Kidney resident macrophages have distinct subsets and multifunctional roles.

Background: The kidney contains distinct glomerular and tubulointerstitial compartments with diverse cell types and extracellular matrix components. The role of immune cells in glomerular environment is crucial for dampening inflammation and maintaining homeostasis. Macrophages are innate immune cells that are influenced by their tissue microenvironment.

The critical role of engineering in the rapid development of COVID-19 diagnostics: Lessons from the RADx Tech Test Verification Core.

Engineering plays a critical role in the development of medical devices, and this has been magnified since 2020 as severe acute respiratory syndrome coronavirus 2 swept over the globe. In response to the coronavirus disease 2019, the National Institutes of Health launched the Rapid Acceleration of Diagnostics (RADx) initiative to help meet the testing needs of the United States and effectively manage the pandemic. As the Engineering and Human Factors team for the RADx Tech Test Verification Core, we directly assessed more than 30 technologies that ultimately contributed to an increase of the country's total testing capacity by 1.

Monocyte migration profiles define disease severity in acute COVID-19 and unique features of long COVID.

Background: COVID-19 is associated with a dysregulated immune response but it is unclear how immune dysfunction contributes to the chronic morbidity persisting in many COVID-19 patients during convalescence (long COVID).

Methods: We assessed phenotypical and functional changes of monocytes in COVID-19 patients during hospitalisation and up to 9 months of convalescence following COVID-19, respiratory syncytial virus or influenza A. Patients with progressive fibrosing interstitial lung disease were included as a positive control for severe, ongoing lung injury.

Imbalanced prostanoid release mediates cigarette smoke-induced human pulmonary artery cell proliferation.

Background: Pulmonary hypertension is a common and serious complication of chronic obstructive pulmonary disease (COPD). Studies suggest that cigarette smoke can initiate pulmonary vascular remodelling by stimulating cell proliferation; however, the underlying cause, particularly the role of vasoactive prostanoids, is unclear. We hypothesize that cigarette smoke extract (CSE) can induce imbalanced vasoactive prostanoid release by differentially modulating the expression of respective synthase genes in human pulmonary artery smooth muscle cells (PASMCs) and endothelial cells (PAECs), thereby contributing to cell proliferation.

Don't forget about human factors: Lessons learned from COVID-19 point-of-care testing.

During the COVID-19 pandemic, the development of point-of-care (POC) diagnostic testing accelerated in an unparalleled fashion. As a result, there has been an increased need for accurate, robust, and easy-to-use POC testing in a variety of non-traditional settings (i.e.

Designing for simplicity: lessons from Mesa Biotech for microfluidic entrepreneurs and early-stage companies.

The COVID-19 pandemic has proven the need for point-of-care diagnosis of respiratory diseases and microfluidic technology has risen to the occasion. Mesa Biotech (San Diego, CA) originally developed the Accula platform for the diagnosis of influenza A and B and then extended the platform to SARS-CoV-2. Mesa Biotech has experienced tremendous success, culminating in acquisition by Thermo Fisher for up to $550m USD.

The RADx Tech Clinical Studies Core: A Model for Academic Based Clinical Studies.

The National Institutes of Health (NIH) launched the Rapid Acceleration of Diagnostics (RADx) Tech initiative to support the development and commercialization of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) point-of-care test devices. The primary objective of the Clinical Studies Core (CSC) was to perform SARS-CoV-2 device studies involving diverse populations and settings. Within a few months, the infrastructure for clinical studies was developed, including a master protocol, digital study platform, data management system, single IRB, and multi-site partnerships.

The RADx Tech Test Verification Core and the ACME POCT in the Evaluation of COVID-19 Testing Devices: A Model for Progress and Change.

Faced with the COVID-19 pandemic, the US system for developing and testing technologies was challenged in unparalleled ways. This article describes the multi-institutional, transdisciplinary team of the "RADx Tech Test Verification Core" and its role in expediting evaluations of COVID-19 testing devices. Expertise related to aspects of diagnostic testing was coordinated to evaluate testing devices with the goal of significantly expanding the ability to mass screen Americans to preserve lives and facilitate the safe return to work and school.

