Template-free, controllable and scalable synthesis of poly(5-aminoindole) nanoparticles for printable electrochemical immunosensor with ultra-high sensitivity.

Conductive polymer polyindole derivatives have good conductivities and abundant functional groups, which would offer great potential for versatile applications including biosensors, bioelectronics and energy devices. However, the polyindole derivatives are mainly synthesized by the electropolymerization method on conductive electrode surfaces, which limits large-scale synthesis and practical applications. Herein, we explore a strategy of template-free, controllable and scalable synthesis of poly-5-aminoindole (PIn-5-NH2) nanoparticles (NPs) and demonstrate the application of PIn-5-NH2 NPs in printable multiplexed electrochemical biosensors with ultra-high sensitivity. The synthesis of PIn-5-NH2 NPs is based on a self-templated method since the In-5-NH2 monomer with amphiphilic structures can form micelles by self-assembly in an aqueous solution. The diameter of PIn-5-NH2 NPs could be controlled by adjusting the synthesis conditions, such as monomer concentration, oxidant/monomer ratio and reaction time. The PIn-5-NH2 NPs possess distinct features, including good conductivity, large surface area, and abundant -NH2 functional groups for covalent binding of the antibody, and therefore offer substantial possibilities for developing an all-printable process to fabricate multiplexed electrochemical immunosensors. The printed multiplexed electrochemical immunosensors on the basis of the aqueous suspension of PIn-5-NH2 NPs linked with antibodies can simultaneously detect multiple cancer markers, and exhibit high sensitivity and good selectivity. Our facile and scalable synthesis strategy would offer great opportunities for versatile applications of PIn-5-NH2 NPs.

Highly Conductive PPy-PEDOT:PSS Hybrid Hydrogel with Superior Biocompatibility for Bioelectronics Application.

Conductive polymer hydrogels (CPHs) hold significant promise in broad applications, such as bioelectronics and energy devices. Hitherto, the development of a facile and scalable synthesis method for CPHs with high electrical conductivity and biocompatibility has still been a challenge. Herein, we demonstrate highly conductive PPy-PEDOT:PSS hybrid hydrogels which are prepared by a simple solution-mixing method. This fabrication method involves the mixing of a pyrrole monomer with a PEDOT:PSS dispersion, followed by in situ chemical oxidative polymerization to form polypyrrole (PPy). The electrostatic interaction between negatively charged PSS and positively charged conjugated PPy facilitates the formation of PPy-PEDOT:PSS hybrid hydrogels. The conductivity of the PPy-PEDOT:PSS hybrid hydrogels is 867 S m-1. The PPy-PEDOT:PSS hybrid hydrogels show excellent biocompatibility. Moreover, the PPy-PEDOT:PSS hybrid hydrogels have a hierarchical porous structure which facilitates the 3D cell culture within the hydrogels. The PPy-PEDOT:PSS hybrid hydrogels exhibit excellent in situ biomolecular detection and real-time cell proliferation monitoring performance, indicating their potential as highly sensitive electrochemical biosensors for bioelectronics applications. Our strategy for the fabrication of CPHs with the electrostatic interaction between the negatively charged conductive polymer and positively charged conductive polymer would provide new opportunities for the design of highly conductive conjugated hydrogels for bioelectronics applications and energy devices.

LncRNA ANCR Suppresses the Progression of Hepatocellular Carcinoma Through the Inhibition of Wnt/ß-Catenin Signaling Pathway.

OBJECTIVE: Our study aimed to investigate the effect of anti-differentiation noncoding RNA (ANCR) on hepatocellular carcinoma (HCC) and its potential molecular mechanisms. METHODS: The expression of ANCR was detected by qRT-RCR in both HCC tissues and HCC cells. Moreover, the relationship between ANCR expression and clinical parameters in HCC patients was investigated. The proliferation, cell clones, migration, invasion and apoptosis of MHCC97H and HCCLM3 cells were measured by MTT assay, colony formation assay, transwell assay and flow cytometry, respectively. The expressions of N-cadherin, vimentin, E-cadherin, cleaved caspase-3, Bax, Bcl-2, Wnt1, ß-catenin and GSK-3ß in MHCC97H and HCCLM3 cells were measured by Western blot. RESULTS: Our results showed that ANCR was lowly expressed in both HCC tissues and HCC cells. ANCR expression was closely associated with tumor size, tumor-node-metastasis (TNM) stages and vascular invasion in HCC. ANCR could dramatically inhibit cell proliferation, migration and invasion, as well as promote apoptosis in MHCC97H and HCCLM3 cells. ANCR could significantly increase the expression of cleaved caspase-3, Bax, E-cadherin and GSK-3ß but reduce the expression of Bcl-2, N-cadherin, vimentin, Wnt1 and ß-catenin in MHCC97H and HCCLM3 cells. In addition, Wnt/ß-catenin pathway inhibitor (IWP-2) partially reversed the effects of silencing ANCR on the proliferation, migration, invasion and apoptosis of HCCLM3 cells. CONCLUSION: Our study demonstrated that ANCR can suppress cell proliferation, migration and invasion, as well as promote apoptosis of HCC cells via modulation of the Wnt/ß-catenin signaling pathway.

