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.
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.
Alginate microribbons with longitudinally grooved microstructures are continuously fabricated by means of a microfluidic system. The number and dimensions of the microgroovesare successfully ...controlled by regulation of the slit‐shaped channel (yellow in figure). This method opens up the possibility of mass production of scaffolds for tissue engineering purposes, as it is proved that the grooved flat fibers can be used to align other types of cells in culture.
The endoplasmic reticulum (ER) is a dynamic organelle that synthesizes and folds proteins. An imbalance between the ER protein synthesis load and its folding capacity triggers the unfolded protein ...response, thereby restoring normal ER functions via size adjustment. Inspired by such inherent genetic programming events, we engineered Saccharomyces cerevisiae to expand the ER by overexpressing a key ER size regulatory factor, INO2. ER space expansion enhanced ER protein synthesis and folding capacity, and relieved metabolic constraints imposed by the limited enzyme abundance. Harnessing the yeast ER for metabolic engineering, we ultimately increased the production of squalene and cytochrome P450-mediated protopanaxadiol by 71-fold and 8-fold, compared to their respective control strains without overexpression of INO2. Furthermore, genome-wide transcriptome analysis of the ER-expanded strain revealed that the significant improvement in terpene production was associated with global rewiring of the metabolic network. Therefore, the yeast ER can be engineered as a specialized compartment for enhancing terpene production, representing new possibilities for the high-level production of other value-added chemicals.
•This study aims to harness yeast endoplasmic reticulum (ER) for functional assembly of challenging metabolic pathways.•ER expansion can lead to increased abundance of ER-associated enzymes and consequential improvement in metabolic capacity.•ER expansion increased production of squalene and cytochrome P450-mediated protopanaxadiol by 71- and 8-fold, respectively.•The squalene titer of 634 mg/L was achieved by shake flask fermentation, the highest titer reported to date in S. cerevisiae.•RNA-seq analysis provides novel frameworks for designing genetic network to construct a platform cell for terpene synthesis.
Vitamin D plays an important role in the immune system, and its deficiency has been implicated in various skin diseases, including atopic dermatitis and psoriasis. Acne is a common inflammatory skin ...disease; however, the association with vitamin D remains unclear.
We evaluated vitamin D levels in patients with acne to determine the effect of vitamin D supplementation.
This study included 80 patients with acne and 80 healthy controls. Serum 25-hydroxyvitamin D (25(OH)D) levels were measured, and demographic data were collected. Vitamin D-deficient patients were treated with oral cholecalciferol at 1000 IU/day for 2 months.
Deficiency in 25(OH)D was detected in 48.8% of patients with acne, but in only 22.5% of the healthy controls. The level of 25(OH)D was inversely associated with the severity of acne, and there was a significant negative correlation with inflammatory lesions. In a subsequent trial, improvement in inflammatory lesions was noted after supplementation with vitamin D in 39 acne patients with 25(OH)D deficiency.
Limitations of the study include the small number of patients in the supplementation study and the natural fluctuation of acne.
Vitamin D deficiency was more frequent in patients with acne, and serum 25(OH)D levels were inversely correlated with acne severity, especially in patients with inflammatory lesions.
Streptococcus pneumoniae causes pneumococcal disease, and older adults are at an increased risk. Sequential vaccination of 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent ...pneumococcal polysaccharide vaccine (PPSV23) is recommended for broad protection against pneumococcal disease in some countries.
This phase III trial evaluated the safety, tolerability, and immunogenicity of sequential administration of either V114 (a 15-valent PCV containing serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F) or PCV13, followed 12 months later by PPSV23, in healthy adults aged ≥50 years (NCT03480763). A total of 652 participants were randomized 1:1 to receive either V114 or PCV13, followed by PPSV23.
The most common solicited adverse events (AEs) following PCV vaccination included injection-site pain and fatigue. Higher proportions of participants with these events were observed in the V114 group following PCV; however, these differences were not clinically significant. Following PPSV23 vaccination, the most common solicited AEs were injection-site pain and injection-site swelling; the proportions of participants with these events were comparable between both groups. Incidence of serious AEs was low in both groups following PCV and PPSV23, and none were related to study vaccines. No deaths occurred during the study. Serum opsonophagocytic activity geometric mean titers and immunoglobulin G geometric mean concentrations were comparable between both groups for all 15 serotypes in V114 following PPSV23. Immune responses elicited by V114 persisted for at least 12 months. Immune responses at 30 days and 12 months post-vaccination with PCV were comparable between both groups for the 13 shared serotypes and higher in the V114 group for the V114-unique serotypes (22F and 33F).
Administration of V114 followed by PPSV23 was well tolerated and induced comparable antibody levels to PCV13 followed by PPSV23 in healthy adults aged ≥50 years.
