Flexible Thin Film Functionalized by Initiative Dust Removal and Anti-Fogging for Optical Device Applications.

The deposition of dust and condensation of fog will block the scattering and transmission of light, thus affecting the performance of optical devices. In this work, flexible polyethylene terephthalate (PET) foil functionalized by active dust removal and anti-fogging characteristics is realized which combines electrodynamic screen (EDS) and electro-heating devices. In lieu of traditional measurement methods of dust removal efficiency, the PSNR is employed to characterize the dust removal efficiency of the film for the first time. The results show that both dust removal and anti-fogging improve the image quality, in which the dust removal increases the PSNR from 28.1 dB to 34.2 dB and the anti-fogging function realizes a film temperature rise of 16.7 ∘C in 5 min, reaching a maximum of 41.3 ∘C. According to the high sensitivity of the PSNR, we propose a fully automatic CIS film-driven algorithm, and its feasibility has been demonstrated.

Recent advances in the study of zika virus structure, drug targets, and inhibitors.

Zika Virus (ZIKV) is a positive-strand RNA virus that can lead to Guillain-Barré syndrome or encephalitis in some individuals and hence presents a serious public health risk. Since the first outbreak of ZIKV in Brazil in 2015, no effective clinical inhibitors have been developed, making the development of effective ZIKV drugs an urgent issue that needs to be addressed. ZIKV belongs to the Flaviviridae family, and its structure includes three structural proteins, namely, capsular (C), premembrane (prM), and envelope (E) proteins, as well as seven nonstructural proteins, namely, NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5. To provide a reference for the development of future ZIKV drugs, this paper reviews the structure of the ZIKV based on recent literature reports, analyzes the potential therapeutic targets of various proteins, and proposes feasible drug design strategies. Additionally, this paper reviews and classifies the latest research progress on several protease inhibitors, such as E protein inhibitors, NS2B-NS3 inhibitors, and NS5 inhibitors, so that researchers can quickly understand the current status of development and the interconnections among these inhibitors.

Potassium xanthate-promoted reductive sulfuration reaction: from aldehydes to thiol, disulfide, and thioester derivatives.

Herein, we developed a synthetic strategy for the direct construction of C-S bonds to obtain biologically active sulfur-containing compounds and a methodology involving the reductive sulfuration of aldehydes or ketones to obtain diverse substituted thiol, disulfide, and thioester derivatives. EtOCS2K is demonstrated as a potential substitute for the Berzelius reagent or Lawesson's reagent for the construction of C-S bonds.

Aromatization of cyclic hydrocarbons via thioether elimination reaction.

Herein, the diversity-oriented aromatization of cyclic hydrocarbons via potassium ethyl xanthogenate (EtOCS2K)/NH4I-mediated methylthiyl radical addition and thioether elimination was investigated under transition-metal-free conditions. The methylthiyl radical species were generated in situ via the NH4I-mediated decomposition of DMSO following which EtOCS2K promoted the breaking of carbon-sulfur bonds of thioether.

Metal-organic frameworks for hepatocellular carcinoma therapy and mechanism.

In recent years, metal organic frameworks (MOFs) have attracted increasing attention in cancer therapy, because they can enhance the anticancer efficacy of photodynamic therapy (PDT), photothermal therapy (PTT), photoacoustic imaging, and drug delivery. Owing to stable chemical adjustability, MOFs can be used as carriers to provide excellent loading sites and protection for small-molecule drugs. In addition, MOFs can be used to combine with a variety of therapeutic drugs, including chemotherapeutics drugs, photosensitizers, and radiosensitizers, to efficiently deliver drugs to tumor tissue and achieve desired treatment. There is hardly any review regarding the application of MOFs in hepatocellular carcinoma. In this review, the design, structure, and potential applications of MOFs as nanoparticulate systems in the treatment of hepatocellular carcinoma are presented. Systematic Review Registration: website, identifier registration number.

Access to Thienopyridine and Thienoquinoline Derivatives via Site-Selective C-H Bond Functionalization and Annulation.

To develop of an effective synthetic methodology for biologically relevant thienopyridines, a concise and efficient protocol is described for the synthesis of a series of substituted thienopyridine and thienoquinoline derivatives with high selectivity using EtOCS2K as the sulfur source. The reaction proceeds via metal-free, site-selective C-H bond thiolation and cyclization of the alkynylpyridine and alkynylquinoline substrates.

GLUT1 biological function and inhibition: research advances.

The GLUT is a key regulator of glucose metabolism and is widely expressed on the surface of most cells of the body. GLUT provides a variety of nutrients for the growth, proliferation and differentiation of cells. In recent years, the development of drugs affecting the energy intake of tumor cells has become a research hotspot. GLUT inhibitors are gaining increased attention because they can block the energy supply of malignant tumors. Herein, we elaborate on the structure and function of GLUT1, the structural and functional differences among GLUT1-4 transporters and the relationship between GLUT1 and tumor development, as well as GLUT1 transporter inhibitors, to provide a reference for the development of new GLUT1 inhibitors.

Novel inhibitor of OCT1 enhances the sensitivity of human esophageal squamous cell carcinoma cells to antitumor agents.

