Temperature‐dependent dual fluorescence and switchable circularly polarized luminescence (CPL) are two highly pursued but challenging properties for small organic molecules (SOMs). We herein disclose ...a triarylborane π‐system based on a 2,2′‐diamino‐6,6′‐diboryl‐1,1′‐binaphthyl scaffold that can serve as a versatile building block for achieving these two properties by simply choosing different amino groups. BNMe2‐BNaph with less bulky dimethylamino groups displays temperature‐dependent dual fluorescence, and can thus be used as a highly sensitive ratiometric fluorescence thermometer. On the other hand, BNPh2‐BNaph with bulky diphenylamino groups exhibits intense fluorescence in both solution and in the solid state. A change of solvent from nonpolar cyclohexane to highly polar MeCN not only shifts the CPL position to much longer wavelength but also inverts the CPL sign. In addition, the complexation of BNPh2‐BNaph with fluoride greatly enhances the CPL intensity.
The combination of two donor–π‐acceptor subunits in the 2,2′‐diamino‐6,6′‐diboryl‐1,1′‐binaphthyl scaffold generates a versatile building block for organic fluorophores exhibiting temperature‐dependent dual fluorescence and switchable circularly polarized luminescence.
Temperature‐dependent dual fluorescence with the anti‐Kasha's rule is of great interest, but is a very challenging property to achieve in small organic molecules. The highly sensitive ...temperature‐dependent dual fluorescence of 2,2′‐bis(dimethylamino)‐6,6′‐bis(dimesitylboryl)‐1,1′‐binaphthyl (BNMe2‐BNaph), which essentially consists of two donor–π–acceptor (D‐π‐A) subunits, inspired the exploration of the importance of its structural features and the general utility of this molecular design. The reference compound MBNMe2‐BNaph, which lacks one electron‐accepting Mes2B, is found to show less sensitive temperature‐dependent dual fluorescence, suggesting that the structure of BNMe2‐Bnaph, consisting of two symmetrical D‐π‐A subunits, is very important for achieving highly sensitive temperature‐dependent dual fluorescence. In addition, it is found that another two 1,1′‐binaphthyls, CHONMe2‐BNaph and CNNMe2‐BNaph, which also consist of two D‐π‐A subunits with Mes2B groups replaced by CHO and CN, respectively, also show temperature‐dependent dual fluorescence, with the fluorescence changing in a similar manner to BNMe2‐BNaph, indicating the general utility of the current molecular design for temperature‐dependent dual fluorescence. Furthermore, the temperature‐dependent dual fluorescence behaviors, such as the relative intensities of the two emission bands, the separation of the two emissions bands, and the sensitivity of the fluorescence intensity ratio to temperature, are greatly influence by the electron acceptors.
Shine bright: Various 1,1′‐binaphthyl compounds, which have the characteristic composition of two donor–π–acceptor subunits with two dimethylamino groups and two electron acceptors (dimesitylboryl, formyl, and cyano) at 2,2′‐ and 6,6′‐positions, respectively, display the desirable property of temperature‐dependent dual fluorescence (see figure).
The efficient synthetic route was disclosed to prepare optically active triarylborane-based 5helicenes, 7B-PhHC and 7B5N-PhHC. Their emission wavelengths are tunable by both the chemical structure ...modification and the tuning of excited state charge transfer dynamics via selection of appropriate solvents or addition of external F–, enabling the full-color circularly polarized luminescence with moderate to good quantum yields (0.07–0.51) and high luminescence dissymmetry factors (g lum > 5 × 10–3).
Highlights • Tumor-associated macrophages enhance cancer stem cell-like properties by EMT. • Tumor-associated macrophages induce EMT of hepatoma cells via TGF-β1. • The combination of CSC and TAM ...have a better power to predict the prognosis of HCC.
Background and Aims
Fibroblast growth factor (FGF) 1 demonstrated protection against nonalcoholic fatty liver disease (NAFLD) in type 2 diabetic and obese mice by an uncertain mechanism. This study ...investigated the therapeutic activity and mechanism of a nonmitogenic FGF1 variant carrying 3 substitutions of heparin‐binding sites (FGF1△HBS) against NAFLD.
