Dynamic behavior of a vehicle with rear axle compliance steering

Rear axle compliance steering (RACS) is a technology of passive four-wheel steering, which is designed to improve the vehicle handling and stability at medium or high speed. This paper focuses on the dynamic behavior of the vehicle with RACS. Firstly, the compliance steering principle for different rear suspensions is illustrated. Then, the viscoelastic members with fractional order derivative properties are introduced into RACS, and the fractional order model of RACS is formulated. Next, the dynamic model of the vehicle with RACS is established, the adjusting rules for the compliance steering stiffness are derived, and the vehicle stability is investigated. Finally, numerical experiments are performed to illustrate the effects on the vehicle dynamic behavior caused by the compliance steering stiffness, the viscoelastic members and the vehicle longitudinal velocity. Research results show that, the vehicle with RACS has better dynamic characteristics than that without RACS at medium or high speed; and the compliance steering stiffness, the viscoelastic members and the vehicle longitudinal velocity have different impacts on the vehicle lateral dynamic behavior

Two variants on T2DM susceptible gene HHEX are associated with CRC risk in a Chinese population

Increasing amounts of evidence has demonstrated that T2DM (Type 2 Diabetes Mellitus) patients have increased susceptibility to CRC (colorectal cancer). As HHEX is a recognized susceptibility gene in T2DM, this work was focused on two SNPs in HHEX, rs1111875 and rs7923837, to study their association with CRC. T2DM patients without CRC (T2DM-only, n=300), T2DM with CRC (T2DM/CRC, n=135), cancer-free controls (Control, n=570), and CRC without T2DM (CRC-only, n=642) cases were enrolled. DNA samples were extracted from the peripheral blood leukocytes of the patients and sequenced by direct sequencing. The χ(2) test was used to compare categorical data. We found that in T2DM patients, rs1111875 but not the rs7923837 in HHEX gene was associated with the occurrence of CRC (p= 0.006). for rs1111875, TC/CC patients had an increased risk of CRC (p=0.019, OR=1.592, 95%CI=1.046-2.423). Moreover, our results also indicated that the two variants of HEEX gene could be risk factors for CRC in general population, independent on T2DM (p< 0.001 for rs1111875, p=0.001 for rs7923837). For rs1111875, increased risk of CRC was observed in TC or TC/CC than CC individuals (p<0.001, OR= 1.780, 95%CI= 1.385-2.287; p<0.001, OR= 1.695, 95%CI= 1.335-2.152). For rs7923837, increased CRC risk was observed in AG, GG, and AG/GG than AA individuals (p< 0.001, OR= 1.520, 95%CI= 1.200-1.924; p=0.036, OR= 1.739, 95%CI= 0.989-3.058; p< 0.001, OR= 1.540, 95%CI= 1.225-1.936). This finding highlights the potentially functional alteration with HHEX rs1111875 and rs7923837 polymorphisms may increase CRC susceptibility. Risk effects and the functional impact of these polymorphisms need further validation

Pholidota chinensis alleviates azoxymethane/dextran sulfate sodium-induced colorectal carcinogenesis through inhibition of TLR4 and COX-2

Background: Inflammatory bowel disease (IBD) always progresses to colorectal cancer (CRC) which is the second most frequent cause of death by cancer. It is about 2% of population in the lifetime worldwide who at the risk for development of CRC. Oxaliplatin is an effective anticancer drug used for the treatment of advanced CRC; however, it always causes a robust painful neuropathy. Pholidota chinensis is a Chinese folk herbal medicine which was used for treatment of inflammation such as gastroenteritis, duodenal ulcer and bronchitis.Materials and Methods: The azoxymethane (AOM) and dextran sulfate sodium (DSS) were used to induce the colon tumor of mice. The effect of Pholidota chinensis on colon tumorigenesis was evaluated. Immunohistochemistry and semi-quantitative RT-PCR were used to detect the expression of toll-like receptor 4 (TLR4) and cyclooxygenase-2 (COX-2) in colon.Results: Pholidota chinensis can alleviate the colon tumorigenesis. The prevention effects of Pholidota chinensis are similar to oxaliplatin. Specifically, administration of Pholidota chinensis solution suppresses the expression of the proliferating cell nuclear antigen (PCNA), toll-like receptor 4 (TLR4) and cyclooxygenase-2 (COX-2).Conclusion: Our findings suggested that Pholidota chinensis participate in the regulation of colon cancer development through inhibiting the expression of TLR4 and COX-2.Keywords: Pholidota chinensis; colorectal cancer; Toll-like receptor 4; Cyclooxygenase-

