Pseudo-3D Topological Alignments Regulate Mechanotransduction and Maturation of Smooth Muscle Cells.

Smooth muscle cells (SMCs) sense and respond to mechanical stimuli in their extracellular microenvironments (ECMs), playing a crucial role in muscle tissue engineering. Increasing evidence from topological cues-mediated mechanotransduction of SMCs in ECMs has suggested some potential underlying mechanisms of how SMC functions and maturation are regulated by their mechanosensing leading to transduction. However, how the expression of yes-associated protein 1 (YAP) influences the phenotypic shift from synthetic to contractile is still controversial. Here, pseudo-3D topological alignments mimicking native muscle tissues are generated using laser-cutter engraving to explore the influence of topological cues on SMC mechanotransduction and maturation. The analysis of topological cue-mediated mechanotransduction and maturation marker expression revealed YAP is involved in mechanotransduction for SMCs cultured on cross-patterned substrates in the presence of cell-cell interactions. Moreover, these SMCs with YAP-linked mechanosensing showed higher expression of calponin, indicating a shift toward contractile phenotypes in vitro and in vivo. Furthermore, it showed skeletal muscle cells has different mechanosensing and maturation mechanisms compared to SMCs, revealing muscle type-dependent different sensing of topological cues, and converting into maturation-associated signaling cascades. This study provides insights into the regulation of SMC mechanotransduction and maturation by topological cues, suggesting the involvement of YAP-linked signaling pathways in this process.

The beneficial potential of ginseng for menopause.

Korean Red Ginseng (KRG) has long been used not only as a food supplement but also as a treatment for various diseases. Ginseng originated in South Korea, which later spread to China and Japan, has a wide range of pharmacological activities including immune, endocrine, cardiovascular, and central nervous system effects. KRG is produced by repetitions of steaming and drying of ginseng to extend preservation. During this steaming process, the components of ginseng undergo physio-chemical changes forming a variety of potential active constituents including ginsenoside-Rg3, a unique compound in KRG. Pandemic Coronavirus disease 2019 (COVID-19), has affected both men and women differentially. In particular, women were more vulnerable to COVID-related distress which in turn could aggravate menopause-related disturbances. Complementary and alternative medicinal plants could have aided middle-aged women for several menopause-related symptoms during and post COVID-19 pandemic. This review aimed to explore the beneficial effects of KRG on menopausal symptoms and gynecological cancer.

Unlearned adaptive responses to heterospecific referential alarm calls in two bird species from separate evolutionary lineages.

The interspecific responses to alarm signals may be based on unlearned mechanisms but research is often constrained by the difficulties in differentiating between unlearned and learned responses in natural situations. In a field study of two Paridae species, Parus minor and Sittiparus varius, who originated from a common ancestor 8 million years ago, we found a considerable degree of between-species overlap in acoustic properties of referential snake-alarm calls. Playback of these calls triggered unlearned adaptive fledging behavior in conspecific and heterospecific naive nestlings, suggesting a between-species overlap in the hypothetical unlearned neural templates involved in nestlings' reactions to alarm calls in both species. This suggests that similar calls and similar unlearned sensitivity might have been present in the common ancestor of the two species, and possibly in the ancestor of the whole family Paridae that originated 10-15 million years ago in Asian regions rich in snakes.

Multiresponsive 3D Structured PVDF Cube Switches for Security Systems Using Piezoelectric Anisotropy.

Advancements in flexible electronics using piezoelectric materials have paved the way for numerous applications. In this study, we suggest a three-dimensional (3D) structured poly(vinylidene fluoride) (PVDF) film cube switch to maximize piezoelectric anisotropy and flexibility. Unlike piezoelectric material-based flexible electronics, PVDF cube switches have a simple design and easy fabrication process. Each side of the cube switch demonstrates independent voltage signals with pressing displacements and corresponding directions. With cutting angle variations and planar figure designs, derived cube switches respond with various combinations of voltage waveforms. PVDF switches can endure more than 1000 cycles of 70% vertical strain in terms of both electrical responses and mechanical operations. As an application, we establish a security system with multiresponsibility of a cube switch. This security system can protect users from potential threats owing to its multiresponsibility and user-dependent operability.