Approach and Results
FGF1△HBS administration was effective in 9‐month‐old diabetic mice carrying a homozygous mutation in the leptin receptor gene (db/db) with NAFLD; liver weight, lipid deposition, and inflammation declined and liver injury decreased. FGF1△HBS reduced oxidative stress by stimulating nuclear translocation of nuclear erythroid 2 p45‐related factor 2 (Nrf2) and elevation of antioxidant protein expression. FGF1△HBS also inhibited activity and/or expression of lipogenic genes, coincident with phosphorylation of adenosine monophosphate–activated protein kinase (AMPK) and its substrates. Mechanistic studies on palmitate exposed hepatic cells demonstrated that NAFLD‐like oxidative damage and lipid accumulation could be reversed by FGF1△HBS. In palmitate‐treated hepatic cells, small interfering RNA (siRNA) knockdown of Nrf2 abolished only FGF1△HBS antioxidative actions but not improvement of lipid metabolism. In contrast, AMPK inhibition by pharmacological agent or siRNA abolished FGF1△HBS benefits on both oxidative stress and lipid metabolism that were FGF receptor (FGFR) 4 dependent. Further support of these in vitro findings is that liver‐specific AMPK knockout abolished therapeutic effects of FGF1△HBS against high‐fat/high‐sucrose diet–induced hepatic steatosis. Moreover, FGF1△HBS improved high‐fat/high‐cholesterol diet–induced steatohepatitis and fibrosis in apolipoprotein E knockout mice.
Conclusions
These findings indicate that FGF1△HBS is effective for preventing and reversing liver steatosis and steatohepatitis and acts by activation of AMPK through hepatocyte FGFR4.
The aim of this study was to describe the effects of sodium‐glucose co‐transporter 2 (SGLT2) inhibitors on serum uric acid (SUA) in patients with type 2 diabetes mellitus (T2DM). PubMed, CENTRAL, ...EMBASE and ClinicalTrials.gov were searched for randomized controlled trials of SGLT2 inhibitors in patients with T2DM up to May 20, 2017. A total of 62 studies, comprising 34 941 patients, were included. Any of the SGLT2 inhibitors (empagliflozin, canagliflozin, dapagliflozin, tofogliflozin, luseogliflozin or ipragliflozin) significantly decreased SUA levels compared with control (total weighted mean difference WMD −37.73 μmol/L, 95% CI −40.51, −34.95). Treatment with empagliflozin resulted in a superior reduction in SUA (WMD −45.83 μmol/L, 95% CI −53.03, −38.63). The effect persisted during long‐term treatment. Dapagliflozin decreased SUA in a dose‐dependent manner (from 5 to 50 mg, P = .014). In subgroup analyses, greater reductions could be observed during the course of early diabetes and the SUA‐lowering effect was abolished in patients with chronic kidney disease (estimated glomerular filtration rate <60 mL/min per 1.73 m2). The effect of SGLT2 inhibitors on SUA reduction suggests that this class of drugs might be beneficial for diabetic patients with hyperuricaemia.
Antimony selenide (Sb2Se3) is a highly promising photovoltaic material thanks to its outstanding optoelectronic properties, as well as its cost‐effective and eco‐friendly merits. However, toxic CdS ...is widely used as an electron transport layer (ETL) in efficient Sb2Se3 solar cells, which largely limit their development toward market commercialization. Herein, an effective green Cd‐free ETL of SnOx is introduced and deposited by atomic layer deposition method. Additionally, an important post‐annealing treatment is designed to further optimize the functional layers and the heterojunction interface properties. Such engineering strategy can optimize SnOx ETL with higher nano‐crystallinity, higher carrier density, and less defect groups, modify Sb2Se3/SnOx heterojunction with better interface performance and much desirable “spike‐like” band alignment, and also improve the Sb2Se3 light absorber layer quality with passivated bulk defects and prolonged carrier lifetime, and therefore to enhance carrier separation and transport while suppressing non‐radiative recombination. Finally, the as‐fabricated Cd‐free Mo/Sb2Se3/SnOx/ITO/Ag thin‐film solar cell exhibits a stimulating efficiency of 7.39%, contributing a record value for Cd‐free substrate structured Sb2Se3 solar cells reported to date. This work provides a viable strategy for developing and broadening practical applications of environmental‐friendly Sb2Se3 photovoltaic devices.
