ROS-Mediated Anti-Tumor Effect of Coptidis Rhizoma against Human Hepatocellular Carcinoma Hep3B Cells and Xenografts

Coptidis Rhizoma is the dried rhizome from the Coptis chinensis Franch. that has been shown to have a number of beneficial pharmacological properties including antioxidant, anti-inflammatory, and anti-cancer effects. However, the anti-cancer effects of Coptidis Rhizoma on hepatocellular carcinoma (HCC) remain unclear. In this study, we investigated the anti-cancer properties of Coptidis Rhizoma ethanol extract (CR) in HCC Hep3B cells and in a xenograft mouse model. Our results showed that the CR significantly inhibited cell growth and induced apoptosis in Hep3B cells through increased expression of Bcl-2 associated x-protein (Bax) and cleavage of poly-ADP ribose polymerase (PARP), reduced expression of Bcl-2, and activated caspases. CR also increased the generation of intracellular reactive oxygen species (ROS), which caused a loss of mitochondrial membrane potential (MMP, ΔΨm) and activation of the mitochondria-mediated intrinsic apoptosis pathway. Moreover, N-acetylcysteine (NAC), a ROS inhibitor, markedly blocked the effects of CR on apoptotic pathways. CR also induced the expression of light chain 3 (LC3)-I/II, a key autophagy regulator, whereas CR-mediated autophagy was significantly suppressed by NAC. In addition, pre-treatment with NAC perfectly attenuated the inhibition of cell invasion and migration of CR-stimulated Hep3B cells. Furthermore, oral administration of CR suppressed Hep3B tumor growth in xenograft mice without toxicity, alterations to body weight, or changes in hematological and biochemical profiles. Taken together, our findings suggest that CR has anti-tumor effects that result from ROS generation, and may be a potential pharmacological intervention for HCC.     

E7766, a Macrocycle-Bridged Stimulator of Interferon Genes (STING) Agonist with Potent Pan-Genotypic Activity

A strategy for creating potent and pan-genotypic stimulator of interferon genes (STING) agonists is described. Locking a bioactive U-shaped conformation of cyclic dinucleotides by introducing a transannular macrocyclic bridge between the nucleic acid bases leads to a topologically novel macrocycle-bridged STING agonist (MBSA). In addition to substantially enhanced potency, the newly designed MBSAs, exemplified by clinical candidate E7766 , exhibit broad pan-genotypic activity in all major human STING variants. E7766 is shown to have potent antitumor activity with long lasting immune memory response in a mouse liver metastatic tumor model. Two complementary stereoselective synthetic routes to E7766 are also described.     

Effects of Electromagnetic Waves with LTE and 5G Bandwidth on the Skin Pigmentation In Vitro

With the rapid growth of wireless communication devices, the influences of electromagnetic fields (EMF) on human health are gathering increasing attention. Since the skin is the largest organ of the body and is located at the outermost layer, it is considered a major target for the health effects of EMF. Skin pigmentation represents one of the most frequent symptoms caused by various non-ionizing radiations, including ultraviolet radiation, blue light, infrared, and extremely low frequency (ELF). Here, we investigated the effects of EMFs with long-term evolution (LTE, 1.762 GHz) and 5G (28 GHz) bandwidth on skin pigmentation in vitro. Murine and Human melanoma cells (B16F10 and MNT-1) were exposed to either LTE or 5G for 4 h per day, which is considered the upper bound of average smartphone use time. It was shown that neither LTE nor 5G exposure induced significant effects on cell viability or pigmentation. The dendrites of MNT-1 were neither lengthened nor regressed after EMF exposure. Skin pigmentation effects of EMFs were further examined in the human keratinocyte cell line (MNT-1-HaCaT) co-culture system, which confirmed the absence of significant hyper-pigmentation effects of LTE and 5G EMFs. Lastly, MelanoDerm™, a 3D pigmented human epidermis model, was irradiated with LTE (1.762 GHz) or 5G (28 GHz), and image analysis and special staining were performed. No changes in the brightness of MelanoDerm™ tissues were observed in LTE- or 5G-exposed tissues, except for only minimal changes in the size of melanocytes. Collectively, these results imply that exposure to LTE and 5G EMFs may not affect melanin synthesis or skin pigmentation under normal smartphone use condition.     

