The Synthetic Compound Norcantharidin Induced Apoptosis in Mantle Cell Lymphoma In Vivo and In Vitro through the PI3K-Akt-NF- κ

This study aimed to elucidate the antitumor activity of norcantharidin (NCTD) against human mantle cell lymphoma (MCL). Cell proliferation and apoptosis were examined by MTS and flow cytometry. Caspase-3, -8, and -9 activities were detected with a colorimetric caspase protease assay. Apoptotic proteins—including PARP, cyclin D1, Bcl-2 family proteins, XIAP, and cIAP I—were studied by western blot. The phosphoinositide 3 kinase (PI3K) inhibitor LY294002 was used to investigate the involvement of the PI3K/Akt signaling pathway. In vivo studies were performed using Z138 cell xenografts in nude mice. NCTD inhibited proliferation and induced apoptosis of Z138 and Mino cells, both in vitro and in vivo. PI3Kp110α and p-Akt expressions were downregulated by NCTD treatment. NCTD downregulated NF-κB activity by preventing NF-κB phosphorylation and nuclear translocation. This effect was correlated with the suppression of NF-κB-regulated gene products, such as cyclin D1, BAX, survivin, Bcl-2, XIAP, and cIAP. This phenomenon was blocked by the PI3K inhibitor LY294002. Our results demonstrated that NCTD can induce growth arrest and apoptosis in MCL cells and that the mechanism may involve the PI3K/Akt/NF-κB signaling pathway. NCTD may have therapeutic and/or adjuvant therapeutic applications in the treatment of MCL

Dual-envelop-oriented moving horizon path tracking control for fully automated vehicles

A novel description of dual-envelop-oriented path tracking issue is presented for fully automated vehicles which considers shape of vehicle as inner-envelop (I-ENV) and feasible road region as outer-envelop (O-ENV). Then implicit linear model predictive control (MPC) approach is proposed to design moving horizon path tracking controller in order to solve the situations that may cause collision and run out of road in traditional path tracking method. The proposed MPC controller employed varied sample time and varied prediction horizon and could deal with modelling error effectively. In order to specify the effectiveness of the proposed dual-envelop-oriented moving horizon path tracking method, veDYNA-Simulink joint simulations in different running conditions are carried out. The results illustrate that the proposed path tracking scheme performs well in tracking the desired path, and could increase path tracking precision effectively

Tranquilizing and Allaying Excitement Needling Method Affects BDNF and SYP Expression in Hippocampus

Sleep disorder is a state of sleep loss caused by various reasons, which leads to a series of changes, such as emotion, learning and memory, and immune function. “Tranquilizing and allaying excitement” was widely used in clinical treatment of insomnia; however, the mechanism was still not very clear. We randomly divided rats into three groups: control group, sleep deprivation group, and acupuncture treatment group. We observed BDNF and SYP expression in hippocampus in these three groups. Both protein contents and mRNA contents of BDNF and SYP were measured by western blot, immunohistochemistry, and RT-PCR analysis. The sleep deprivation model was established using modified multiple platform sleep deprivation method (MMPM). Our study explored the BDNF and SYP abnormality in hippocampus caused by sleep deprivation and “tranquilizing and allaying excitement” intervention regulated the abnormal expression of BDNF and SYP caused by sleep deprivation on the short run and the long run. Our study provided a molecular evidence that “tranquilizing and allaying excitement” treatment in rats with sleep disorder affects learning and memory ability

Optimizing the thermoelectric performance of zigzag and chiral carbon nanotubes

Using nonequilibrium molecular dynamics simulations and nonequilibrium Green's function method, we investigate the thermoelectric properties of a series of zigzag and chiral carbon nanotubes which exhibit interesting diameter and chirality dependence. Our calculated results indicate that these carbon nanotubes could have higher ZT values at appropriate carrier concentration and operating temperature. Moreover, their thermoelectric performance can be significantly enhanced via isotope substitution, isoelectronic impurities, and hydrogen adsorption. It is thus reasonable to expect that carbon nanotubes may be promising candidates for high-performance thermoelectric materials