Esophageal squamous cell carcinoma (ESCC) is one of the most fatal malignancies of the digestive system, and shows an especially high incidence in some regions of China. Octamer transcription factors are a family of transcription factors whose DNA-binding domain is a POU domain. OCT transcription factors (OCT-TFs) mediate maintenance of the pluripotency of embryonic stem cells. We measured expression of OCT-TFs in ESCC clinical specimens. Among the OCTs tested, OCT1 showed the highest expression in ESCC tissues. Using molecular docking, we discovered a small-molecule inhibitor, which we named "novel inhibitor of OCT1" (NIO-1), for OCT1. Treatment with NIO-1 inhibited recruitment of OCT1 to the promoter region of its downstream genes and, consequently, repressed OCT1 activation. Treatment with NIO-1 enhanced the susceptibility of ESCC cells to chemotherapeutic agents. Therefore, OCT1 may be a valuable target for ESCC treatment, and NIO-1 could be a promising therapeutic agent.

Novel mTOR Inhibitor Enhances the Sensitivity of Hepatocellular Carcinoma Cells to Molecular Targeting Agents.

BACKGROUND: Although molecular-targeted agents are still the first choice for advanced hepatocellular carcinoma (HCC) treatment, the therapeutic efficacy of these agents is not satisfactory. Recently, the mammalian target of rapamycin (mTOR) is considered to be a promising molecular target that can enhance the sensitivity of HCC cells to antitumor therapy. However, the reported mTOR inhibitors have some shortcomings, and novel mTOR inhibitors need to be developed to enhance the antitumor effect of molecularly targeted agents on advanced HCC. METHODS: In this study, five small-molecular compounds that could serve as potential mTOR-specific inhibitors were identified by virtual screening. The activity of tert-butyl (4-(9-(2-(1,3-dioxolan-2-yl)ethyl)-6-morpholino-9H-purin-2-yl)phenyl)carbamate (compound 4) was measured by enzyme test and Western blot, and its antitumor effect on HCC was examined in nude mice subcutaneous tumor model. RESULTS: The results showed that 4 is the most effective one in inhibiting the activation of mTOR kinase (mTOR IC50 = 17.52±3.67 nmol/L) among the five lead compounds. Further research in this study indicated that treatment with 4 enhanced the sensitivity of HCC cells to the molecular-targeted agents, such as sorafenib, regorafenib, lenvatinib, anlotinib, and apatinib. In addition, this research indicated that mTOR was correlated with the poor prognosis in patients with advanced HCC who received sorafenib. CONCLUSION: Our study identified a new type of small-molecular inhibitors of mTOR and confirmed their ability to enhance the antitumor effect of molecular-targeted agents on advanced HCC.

Hsa_circ_0003732 promotes osteosarcoma cells proliferation via miR-545/CCNA2 axis.

Osteosarcoma (OS) is a primary malignant bone tumor with a high fatality rate. Circular RNAs (circRNAs) are a type of endogenous noncoding RNA that have been verified to participate in cancer pathophysiological processes. We aim to investigate the roles of circRNAs in osteosarcoma tumorigenesis. In the present study, we showed that hsa_circ_0003732 was up-regulated in OS tissues and elevated level of hsa_circ_0003732 was linked to poor prognosis of OS patients. Functional investigation indicated that hsa_circ_0003732 promoted proliferation of OS cells. Furthermore, we identified miR-545 as the hsa_circ_0003732-associated microRNA and CCNA2 was a direct target of miR-545. In addition, hsa_circ_0003732 could elevate CCNA2 expression via miR-545, resulting in the promotion of OS cells proliferation. Altogether, our findings demonstrate that hsa_circ_0003732 promotes OS cells proliferation via miR-545/CCNA2 axis and imply hsa_circ_0003732 may be a potential prognosis biomarker and therapeutic target for OS.

Virtual Screening and Optimization of Novel mTOR Inhibitors for Radiosensitization of Hepatocellular Carcinoma.

BACKGROUND: Radiotherapy has an ameliorative effect on a wide variety of tumors, but hepatocellular carcinoma (HCC) is insensitive to this treatment. Overactivated mammalian target of rapamycin (mTOR) plays an important part in the resistance of HCC to radiotherapy; thus, mTOR inhibitors have potential as novel radiosensitizers to enhance the efficacy of radiotherapy for HCC. METHODS: A lead compound was found based on pharmacophore modeling and molecular docking, and optimized according to the differences between the ATP-binding pockets of mTOR and PI3K. The radiosensitizing effect of the optimized compound (2a) was confirmed by colony formation assays and DNA double-strand break assays in vitro. The discovery and preclinical characteristics of this compound are described. RESULTS: The key amino acid residues in mTOR were identified, and a precise virtual screening model was constructed. Compound 2a, with a 4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidine scaffold, exhibited promising potency against mTOR (mTOR IC50=7.1 nmol/L (nM)) with 126-fold selectivity over PI3Kα. Moreover, 2a significantly enhanced the sensitivity of HCC to radiotherapy in vitro in a dose-dependent manner. CONCLUSION: A new class of selective mTOR inhibitors was developed and their radiosensitization effects were confirmed. This study also provides a basis for developing mTOR-specific inhibitors for use as radiosensitizers for HCC radiotherapy.