Microfluidic Biomaterials For In Vitro 3-D Culture

Clinicians have made practical efforts for over 100 years in replacing damaged tissues and organs. However, organ shortage and rejection still remain major challenges. Rapidly emerging tissue engineering, which is interdisciplinary medical science and technology, has gained attention to resolve the challenges. The grand aim of tissue engineering is to develop implantable tissue constructs via in vitro culture of cells seeded in three-dimensional (3-D) scaffolds formed in biomaterials. Microengineering and microfluidic techniques have demonstrated promising proof-ofconcept in developing potentially valuable in vitro culture systems. However, in conventional microfluidic systems, the culture environment is confined to channels. Moreover, most of currently existing cell culture systems do not allow for the creation of fully functional tissues. This limitation is also due to a lack of understanding principles of tissue function and growth. Tissue-scale biology, combined with molecular and cell biology, would allow for better understandings of the principles, and can be complementarily interconnected to tissue engineering. Therefore, we must develop in vitro tools to overcome the challenges and to enable tissue engineering and tissue-scale biology. The development of the enabling tools could lead to exploitation of detailed principles and mechanisms in the study of physiological and pathological processes in a quantitative manner. First, we present the development of microfluidic scaffolds that are formed by embedding microfluidic networks directly within biomaterials. Experiments with chondrocytes in calcium alginate demonstrated that these embedded microchannels enable the maintenance of a uniform metabolic environment within the bulk of the scaffold and the creation of distinct soluble environments experienced by cells in their 3-D environment. The generalization of the process into type I collagen allows for the embedded microchannels to serve as a template for microvascular endothelialization within a matrix that can support cellular remodeling. In the new experimental context offered by these microfluidic scaffolds, we present detailed mass transport considerations in microfluidic biomaterials. Such considerations include quantitative measurements of 1) diffusion of non-reactive solutes and 2) metabolic activity of reactive solutes such as oxygen, which should be also used in designing and operating microfluidic biomaterials. Finally, we present the development of oxygen-sensing particles that are dispersible in aqueous environment and biocompatible. Experiments show that the oxygen-sensing particles also allow monitoring oxygen concentration in a both spatially and temporally resolved manner. We can use this tool for the direct visualization and optical measurement of oxygen-depletion lengths within cell-seeded 3-D scaffolds in vitro, and the measurement of oxygen levels in animal blood streams in vivo

CR-COPEC: Causal Rationale of Corporate Performance Changes to Learn from Financial Reports

In this paper, we introduce CR-COPEC called Causal Rationale of Corporate Performance Changes from financial reports. This is a comprehensive large-scale domain-adaptation causal sentence dataset to detect financial performance changes of corporate. CR-COPEC contributes to two major achievements. First, it detects causal rationale from 10-K annual reports of the U.S. companies, which contain experts' causal analysis following accounting standards in a formal manner. This dataset can be widely used by both individual investors and analysts as material information resources for investing and decision making without tremendous effort to read through all the documents. Second, it carefully considers different characteristics which affect the financial performance of companies in twelve industries. As a result, CR-COPEC can distinguish causal sentences in various industries by taking unique narratives in each industry into consideration. We also provide an extensive analysis of how well CR-COPEC dataset is constructed and suited for classifying target sentences as causal ones with respect to industry characteristics. Our dataset and experimental codes are publicly available.Comment: Accepted in Findings of EMNLP 202

Longitudinal changes in health-related quality of life according to clinical course among patients with non-tuberculous mycobacterial pulmonary disease: a prospective cohort study

Improvement in health-related quality of life (HRQL) has been suggested as an alternative treatment goal of non-tuberculous mycobacterial pulmonary disease (NTM-PD). This study was performed to elucidate the longitudinal changes in HRQL using St. Georges Respiratory Questionnaire (SGRQ) among patients with NTM-PD according to their clinical course. Patients with NTM-PD who participated in Seoul National University Hospitals prospective NTM cohort were screened. Participants for whom the SGRQ score was estimated with the one-year interval for ≥ three times were included. The longitudinal trends of the SGRQ score were assessed. The impact of the clinical course on the change in the SGRQ score was elucidated using multilevel mixed-effects linear regression with a repeated-measures model. In total, 114 patients were analyzed. During the median 5-year observation period, 53 patients started anti-mycobacterial treatment and 61 patients were observed without treatment. Among the treated patients, 24 (45.2%) achieved microbiological cure. Patients who required treatment eventually had worsening SGRQ scores with time compared with patients who could be observed without treatment (P < 0.001). In cured patients, the SGRQ score decreased from 33.9 at baseline to 20.8 at 1 year post-treatment (P < 0.001), 21.3 at 2 years (P < 0.001), and 17.6 at 3 years (P < 0.001). The SGRQ scores also decreased for 2 years of treatment in patients with NTM-PD that could not be cured, although this decrease did not last for 3 years of treatment. Worsening HRQL scores were associated with the initiation of treatment and, in turn, treatment improved HRQL scores of patients with NTM-PD. This study was registered to the ClinicalTrials.gov (Identifier: NCT01616745 / registration date: June 12, 2012). The protocol was retrospectively registered