Actomic layer deposition processed SnOx is introduced as electron transport layer in Sb2Se3 thin‐film solar cells. An additional post‐annealing can remarkably enhance the photovoltaic performance, thanks to the optimized carrier dynamics under simultaneously improving the properties of SnOx, Sb2Se3/SnOx heterojunction and Sb2Se3 absorber layer. A stimulating efficiency of 7.39% represents the record value for Cd‐free substrate structured Sb2Se3 solar cells.
FAM64A is a mitogen-induced regulator of the metaphase and anaphase transition. Here, we found that FAM64A messenger RNA (mRNA) and protein expression levels were higher in gastric cancer tissue than ...in normal mucosa (p < .05). FAM64A methylation was negatively correlated with FAM64A mRNA expression (p < .05). The differentially expressed genes of FAM64A were mainly involved in digestion, potassium transporting or exchanging ATPase, contractile fibers, endopeptidase, and pancreatic secretion (p < .05). The FAM64A-related genes were principally categorized into ubiquitin-mediated proteolysis, cell cycle, chromosome segregation and mitosis, microtubule binding and organization, metabolism of amino acids, cytokine receptors, lipid droplet, central nervous system, and collagen trimer (p < .05). FAM64A protein expression was lower in normal gastric mucosa than intestinal metaplasia, adenoma, and primary cancer (p < .05), negatively correlated with older age, T stage, lymphatic and venous invasion, tumor, node, metastasis stage, and dedifferentiation (p < .05), and associated with a favorable overall survival of gastric cancer patients. FAM64A overexpression promoted proliferation, antiapoptosis, migration, invasion, and epithelial-mesenchymal transition via the EGFR/Akt/mTOR/NF-κB, while the opposite effect was observed for FAM64A knockdown. FAM64A also induced chemoresistance directly or indirectly through lipid droplet formation via ING5. These results suggested that upregulation of FAM64A expression might induce aggressive phenotypes, leading to gastric carcinogenesis and its subsequent progression. Thus, FAM64A could be regarded as a prognosis biomarker and a target for gene therapy.
The mechanisms underlying the role of CXCL5 in tumor angiogenesis have not been fully defined. Here, we examined the effect of CXCL5 on tumor angiogenesis in colorectal cancer (CRC). ...Immunohistochemistry was used to monitor the expression of CXCL5 and CD31 in CRC patients' tissues. HUVEC cell lines stably transfected with shCXCR2 and shFOXD1 lentivirus plasmids were used in an in vitro study. Based on some molecular biological experiments in vitro and in vivo, we found that CXCL5 was upregulated in tumor tissues and that its level positively correlated with the expression of CD31. Next, we used recombinant human CXCL5 (rhCXCL5) to stimulate HUVECs and found that their tube formation ability, proliferation, and migration were enhanced by the activation of the AKT/NF-κB/FOXD1/VEGF-A pathway in a CXCR2-dependent manner. However, silencing of CXCR2 and FOXD1 or inhibition of the AKT and NF-κB pathways could attenuate the tube formation ability, proliferation, and migration of rhCXCL5-stimulated HUVECs in vitro. rhCXCL5 can promote angiogenesis in vivo in Matrigel plugs, and the overexpression of CXCL5 can also increase microvessel density in vivo in a subcutaneous xenotransplanted tumor model in nude mice. Taken together, our findings support CXCL5 as an angiogenic factor that can promote cell metastasis through tumor angiogenesis in CRC. Furthermore, we propose that FOXD1 is a novel regulator of VEGF-A. These observations open new avenues for therapeutic application of CXCL5 in tumor anti-angiogenesis.