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Recent advancements in ultra-sensitive detection, particularly the Aggregation Induced Emission (AIE) materials, have demonstrated a promising detection method due to their low cost, real-time detection, and simplicity of operation.

Supplementary Figure 5 from EGFR Signals Downregulate Tumor Suppressors miR-143 and miR-145 in Western Diet–Promoted Murine Colon Cancer: Role of G1 Regulators

Supplementary Figure 1 from EGFR Signals Downregulate Tumor Suppressors miR-143 and miR-145 in Western Diet–Promoted Murine Colon Cancer: Role of G1 Regulators

Figure legends for supplemental figures

Supplementary Figure 2 from EGFR Signals Downregulate Tumor Suppressors miR-143 and miR-145 in Western Diet–Promoted Murine Colon Cancer: Role of G1 Regulators

Colorectal cancer is a leading cause of cancer deaths. The renin-angiotensin system (RAS) is upregulated in colorectal cancer, and epidemiologic studies suggest RAS inhibitors reduce cancer risk. Because vitamin D (VD) receptor negatively regulates renin, we examined anticancer efficacy of VD and losartan (L), an angiotensin receptor blocker. Control Apc+/LoxP mice and tumor-forming Apc+/LoxP Cdx2P-Cre mice were randomized to unsupplemented Western diet (UN), or diets supplemented with VD, L, or VD+L, the latter to assess additive or synergistic effects. At 6 months, mice were killed. Plasma Ca2+, 25(OH)D3, 1α, 25(OH)2D3, renin, and angiotensin II (Ang II) were quantified. Colonic transcripts were assessed by qPCR and proteins by immunostaining and blotting. Cancer incidence and tumor burden were significantly lower in Cre+ VD and Cre+ L, but not in the Cre+ VD+L group. In Apc+/LoxP mice, VD increased plasma 1,25(OH)2D3 and colonic VDR. In Apc+/LoxP-Cdx2P-Cre mice, plasma renin and Ang II, and colonic tumor AT1, AT2, and Cyp27B1 were increased and VDR downregulated. L increased, whereas VD decreased plasma renin and Ang II in Cre+ mice. VD or L inhibited tumor development, while exerting differential effects on plasma VD metabolites and RAS components. We speculate that AT1 is critical for tumor development, whereas RAS suppression plays a key role in VD chemoprevention. When combined with L, VD no longer increases active VD and colonic VDR in Cre- mice nor suppresses renin and Ang II in Cre+ mice, likely contributing to lack of chemopreventive efficacy of the combination.

Epidermal growth factor receptors (EGFR) contribute to colonic tumorigenesis in experimental models of colon cancer. We previously showed that EGFR was also required for colonic tumor promotion by Western diet. The goal of this study was to identify EGFR-regulated microRNAs that contribute to diet-promoted colonic tumorigenesis. Murine colonic tumors from Egfrwt and hypomorphic Egfrwa2 mice were screened using micro RNA (miRNA) arrays and miR-143 and miR-145 changes confirmed by Northern, real-time PCR, and in situ analysis. Rodent and human sporadic and ulcerative colitis (UC)-associated colon cancers were examined for miR-143 and miR-145. Effects of EGFR on miR-143 and miR-145 expression were assessed in murine and human colonic cells and their putative targets examined in vitro and in vivo. miR-143 and miR-145 were readily detected in normal colonocytes and comparable in Egfrwt and Egfrwa2 mice. These miRNAs were downregulated in azoxymethane and inflammation-associated colonic tumors from Egfrwt mice but upregulated in Egfrwa2 tumors. They were also reduced in human sporadic and UC colon cancers. EGFR signals suppressed miR-143 and miR-145 in human and murine colonic cells. Transfected miR-143 and miR-145 inhibited HCT116 cell growth in vitro and in vivo and downregulated G1 regulators, K-Ras, MYC, CCND2, cdk6, and E2F3, putative or established targets of these miRNAs. miRNA targets Ras and MYC were increased in colonic tumors from Egfrwt but not Egfrwa2 mice fed a Western diet. EGFR suppresses miR-143 and miR-145 in murine models of colon cancer. Furthermore, Western diet unmasks the tumor suppressor roles of these EGFR-regulated miRNAs. Mol Cancer Res; 9(7); 960–75. ©2011 AACR.

