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1.
PloS one ; 18(3), 2023.
Article in English | EuropePMC | ID: covidwho-2263749

ABSTRACT

Effective masking policies to prevent the spread of airborne infections depend on public access to masks with high filtration efficacy. However, poor face-fit is almost universally present in pleated multilayer disposable face masks, severely limiting both individual and community respiratory protection. We developed a set of simple mask modifications to mass-manufactured disposable masks, the most common type of mask used by the public, that dramatically improves both their personalized fit and performance in a low-cost and scalable manner. These modifications comprise a user-moldable full mask periphery wire, integrated earloop tension adjusters, and an inner flange to trap respiratory droplets. We demonstrate that these simple design changes improve quantitative fit factor by 320%, triples the level of protection against aerosolized droplets, and approaches the model efficacy of N95 respirators in preventing the community spread of COVID-19, for an estimated additional cost of less than 5 cents per mask with automated production.

2.
PLoS One ; 18(3): e0281050, 2023.
Article in English | MEDLINE | ID: covidwho-2263750

ABSTRACT

Effective masking policies to prevent the spread of airborne infections depend on public access to masks with high filtration efficacy. However, poor face-fit is almost universally present in pleated multilayer disposable face masks, severely limiting both individual and community respiratory protection. We developed a set of simple mask modifications to mass-manufactured disposable masks, the most common type of mask used by the public, that dramatically improves both their personalized fit and performance in a low-cost and scalable manner. These modifications comprise a user-moldable full mask periphery wire, integrated earloop tension adjusters, and an inner flange to trap respiratory droplets. We demonstrate that these simple design changes improve quantitative fit factor by 320%, triples the level of protection against aerosolized droplets, and approaches the model efficacy of N95 respirators in preventing the community spread of COVID-19, for an estimated additional cost of less than 5 cents per mask with automated production.


Subject(s)
COVID-19 , Respiratory Protective Devices , Humans , COVID-19/prevention & control , Masks , N95 Respirators , Filtration
3.
Composites Communications ; : 101445, 2022.
Article in English | ScienceDirect | ID: covidwho-2130502

ABSTRACT

The hazards of epoxy resin (EP) are not only reflected in the large amount of smoke and heat released during combustion, but also in the long survival time of bacterial on their surfaces at a time when COVID-19 are prevalent. Therefore, it is crucial to improve the antibacterial properties and fire-resistance of EP. Herein, this paper reports a multifunctional nanoparticle (Cu2O@KF) to overcome this issue. It is found that Cu2O@KF can confer great fire-resistance (LOI = 34.7% and pHRR reduced by 56.3%), antibacterial properties (over 99.99% antibacterial efficiency), and mechanical properties (hardness and Young's modulus increased by 80.0% and 24.0%, respectively) at a low loading level (7wt.%). These ideal characteristics are derived from the multi-synergistic properties among Cu2O and KF.

4.
Radiology of Infectious Diseases ; 8(3):101-107, 2021.
Article in English | ProQuest Central | ID: covidwho-2118992

ABSTRACT

OBJECTIVE: Since the coronavirus disease 2019 (COVID-19) outbreak in Wuhan in 2019, the virus has spread rapidly. We investigated the clinical and computed tomography (CT) characteristics of different clinical types of COVID-19. MATERIALS AND METHODS: We retrospectively analyzed clinical and chest CT findings of 89 reverse transcription polymerase chain reaction confirmed cases from five medical centers in China. All the patients were classified into the common (n = 65), severe (n = 18), or fatal (n = 6) type. CT features included lesion distribution, location, size, shape, edge, density, and the ratio of lung lesions to extra-pulmonary lesions. A COVID-19 chest CT analysis tool (uAI-discover-COVID-19) was used to calculate the number of infections from the chest CT images. RESULTS: Fatal type COVID-19 is more common in older men, with a median age of 65 years. Fever was more common in the severe and fatal type COVID-19 patients than in the common type patients. Patients with fatal type COVID-19 were more likely to have underlying diseases. On CT examination, common type COVID-19 showed bilateral (68%), patchy (83%), ground-glass opacity (48%), or mixed (46%) lesions. Severe and fatal type COVID-19 showed bilateral multiple mixed density lesions (56%). The infection ratio (IR) increased in the common type (2.4 [4.3]), severe type (15.7 [14.3]), and fatal type (36.9 [14.2]). The IR in the inferior lobe of both lungs was statistically different from that of other lobes in common and severe type patients (P < 0.05). However, in the fatal type group, only the IR in the right inferior lung (RIL) was statistically different from that in the right superior lung(RUL), right middle lung (RML), and the left superior lung (LSL) (P < 0.05). CONCLUSION: The CT findings and clinical features of the various clinical types of COVID-19 pneumonia are different. Chest CT findings have unique characteristics in the different clinical types, which can facilitate an early diagnosis and evaluate the clinical course and severity of COVID-19.