Hybrid-learning-based classification and quantitative inference of driver braking intensity of an electrified vehicle

The recognition of driver's braking intensity is of great importance for advanced control and energy management for electric vehicles. In this paper, the braking intensity is classified into three levels based on novel hybrid unsupervised and supervised learning methods. First, instead of selecting threshold for each braking intensity level manually, an unsupervised Gaussian Mixture Model is used to cluster the braking events automatically with brake pressure. Then, a supervised Random Forest model is trained to classify the correct braking intensity levels with the state signals of vehicle and powertrain. To obtain a more efficient classifier, critical features are analyzed and selected. Moreover, beyond the acquisition of discrete braking intensity level, a novel continuous observation method is proposed based on Artificial Neural Networks to quantitative analyze and recognize the brake intensity using the prior determined features of vehicle states. Experimental data are collected in an electric vehicle under real-world driving scenarios. Finally, the classification and regression results of the proposed methods are evaluated and discussed. The results demonstrate the feasibility and accuracy of the proposed hybrid learning methods for braking intensity classification and quantitative recognition with various deceleration scenarios

Hazard-evaluation-oriented moving horizon parallel steering control for driver-automation collaboration during automated driving

Prompted by emerging developments in connected and automated vehicles, parallel steering control, one aspect of parallel driving, has become highly important for intelligent vehicles for easing the burden and ensuring the safety of human drivers. This paper presents a parallel steering control framework for an intelligent vehicle using moving horizon optimization. The framework considers lateral stability, collision avoidance and actuator saturation and describes them as constraints, which can blend the operation of a human driver and a parallel steering controller effectively. Moreover, the road hazard and the steering operation error are employed to evaluate the operational hazardous of an intelligent vehicle. Under the hazard evaluation, the intelligent vehicle will be mainly operated by the human driver when the vehicle operates in a safe and stable manner. The automated steering driving objective will play an active role and regulate the steering operations of the intelligent vehicle based on the hazard evaluation. To verify the effectiveness of the proposed hazard-evaluation-oriented moving horizon parallel steering control approach, various validations are conducted, and the results are compared with a parallel steering scheme that does not consider automated driving situations. The results illustrate that the proposed parallel steering controller achieves acceptable performance under both conventional conditions and hazardous conditions

Solute Carrier Family 1 (SLC1A1) Contributes to Susceptibility and Psychopathology Symptoms of Schizophrenia in the Han Chinese Population

Objective: Schizophrenia (SZ) is a common and complex psychiatric disorder that has a significant genetic component. The glutamate hypothesis describes one possible pathogenesis of SZ. The solute carrier family 1 gene (SLC1A1) is one of several genes thought to play a critical role in regulating the glutamatergic system and is strongly implicated in the pathophysiology of SZ. In this study, we identify polymorphisms of the SLC1A1 gene that may confer susceptibility to SZ in the Han Chinese population. Methods: We genotyped 36 single-nucleotide polymorphisms (SNPs) using Illumina GoldenGate assays on a BeadStation 500G Genotyping System in 528 paranoid SZ patients and 528 healthy controls. Psychopathology was rated by the Positive and Negative Symptom Scale. Results: Significant associations were found in genotype and allele frequencies for SNPs rs10815017 (p = 0.002, 0.030, respectively) and rs2026828 (p = 0.020, 0.005, respectively) between SZ and healthy controls. There were significant associations in genotype frequency at rs6476875 (p = 0.020) and rs7024664 (p = 0.021) and allele frequency at rs3780412 (p = 0.026) and rs10974573 (p = 0.047) between SZ and healthy controls. Meanwhile, significant differences were found in genotype frequency at rs10815017 (p = 0.015), rs2026828 (p = 0.011), and rs3780411 (p = 0.040) in males, and rs7021569 in females (p = 0.020) between cases and controls when subdivided by gender. Also, significant differences were found in allele frequency at rs2026828 (p = 0.003), and rs7021569 (p = 0.045) in males, and rs10974619 in females (p = 0.044). However, those associations disappeared after Bonferroni\u27s correction (p\u27s \u3e 0.05). Significant associations were found in the frequencies of four haplotypes (AA, CA, AGA, and GG) between SZ and healthy controls (chi (2) = 3.974, 7.433, 4.699, 4.526, p = 0.046, 0.006, 0.030, 0.033, respectively). There were significant associations between rs7032326 genotypes and PANSS total, positive symptoms, negative symptoms, and general psychopathology in SZ (p = 0.002, 0.011, 0.028, 0.008, respectively). Conclusion: The present study provides further evidence that SLC1A1 may be not a susceptibility gene for SZ. However, the genetic variations of SLC1A1 may affect psychopathology symptoms

