Image-Guided Optical Coherence Tomography to Assess Structural Changes in Rodent Retinas.

Ocular diseases, such as age-related macular degeneration, glaucoma, retinitis pigmentosa, and uveitis, are always accompanied by retinal structural changes. These diseases affecting the fundus always exhibit typical abnormalities in certain cell types in the retina, including photoreceptor cells, retinal ganglion cells, cells in the retinal blood vessels, and cells in the choroidal vascular cells. Noninvasive, highly efficient, and adaptable imaging techniques are required for both clinical practice and basic research. Image-guided optical coherence tomography (OCT) satisfies these requirements because it combines fundus photography and high-resolution OCT, providing an accurate diagnosis of tiny lesions as well as important changes in the retinal architecture. This study details the procedures of data collection and data analysis for image-guided OCT and demonstrates its application in rodent models of choroidal neovascularization (CNV), optic nerve crush (ONC), light-induced retinal degeneration, and experimental autoimmune uveitis (EAU). This technique helps researchers in the eye field to identify rodent retinal structural changes conveniently, reliably, and tractably.

Loss of atm in Zebrafish as a Model of Ataxia-Telangiectasia Syndrome.

Ataxia-telangiectasia mutated (ATM) is a key DNA damage signaling kinase that is mutated in humans with ataxia-telangiectasia (A-T) syndrome. This syndrome is characterized by neurodegeneration, immune abnormality, cancer predisposition, and premature aging. To better understand the function of ATM in vivo, we engineered a viable zebrafish model with a mutated atm gene. Zebrafish atm loss-of-function mutants show characteristic features of A-T-like motor disturbance, including coordination disorders, immunodeficiency, and tumorigenesis. The immunological disorder of atm homozygote fish is linked to the developmental blockade of hematopoiesis, which occurs at the adulthood stage and results in a decrease in infection defense but, with little effect on wound healing. Malignant neoplasms found in atm mutant fish were mainly nerve sheath tumors and myeloid leukemia, which rarely occur in A-T patients or Atm-/- mice. These results underscore the importance of atm during immune cell development. This zebrafish A-T model opens up a pathway to an improved understanding of the molecular basis of tumorigenesis in A-T and the cellular role of atm.

Yeast-derived nanoparticles remodel the immunosuppressive microenvironment in tumor and tumor-draining lymph nodes to suppress tumor growth.

Microbe-based cancer immunotherapy has recently emerged as a hot topic for cancer treatment. However, serious limitations remain including infection associated side-effect and unsatisfactory outcomes in clinic trials. Here, we fabricate different sizes of nano-formulations derived from yeast cell wall (YCW NPs) by differential centrifugation. The induction of anticancer immunity of our formulations appears to inversely correlate with their size due to the ability to accumulate in tumor-draining lymph node (TDLN). Moreover, we use a percolation model to explain their distribution behavior toward TDLN. The abundance and functional orientation of each effector component are significantly improved not only in the microenvironment in tumor but also in the TDLN following small size YCW NPs treatment. In combination with programmed death-ligand 1 (PD-L1) blockade, we demonstrate anticancer efficiency in melanoma-challenged mice. We delineate potential strategy to target immunosuppressive microenvironment by microbe-based nanoparticles and highlight the role of size effect in microbe-based immune therapeutics.

Synthesis, characterization and antitumor properties of selenium nanoparticles coupling with ferulic acid.

Selenium nanoparticles (Se NPs) attract a lot of attention as potential cancer therapeutic agents. However, the antitumor activities of pure Se NPs are poor, and some modifiers are needed to enhance the activities. In the present study, we prepared Ferulic Acid (FA)-modified selenium nanoparticles in a facile synthetic approach. The obtained FA-Se NPs were characterized using transmission electron microscope (TEM), dynamic light scattering (DLS), ultraviolet-visible spectrophotometer (UV-VIS), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and Energy dispersive X-ray (EDX) spectroscopy. In vitro antitumor effects of FA, Se NPs and FA-Se NPs in HepG-2 cells were examined by methyl thiazolyl tetrazolium (MTT) assay. It showed that FA-Se NPs effectively inhibited the growth of HepG-2 cells with IC50 value of 11.57 ±â€¯3.6 µg/ml, while the value of Se NPs was >100 µg/ml. In addition, FA behaves no obvious antitumor effects at high concentrations up to 100 µg/ml. In order to investigate the antitumor mechanism of FA-Se NPs, fluorescence morphological examination and Annexin V-FITC/PI staining analysis were performed to observe the apoptosis of HepG-2 cells induced by FA-Se NPs. Meanwhile, mitochondrial membrane potential (MMP), intracellular reactive oxygen species (ROS) levels and caspase-3 and -9 activities were detected. The results revealed that FA-Se NPs induced intracellular ROS generation and MMP disruption by finally activating caspase-3/9 to trigger HepG-2 cells apoptosis through mitochondrial pathway. Further investigation on the interactions of FA-Se NPs with calf thymus DNA (ctDNA) indicated that the antitumor activities may be associated with the DNA-binding properties of FA-Se NPs.

