Microenvironment Restruction of Emerging 2D Materials and their Roles in Therapeutic and Diagnostic Nano-Bio-Platforms

Engineering advanced therapeutic and diagnostic nano-bio-platforms (NBPFs) have emerged as rapidly-developed pathways against a wide range of challenges in antitumor, antipathogen, tissue regeneration, bioimaging, and biosensing applications. Emerged 2D materials have attracted extensive scientific interest as fundamental building blocks or nanostructures among material scientists, chemists, biologists, and doctors due to their advantageous physicochemical and biological properties. This timely review provides a comprehensive summary of creating advanced NBPFs via emerging 2D materials (2D-NBPFs) with unique insights into the corresponding molecularly restructured microenvironments and biofunctionalities. First, it is focused on an up-to-date overview of the synthetic strategies for designing 2D-NBPFs with a cross-comparison of their advantages and disadvantages. After that, the recent key achievements are summarized in tuning the biofunctionalities of 2D-NBPFs via molecularly programmed microenvironments, including physiological stability, biocompatibility, bio-adhesiveness, specific binding to pathogens, broad-spectrum pathogen inhibitors, stimuli-responsive systems, and enzyme-mimetics. Moreover, the representative therapeutic and diagnostic applications of 2D-NBPFs are also discussed with detailed disclosure of their critical design principles and parameters. Finally, current challenges and future research directions are also discussed. Overall, this review will provide cutting-edge and multidisciplinary guidance for accelerating future developments and therapeutic/diagnostic applications of 2D-NBPFs

Quantitative proteomics identification of phosphoglycerate mutase 1 as a novel therapeutic target in hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with poor prognosis due to resistance to conventional chemotherapy and limited efficacy of radiotherapy. There is an urgent need to develop novel biomarkers for early diagnosis, as well as to identify new drug targets for therapeutic interventions. PATIENTS AND METHODS: 54 paired HCC samples and 21 normal liver tissues were obtained from West China Hospital of Sichuan University. Informed consent was obtained from all the patients or their relatives prior to analysis, and the project was approved by the Institutional Ethics Committee of Sichuan University. Stable Isotope Labeling with Amino Acids in Cell Culture (SILAC)-based proteomics was employed to profile the differentially expressed proteins between a HepG2 human hepatoma cell line and an immortal hepatic cell line L02. Validation of PGAM1 expression was performed by semi-quantitative RT-PCR, immunoblot and immunohistochemistry using clinical samples. shRNA expressing plasmids specifically targeting PGAM1 were designed and constructed by GenePharma Corporation (Shanghai, China), and were utilized to silence expression of PGAM1 in vitro and in vivo. Cell proliferation was measured by a combination of colony formation assay and Ki67 staining. Apoptosis was examined by flow cytometry and TUNEL assay. RESULTS: A total of 63 dysregulated proteins were identified, including 51 up-regulated proteins, and 12 down-regulated proteins (over 2-fold, p < 0.01). Phosphoglycerate mutase 1 (PGAM1) was found markedly upregulated. Clinico-pathological analysis indicated that overexpression of PGAM1 was associated with 66.7% HCC, and strongly correlated with poor differentiation and decreased survival rates (p < 0.01). shRNAs-mediated repression of PGAM1 expression resulted in significant inhibition in liver cancer cell growth both in vitro and in vivo. CONCLUSION: Our studies suggested that PGAM1 plays an important role in hepatocarcinogenesis, and should be a potential diagnostic biomarker, as well as an attractive therapeutic target for hepatocellular carcinoma

3D Mineral Prospectivity Modeling for the Low-Sulfidation Epithermal Gold Deposit: A Case Study of the Axi Gold Deposit, Western Tianshan, NW China