Modulating and monitoring the functionality of corticostriatal circuits using an electrostimulable microfluidic device

Abstract The central nervous system is organized into different neural circuits, each with particular functions and properties. Studying neural circuits is essential to understanding brain function and neuronal diseases. Microfluidic systems are widely used for reconstructing and studying neural circuits but still need improvement to allow modulation and monitoring of the physiological properties of circuits. In this study, we constructed an improved microfluidic device that supports the electrical modulation of neural circuits and proper reassembly. We demonstrated that our microfluidic device provides a platform for electrically modulating and monitoring the physiological function of neural circuits with genetic indicators for synaptic functionality in corticostriatal (CStr) circuits. In particular, our microfluidic device measures activity-driven Ca2+ dynamics using Ca2+ indicators (synaptophysin-GCaMP6f and Fluo5F-AM), as well as activity-driven synaptic transmission and retrieval using vGlut-pHluorin. Overall, our findings indicate that the improved microfluidic platform described here is an invaluable tool for studying the physiological properties of specific neural circuits

Tumor spheroid-based and microtumor-based vascularized models for replicating the vascularized tumor microenvironment

Background Tumor vasculature is a crucial pathway for supplying nutrients and oxygen to tumors during their progression, as well as facilitating the delivery of anticancer drugs or immunotherapeutic agents. Microfluidic technology has emerged as a powerful tool in creating microenvironments within 3-dimensional cell cultures that more closely resemble in vivo conditions, by enabling precise control of fluid flow. As a result, microfluidic devices have made significant progress in replicating both the structural and functional characteristics of the tumor microenvironment in vitro. Methods and Results In this study, we present two approaches for reconstructing the tumor vasculature using tumor spheroids or microtumors, with a particular focus on in vivo functional mimicry and experimental reproducibility. Tumor spheroid-based vascular models provide an observatory window into tumor vasculature centered on tumor spheroids, enabling quantitative measurement of the degree of abnormality of blood vessels developing around the tumor spheroid and the invasiveness of metastatic tumors. Microtumor-based vascular models, on the other hand, have the potential to enhance our comprehension of advanced and metastatic cancers at the single-cell level by elucidating the proliferative and metastatic capacities of tumor cells, as well as the vascular permeability that is contingent upon the subtypes of tumor cells. Conclusion Our platforms provide valuable insights into the development of novel in vitro models for studying the tumor microenvironment and advancing our understanding of cancer biology

Interference-free, lightweight wireless neural probe system for investigating brain activity during natural competition

© 2021 The Author(s)Competition is one of the most fundamental, yet complex, conflicts between social animals, and previous studies have indicated that the medial prefrontal cortex (mPFC) region of a brain is involved in social interactions. However, because we do not have a lightweight, wireless recording system that is free of interference, it is still unclear how the neural activity of the mPFC region is involved in the diverse, interacting behaviors that comprise competition. Herein, we present an interference-free, lightweight, wireless neural probe system that we applied to two mice to measure mPFC neural activities during a food competition test. In the test, we categorized 18 behavioral repertoires expressed by the mice. From the analysis of the neural signals during each repetition of the test, we found that the mPFC neural activity had the most positive correlation with goal-driven competitive behaviors, such as guarding resources and behaviors related to the extortion of resources. Remarkably, we found that the neural activity associated with guarding behavior was higher than that of extorting behavior, and this highlighted the importance of resource-guarding behavior for winning the competition, i.e., ‘winning a trophy is hard, but keeping it is harder’. Our approach in which a wireless system is used will enable in-depth studies of the brains of mice in their natural social interactions.11Nsciescopu

Effect of chlorhexidine Mouthrinse on prevention of microbial contamination during EBUS-TBNA: a randomized controlled trial

