The two oxidation states of ceria nanoparticles, Ce3+ and Ce4+, play a pivotal role in scavenging reactive oxygen species (ROS). In particular, Ce3+ is largely responsible for removing O2− and .OH ...that are associated with inflammatory response and cell death. The synthesis is reported of 2 nm ceria–zirconia nanoparticles (CZ NPs) that possess a higher Ce3+/Ce4+ ratio and faster conversion from Ce4+ to Ce3+ than those exhibited by ceria nanoparticles. The obtained Ce0.7Zr0.3O2 (7CZ) NPs greatly improve ROS scavenging performance, thus regulating inflammatory cells in a very low dose. Moreover, 7CZ NPs are demonstrated to be effective in reducing mortality and systemic inflammation in two representative sepsis models. These findings suggest that 7CZ NPs have the potential as a therapeutic nanomedicine for treating ROS‐related inflammatory diseases.
An optimized ROS scavenging agent: 2 nm‐sized ceria–zirconia nanoparticles (CZ NPs) with increased Ce3+ ratios outperform ceria NPs as scavengers of reactive oxygen species (ROS). The composition‐tuned 7CZ (Ce0.7Zr0.3O2) NPs are superior in reducing inflammation in vitro and decrease the mortality in sepsis in vivo.
This paper presents power-control strategies of a grid-connected hybrid generation system with versatile power transfer. The hybrid system is the combination of photovoltaic (PV) array, wind turbine, ...and battery storage via a common dc bus. Versatile power transfer was defined as multimodes of operation, including normal operation without use of battery, power dispatching, and power averaging, which enables grid- or user-friendly operation. A supervisory control regulates power generation of the individual components so as to enable the hybrid system to operate in the proposed modes of operation. The concept and principle of the hybrid system and its control were described. A simple technique using a low-pass filter was introduced for power averaging. A modified hysteresis-control strategy was applied in the battery converter. Modeling and simulations were based on an electromagnetic-transient-analysis program. A 30-kW hybrid inverter and its control system were developed. The simulation and experimental results were presented to evaluate the dynamic performance of the hybrid system under the proposed modes of operation.
Induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) serve as a unique source for cell therapy. We investigated whether exosomes from iMSCs promote the proliferation of human ...keratinocytes (HaCaT) and human dermal fibroblasts (HDFs). iPSCs were established from human Wharton's jelly MSCs and were allowed to differentiate into iMSCs. Exosomes were collected from the culture supernatant of MSCs (MSC-exo) and iMSCs (iMSC-exo), and their characteristics were investigated. Both exosome types possessed basic characteristics of exosomes and were taken up by skin cells in vitro and in vivo. A significant increase in HaCaT proliferation was observed with iMSC-exo, although both exosomes increased the viability and cell cycle progression in HaCaT and HDFs. No significant difference was observed in the closure of wound scratch and the expression of reparative genes between cells treated with the two exosome types. Both exosomes enhanced the secretion of collagen in HaCaT and HDFs; however, an increase in fibronectin level was observed only in HaCaT, and this effect was better with iMSC-exo treatment. Only iMSC-exo increased the phosphorylation of extracellular signal-regulated kinase (ERK)-1/2. Our results indicate that iMSC-exo promote the proliferation of skin cells by stimulating ERK1/2 and highlight the application of iMSCs for producing exosomes.
Systemic inflammatory response syndrome (SIRS) is self‐destructive and uncontrollable inflammatory response of the whole body triggered by infection, trauma, or a variety of severe injuries. Although ...reactive oxygen species play a pivotal role in the development of SIRS, the trials with conventional antioxidants have failed to improve patient outcome. Ceria nanoparticles (CeNPs) have potent, autocatalytic reactive oxygen species scavenging activities, which may have sufficient therapeutic effects for SIRS. Herein, 3 nm CeNPs are fabricated totally in aqueous phase by using 6‐aminohexanoic acid (6‐AHA) and their Ce3+ to Ce4+ ratio is increased to enhance antioxidative properties. The obtained 6‐AHA‐CeNPs demonstrate strong antioxidative and anti‐inflammatory effects in various biofluids and inflammatory cells. In SIRS animal models, 6‐AHA‐CeNPs are demonstrated to reduce multiple organ injuries and inflammation. Moreover, 6‐AHA‐CeNPs decrease mortality and improve clinical scores of SIRS models. These findings suggest that 6‐AHA‐CeNPs have potential as a therapeutic nanomedicine for SIRS.
Systemic inflammatory response syndrome (SIRS) is a complex, self‐destructive process that occurs when the local control is lost and inflammation is overactivated throughout the body. Ceria nanoparticles (CeNPs) synthesized in aqueous phase using 6‐aminohexanoic acid (6‐AHA‐CeNPs) effectively treat remote organ injuries and improve survival rate in SIRS animal models.
Energy expenditure and energy intake need to be balanced to maintain proper energy homeostasis. Energy homeostasis is tightly regulated by the central nervous system, and the hypothalamus is the ...primary center for the regulation of energy balance. The hypothalamus exerts its effect through both humoral and neuronal mechanisms, and each hypothalamic area has a distinct role in the regulation of energy expenditure. Recent studies have advanced the understanding of the molecular regulation of energy expenditure and thermogenesis in the hypothalamus with targeted manipulation techniques of the mouse genome and neuronal function. In this review, we elucidate recent progress in understanding the mechanism of how the hypothalamus affects basal metabolism, modulates physical activity, and adapts to environmental temperature and food intake changes.
