Brain organoids derived from human pluripotent stem cells provide a highly valuable in vitro model to recapitulate human brain development and neurological diseases. However, the current systems for ...brain organoid culture require further improvement for the reliable production of high-quality organoids. Here, we demonstrate two engineering elements to improve human brain organoid culture, (1) a human brain extracellular matrix to provide brain-specific cues and (2) a microfluidic device with periodic flow to improve the survival and reduce the variability of organoids. A three-dimensional culture modified with brain extracellular matrix significantly enhanced neurogenesis in developing brain organoids from human induced pluripotent stem cells. Cortical layer development, volumetric augmentation, and electrophysiological function of human brain organoids were further improved in a reproducible manner by dynamic culture in microfluidic chamber devices. Our engineering concept of reconstituting brain-mimetic microenvironments facilitates the development of a reliable culture platform for brain organoids, enabling effective modeling and drug development for human brain diseases.
Pattern-recognition receptors (PRRs) initiate innate immunity through pathogen recognition. Serum PRRs opsonize pathogens for enhanced phagocytic clearance. Toll-like receptors (TLRs) initiate common ...NF-kappaB/AP-1 and distinct IRF3/7 pathways to coordinate innate immunity and to initiate adaptive immunity against diverse pathogens. Cytoplasmic caspase-recruiting domain (CARD) helicases, such as RIG-I/MDA5, mediate antiviral immunity by inducing the production of type I interferons via the adaptor IPS-1, whereas nucleotide-binding oligomerization domain (NOD)-like receptors mediate mainly antibacterial immunity by activating NF-kappaB or inflammasomes. Dectin-1 is important for antifungal immunity, promoting phagocytosis and activating NF-kappaB. Potentially harmful TLR signaling pathways can be negatively regulated by negative feedback mechanisms and also by anti-inflammatory factors such as TGFbeta, interleukin (IL)-10, and steroids. Many combinations of TLR-TLR and TLR-NOD modulate inflammatory responses. TLRs and NALP3 interplay to produce mature IL-1beta. Thus signaling pathways downstream of PRRs and their cross talk control immune responses in effective manners.
A bioengineered skeletal muscle construct that mimics structural and functional characteristics of native skeletal muscle is a promising therapeutic option to treat extensive muscle defect injuries. ...We previously showed that bioprinted human skeletal muscle constructs were able to form multi-layered bundles with aligned myofibers. In this study, we investigate the effects of neural cell integration into the bioprinted skeletal muscle construct to accelerate functional muscle regeneration in vivo. Neural input into this bioprinted skeletal muscle construct shows the improvement of myofiber formation, long-term survival, and neuromuscular junction formation in vitro. More importantly, the bioprinted constructs with neural cell integration facilitate rapid innervation and mature into organized muscle tissue that restores normal muscle weight and function in a rodent model of muscle defect injury. These results suggest that the 3D bioprinted human neural-skeletal muscle constructs can be rapidly integrated with the host neural network, resulting in accelerated muscle function restoration.
For incompletely reduced graphene oxides (RGOs), an effect of oxygen functional groups such as carboxyl, phenol, carbonyl, and quinone on electrochemical capacitive behavior was studied. To prepare ...RGO thin-film electrodes, a simple fabrication process by (i) dropping and evaporating the graphene oxide (GO) solution, (ii) irradiating pulsed light, and (iii) heat-treating at 200 ∼ 360°C was applied. It was notable that the pulsed light irradiation was effective to prevent the disfiguring of deposited GO thin-film during the thermal reduction. From XRD analyses, interlayer distances of the RGOs were gradually decreased from 0.379 to 0.354nm. As increasing the thermal reduction temperature from 200 to 360°C, XPS O 1s spectra analyses showed that the atomic percentages of carboxyl and phenol of the RGOs were sustained as 5.40±0.36 and 4.77±0.41 at% respectively. Meanwhile, those of carbonyl and quinone of the RGOs were gradually declined from 3.10 to 1.81 and from 1.32 to 0.65 at% with different thermal reduction temperature respectively. For all RGO thin-film electrodes, the specific capacitance from the CV measurement in 6M KOH was sustained as ca. 220 F g−1 at the scan of 5mV s−1. However, in 1M H2SO4, the specific capacitance was gradually decreased from 171 to 136 F g−1. After 100,000 cycles in 6M KOH, 1M H2SO4, and 0.5M Na2SO4, the RGO (200°C) electrodes showed ca. 92, 54, and 104% of the initial capacitances respectively. The atomic percentages of the oxygen functional groups involved in the pseudocapacitive Faradaic reaction were decreased after the cycle test. Especially in 1M H2SO4, quinone group was decreased to ca. 48% of initial atomic percentage, which seems to be a main reason for the drastic reduction of capacitance. The specific pseudocapacitance per unit atomic percentage for either carboxyl or phenol group in 6M KOH was obtained as 12.59 F g−1 at%−1. For carbonyl group in 1M H2SO4, it was a slightly deviated value as 13.55 F g−1 at%−1. For quinone group in 1M H2SO4, it was 27.09 F g−1at%−1.
