Coxsackievirus A16 (CA16) is a member of the Picornaviridae family and causes mild and self-limiting hand, foot, and mouth disease (HFMD) in infants and young children. CA16 infection can also progress to central nervous system (CNS) complications; however, the underlying mechanism by which CA16 penetrates the blood-brain barrier (BBB) and then causes CNS damage remains unclear. This study aimed to explore the mechanism of CA16 neurotropic tropism by establishing an in vitro BBB model with CA16 infection and an in vivo CA16 rhesus monkey infant infection model. The results showed that CA16 infection induced increased permeability of the BBB accompanied by upregulation of matrix metalloproteinase 9 (MMP9) expression. Subsequently, high-throughput miRNA sequencing technology and bioinformatics analysis revealed that miR-1303 may regulate BBB permeability by targeting MMP9. Next, we used dual-luciferase, qRT-PCR, and western blot assays to provide evidence of MMP9 targeting by miR-1303. Further experiments revealed that CA16 infection promoted the degradation of junctional complexes (Claudin4, Claudin5, VE-Cadherin, and ZO-1), likely by downregulating miR-1303 and upregulating MMP9. Finally, EGFP-CA16 infection could enter the CNS by facilitating the degradation of junctional complexes, eventually causing neuroinflammation and injury to the CNS, which was confirmed using the in vivo rhesus monkey model. Our results indicate that CA16 might penetrate the BBB and then enter the CNS by downregulating miR-1303, which disrupts junctional complexes by directly regulating MMP9 and ultimately causing pathological CNS changes. These results provide new therapeutic targets in HFMD patients following CA16 infection.

Ventilator-associated pneumonia (VAP) infection caused by carbapenem-resistant Enterobacteriaceae (CRE) is becoming more prevalent, thus seriously affecting patient outcomes. In this paper, we studied the drug resistance mechanism and epidemiological characteristics of CRE, and analyzed the infection and prognosis factors of VAP caused by CRE, to provide evidence for effective control of nosocomial infection in patients with VAP. A total of 58 non-repetitive CRE strains of VAP were collected from January 2016 to June 2018. To explore the risk factors of CRE infection, 1:2 group case control method was used to select non CRE infection patients at the same period as the control group. Among the 58 CRE strains, the most common isolates included Klebsiella pneumoniae and Escherichia coli . All strains were sensitive to polymyxin B, which features better sensitivity to other antibiotics such as minocycline, trimethoprim/sulfamethoxazole, and amikacin. Multiple drug resistance genes were detected at the same time in most strains. KPC-2 was the most common carbapenemase-resistant gene in Klebsiella pneumoniae , whereas NDM-1 was more common in Escherichia coli . The risk factors correlated with CRE infection included intensive care unit (ICU) occupancy time >7 days (OR = 2.793; 95% CI 1.439~5.421), antibiotic exposure during hospital stay including those to enzyme inhibitors (OR = 1.977; 95% CI 1.025~3.812), carbapenems (OR = 3.268; 95% CI 1.671~6.392), antibiotic combination therapy(OR = 1.951; 95% CI 1.020~3.732), and nerve damage (OR = 3.013; 95% CI 1.278~7.101). Multivariable analysis showed that ICU stay >7 days (OR = 1.867; 95% CI 1.609~20.026), beta-lactamase inhibitor antibiotics (OR = 7.750; 95% CI 2.219~27.071), and carbapenem (OR = 9.143; 95% CI 2.259~37.01) are independent risk factors for VAP carbapenem caused by Carbapenem-resistant Enterobacteriaceae. A high resistance rate of CRE isolated from VAP indicated that the infected patients featured higher mortality and longer hospital stay time than the control group. Multiple risk factors for CRE infection and their control can effectively prevent the spread of VAP.

To build an ideal animal model for studying the mechanism of occurrence, developing and treating of diabetes become a more important issue, facing with the fact that the big threat of diabetes to human health has been worsen. First, we used the normal control diets or the high-fat/high-sucrose diets to feed the adult rhesus monkeys and the macaques induced by the high-fat/high-sucrose diets in the high-fat/high-sucrose group and the type 2 diabetes mellitus (T2DM) group developed the hyperglycemia, hyperinsulinemia at 6 months in accordance with the precious researches that reported that minipigs, rats and mice could develop hyperglycemia, hyperinsulinemia, hyperlipidemia and obesity after being induced with high-fat/high-carbohydrate diets. Second, the rhesus monkeys in T2DM group were injected STZ at a low dosage of 35 mg/kg BW to induce glucose persistent elevation which maintained pretty well after 12 months. Third, we took the assay of glucose tolerance test and insulin resistance index, assessed the changing tendency of serum resistin and analysed the pathological characteristics of the tissues like pancreas and liver by staining in different ways. The results indicate the rhesus monkeys in T2DM group have lots of clinical features of T2DM. The experimental non-genetic T2DM rhesus monkeys model not only contribute to simulating of clinical manifestations and pathological features of human T2DM, but also may be a good kind of model for research on the treatment of T2DM and for new drugs evaluation.

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Tumor cells may develop multidrug resistance (MDR) to various chemotherapy regimens. Such resistance reduces the sensitivity of cells to chemotherapy drugs, leading to the failure of cervical cancer (CC) treatment and disease progression. The present study aimed to investigate the role of MDR1, lung resistance protein (LRP) and placental glutathione S‑transferase π 1 (GSTP1) in CC and MDR, and the prognostic value of these genes. The mRNA expression levels of these resistance‑associated genes were determined in 47 CC and 20 healthy cervical tissue samples. Subsequently, the data was analyzed alongside clinicopathological parameters. The mRNA expression levels of MDR1, LRP and GSTP1 in CC were 0.57±0.32, 0.58±0.29 and 0.44±0.24, respectively, whereas those in healthy cervical tissues were 0.19±0.10, 0.17±0.14 and 0.18±0.10, respectively. Therefore, the expression levels of these genes were significantly greater in CC compared with healthy cervical tissue (P<0.05). mRNA expression levels of MRD1 were increased in the well differentiated group (0.68±0.27) compared with the poorly differentiated group (0.38±0.33; P<0.05). No significant differences were observed between LRP and GSTP1 mRNA expression levels and tumor differentiation or clinical stage of the patients (P>0.05). Multivariate logistic regression indicated that the degree of differentiation and the MDR1 gene expression levels were predictors of CC prognosis (P<0.05). The survival rate of patients in the MDR1‑negative group was significantly greater compared with the MDR1‑positive group (P<0.05). The results of the present study therefore suggested that MDR1 gene expression is a predictor of poor survival in CC.

Nano drug delivery system is a research hotspot in the field of tumor therapy. Molybdenum disulfide (MoS2) nanosheet was selected as the base material and natural red blood cell membrane...

Biased magnetic flux produced by a permanent magnet can reduce the power consumption of the suspension system in bearingless motors or magnetic bearings. However, the ability to generate suspension biased magnetic flux with a single permanent magnet tends to be saturated with the increase of the magnetising width. In order to solve the above problem, an axially superposed permanent magnet biased bearingless motor, which consists of a 12/8 reluctance motor for producing torque and two permanent magnets for producing desired biased magnetic flux density is present. The structure and working principle are introduced, and the electromagnetic characteristics are analysed by finite element analysis. The results verify that the proposed bearingless motor has the excellent merits of weak coupling between the torque system and suspension force and satisfactory suspension performance. Furthermore, much more biased permanent magnets could also be used for the suspension system of ultra-high speed, high power and slender bearingless motors such as flywheel energy storage systems.

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