Conductive, stretchable, environmentally‐friendly, and strain‐sensitive elastomers are attracting immense research interest because of their potential applications in various areas, such as ...human–machine interfaces, healthcare monitoring, and soft robots. Herein, a binary networked elastomer is reported based on a composite hydrogel of polyvinyl alcohol (PVA) and polyethyleneimine (PEI), which is demonstrated to be ultrastretchable, mechanically robust, biosafe, and antibacterial. The mechanical stretchability and toughness of the hydrogels are optimized by tuning the constituent ratio and water content. The optimal hydrogel (PVA2PEI1‐75) displays an impressive tensile strain as high as 500% with a corresponding tensile stress of 0.6 MPa. Furthermore, the hydrogel elastomer is utilized to fabricate piezoresistive sensors. The as‐made strain sensor displays seductive capability to monitor and distinguish multifarious human motions with high accuracy and sensitivity, like facial expressions and vocal signals. Therefore, the elastomer reported in this study holds great potential for sensing applications in the era of the Internet of Things (IoTs).
A binary networked elastomer based on polyvinyl alcohol (PVA) and polyethyleneimine (PEI) exhibits ultrastretchable, mechanically robust, biosafety, and antibacterial properties. Through optimizing the constituent ratio and water content, the composite hydrogel displays seductive elasticity and is further used to monitor and distinguish multifarious human motions with high accuracy and sensitivity, like facial expressions and vocal signals.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
The use of photothermal agents (PTAs) in cancer photothermal therapy (PTT) has shown promising results in clinical studies. The rapid degradation of PTAs may address safety concerns but ...usually limits the photothermal stability required for efficacious treatment. Conversely, PTAs with high photothermal stability usually degrade slowly. The solutions that address the balance between the high photothermal stability and rapid degradation of PTAs are rare. Here, we report that the inherent Cu
2+
-capturing ability of black phosphorus (BP) can accelerate the degradation of BP, while also enhancing photothermal stability. The incorporation of Cu
2+
into BP@Cu nanostructures further enables chemodynamic therapy (CDT)-enhanced PTT. Moreover, by employing
64
Cu
2+
, positron emission tomography (PET) imaging can be achieved for in vivo real-time and quantitative tracking. Therefore, our study not only introduces an “ideal” PTA that bypasses the limitations of PTAs, but also provides the proof-of-concept application of BP-based materials in PET-guided, CDT-enhanced combination cancer therapy.
Squamous cell carcinomas (SCCs) are aggressive malignancies. Previous report demonstrated that master transcription factors (TFs) TP63 and SOX2 exhibited overlapping genomic occupancy in SCCs. ...However, functional consequence of their frequent co-localization at super-enhancers remains incompletely understood. Here, epigenomic profilings of different types of SCCs reveal that TP63 and SOX2 cooperatively and lineage-specifically regulate long non-coding RNA (lncRNA) CCAT1 expression, through activation of its super-enhancers and promoter. Silencing of CCAT1 substantially reduces cellular growth both in vitro and in vivo, phenotyping the effect of inhibiting either TP63 or SOX2. ChIRP analysis shows that CCAT1 forms a complex with TP63 and SOX2, which regulates EGFR expression by binding to the super-enhancers of EGFR, thereby activating both MEK/ERK1/2 and PI3K/AKT signaling pathways. These results together identify a SCC-specific DNA/RNA/protein complex which activates TP63/SOX2-CCAT1-EGFR cascade and promotes SCC tumorigenesis, advancing our understanding of transcription dysregulation in cancer biology mediated by master TFs and super-enhancers.
•BNCT has more potential to effectively target multicentric deposits of tumors.•This review focuses on tumor-targeting boron delivery agents developed recently.•This review provides a summary and ...critical perspective of boron delivery agents.