Background Although endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive procedure, fatal infectious complications have been reported. However, adequate preventive strategies have not been determined. We aimed to investigate the effect of chlorhexidine mouthrinse on the prevention of microbial contamination during EBUS-TBNA. Methods In this single-center, assessor-blinded, parallel-group randomized controlled trial, we randomly assigned adult participants undergoing EBUS-TBNA using a convex probe to gargle for 1 minute with 100 mL of 0.12% chlorhexidine gluconate before EBUS-TBNA or to receive usual care (no chlorhexidine mouthrinse). Aspiration needle wash samples were collected immediately after completion of EBUS-TBNA by instilling sterile saline into the used needle. The primary outcome was colony forming unit (CFU) counts per mL of needle wash samples in aerobic cultures. Secondary outcomes were CFU counts per mL of needle wash samples in anaerobic cultures, fever within 24 hours after EBUS-TBNA, and infectious complications within 4 weeks after EBUS-TBNA. Results From January 2021 to June 2021, 106 patients received either chlorhexidine mouthrinse (n = 51) or usual care (n = 55). The median CFU counts of needle wash samples in aerobic cultures were not significantly different in the two groups (10 CFU/mL vs 20 CFU/mL; P = 0.70). There were no significant differences between the groups regarding secondary outcomes, including median CFU counts in anaerobic cultures (P = 0.41) and fever within 24 hours after EBUS-TBNA (11.8% vs 5.6%, P = 0.31). There were no infectious complications within 4 weeks in both groups. Conclusions Chlorhexidine mouthrinse did not reduce CFU counts in needle wash samples of EBUS-TBNA.This study was supported by a 2020 Grant from the Korean Academy of Tuberculosis and Respiratory Diseases

Microstructural control of a SSZ-13 zeolite film via rapid thermal processing

A SSZ-13 zeolite (CHA type zeolite having a pore size of 0.37 × 0.42 nm2) can separate CO2 (0.33 nm) from larger molecules (N2 (0.364 nm) or CH4 (0.38 nm)) because of the molecular size differences. However, methods to control the non-zeolitic defects of SSZ-13 membranes are lacking. Here, we demonstrate that rapid thermal processing (RTP) of as-synthesized SSZ-13 films tunes their microstructural defect properties and increases their CO2 separation ability. The maximum CO2/N2 separation factor (SF) at 30 °C increased from ~2.9 to ~4.8 due to RTP because the defective region was reduced. Furthermore, the addition of water vapor (the third main component of coal-fired power plant flue gas) to the feed markedly improved the CO2/N2 SF of the RTP-treated SSZ-13 membrane; from ~4.3 at 50 °C (a representative flue gas stream temperature) under dry conditions to ~10.1 under wet conditions (vs. ~1.6 across the conventionally calcined counterpart). Furthermore, the less-defective RTP-treated SSZ-13 membranes achieved a CO2/CH4 SF as high as ~43.7 under wet conditions at 50 °C. Fluorescence confocal optical microscopy analyses complemented with the permeation modeling revealed that the reduced defect size after RTP (~2.2 nm against ~3.9 nm for the conventionally calcined counterpart) improved the CO2 permselectivity, even though the defect porosities were low (~0.1%)

An Oriented, Siliceous Deca-dodecasil 3R (DDR) Zeolite Film for Effective Carbon Capture: Insight into Its Hydrophobic Effect

An all-silica deca-dodecasil 3R (Si-DDR) zeolite with a pore size of 0.36 ?? 0.44 nm2 is highly desirable for membrane-based separation of CO2 (0.33 nm) from N2 (0.364 nm), which is critical in the post-combustion carbon capture process, via molecular recognition of their slight size difference. For the first time, we acquired h0h-oriented, hydrophobic DDR zeolite films through the epitaxial growth of a DDR seed layer with a structure directing agent of methyltropinium iodide. The degree of the out-of-plane orientation and inter-growth was increased with the secondary growth time, while reducing the defects that provide non-selective pathways. The resulting DDR membrane showed a CO2/N2 separation factor (SF) as high as 11.9 at 50 ??C (a representative flue-gas temperature) under the dry condition. More desirably, it could achieve a much enhanced CO2/N2 SF up to 15.9 at 50 ??C in the presence of H2O vapor (3rd largest component in the flue-gas). The transport of the larger N2 molecule, plausibly its entering the pore mouth of DDR zeolites, was more inhibited by H2O molecules adsorbed on the membrane surface; it appears that this surface resistance was due to the hydrophobicity of the highly siliceous DDR membrane and beneficial for improving CO2/N2 SFs under the wet condition.clos