5.
Mar Drugs ; 19(2)2021 Jan 27.
Article in English | MEDLINE | ID: covidwho-1969360

ABSTRACT

Inorganic polyphosphate (polyP) is a widely distributed polymer found from bacteria to animals, including marine species. This polymer exhibits morphogenetic as well as antiviral activity and releases metabolic energy after enzymatic hydrolysis also in human cells. In the pathogenesis of the coronavirus disease 2019 (COVID-19), the platelets are at the frontline of this syndrome. Platelets release a set of molecules, among them polyP. In addition, the production of airway mucus, the first line of body defense, is impaired in those patients. Therefore, in this study, amorphous nanoparticles of the magnesium salt of polyP (Mg-polyP-NP), matching the size of the coronavirus SARS-CoV-2, were prepared and loaded with the secondary plant metabolite quercetin or with dexamethasone to study their effects on the respiratory epithelium using human alveolar basal epithelial A549 cells as a model. The results revealed that both compounds embedded into the polyP nanoparticles significantly increased the steady-state-expression of the MUC5AC gene. This mucin species is the major mucus glycoprotein present in the secreted gel-forming mucus. The level of gene expression caused by quercetin or with dexamethasone, if caged into polyP NP, is significantly higher compared to the individual drugs alone. Both quercetin and dexamethasone did not impair the growth-supporting effect of polyP on A549 cells even at concentrations of quercetin which are cytotoxic for the cells. A possible mechanism of the effects of the two drugs together with polyP on mucin expression is proposed based on the scavenging of free oxygen species and the generation of ADP/ATP from the polyP, which is needed for the organization of the protective mucin-based mucus layer.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Dexamethasone/pharmacology , Mucin 5AC/biosynthesis , Mucin 5AC/drug effects , Quercetin/pharmacology , A549 Cells , Anti-Inflammatory Agents/chemistry , Antioxidants/chemistry , COVID-19 , Dexamethasone/chemistry , Free Radical Scavengers/pharmacology , Gene Expression Regulation/drug effects , Humans , Magnesium/chemistry , Mucin 5AC/genetics , Mucins/biosynthesis , Mucins/chemistry , Nanoparticles , Particle Size , Plants/chemistry , Polyphosphates/chemistry , Quercetin/chemistry , Reactive Oxygen Species
6.
Invest Ophthalmol Vis Sci ; 63(6): 16, 2022 06 01.
Article in English | MEDLINE | ID: covidwho-1956961

ABSTRACT

Purpose: The purpose of this study was to investigate the effects of lysozyme, an antimicrobial enzyme found in tears that protects the eye against pathogens, on pseudotyped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through corneal epithelial cells. Methods: The expression of the angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease (TMPRSS2) in human corneal epithelial cells (HCECs) was measured by RT-PCR and Western blotting. The altered expression of the pro-inflammatory molecules induced by spike protein and lysozyme was analyzed by RT-PCR. Cell toxicity was tested by CCK8 assay. The cell entry of SAR-CoV-2 in HCECs and primary rabbit corneal epithelial cells (RbCECs) was detected by luciferase assay. Results: ACE2 and TMPRSS2 were highly expressed in HCECs. The spike proteins of SARS-CoV-2 stimulated a robust inflammatory response in HCECs, characterized by increased secretion of pro-inflammatory molecules, including IL-6, TNF-α, iNOS, and MCP-1, and pretreatment with lysozyme in HCECs markedly decreased the production of proinflammatory molecules induced by spike proteins. In addition, the inflammatory cytokine TNF-α enhanced the entry of SARS-CoV-2 into HCECs, which can be mitigated by pretreatment with lysozyme. Conclusions: In this study, we analyzed the susceptibility of human corneal epithelial cells to SARS-CoV-2 infection and suggested the protective effects of lysozyme on SARS-CoV-2 infection.


Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 , Animals , Antiviral Agents , Epithelial Cells/metabolism , Humans , Inflammation/metabolism , Muramidase/metabolism , Peptidyl-Dipeptidase A , Rabbits , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolism , Tumor Necrosis Factor-alpha/metabolism
7.
Prog Mol Subcell Biol ; 61: 145-189, 2022.
Article in English | MEDLINE | ID: covidwho-1888828

ABSTRACT

Polyanions as polymers carrying multiple negative charges have been extensively studied with regard to their potential antiviral activity. Most studies to date focused on organic polyanionic polymers, both natural and synthetic. The inorganic polymer, polyphosphate (polyP), despite the ubiquitous presence of this molecule from bacteria to man, has attracted much less attention. More recently, and accelerated by the search for potential antiviral agents in the fight against the pandemic caused by the coronavirus SARS-CoV-2, it turned out that polyP disrupts the first step of the viral replication cycle, the interaction of the proteins in the virus envelope and in the cell membrane that are involved in the docking process of the virus with the target host cell. Experiments on a molecular level using the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and the cellular angiotensin converting enzyme 2 (ACE2) receptor revealed that polyP strongly inhibits the binding reaction through an electrostatic interaction between the negatively charged centers of the polyP molecule and a cationic groove, which is formed by positively charged amino acids on the RBD surface. In addition, it was found that polyP, due to its morphogenetic and energy delivering activities, enhances the antiviral host innate immunity defense of the respiratory epithelium. The underlying mechanisms and envisaged application of polyP in the therapy and prevention of COVID-19 are discussed.


Subject(s)
COVID-19 Drug Treatment , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , Humans , Polyelectrolytes , Polymers , Polyphosphates/chemistry , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
8.
Healthcare (Basel) ; 10(1)2022 Jan 17.
Article in English | MEDLINE | ID: covidwho-1625759

ABSTRACT

(1) Background: Chest radiographs are the mainstay of initial radiological investigation in this COVID-19 pandemic. A reliable and readily deployable artificial intelligence (AI) algorithm that detects pneumonia in COVID-19 suspects can be useful for screening or triage in a hospital setting. This study has a few objectives: first, to develop a model that accurately detects pneumonia in COVID-19 suspects; second, to assess its performance in a real-world clinical setting; and third, by integrating the model with the daily clinical workflow, to measure its impact on report turn-around time. (2) Methods: The model was developed from the NIH Chest-14 open-source dataset and fine-tuned using an internal dataset comprising more than 4000 CXRs acquired in our institution. Input from two senior radiologists provided the reference standard. The model was integrated into daily clinical workflow, prioritising abnormal CXRs for expedited reporting. Area under the receiver operating characteristic curve (AUC), F1 score, sensitivity, and specificity were calculated to characterise diagnostic performance. The average time taken by radiologists in reporting the CXRs was compared against the mean baseline time taken prior to implementation of the AI model. (3) Results: 9431 unique CXRs were included in the datasets, of which 1232 were ground truth-labelled positive for pneumonia. On the "live" dataset, the model achieved an AUC of 0.95 (95% confidence interval (CI): 0.92, 0.96) corresponding to a specificity of 97% (95% CI: 0.97, 0.98) and sensitivity of 79% (95% CI: 0.72, 0.84). No statistically significant degradation of diagnostic performance was encountered during clinical deployment, and report turn-around time was reduced by 22%. (4) Conclusion: In real-world clinical deployment, our model expedites reporting of pneumonia in COVID-19 suspects while preserving diagnostic performance without significant model drift.