Network pharmacology-based elucidation of the molecular mechanism underlying the anti-migraine effect of Asari Radix et Rhizoma

Purpose: To determine the molecular mechanism involved in the anti-migraine effect of Asari Radix et Rhizoma (ARR) using network pharmacology. Methods: The compounds present in ARR were identified through information retrieval from literature and public databases, and were screened based on absorption, distribution, metabolism, excretion and toxicity. Target genes related to the selected compounds and migraine were identified or predicted from public databases. Hub genes in ARR against migraine were identified through analysis of interactions in overlapping genes between compounds and migraine target genes, based on STRING database. Gene enrichment analysis of overlapping genes was performed using Database for Annotation, Visualization and Integrated Discovery. Results: A total of 138 compounds were selected as potential bioactive compounds in ARR. Target genes related to the selected compounds (611 genes) and migraine (278 genes) were obtained, including 71 overlapping genes. The hub genes in the anti-migraine effect of ARR were BDNF, IL6, COMT, APP and TNF. Gene enrichment analysis showed the top 10 biological processes or pathways involved in the mechanism of anti-migraine action of ARR. The tissue source of the overlapping genes was not limited to the brain. The results from gene enrichment analysis revealed that the effect of ARR on migraine was holistic, which is characteristic of traditional Chinese medicines. Conclusion: Network pharmacology has been used to decipher the molecular mechanism involved in the action of ARR against migraine. The results provide a scientific basis for the clinical effect of ARR on migraine

Studies on the protective effect of total flavonoids from Cichorium glandulosum roots against carbon tetrachloride-induced liver fibrosis in rats

Purpose: To study the protective influence of total flavonoids from Cichorium glandulosum roots (TFCG) against carbon tetrachloride-mediated hepatic fibrosis in rats, and the probable mechanism of action involved.Methods: Rats with liver fibrosis were orally administered TFCG (50, 100 or 200 mg/kg) once a day for 13 weeks. Liver index and liver injury indices in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), lactate dehydrogenase (LDH), γ-glutamyl transpeptidase (γ-GT), hydroxyproline (HYP), albumin (ALB) and malondialdehyde (MDA) were determined using electronic balance or corresponding assay kits, as appropriate. Following staining with hematoxylin and eosin and Van Gieson, histopathological changes in liver tissues were examined by light microscopy. TGF-β/Smad pathway-related protein expressions in liver tissues, viz, transforming growth factor-β1 (TGF-β1), mothers against decapentaplegic homolog 3 (Smad3), Smad7, toll-like receptor 4 (TLR4) and α-smooth muscle actin (α-SMA) were determined using immunohistochemical techniques.Results: Exposure to TFCG significantly reversed abnormal serum levels of ALT, AST, AKP, LDH, γ- GT, HYP, ALB and MDA rats with liver fibrosis to normal levels, and also decreased their liver index values (p &lt; 0.01). Moreover, TFCG improved histopathological changes in the liver tissues of fibrotic rats, and significantly reversed abnormal TGF-β1, Smad3, Smad7, TLR4 and α-SMA protein expressions in the liver tissues of fibrotic rats to normal levels (p &lt; 0.05 or 0.01).Conclusion: These results indicate that TFCG exerts protective effect against liver fibrosis via a mechanism related to inactivation of TGF-β/Smad pathway. Thus, TFCG may find application in liver fibrosis therapy.Keywords: Cichorium glandulosum, Flavonoids, Liver, Fibrosis, TGF-β/Smad pathwa

Tunable Fano Resonances Based on Two-beam Interference in Microring Resonator

In this paper, a resonant system is demonstrated on silicon-on-insulator wafer to achieve tunable Fano resonances. In this system, the Fano resonance originates from the interference of two beams resonant in the microring resonator. The shapes of the Fano resonances are tunable through controlling the phase difference of the two beams. Both large slope and high extinctionratio (ER) are obtained when the phase difference is 0.5π or 1.5π. Experimental results show that Fano resonances with steep slope and ER over 20 dB are achieved in the whole free spectral range by controlling the microheaters to meet the phase condition

