Multi‐Channel Lanthanide Nanocomposites for Customized Synergistic Treatment of Orthotopic Multi‐Tumor Cases

Simultaneous photothermal ablation of multiple tumors is limited by unpredictable photo-induced apoptosis, caused by individual intratumoral differences. Here, a multi-channel lanthanide nanocomposite was used to achieve tailored synergistic treatment of multiple subcutaneous orthotopic tumors under non-uniform whole-body infrared irradiation prescription. The nanocomposite reduces intratumoral glutathione by simultaneously activating the fluorescence and photothermal channels. The fluorescence provides individual information on different tumors, allowing customized prescriptions to be made. This enables optimal induction of hyperthermia and dosage of chemo drugs, to ensure treatment efficacy, while avoiding overtherapy. With an accessional therapeutic laser system, customized synergistic treatment of subcutaneous orthotopic cancer cases with multiple tumors is possible with both high efficacy and minimized side effects

LQTS Gene LOVD Database

The Long QT Syndrome (LQTS) is a group of genetically heterogeneous disorders that predisposes young individuals to ventricular arrhythmias and sudden death. LQTS is mainly caused by mutations in genes encoding subunits of cardiac ion channels (KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2). Many other genes involved in LQTS have been described recently (KCNJ2, AKAP9, ANK2, CACNA1C, SCNA4B, SNTA1, and CAV3). We created an online database (http://www.genomed.org/LOVD/introduction.html) that provides information on variants in LQTS-associated genes. As of February 2010, the database contains 1738 unique variants in 12 genes. A total of 950 variants are considered pathogenic, 265 are possible pathogenic, 131 are unknown/unclassified, and 292 have no known pathogenicity. In addition to these mutations collected from published literature, we also submitted information on gene variants, including one possible novel pathogenic mutation in the KCNH2 splice site found in ten Chinese families with documented arrhythmias. The remote user is able to search the data and is encouraged to submit new mutations into the database. The LQTS database will become a powerful tool for both researchers and clinicians. © 2010 Wiley-Liss, Inc

NHERF1, a novel GPER associated protein, increases stability and activation of GPER in ER-positive breast cancer

G protein-coupled estrogen receptor (GPER) plays an important role in mediating the effects of estradiol. High levels of GPER have been implicated to associate with the malignant progress of invasive breast cancer (IBC). However, the mechanisms by which GPER protein levels were regulated remain unclear. In this study, PDZ protein Na+/H+ exchanger regulatory factor (NHERF1) was found to interact with GPER in breast cancer cells. This interaction was mediated by the PDZ2 domain of NHERF1 and the carboxyl terminal PDZ binding motif of GPER. NHERF1 was demonstrated to facilitate GPER expression at post-transcriptional level and improve GPER protein stability by inhibiting the receptor degradation via ubiquitin-proteasome pathway in a GPER/NHERF1 interaction-dependent manner. In addition, GPER protein levels are positively associated with NHERF1 protein levels in a panel of estrogen receptor (ER)-positive breast cancer cells. Furthermore, analysis of clinical IBC data from The Cancer Genome Atlas (TCGA) showed no significant difference in GPER mRNA levels between ER-positive IBC and normal breast tissues. However, gene set enrichment analysis (GSEA) showed that GPER signaling is ultra-activated in ER-positive IBC when compared with normal and its activation is positively associated with NHERF1 mRNA levels. Taken together, our findings identify NHERF1 as a new binding partner for GPER and its overexpression promotes protein stability and activation of GPER in ER-positive IBC. Our data indicate that regulation of GPER stability by NHERF1 may contribute to GPER-mediated carcinogenesis in ER-positive IBC

Fast Green FCF Attenuates Lipopolysaccharide-Induced Depressive-Like Behavior and Downregulates TLR4/Myd88/NF-κB Signal Pathway in the Mouse Hippocampus

Depression is a common neuropsychiatric disorder and new anti-depressive treatments are still in urgent demand. Fast Green FCF, a safe biocompatible color additive, has been suggested to mitigate chronic pain. However, Fast green FCF’s effect on depression is unknown. We aimed to investigate Fast green FCF’s effect on lipopolysaccharide (LPS)-induced depressive-like behavior and the underlying mechanisms. Pretreatment of Fast green FCF (100 mg/kg, i.p. daily for 7 days) alleviated depressive-like behavior in LPS-treated mice. Fast green FCF suppressed the LPS-induced microglial and astrocyte activation in the hippocampus. Fast green FCF decreased the mRNA and protein levels of Toll-like receptor 4 (TLR4) and Myeloid differentiation primary response 88 (Myd88) and suppressed the phosphorylation of nuclear factor-κB (NF-κB) in the hippocampus of LPS-treated mice. Fast green FCF also downregulated hippocampal tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, but did not alter the level of the brain-derived neurotrophic factor (BDNF) in the hippocampus of LPS-treated mice. The molecular docking simulation predicts that Fast green FCF may interact with TLR4 and interrupt the formation of the TLR4-MD2 complex. In conclusion, the anti-depressive action of Fast green FCF in LPS-treated mice may involve the suppression of neuroinflammation and the downregulation of TLR4/Myd88/NF-κB signal pathway in mouse hippocampus. Our findings indicate the potential of Fast green FCF for controlling depressive symptoms