Supplementary Figure 4 from EGFR Signals Downregulate Tumor Suppressors miR-143 and miR-145 in Western Diet–Promoted Murine Colon Cancer: Role of G1 Regulators

Supplementary Figure 3 from EGFR Signals Downregulate Tumor Suppressors miR-143 and miR-145 in Western Diet–Promoted Murine Colon Cancer: Role of G1 Regulators

Plasma calciums

Transcripts of Notch signaling components

Supplementary Methods

Note loss of ADAM17 staining in tumor epithelial cells in ADAM17Î"Î" tumors.

Supplemental Figure S3. Marimastat suppresses colonic EGFR signals. Mice received vehicle or marimastat and were fed WD. After 2 wks, colonic proteins measured by WB. A. Alzet pump. B. Protocol. C. EGFR signals. D. Quantitative levels (*p

Supplemental Methods and Figure Legends

Purpose: Epidermal growth factor receptors (EGFR) are required for tumor promotion by Western diet. The metalloprotease, ADAM17 activates EGFR by releasing pro-EGFR ligands. ADAM17 is regulated by G-protein–coupled receptors, including CXCR4. Here we investigated CXCR4–ADAM17 crosstalk and examined the role of ADAM17 in tumorigenesis.Experimental Design: We used CXCR4 inhibitor, AMD3100 and ADAM17 inhibitor, BMS566394 to assess CXCR4–ADAM17 crosstalk in colon cancer cells. We compared the expression of CXCR4 ligand, CXCL2, and ADAM17 in mice fed Western diet versus standard diet. Separately, mice were treated with marimastat, a broad-spectrum ADAM17 inhibitor, or AMD3100 to assess EGFR activation by ADAM17 and CXCR4. Using Apc-mutant Min mice, we investigated the effects of ADAM17/10 inhibitor INCB3619 on tumorigenesis. To assess the effects of colonocyte ADAM17, mice with ADAM17 conditional deletion were treated with azoxymethane (AOM). ADAM17 expression was also compared in colonocytes from primary human colon cancers and adjacent mucosa.Results: CXCL12 treatment activated colon cancer cell EGFR signals, and CXCR4 or ADAM17 blockade reduced this activation. In vivo, Western diet increased CXCL12 in stromal cells and TGFα in colonocytes. Marimastat or AMD3100 caused >50% reduction in EGFR signals (P < 0.05). In Min mice, INCB3619 reduced EGFR signals in adenomas and inhibited intestinal tumor multiplicity (P < 0.05). In the AOM model, colonocyte ADAM17 deletion reduced EGFR signals and colonic tumor development (P < 0.05). Finally, ADAM17 was upregulated >2.5-fold in human malignant colonocytes.Conclusions: ADAM17 is a Western diet–inducible enzyme activated by CXCL12–CXCR4 signaling, suggesting the pathway: Western diet→CXCL12→CXCR4→ADAM17→TGFα→EGFR. ADAM17 might serve as a druggable target in chemoprevention strategies. Clin Cancer Res; 23(2); 549–61. ©2016 AACR.

Supplemental Materials and Methods: real time PCR, immunostaining, Western blotting, ADAM17 activity; Supplemental references for supplemental Methods Supplemental Figure Legends; Supplemental Table 1: real time PCR primer sequences

Supplemental Figure S2. EGF induces Snail in HT29 colon cancer cells. Cells were plated on collagen-coated 6 well plates in 10% serum. Twenty-four hrs later cells were deprived of serum and treated with vehicle (phosphate-buffered saline), 10 ng/ml EGF or 40 ng/ml TGFβ. After 72 hrs cells were lysed and extracts probed for indicated proteins. Shown are blots representative of three independent platings.

Fig S1. BMS566394 inhibits EGFR signaling in CXCL12 treated HCT116 cells; Fig S2. Schema for CXCL12-CXCR4 transactivation of colon cancer cell EGFR. Shown in the figure are inhibitors or antibodies used in this study: AMD3100 blocks CXCR4; BMS566394 blocks ADAM17 and INCB3619 blocks ADAM17 and ADAM10; C225 antibodies block ligand binding to EGFR.

