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.     

Lithiophilic MXene-Guided Lithium Metal Nucleation and Growth Behavior

The positive effects of a lithiophilic substrate on the electrochemical performance of lithium metal anodes are confirmed in several reports, while the understanding of lithiophilic substrate-guided lithium metal nucleation and growth behavior is still insufficient. In this study, the effect of a lithiophilic surface on lithium metal nucleation and growth behaviors is investigated using a large-area Ti₃C₂T_x MXene substrate with a large number of oxygen and fluorine dual heteroatoms. The use of the MXene substrate results in a high lithium-ion concentration as well as the formation of uniform solid–electrolyte-interface (SEI) layers on the lithiophilic surface. The solid–solid interface (MXene-SEI layer) significantly affects the surface tension of the deposited lithium metal nuclei as well as the nucleation overpotential, resulting in the formation of uniformly dispersed lithium nanoparticles ( ≈ 10–20 nm in diameter) over the entire MXene surface. The primary lithium nanoparticles preferentially coalesce and agglomerate into larger secondary particles while retaining their primary particle shapes. Subsequently, they form close-packed structures, resulting in a dense metal layer composed of particle-by-particle microstructures. This distinctive lithium metal deposition behavior leads to highly reversible cycling performance with high Columbic efficiencies >  99.0% and long cycle lives of over 1000 cycles.     

Antioxidant and antimicrobial activities of fresh garlic and aged garlic by-products extracted with different solvents

Food Science and Biotechnology - This study aims to investigate antioxidative and antibacterial properties of fresh garlic (non-aged, NG) and aged garlic (AG) by-products extracted with distilled...     

Recent advances in finite element modeling of the human cervical spine

The human cervical spine is a complex structure that is the most frequently injured site among all spinal injuries. Therefore, understanding of the cervical spine injury and dysfunction, and also biomechanical response to external stimuli is important. Finite element (FE) modeling can help researchers to access the internal stresses and strains in the bones, ligaments and soft tissues more realistically, and it has been widely adopted for spine biomechanics research. Although in recent years numerous techniques have been developed, there are no recent literature reviews on FE models of the cervical spine. Our objective was to present recent advances in FE modeling of the human cervical spine in terms of component modeling, material properties, and validation procedures. Model applications and further development are also discussed. The integration of new technologies will allow us to generate more accurate and comprehensive model of the cervical spine, which can increase efficiency and model applicability. Finally, the FE modeling can help to facilitate diagnosis, treatment, and prevention technologies for cervical spine injuries.     

A Polyallylamine Anchored Amine‐Rich Laser‐Ablated Graphene Platform for Facile and Highly Selective Electrochemical IgG Biomarker Detection

Current immunosensors have an insufficient number of binding sites for the recognition of biomolecules, which leads to false positive or negative results. In this research, a facile, cost‐effective, disposable, and highly selective electrochemical immunosensing platform is developed based on cationic polyelectrolyte polyallylamine (PAAMI) anchored laser‐ablated graphene (LAG). Here, for the first time, PAAMI is introduced to stabilize LAG flakes, while retaining the intrinsic thermal and electronic properties of the substrate by noncovalent π–π interaction and electrostatic physical absorption. The sensing platform offers a suitable number of anchoring sites for the immobilized antibodies by providing ? NH₂ functional groups. The proper grafting of PAAMI is confirmed through X‐ray photoelectron spectroscopy and Raman spectroscopy. The immunosensing platform is applied to detect immunoglobulin (IgG) biomarkers as a proof of concept. Under optimized conditions, the sensing platform exhibits a linear range of 0.012–15 and 15–352 ng mL^?1 with a limit of detection of 6 pg mL^?1 for IgG detection with high selectivity. Based on the analysis, the developed immunosensing platform can be used for point‐of‐care detection of IgG in clinical diagnostic centers. Furthermore, the developed strategy is well suited for the detection of other cancer biomarkers after immobilizing the relevant antibodies.     

A priori risk-informed approach to ensure the compliance with discharge limits for liquid radioactive effluent to be discharged from APR 1400

ABSTRACT

In order to develop a methodology to guarantee the conformance to operational discharge limits for liquid effluent from a NPP at an early stage of design, a risk-informed approach was proposed and its applicability was verified for APR 1400. Existing methodology to calculate risk-based detection limit for a single radionuclide was improved by incorporating a new model to derive more realistic pathway dose factors. A new simple expression was also proposed to adjust risk-based detection limits for multiple radionuclides mixture if necessary. In addition, a new procedure to warrant the compliance with discharge limits by controlling detection limits of only a few principal radionuclides was established in accordance with risk-informed concept. Through case studies for APR 1400 to be commissioned at a hypothetical site, it was shown that calculated pathway dose factors are more realistic for majority of radionuclides. It also turns out that neither present detection limits nor unadjusted risk-based detection limits can be justified when the radionuclide composition is unknown, however further adjustment of detection limits or increasing additional dilution factor resolves the problem. Finally, ten principal radionuclides were identified and shown to be enough for liquid effluent control at APR 1400 from a risk-informed point of view.     

How latecomers catch up to leaders in high-energy physics as Big Science: transition from national system to international collaboration

Scientometrics - This study describes the increase of research productivity of latecomer countries (latecomers) in the high-energy physics (HEP) community by research strategies based on a national...