Jason-1/2 radar altimeters were used as a training dataset, and the other 2 cycles of the GDR from Jason-1/2 were used for testing. The inputs to this SAE model include the significant wave height (SWH), wind speed (U), sea surface height (SSH), backscatter coefficient (σ0) and automatic gain control (AGC), and the model outputs the SSB. The model includes one input layer, three hidden layers and one output layer. The SSBs in the GDR of Jason-1/2 were obtained from a nonparametric model based on the SWH and U as input variables; thus, the model has high accuracy but low efficiency. The SSBs in the GDR of HY-2A were computed using a four-parameter parametric model that uses the SWH and U as input variables; therefore, this model's computational speed is high but its accuracy is low. Thus, we used the HY-2A radar altimeter as an unseen validation dataset to evaluate the performance of the SAE model. Then, we analyzed the contrasting results of these methods, including the differences in the SSB, explained variance, residual error and operational efficiency. The results demonstrate not only that the accuracy of the SAE model is superior to that of the conventional parametric model but also that its operational efficiency is better than that of the nonparametric model

Nonlinear Dynamic Analysis of Macrofiber Composites Laminated Shells

This work presents the nonlinear dynamical analysis of a multilayer d31 piezoelectric macrofiber composite (MFC) laminated shell. The effects of transverse excitations and piezoelectric properties on the dynamic stability of the structure are studied. Firstly, the nonlinear dynamic models of the MFC laminated shell are established. Based on known selected geometrical and material properties of its constituents, the electric field of MFC is presented. The vibration mode-shape functions are obtained according to the boundary conditions, and then the Galerkin method is employed to transform partial differential equations into two nonlinear ordinary differential equations. Next, the effects of the transverse excitations on the nonlinear vibration of MFC laminated shells are analyzed in numerical simulation and moderating effects of piezoelectric coefficients on the stability of the system are also presented here. Bifurcation diagram, two-dimensional and three-dimensional phase portraits, waveforms phases, and Poincare diagrams are shown to find different kinds of periodic and chaotic motions of MFC shells. The results indicate that piezoelectric parameters have strong effects on the vibration control of the MFC laminated shell