Purpose: We previously showed that EGF receptor (EGFR) promotes tumorigenesis in the azoxymethane/dextran sulfate sodium (AOM/DSS) model, whereas vitamin D suppresses tumorigenesis. EGFR–vitamin D receptor (VDR) interactions, however, are incompletely understood. Vitamin D inhibits the renin–angiotensin system (RAS), whereas RAS can activate EGFR. We aimed to elucidate EGFR–VDR cross-talk in colorectal carcinogenesis.Experimental Design: To examine VDR–RAS interactions, we treated Vdr+/+ and Vdr−/− mice with AOM/DSS. Effects of VDR on RAS and EGFR were examined by Western blotting, immunostaining, and real-time PCR. We also examined the effect of vitamin D3 on colonic RAS in Vdr+/+ mice. EGFR regulation of VDR was examined in hypomorphic EgfrWaved2 (Wa2) and Egfrwild-type mice. Angiotensin II (Ang II)–induced EGFR activation was studied in cell culture.Results:Vdr deletion significantly increased tumorigenesis, activated EGFR and β-catenin signaling, and increased colonic RAS components, including renin and angiotensin II. Dietary VD3 supplementation suppressed colonic renin. Renin was increased in human colon cancers. In studies in vitro, Ang II activated EGFR and stimulated colon cancer cell proliferation by an EGFR-mediated mechanism. Ang II also activated macrophages and colonic fibroblasts. Compared with tumors from EgfrWaved2 mice, tumors from Egfrwild-type mice showed upregulated Snail1, a suppressor of VDR, and downregulated VDR.Conclusions: VDR suppresses the colonic RAS cascade, limits EGFR signals, and inhibits colitis-associated tumorigenesis, whereas EGFR increases Snail1 and downregulates VDR in colonic tumors. Taken together, these results uncover a RAS-dependent mechanism mediating EGFR and VDR cross-talk in colon cancer. Clin Cancer Res; 20(22); 5848–59. ©2014 AACR.

GH3536 superalloy powder was prepared by the plasma spheroidization. The powder characteristics and effects of the plasma power on the percento spheroidization were studied.The phase and morphological properties of the powder were characterized by scanning electron microscope (SEM),Malven M4 particle size and shape analyzer and Leco ON736 oxygen-nitrogen analyzer.The results show that GH3536 fine spherical powder has favorable dispersity, smooth surface and high spheroidizing rate of 99%.The particle size distribution of the powder is narrowed,and the apparent density and tap density are significantly increased,which can meet the requirements of addictive manufacturing.

Types and recently collected samples of two Paxillus species namely P. rhytidophyllus and P. yunnanensis, originally described from southwestern China, were critically restudied based on morphology and molecular phylogenetic data of DNA sequences from the large subunit of the nuclear ribosomal RNA (nrLSU), the nuclear ribosomal internal transcribed spacer (ITS), and the translation elongation factor 1-α (tef1-α). The results showed that these two species belong to Boletinellus and Tricholomopsis, respectively. Thus, two new combinations, Boletinellus rhytidophyllus and Tricholomopsis yunnanensis are proposed. Boletinellus rhytidophyllus is characterized by a deeply decurrent and shallow hymenophore which is poroid-lamellate to alveolate, slightly thick-walled (0.6–1 μm) basidiospores, occasionally 2- to 4-spored basidia, rare or infrequent hymenial cystidia, and a trichodermal pileipellis. Tricholomopsis yunnanensis is characterized by a convex pileus densely covered by red-violet to red-brown fibrillose squamules, a yellowish stipe sparsely covered with red to red-brown fibrillose squamules, subglobose to broadly ellipsoid basidiospores, prominent large cheilocystidia measuring 60–195 × 11–39 μm, and a palisadic pileipellis. New descriptions and line drawings of these two species and their comparisons with allied taxa are presented.

Here, we report on the abundant formation of phenol and molecular hydrogen when benzene vapor was exposed to gas plasma generated by +5.5 kV corona discharge of water vapor in argon in the absence of oxygen. Systematic analysis using a series of isotopic standards (

Relationships between species of Retiboletus were inferred from morphology and nucleotide sequences of the translation elongation factor 1-α gene (tef1-α), the second largest subunit of RNA polymerase II (rpb2), the nuclear ribosomal large subunit (nrLSU), and the nuclear ribosomal internal transcribed spacer (ITS), based on Maximum Likelihood and Bayesian analyses. Our analyses indicated that the genus Retiboletus is divided into two major clades, with at least 10 species-level lineages in China. Accordingly, we describe a new subgenus, i.e. R. subg. Nigroretiboletorum, and a new species R. cyanescens of this subgenus. The newly proposed subgenus accommodates R. griseus and its allied taxa characterized by grayish white, white, or grayish pink hymenophores and white to gray context in pileus. Color pictures of fresh basidiomata and line drawings of the new species are provided, with a discussion concerning its taxonomic and phylogenetic relationships within the genus. In addition, a key to the species of Retiboletus in China is provided.