We describe the epidemiology of a coronavirus disease (COVID-19) outbreak in a call center in South Korea. We obtained information on demographic characteristics by using standardized epidemiologic ...investigation forms. We performed descriptive analyses and reported the results as frequencies and proportions for categoric variables. Of 1,143 persons who were tested for COVID-19, a total of 97 (8.5%, 95% CI 7.0%-10.3%) had confirmed cases. Of these, 94 were working in an 11th-floor call center with 216 employees, translating to an attack rate of 43.5% (95% CI 36.9%-50.4%). The household secondary attack rate among symptomatic case-patients was 16.2% (95% CI 11.6%- 22.0%). Of the 97 persons with confirmed COVID-19, only 4 (1.9%) remained asymptomatic within 14 days of quarantine, and none of their household contacts acquired secondary infections. Extensive contact tracing, testing all contacts, and early quarantine blocked further transmission and might be effective for containing rapid outbreaks in crowded work settings.
Plants adjust their architecture to optimize growth and reproductive success under changing climates. Hypocotyl elongation is a pivotal morphogenic trait that is profoundly influenced by light and ...temperature conditions. While hypocotyl photomorphogenesis has been well characterized at the molecular level, molecular mechanisms underlying hypocotyl thermomorphogenesis remains elusive. Here, we demonstrate that the E3 ubiquitin ligase CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) conveys warm temperature signals to hypocotyl thermomorphogenesis.
To investigate the roles of COP1 and its target ELONGATED HYPOCOTYL 5 (HY5) during hypocotyl thermomorphogenesis, we employed Arabidopsis mutants that are defective in their genes. Transgenic plants overexpressing the genes were also produced. We examined hypocotyl growth and thermoresponsive turnover rate of HY5 protein at warm temperatures under both light and dark conditions.
Elevated temperatures trigger the nuclear import of COP1, thereby alleviating the suppression of hypocotyl growth by HY5. While the thermal induction of hypocotyl growth is circadian-gated, the degradation of HY5 by COP1 is uncoupled from light responses and timing information.
We propose that thermal activation of COP1 enables coincidence between warm temperature signaling and circadian rhythms, which allows plants to gate hypocotyl thermomorphogenesis at the most profitable time at warm temperatures.
In a multiple-receiver wireless power transfer (WPT) system, determining the condition for uniform power distribution at a high transfer efficiency is a challenging issue. In this paper, a selective ...WPT technique using magnetic resonance coupling (MRC) is introduced for smart power delivery in a multiple-receiver system. The proposed method selectively and exclusively delivers power to only one designated receiver among multiple receivers, eliminating the cross-coupling effect and unbalanced power division problem across the receivers. This is achieved by separating the resonant frequencies of the receivers to isolate the coupling effects between coils. The power division ratio of the receivers is controlled by changing the duration time ratio for power transfer. In this paper, a one-transmitter three-receiver selective MRC system is designed and fabricated. The power distribution is demonstrated under impedance matched condition, showing a power transfer efficiency of 24%-29% at a very small coupling coefficient of 0.01 with a 12-mm-diameter receiver coil. Distance compensation and a one-way communication of time division multiple access are demonstrated for a multiple-receiver system, using the proposed method.