Identification of microRNAs specific for epithelial cell adhesion molecule-positive tumor cells in hepatocellular carcinoma: HEPATOLOGY, Vol. XX, No. X, 2015

Therapies that target cancer stem cells (CSCs) hold promise in eliminating cancer burden. However, normal stem cells are likely to be targeted due to their similarities to CSCs. It is established that EpCAM is a biomarker for normal hepatic stem cells and EpCAM+AFP+ hepatocellular carcinoma (HCC) cells have enriched hepatic CSCs. We sought to determine if specific miRNAs exist in hepatic CSCs that are not expressed in normal hepatic stem cells. We performed a pair-wised comparison of the miRNA transcriptome of EpCAM+ and corresponding EpCAM− cells isolated from two primary HCC specimens, as well as from two fetal livers and three healthy adult liver donors via small RNA deep sequencing. We found that miR-150, miR-155 and miR-223 were preferentially highly expressed in EpCAM+ HCC cells, which was further validated. Their gene surrogates, identified using miRNA and mRNA profiling in a cohort of 292 HCC patients, were associated with patient prognosis. We further demonstrated that miR-155 was highly expressed in EpCAM+ HCC cells compared to corresponding EpCAM− HCC cells, fetal livers with enriched normal hepatic progenitors, and normal adult livers with enriched mature hepatocytes. Suppressing miR-155 resulted in a decreased EpCAM+ fraction in HCC cells and reduced HCC cell colony formation, migration and invasion in vitro. The reduced levels of identified miR-155 targets predicted the shortened overall survival and time to recurrence of HCC patients. Conclusion: MiR-155 was highly elevated in EpCAM+ HCC cells and might serve as a molecular target to eradicate the EpCAM+ CSC population in human HCCs

Low-Temperature, Highly Selective, Gas-Phase Oxidation of Benzyl Alcohol over Mesoporous K-Cu-TiO2 with Stable Copper(I) Oxidation State

通讯作者地址: Fan, J (通讯作者), Zhejiang Univ, Dept Chem, Key Lab Appl Chem Zhejiang Prov, Hangzhou 310027, Zhejiang Peoples R China 地址: 1. Zhejiang Univ, Dept Chem, Key Lab Appl Chem Zhejiang Prov, Hangzhou 310027, Zhejiang Peoples R China 2. Univ Calif Santa Barbara, Dept Chem & Biochem, Santa Barbara, CA 93106 USA 电子邮件地址: [email protected], [email protected] newly developed mesoporous mixed metal oxide (K-Cu-TiO2) catalyst is capable of highly selective, gas-phase benzyl alcoholbenzaldehyde transformation at excellent yields (>99%) under surprisingly low temperatures (203 degrees C, bp of benzyl alcohol). The tow-temperature reaction conditions and integration of K and Cu(I) components into the TiO2 matrix are of vital importance for the stabilization of an active Cu(I) oxidation state and resultant stable, excellent catalytic performance.National Science Foundations of China 20873122 J0830413 National Science Foundation DMR 02-3372

Application Research of Frequency-Modulated Continuous-Wave Displacement Sensor Based on Zero-Crossing Phase Detecting Algorithm

Frequency-modulated continuous-wave (FMCW) interference, as a new technology of laser interferometry, has the advantages of length traceability, large range, high accuracy, simple structure, and optical fiber transmission. Based on the formula of FMCW laser interference displacement, a zero-crossing phase detection algorithm is proposed, which can accurately calculate the initial phase of a cosine signal in a modulation period, and it is successfully applied to the contact laser interference displacement sensor. The experimental results show that the FMCW technology based on the zero-crossing phase detection algorithm can achieve the technical specifications of the contact displacement sensor with a measurement range greater than 15 mm and the standard deviation is less than 0.01 μm. The conversion of noncontact measurement to contact measurement can realize the direct measurement of workpieces with complex surface conditions on the production line, breaking through the limitation of optical measurement and expanding the application of optical fiber interferometry