Characteristic analysis of α-fetoprotein-producing gastric carcinoma in China

α-Fetoprotein-producing gastric cancer (AFPGC) is a rare type of gastric cancer. The largest population of patients with AFPGC is found in China. In the present study, a total of 4,779 GC patients, including 317 AFPGC patients, from 11 clinical studies in China with a general AFPGC/GC ratio of 6.63% were summarized and analyzed. On the basis of analysis of the clinical data, the patients with AFPGC had larger tumor size, weaker cell differentiation, worse histopathological types, deeper serosal infiltration, more lymph node and liver metastases, poorer stages, shorter survival time and more positive expression of vascular endothelial growth factors than the patients without AFPGC. Our observation is consistent with previous results reported in studies of AFPGC. Overall, AFPGC is a subtype of GC with a poor prognosis

Sound insulation performance optimization of lightweight sandwich panels

Optimization of lightweight sandwich panels has been intensively studied, but optimization in terms of the acoustic objective is still a hot topic, and the influence on optimization results caused by sandwich panel geometric constraints is also rarely investigated. In this study, the optimization on lightweight sandwich panel designs is investigated by maximizing the sound insulation performance and minimizing the panel mass simultaneously. Firstly, the acoustic model of sandwich panels is discussed, which provides basic formulas to model the acoustic objective function. Secondly, the optimization problem is formulated as a bi-objective programming model, and a solution algorithm based on the non-dominated sorting genetic algorithm II (NSGA-II) is provided. Finally, the numerical experiments are carried out to verify the effectiveness of the proposed model and solution algorithm. Numerical results demonstrate the tradeoff between two objectives, the panel transmission loss corresponding to the three typical points in the Pareto front, and how the geometric constraints impact the optimization results for lightweight sandwich panels

The significance of Notch ligand expression in the peripheral blood of children with hand, foot and mouth disease (HFMD)

BACKGROUND: Hand, foot and mouth disease (HFMD), a virus-induced infectious disease that usually affects infants and children, has an increased incidence in China in recent years. This study attempted to investigate the role of the Notch signaling pathway in the pathogenesis of HFMD. METHODS: Eighty-two children diagnosed with HFMD were enrolled into this study. The HFMD group was further divided into the uncomplicated HFMD and HFMD with encephalitis groups. The control group included 40 children who underwent elective surgery for treatment of inguinal hernias. RESULTS: Children with HFMD displayed significantly reduced CD3+, CD3+CD4+ and CD3+CD8+ cell subsets, but substantially enhanced CD3−CD19+ cell subset (p < 0.05 versus control subjects). The expression levels of Notch ligands Dll1 and Dll4 in the peripheral blood of the HFMD group were significantly higher than those in the control group (p < 0.05). There were statistically significant differences in CD3+, CD3+CD4+ and CD3−CD19+ cell subsets, but not in Notch ligand expression, between the uncomplicated HFMD and HFMD with encephalitis groups. Dll4 expression in HFMD subjects correlated negatively with the CD3+ and CD3+CD8+ cell subsets (p < 0.05), but positively with the CD3−CD19+ cell subset (p < 0.05). Furthermore, Dll4 expression in HFMD with encephalitis subjects correlated positively with total white blood cell (WBC) counts and total protein contents in cerebrospinal fluid (CSF) (p < 0.05). CONCLUSIONS: The Notch ligand Dll4 exhibits a strong correlation with the CD3+, CD3+CD8+ and CD3−CD19+ cell subsets in children with HFMD, indicating that the Notch signaling may be involved in the development of HFMD by affecting the number and status of peripheral lymphocytes

MiR-143 acts as a tumor suppressor by targeting N-RAS and enhances temozolomide-induced apoptosis in glioma.

Therapeutic applications of microRNAs (miRNAs) in RAS-driven glioma were valuable, but their specific roles and functions have yet to be fully elucidated. Here, we firstly report that miR-143 directly targets the neuroblastoma RAS viral oncogene homolog (N-RAS) and functions as a tumor-suppressor in glioma. Overexpression of miR-143 decreased the expression of N-RAS, inhibited PI3K/AKT, MAPK/ERK signaling, and attenuated the accumulation of p65 in nucleus of glioma cells. In human clinical specimens, miR-143 was downregulated where an adverse with N-RAS expression was observed. Furthermore, overexpression of miR-143 decreased glioma cell migration, invasion, tube formation and slowed tumor growth and angiogenesis in a manner associated with N-RAS downregulation in vitro and in vivo. Finally, miR-143 also sensitizes glioma cells to temozolomide (TMZ),the first-line drug for glioma treatment. Taken together, for the first time, our results demonstrate that miR-143 plays a significant role in inactivating the RAS signaling pathway through the inhibition of N-RAS, which may provide a novel therapeutic strategy for treatment of glioma and other RAS-driven cancers