Activation of the Complement System on Human Endothelial Cells by Urban Particulate Matter Triggers Inflammation-Related Protein Production

Exposure to particulate matter (PM) is becoming a major global health issue. The amount and time of exposure to PM are known to be closely associated with cardiovascular diseases. However, the mechanism through which PM affects the vascular system is still not clear. Endothelial cells line the interior surface of blood vessels and actively interact with plasma proteins, including the complement system. Unregulated complement activation caused by invaders, such as pollutants, may promote endothelial inflammation. In the present study, we sought to investigate whether urban PM (UPM) acts on the endothelial environment via the complement system. UPM-treated human endothelial cells with normal human serum showed the deposition of membrane attack complexes (MACs) on the cell surface via the alternative pathway of the complement system. Despite the formation of MACs, cell death was not observed, and cell proliferation was increased in UPM-mediated complement activation. Furthermore, complement activation on endothelial cells stimulated the production of inflammation-related proteins. Our results revealed that UPM could activate the complement system in human endothelial cells and that complement activation regulated inflammatory reaction in microenvironment. These findings provide clues with regard to the role of the complement system in pathophysiologic events of vascular disease elicited by air pollution.     

Magnetically Guidable Proteinaceous Adhesive Microbots for Targeted Locoregional Therapeutics Delivery in the Highly Dynamic Environment of the Esophagus

The esophagus is a tubular-shaped muscular organ where swallowed fluids and muscular contractions constitute a highly dynamic environment. The turbulent, coordinated processes that occur through the oropharyngeal conduit can often compromise targeted administration of therapeutic drugs to a lesion, significantly reducing therapeutic efficacy. Here, magnetically guidable drug vehicles capable of strongly adhering to target sites using a bioengineered mussel adhesive protein (MAP) to achieve localized delivery of therapeutic drugs against the hydrodynamic physiological conditions are proposed. A suite of highly uniform microparticles embedded with iron oxide (IO) nanoparticles (MAP@IO MPs) is microfluidically fabricated using the genipin-mediated covalent cross-linking of bioengineered MAP. The MAP@IO MPs are successfully targeted to a specific region and prolongedly retained in the tubular-structured passageway. In particular, orally administered MAP@IO MPs are effectively captured in the esophagus in vivo in a magnetically guidable manner. Moreover, doxorubicin (DOX)-loaded MAP@IO MPs exhibit a sustainable DOX release profile, effective anticancer therapeutic activity, and excellent biocompatibility. Thus, the magnetically guidable locomotion and robust underwater adhesive properties of the proteinaceous soft microbots can provide an intelligent modular approach for targeted locoregional therapeutics delivery to a specific lesion site in dynamic fluid-associated tubular organs such as the esophagus.     

On the Catalytic Activity of Sn Monomers and Dimers at Graphene Edges and the Synchronized Edge Dependence of Diffusing Atoms in Sn Dimers

In this study, in situ transmission electron microscopy is performed to study the interaction between single (monomer) and paired (dimer) Sn atoms at graphene edges. The results reveal that a single Sn atom can catalyze both the growth and etching of graphene by the addition and removal of C atoms respectively. Additionally, the frequencies of the energetically favorable configurations of an Sn atom at a graphene edge, calculated using density functional theory calculations, are compared with experimental observations and are found to be in good agreement. The remarkable dynamic processes of binary atoms (dimers) are also investigated and is the first such study to the best of the knowledge. Dimer diffusion along the graphene edges depends on the graphene edge termination. Atom pairs (dimers) involving an armchair configuration tend to diffuse with a synchronized shuffling (step-wise shift) action, while dimer diffusion at zigzag edge terminations show a strong propensity to collapse the dimer with each atom diffusing in opposite directions (monomer formation). Moreover, the data reveals the role of C feedstock availability on the choice a single Sn atom makes in terms of graphene growth or etching. This study advances the understanding single atom catalytic activity at graphene edges.     