BackgroundRecently, there was an outbreak in China of the Omicron (B.1.1.529) variant, the corresponding clinical characteristics of Chinese children with the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were then reviewed and summarized retrospectively.MethodsFrom March to April 2022, a total of 134 children infected with the Omicron variant were included in the study. Data such as sex, age, clinical symptoms, laboratory examinations, and imaging features were collected for further analyses.ResultsHalf of the children were male and the median age was 5.67 years. The most SARS-CoV-2 Omicron variant was identified in mild (122, 91%), and the most three frequent symptoms were as cough (108, 80.6%), fever (75, 56%), and sore throat (38, 28.4%). Among age groups, no significant difference was observed in the distribution of symptoms, and no statistical difference was found in different clinical types among sex or age groups. Laboratory examinations revealed that white blood cells, neutrophils, and hemoglobin decreased; and monocytes, C-reactive protein (CRP), and aspartate aminotransferase (AST) increased. Further analyses showed that neutrophils, hemoglobin, CRP, and AST exhibited significant differences among age groups. Radiological abnormalities were found in nine cases, with small patchy high-density shadows. Of the 76 cured cases discharged from the hospital, the median hospital stay was 13 days (mean, 12 days).ConclusionsIn China, most children with Omicron SARS-CoV-2 infection have mild presentation. The findings of this study may help other districts improve the management of children with Omicron SARS-CoV-2 infection in China.

We report spinel-type CoFe2O4 nanocrystals (NCs) synthesized through facile hydrothermal growth and their attachment on a cage-like carbon (CC) for efficient and durable oxygen evolution/reduction reaction (OER/ORR) performance. As a catalyst, the so-constructed CoFe2O4 NCs show significantly higher OER performance than bare CoFe2O4 and CC, leading to an overpotential of 1.59 V for the OER at a current density of 10 mA/cm. Furthermore, CoFe2O4 NCs on CC electrodes also exhibit good ORR performance, which is comparable to Pt/C, significantly higher than that of bare carbon fiber paper, and acts as a bifunctional electrocatalyst. The CoFe2O4 NCs anchored on the CC electrodes exhibit remarkably long-term stability, which is evaluated by continuous cycling (over 5,000 cycles), without any morphological change, but preserving all the materials within the electrode. The results indicate that the CoFe2O4 NCs have a promising potential for efficient, cost-effective, and durable oxygen electrocatalysis at large scales using earth-abundant materials and low-cost fabrication processes.

Idiopathic pulmonary fibrosis (IPF) is a severe disorder leading to progressive and irreversible loss of pulmonary function. In this study we investigated the anti-fibrotic effect of vitamin D using a mouse model of IPF. Lung fibrosis was induced with bleomycin in vitamin D-sufficient and vitamin D-deficient C57BL/6 mice. We found that treatment with active vitamin D analog paricalcitol prevented mouse body weight loss and alleviated lung fibrosis, whereas vitamin D deficiency severely aggravated lung injury. At the molecular level, paricalcitol treatment suppressed the induction of fibrotic inducer TGF-β and extracellular matrix proteins α-SMA, collagen type I and fibronectin in the lung, whereas vitamin D deficiency exacerbated the induction of these proteins. Interestingly, bleomycin treatment activated the local renin–angiotensin system (RAS) in the lung, manifested by the induction of renin, angiotensinogen, angiotensin II and angiotensin receptor type 1 (AT1R). Paricalcitol treatment suppressed the induction of these RAS components, whereas vitamin D deficiency enhanced the activation of the lung RAS. We also showed that treatment of bleomycin-induced vitamin D-deficient mice with AT1R antagonist losartan relieved weight loss, substantially ameliorated lung fibrosis and markedly blocked TGF-β induction in the lung. Moreover, we demonstrated that in lung fibroblast cultures, TGF-β and angiotensin II synergistically induced TGF-β, AT1R, α-SMA, collagen type I and fibronectin, whereas 1,25-dihydroxyvitamin D markedly suppressed the induction of these fibrotic markers. Collectively, these observations strongly suggest that vitamin D mitigates lung fibrosis by blocking the activation of the lung RAS in this mouse model of IPF.

Graphene(Gr) reinforced copper matrix composites(Gr/Cu) were prepared by powder metallurgy process, and the effects of graphene content on microstructure and properties of the composites were investigated. The microstructure, density, hardness and electrical conductivity of the composites were analyzed by scanning electron microscopy (SEM), transmission electron microscopy (TEM), density measurement, hardness tester and conductivity meter. The results show that the interface bonding of the composite is good, there is no crack and no obvious interface reaction; there are a lot of dislocations and twins in Cu matrix. With the increase of graphene content, the density, heat capacity and thermal conductivity of the composites decrease, but the hardness increases first and then decreases.