9.
Zhongguo Yi Liao Qi Xie Za Zhi ; 45(4): 384-389, 2021 Jul 30.
Article in Chinese | MEDLINE | ID: covidwho-1344943

ABSTRACT

In order to improve the level of epidemic prevention and control, and strengthen the observation and monitoring of potential patients with viral pneumonia in isolated state, a medical intelligent monitoring collar based on DA14699 Bluetooth low-power chip was proposed. DA14699 chip is used as the main controller in the design scheme, and the temperature, cough and location information of potential patients are recorded and analyzed by its high-efficiency wireless multi-core processing ability. The LIS3DH three-axis acceleration sensor is used to judge the cough symptoms. The MLX90640 infrared sensor is used to continuously measure the body temperature. The L218 four frequency GSM / GPRS positioning module is used to complete the rapid and accurate positioning of personnel, so as to realize the comprehensive supervision of the implementation of home isolation measures. DA14699 chip supports Bluetooth BLE5.1 protocol. Epidemic prevention personnel can transmit and read the data recorded in the smart collar from a long distance, and display it directly on the intelligent Bluetooth handheld terminal, effectively avoid the risk of infection caused by close contact. Through the actual test, the monitoring function of the key parameters of the collar is reliable and has high application value.


Subject(s)
Pneumonia, Viral , Humans , Monitoring, Physiologic
10.
Mater Today (Kidlington) ; 51: 504-524, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1336717

ABSTRACT

No other virus after the outbreak of the influenza pandemic of 1918 affected the world's population as hard as the coronavirus SARS-CoV-2. The identification of effective agents/materials to prevent or treat COVID-19 caused by SARS-CoV-2 is an urgent global need. This review aims to survey novel strategies based on inorganic polyphosphate (polyP), a biologically formed but also synthetically available polyanionic polymeric material, which has the potential of being a potent inhibitor of the SARS-CoV-2 virus-cell-docking machinery. This virus attaches to the host cell surface receptor ACE2 with its receptor binding domain (RBD), which is present at the tips of the viral envelope spike proteins. On the surface of the RBD an unusually conserved cationic groove is exposed, which is composed of basic amino acids (Arg, Lys, and His). This pattern of cationic amino acids, the cationic groove, matches spatially with the anionic polymeric material, with polyP, allowing an electrostatic interaction. In consequence, the interaction between the RBD and ACE2 is potently blocked. PolyP is a physiological inorganic polymer, synthesized by cells and especially enriched in the blood platelets, which releases metabolically useful energy through enzymatic degradation and coupled ADP/ATP formation. In addition, this material upregulates the steady-state-expression of the mucin genes in the epithelial cells. We propose that polyP, with its two antiviral properties (blocking the binding of the virus to the cells and reinforcing the defense barrier against infiltration of the virus) has the potential to be a novel protective/therapeutic anti-COVID-19 agent.

11.
EMBO Mol Med ; 13(7): e13810, 2021 07 07.
Article in English | MEDLINE | ID: covidwho-1299729

ABSTRACT

Streptococcus suis, a ubiquitous bacterial colonizer in pigs, has recently extended host range to humans, leading to a global surge of deadly human infections and three large outbreaks since 1998. To better understand the mechanisms for the emergence of cross-species transmission and virulence in human, we have sequenced 366 S. suis human and pig isolates from 2005 to 2016 and performed a large-scale phylogenomic analysis on 1,634 isolates from 14 countries over 36 years. We show the formation of a novel human-associated clade (HAC) diversified from swine S. suis isolates. Phylogeographic analysis identified Europe as the origin of HAC, coinciding with the exportation of European swine breeds between 1960s and 1970s. HAC is composed of three sub-lineages and contains several healthy-pig isolates that display high virulence in experimental infections, suggesting healthy-pig carriers as a potential source for human infection. New HAC-specific genes are identified as promising markers for pathogen detection and surveillance. Our discovery of a human-associated S. suis clade provides insights into the evolution of this emerging human pathogen and extend our understanding of S. suis epidemics worldwide.