Tunable hybrid hydrogels with multicellular spheroids for modeling desmoplastic pancreatic cancer.

The tumor microenvironment consists of diverse, complex etiological factors. The matrix component of pancreatic ductal adenocarcinoma (PDAC) plays an important role not only in physical properties such as tissue rigidity but also in cancer progression and therapeutic responsiveness. Although significant efforts have been made to model desmoplastic PDAC, existing models could not fully recapitulate the etiology to mimic and understand the progression of PDAC. Here, two major components in desmoplastic pancreatic matrices, hyaluronic acid- and gelatin-based hydrogels, are engineered to provide matrices for tumor spheroids composed of PDAC and cancer-associated fibroblasts (CAF). Shape analysis profiles reveals that incorporating CAF contributes to a more compact tissue formation. Higher expression levels of markers associated with proliferation, epithelial to mesenchymal transition, mechanotransduction, and progression are observed for cancer-CAF spheroids cultured in hyper desmoplastic matrix-mimicking hydrogels, while the trend can be observed when those are cultured in desmoplastic matrix-mimicking hydrogels with the presence of transforming growth factor-ß1 (TGF-ß1). The proposed multicellular pancreatic tumor model, in combination with proper mechanical properties and TGF-ß1 supplement, makes strides in developing advanced pancreatic models for resembling and monitoring the progression of pancreatic tumors, which could be potentially applicable for realizing personalized medicine and drug testing applications.

Protection of Skin Fibroblasts from Infrared-A-Induced Photo-Damage Using Ginsenoside Rg3(S)-Incorporated Soybean Lecithin Liposomes.

Protection of skin cells from chronic infrared-A (IRA) irradiation is crucial for anti-photoaging of the skin. In this study, we investigated the protective activity of Rg3(S) and Rg3(S)-incorporated anionic soybean lecithin liposomes (Rg3/Lipo) with a size of approximately 150 nm against IRA-induced photodamage in human fibroblasts. The formulated Rg3/Lipo showed increased solubility in aqueous solution up to a concentration of 200 µg/ml, compared to free Rg3(S). In addition, Rg3/Lipo exhibited superior colloidal stability in aqueous solutions and biocompatibility for normal human dermal fibroblasts (NHDFs). After repeated IRA irradiation on NHDFs, elevated levels of cellular and mitochondrial reactive oxygen species (ROS) were greatly reduced by Rg3(S) and Rg3/Lipo. In addition, cells treated with Rg3/Lipo exhibited noticeably reduced apoptotic signals following IRA irradiation compared to untreated cells. Thus, considering aqueous solubility and cellular responses, Rg3/Lipo could serve as a promising infrared protector for healthy aging of skin cells.

Protective role of ginseng in endometriosis during covid-19.

The coronavirus disease 2019 (COVID) pandemic began in December 2019. Many countries have implemented restrictions such as mandatory mask wearing and social distancing. These measures have caused diverse and complex health problems, particularly in women's health, anxiety, and depression. This review examines an alternative approach to the treatment of endometriosis during the COVID pandemic. The efficacy of ginseng with anti-inflammatory activity and ability to relieve or prevent symptoms of endometriosis is discussed and reviewed.

Improved performance of stretchable piezoelectric energy harvester based on stress rearrangement.

With the development of wearable devices and soft electronics, the demand for stretchable piezoelectric energy harvesters (SPEHs) has increased. Energy harvesting can provide energy when large batteries or power sources cannot be employed, and stretchability provides a user-friendly experience. However, the performance of SPEHs remains low, which limits their application. In this study, a wearable SPEH is developed by adopting a kirigami structure on a polyvinylidene fluoride film. The performance of the SPEH is improved by rearranging the stress distribution throughout the film. This is conducted using two approaches: topological depolarization, which eliminates the opposite charge generation by thermal treatment, and optimization of the neutral axis, which maximizes the stress applied at the surface of the piezoelectric film. The SPEH performance is experimentally measured and compared with that of existing SPEHs. Using these two approaches, the stress was rearranged in both the x-y plane and z-direction, and the output voltage increased by 21.57% compared with that of the original film with the same stretching motion. The generated energy harvester was successfully applied to smart transmittance-changing contact lenses.

