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Cell Apr 2020The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency....
The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.
Topics: Ammonium Chloride; Angiotensin-Converting Enzyme 2; Animals; Antibodies, Neutralizing; Antibodies, Viral; Betacoronavirus; COVID-19; Cell Line; Coronavirus; Coronavirus Infections; Drug Development; Esters; Gabexate; Guanidines; Humans; Immunization, Passive; Leucine; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Protease Inhibitors; Receptors, Virus; Severe acute respiratory syndrome-related coronavirus; SARS-CoV-2; Serine Endopeptidases; Spike Glycoprotein, Coronavirus; Vesiculovirus; Virus Internalization; COVID-19 Serotherapy
PubMed: 32142651
DOI: 10.1016/j.cell.2020.02.052 -
Journal of the American Chemical Society Feb 2023Conventional desalination membrane technologies, although offer portable drinking water, are still energy-intensive processes. This paper proposes a potentially new...
Conventional desalination membrane technologies, although offer portable drinking water, are still energy-intensive processes. This paper proposes a potentially new approach for performing water desalination and purification by utilizing the reversible interaction of carbon dioxide (CO) with nucleophilic amines─reminiscent of the Solvay process. Based on our model studies with small molecules, CO-responsive amphiphilic insoluble diamines were prepared, characterized, and applied in the formation of soda and ammonium chloride upon exposure to ambient CO (1 atm), thus removing chloride ions from model and real seawater. This ion-exchange process and separation of chloride from the aqueous phase are spontaneous in the presence of CO without the need for external energy sources. We demonstrate a flow system to envisage energy-efficient CO-mediated desalination and simultaneous carbon capture and sequestration.
PubMed: 36731027
DOI: 10.1021/jacs.2c11880 -
IUCrData Feb 2023The title compound, CHN·Cl·2HO, crystallizes in the space group 2 with one organic mol-ecule in the asymmetric unit. The compound belongs to a class of benzalkonium...
The title compound, CHN·Cl·2HO, crystallizes in the space group 2 with one organic mol-ecule in the asymmetric unit. The compound belongs to a class of benzalkonium chlorides (BACs) with an alkyl chain length of 16 carbon atoms in an all- conformation.
PubMed: 36911083
DOI: 10.1107/S2414314623000962 -
BioRxiv : the Preprint Server For... May 2023Ammonia is a ubiquitous, toxic by-product of cell metabolism. Its high membrane permeability and proton affinity causes ammonia to accumulate inside acidic lysosomes in...
Ammonia is a ubiquitous, toxic by-product of cell metabolism. Its high membrane permeability and proton affinity causes ammonia to accumulate inside acidic lysosomes in its poorly membrane-permeant form: ammonium (NH ). Ammonium buildup compromises lysosomal function, suggesting the existence of mechanisms that protect cells from ammonium toxicity. Here, we identified SLC12A9 as a lysosomal ammonium exporter that preserves lysosomal homeostasis. SLC12A9 knockout cells showed grossly enlarged lysosomes and elevated ammonium content. These phenotypes were reversed upon removal of the metabolic source of ammonium or dissipation of the lysosomal pH gradient. Lysosomal chloride increased in SLC12A9 knockout cells and chloride binding by SLC12A9 was required for ammonium transport. Our data indicate that SLC12A9 is a chloride-driven ammonium co-transporter that is central in an unappreciated, fundamental mechanism of lysosomal physiology that may have special relevance in tissues with elevated ammonia, such as tumors.
PubMed: 37292735
DOI: 10.1101/2023.05.22.541801 -
Molecules (Basel, Switzerland) Feb 2022Quaternary ammonium salt polymers, a kind of polyelectrolyte with a quaternary ammonium group, are widely used in traditional and emerging industries due to their good... (Review)
Review
Quaternary ammonium salt polymers, a kind of polyelectrolyte with a quaternary ammonium group, are widely used in traditional and emerging industries due to their good water-solubility, adjustable cationicity and molecular weight, high efficiency and nontoxicity. In this paper, firstly, the properties and several synthesis methods of typical quaternary ammonium salt monomers were introduced. Secondly, the research progress on the synthesis of polymers was summarized from the perspective of obtaining products with high molecular weight, narrow molecular weight distribution and high monomer conversion, and special functional polymers. Thirdly, the relationships between the structures and properties of the polymer were analyzed from the perspectives of molecular weight, charge density, structural stability, and microstructural regulation of the polymer chain unit. Fourthly, typical examples of quaternary ammonium salt polymers in the application fields of water treatment, daily chemicals, petroleum exploitation, papermaking, and textile printing and dyeing were listed. Finally, constructive suggestions were put forward on developing quaternary ammonium salt polymers with high molecular weights, strengthening the research on the relationships between the structures and their properties and pinpointing relevant application fields.
