Shp2 deletion in hepatocytes suppresses hepatocarcinogenesis driven by oncogenic β-Catenin,PIK3CA and MET

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Effects of Polygonatum sibiricum polysaccharide on the osteogenic differentiation of bone mesenchymal stem cells in mice

Polygonatum sibiricum polysaccharide (PSP) is a traditional Chinese medicine and is widely used to treat many diseases for hundreds of years conventionally. This study was to access the effects of PSP on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in the mice. Cells collected from BALB/C mice in the bone marrow were isolated and cultured with osteogenic medium (OM) with different concentrations of PSP. The proliferation and morphological changes of BMSCs were observed using an inverted microscope. Flow cytometric analysis was used to identify the BMSCs. MTT test was performed to analyze the proliferation and viability of the cells. ELISA was used to determine the expression levels of alkaline phosphatase (ALP), osteocalcin (OC), N-terminal propeptide of type I procollagen (PINP) and bone morphogenetic protein-2 (BMP-2). Immunocytochemistry and western blot were respectively used to determine the expressions of bone sialoprotein (BSP) and SPARC/osteonectin (OSN). The growth curves of the proliferation and differentiation of the Control, OM, 17β-E₂ and PSP groups were increased. Compared to the Control and OM groups, the expression levels of ALP, OC, PINP and BMP-2 were significantly increased in the PSP induced group (P<0.05). Immunocytochemistry and western blot showed that BSP and SPARC were increased after induction of PSP compared to the OM group (P<0.05). The study demonstrates that PSP promotes the proliferation and enhances the viability of BMSCs during osteogenic differentiation. Therefore, PSP may be a potential treatment of osteoporosis in the clinic.     

Role of miR-101 in pheochromocytoma patients with SDHD mutation

This study aimed to screen the potential diagnostic biomarkers for distinguishing the malignant pheochromocytoma (PCC) from benign PCC. A total of 59 patients with PCC (benign and malignant) were enrolled in this study. The expression level of miRNAs in patients with different kind PCCs (healthy control, benign, malignant, malignant with or without SDHD mutation, adrenal and extra-adrenal) was analyzed using the qRT-PCR analysis. Besides, the diagnosis accuracy of miRNA in PCC samples was analyzed using the ROC analysis. Moreover, level of miR-101 in serum was detected by qRT-PCR analysis and serum VEGF level in patients with PCC was detected using the ELISA kit. Compared with benign PCC, miR-101 level was higher in patients with malignant PCC (P < 0.05), while the level of miR-513-5p and miR-26b showed no difference between malignant PCC and benign PCC (P > 0.05). miR-101 expression was significantly increased in malignant tumor tissue with SDHD mutation (P < 0.05) and in extra-adrenal tissues (P < 0.05), respectively. Besides, AUCs for miR-101 in PCC samples was 0.79 and for which in PCC samples with non-SDHD mutation was 0.77. Besides, serum miR-101 in malignant PCC was high but showed no difference among groups (P > 0.05). Moreover, serum VEGF level in malignant tumors was significantly high compared with benign tumor, as well as that in malignant PCC with SDHD mutation (P < 0.05). Our study suggested that SDHD mutation may enhance the overexpression of miR-101 in malignant tumors and miR-101 may be a potential diagnostic biomarker for malignant PCC and benign PCC.     

IncA/C Plasmid Carrying blaNDM-1, blaCMY-16, and fosA3 in a Salmonella enterica Serovar Corvallis Strain Isolated from a Migratory Wild Bird in Germany

A Salmonella enterica serovar Corvallis strain was isolated from a wild bird in Germany. This strain carried the IncA/C₂ pRH-1238 plasmid. Complete sequencing of the plasmid was performed, identifying the bla_NDM-1, bla_CMY-16, fosA3, sul1, sul2, strA, strB, aac(6′)-Ib, aadA5, aphA6, tetA(A), mphA, floR, dfrA7, and merA genes, which confer clinically relevant resistance to most of the antimicrobial classes, including β-lactams with carbapenems, fosfomycin, aminoglycosides, co-trimoxazole, tetracyclines, and macrolides. The strain likely originated from the Asiatic region and was transferred to Germany through the Milvus migrans migratory route.     

地塞米松鞘内注射与静脉注射在显微血管减压术后无菌性脑膜炎中的疗效比较

目的比较腰椎穿刺鞘内注射地塞米松与静脉推注地塞米松治疗显微血管减压术（MVD）术后无菌性脑膜炎（AM）的临床疗效。 方法选择自2015年1月至2020年1月于胜利油田中心医院神经外科就诊行MVD并诊断为AM的138例患者为研究对象,将患者分为对照组（68例）和观察组（70例）。对照组患者采用静脉推注地塞米松（10 mg/次）治疗,频率为按需给药;观察组患者采用腰穿放液联合鞘内注射地塞米松[60 μg/（kg·次）]治疗,频率为每日或隔日1次。比较2组患者治疗后的头痛及发热缓解情况、术后住院时间、治疗次数及激素不良反应情况。 结果治疗后8、72 h后,2组患者头痛、发热症状均明显好转,且观察组明显优于对照组,差异均有统计学意义（P<0.05）;观察组患者的术后住院时间[（7.68±2.23）d]短于对照组[（12.76±2.37）d],治疗次数[（3.5±0.6）次]明显低于对照组[（6.8±0.9）次],差异具有统计学意义（P<0.05）,2组患者均未见明显的激素不良反应。 结论腰穿放液联合鞘内注射地塞米松在治疗MVD术后AM患者中疗效确切,可有效改善患者头痛、发热等临床症状,减轻激素用量,缩短术后住院时间,具有重要的临床推广价值。     

