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PDF file - 44K, S1. The predicted truncated merlin protein was not detected in Ben-Men-1 cells. S2. IC50 determination of AR-42 in normal meningeal cells. S3. AR-42 treatment increased protein acetylation and decreased p-AKT. S4. Normal meningeal cells proliferate with a doubling time of about three days. S5. Ben-Men-1-LucB and parental Ben-Men-1 cells exhibit similar sensitivities to AR-42. S6. Intracranial NF2-deficient KT21-MG1 xenograft tumors demonstrated features of malignant meningiomas. S7. Ben-Men-1-LucB xenografts strongly expressed vimentin, amesenchymal marker for meningiomas. S8. AR-42 treatment caused tumor regression, whereas AR-12 treatment slowed tumor growth over time. S9. MRI detected a small tumor in a Ben-Men-1-LucB tumorbearing mouse treated with AR-42 for three months. S10. MRI did not detect the residual tumor in an AR-42-treated mouse after removal from AR-42 diet for six months.

Despite the success in the fabrication of various arbitrary-sized one-dimensional architectures, researches still face specific disadvantages of uncontrollable porosity and disordered structures, leading to a deficiency in micro-sized porous for efficient catalytic performance. To improve these limitations, herein, fabricating controllable microstructures based on three-dimensional (3D) printing technology was conducted for catalysis applications. Initially, a multi-channel organized structure printed by silica (SiO2) powder was as the support, onto which different organic functional groups were immobilized. Prior to exploring the catalytic efficiency, different techniques were used to investigate the characterization of 3D-SiO2 systematically. Amongst various immobilized functional groups, the 3D-SiO2 modified with diethylenetriamine showed the best catalytic activity for Knoevenagel condensation reaction. Moreover, the results showed that 3D-SiO2 enhanced catalytic activities of over 90% in only 30 min and could be reused more than ten times with high-performance efficiency while transforming various aldehydes in the presence of malononitrile.

Objective To investigate the effects of simulated microgravity by rotary cell culture system (RCCS) on expression profiles of long non-coding RNA (lncRNA) in mouse fibroblasts L929 cell line. Methods L929 cells were cultured in vitro and randomly divided into simulated microgravity (SMG) group and normal gravity (NG) group. Each group had three samples, the rotator axis of SMG group was paralleled to the ground rotation, while the rotator axis of NG group was vertical to the ground rotation, and the speed of rotation was consistent for the two groups. The samples of two groups were collected on 7th day of culture and the total RNAs were extracted, labeled and hybridized in sequence. The lncRNA and mRNA were detected by Agilent Mouse lncRNA Chips respectively. Differentially expressed lncRNA were identified and then validated by RT-qPCR. GO and Pathway analysis were applied to determine the functional distribution of these target genes. The integration predictions of the lncRNA and mRNA co-expression had been proposed to refine the functional lncRNA-mRNA relationships. Results There were 238 differentially ex-pressed lncRNAs including 134 lncRNAs up-regulated and 104 lncRNAs down-regulated, and 237 differentially expressed mRNAs including 53 mRNAs up-regulated and 184 mRNAs down-regulated significantly in mouse fibroblasts L929 cell line under simulated microgravity by RCCS. The RT-qPCR showed a high concordance with chip microarray results in 4 differentially expressed lncRNA. GO analysis showed that the differentially expressed lncRNAs were related to the biological processes such as negative regulation of megakaryocyte differentiation and negative regulation of wound healing. Pathway analysis showed that these target genes were related to the signal pathways of systemic lupus erythematosus and TGF-β. The lncRNA-mRNA co-expression networks were also established. Conclusion The simulated microgravity by RCCS could significantly affect the expression profiles of lncRNA and mRNA in mouse fibroblasts L929. The lncRNA target genes prediction and functional enrichment analysis based on gene chip technology may provide the theoretical basis for illustrating the mechanism and management of weightlessness stress injury. DOI: 10.11855/j.issn.0577-7402.2017.10.07

Recently, the fabrication of nanotechnology-based co-delivery systems has garnered enormous interest for efficacious cancer therapy. However, these systems still face certain challenges such as codelivery of drugs with different chemistries, inadequate loading efficiency, immune rejection resulting in rapid clearance and substantially poor bioavailability in vivo. To address the challenges, we have developed a biomimetic and stable design based on bovine serum albumin (BSA) nanoparticles that are encapsulated with a hydrophilic photothermal agent, indocyanine green (ICG), as well as a hydrophobic agent, gambogic acid (GA), via the desolvation method. Furthermore, these nanoconstructs have been coated with the red blood cell membranes (RBCm), which exhibit pronounced long-term circulation in addition to avoiding premature leakage of drugs. RBCm-coated BSA nanoparticles show a higher affinity towards both GA and ICG (RmGIB NPs), resulting in high loading efficiencies of 24.3 ± 1.2 % and 25.0 ± 1.2 %, respectively. Moreover, the bio-efficacy investigations of these biomimetic constructs (RmGIB NPs) in cells in vitro as well as in tumor-bearing mice in vivo confirm augmented inhibition, demonstrating potential synergistic chemo-photothermal therapeutic efficacy. Altogether, we provide an efficient delivery platform for designing and constructing BSA nanovehicles toward synergistic and effective co-delivery of therapeutics.