The Effect of Interface Cracks on the Electrical Performance of Solar Cells

Among a variety of solar cell types, thin-film solar cells have been rigorously investigated as cost-effective and efficient solar cells. In many cases, flexible solar cells are also fabricated as thin films and undergo frequent stress due to the rolling and bending modes of applications. These frequent motions result in crack initiation and propagation (including delamination) in the thin-film solar cells, which cause degradation in efficiency. Reliability evaluation of solar cells is essential for developing a new type of solar cell. In this paper, we investigated the effect of layer delamination and grain boundary crack on 3D thin-film solar cells. We used finite element method simulation for modeling of both electrical performance and cracked structure of 3D solar cells. Through simulations, we quantitatively calculated the effect of delamination length on 3D copper indium gallium diselenide (CIGS) solar cell performance. Moreover, it was confirmed that the grain boundary of CIGS could improve the solar cell performance and that grain boundary cracks could decrease cell performance by altering the open circuit voltage. In this paper, the investigated material is a CIGS solar cell, but our method can be applied to general polycrystalline solar cells.     

Variables Applicable to Benchmarking of Tap-Hole Life-Cycle Management Practices in Coke-Bed-Based Ferroalloy Production

Benchmarking is a tool available to furnace operators to evaluate their tap-hole life-cycle management practices against those of their peers. It allows furnace operators to challenge their own practices in order to increase furnace utilization. To facilitate the benchmarking process, it is necessary to define the variables to be considered and how they relate to one another. This article develops, from the literature and industry interviews, a holistic conceptualization of the variables that form part of tap-hole lifecycle management and performance. Specifically, the article focuses on the variables related to coke-bed-based processes (FeCr, SiMn, and HCFeMn) applying SAF technology of circular design.     

Removal of Antimony and Bismuth from Copper Electrorefining Electrolyte: Part II—An Investigation of Two Proprietary Solvent Extraction Extractants

Antimony and bismuth recovery from copper electrorefining electrolyte could reduce the impacts of these problem elements and produce a new primary source for them. Two proprietary phosphonic acid ester extractants were examined (REX-1 and REX-2) for the removal of antimony and bismuth from copper electrorefining electrolytes. Experimentation included shakeout and break tests to determine the basic parameters for the extractants in terms of maximum loading, break times, and extraction and stripping efficiency. Five permutations of extractant mixtures (100 wt.% REX-1 and 25 wt.%, 50 wt.%, 75 wt.% and 100 wt.% REX-2) were studied. It was determined that REX-2 was able to extract Sb and Bi from the electrolyte, but required some mixture with REX-1 to better facilitate stripping with 400 g/L sulfuric acid. The laboratory electrorefining electrolyte containing glue had faster disengagement times than a synthetic solution without glue.     

Measurement of Young’s Modulus and Poisson’s Ratio of Thermal Barrier Coating Based on Bending of Three-Layered Plate

Thermal barrier coatings (TBCs) are used to protect the hot sections of gas turbine engines and airplane engines. A TBC system comprises a substrate, bond coat, and TBC topcoat. The development of an accurate method for determining the Young’s modulus and Poisson’s ratio of TBC using a multilayered specimen is of importance. In this study, we applied the bending theory of a laminated plate to a three-layered material and proposed models to determine the Young’s modulus and Poisson’s ratio of the TBC layer using the bending strain of the TBC system specimen. Three methods were developed by utilizing (i) the coating biaxial strain, (ii) substrate biaxial strain, or (iii) coating and substrate biaxial strains. Subsequently, we determined appropriate dimensions of the specimen and span by using three-dimensional finite element analysis, and numerically verified the usefulness of the three proposed methods. However, the Young’s modulus and Poisson’s ratio determined using the multilayered specimen with a substrate are sensitive to experimental errors. Therefore, we evaluated the sensitivity of the three proposed methods to experimental error, and we determined the most insensitive method among them. Finally, we experimentally demonstrated the usefulness of this method.