No abstract

A growing body of evidence implicates macrophage migration inhibitory factor (MIF) in tumorigenesis and metastasis. In this study, we investigated whether MIF expression was associated with clinicopathologic features of colorectal carcinoma (CRC), especially in tumors with hepatic metastasis, and whether neutralization of endogenous MIF using anti-MIF therapeutics would inhibit tumor growth and/or decrease the frequency of colorectal hepatic metastases in a mouse colon carcinoma model. The concentration of serum MIF was positively correlated with an increased risk of hepatic metastasis in human patients with CRC (R = 1.25, 95% confidence internal = 1.02-1.52, P = 0.03). MIF was also dramatically upregulated in human colorectal tissue, with 20-40 times as many MIF-positive cells found in the mucosa of patients with CRC than in normal tissue (P < 0.001 ANOVA). Moreover, in those patients with metastatic colorectal cancer in the liver, MIF-positive cells were similarly increased in the diseased hepatic tissue. This increased MIF expression was restricted to diseased tissue and not found in areas of the liver with normal morphology. In subsequent in vitro experiments, we found that addition of recombinant MIF to colonic cell lines significantly increased their invasive properties and the expression of several genes (for example, matrix metalloproteinase 9 and vascular endothelial growth factor) known to be upregulated in cancerous tissue. Finally, we treated mice that had been given CT26 colon carcinoma cell transplants with anti-MIF therapeutics-either the MIF-specific inhibitor ISO-1 or neutralizing anti-MIF antibodies-and observed a significant reduction in tumor burden relative to vehicle-treated animals. Taken together, these data demonstrate that MIF expression was not only correlated with the presence of colorectal cancer but also may play a direct role in cancer development.

No abstract

Solid-state electrolyte (SSE) is promising for application in all-solid-state lithium metal batteries because of its reliable safety and longevity. The failure of SSE to suppress dendrite formation of Li metal anodes has been conventionally explained by uneven Li deposition at Li/SSE interfaces and its subsequent dendritic growth. While Li deposition within SSE has been recently proposed as another key cause for SSE failure, little is known regarding the Li growth details inside the SSE itself. In this work, we performed in situ microscopic observation of Li deposition inside the SSE and obtained visualized evidence regarding the dynamic process of Li dendrite formation and growth. Li is seen to directly nucleate and propagate within the SSE, leading to its structural cracking. Such behavior should be caused by the presence of P- and S-based crystalline defects in Li3PS4 SSE, which is consistent with the cryo-transmission electron microscopy observations and theoretical calculations. This observation provides important insights into the growth mechanisms of Li dendrites within a working lithium battery.

Atropisomerism is one of the basic concepts in stereochemistry. Chiral crystals of stereochemically labile atropisomers that originated from Mirror Symmetry Breaking (MSB) can only be characterized by solid-state chiroptical techniques. Herein, solid-state circular dichroism and UV-Vis spectra of six atropisomeric compounds (most of them were obtained from MSB) have been studied. A concentration effect including a wavelength shift and inverse concentration-dependence has been found and preliminarily explained by the absorption flattening effect, scattering effect and the torsion in the molecular structures.National Natural Science Foundation of China[20973136, 20974028, 20732004]; Natural Science Foundation of Fujian Province[2010J01048

Dramatic growth of lithium (Li) dendrite and structural deterioration of LiCoO2 (LCO) lead to rapid failure of a high-voltage Li∥LCO battery. The nitrile group (−CN) is beneficial to maintain the integrity of the LCO lattice due to its strong affiliation to Co ions, whereas the −CN bond is incompatible with the Li metal anode, leading to form a deleterious solid electrolyte interphase (SEI) film. Herein, a dual-functional electrolyte additive potassium selenocyanate (KSeCN) is introduced to construct stable and dense SEI/cathode electrolyte interphase (CEI) films by synergistic effects with −Se and −CN groups, resulting in uniform Li deposition and a stabilized LCO lattice during cycling. With a trace amount of KSeCN (0.1 wt %) in conventional carbonated electrolyte, the Li∥LCO battery exhibits promoted cycling performance at high charge cutoff 4.6 V. This work provides a strategic guidance for rational design of electrolyte to construct stable SEI and CEI films, to achieve a high-energy-density Li∥LCO battery with great performance.

Background Traumatic brain injury (TBI) remains one of the main causes for disability and death worldwide. While the primary mechanical injury cannot be avoided, the prevention of secondary injury is the focus of TBI research. Present study aimed to elucidate the effects and mechanisms of S100B and its receptor RAGE on mediating secondary injury after TBI. Methods This study established TBI animal model by fluid percussion injury in rats, cell model by stretch-injured in astrocytes, and endothelial injury model with conditioned medium stimulation. Pharmacological intervention was applied to interfere the activities of S100B/RAGE/ADAM17 signaling pathway, respectively. The expressions or contents of S100B, RAGE, syndecan-1 and ADAM17 in brain and serum, as well as in cultured cells and medium, were detected by western blot. The distribution of relative molecules was observed with immunofluorescence. Results We found that TBI could activate the release of S100B, mostly from astrocytes, and S100B and RAGE could mutually regulate their expression and activation. Most importantly, present study revealed an obvious increase of syndecan-1 in rat serum or in endothelial cultured medium after injury, and a significant decrease in tissue and in cultured endothelial cells, indicating TBI-induced shedding of endothelial glycocalyx. The data further proved that the activation of S100B/RAGE signaling could promote the shedding of endothelial glycocalyx by enhancing the expression, translocation and activity of ADAM17, an important sheddase, in endothelial cells. The damage of endothelial glycocalyx consequently aggravated blood brain barrier (BBB) dysfunction and systemic vascular hyper-permeability, overall resulting in secondary brain and lung injury. Conclusions TBI triggers the activation of S100B/RAGE signal pathway. The regulation S100B/RAGE on ADAM17 expression, translocation and activation further promotes the shedding of endothelial glycocalyx, aggravates the dysfunction of BBB, and increases the vascular permeability, leading to secondary brain and lung injury. Present study may open a new corridor for the more in-depth understanding of the molecular processes responsible for cerebral and systemic vascular barrier impairment and secondary injury after TBI.

No abstract