N-myristoylation of Antimicrobial Peptide CM4 Enhances Its Anticancer Activity by Interacting With Cell Membrane and Targeting Mitochondria in Breast Cancer Cells

Development of antimicrobial peptides (AMPs) as highly effective and selective anticancer agents would represent great progress in cancer treatment. Here we show that myristoyl-CM4, a new synthetic analog generated by N-myristoylation of AMPs CM4, had anticancer activity against MCF-7, MDA-MB-231, MX-1 breast cancer cells (IC50 of 3–6 μM) and MDA-MB-231 xenograft tumors. The improved activity was attributed to the effect of myristoyl on the cell membrane. Flow cytometry and confocal laser scanning microscopy results showed that N-myristoylation significantly increased the membrane affinity toward breast cancer cells and also effectively mediated cellular entry. Despite increasing cytotoxicity against HEK293 and NIH3T3 cells and erythrocytes associated with its anticancer activity, myristoyl-CM4 maintained a certain selectivity toward breast cancer cells. Accordingly, the membrane affinity toward breast cancer cells was two to threefold higher than that of normal cells. Glycosylation analysis showed that sialic acid-containing oligosaccharides (including O-mucin and gangliosides) were important targets for myristoyl-CM4 binding to breast cancer cells. After internalization, co-localization analysis revealed that myristoyl-CM4 targeted mitochondria and induced mitochondrial dysfunction, including alterations in mitochondrial transmembrane potential, reactive oxygen species (ROS) generation and cytochrome c release. Activation of caspase 9, caspase 3 and cleavage of PARP were observed in MX-1, MCF-7, and MDA-MB-231 cells after myristoyl-CM4 treatment. The current work indicates that increasing hydrophobicity by myristoylation to modulate peptide-membrane interactions and then target mitochondria is a good strategy to develop AMPs as anticancer agents in the future

Axial Higgs Mode Detected by Quantum Pathway Interference in RTe3

The observation of the Higgs boson solidified the standard model of particle physics. However, explanations of anomalies (e.g. dark matter) rely on further symmetry breaking calling for an undiscovered axial Higgs mode. In condensed matter the Higgs was seen in magnetic, superconducting and charge density wave(CDW) systems. Uncovering a low energy mode's vector properties is challenging, requiring going beyond typical spectroscopic or scattering techniques. Here, we discover an axial Higgs mode in the CDW system RTe3 using the interference of quantum pathways. In RTe3 (R=La,Gd), the electronic ordering couples bands of equal or different angular momenta. As such, the Raman scattering tensor associated to the Higgs mode contains both symmetric and antisymmetric components, which can be excited via two distinct, but degenerate pathways. This leads to constructive or destructive interference of these pathways, depending on the choice of the incident and Raman scattered light polarization. The qualitative behavior of the Raman spectra is well-captured by an appropriate tight-binding model including an axial Higgs mode. The elucidation of the antisymmetric component provides direct evidence that the Higgs mode contains an axial vector representation (i.e. a pseudo-angular momentum) and hints the CDW in RTe3 is unconventional. Thus we provide a means for measuring collective modes quantum properties without resorting to extreme experimental conditions