Alterations in T and B cell function persist in convalescent COVID-19 patients.

Background: Emerging studies indicate that some coronavirus disease 2019 (COVID-19) patients suffer from persistent symptoms, including breathlessness and chronic fatigue; however, the long-term immune response in these patients presently remains ill-defined.

Methods: Here, we describe the phenotypic and functional characteristics of B and T cells in hospitalized COVID-19 patients during acute disease and at 3-6 months of convalescence.

Findings: We report that the alterations in B cell subsets observed in acute COVID-19 patients were largely recovered in convalescent patients.

Neurturin regulates the lung-resident macrophage inflammatory response to viral infection.

Lung-resident macrophages are crucial to the maintenance of health and in the defence against lower respiratory tract infections. Macrophages adapt to local environmental cues that drive their appropriate function; however, this is often dysregulated in many inflammatory lung pathologies. In mucosal tissues, neuro-immune interactions enable quick and efficient inflammatory responses to pathogenic threats.

All-Soft Supercapacitors Based on Liquid Metal Electrodes with Integrated Functionalized Carbon Nanotubes.

Soft energy storage devices, such as supercapacitors, are an essential component for powering integrated soft microsystems. However, conventional supercapacitors are mainly manufactured using hard/brittle materials that easily crack and eventually delaminate from the current collector by mechanical deformation. Therefore, to realize all-soft supercapacitors, the electrodes should be soft, stretchable, and highly conductive without compromising the electrochemical performance.

Nanofabrication for all-soft and high-density electronic devices based on liquid metal.

Innovations in soft material synthesis and fabrication technologies have led to the development of integrated soft electronic devices. Such soft devices offer opportunities to interact with biological cells, mimicking their soft environment. However, existing fabrication technologies cannot create the submicron-scale, soft transducers needed for healthcare and medical applications involving single cells.

In-Plane Vibration of Hammerhead Resonators for Chemical Sensing Applications.

Thermally excited and piezoresistively detected in-plane cantilever resonators have been previously demonstrated for gas- and liquid-phase chemical and biosensing applications. In this work, the hammerhead resonator geometry, consisting of a cantilever beam supporting a wider semicircular "head", vibrating in an in-plane vibration mode, is shown to be particularly effective for gas-phase sensing with estimated limits of detection in the sub-ppm range for volatile organic compounds. This paper discusses the hammerhead resonator design and the particular advantages of the hammerhead geometry, while also presenting mechanical characterization, optical characterization, and chemical sensing results.

Diagnosis of acute serious illness: the role of point-of-care technologies.

Access to rapid diagnostic information is a core value of point-of-care (POC) technology. This is particularly relevant in acute, emergency, and critical care settings where diagnostic speed and precision directly guide the management of patients with potentially life-threatening conditions. Many POC diagnostics described in the literature, however, remain largely unproven and have yet to enter the market entirely.

Point-of-Care Technology Research Network: An evolving model for collaborative translational research in biomedical engineering.

As the healthcare system evolves from a centralized, hospital- and office-based model to an emphasis on patient-centric care delivered in decentralized settings from the community and/or home to low resource settings domestically and internationally, some Point-of-Care Technologies (POCT) have become important and others may soon become important in facilitating care. These portable diagnostic and monitoring devices enable moving care closer to the patient. We review recent developments in a national model to accelerate the development of POCT, specifically the Point-of-Care Technology Research Network (POCTRN), comprising a multi-center scientific network supported by a coordinating center.

Sensing of apoptotic cells through Axl causes lung basal cell proliferation in inflammatory diseases.

Epithelial cell proliferation, division, and differentiation are critical for barrier repair following inflammation, but the initial trigger for this process is unknown. Here we define that sensing of apoptotic cells by the TAM receptor tyrosine kinase Axl is a critical indicator for tracheal basal cell expansion, cell cycle reentry, and symmetrical cell division. Furthermore, once the pool of tracheal basal cells has expanded, silencing of Axl is required for their differentiation.

Innate Immune Cell Suppression and the Link With Secondary Lung Bacterial Pneumonia.