PIK3CA is a frequently mutated gene in cancer, including about ~15 to 20% of colorectal cancers (CRC). PIK3CA mutations lead to activation of the PI3K/AKT/mTOR signaling pathway, which plays pivotal ...roles in tumorigenesis. Here, we investigated the mechanism of resistance of PIK3CA‐mutant CRC cell lines to gedatolisib, a dual PI3K/mTOR inhibitor. Out of a panel of 29 CRC cell lines, we identified 7 harboring one or more PIK3CA mutations; of these, 5 and 2 were found to be sensitive and resistant to gedatolisib, respectively. Both of the gedatolisib‐resistant cell lines expressed high levels of active glycogen synthase kinase 3‐beta (GSK3β) and harbored the same frameshift mutation (c.465_466insC; H155fs*) in TCF7, which encodes a positive transcriptional regulator of the WNT/β‐catenin signaling pathway. Inhibition of GSK3β activity in gedatolisib‐resistant cells by siRNA‐mediated knockdown or treatment with a GSK3β‐specific inhibitor effectively reduced the activity of molecules downstream of mTOR and also decreased signaling through the WNT/β‐catenin pathway. Notably, GSK3β inhibition rendered the resistant cell lines sensitive to gedatolisib cytotoxicity, both in vitro and in a mouse xenograft model. Taken together, these data demonstrate that aberrant regulation of WNT/β‐catenin signaling and active GSK3β induced by the TCF7 frameshift mutation cause resistance to the dual PI3K/mTOR inhibitor gedatolisib. Cotreatment with GSK3β inhibitors may be a strategy to overcome the resistance of PIK3CA‐ and TCF7‐mutant CRC to PI3K/mTOR‐targeted therapies.
What's new?
Mutations in the PI3K/mTOR and WNT/β‐catenin pathways are common in colorectal cancer. Here, in colorectal cancer cells, the authors show that the frameshift mutation H155fs* in transcription factor TCF7 serves a critical role in mediating resistance to the PI3K/mTOR dual inhibitor gedatolisib. TCF7 H155fs* maintained mTOR signaling by inducing the active form of glycogen synthase kinase 3‐beta (GSK3β) and aberrant WNT/β‐catenin signaling. The latter conferred resistance to gedatolisib. Co‐treatment with a GSK3β inhibitor increased sensitivity to gedatolisib, a combination that synergistically inhibited colorectal tumor growth in mice. The findings shed light on gedatolisib resistance mechanisms and potential resistance biomarkers.
This article describes the relationship between the design features of green infrastructure and the benefits of multifunctionality. To do so, it examines the descriptive linkages between 12 design ...features and nine benefits using 447 project case studies from the American Society of Landscape Architects. Multiple benefits of green infrastructure were found in 65% of the projects, regardless of the number of applied design features. The major green infrastructure design features with multiple benefits were: bioretention areas, permeable pavements, grassed swales, rainwater harvesting, rain gardens, and curb cuts. The major benefits of applied design features were: enhanced economic capacity, educational opportunities, improvements to the built environment, and enhanced environmental soundness. The findings show that the multiple benefits of green infrastructure’s multifunctionality can be inferred in many current cases. Knowing the relationship between design features and their benefits for green infrastructure would facilitate selecting optimal design features to achieve specific goals and planning outcomes. For communities that require a range of complex benefits, a multifunctionality-based green infrastructure will advance highly acceptable climate change adaptation measures.
With the increasing use of renewable energy resources in power systems, it is necessary to overcome the limitations of these resources in terms of the supply and demand balance in high-voltage power ...systems. A viable solution is employing zero net energy community microgrids, which can manage the demand locally and minimize the impact to the power grid. To this end, this paper proposes an optimal scheduling method for a zero net energy community microgrid with customer-owned energy storage systems (CES). It is assumed that the microgrid operator operates in the CES market based on a bilateral contract. The CES aggregators constitute the CES and participate in the market. The aggregated CES (ACES) is considered as a single energy storage system in the proposed scheduling method. Numerical examples are presented to demonstrate the effectiveness of the proposed method.
Unlike previous literature that mainly examined the cognitive effects of single-sex education, this study investigates its effects on students’ mental health, focusing on depression, suicide-related ...behaviours, and the various causes of stress. Utilizing a national-level large-scale dataset of middle school students in South Korea and employing an instrument variable approach, we find that attending single-sex schools reduces the probability of depression in female students by about 9.9% points, while no significant effect is observed for male students. Additionally, our research regarding the causes of stress uncovers that single-sex schooling reduces the stress associated with peer relationships, particularly for girls. These findings imply that the non-cognitive benefits of single-sex education may be stronger than previously thought. As a result, we advocate for a more thoughtful and inclusive implementation of school policies, taking into consideration the impact of gender peer effects at school.
Energy storage systems (ESSs) are essential in future power systems because they can improve power usage efficiency. In this paper, a novel coordinated control algorithm is proposed for distributed ...battery ESSs (BESSs). The neighboring BESSs of a simulation system are grouped and controlled by a main control center. The main control center sends charging or discharging operation signals to each BESS. The primary objective of the proposed coordinated control scheme is to mitigate voltage and frequency deviations. In order to verify the proposed algorithm, the BESSs are connected to a distribution system of the Korea Electric Power Corporation. The results are compared with those obtained using uncoordinated control scheme with on-load tap changer considering aspects of power quality (voltage and frequency variation). The simulation results show that the voltage and frequency deviations are reduced with the proposed coordinated control algorithm.
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