Dynamic Tensile Properties and Energy Dissipation of High-Strength Concrete after Exposure to Elevated Temperatures

In view of the devastating outcomes of fires and explosions, it is imperative to research the dynamic responses of concrete structures at high temperatures. For this purpose, the effects of the strain rate and high temperatures on the dynamic tension behavior and energy characteristics of high-strength concrete were investigated in this paper. Dynamic tests were conducted on high-strength concrete after exposure to the temperatures of 200, 400, and 600 °C by utilizing a 74 mm diameter split Hopkinson pressure bar (SHPB) apparatus. We found that the quasi-static and dynamic tensile strength of high-strength concrete gradually decreased and that the damage degree rose sharply with the rise of temperature. The dynamic tensile strength and specific energy absorption of high-strength concrete had a significant strain rate effect. The crack propagation law gradually changed from directly passing through the coarse aggregate to extending along the bonding surface between the coarse aggregate and the mortar matrix with the elevation of temperature. When designing the material ratio, materials with high-temperature resistance and high tensile strength should be added to strengthen the bond between the mortar and the aggregate and to change the failure mode of the structure to resist the softening effect of temperature.     

MFC/NFC-Based Foam/Aerogel for Production of Porous Materials: Preparation,Properties and Applications

Nanofibrillated cellulose and microfibrillated cellulose are potential raw materials separated from plant fibers with a high aspect ratio and excellent mechanical properties, which can be applied in various fields (packaging, medicine, etc.). They have unique advantages in the preparation of aerogels and foams, and have attracted widespread attention in recent years. Cellulose-based porous materials have good biodegradability and biocompatibility, while high porosity and high specific surface area endow them with strong mechanical properties and liquid retention performance, which can be used in wall construction, sewage treatment and other fields. At present, the preparation method of this material has been widely reported, however, due to various process problems, the actual production has not been realized. In this paper, we summarize the existing technical problems and main solutions; in the meantime, two stable systems and several drying processes are described, and the application potential of cellulose-based porous materials in the future is described, which provides a reference for subsequent research.     

TolC-Dependent Modulation of Host Cell Death by the Francisella tularensis Live Vaccine Strain

Francisella tularensis is a facultative intracellular, Gram-negative pathogen and the causative agent of tularemia. We previously identified TolC as a virulence factor of the F. tularensis live vaccine strain (LVS) and demonstrated that a ΔtolC mutant exhibits increased cytotoxicity toward host cells and elicits increased proinflammatory responses compared to those of the wild-type (WT) strain. TolC is the outer membrane channel component used by the type I secretion pathway to export toxins and other bacterial virulence factors. Here, we show that the LVS delays activation of the intrinsic apoptotic pathway in a TolC-dependent manner, both during infection of primary macrophages and during organ colonization in mice. The TolC-dependent delay in host cell death is required for F. tularensis to preserve its intracellular replicative niche. We demonstrate that TolC-mediated inhibition of apoptosis is an active process and not due to defects in the structural integrity of the ΔtolC mutant. These findings support a model wherein the immunomodulatory capacity of F. tularensis relies, at least in part, on TolC-secreted effectors. Finally, mice vaccinated with the ΔtolC LVS are protected from lethal challenge and clear challenge doses faster than WT-vaccinated mice, demonstrating that the altered host responses to primary infection with the ΔtolC mutant led to altered adaptive immune responses. Taken together, our data demonstrate that TolC is required for temporal modulation of host cell death during infection by F. tularensis and highlight how shifts in the magnitude and timing of host innate immune responses may lead to dramatic changes in the outcome of infection.     

The toxic effects of alizarin red S on catalase at the molecular level

Alizarin red S (ARS) is a widespread mordant dye derived from alizarin. However, it was reported to be mutagenic and carcinogenic probably because it could induce oxidative damages in organisms. Catalase (CAT) is an important antioxidant enzyme defensing oxidative damages induced by xenobiotics. The underlying mechanisms of ARS interacting with CAT have not been clarified yet. This study is conducted to characterize the functional and conformational changes on CAT by ARS and the binding details to further investigate their interaction mechanisms. Under exposure of ARS at 5 μM, CAT activity was significantly decreased to 76.2%. Inhibition of CAT probably resulted in promotion of intracellular oxidative stress and pro-oxidant property of ARS. The interaction between ARS and CAT was proved to be spontaneous and exothermic. However, limited structural changes were observed according to spectroscopic results. Results showed that ARS prefers to bind with residues buried in the active site and could alter the activity of CAT, which were agree with the molecular docking results. This work proves the adverse effects of ARS on CAT mainly at molecular level and further highlights its potential risks to heath.

Alizarin red S is confirmed to be toxic to catalase at molecular level attributing to the structural and functional changes of catalase.