The Axi low-sulfidation (LS) epithermal deposit in northwestern China is the result of geological controls on hydrothermal fluid flow through strike-slip faults. Such controls occur commonly in LS epithermal deposits worldwide, but unfortunately, these have not been quantitatively analyzed to determine their spatial relationships with gold distribution and further guide mineral prospecting. In this study, we conduct a 3D mineral prospectivity modeling approach for the Axi deposit involving 3D geological modeling, 3D spatial analysis, and prospectivity modeling. The spatial analysis of geometric features revealed the gold mineralization trends in convex segments (0&ndash;20 m) with a specific distance from fault 2, the lower interface of late volcanic phase, and the upper interface of phyllic alteration with steep slopes (&gt;65&deg;), implying that gold deposition was significantly controlled by the morphological characteristics and distance fields of geologic features. The present alteration&ndash;mineralization zone at Axi has a larger width in bending sites (sections No. 35&ndash;15 and No. 40&ndash;56) than elsewhere, indicating the location of two fluid conduits extending to depth. The prediction-area plots and receiver operating characteristic curves demonstrated that (genetic algorithm optimized support vector regression (GA-SVR)) outperformed multiple nonlinear regression and fuzzy weights-of-evidence, which was proposed as a robust method to solve complicated nonlinear and high-dimensional issues in prospectivity modeling. Our study manifests spatial controls of structure, host rock, and alteration on LS epithermal gold deposition, and highlights the capability of GA-SVR for identifying deposit-scale potential epithermal gold mineralization

Crystal Growth and Investigation of High-Pressure Physical Properties of Fe2As

We reported the growth of Fe2As single crystals and the study of its physical properties via comprehensive measurements, such as transport properties under pressure and high-pressure synchrotron radiation X-ray diffraction. Fe2As is an antiferromagnetic metal with TN ~ 355 K. Within the pressure range of 100 GPa, no superconductivity was observed above 2 K. The abrupt drop in resistance from 21 to 31.7 GPa suggests a high-pressure phase transition happens. The high-pressure X-ray experiments indicate a new high-pressure phase appears, starting from 27.13 GPa. After the refinement of the high-pressure X-ray data, the pressure dependence of lattice constants of Fe2As (P4/nmm phase) was plotted and the bulk modulus B0 was obtained to be 168.6 GPa

RhoB expression decreases or loss in ovary carcinoma development.

<p>RhoB expression levels were analyzed in normal ovaries, benign, borderline tumors and malignant ovary carcinoma respectively. Immunohistochemistry reveals that moderate or strong cytoplasmic expressions of RhoB were detected in most of the normal ovaries (A) and benign (B, serous cystadenoma) and borderline (C) tumors. Staining was well visualized along ovary epithelium (arrows), with negative (D) or weak expression in malignant invasive tumor. (E) It is clear that RhoB expression is detected in normal ovary epithelium (100%), benign diseases (100%), borderline tumors (92.8%), and decreases significantly in the malignant invasive tumors (42.1%, <b>*</b><i>P</i><05).</p

Revivification of RhoB gene and apoptosis of ovary carcinoma cells.

<p>Flow cytometric analysis (FCM) together with fluorescence microscopy was adopted to assess apoptosis of ovary carcinoma cells after treated with TSA. <b>Top and middle panels</b>: when cells were treated for 10 h with 0 µmol/L (control), 0.05 µmol/L, 0.1 µmol/L, 0.25 µmol/L, 0.5 µmol/L and 1.0 µmol/L of TSA, the apoptosis rate revealed by FCM was 9.5% (A), 26.9% (B), 28% (C), 41% (D), 45.9% (E) and 66.9% (F) respectively. <b>Bottom panel</b>: PI stained fluorescence photomicrographs of ovary carcinoma cells after treated with TSA. Cells were treated for 10h with 0 µmol/L (G, control), 0.1 µmol/L and 0.5 µmol/L of TSA respectively, both 0.1 µmol/L (H) and 0.5µmol/L (I) of TSA could result in cellular morphological changes characterized as apoptosis: a brightly red-fluorescent condensed nuclei (intact or fragmented), reduction of cell volume, and apoptotic bodies.</p