Vivid Colored Cooling Structure Managing Full Solar Spectrum via Near-Infrared Reflection and Photoluminescence.

Colored radiative cooling (CRC) offers an attractive alternative for surface and space cooling, while preserving the aesthetics of an object. However, there has been no study on the CRC using phosphors in regard to vivid coloration, sophisticated performance investigation, retention of properties, functionality, and structural flexibility all at once. Thus, to manage the entire solar spectrum, a colored cooling structure comprising a near-infrared (NIR)-reflective bottom layer and a top colored layer with a phosphor-embedded polymer matrix is proposed. The structure is paintable, vividly colored, hydrophobic, and ultraviolet (UV) and water resistant. In the daytime outdoor measurement, the structure with red, orange, and yellow colors exhibited lower temperature than a control group using commercial white paint by 4.7 °C, 7.2 °C, and 7.4 °C, respectively. After precise theoretical and experimental time-tracing temperature validation, the CRC performance enhancement from NIR reflection and photoluminescence effects was thoroughly analyzed, and a temperature reduction of up to 16.1 °C was achieved for the orange-colored structure. Furthermore, experiments of hydrophobicity infusion and exposure to UV and deionized water verified the durability of the colored cooling structure. In addition, flexible-film-type colored cooling structures were demonstrated using different bottom reflective layers, such as a silver thin film and porous aluminum oxide particle-embedded poly(vinylidene fluoride-co-hexafluoropropylene), suggesting the potential applicability of these colored cooling structures for vivid-colored, functional, and durable CRC.

The patient-specific mouse model with Foxg1 frameshift mutation uncovers the pathophysiology of FOXG1 syndrome.

Single allelic mutations in the gene encoding the forebrain-specific transcription factor FOXG1 lead to FOXG1 syndrome (FS). Patient-specific animal models are needed to understand the etiology of FS, as FS patients show a wide spectrum of symptoms correlated with location and mutation type in the FOXG1 gene. Here we report the first patient-specific FS mouse model, Q84Pfs heterozygous (Q84Pfs-Het) mice, mimicking one of the most predominant single nucleotide variants in FS. Intriguingly, we found that Q84Pfs-Het mice faithfully recapitulate human FS phenotypes at the cellular, brain structural, and behavioral levels. Importantly, Q84Pfs-Het mice exhibited myelination deficits like FS patients. Further, our transcriptome analysis of Q84Pfs-Het cortex revealed a new role for FOXG1 in synapse and oligodendrocyte development. The dysregulated genes in Q84Pfs-Het brains also predicted motor dysfunction and autism-like phenotypes. Correspondingly, Q84Pfs-Het mice showed movement deficits, repetitive behaviors, increased anxiety, and prolonged behavior arrest. Together, our study revealed the crucial postnatal role of FOXG1 in neuronal maturation and myelination and elucidated the essential pathophysiology mechanisms of FS.

Leukotriene B4 receptor-2 contributes to KRAS-driven lung tumor formation by promoting interleukin-6-mediated inflammation.

Although lung cancer is the leading cause of cancer-related deaths worldwide and KRAS is the most frequently mutated oncogene in lung cancer cases, the mechanism by which KRAS mutation drives lung cancer has not been fully elucidated. Here, we report that the expression levels of leukotriene B4 receptor-2 (BLT2) and its ligand-producing enzymes (5-LOX, 12-LOX) were highly increased by mutant KRAS and that BLT2 or 5-/12-LOX blockade attenuated KRAS-driven lung cell proliferation and production of interleukin-6 (IL-6), a principal proinflammatory mediator of lung cancer development. Next, we explored the roles of BLT2 and 5-/12-LOX in transgenic mice with lung-specific expression of mutant KRAS (KrasG12D) and observed that BLT2 or 5-/12-LOX inhibition decreased IL-6 production and tumor formation. To further determine whether BLT2 is involved in KRAS-driven lung tumor formation, we established a KrasG12D/BLT2-KO double-mutant mouse model. In the double-mutant mice, we observed significantly suppressed IL-6 production and lung tumor formation. Additionally, we observed high BLT2 expression in tissue samples from patients with KrasG12D-expressing lung adenocarcinoma, supporting the contributory role of BLT2 in KRAS-driven human lung cancer. Collectively, our results suggest that BLT2 is a potential contributor to KRAS-driven lung cancer and identify an attractive therapeutic target for KRAS-driven lung cancer.

Mediatory role of BLT2 in the proliferation of KRAS mutant colorectal cancer cells.

Inflammatory lipid mediators play various roles in colorectal cancer progression through complex pathways. However, the mechanism by which lipoxygenase-derived inflammatory lipid mediators contribute to colorectal cancer progression remains elusive. In this study, we found that BLT2, a cell surface GPCR for leukotriene B4 and 12­hydroxyeicosatetraenoic acid, is highly upregulated in KRAS mutant LOVO and SW480 colorectal cancer cells and plays critical roles in mediating proliferation through activation of phosphatidylinositol 3­kinase (PI3K)/protein kinase B (Akt) and subsequent upregulation of cyclin D1. Exposure to BLT2 siRNA or LY255283, a specific BLT2 inhibitor, clearly suppressed the proliferation of KRAS mutant colorectal cancer cells and markedly increased cell cycle arrest by downregulating the PI3K/Akt-cyclin D1 cascade. Xenograft tumor formation by LOVO and SW480 cells in athymic mice was also substantially reduced by treatment with the BLT2 inhibitor in vivo. Together, our study demonstrates that BLT2 is necessary for the proliferation of LOVO and SW480 cells and thus may be a potential therapeutic target for the treatment of KRAS mutant colorectal cancer.

