Emerging Roles of Microfluidics in Brain Research: From Cerebral Fluids Manipulation to Brain-on-a-Chip and Neuroelectronic Devices Engineering.

Remarkable progress made in the past few decades in brain research enables the manipulation of neuronal activity in single neurons and neural circuits and thus allows the decipherment of relations between nervous systems and behavior. The discovery of glymphatic and lymphatic systems in the brain and the recently unveiled tight relations between the gastrointestinal (GI) tract and the central nervous system (CNS) further revolutionize our understanding of brain structures and functions. Fundamental questions about how neurons conduct two-way communications with the gut to establish the gut-brain axis (GBA) and interact with essential brain components such as glial cells and blood vessels to regulate cerebral blood flow (CBF) and cerebrospinal fluid (CSF) in health and disease, however, remain. Microfluidics with unparalleled advantages in the control of fluids at microscale has emerged recently as an effective approach to address these critical questions in brain research. The dynamics of cerebral fluids (i.e., blood and CSF) and novel in vitro brain-on-a-chip models and microfluidic-integrated multifunctional neuroelectronic devices, for example, have been investigated. This review starts with a critical discussion of the current understanding of several key topics in brain research such as neurovascular coupling (NVC), glymphatic pathway, and GBA and then interrogates a wide range of microfluidic-based approaches that have been developed or can be improved to advance our fundamental understanding of brain functions. Last, emerging technologies for structuring microfluidic devices and their implications and future directions in brain research are discussed.

iWRAP: A Theranostic Wearable Device With Real-Time Vital Monitoring and Auto-Adjustable Compression Level for Venous Thromboembolism.

OBJECTIVE: Venous Thromboembolism (VTE) is a commonly underdiagnosed disease with severe consequences and an exceedingly high mortality rate. Conventional compression wraps are devised for therapeutic purpose but lack diagnostic capacity. Recent advances in flexible electronics and wearable technologies offer many possibilities for chronic disease management. In particular, vital signs have been studied to show a strong correlation with the risk of VTE patients. In this study, we aim to develop an intelligent theranostic compression device, referred to as iWRAP, with the built-in capacity of real-time vital sign monitoring together with auto-adjustable compression level. METHODS: An instantaneous pneumatic feedback control with a high-resolution pressure sensor is integrated to provide a highly stabilized compression level at the prescribed interface pressure for an improved therapeutic outcome. Meanwhile, arterial pulse waveforms extracted from the pressure readings from the smart compression device can be utilized to derive the body vital signs, including heart rate (HR), respiratory rate (RR) and blood pressure (BP). RESULTS: A reliable delivery of the targeted compression level within ±5% accuracy in the range of 20-60 mmHg has been achieved through the feedback of the interface pressure. Both HR and RR have been measured within clinical-grade accuracies. Moreover, BP estimated using an ALA model has been achieved at low compression levels, which is also within a clinical-acceptable accuracy. The acquired vital information has been instantaneously fit into the clinically acceptable criteria for life-threatening PE risk with timely assessments. CONCLUSION: The iWRAP has shown the potential to become the first theranostic wearable device with both continuous delivery of accurate and effective compression therapy and real-time monitoring of life-threatening conditions for VTE patients.

Upregulated microRNA­330­3p promotes calcification in the bicuspid aortic valve via targeting CREBBP.

