In Vivo Capture and Label-Free Detection of Early Metastatic Cells

Breast cancer is a leading cause of death for women, with mortality resulting from metastasis. Metastases are often detected once tumour cells affect the function of solid organs, with a high disease burden limiting effective treatment. Here we report a method for the early detection of metastasis using an implanted scaffold to recruit and capture metastatic cells in vivo, which achieves high cell densities and reduces the tumour burden within solid organs 10-fold. Recruitment is associated with infiltration of immune cells, which include Gr1hiCD11b+cells. We identify metastatic cells in the scaffold through a label-free detection system using inverse spectroscopic optical coherence tomography, which identifies changes to nanoscale tissue architecture associated with the presence of tumour cells. For patients at risk of recurrence, scaffold implantation following completion of primary therapy has the potential to identify metastatic disease at the earliest stage, enabling initiation of therapy while the disease burden is low

An Asymmetric Electrochemical System with Complementary Tunability in Hydrophobicity for Selective Separations of Organics

Copyright © 2019 American Chemical Society. Conducting polymers modified with redox-active moieties or amphiphilic surfactants are promising adsorbent materials for the separation of neutral organic species from water. We develop an asymmetric system combining a polyvinylferrocene-polypyrrole hybrid (PVF-PPy) and an amphiphilic surfactant dioctyl sulfosuccinate (AOT)-doped polypyrrole (PPy(AOT)) that have complementary hydrophobicity tunability in response to electrochemical modulations. Both materials are hydrophobic in their respective neutral states, exhibiting high affinities toward organics. Upon application of a mild potential to oxidize PVF-PPy and reduce PPy(AOT), these polymers can be simultaneously rendered hydrophilic, thereby driving desorption of organics and regeneration of the materials. The asymmetric system can be used in a cyclic fashion, through repeated electrical shorting of the two electrodes to program the capture of organics from a large volume of feed solution, and application of a potential (above 0.9 V) to stimulate the release of the adsorbed organics into a small volume of desorption solution. The asymmetric configuration has multiple benefits, including suppression of water parasitic reactions, high energetic efficiency, and selectivity for target organic species. Therefore, the electrode system has the potential to reduce the energy consumption in the mitigation of organic contaminants over conventional methods, with the additional ability to recover valuable organic products, opening up new possibilities for addressing the water-energy nexus

Risk factors associated with the presence of diabetes in Chinese communities in Beijing

Objective: To identify risk factors associated with the presence of diabetes. Methods: A diabetes survey was conducted in 2801 citizens aged 35-79 years living in 10 communities in Beijing, China. Participants were recruited by residents committees. 75 g oral glucose tolerance test was performed to define diabetes according to the WHO 1999 criteria. Logistic regression analysis was used to estimate odds ratios (OR) for diabetes. Results: The prevalence of diabetes and impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) was 24.2% and 20.4% in men, respectively and 19.4% and 19.0% in women, respectively. The multivariate adjusted OR (95% CI) corresponding to a one standard deviation increase in age (year) was 1.52 (1.25,1.86), waist circumference (cm) 1.35 (1.12,1.63), serum triglycerides (mmol/L) 1.29 (1.09,1.54) and high density lipoprotein cholesterol (mmol/L) 0.74 (0.61,0.91) in men and 2.03 (1.77,2.33),1.21 (1.06,1.38), 1.34 (1.21,1.49),0.74 (0.66,0.84) in women, respectively. For diabetes family history they were 2.46 (1.66,3.65) in men and 2.39 (1.84,3.10) in women, and for hypertension 1.14 (0.77,1.68) in men and 1.54 (1.18,2.01) in women. There were no significant associations between the presence of diabetes and occupation, education level, household income, leisure time physical activities, current smoking and drinking status. Conclusions: Age, diabetes family history, obesity, dyslipidemia and hypertension were all associated with the presence of diabetes in this study population. (C) 2009 Elsevier Ireland Ltd. All rights reserved.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000272521800012&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Endocrinology & MetabolismSCI(E)PubMed6ARTICLE3233-2388

Energetically efficient electrochemically tunable affinity separation using multicomponent polymeric nanostructures for water treatment

We describe a water treatment strategy, electrochemically tunable affinity separation (ETAS), which, unlike other previously developed electrochemical processes, targets uncharged organic pollutants in water. Key to achieving ETAS resides in the development of multicomponent polymeric nanostructures that simultaneously exhibit the following characteristics: an oxidation-state dependent affinity towards neutral organics, high porosity for sufficient adsorption capacity, and high conductivity to permit electrical manipulation. A prototype ETAS adsorbent composed of nanostructured binary polymeric surfaces that can undergo an electrically-induced hydrophilic–hydrophobic transition can provide programmable control of capture and release of neutral organics in a cyclic fashion. A quantitative energetic analysis of ETAS offers insights into the tradeoff between energy cost and separation extent through manipulation of electrical swing conditions. We also introduce a generalizable materials design approach to improve the separation degree and energetic efficiency simultaneously, and identify the critical factors responsible for such enhancement via redox electrode simulations and theoretical calculations of electron transfer kinetics. The effect of operation mode and multistage configuration on ETAS performance is examined, highlighting the practicality of ETAS and providing useful guidelines for its operation at large scale. The ETAS approach is energetically efficient, environmentally friendly, broadly applicable to a wide range of organic contaminants of various molecular structures, hydrophobicity and functionality, and opens up new avenues for addressing the urgent, global challenge of water purification and wastewater management