Subject(s)
Streptococcal Infections , Streptococcus suis , Swine Diseases , Animals , Europe , Humans , Streptococcal Infections/epidemiology , Streptococcal Infections/veterinary , Streptococcus suis/genetics , Swine , Swine Diseases/epidemiology , Virulence
12.
Biomater Sci ; 9(18): 6052-6063, 2021 Sep 14.
Article in English | MEDLINE | ID: covidwho-1287827

ABSTRACT

Conventional face masks to prevent SARS-CoV-2 transmission are mostly based on a passive filtration principle. Ideally, anti-COVID-19 masks should protect the carrier not only by size exclusion of virus aerosol particles, but also be able to capture and destroy or inactivate the virus. Here we present the proof-of-concept of a filter mat for such a mask, which actively attracts aerosol droplets and kills the virus. The electrospun mats are made of polycaprolactone (PCL) a hydrophilic, functionalizable and biodegradable polyester, into which inorganic polyphosphate (polyP) a physiological biocompatible, biodegradable and antivirally active polymer (chain length, ∼40 Pi units) has been integrated. A soluble Na-polyP as well as amorphous calcium polyP nanoparticles (Ca-polyP-NP) have been used. In this composition, the polyP component of the polyP-PCL mats is stable in aqueous protein-free environment, but capable of transforming into a gel-like coacervate upon contact with divalent cations and protein like mucin present in (virus containing) aerosol droplets. In addition, the Ca-polyP-NP are used as a carrier of tretinoin (all-trans retinoic acid) which blocks the function of the SARS-CoV-2 envelope (E) protein, an ion channel forming viroporin. The properties of this novel mask filter mats are as follows: First, to attract and to trap virus-like particles during the polyP coacervate formation induced in situ by aerosol droplets on the spun PCL fibers, as shown here by using SARS-CoV-2 mimicking fluorescent nanoparticles. Second, after disintegration the NP by the aerosol-mucus constituents, to release polyP that binds to and abolishes the function of the receptor binding domain of the viral spike protein. Third, to destroy the virus by releasing tretinoin, as shown by the disruption of virus-mimicking liposomes with the integrated recombinant viral viroporin. It is proposed that these properties, which are inducible (stimuli responsive), will allow the design of antiviral masks that are smart.


Subject(s)
COVID-19 , Nanoparticles , Humans , Masks , Polyphosphates , SARS-CoV-2
13.
Theranostics ; 11(13): 6193-6213, 2021.
Article in English | MEDLINE | ID: covidwho-1224320

ABSTRACT

Rationale: The pandemic caused by the novel coronavirus SARS-CoV-2 is advancing rapidly. In particular, the number of severe courses of the disease is still dramatically high. An efficient drug therapy that helps to improve significantly the fatal combination of damages in the airway epithelia, in the extensive pulmonary microvascularization and finally multiorgan failure, is missing. The physiological, inorganic polymer, polyphosphate (polyP) is a molecule which could prevent the initial phase of the virus life cycle, the attachment of the virus to the target cells, and improve the epithelial integrity as well as the mucus barrier. Results: Surprisingly, polyP matches perfectly with the cationic groove on the RBD. Subsequent binding studies disclosed that polyP, with a physiological chain length of 40 phosphate residues, abolishes the binding propensity of the RBD to the ACE2 receptor. In addition to this first mode of action of polyP, this polymer causes in epithelial cells an increased gene expression of the major mucins in the airways, of MUC5AC and MUC1, as well as a subsequent glycoprotein production. MUC5AC forms a gel-like mucus layer trapping inhaled particles which are then transported out of the airways, while MUC1 constitutes the periciliary liquid layer and supports ciliary beating. As a third mode of action, polyP undergoes enzymatic hydrolysis of the anhydride bonds in the airway system by alkaline phosphatase, releasing metabolic energy. Conclusions: This review summarizes the state of the art of the biotherapeutic potential of the polymer polyP and the findings from basic research and outlines future biomedical applications.