One key risk factor of aortic valve stenosis in clinical practice is bicuspid aortic valve (BAV). Increasing evidence indicates that numerous microRNAs (miRs/miRNAs) are involved in BAV calcification via their target genes. miR­330­3p was found to be involved in the deterioration of BAV calcification by miR profiling in human calcified BAV and tricuspid aortic valve (TAV) tissues in the present study and the underlying mechanism was investigated. RNA sequencing was performed on four BAV and four TAV tissues from patients with aortic stenosis before these leaflets were examined for the expression levels of miR­330­3p and CREB­binding protein (CREBBP) by reverse transcription­PCR. The alteration of functional factors associated with calcification was also assessed by Western blotting and immunohistochemistry in human aortic tissue samples. The putative target of miR­330­3p was detected by dual­luciferase assay in 293 cells. Furthermore, the influence of miR­330­3p expression on osteogenic progression was explored in cultured porcine valve interstitial cells (VICs). Rescue experiments of CRBBP were performed to confirm the influence of the miR­330­3p­CREBBP pathway in the calcification progress in porcine VICs. RNA sequencing indicated distinct expression of miR­330­3p in human BAV tissues compared with TAV, which was then confirmed by PCR. CREBBP expression levels in human BAV and TAV leaflets also demonstrated the opposite alterations. This negative correlation was then confirmed in cultured porcine VICs. Under an osteogenic environment, cellular calcification was promoted in miR­330­3p­overexpressed porcine VICs expressing higher bone morphogenetic protein 2, Runt­related transcription factor 2, matrix metalloproteinase (MMP)­2, MMP­9 and collagen I compared with controls. Rescue experiments further confirmed that miR­330­3p played its role via targeting CREBBP in porcine VICs. Collectively, miR­330­3p was upregulated in calcified BAV compared with TAV. The upregulation of miR­330­3p promotes the calcification progress partially via targeting CREBBP.

Supercapacitive Iontronic Nanofabric Sensing.

The study of wearable devices has become a popular research topic recently, where high-sensitivity, noise proof sensing mechanisms with long-term wearability play critical roles in a real-world implementation, while the existing mechanical sensing technologies (i.e., resistive, capacitive, or piezoelectric) have yet offered a satisfactory solution to address them all. Here, we successfully introduced a flexible supercapacitive sensing modality to all-fabric materials for wearable pressure and force sensing using an elastic ionic-electronic interface. Notably, an electrospun ionic fabric utilizing nanofibrous structures offers an extraordinarily high pressure-to-capacitance sensitivity (114 nF kPa-1 ), which is at least 1000 times higher than any existing capacitive sensors and one order of magnitude higher than the previously reported ionic devices, with a pressure resolution of 2.4 Pa, achieving high levels of noise immunity and signal stability for wearable applications. In addition, its fabrication process is fully compatible with existing industrial manufacturing and can lead to cost-effective production for its utility in emerging wearable uses in a foreseeable future.

Proteome analysis of up-regulated proteins in the rat spinal cord induced by transection injury.

The inability of the CNS to regenerate in adult mammals propels us to reveal associated proteins involved in the injured CNS. In this paper, either thoracic laminectomy (as sham control) or thoracic spinal cord transection was performed on male adult rats. Five days after surgery, the whole spinal cord tissue was dissected and fractionated into water-soluble (dissolved in Tris buffer) and water-insoluble (dissolved in a solution containing chaotropes and surfactants) portions for 2-DE. Protein identification was performed by MS and further confirmed by Western blot. As a result, over 30 protein spots in the injured spinal cord were shown to be up-regulated no less than 1.5-fold. These identified proteins possibly play various roles during the injury and repair process and may be functionally categorized as several different groups, such as stress-responsive and metabolic changes, lipid and protein degeneration, neural survival and regeneration. In particular, over-expression of 11-zinc finger protein and glypican may be responsible for the inhibition of axonal growth and regeneration. Moreover, three unknown proteins with novel sequences were found to be up-regulated by spinal cord injury. Further characterization of these molecules may help us come closer to understanding the mechanisms that underlie the inability of the adult CNS to regenerate.

Unmatched masses in peptide mass fingerprints caused by cross-contamination: an updated statistical result.

Unmatched masses are often observed in the experimental peptide mass spectra when database searching is performed with the ProFound program. Comparison between theoretical and experimental mass spectra of standard proteins shows that contamination accounts for most of the unmatched masses. In this retrospective analysis, the top 100 most probable contaminating masses, as listed in order of their probability, are statistically filtered out from 118 different experimental peptide mass fingerprinting (PMF) maps. Most of the interfering masses originate from trypsin autolysis and human keratins. Subtraction of known contaminants from raw data and using cleaner masses for searching can enhance protein identification by PMF.