Machine learning-based quantitative prediction of drug exposure in drug-drug interactions using drug label information.

Many machine learning techniques provide a simple prediction for drug-drug interactions (DDIs). However, a systematically constructed database with pharmacokinetic (PK) DDI information does not exist, nor is there a machine learning model that numerically predicts PK fold change (FC) with it. Therefore, we propose a PK DDI prediction (PK-DDIP) model for quantitative DDI prediction with high accuracy, while constructing a highly reliable PK-DDI database. Reliable information of 3,627 PK DDIs was constructed from 3,587 drugs using 38,711 Food and Drug Administration (FDA) drug labels. This PK-DDIP model predicted the FC of the area under the time-concentration curve (AUC) within ± 0.5959. The prediction proportions within 0.8-1.25-fold, 0.67-1.5-fold, and 0.5-2-fold of the AUC were 75.77, 86.68, and 94.76%, respectively. Two external validations confirmed good prediction performance for newly updated FDA labels and FC from patients'. This model enables potential DDI evaluation before clinical trials, which will save time and cost.

Formulation of Glycyrrhizic Acid-based Nanocomplexes for Enhanced Anti-cancer and Anti-inflammatory Effects of Curcumin.

In this study, nanocomplexes composed of glycyrrhizic acid (GA) derived from the root of the licorice plant (Glycyrrhiza glabra) were formulated for the delivery of curcumin (CUR). Sonication of amphiphilic GA solution with hydrophobic CUR resulted in the production of nanosized complexes with a size of 164.8 ± 51.7 nm, which greatly enhanced the solubility of CUR in aqueous solution. A majority of the CURs were released from these GA/ CUR nanocomplexes within 12 h. GA/CUR nanocomplexes exhibited excellent intracellular uptake in human breast cancer cells (Michigan cancer foundation-7/multi-drug resistant cells), indicating enhanced anti-cancer effects compared to that of free CUR. In addition, GA/CUR nanocomplexes demonstrated high intracellular uptake into macrophages (RAW264.7 cells), consequently reducing the release of the pro-inflammatory cytokine tumor necrosis factor-α. Furthermore, GA/CUR nanocomplexes successfully reduced the levels of serum pro-inflammatory cytokines and splenomegaly in a rheumatoid arthritis model.

Chronic infrared-A irradiation-induced photoaging of human dermal fibroblasts from different donors at physiological temperature.

BACKGROUND: In this study, we examined cellular responses to acute and chronic IRA irradiation at mild and natural levels of exposure in two types of human fibroblasts, each isolated from a different donor, at physiological temperature (34°C). METHOD: Two types of human dermal fibroblasts (derived from a 20- and 50-year-old women, respectively) were exposed to different repeat numbers of IRA exposure (3, 6, 10, and 14 times; 42 mW/cm2 ) at a frequency of 3-4 times per week (4 h per irradiation). Cellular responses to acute and chronic IRA irradiation were examined by reactive oxygen species (ROS) level, apoptotic signals, cellular morphology, and collagen level. RESULTS: We demonstrated that chronic IRA irradiation-induced severe cellular damage, including prolonged cell proliferation, increased intracellular ROS levels, activated cellular apoptosis, and elongated cell morphology, whereas acute IRA irradiation had negligible effects at 34°C. In addition, it was evident that the degree of cellular damage due to IRA irradiation differed according to the type of fibroblasts. CONCLUSIONS: Considering the severe cellular damage induced by chronic IRA irradiation without heat, continuous exposure of skin to IRA irradiation during daily life may be harmful enough to induce photoaging.

Exosome-mediated delivery of transforming growth factor-ß receptor 1 kinase inhibitors and toll-like receptor 7/8 agonists for combination therapy of tumors.