Lactic acid bacteria (LAB) are significant groups of probiotic organisms in fermented food and are generally considered safe. LAB regulate soil organic matter and the biochemical cycle, detoxify ...hazardous chemicals, and enhance plant health. They are found in decomposing plants, traditional fermented milk products, and normal human gastrointestinal and vaginal flora. Exploring LAB identified in unknown niches may lead to isolating unique species. However, their classification is quite complex, and they are adapted to high sugar concentrations and acidic environments. LAB strains are considered promising candidates for sustainable agriculture, and they promote soil health and fertility. Therefore, they have received much attention regarding sustainable agriculture. LAB metabolites promote plant growth and stimulate shoot and root growth. As fertilizers, LAB can promote biodegradation, accelerate the soil organic content, and produce organic acid and bacteriocin metabolites. However, LAB show an antagonistic effect against phytopathogens, inhibiting fungal and bacterial populations in the rhizosphere and phyllosphere. Several studies have proposed the LAB bioremediation efficiency and detoxification of heavy metals and mycotoxins. However, LAB genetic manipulation and metabolic engineered tools provide efficient cell factories tailor-made to produce beneficial industrial and agro-products. This review discusses lactic acid bacteria advantages and limitations in sustainable agricultural development.
Although approved programmed cell death protein (PD)-1 inhibitors show durable responses, clinical benefits to these agents are only seen in one-third of patients in most cancer types. Therefore, ...strategies for improving the response to PD-1 inhibitor for treating various cancers including non-small cell lung cancer (NSCLC) are urgently needed. Compared with genome and transcriptome, tumor DNA methylome in anti-PD-1 response was relatively unexplored. We compared the pre-treatment methylation status of cis-regulatory elements between responders and non-responders to treatment with nivolumab or pembrolizumab using the Infinium Methylation EPIC Array, which can profile ~850,000 CpG sites, including ~350,000 CpG sites located in enhancer regions. Then, we analyzed differentially methylated regions overlapping promoters (pDMRs) or enhancers (eDMRs) between responders and non-responders to PD-1 inhibitors. We identified 1007 pDMRs and 607 eDMRs associated with the anti-PD-1 response. We also identified 1109 and 1173 target genes putatively regulated by these pDMRs and eDMRs, respectively. We found that eDMRs contribute to the epigenetic regulation of the anti-PD-1 response more than pDMRs. Hypomethylated pDMRs of Cytohesin 1 Interacting Protein (CYTIP) and TNF superfamily member 8 (TNFSF8) were more predictive than programmed cell death protein ligand 1 (PD-L1) expression for anti-PD-1 response and progression-free survival (PFS) and overall survival (OS) in a validation cohort, suggesting their potential as predictive biomarkers for anti-PD-1 immunotherapy. The catalog of promoters and enhancers differentially methylated between responders and non-responders to PD-1 inhibitors presented herein will guide the development of biomarkers and therapeutic strategies for improving anti-PD-1 immunotherapy in NSCLC.
We present a compact, filtering power divider (FPD) using integrated passive device technology (IPD) for mm‐wave applications. Our proposed FPD design integrates quarter‐wavelength coupled‐resonator ...bandpass filters with a Wilkinson power divider, using size reduction techniques. Coupled coplanar waveguides provide excellent coupling while occupying a small area, and metal‐insulator‐metal capacitors offer the required λ/4 phase shift without length extension. The center frequency of the filtering power divider/combiner (FPD/C) is located at 30‐GHz. We demonstrate our FPD design by fabricating four prototypes with parameter variations. The insertion loss, fractional bandwidth, and size of the FPD/C designed in this study are from 2.56 to 3.3 dB, from 9.67% to 19.4%, and from 0.592 to 0.220‐mm2, respectively. In addition, the return loss of all models at the center frequency is 28.5 dB or more, and the isolation is 16.6 dB or more.
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