Wogonin suppresses the LPS­enhanced invasiveness of MDA­MB­231 breast cancer cells by inhibiting the 5­LO/BLT2 cascade.

Wogonin, a naturally occurring bioactive monoflavonoid isolated from Scutellariae radix (roots of Scutellariae baicalensis Georgi), has known anticancer effects. However, the molecular signaling mechanism by which wogonin inhibits invasiveness in breast cancer cells remains unclear. In the present study, it was observed that wogonin exerted an inhibitory effect on the lipopolysaccharide (LPS)­enhanced invasiveness of MDA­MB­231 cells. In addition, wogonin inhibited the synthesis of interleukin­8 (IL­8) and matrix metallopeptidase­9 (MMP­9), which are critical for promoting invasiveness in MDA­MB­231 cells. Wogonin also suppressed the expression of leukotriene B4 receptor 2 (BLT2) and the synthesis of its ligand, by inhibiting 5­lipoxygenase (5­LO) in LPS­stimulated MDA­MB­231 cells. Notably, wogonin attenuated the production of IL­8 and MMP­9 by inhibiting the BLT2/extracellular signal­regulated kinase (ERK)­linked cascade. Finally, in vivo, LPS­driven MDA­MB­231 cell metastasis was markedly suppressed by wogonin administration. Overall, the present results suggested that wogonin inhibited the 5­LO/BLT2/ERK/IL­8/MMP­9 signaling cascade and demonstrated that this cascade may be an important target through which wogonin exerts its anticancer effects in breast cancer.

BLT2, a leukotriene B4 receptor 2, as a novel prognostic biomarker of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is considered to be a notorious type of cancer due to its aggressive metastatic potential and poor prognosis. Recent evidence suggests that BLT2, a low-affinity LTB4 receptor is critically associated with the phenotypes of TNBC cells, including invasion, metastasis, and survival. Furthermore, in a group of 545 breast cancer patients with metastasis, we observed that the high-BLT2 subgroup had a lower disease-free-survival rate than the low-BLT2 subgroup. Thus, we theorized that anti-BLT2 strategies could facilitate the development of new therapies used for TNBC. This review focuses on recent discoveries regarding BLT2 and its roles in as a novel prognostic biomarker in TNBC. [BMB Reports 2018; 51(8): 373-377].

Leukotriene B4 receptor-2 contributes to chemoresistance of SK-OV-3 ovarian cancer cells through activation of signal transducer and activator of transcription-3-linked cascade.

Inflammation and inflammatory mediators are intimately linked with chemoresistance through complex pathways in the tumor microenvironment. However, the mechanism by which inflammatory mediators (e.g., eicosanoids) contribute to chemoresistance remains elusive. In this study, we found that the low-affinity leukotriene B4 receptor-2 (BLT2) and its ligand leukotriene B4 were highly up-regulated in cisplatin-resistant SK-OV-3 ovarian cancer cells and play critical roles in mediating the chemoresistance through the activation of signal transducer and activator of transcription-3 (STAT-3) and the subsequent up-regulation of interleukin-6 (IL-6). BLT2 depletion with siRNA clearly abolished the chemoresistance to cisplatin in SK-OV-3 ovarian cancer cells and further increased cell sensitivity to cisplatin chemotherapy by down-regulating the 'STAT-3-IL-6' cascade. Enlarged tumor formation due to the cisplatin resistance of SK-OV-3 cells in cisplatin-treated athymic mice was also substantially reduced by co-treatment with the BLT2 inhibitor in vivo. Our study demonstrates that BLT2 is a novel contributor to cisplatin resistance in SK-OV-3 ovarian cancer cells and thus may be a potential therapeutic target for the treatment of cisplatin-resistant ovarian cancer.

Catalponol enhances dopamine biosynthesis and protects against L-DOPA-induced cytotoxicity in PC12 cells.

The effects of catalponol (1) on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells were investigated. Catalponol at concentration ranges of 1-5 microM increased the intracellular levels of dopamine at 12-48 h. Catalponol at concentrations of up to 10 microM did not alter cell viability. Tyrosine hydroxylase (TH) activity was enhanced by 1 at 3 microM in a time-dependent manner, but aromatic L-amino acid decarboxylase activity was not. Catalponol also increased the intracellular levels of cyclic AMP and TH phosphorylation. In addition, catalponol at 3 microM associated with L-DOPA (20-50 microM) further enhanced the increases in dopamine levels induced by L-DOPA (50-100 microM) at 24 h. Catalponol at 2-5 microM inhibited L-DOPA (100-200 microM)-induced cytotoxicity at 48 h. These results suggest that 1 enhanced dopamine biosynthesis by inducing TH activity and protected against L-DOPA-induced cytotoxicity in PC12 cells, which was mediated by the increased levels of cyclic AMP.