In this study, combination therapy with the transforming growth factor-ß receptor I (TGFßRI) kinase inhibitor SD-208 and a toll-like receptor (TLR)-7/8 agonist resiquimod (R848) was examined along with serum-derived exosomes (EXOs) as versatile carriers. SD-208-encapsulated EXOs (SD-208/EXOs) and R848-encapsulated EXOs (R848/EXOs) were successfully prepared with a size of 87 ± 8 nm and 51 ± 4 nm, respectively, which were stable in aqueous solution at pH 7.4. SD-208/EXOs and R848/EXOs reduced the migration of cancer cells (B16F10 and PC-3) and triggered the release of proinflammatory cytokines from stimulated macrophages and dendritic cells, respectively. The fluorescent dye-labeled EXOs showed significantly improved penetration through the PC-3/fibroblast co-culture spheroids and enhanced accumulation in the B16F10 mouse tumor model compared with the free fluorescent dye. In addition, the combination therapy of R848/EXOs (R848 dose of 0.36 mg/kg) and SD-208/EXOs (SD-208 dose of 0.75 mg/kg) reduced tumor growth and improved survival rate at low doses in the B16F10 tumor xenograft model. Taken together, the combination therapy using the TGFßRI kinase inhibitor and TLR 7/8 agonist with EXOs may serve as a promising strategy to treat melanoma and prostate cancer. STATEMENT OF SIGNIFICANCE: Owing to the prevalence of several non-responding cancers that resist treatment, it is necessary to identify a novel combined treatment strategy with biomaterials to maximize therapeutic efficacy and minimize the undesirable side effects. In this study, we aimed to examine the use of the TGFßRI kinase inhibitor SD-208 and the TLR7/8 agonist resiquimod (R848) encapsulated within serum-derived EXOs for their synergistic antitumor effects. We first demonstrated that combined treatment with SD-208 and R848 can be a convincing strategy to circumvent tumor growth in vivo using serum-derived exosomes as promising carriers. Therefore, we believe this manuscript would be of great interest to the biomaterial communities especially who are studying immunotherapy.

Cancer-Cell-Derived Hybrid Vesicles from MCF-7 and HeLa Cells for Dual-Homotypic Targeting of Anticancer Drugs.

Here, as a proof of concept, hybrid vesicles (VEs) are developed from two types of cancer cells, MCF-7 and HeLa, for the dual targeting of the anticancer drug doxorubicin (Dox) to cancer cells via homotypic interactions. Hybrid VEs with a size of 181.8 ± 28.2 nm and surface charge of -27.8 ± 1.9 mV are successfully prepared by the fusion of MCF-7 and HeLa VEs, as demonstrated by the fluorescence resonance energy transfer assay. The hybrid VEs exhibit enhanced intracellular uptake both in MCF-7 and HeLa cells. Dox-encapsulated hybrid VEs (Dox-hybrid VEs) also exhibit promising anticancer and antiproliferative activities against MCF-7/multidrug-resistant cells and HeLa cells. In addition, compared to free Dox, the Dox-hybrid VEs exhibit low intracellular uptake and reduced cytotoxicity for RAW264.7 cells. Thus, hybrid VEs with dual-targeting activity toward two types of cancer cells may be useful for the specific targeting of anticancer drugs for improved anticancer effects with reduced nonspecific toxicity.

Catalytic Oxidation of Toluene with Ozone Over the Ru-Mn/Desilicated Nanoporous H-Zeolite Socony Mobil-5 at Room Temperature.

In this study, the effect of Ru-Mn bimetallic catalysts in combination with a zeolite support on the removal of toluene in the presence of ozone at room temperature was investigated. Desili-cated HZSM-5 (DZSM) was fabricated and applied as a Ru-Mn support for the removal of toluene (100 ppm) in the presence of ozone (1000 ppm) at room temperature. The surface area, pore volume, and average pore size of Ru-Mn with a DZSM support (RuMn/DZSM) were measured and compared with those of Ru-Mn/HZSM-5 (RuMn/HZSM). The pore size of RuMn/DZSM (69 Å) was much larger than that of RuMn/HZSM-5 (5.5 Å). In addition, the pore volumes of RuMn/DZSM and RuMn/HZSM were 0.64 and 0.25 cm³/g, respectively. Furthermore, the ratios of Mn³+/Mn4+ and Ovacancy/Olattice of RuMn/DZSM were larger than those of RuMn/HZSM-5. The removal efficiency of toluene of RuMn/DZSM was higher than that of RuMn/HZSM due to its larger pore volume, pore size, and the increased ratios of Mn³+/Mn4+ and Ovacancy/Olattice.

