Purpose To propose and evaluate a novel multidimensional approach for imaging sub-voxel tissue compartments called Diffusion-Relaxation Correlation Spectroscopic Imaging (DR-CSI). Theory and Methods Multi-exponential modeling of MR diffusion or relaxation data is commonly used to infer the many different microscopic tissue compartments that contribute signal to macroscopic MR imaging voxels. However, multi-exponential estimation is known to be difficult and ill-posed. Observing that this ill-posedness is theoretically reduced in higher dimensions, DR-CSI uses a novel multidimensional imaging experiment that jointly encodes diffusion and relaxation information, and then uses a novel constrained reconstruction technique to generate a multidimensional diffusion-relaxation correlation spectrum for every voxel. The peaks of the multidimensional spectrum are expected to correspond to the distinct tissue microenvironments that are present within each macroscopic imaging voxel. Results Using numerical simulations, experiment data from a custom-built phantom, and experiment data from a mouse model of traumatic spinal cord injury, DR-CSI is demonstrated to provide substantially better multi-compartment resolving power compared to conventional diffusion- and relaxation-based methods. Conclusion The DR-CSI approach provides powerful new capabilities for resolving the different components of multi-compartment tissue models, and can be leveraged to significantly expand the insights provided by MRI in studies of tissue microstructure.

The circadian clock is closely related to human health, such as metabolic syndrome and cardiovascular disease. Our previous study revealed that irregular feeding induced abnormal lipid metabolism with disruption of the hepatic circadian clock. We hypothesized that breakfast skipping induces lipid abnormalities, such as adiposity, by altering the hepatic circadian oscillation of clock and lipid metabolism-related genes. Here, we established a delayed first active-phase meal (DFAM) protocol as a breakfast-skipping model. Briefly, rats were fed a high-fat diet during zeitgeber time (ZT) 12–24 in a control group and ZT 16–4 in the DFAM group. The DFAM group showed increased body weight gain and perirenal adipose tissue weight without a change in total food intake. The circadian oscillations of hepatic clock and de novo fatty acid synthesis genes were delayed by 2–4 h because of DFAM. The peaks of serum insulin, a synchronizer for the liver clock, bile acids, and non-esterified fatty acid (NEFA) were delayed by 4–6 h because of DFAM. Moreover, DFAM delayed the surge in body temperature by 4 h and may have contributed to the increase in body weight gain and adipose tissue weight because of decreased energy expenditure. These data indicated a potential molecular mechanism by which breakfast skipping induces abnormal lipid metabolism, which is related to the altered circadian oscillation of hepatic gene expression. The results also suggested that the delayed peaks of serum NEFA, bile acids, and insulin entrain the circadian rhythm of hepatic clock and lipid metabolism-related genes.

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Ever since the discovery of carbon nanotubes (CNTs), it has long been a challenging goal to create macroscopically ordered assemblies, or crystals, of CNTs that preserve the one-dimensional quantum properties of individual CNTs on a macroscopic scale.Recently, a simple and well-controlled method was reported for producing wafer-scale crystalline films of highly aligned and densely packed CNTs through spontaneous global alignment that occurs during vacuum filtration [Nat. Nanotechnol. 11, 633 (2016)].However, a full understanding of the mechanism of such global alignment has not been achieved. Here, we report results of a series of systematic experiments that demonstrate that the CNT alignment direction can be controlled by the surface morphology of the filter membrane used in the vacuum filtration process. More specifically, we found that the direction of parallel grooves pre-existing on the surface of the filter membrane dictates the direction of the resulting CNT alignment. Furthermore, we intentionally imprinted periodically spaced parallel grooves on a filter membranes using a diffraction grating, which successfully defined the direction of the global alignment of CNTs in a precise and reproducible manner.

Heat shock factor 1 (HSF1) is a transcription factor for heat shock proteins (HSPs) expression that enhances the survival of cancer cells exposed to various stresses. HSF1 knockout suppresses carcinogen-induced cancer induction in mice. Therefore, HSF1 is a promising therapeutic and chemopreventive target. We performed cell-based screening with a natural compound collection and identified fisetin, a dietary flavonoid, as a HSF1 inhibitor. Fisetin abolished heat shock-induced luciferase activity with an IC50 of 14 μM in HCT-116 cancer cells. The treatment of HCT-116 with fisetin inhibited proliferation with a GI50 of 23 μM. When the cells were exposed to heat shock in the presence of fisetin, the induction of HSF1 target proteins, such as HSP70, HSP27 and BAG3 (Bcl-2-associated athanogene domain 3), were inhibited. HSP70/BAG3 complexes protect cancer cells from apoptosis by stabilizing anti-apoptotic Bcl-2 family proteins. The downregulation of HSP70/BAG3 by fisetin significantly reduced the amounts of Bcl-2, Bcl-xL and Mcl-1 proteins, subsequently inducing apoptotic cell death. Chromatin immunoprecipitation assays showed that fisetin inhibited HSF1 activity by blocking the binding of HSF1 to the hsp70 promoter. Intraperitoneal treatment of nude mice with fisetin at 30mg/kg resulted in a 35.7% (P < 0.001) inhibition of tumor growth.

The organosolv ethanol process was adapted for converting hybrid poplar (Populus nigra L. × P. maximowiczii) into organosolv lignin and saccharide-derived chemicals, such as levulinic acid (LA), hydroxymethylfurfural (HMF), and furfural. The effect of process conditions (temperature, ethanol concentration, sulfuric acid dosage, and reaction time) on product yields was investigated using an experimental matrix designed with response surface methodology (RSM) and small Hartley composite design. The conditions ranged over 173−207 °C, 15−66 min, 2.3−5.7% H2SO4 (SA) on oven-dry wood (w/w), and 33−67% ethanol concentration (v/v). Results indicated that temperature, sulfuric acid loading, and their interaction had a significant effect on the yields of lignin and saccharide-derived chemicals. Comparative investigation of the organosolv process and acid process indicated that ethanol not only enhanced the delignification and production of organosolv lignin, but also improved the conversion yields of pentoses to furfural and hexoses to HMF and LA.

Epithelial-to-mesenchymal transition (EMT) is the first step in the development of the invasive and migratory properties of cancer metastasis. Since the transcriptional reprogramming of a number of genes occurs in EMT, the regulation of EMT transcription factors has been intensively investigated. EMT transcriptional factors are commonly classified by the direct or indirect repression of E-cadherin because one of hallmarks of EMT is the loss of E-cadherin. This facilitates the expression of genes for EMT, tumor invasion, and metastasis. The posttranslational modification of EMT transcriptional factors, such as Snail and Slug, directly regulates their functions, including their stability, nuclear localization, protein-protein interaction, and ubiquitination for the promotion or termination of EMT at the specific points. Here, we discuss how posttranslational modifications regulate gene expression in a dynamic and reversible manner by modifying upstream signaling pathways, focusing in particular on the posttranslational modifications of Snail, Slug, ZEB1, ZEB2, and TWIST1. This review demonstrates that EMT transcription factors regulate metastasis through their posttranslational modifications and that the flexibility and reversibility of EMT can be modified by phosphorylation.

A mesostructured TiO2–graphitic carbon (TiO2–gC) composite was synthesized through a simple and scalable one-step hydrothermal method, exhibiting high capacity, advanced rate capability and a very stable cycle life.