Aging is associated with vulnerability to cardiovascular diseases, and mitochondrial dysfunction plays a critical role in cardiovascular disease pathogenesis. Exercise training is associated with ...benefits against chronic cardiac diseases. The purpose of this study was to determine the effects of aging and treadmill exercise training on mitochondrial function and apoptosis in the rat heart. Fischer 344 rats were divided into young sedentary (YS;
n
= 10, 4 months), young exercise (YE;
n
= 10, 4 months), old sedentary (OS;
n
= 10, 20 months), and old exercise (OE;
n
= 10, 20 months) groups. Exercise training groups ran on a treadmill at 15 m/min (young) or 10 m/min (old), 45 min/day, 5 days/week for 8 weeks. Morphological parameters, mitochondrial function, mitochondrial dynamics, mitophagy, and mitochondria-mediated apoptosis were analyzed in cardiac muscle. Mitochondrial O
2
respiratory capacity and Ca
2+
retention capacity gradually decreased, and mitochondrial H
2
O
2
emitting potential significantly increased with aging. Exercise training attenuated aging-induced mitochondrial H
2
O
2
emitting potential and mitochondrial O
2
respiratory capacity, while protecting Ca
2+
retention in the old groups. Aging triggered imbalanced mitochondrial dynamics and excess mitophagy, while exercise training ameliorated the aging-induced imbalance in mitochondrial dynamics and excess mitophagy. Aging induced increase in Bax and cleaved caspase-3 protein levels, while decreasing Bcl-2 levels. Exercise training protected against the elevation of apoptotic signaling markers by decreasing Bax and cleaved caspase-3 and increasing Bcl-2 protein levels, while decreasing the Bax/Bcl-2 ratio and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive myonuclei. These data demonstrate that regular exercise training prevents aging-induced impairment of mitochondrial function and mitochondria-mediated apoptosis in cardiac muscles.
The maximum reflection at an open end of a standard rectangular waveguide is about −10 dB in its operating frequency range. It is often used without matching. For critical applications, it is ...desirable to further reduce the reflection coefficient. In this paper, a new technique is presented for the broadband impedance matching of an open-ended rectangular waveguide. The proposed technique employs three thin capacitive matching elements placed at proper intervals via a low-loss dielectric material. The capacitance of, and distance between, the matching elements are optimized for broadband impedance matching using a simulation tool. Based on the proposed technique, two design examples are presented for the matching of a WR75 waveguide radiator. A reflection coefficient of less than −16 dB and −20 dB has been achieved over a ratio bandwidth of 2.13:1 and 1.62:1, respectively.
Optogenetic techniques permit non-invasive, spatiotemporal, and reversible modulation of cellular activities. Here, we report a novel optogenetic regulatory system for insulin secretion in human ...pluripotent stem cell (hPSC)-derived pancreatic islet-like organoids using monSTIM1 (monster-opto-Stromal interaction molecule 1), an ultra-light-sensitive OptoSTIM1 variant. The monSTIM1 transgene was incorporated at the AAVS1 locus in human embryonic stem cells (hESCs) by CRISPR-Cas9-mediated genome editing. Not only were we able to elicit light-induced intracellular Ca2+ concentration (Ca2+i) transients from the resulting homozygous monSTIM1+/+-hESCs, but we also successfully differentiated them into pancreatic islet-like organoids (PIOs). Upon light stimulation, the β-cells in these monSTIM1+/+-PIOs displayed reversible and reproducible Ca2+i transient dynamics. Furthermore, in response to photoexcitation, they secreted human insulin. Light-responsive insulin secretion was similarly observed in monSTIM1+/+-PIOs produced from neonatal diabetes (ND) patient-derived induced pluripotent stem cells (iPSCs). Under LED illumination, monSTIM1+/+-PIO-transplanted diabetic mice produced human c-peptide. Collectively, we developed a cellular model for the optogenetic control of insulin secretion using hPSCs, with the potential to be applied to the amelioration of hyperglycemic disorders.