Effective toluene oxidation under ozone over mesoporous MnOx/γ-Al2O3 catalyst prepared by solvent deficient method: Effect of Mn precursors on catalytic activity.

In this study, the role of manganese precursors in mesoporous (meso) MnOx/γ-Al2O3 catalysts was examined systematically for toluene oxidation under ozone at ambient temperature (20 °C). The meso MnOx/γ-Al2O3 catalysts developed with Mn(CH3COO)2, MnCl2, Mn(NO3)2.4H2O and MnSO4 were prepared by an innovative single step solvent-deficient method (SDM); the catalysts were labeled as MnOx/Al2O3(A), MnOx/Al2O3(C), MnOx/Al2O3(N), and MnOx/Al2O3(S), respectively. Among all, MnOx/Al2O3(C) showed superior performance both in toluene removal (95%) as well as ozone decomposition (88%) followed by acetate, nitrate and sulphated precursor MnOx/Al2O3. The superior performance of MnOx/Al2O3(C) in the oxidation of toluene to COx is associated with the ozone decomposition over highly dispersed MnOx in which extremely active oxygen radicals (O2-, O22- and O-) are generated to enhance the oxidation ability of the catalysts greatly. In addition, toluene adsorption over acid support played a vital role in this reaction. Hence, the properties such as optimum Mn3+/Mn4+ ratio, acidic sites, and smaller particle size (≤2 nm) examined by XPS, TPD of NH3, and TEM results are playing vital role in the present study. In summary, the MnOx/Al2O3 (C) catalyst has great potential in environmental applications particularly for the elimination of volatile organic compounds with low loading of manganese developed by SDM.

Effect of zeolite acidity and structure on ozone oxidation of toluene using Ru-Mn loaded zeolites at ambient temperature.

Five different Ru-Mn/zeolites were used to investigate their catalytic efficiencies for removing toluene (100 ppm) with ozone (1000 ppm) at room temperature. In general, most of metal oxide catalysts for removal of organic compounds need higher temperature than the ambient temperature, but Mn-based catalysts shows activity for prevalent organic pollutants even at room temperature with ozone. For the removal of toluene at room temperature without further heating, bimetallic Ru added Mn catalysts were applied in combination with different zeolite supports. The catalytic activity of the Ru-Mn catalysts strongly depended on the zeolite, of which the characteristics such as acidity and adsorption degree of toluene are dependent on the ratio of SiO2/Al2O3. Among the five Ru-Mn catalysts used, Ru-Mn/HY (SiO2/Al2O3 ratio: 80) and Ru-Mn/ZSM-5 (SiO2/Al2O3 ratio: 80) had higher toluene and ozone removal efficiencies. The toluene removal efficiency of Ru-Mn/zeolites was proportional to the pore volume and surface area. In terms of ozone degradation, Ru-Mn/HY(80) and Ru-Mn/HZSM-5(80) had the highest removal efficiencies. Overall, the catalytic ozone oxidation of toluene using Ru-Mn/zeolites seemed to be affected by a combination of the acidic properties of zeolites, Mn3+/Mn4+ ratio, and concentration ratio of oxygen vacancies to oxygen lattices on the catalyst surface.

Catalytic ozonation of toluene using Mn-M bimetallic HZSM-5 (M: Fe, Cu, Ru, Ag) catalysts at room temperature.

