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.
Mechanosensory feedback from the digestive tract to the brain is critical for limiting excessive food and water intake, but the underlying gut-brain communication pathways and mechanisms remain ...poorly understood
. Here we show that, in mice, neurons in the parabrachial nucleus that express the prodynorphin gene (hereafter, PB
neurons) monitor the intake of both fluids and solids, using mechanosensory signals that arise from the upper digestive tract. Most individual PB
neurons are activated by ingestion as well as the stimulation of the mouth and stomach, which indicates the representation of integrated sensory signals across distinct parts of the digestive tract. PB
neurons are anatomically connected to the digestive periphery via cranial and spinal pathways; we show that, among these pathways, the vagus nerve conveys stomach-distension signals to PB
neurons. Upon receipt of these signals, these neurons produce aversive and sustained appetite-suppressing signals, which discourages the initiation of feeding and drinking (fully recapitulating the symptoms of gastric distension) in part via signalling to the paraventricular hypothalamus. By contrast, inhibiting the same population of PB
neurons induces overconsumption only if a drive for ingestion exists, which confirms that these neurons mediate negative feedback signalling. Our findings reveal a neural mechanism that underlies the mechanosensory monitoring of ingestion and negative feedback control of intake behaviours upon distension of the digestive tract.
Diverse intestinal components (e.g., gut-associated neurons, immune cells, gut microbes, and epithelium) are intimately intertwined with each other to maintain homeostasis in the gut. In a recent ...issue of Cell, Zhang et al. (2022) and Yang et al. (2022) present complementary studies uncovering interactions between nociceptor neurons, gut epithelium, and the microbiome to protect intestinal tissue from inflammation.
Diverse intestinal components (e.g., gut-associated neurons, immune cells, gut microbes, and epithelium) are intimately intertwined with each other to maintain homeostasis in the gut. In a recent issue of Cell, Zhang et al. and Yang et al. present complementary studies uncovering interactions between nociceptor neurons, gut epithelium, and the microbiome to protect intestinal tissue from inflammation.
Electric vehicle (EV) demand is considerably increasing, aided by battery technology development and government policy support. Therefore, it is necessary to consider various charging infrastructures ...and secure sufficient power to support this. In several cities or countries, a large population lives in a small area, and the supply of large residential complexes such as apartments is common. Given that old apartments may not have sufficient power capacity, it is challenging to secure additional power for charging EVs. In particular, power shortages can intensify during high power usage, such as the summer season, and may become an obstacle to the spread of EVs. Therefore, an efficient charging strategy for residential complexes must be established under the condition of limited power supply. This study proposes two scheduling methods to optimally charge EVs in residential complexes considering limited power supply. The proposed scheduling algorithms are thoroughly examined through extensive simulations with parking data collected from real situations and are demonstrated to be effective for online EV charging systems.
In the present study, composite sandwich structures were investigated to evaluate the effects of porous foams and surface patterns on structural stability and mass reduction of the composite sandwich ...structures. The composite structures used in the experiments consisted of three layers; the top and bottom polycarbonate (PC) layers and the core porous foam layers. Copper, nickel, and polypropylene (PP) foams were considered in the modeling of composite structures. Laser cutting technology was applied to the top PC layers of the composite structures to realize the surface patterns. Impact hammer and mass drop tests were performed on the composite structures to investigate their vibration attenuation and shock absorption performances. Numerous combinations of composite structures were considered by varying the foam materials and layer thicknesses to determine the best configuration. Finite element method (FEM)-based simulations were conducted to verify the experimental results. The results of this study support the implementation of porous foams and surface patterns for the increase in vibration attenuation and shock absorption performance, while achieving mass reduction for various applications in the engineering field.
•Surface patterns are realized on sandwich structures using laser cutting technology.•Porous foam and surface patterns are utilized to enhance vibration attenuation performance.•Increased shock absorption is induced by core porous foam layers of sandwich structures.•Finite element simulations are done to verify the experimental results of impact hammer and mass drop tests.