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Han, Heo and colleagues applied optogenetic Ca2+ regulatory module monSTIM1 to human pluripotent stem cell-derived islet-like organoids to establish a photoinducible insulin secretion model. Instead of preexisting studies based on the rodent model or immortalized cells, this study suggests an advanced scheme exploiting optogenetics for personalized diabetes cell therapy.
Receptor tyrosine kinases (RTKs) are a family of cell-surface receptors that have a key role in regulating critical cellular processes. Here, to understand and precisely control RTK signalling, we ...report the development of a genetically encoded, photoactivatable Trk (tropomyosin-related kinase) family of RTKs using a light-responsive module based on Arabidopsis thaliana cryptochrome 2. Blue-light stimulation (488 nm) of mammalian cells harbouring these receptors robustly upregulates canonical Trk signalling. A single light stimulus triggers transient signalling activation, which is reversibly tuned by repetitive delivery of blue-light pulses. In addition, the light-provoked process is induced in a spatially restricted and cell-specific manner. A prolonged patterned illumination causes sustained activation of extracellular signal-regulated kinase and promotes neurite outgrowth in a neuronal cell line, and induces filopodia formation in rat hippocampal neurons. These light-controllable receptors are expected to create experimental opportunities to spatiotemporally manipulate many biological processes both in vitro and in vivo.
In this paper, we discuss a method for fabricating an ultrathin polymer substrate with one-dimensional nanograting patterns to improve the power conversion efficiency (PCE) of ultrathin polymer solar ...cells (PSCs) and suppress the dependence on the incident angle of light. Because the fabricating process of the ultrathin polymer substrate was carried out using a solution process, it can be manufactured in a large area, and the PCE of the patterned ultrathin substrate-based PSC is improved by 8.9% compared to the non-patterned device. In addition, triple-patterned ultrathin PSCs incorporating the same nanograting pattern as the substrate were fabricated in the electron transport (ZnO) layer and the photoactive layer (PBDTTT-OFT and PC71BM mixture (ratio-1: 1.5)) to achieve PCE of 10.26%. Thanks to the nanograting pattern introduced in the substrate, ZnO layer, and photoactive layer, it was possible to minimize the PCE change according to the incident angle of light. Moreover, we performed 1000 cycles of compression/relaxation tests to evaluate the mechanical properties of the triple-patterned ultrathin PSCs, after which the PCE remained at 71% of the initial PCE.
Intracellular antibody fragments such as nanobodies and scFvs are powerful tools for imaging and for modulating and neutralizing endogenous target proteins. Optogenetically activated intracellular ...antibodies (optobodies) constitute a light-inducible system to directly control intrabody activities in cells, with greater spatial and temporal resolution than intracellular antibodies alone. Here, we describe optogenetic and microscopic methods to activate optobodies in cells using a confocal microscope and an automated fluorescence microscope. In the protocol, we use the examples of an optobody targeting green fluorescent protein and an optobody that inhibits the endogenous gelsolin protein.
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•Ti element was embedded into LN92 cathode using nano-TiO2 precursor.•Incorporating the Ti enhanced the mechanical strength of LN92 cathode materials.•Ti-incorporated LN92 cathodes ...exhibited improved retention after 100 cycles.•Ti-incorporated LN92 cathodes offered a stable interface by inhibiting microcracks.
Given the exponential rising demand for high-performance lithium-ion batteries (LIBs), Ni-rich layered LiNixCoyMn(1-x-y)O2 (LN) cathode materials have gained significant attention. Nevertheless, poor structural stability of LN cathode materials is a critical hurdle to their use in LIBs. In this regard, Ti-doped LN cathode materials are designed to enrich the structural reliability of LN cathode materials, and their underlying behaviors are elucidated. Once Ti is replaced in the layered sites of the LN cathode materials, it strongly binds to lattice oxygen owing to its outstanding binding affinity. Therefore, Ti-doped Ni-rich LN cathode materials exhibit increased thermal stability and mechanical rigidity compared with bare LN cathode materials. In terms of cycling behavior, the Ti-doped Ni-rich LN cathode materials deliver remarkably improved cycling retention; the 2.0% Ti-doped Ni-rich LN cathode material yields an 88.0% retention, while the bare Ni-rich LN cathode material yield a 52.2% retention after 100 cycles. Further analyses of the recovered Ni-rich LN cathodes indicate that structural deformations, such as microcracks and phase transitions, are evidently suppressed in the Ti-doped LN cathode, and additional parasitic reactions, such as electrolyte decomposition, are also inhibited after cycling. This means that incorporating Ti in Ni-rich LN cathode materials not only suppresses structural deformation but also simultaneously increases the interfacial stability upon cycling, thus leading to a comprehensively improved cycling behavior.