Subject(s)
COVID-19 Drug Treatment , Pandemics/prevention & control , Polyphosphates/pharmacology , Animals , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , COVID-19/epidemiology , COVID-19/transmission , COVID-19/virology , Disease Models, Animal , Drug Evaluation, Preclinical , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Humans , Mice , Mucins/metabolism , Nanoparticles/chemistry , Polyphosphates/chemistry , Polyphosphates/therapeutic use , Respiratory Mucosa/drug effects , Respiratory Mucosa/metabolism , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity , Virus Attachment/drug effects
14.
Cancers (Basel) ; 13(4)2021 Feb 11.
Article in English | MEDLINE | ID: covidwho-1090373

ABSTRACT

The anti-cancer antitumor antibiotic bleomycin(s) (BLM) induces athyminic sites in DNA after its activation, a process that results in strand splitting. Here, using A549 human lung cells or BEAS-2B cells lunc cells, we show that the cell toxicity of BLM can be suppressed by addition of inorganic polyphosphate (polyP), a physiological polymer that accumulates and is released from platelets. BLM at a concentration of 20 µg ml-1 causes a decrease in cell viability (by ~70%), accompanied by an increased DNA damage and chromatin expansion (by amazingly 6-fold). Importantly, the BLM-caused effects on cell growth and DNA integrity are substantially suppressed by polyP. In parallel, the enlargement of the nuclei/chromatin in BLM-treated cells (diameter, 20-25 µm) is normalized to ~12 µm after co-incubation of the cells with BLM and polyP. A sequential application of the drugs (BLM for 3 days, followed by an exposure to polyP) does not cause this normalization. During co-incubation of BLM with polyP the gene for the BLM hydrolase is upregulated. It is concluded that by upregulating this enzyme polyP prevents the toxic side effects of BLM. These data might also contribute to an application of BLM in COVID-19 patients, since polyP inhibits binding of SARS-CoV-2 to cellular ACE2.

16.
Technol Cancer Res Treat ; 19: 1533033820974021, 2020.
Article in English | MEDLINE | ID: covidwho-983619

ABSTRACT

PURPOSE: With the widespread prevalence of Corona Virus Disease 2019 (COVID-19), cancer patients are suggested to wear a surgical mask during radiation treatment. In this study, cone beam CT (CBCT) was used to investigate the effect of surgical mask on setup errors in head and neck radiotherapy. METHODS: A total of 91 patients with head and neck tumors were selected. CBCT was performed to localize target volume after patient set up. The images obtained by CBCT before treatment were automatically registered with CT images and manually fine-tuned. The setup errors of patients in 6 directions of Vrt, Lng, Lat, Pitch, Roll and Rotation were recorded. The patients were divided into groups according to whether they wore the surgical mask, the type of immobilization mask used and the location of the isocenter. The setup errors of patients were calculated. A t-test was performed to detect whether it was statistically significant. RESULTS: In the 4 groups, the standard deviation in the directions of Lng and Pitch of the with surgical mask group were all higher than that in the without surgical mask group. In the head-neck-shoulder mask group, the mean in the Lng direction of the with surgical mask group was larger than that of the without surgical mask group. In the lateral isocenter group, the mean in the Lng and Pitch directions of the with surgical mask group were larger than that of the without surgical mask group. The t-test results showed that there was significant difference in the setup error between the 2 groups (p = 0.043 and p = 0.013, respectively) only in the Lng and Pitch directions of the head-neck-shoulder mask group. In addition, the setup error of 6 patients with immobilization open masks exhibited no distinguished difference from that of the patients with regular immobilization masks. CONCLUSION: In the head and neck radiotherapy patients, the setup error was affected by wearing surgical mask. It is recommended that the immobilization open mask should be used when the patient cannot finish the whole treatment with a surgical mask.


Subject(s)
COVID-19/prevention & control , Head and Neck Neoplasms/radiotherapy , Masks , Radiotherapy Setup Errors/statistics & numerical data , Adolescent , Adult , Aged , COVID-19/epidemiology , Case-Control Studies , Cone-Beam Computed Tomography/methods , Female , Head and Neck Neoplasms/epidemiology , Humans , Immobilization/instrumentation , Immobilization/methods , Immobilization/statistics & numerical data , Male , Masks/adverse effects , Masks/statistics & numerical data , Middle Aged , Pandemics , Radiation Oncology/methods , Radiation Oncology/standards , Radiotherapy Planning, Computer-Assisted/adverse effects , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy Planning, Computer-Assisted/statistics & numerical data , Radiotherapy, Image-Guided/adverse effects , Radiotherapy, Image-Guided/methods , Radiotherapy, Image-Guided/statistics & numerical data , Radiotherapy, Intensity-Modulated/methods , SARS-CoV-2/physiology , Shoulder , Young Adult
17.
Mar Drugs ; 18(12)2020 Dec 14.
Article in English | MEDLINE | ID: covidwho-977761