Matrix stiffness-upregulated LOXL2 promotes fibronectin production, MMP9 and CXCL12 expression and BMDCs recruitment to assist pre-metastatic niche formation

Abstract Background Higher matrix stiffness affects biological behavior of tumor cells, regulates tumor-associated gene/miRNA expression and stemness characteristic, and contributes to tumor invasion and metastasis. However, the linkage between higher matrix stiffness and pre-metastatic niche in hepatocellular carcinoma (HCC) is still largely unknown. Methods We comparatively analyzed the expressions of LOX family members in HCC cells grown on different stiffness substrates, and speculated that the secreted LOXL2 may mediate the linkage between higher matrix stiffness and pre-metastatic niche. Subsequently, we investigated the underlying molecular mechanism by which matrix stiffness induced LOXL2 expression in HCC cells, and explored the effects of LOXL2 on pre-metastatic niche formation, such as BMCs recruitment, fibronectin production, MMPs and CXCL12 expression, cell adhesion, etc. Results Higher matrix stiffness significantly upregulated LOXL2 expression in HCC cells, and activated JNK/c-JUN signaling pathway. Knockdown of integrin β1 and α5 suppressed LOXL2 expression and reversed the activation of above signaling pathway. Additionally, JNK inhibitor attenuated the expressions of p-JNK, p-c-JUN, c-JUN and LOXL2, and shRNA-c-JUN also decreased LOXL2 expression. CM-LV-LOXL2-OE and rhLOXL2 upregulated MMP9 expression and fibronectin production obviously in lung fibroblasts. Moreover, activation of Akt pathway contributed to LOXL2-induced fibronectin upregulation. LOXL2 in CM as chemoattractant increased motility and invasion of BMCs, implicating a significant role of LOXL2 in BMCs recruitment. Except that, CM-LV-LOXL2-OE as chemoattractant also increased the number of migrated HCC cells, and improved chemokine CXCL12 expression in lung fibroblasts. The number of HCC cells adhered to surface of lung fibroblasts treated with CM-LV-LOXL2-OE was remarkably higher than that of the control cells. These results indicated that the secreted LOXL2 facilitated the motility of HCC cells and strengthened CTCs settlement on the remodeled matrix “soil”. Conclusion Integrin β1/α5/JNK/c-JUN signaling pathway participates in higher matrix stiffness-induced LOXL2 upregulation in HCC cells. The secreted LOXL2 promotes fibronectin production, MMP9 and CXCL12 expression and BMDCs recruitment to assist pre-metastatic niche formation

Higher Matrix Stiffness Upregulates Osteopontin Expression in Hepatocellular Carcinoma Cells Mediated by Integrin β1/GSK3β/β-Catenin Signaling Pathway

<div><p>Increased stromal stiffness is associated with hepatocellular carcinoma (HCC) development and progression. However, the molecular mechanism by which matrix stiffness stimuli modulate HCC progress is largely unknown. In this study, we explored whether matrix stiffness-mediated effects on osteopontin (OPN) expression occur in HCC cells. We used a previously reported in vitro culture system with tunable matrix stiffness and found that OPN expression was remarkably upregulated in HCC cells with increasing matrix stiffness. Furthermore, the phosphorylation level of GSK3β and the expression of nuclear β-catenin were also elevated, indicating that GSK3β/β-catenin pathway might be involved in OPN regulation. Knock-down analysis of integrin β1 showed that OPN expression and p-GSK3β level were downregulated in HCC cells grown on high stiffness substrate compared with controls. Simultaneously, inhibition of GSK-3β led to accumulation of β-catenin in the cytoplasm and its enhanced nuclear translocation, further triggered the rescue of OPN expression, suggesting that the integrin β1/GSK-3β/β-catenin pathway is specifically activated for matrix stiffness-mediated OPN upregulation in HCC cells. Tissue microarray analysis confirmed that OPN expression was positively correlated with the expression of LOX and COL1. Taken together, high matrix stiffness upregulated OPN expression in HCC cells via the integrin β1/GSK-3β/β-catenin signaling pathway. It highlights a new insight into a pathway involving physical mechanical signal and biochemical signal molecules which contributes to OPN expression in HCC cells.</p></div

Higher matrix stiffness activates GSK3β/β-catenin signaling pathway mediated by integrin-β1 to modulate OPN expression.

<p>(A) Levels of P-GSK3β and β-catenin were attenuated in HCC cells infected with LV-INTGB1-RNAi on high stiffness substrate. Nuclear expression of β-catenin and TCF dropped sharply, and the expression of OPN also decreased significantly. (B) OPN expression Huh7 and Hep3B cells infected with LV-ITGB1-RNAi on high stiffness substrate. In each case, error bars represent SD, *p < 0.05, **p < 0.01, ***p<0.0001.</p