The impact of national projects such as disaster prevention, should be analyzed by simultaneously considering the results of direct and indirect effect analyses. Existing research has verified the ...effectiveness of disaster prevention projects only through direct effect analysis. This study proposed an impact analysis approach that employed both direct and indirect effect analyses to assess their effectiveness. For the impact analysis, both direct effect and indirect effect analyses were conducted, using cost–benefit analysis (CBA) along with a safety sentiment index of residents and the efforts of the local government in implementing disaster prevention projects in 33 areas in South Korea. CBA calculates the scale of damage through a survey of properties (e.g., crops and public facilities) and the estimated damage according to the conditions of the disaster area. Matrix analysis was performed by applying the results of the CBA and safety sentiment index. The direct and indirect effect analyses identified the highly affected groups and areas where the results of the aforementioned analyses were above average, compared with the lowly affected groups and areas where the results were below average. An area belonging to the group with negative effects could be considered as part of the group with relatively good effects by supplementing its projects. The proposed method of impact analysis can be used to determine the efficiency of a disaster prevention project and comprehensively analyze its effects.
•This study suggested an impact analysis system that can consider both direct or indirect effect.•The analysis method that along with two methods were considered was not studied.•Direct effect analysis using CBA(cost benefit analysis) and indirect effect analysis using safety sentiment index of residents.•The matrix analysis was performed by applying the results of the CBA and safety sentiment index of residents.•It is ideal to analyze in two methods to reason out a comprehensive and reasonable result.
Neuroinflammation is a central pathological feature of several acute and chronic brain diseases, including Alzheimer disease (AD), Parkinson disease (PD), amyotrophic lateral sclerosis (ALS), and ...multiple sclerosis (MS). It induces microglia activation, mitochondrial dysfunction, the production of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), pro-inflammatory cytokines, and reactive oxygen species. Exercise, which plays an important role in maintaining and improving brain health, might be a highly effective intervention for preventing neuroinflammation-related diseases. Thus, since exercise can improve the neuroimmune response, we hypothesized that exercise would attenuate neuroinflammation-related diseases. In this review, we will highlight (1) the biological mechanisms that underlie AD, PD, ALS, and MS, including the neuroinflammation pathways associated with microglia activation, NF-κB, pro-inflammatory cytokines, mitochondrial dysfunction, and reactive oxygen species, and (2) the role of exercise in neuroinflammation-related neurodegenerative diseases.
mTOR signaling, involving mTORC1 and mTORC2 complexes, critically regulates neural development and is implicated in various brain disorders. However, we do not fully understand all of the upstream ...signaling components that can regulate mTOR signaling, especially in neurons. Here, we show a direct, regulated inhibition of mTOR by Tanc2, an adaptor/scaffolding protein with strong neurodevelopmental and psychiatric implications. While Tanc2-null mice show embryonic lethality, Tanc2-haploinsufficient mice survive but display mTORC1/2 hyperactivity accompanying synaptic and behavioral deficits reversed by mTOR-inhibiting rapamycin. Tanc2 interacts with and inhibits mTOR, which is suppressed by mTOR-activating serum or ketamine, a fast-acting antidepressant. Tanc2 and Deptor, also known to inhibit mTORC1/2 minimally affecting neurodevelopment, distinctly inhibit mTOR in early- and late-stage neurons. Lastly, Tanc2 inhibits mTORC1/2 in human neural progenitor cells and neurons. In summary, our findings show that Tanc2 is a mTORC1/2 inhibitor affecting neurodevelopment.
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