ABSTRACT

The mucus layer of the nasopharynx and bronchial epithelium has a barrier function against inhaled pathogens such as the coronavirus SARS-CoV-2. We recently found that inorganic polyphosphate (polyP), a physiological, metabolic energy (ATP)-providing polymer released from blood platelets, blocks the binding of the receptor binding domain (RBD) to the cellular ACE2 receptor in vitro. PolyP is a marine natural product and is abundantly present in marine bacteria. Now, we have approached the in vivo situation by studying the effect of polyP on the human alveolar basal epithelial A549 cells in a mucus-like mucin environment. These cells express mucins as well as the ectoenzymes alkaline phosphatase (ALP) and adenylate kinase (ADK), which are involved in the extracellular production of ATP from polyP. Mucin, integrated into a collagen-based hydrogel, stimulated cell growth and attachment. The addition of polyP to the hydrogel significantly increased cell attachment and also the expression of the membrane-tethered mucin MUC1 and the secreted mucin MUC5AC. The increased synthesis of MUC1 was also confirmed by immunostaining. This morphogenetic effect of polyP was associated with a rise in extracellular ATP level. We conclude that the nontoxic and non-immunogenic polymer polyP could possibly also exert a protective effect against SARS-CoV-2-cell attachment; first, by stimulating the innate antiviral response by strengthening the mucin barrier with its antimicrobial proteins, and second, by inhibiting virus attachment to the cells, as deduced from the reduction in the strength of binding between the viral RBD and the cellular ACE2 receptor.


Subject(s)
Aquatic Organisms/metabolism , Biological Products/pharmacology , COVID-19/prevention & control , Polyphosphates/pharmacology , Respiratory Mucosa/drug effects , A549 Cells , Bacteria/metabolism , Biological Products/therapeutic use , COVID-19/virology , Humans , Immunity, Innate/drug effects , Mucin 5AC/metabolism , Mucin-1/metabolism , Polyphosphates/metabolism , Polyphosphates/therapeutic use , Respiratory Mucosa/immunology , Respiratory Mucosa/metabolism , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Secondary Metabolism , Virus Attachment/drug effects
18.
Biomater Sci ; 8(23): 6603-6610, 2020 Dec 07.
Article in English | MEDLINE | ID: covidwho-968358

ABSTRACT

The effect of the polyanionic polymer of inorganic polyphosphate (polyP) involved in innate immunity on the binding of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein to the cellular ACE2 receptor was studied. The RBD surface comprises a basic amino acid stretch of four arginine residues which interact with the physiological polyP (polyP40) and polyP3. Subsequently, the interaction of RBD with ACE2 is sensitively inhibited. After the chemical modification of arginine, an increased inhibition by polyP, at a 1 : 1 molar ratio (polyP : RBP), is measured already at 0.1 µg mL-1. Heparin was ineffective. The results suggest a potential therapeutic benefit of polyP against SARS-CoV-2 infection.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Antiviral Agents/pharmacology , Polymers/pharmacology , Polyphosphates/pharmacology , Spike Glycoprotein, Coronavirus/metabolism , Angiotensin-Converting Enzyme 2/chemistry , Antiviral Agents/chemistry , Binding Sites , Humans , Molecular Docking Simulation , Polyelectrolytes , Polymers/chemistry , Polyphosphates/chemistry , Protein Binding/drug effects , Spike Glycoprotein, Coronavirus/chemistry
19.
Anal Chem ; 92(19): 13396-13404, 2020 10 06.
Article in English | MEDLINE | ID: covidwho-933642