PubMed: 35209058
DOI: 10.3390/molecules27041267 -
Nature Communications Oct 2023Ammonium (NH), a breakdown product of amino acids that can be toxic at high levels, is detected by taste systems of organisms ranging from C. elegans to humans and has...
Ammonium (NH), a breakdown product of amino acids that can be toxic at high levels, is detected by taste systems of organisms ranging from C. elegans to humans and has been used for decades in vertebrate taste research. Here we report that OTOP1, a proton-selective ion channel expressed in sour (Type III) taste receptor cells (TRCs), functions as sensor for ammonium chloride (NHCl). Extracellular NHCl evoked large dose-dependent inward currents in HEK-293 cells expressing murine OTOP1 (mOTOP1), human OTOP1 and other species variants of OTOP1, that correlated with its ability to alkalinize the cell cytosol. Mutation of a conserved intracellular arginine residue (R292) in the mOTOP1 tm 6-tm 7 linker specifically decreased responses to NHCl relative to acid stimuli. Taste responses to NHCl measured from isolated Type III TRCs, or gustatory nerves were strongly attenuated or eliminated in an Otop1 mouse strain. Behavioral aversion of mice to NHCl, reduced in Skn-1a mice lacking Type II TRCs, was entirely abolished in a double knockout with Otop1. These data together reveal an unexpected role for the proton channel OTOP1 in mediating a major component of the taste of NHCl and a previously undescribed channel activation mechanism.
Topics: Animals; Humans; Mice; Ammonium Chloride; HEK293 Cells; Protons; Taste; Taste Buds
PubMed: 37798269
DOI: 10.1038/s41467-023-41637-4 -
Physiological Reports Sep 2022Acute pyelonephritis caused by uropathogenic E. coli (UPEC) can cause renal scarring and lead to development of chronic kidney disease. Prevention of kidney injury...
Acute pyelonephritis caused by uropathogenic E. coli (UPEC) can cause renal scarring and lead to development of chronic kidney disease. Prevention of kidney injury requires an understanding of host factors and/or UPEC adaptive responses that are permissive for UPEC colonization of the urinary tract. Although some studies have suggested urine acidification limits UPEC growth in culture, other studies have described acid-resistance mechanisms (AR) in E. coli such as the CadC/CadBA module that promotes adaptation to acid and nitrosative stress. Herein we confirm and extend our previous study by demonstrating that despite urine acidification, metabolic acidosis induced by dietary ammonium chloride (NH Cl-A) exacerbates cystitis and pyelonephritis in innate immune competent (C3H-HeN) mice characterized by: (1) markedly elevated UPEC burden and increased chemokine/cytokine and NOS2 mRNA expression, (2) accumulation of intravesicular debris noninvasively detected by Power Doppler Ultrasound (PDUS), and (3) collecting duct (CD) dysfunction that manifests as a urine concentration defect. Bladder debris and CD dysfunction were due to the inflammatory response, as neither was observed in Tlr4-deficient (C3H-HeJ) mice. The effect of NH Cl-A was unrelated to acidosis as dietary administration of hydrochloric acid (HCl-A) yielded a comparable acid-base status yet did not increase UPEC burden. NH Cl-A increased polyamines and decreased nitric oxide (NO) metabolites in urine indicating that excess dietary ammonium shifts arginine metabolism toward polyamines at the expense of NO synthesis. Furthermore, despite increased expression of NOS2, NO production post UPEC infection was attenuated in NH Cl-A mice compared to controls. Thus, in addition to induction of metabolic acidosis and urine acidification, excess dietary ammonium alters the polyamine:NO balance and thereby compromises NOS2-mediated innate immune defense.
Topics: Acidosis; Ammonium Chloride; Animals; Arginine; Chemokines; Cystitis; Cytokines; Escherichia coli Infections; Hydrochloric Acid; Mice; Mice, Inbred C3H; Nitric Oxide; Polyamines; Pyelonephritis; RNA, Messenger; Toll-Like Receptor 4; Urinary Tract Infections; Uropathogenic Escherichia coli
PubMed: 36151614
DOI: 10.14814/phy2.15471