Boron neutron capture therapy (BNCT) is a potential cancer radiotherapeutic modality, which takes advantage of the neutron capture response that occurs when boron (10B) is struck by low-energy thermal neutrons, triggering a nuclear fission reaction that ultimately causes cell death. Because the fatal radiation is restricted to approximately a single cell diameter, only cells with significant boron accumulation that are in the neutron field will be destroyed. Tumor-targeted 10B delivery agents are an essential component of BNCT. Currently, two low molecular weight boron-containing compounds, sodium mercaptoundecahydro-closo-dodecaborate (BSH) and borylphenylalanine (BPA), are mainly used in BNCT. Although both have suboptimal tumor selectivity, they have shown some therapeutic effect in patients with high-grade gliomas and several other kinds of tumors. In order to improve the efficacy of BNCT, significant effort has been devoted to developing new boron delivery agents that possess better uptake and favorable pharmacokinetic characteristics for clinical use. This review focuses on various boron delivery agents that have been developed over the past 40 years, including boron-containing amino acids, boron-containing compound conjugated-nucleosides, porphyrin derivatives, peptides, monoclonal antibodies, and different types of nanomaterials for 10B delivery. The principles underlying BNCT and the clinical trials with BNCT are briefly introduced in the first part of this review. In the second part, we provide a detailed overview of various boron delivery agents and discuss their merits and limitations. Additionally, the preclinical outcomes of these agents are included in this review and the most promising delivery agents are highlighted and compared. In summary, this article provides an overview of boron delivery agents, and critically analyzes their clinical prospects, from the view of medicinal chemists and nuclear medicine physicians.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Squamous cell carcinomas (SCCs) comprise one of the most common histologic types of human cancer. Transcriptional dysregulation of SCC cells is orchestrated by
tumor protein p63 (TP63)
, a ...master transcription factor (TF) and a well-researched SCC-specific oncogene. In the present study, both Gene Set Enrichment Analysis (GSEA) of SCC patient samples and in vitro loss-of-function assays establish fatty-acid metabolism as a key pathway downstream of TP63. Further studies identify
sterol regulatory element binding transcription factor 1 (SREBF1)
as a central mediator linking TP63 with fatty-acid metabolism, which regulates the biosynthesis of fatty-acids, sphingolipids (SL), and glycerophospholipids (GPL), as revealed by liquid chromatography tandem mass spectrometry (LC-MS/MS)-based lipidomics. Moreover, a feedback co-regulatory loop consisting of SREBF1/TP63/
Kruppel like factor 5 (KLF5)
is identified, which promotes overexpression of all three TFs in SCCs. Downstream of SREBF1, a non-canonical, SCC-specific function is elucidated: SREBF1 cooperates with TP63/KLF5 to regulate hundreds of cis-regulatory elements across the SCC epigenome, which converge on activating cancer-promoting pathways. Indeed, SREBF1 is essential for SCC viability and migration, and its overexpression is associated with poor survival in SCC patients. Taken together, these data shed light on mechanisms of transcriptional dysregulation in cancer, identify specific epigenetic regulators of lipid metabolism, and uncover SREBF1 as a potential therapeutic target and prognostic marker in SCC.
Phosphorene is a promising candidate for gas sensing materials. This letter describes our study of the adsorption of SF 6 and SF 6 decomposition gases (SO 2 and H 2 S) on phosphorene. We used first ...principles calculations to explore phosphorene's potential applications as gas sensor to diagnose the state of online gas insulated switchgear (GIS). The calculation results showed that only the adsorption of SO 2 induced a moderate adsorption energy and apparent charge transfer. We further investigated the current-voltage (I-V) relationships before and after gas absorption through the non-equilibrium Green's function method. It was found that only SO 2 induced a dramatic change in the I-V relationships. Therefore, phosphorene appears to be a promising candidate for highly sensitive and selective SF 6 decomposition gas sensors for online GIS diagnosis.
Supramolecular soft crystals are periodic structures that are formed by the hierarchical assembly of complex constituents, and occur in a broad variety of 'soft-matter' systems
. Such soft crystals ...exhibit many of the basic features (such as three-dimensional lattices and space groups) and properties (such as band structure and wave propagation) of their 'hard-matter' atomic solid counterparts, owing to the generic symmetry-based principles that underlie both
. 'Mesoatomic' building blocks of soft-matter crystals consist of groups of molecules, whose sub-unit-cell configurations couple strongly to supra-unit-scale symmetry. As yet, high-fidelity experimental techniques for characterizing the detailed local structure of soft matter and, in particular, for quantifying the effects of multiscale reconfigurability are quite limited. Here, by applying slice-and-view microscopy to reconstruct the micrometre-scale domain morphology of a solution-cast block copolymer double gyroid over large specimen volumes, we unambiguously characterize its supra-unit and sub-unit cell morphology. Our multiscale analysis reveals a qualitative and underappreciated distinction between this double-gyroid soft crystal and hard crystals in terms of their structural relaxations in response to forces-namely a non-affine mode of sub-unit-cell symmetry breaking that is coherently maintained over large multicell dimensions. Subject to inevitable stresses during crystal growth, the relatively soft strut lengths and diameters of the double-gyroid network can easily accommodate deformation, while the angular geometry is stiff, maintaining local correlations even under strong symmetry-breaking distortions. These features contrast sharply with the rigid lengths and bendable angles of hard crystals.