Quetiapine is a drug used to treat schizophrenia, bipolar disorder, and major depressive disorder. However, it can cause mild or severe hepatic adverse events and rarely fatal liver damage. This ...study was aimed at investigating hepatic toxicity caused by quetiapine use by analyzing the information captured from hospital electronic health records by using the Observational Medical Outcomes Partnership common data model (CDM).
This was a retrospective observational study involving a nested case-control method. A CDM based on an electronic health record database from five hospitals between January 2009 and May 2020 was used. We analyzed the status of quetiapine use, adverse events, and hepatic impairment.
The numbers of patients with non-serious and severe hepatic adverse reactions were 2566 (5.05%) and 835 (1.64%) out of 50 766 patients, respectively. After adjusting for covariates, the odds ratio of hepatic adverse events was 2.35 (95% CI: 2.03-2.72), and the odds ratio of severe hepatic adverse events was 1.76 (95% CI: 1.16-2.66).
Our findings suggest that quetiapine should be cautiously used, and hepatic function should be monitored in patients using quetiapine because it can cause mild or severe hepatic adverse events, complications, and in rare cases, fatal liver damage.
Ultra-wideband (UWB) wireless communication is prospering as a powerful partner of the Internet-of-things (IoT). Due to the ongoing development of UWB wireless communications, the demand for ...high-speed and medium resolution analog-to-digital converters (ADCs) continues to grow. The successive approximation register (SAR) ADCs are the most powerful candidate to meet these demands, attracting both industries and academia. In particular, recent time-interleaved SAR ADCs show that multi-giga sample per second (GS/s) can be achieved by overcoming the challenges of high-speed implementation of existing SAR ADCs. However, there are still critical issues that need to be addressed before the time-interleaved SAR ADCs can be applied in real commercial applications. The most well-known problem is that the time-interleaved SAR ADC architecture requires multiple sub-ADCs, and the mismatches between these sub-ADCs can significantly degrade overall ADC performance. And one of the most difficult mismatches to solve is the sampling timing skew. Recently, research to solve this timing-skew problem has been intensively studied. In this paper, we focus on the cutting-edge timing-skew calibration technique using a window detector. Based on the pros and cons analysis of the existing techniques, we come up with an idea that increases the benefits of the window detector-based timing-skew calibration techniques and minimizes the power and area overheads. Finally, through the continuous development of this idea, we propose a timing-skew calibration technique using a comparator offset-based window detector. To demonstrate the effectiveness of the proposed technique, intensive works were performed, including the design of a 7-bit, 2.5 GS/s 5-channel time-interleaved SAR ADC and various simulations, and the results prove excellent efficacy of signal-to-noise and distortion ratio (SNDR) and spurious-free dynamic range (SFDR) of 40.79 dB and 48.97 dB at Nyquist frequency, respectively, while the proposed window detector occupies only 6.5% of the total active area, and consumes 11% of the total power.
To investigate the visual/anatomical outcome of diabetic macular edema (DME) patients lost to follow-up (LTFU) for more than 1 year during intravitreal anti-VEGF treatment. A retrospective review of ...182 treatment-naïve DME patients was performed. Among them, we identified patients LTFU for more than 1 year during anti-VEGF treatment. Visual acuity and anatomic outcomes at the first visit, last visit before being LTFU, return visit, and after re-treatment were analyzed and compared with those of DME patients with regular follow-up. Patients who had continuous follow-up visits were assigned to the control group. Sixty patients (33%) with DME were LTFU for more than 1 year during anti-VEGF treatment. Multivariate analysis revealed that the ratio of male (p = 0.004), diabetes mellitus (DM) duration less than 5 years (p = 0.015), and poor early anatomic response (p = 0.012) were higher compared to the control group. Eighteen patients returned to the clinic and received re-treatment. After re-treatment with anti-VEGF, central subfield thickness (CST) was significantly improved to the CST of before LTFU. However, visual acuity did not recover to the level before LTFU (0.63 ± 0.26 vs. 0.45 ± 0.28, p = 0.003). About thirty percent of DME patients were LTFU for more than 1 year. Permanent visual loss was observed in these LTFU patients. Patients with a high risk of LTFU such as male, early DM, and poor response after initial injections should be treated more aggressively to improve the visual outcomes.
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