Synthesis and cytotoxic activities of novel 4-methoxy-substituted and 5-methyl-substituted (3'S,4'S)-(-)-cis-khellactone derivatives that induce apoptosis via the intrinsic pathway.

This study deals with the design and synthesis of a series of novel 4-methoxy-substituted and 5-methyl-substituted (3'S,4'S)-(-)-cis-khellactones. The newly synthesized compounds were characterized by 1H nuclear magnetic resonance (NMR), 13C-NMR, mass spectrometry, and elemental analysis. All the derivatives were subjected to in vitro cytotoxicity screening against HEPG-2 (human liver carcinoma), SGC-7901 (human gastric carcinoma), and LS174T (human colon carcinoma), by using the MTT assay. The results revealed that several of the 4-methoxy-substituted compounds exhibited potent cytotoxicity. Among these, compound 12e showed the highest activity against cancer cells which 50% inhibitory concentration (IC50) values were in the range of 6.1-9.2 µM with low toxicity on normal human hepatocyte. Preliminary investigation of possible mechanisms of action of compound 12e against HEPG-2 cells indicated possible induction of apoptosis, as determined by morphological observations and Annexin V/propidium iodide (PI) double staining, in addition to apparent dissipation of mitochondrial membrane potential (MMP), as measured by 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide (JC-1) staining in combination with the activation of caspase-9 and caspase-3 by Western blot analysis. Overall, the data suggest that compound 12e may be a promising potential anti-cancer agent that could act primarily by inducing apoptosis through the mitochondria-mediated intrinsic pathway in human hepatoma cells.

Unconventional Behavior of Friction at the Nanoscale beyond Amontons' Law.

By means of a many-body van der Waals (vdW)-corrected density functional theory approach, the atomic-scale friction of a prototypical tip-substrate system consisting of an Si tip and a graphene substrate is studied. In a loading-sliding process, the tip-substrate distance is found to be essential for nanofrictional behavior, through determining the competition between vdW contributions and electronic contributions. As the tip approaches the substrate, this competition results in a smooth transition of normal forces from attraction to repulsion, and the friction coefficient in turn undergoes a sign change from negative to positive with possible giant magnitude and strong anisotropy. The loading-sliding process does not introduce any chemical modification of the underlying system. These findings reveal the boundary of validity of Amontons' law, unify negative and giant friction coefficients, rationalize the experimentally observed anisotropy of nanofriction, and are universal when vdW interactions are crucial, all of which are helpful to establish a comprehensive picture of nanofriction.

Direct observation of cyclic carbenium ions and their role in the catalytic cycle of the methanol-to-olefin reaction over chabazite zeolites.

Carbenium ions in zeolites: Two important carbenium ions have been observed for the first time under working conditions of the methanol-to-olefins (MTO) reaction over chabazite zeolites using (13) C NMR spectroscopy. Their crucial roles in the MTO reaction cycles have been demonstrated by combining experiments and theoretical calculations.

Coke formation and carbon atom economy of methanol-to-olefins reaction.

The methanol-to-olefins (MTO) process is becoming the most important non-petrochemical route for the production of light olefins from coal or natural gas. Maximizing the generation of the target products, ethene and propene, and minimizing the production of byproducts and coke, are major considerations in the efficient utilization of the carbon resource of methanol. In the present work, the heterogeneous catalytic conversion of methanol was evaluated by performing simultaneous measurements of the volatile products generated in the gas phase and the confined coke deposition in the catalyst phase. Real-time and complete reaction profiles were plotted to allow the comparison of carbon atom economy of methanol conversion over the catalyst SAPO-34 at varied reaction temperatures. The difference in carbon atom economy was closely related with the coke formation in the SAPO-34 catalyst. The confined coke compounds were determined. A new type of confined organics was found, and these accounted for the quick deactivation and low carbon atom economy under low-reaction-temperature conditions. Based on the carbon atom economy evaluation and coke species determination, optimized operating conditions for the MTO process are suggested; these conditions guarantee high conversion efficiency of methanol.

Generation of diamondoid hydrocarbons as confined compounds in SAPO-34 catalyst in the conversion of methanol.

Formation of adamantane hydrocarbons and their confinement in SAPO-34 caused the long induction period and the quick catalyst deactivation in methanol conversion. Via ship-in-a-bottle synthesis, adamantane and methyladamantanes could be produced from methanol conversion in the cage of 8-ring SAPO catalysts under very mild reaction conditions.

Observation of heptamethylbenzenium cation over SAPO-type molecular sieve DNL-6 under real MTO conversion conditions.

The heptamethylbenzenium cation (heptaMB(+)) has been speculated to be one of the most important active intermediates involved in the "hydrocarbon pool" mechanism of methanol-to-olefin (MTO) conversion. By the use of DNL-6, a newly synthesized SAPO-type molecular sieve with large cavities, heptaMB(+) has for the first time been directly observed during methanol conversion under real working conditions. (13)C-labeling experiments suggested that olefin formation mediated by heptaMB(+) mainly follows the side-chain mechanism.