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1.
Adv Mater ; : e2207138, 2022 Nov 17.
Article in English | MEDLINE | ID: covidwho-2235816

ABSTRACT

Prompt on-site diagnosis of SARS-CoV-2 with other respiratory infections would have minimized the global impact of the COVID-19 pandemic through rapid, effective management. However, no such multiplex point-of-care (POC) chip has satisfied a suitable sensitivity of gold-standard nucleic acid amplification tests (NAATs). Here, we present a rapid multiplexed ultrasensitive sample-to-answer LAMP (MUSAL) chip operated by simple LED-driven photothermal amplification to detect six targets from single-swab sampling. First, our MUSAL chip allows ultrafast on-chip sample preparation with ∼500-fold preconcentration at a rate of 1.2 mL min-1 . Second, our chip enables contamination-free amplification using autonomous target elution into on-chip reagents by photothermal activation. Finally, our chip accomplishes multiplexed on-chip diagnostics of SARS-CoV-2 and influenza viruses with a limit of detection (LoD) of 0.5 copies µL-1 . Our rapid, ultra-sensitive, cost-effective sample-to-answer chip with a multiplex capability will allow timely management of various pandemics situations we may face shortly. This article is protected by copyright. All rights reserved.

2.
Front Immunol ; 13: 907804, 2022.
Article in English | MEDLINE | ID: covidwho-2009862

ABSTRACT

Recent epidemiological studies show a noticeable correlation between chronic microbial infections and neurological disorders. However, the underlying mechanisms are still not clear due to the biological complexity of multicellular and multiorgan interactions upon microbial infections. In this review, we show the infection leading to neurodegeneration mediated by multiorgan interconnections and neuroinflammation. Firstly, we highlight three inter-organ communications as possible routes from infection sites to the brain: nose-brain axis, lung-brain axis, and gut-brain axis. Next, we described the biological crosstalk between microglia and astrocytes upon pathogenic infection. Finally, our study indicates how neuroinflammation is a critical player in pathogen-mediated neurodegeneration. Taken together, we envision that antibiotics targeting neuro-pathogens could be a potential therapeutic strategy for neurodegeneration.


Subject(s)
Microglia , Neuroinflammatory Diseases , Astrocytes , Brain , Humans , Microglia/pathology
3.
Nat Commun ; 13(1): 3459, 2022 06 16.
Article in English | MEDLINE | ID: covidwho-1921608

ABSTRACT

Newly developed acoustic technologies are playing a transformational role in life science and biomedical applications ranging from the activation and inactivation of mechanosensitive ion channels for fundamental physiological processes to the development of contact-free, precise biofabrication protocols for tissue engineering and large-scale manufacturing of organoids. Here, we provide our perspective on the development of future acoustic technologies and their promise in addressing critical challenges in biomedicine.


Subject(s)
Acoustics , Sound , Delivery of Health Care , Organoids , Tissue Engineering
4.
Sci Adv ; 8(21): eabn3481, 2022 05 27.
Article in English | MEDLINE | ID: covidwho-1865136

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has become an immense global health crisis. However, the lack of efficient and sensitive on-site testing methods limits early detection for timely isolation and intervention. Here, we present a quantitative and ultrasensitive in situ immunoassay technology for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection in saliva (QUIT SARS-CoV-2). Our nanoporous membrane resonator generates a rapid oscillating flow to purify and concentrate fully intact SARS-CoV-2 virus in saliva by 40-fold for in situ detection of viral antigens based on chemiluminescent immunoassay within 20 min. This method can not only achieve a detection sensitivity below 100 copies/ml of virus, comparable to the bench-top PCR equipment; it can also improve detection specificity via direct monitoring of viral loads. The integrated portable QUIT SARS-CoV-2 system, which enables rapid and accurate on-site viral screening with a high-throughput sample pooling strategy, can be performed in primary care settings and substantially improve the detection and prevention of COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , Humans , Immunoassay , Saliva , Sensitivity and Specificity , Technology
5.
medRxiv ; 2022 Jan 11.
Article in English | MEDLINE | ID: covidwho-808244

ABSTRACT

SARS-CoV-2 precipitates respiratory distress by infection of airway epithelial cells and is often accompanied by acute kidney injury. We report that Kidney Injury Molecule-1/T cell immunoglobulin mucin domain 1 (KIM-1/TIM-1) is expressed in lung and kidney epithelial cells in COVID-19 patients and is a receptor for SARS-CoV-2. Human and mouse lung and kidney epithelial cells express KIM-1 and endocytose nanoparticles displaying the SARS-CoV-2 spike protein (virosomes). Uptake was inhibited by anti-KIM-1 antibodies and TW-37, a newly discovered inhibitor of KIM-1-mediated endocytosis. Enhanced KIM-1 expression by human kidney tubuloids increased uptake of virosomes. KIM-1 binds to the SARS-CoV-2 Spike protein in vitro . KIM-1 expressing cells, not expressing angiotensin-converting enzyme 2 (ACE2), are permissive to SARS-CoV-2 infection. Thus, KIM-1 is an alternative receptor to ACE2 for SARS-CoV-2. KIM-1 targeted therapeutics may prevent and/or treat COVID-19.

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