We investigated the catalytic efficiency of Mn-based bimetallic oxides in degrading toluene and ozone at room temperature. The room temperature-active bimetallic oxide catalysts were prepared by the addition of Fe, Cu, Ru, and Ag precursors to Mn/HZSM-5. We obtained H2-temperature-programmed reduction (H2-TPR) profiles, X-ray diffraction patterns, and X-ray photoelectron spectra to investigate the characteristics of the prepared catalysts. The catalytic efficiency of Mn-based bimetallic oxide catalysts in degrading toluene and ozone at room temperature was mostly improved by the addition of the secondary metals. The prepared bimetallic oxide catalysts, Cu-Mn/HZSM-5, Fe-Mn/HZSM-5, Ru-Mn/HZSM-5, and Ag-Mn/HZSM-5, enhanced efficiency for toluene removal compared to Mn/HZSM-5. The H2-TPR profiles of the Mn-based bimetallic oxide catalysts showed stronger and broader adsorption-desorption bands at lower temperatures than the profile of Mn/HZSM-5. Additionally, the ratio of the surface defective oxygen over the lattice oxygen on the bimetallic oxide catalysts was higher than that of Mn-only catalysts; the ratio of Mn3+ over Mn4+ was higher for all bimetallic oxide catalysts, as well. Among the bimetallic oxide catalysts, Ru-Mn/HZSM-5 showed the highest efficiency for the removal of toluene to COx due to the synergetic effect of the oxidation state and reducible potential at room temperature.

Korean Red Ginseng and Korean black ginseng extracts, JP5 and BG1, prevent hepatic oxidative stress and inflammation induced by environmental heat stress.

BACKGROUND: Continuous exposure to high temperatures can lead to heat stress. This stress response alters the expression of multiple genes and can contribute to the onset of various diseases. In particular, heat stress induces oxidative stress by increasing the production of reactive oxygen species. The liver is an essential organ that plays a variety of roles, such as detoxification and protein synthesis. Therefore, it is important to protect the liver from oxidative stress caused by heat stress. Korean ginseng has a variety of beneficial biological properties, and our previous studies showed that it provides an effective defense against heat stress. METHODS: We investigated the ability of Korean Red Ginseng and Korean black ginseng extracts (JP5 and BG1) to protect against heat stress using a rat model. We then confirmed the active ingredients and mechanism of action using a cell-based model. RESULTS: Heat stress significantly increased gene and protein expression of oxidative stress-related factors such as catalase and SOD2, but treatment with JP5 (Korean Red Ginseng extract) and BG1 (Korean black ginseng extract) abolished this response in both liver tissue and HepG2 cells. In addition, JP5 and BG1 inhibited the expression of inflammatory proteins such as p-NF-κB and tumor necrosis factor alpha-α. In particular, JP5 and BG1 decreased the expression of components of the NLRP3 inflammasome, a key inflammatory signaling factor. Thus, JP5 and BG1 inhibited both oxidative stress and inflammation. CONCLUSIONS: JP5 and BG1 protect against oxidative stress and inflammation induced by heat stress and help maintain liver function by preventing liver damage.

Recent advances in volatile organic compounds abatement by catalysis and catalytic hybrid processes: A critical review.

Air pollution, particularly for toxic and harmful compounds to humans and the environment, has aroused increasing public concerns. Among air pollutants, volatile organic compounds (VOCs) are the main sources of air pollution. Many attempts have been made to control VOCs using catalysts, plasma, photolysis, and adsorption. Among them, oxidative catalysis by noble metals or transition metal oxides is considered one of the most feasible and effective methods to control VOCs. This paper reviews the experimental achievements on the abatement of VOCs using noble metals, transition metals and modified metal oxide catalysts. Although the catalytic degradation of VOCs appears to be feasible, there are unavoidable problems when only catalysis treatments are applied to the field. Therefore, catalysts including hybrid processes are developed to improve the removal efficiency of VOCs. This review addresses new hybrid treatments to remove VOCs using catalysts, including hybrid treatment combined with plasma, photolysis, and adsorption. The mechanism of the oxidation of VOCs by catalysts is explained by adsorption-desorption principles, such as the Langmuir-Hinshelwood, Eley-Rideal, and Mars-van-Krevelen mechanisms. A π-backbonding interaction between unsaturated compounds and transition metals is introduced to better understand the mechanism of VOC removals. Finally, several factors affecting the catalytic activities, such as support, component ratio, preparation method, metal loading, and deactivation factor, are discussed.