ABSTRACT

Rapid, accurate, reliable, and risk-free tracking of pathogenic microorganisms at the single-cell level is critical to achieve efficient source control and prevent outbreaks of microbial infectious diseases. For the first time, we report a promising approach for integrating the concepts of a remarkably large Stokes shift and dual-recognition into a single matrix to develop a pathogenic microorganism stimuli-responsive ratiometric fluorescent nanoprobe with speed, cost efficiency, stability, ultrahigh specificity, and sensitivity. As a proof-of-concept, we selected the Gram-positive bacterium Staphylococcus aureus (S. aureus) as the target analyte model, which easily bound to its recognition aptamer and the broad-spectrum glycopeptide antibiotic vancomycin (Van). To improve the specificity and short sample-to-answer time, we employed classic noncovalent π-π stacking interactions as a driving force to trigger the binding of Van and aptamer dual-functionalized near-infrared (NIR) fluorescent Apt-Van-QDs to the surface of an unreported blue fluorescent π-rich electronic carbon nanoparticles (CNPs), achieving S. aureus stimuli-responsive ratiometric nanoprobe Apt-Van-QDs@CNPs. In the assembly of Apt-Van-QDs@CNPs, the blue CNPs (energy donor) and NIR Apt-Van-QDs (energy acceptor) became close to allow the fluorescence resonance energy transfer (FRET) process, leading to a remarkable blue fluorescence quenching for the CNPs at ∼465 nm and a clear NIR fluorescence enhancement for Apt-Van-QDs at ∼725 nm. In the presence of S. aureus, the FRET process from CNPs to Apt-Van-QDs was disrupted, causing the nanoprobe Apt-Van-QDs@CNPs to display a ratiometric fluorescent response to S. aureus, which exhibited a large Stokes shift of ∼260 nm and rapid sample-to-answer detection time (∼30.0 min). As expected, the nanoprobe Apt-Van-QDs@CNPs showed an ultrahigh specificity for ratiometric fluorescence detection of S. aureus with a good detection limit of 1.0 CFU/mL, allowing the assay at single-cell level. Moreover, we also carried out the precise analysis of S. aureus in actual samples with acceptable results. We believe that this work offers new insight into the rational design of efficient ratiometric nanoprobes for rapid on-site accurate screening of pathogenic microorganisms at the single-cell level in the early stages, especially during the worldwide spread of COVID-19 today.


Subject(s)
Bacteria/chemistry , Bacterial Infections/diagnosis , Bacterial Infections/microbiology , Biosensing Techniques/methods , Fluorescent Dyes/chemical synthesis , Nanotechnology/methods , Anti-Bacterial Agents/pharmacology , Aptamers, Nucleotide , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/microbiology , Fluorescence , Fluorescence Resonance Energy Transfer , Food Microbiology/methods , Humans , Nanoparticles , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/microbiology , Sensitivity and Specificity , Spectroscopy, Near-Infrared , Staphylococcal Infections/diagnosis , Staphylococcal Infections/microbiology , Staphylococcus aureus/chemistry , Vancomycin/pharmacology
20.
J Bone Joint Surg Am ; 103(1): 10-14, 2021 01 06.
Article in English | MEDLINE | ID: covidwho-916399

ABSTRACT

ABSTRACT: Coronavirus disease 2019 (COVID-19) is spreading worldwide, with its outlook not looking optimistic. Simultaneously, the epidemic is currently under control in many areas. The resumption of work and production in areas that have achieved control of outbreaks is a problem. Considering the extremely transmissible nature of COVID-19, and the presence of asymptomatic infected people, avoiding nosocomial infection and protecting medical staff and patients during the post-epidemic period remain difficult problems that need to be solved. At present, few articles have examined relevant experiences in the field of sports medicine. Wuhan, the People's Republic of China, was the original epicenter of COVID-19, with physicians as the initial frontline workers. Wuhan is now gradually returning to a more normal state after a series of urgent, strict, and effective measures were utilized to combat the epidemic. During this time, we collected first-hand experiences of sports medicine work resumption in the initial 2-month period, including preparations before resuming work, outpatient management methods, online outpatient services, inpatient ward management, principles for determination of the examination results, and preparations for operations. The strict and feasible management strategies that we conducted were useful in avoiding hospital-based infections. We intend to share our own experiences and thoughts in this area. We hope that this will be helpful and inspiring to our sports medicine colleagues around the world.


Subject(s)
COVID-19/epidemiology , Infection Control/organization & administration , Return to Work , Sports Medicine/organization & administration , COVID-19/prevention & control , COVID-19/transmission , China , Humans
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