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Ovarian cancer (OC) is a gynecological cancer with high mortality. OC‐derived exosomal circRNAs can regulate angiogenesis. This study aims to explore the role and mechanism of exosomal circRNA ...nuclear factor I X (CircNFIX) derived from OC cells in angiogenesis. Quantitative real‐time polymerase chain reaction was employed to evaluate the levels of circNFIX, miR‐518a‐3p, and tripartite motif protein 44 (TRIM44) in OC and adjacent tissues. Exosomes from the ovarian surface epithelial cell (HOSEpiC) and OC cells (SKOV3 or OVCAR3) were isolated by differential centrifugation. Exosomes were cocultured with the human umbilical vein endothelial cells (HUVECs). The angiogenesis capacity was analyzed by Tube formation assay. 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide (MTT) and Transwell assays were used to determine the cell viability and migration ability. The dual‐luciferase report, RNA immunoprecipitation (RIP), and RNA pull‐down assays were applied to validate the gene's interaction. CircNFIX and TRIM44 expression were higher and miR‐518a‐3p was lower in OC tissues than in the adjacent tissues. Upregulated circNFIX and TRIM44 were significantly correlated with the tumor size and International Federation of Gynecology and Obstetrics (FIGO) stage of OC patients. HUVECs treated OC‐derived exosomes had higher proliferation, migration, and angiogenesis capacities than the control group. While OC‐derived exosomal circNFIX silencing restrained HUVECs' proliferation, migration, and angiogenesis, compared with the OC‐derived exosomes group. OC‐derived exosomal circNFIX positively regulated TRIM44 expression by targeting miR‐518a‐3p in HUVECs. OC‐derived exosomal circNFIX promoted angiogenesis by regulating the Janus‐activated kinase/signal transducer and activator of transcription 1 (JAK/STAT1) pathway via miR‐518a‐3p/TRIM44 axis in HUVECs.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
A major active constituent of
Lam. is 4-(α-L-rhamnose oxy) benzyl isothiocyanate (MITC). To broaden MITC's application and improve its biological activity, we synthesized a series of MITC ...quinazolinone derivatives and evaluated their anticancer activity. The anticancer effects and mechanisms of the compound with the most potent anticancer activity were investigated further. Among 16 MITC quinazolinone derivatives which were analyzed, MITC-12 significantly inhibited the growth of U251, A375, A431, HCT-116, HeLa, and MDA-MB-231 cells. MITC-12 significantly inhibited U251 cell proliferation in a time- and dose-dependent manner and decreased the number of EdU-positive cells, but was not toxic to normal human gastric mucosal cells (GES-1). Further, MITC-12 induced apoptosis of U251 cells, and increased caspase-3 expression levels and the Bax:Bcl-2 ratio. In addition, MITC-12 significantly decreased the proportion of U251 cells in the G1 phase and increased it in S and G2 phases. Transcriptome sequencing showed that MITC-12 had a significant regulatory effect on pathways regulating the cell cycle. Further, MITC-12 significantly decreased the expression levels of the cell cycle-related proteins CDK2, cyclinD1, and cyclinE, and increased those of cyclinA2, as well as the p-JNK:JNK ratio. These results indicate that MITC-12 inhibits U251 cell proliferation by inducing apoptosis and cell cycle arrest, activating JNK, and regulating cell cycle-associated proteins. MITC-12 has potential for use in the prevention and treatment of glioma.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
ANXA2 (Annexin A2) is a pleiotropic calcium-dependent phospholipid binding protein that is abnormally expressed in various cancers. We previously found that ANXA2 is upregulated in esophageal ...squamous cell carcinoma (ESCC). This study was designed to investigate the functional significance of ANXA2 dysregulation and underlying mechanism in ESCC.
Proliferation, migration, invasion and metastasis assay were performed to examine the functional roles of ANXA2 in ESCC cells in vitro and in vivo. Real-time RT-PCR, immunoblotting, ChIP, reporter assay, confocal-immunofluorescence staining, co-immunoprecipitation and ubiquitination assay were used to explore the molecular mechanism underlying the actions of deregulated ANXA2 in ESCC cells.
Overexpression of ANXA2 promoted ESCC cells migration and invasion in vitro and metastasis in vivo through activation of the MYC-HIF1A-VEGF cascade. Notably, ANXA2 phosphorylation at Tyr23 by SRC led to its translocation into the nucleus and enhanced the metastatic potential of ESCC cells. Phosphorylated ANXA2 (Tyr23) interacted with MYC and inhibited ubiquitin-dependent proteasomal degradation of MYC protein. Accumulated MYC directly potentiated HIF1A transcription and then activated VEGF expression. Correlation between these molecules were also found in ESCC tissues. Moreover, dasatinib in combination with bevacizumab or ANXA2-siRNA produced potent inhibitory effects on the growth of ESCC xenograft tumors in vivo.
This study provides evidence that highly expressed p-ANXA2 (Tyr23) contributes to ESCC progression by promoting migration, invasion and metastasis, and suggests that targeting the SRC-ANXA2-MYC-HIF1A-MYC axis may be an efficient strategy for ESCC treatment.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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