LncRNA RHPN1-AS1 Promotes Cell Proliferation, Migration and Invasion Through Targeting miR-7-5p and Activating PI3K/AKT/mTOR Pathway in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a severe disease with high mortality in the world. Emerging evidence has suggested that lncRNAs play an important role in cancer progression, including HCC. This study aimed to comprehensively investigate the effect of lncRNA RHPN1 antisense RNA 1 (RHPN1-AS1) on HCC and its underlying molecular mechanism. In this study, we evaluated the expressions of lncRNA RHPN1-AS1 and miR-7-5p by qRT-RCR in both HCC tissue and HCC cells. Our findings showed that lncRNA RHPN1-AS1 was upregulated in HCC tissue and HCC cells, while miR-7-5p was downregulated. LncRNA RHPN1-AS1 expression in HCC patients was closely related to vascular invasion, tumor-node-metastasis (TNM) stage and barcelona clinic liver cancer (BCLC) stage. Furthermore, we quantified cell clone-formation ability, proliferation, migration and invasion of HCCLM3 and MHCC97 H cells using several assays (colony formation assay, 5-Ethynyl-2'-deoxyuridine (EdU) assay and transwell assay, respectively). Functional experiments confirmed that silencing lncRNA RHPN1-AS1 inhibited cell proliferation, migration and invasion in HCCLM3 and MHCC97 H cells. After that, bioinformatics analysis, dual luciferase reporter gene assay, qRT-PCR and western blot were used to investigate the molecular mechanism of lncRNA RHPN1-AS1 on HCC. Mechanistically, the rescue experiments demonstrated that miR-7-5p inhibitor reversed the inhibition effect of silencing lncRNA RHPN1-AS1 on HCCLM3 cells proliferation, migration and invasion. Moreover, silencing lncRNA RHPN1-AS1 also inhibited the activation of PI3K/AKT/mTOR pathway. Taken together our findings demonstrated that lncRNA RHPN1-AS1 could facilitate cell proliferation, migration and invasion via targeting miR-7-5p and activating PI3K/AKT/mTOR pathway in HCC.

Multifunctional hierarchical mesoporous silica and black phosphorus nanohybrids as chemo-photothermal synergistic agents for enhanced cancer therapy.

Synergistic therapy with high efficacy and low side effects is of great significance in cancer treatment, and therefore the elaborate design of advanced nanocarriers to benefit diverse loading requirements of size-varied therapy agents is of critical importance. Herein, we demonstrate a multifunctional drug carrier platform based on a hierarchical porous and -NH2-modified silica nanocarrier (FMSN) with a super high specific surface area and a large pore volume, which not only improves the loading capacity of both doxorubicin, a chemotherapeutic drug, and black phosphorus quantum dots (BPQDs), a kind of biocompatible photothermal agent, but also enhances the photothermal stability and biostability of the degradable BPQDs. The unique structure and surface design enable our multimodal platform with heat-stimulative, pH-responsive and sustained-release properties for chemo-photothermal synergistic cancer therapy. Both cytotoxicity experiments and in vivo study reveal that the combined therapy based on our multifunctional nanohybrids mediates the highest death rate of cancer cells compared to that of single chemotherapy or photothermal therapy. Our hierarchical mesoporous strategy provides an excellent drug delivery model for advanced chemo-photothermal synergistic targeted cancer therapy.

Johne's disease in cattle is associated with enhanced expression of genes encoding IL-5, GATA-3, tissue inhibitors of matrix metalloproteinases 1 and 2, and factors promoting apoptosis in peripheral blood mononuclear cells.

Infection of ruminants with Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) leads to a chronic and often fatal granulomatous enteritis known as Johne's disease. Most infections with M. paratuberculosis occur during the first 6 months of life, and there is some evidence for transmission in utero. Once established, infections typically exist in a subclinical state for several years. Recent gene-expression profiling studies suggested the hypothesis that inherent gene-expression profiles in peripheral blood mononuclear cells (PBMCs) from M. paratuberculosis-infected cattle may be different than expression profiles in PBMCs from uninfected controls. If true, this would suggest that it is possible to identify an M. paratuberculosis infection "signature" through transcriptional profiling of peripheral immune cells. In addition, identification of groups or classes of genes showing inherently different expression in PBMCs from M. paratuberculosis-infected cattle relative to PBMCs from uninfected controls might highlight important interactions between this pathogen and the host immune system. In this report, we describe studies aimed at testing this hypothesis. Our novel results indicate that, indeed expression profiles of at least 42 genes are inherently different in freshly isolated PBMCs from M. paratuberculosis-infected cattle when compared to similar cells from uninfected controls. Gene-expression differences observed following microarray analysis were verified and expanded upon by quantitative real-time PCR (Q-RT-PCR). Our results indicate that T cells within PBMCs from M. paratuberculosis-infected cows have adopted a predominant Th 2-like phenotype (enhanced expression of IL-5, GATA 3, and possibly IL-4 mRNA), that cells within infected cow PBMCs may exhibit tissue remodeling deficiencies through higher expression of tissue inhibitor of matrix metalloproteinase (TIMP) 1 and TIMP2 RNA and lower expression of matrix metalloproteinase (MMP) 14 RNA than similar cells from healthy controls, and that cells within the PBMC population of M. paratuberculosis-infected cows are likely poised for rapid apoptosis (upregulation of CIDE-A, Bad, TNFRI, and Fas).