Xiao-Yan-Hua-Jie-San (XYHJS), a traditional Chinese prescription, is used as a medication recipe to clinically treat inflammation and hepatitis. In previous study, we reported the hepatoprotective effects of XYHJS by increasing an antioxidant enzyme activity in mice. In the present study, the main bioactive components of XYHJS and their antioxidant activity were further investigated by using different model systems in vitro. The total phenolics content in the extract of XYHJS was determined by the Folin-Ciocalteu method. Analysis of the major phenolic compounds in the extract of XYHYS was carried out by high-performance liquid chromatography (HPLC) and thin layer chromatographic (TLC) method. The total phenolic content of the extract was 2.84 ± 0.06 mg gallic acid equivalent (GAE)/g extract powder. The phenolic acid in XYHJS was found to be gallic acid (GA). The content of GA was 2.80 mg/ml by HPLC (n=5, RSD=1.26%). Furthermore, the antioxidant activity of XYHJS extract was determined by 1, 1-diphenyl-2-picrylhydrazyl radical (DPPH) scavenging activity and hydroxyl free radicals (·OH) scavenging activity assay. The radical scavenging activity of XYHJS increased significantly in a concentration-dependent manner. At a concentration of 2.5 mg/ml, the DPPH and ·OH scavenging activity was 89.94% and 91.53%, respectively. It can be concluded that the content of GA in XYHJS is very high and it is the main contributor to the antioxidant activity of XYHJS. Our study indicates that XYHJS prescription could be considered to be an effective agent in the prevention of various liver diseases associated with oxidative stress.

To explore the effect of negative emotions on serum levels of adrenocorticotropic hormone (ACTH) and neuropeptide Y (NYP) in hepatitis B liver cirrhosis (HBLC) patients.Totally 617 HBLC patients were assigned to the negative emotion group (415 cases) and the non-negative emotion group (202 cases) judged by negative emotions. Case numbers of various grading Child-Pugh were recorded in the two groups. Their liver functions were compared between the two groups. Serum levels of ACTH and NPY were detected using double antibody sandwich enzyme-linked immunosorbent assay (ELISA) in the two groups.There was no statistical difference in Child-Pugh grading between the two groups (χ2 = 0.65, P = 0.72). Compared with the non-negative emotional group, serum ACTH levels decreased significantly in the negative emotion group with statistical difference (P0.05). There was no statistical difference in serum ACTH levels between the two groups (P0.05).The negative emotion of HBLC patients was not related to the serum ACTH level, but to relatively lower-concentration serum NPY levels.

Nur77, an immediate-early response gene, participates in a wide range of biological functions. Its human homologue, NUR77, is known by several names and has the HGNC-approved gene symbol NR4A1. However, the role of Nur77 in inflammatory bowel disease (IBD) and its underlying mechanisms remain elusive. Here, using public data from the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC) on the most recent genome-wide association studies (GWAS) for ulcerative colitis (UC) and Crohn's disease (CD), we found that genetic variants of the NUR77 gene are associated with increased risk for both UC and CD. Accordingly, Nur77 expression was significantly reduced in colon tissues from patients with UC or CD and mice treated with DSS. Nur77 deficiency increased the susceptibility of mice to DSS-induced experimental colitis and prevented intestinal recovery, whereas treatment with cytosporone B (Csn-B), an agonist for Nur77, significantly attenuated excessive inflammatory response in the DSS-induced colitis mouse model. Mechanistically, NUR77 acts as a negative regulator of TLR-IL-1R signalling by interacting with TRAF6. This interaction prevented auto-ubiquitination and oligomerization of TRAF6 and subsequently inhibited NF-κB activation and pro-inflammatory cytokine production. Taken together, our GWAS-based analysis and in vitro and in vivo studies have demonstrated that Nur77 is an important regulator of TRAF6/TLR-IL-1R-initiated inflammatory signalling, and loss of Nur77 may contribute to the development of IBD, suggesting Nur77 as a potential target for the prevention and treatment of IBD.