Secondary infections arise as a consequence of previous or concurrent conditions and occur in the community or in the hospital setting. The events allowing secondary infections to gain a foothold have been studied for many years and include poor nutrition, anxiety, mental health issues, underlying chronic diseases, resolution of acute inflammation, primary immune deficiencies, and immune suppression by infection or medication. Children, the elderly and the ill are particularly susceptible.

The consequence of matrix dysfunction on lung immunity and the microbiome in COPD.

The pulmonary extracellular matrix (ECM) is a complex network of proteins which primarily defines tissue architecture and regulates various biochemical and biophysical processes. It is a dynamic system comprising two main structures (the interstitial matrix and the basement membrane) which undergo continuous, yet highly regulated, remodelling. This remodelling process is essential for tissue homeostasis and uncontrolled regulation can lead to pathological states including chronic obstructive pulmonary disease (COPD).

Defective lung function following influenza virus is due to prolonged, reversible hyaluronan synthesis.

Little is known about the impact of viral infections on lung matrix despite its important contribution to mechanical stability and structural support. The composition of matrix also indirectly controls inflammation by influencing cell adhesion, migration, survival, proliferation and differentiation. Hyaluronan is a significant component of the lung extracellular matrix and production and degradation must be carefully balanced.

Suberanilohydroxamic acid prevents TGF-β1-induced COX-2 repression in human lung fibroblasts post-transcriptionally by TIA-1 downregulation.

Cyclooxygenase-2 (COX-2), with its main antifibrotic metabolite PGE, is regarded as an antifibrotic gene. Repressed COX-2 expression and deficient PGE have been shown to contribute to the activation of lung fibroblasts and excessive deposition of collagen in pulmonary fibrosis. We have previously demonstrated that COX-2 expression in lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF) is epigenetically silenced and can be restored by epigenetic inhibitors.

Interplay between EZH2 and G9a Regulates CXCL10 Gene Repression in Idiopathic Pulmonary Fibrosis.

Selective repression of the antifibrotic gene CXCL10 contributes to tissue remodeling in idiopathic pulmonary fibrosis (IPF). We have previously reported that histone deacetylation and histone H3 lysine 9 (H3K9) methylation are involved in CXCL10 repression. In this study, we explored the role of H3K27 methylation and the interplay between the two histone lysine methyltransferases enhancer of zest homolog 2 (EZH2) and G9a in CXCL10 repression in IPF.

Microfluidic Transduction Harnesses Mass Transport Principles to Enhance Gene Transfer Efficiency.

Ex vivo gene therapy using lentiviral vectors (LVs) is a proven approach to treat and potentially cure many hematologic disorders and malignancies but remains stymied by cumbersome, cost-prohibitive, and scale-limited production processes that cannot meet the demands of current clinical protocols for widespread clinical utilization. However, limitations in LV manufacture coupled with inefficient transduction protocols requiring significant excess amounts of vector currently limit widespread implementation. Herein, we describe a microfluidic, mass transport-based approach that overcomes the diffusion limitations of current transduction platforms to enhance LV gene transfer kinetics and efficiency.

All-soft, battery-free, and wireless chemical sensing platform based on liquid metal for liquid- and gas-phase VOC detection.

Lightweight, flexible, stretchable, and wireless sensing platforms have gained significant attention for personal healthcare and environmental monitoring applications. This paper introduces an all-soft (flexible and stretchable), battery-free, and wireless chemical microsystem using gallium-based liquid metal (eutectic gallium-indium alloy, EGaIn) and poly(dimethylsiloxane) (PDMS), fabricated using an advanced liquid metal thin-line patterning technique based on soft lithography. Considering its flexible, stretchable, and lightweight characteristics, the proposed sensing platform is well suited for wearable sensing applications either on the skin or on clothing.

Transforming Growth Factor-β and Interleukin-1β Signaling Pathways Converge on the Chemokine CCL20 Promoter.

CCL20 is the only chemokine ligand for the chemokine receptor CCR6, which is expressed by the critical antigen presenting cells, dendritic cells. Increased expression of CCL20 is likely involved in the increased recruitment of dendritic cells observed in fibroinflammatory diseases such as chronic obstructive pulmonary disease (COPD). CCL20 expression is increased by the proinflammatory cytokine IL-1β.