•An 4D printed SMC actuator was fabricated using SMA and SMP with a FDM 3D printer.•A volume fraction of SMA:SMP of 1:5 showed the largest length change of 8 mm, and the most rapid response time of 4 ...s.•The reversible actuator mechanism explains the SMC actuation via each shape memory effect.•SMC showed potential application for stents and valve controllers via 3D printing technology to achieve customized designs.
A fused deposition modeling (FDM) tool was used to fabricate a shape memory composite (SMC) that combined a shape memory alloy (SMA) with a shape memory polymer (SMP). The SMA caused a shape memory effect due to a phase change between martensite and austenite phases, in turn due to a temperature change. Also, the SMP had a shape memory effect caused by changes in the proportions of hard and soft segments near the glass transition temperature (Tg). Usually, common SMAs and SMPs are not reversible, so these materials do not go back to their original shapes once they are deformed. In this study, we fabricated 4D printing actuator via reversible SMC actuations using 3D printing technology. Nylon 12 was used as the 3D printing material in filament form. Moreover, the volume fraction of SMA to SMP was varied to find the optimum ratio for good operation cycles. A volume fraction of SMA:SMP of 1:5 showed the largest length change, of 8 mm, and the most rapid response time, of 4 s in overall dimension of 140mm×10mm×1mm (length×width×thickness).Thus, the SMC showed promising results for the application of stents and valve controllers that could be manufactured by 3D printing technology.
Stimuli-responsive nanoparticles are regarded as an ideal candidate for anticancer drug targeting. We synthesized glutathione (GSH) and magnetic-sensitive nanocomposites for a dual-targeting ...strategy. To achieve this goal, methoxy poly (ethylene glycol) (MePEG) was grafted to water-soluble chitosan (abbreviated as ChitoPEG). Then doxorubicin (DOX) was conjugated to the backbone of chitosan via disulfide linkage. Iron oxide (IO) magnetic nanoparticles were also conjugated to the backbone of chitosan to provide magnetic sensitivity. In morphological observation, images from a transmission electron microscope (TEM) showed that IO nanoparticles were embedded in the ChitoPEG/DOX/IO nanocomposites. In a drug release study, GSH addition accelerated DOX release rate from nanocomposites, indicating that nanocomposites have redox-responsiveness. Furthermore, external magnetic stimulus concentrated nanocomposites in the magnetic field and then provided efficient internalization of nanocomposites into cancer cells in cell culture experiments. In an animal study with CT26 cell-bearing mice, nanocomposites showed superior magnetic sensitivity and then preferentially targeted tumor tissues in the field of external magnetic stimulus. Nanocomposites composed of ChitoPEG/DOX/IO nanoparticle conjugates have excellent anticancer drug targeting properties.
Recently, several studies have proposed methods for measuring cuffless blood pressure (BP) using finger photoplethysmogram (PPG) signals. This study presents a new BP estimation system that measures ...PPG signals under progressive finger pressure, making the system relatively robust to errors caused by finger position when using the cuffless oscillometric method. To reduce errors caused by finger position, we developed a sensor that can simultaneously measure multi-channel PPG and force signals in a wide field of view (FOV). We propose a deep-learning-based algorithm that can learn to focus on the optimal PPG channel from multi channel PPG using an attention mechanism. The errors (ME ± STD) of the proposed multi channel system were 0.43±9.35 mmHg and 0.21 ± 7.72 mmHg for SBP and DBP, respectively. Through extensive experiments, we found a significant performance difference depending on the location of the PPG measurement in the BP estimation system using finger pressure.
Hair growth is the cyclically regulated process that is characterized by growing phase (anagen), regression phase (catagen) and resting phase (telogen). Hair follicle stem cells (HFSCs) play pivotal ...role in the control of hair growth cycle. It has been notified that stem cells have the distinguished metabolic signature compared to differentiated cells, such as the preference to glycolysis rather than mitochondrial respiration. Crif1 is a mitochondrial protein that regulates the synthesis and insertion of oxidative phosphorylation (OXPHOS) polypeptides to inner membrane of mitochondria. Several studies demonstrate that tissue-specific knockout of Crif1 leads to mitochondrial dysfunction. In this study, we investigated the effect of mitochondrial dysfunction in terms of Crif1 deficiency on the hair growth cycle of adult mice. We created two kinds of inducible conditional knockout (icKO) mice. In epidermal specific icKO mice (Crif1 K14icKO), hair growth cycle was significantly retarded compared to wild type mice. Similarly, HFSC specific icKO mice (Crif1 K15icKO) showed significant retardation of hair growth cycle in depilation-induced anagen model. Interestingly, flow cytometry revealed that HFSC populations were maintained in Crif1 K15icKO mice. These results suggest that mitochondrial function in HFSCs is important for the progression of hair growth cycle, but not for maintenance of HFSCs.
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