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1.
Mol Ther ; 31(11): 3322-3336, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37689971

ABSTRACT

The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in the emergence of new variants that are resistant to existing vaccines and therapeutic antibodies, has raised the need for novel strategies to combat the persistent global COVID-19 epidemic. In this study, a monoclonal anti-human angiotensin-converting enzyme 2 (hACE2) antibody, ch2H2, was isolated and humanized to block the viral receptor-binding domain (RBD) binding to hACE2, the major entry receptor of SARS-CoV-2. This antibody targets the RBD-binding site on the N terminus of hACE2 and has a high binding affinity to outcompete the RBD. In vitro, ch2H2 antibody showed potent inhibitory activity against multiple SARS-CoV-2 variants, including the most antigenically drifted and immune-evading variant Omicron. In vivo, adeno-associated virus (AAV)-mediated delivery enabled a sustained expression of monoclonal antibody (mAb) ch2H2, generating a high concentration of antibodies in mice. A single administration of AAV-delivered mAb ch2H2 significantly reduced viral RNA load and infectious virions and mitigated pulmonary pathological changes in mice challenged with SARS-CoV-2 Omicron BA.5 subvariant. Collectively, the results suggest that AAV-delivered hACE2-blocking antibody provides a promising approach for developing broad-spectrum antivirals against SARS-CoV-2 and potentially other hACE2-dependent pathogens that may emerge in the future.


Subject(s)
Antibodies, Monoclonal , Broadly Neutralizing Antibodies , COVID-19 , Animals , Humans , Mice , Angiotensin-Converting Enzyme 2/genetics , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , Antibodies, Viral , COVID-19/therapy , Dependovirus/genetics , RNA, Viral , SARS-CoV-2/genetics , Broadly Neutralizing Antibodies/pharmacology , Broadly Neutralizing Antibodies/therapeutic use
2.
Health Commun ; 31(8): 998-1007, 2016 08.
Article in English | MEDLINE | ID: mdl-26756069

ABSTRACT

Previous literature has suggested that examining Twitter messages can be productive for studying how the public shares and spreads health information on social media. Preexposure prophylaxis (PrEP) is a promising approach to HIV prevention, yet there are many issues that may influence its effective implementation. This study examined social representations of PrEP on Twitter. One thousand four hundred and thirty-five Tweets were collected and 774 English Tweets were content-analyzed to explore propagation of various issues around daily oral PrEP, as well as characteristics of the sources of those Tweets. We also examined how Twitter message content influenced information propagation. Our findings revealed that PrEP-related information on Twitter covered a wide range of issues, and individual users constituted the majority of the Tweet creators among all the sources, including news media, nonprofit and academic groups, and commercial entities. Using Poisson regression, we also found that a Tweet's affective tone was a significant predictor of message propagation frequency. Implications for health practitioners are discussed.


Subject(s)
HIV Infections/prevention & control , Information Dissemination/methods , Pre-Exposure Prophylaxis/statistics & numerical data , Social Media/statistics & numerical data , Health Knowledge, Attitudes, Practice , Humans
3.
Methods ; 66(2): 237-45, 2014 Mar 15.
Article in English | MEDLINE | ID: mdl-23891802

ABSTRACT

We report on measurements and characterization of polarization properties of Second Harmonic (SH) signals using a four-channel photon counting based Stokes polarimeter. In this way, the critical polarization parameters can be obtained concurrently without the need of repeated image acquisition. The critical polarization parameters, including the degree of polarization (DOP), the degree of linear polarization (DOLP), and the degree of circular polarization (DOCP), are extracted from the reconstructed Stokes vector based SH images in a pixel-by-pixel manner. The measurements are further extended by varying the polarization states of the incident light and recording the resulting Stokes parameters of the SH signal. In turn this allows the molecular structure and orientation of the samples to be determined. Use of Stokes polarimetry is critical in determination of the full polarization state of light, and enables discrimination of material properties not possible with conventional crossed-polarized detection schemes. The combination of SHG microscopy and Stokes polarimeter hence makes a powerful tool to investigate the structural order of targeted specimens.


Subject(s)
Collagen/chemistry , Calibration , Collagen/ultrastructure , Crystallization , Light , Microscopy, Confocal , Microscopy, Polarization , Phosphates/chemistry , Potassium Compounds/chemistry , Protein Conformation , Scattering, Radiation
4.
Chemosphere ; 363: 142746, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38969223

ABSTRACT

Vanadate-based photocatalysts have recently attracted substantial attention owing to their outstanding photocatalytic activity for degrading organic pollutants and generating energy via photocatalytic processes. However, the relatively high price of vanadium has hindered the development of vanadate-based photocatalysts for various applications. Spent catalysts obtained from oil refineries typically contain a significant quantity of vanadium, making them valuable for recovery and utilization as precursors for the production of high-value-added photocatalysts. In this study, we transformed the V present in spent catalysts produced by the petrochemical industry into ternary vanadate-based photocatalysts [BiVO4/InVO4/Ag3VO4 (BVO/IVO/AVO, respectively)] designed for water remediation. The ternary composites revealed an enhanced photocatalytic capability, which was 1.42 and 5.1 times higher than those of the binary BVO/IVO and pristine AVO due to the facilitated charge separation. The ternary photocatalysts not only effectively treated wastewater containing various organic dyes, such as methylene blue (MB), rhodamine 6G (R6G), and brilliant green (BG), but also exhibited remarkable photocatalytic performance in the degradation of antibiotics, reduction of Cr(VI), and bacterial inactivation. This paper proposes a feasible route for recycling industrial waste as a source of vanadium to produce highly efficient vanadate-based photocatalysts.


Subject(s)
Bismuth , Vanadates , Vanadium , Water Pollutants, Chemical , Water Purification , Catalysis , Vanadates/chemistry , Water Pollutants, Chemical/chemistry , Vanadium/chemistry , Water Purification/methods , Bismuth/chemistry , Coloring Agents/chemistry , Wastewater/chemistry , Photochemical Processes
5.
Antiviral Res ; 219: 105735, 2023 11.
Article in English | MEDLINE | ID: mdl-37858764

ABSTRACT

A class of 1-(4-(arylethylenylcarbonyl)phenyl)-4-carboxy-2-pyrrolidinones were designed and synthesized via Michael addition, cyclization, aldol condensation, and deprotonation to inhibit the human transmembrane protease serine 2 (TMPRSS2) and Furin, which are involved in priming the SARS-CoV-2 Spike for virus entry. The most potent inhibitor 2f (81) was found to efficiently inhibit the replication of various SARS-CoV-2 delta and omicron variants in VeroE6 and Calu-3 cells, with EC50 range of 0.001-0.026 µM by pre-incubation with the virus to avoid the virus entry. The more potent antiviral activities than the proteases inhibitory activities led to discovery that the synthesized compounds also inhibited Spike's receptor binding domain (RBD):angiotensin converting enzyme 2 (ACE2) interaction as a main target, and their antiviral activities were enhanced by inhibiting TMPRSS2 and/or Furin. To further confirm the blocking effect of 2f (81) on virus entry, SARS-CoV-2 Spike pseudovirus was used in the entry assay and the results showed that the compound inhibited the pseudovirus entry in a ACE2-dependent pathway, via mainly inhibiting RBD:ACE2 interaction and TMPRSS2 activity in Calu-3 cells. Finally, in the in vivo animal model of SARS-CoV-2 infection, the oral administration of 25 mg/kg 2f (81) in hamsters resulted in reduced bodyweight loss and 5-fold lower viral RNA levels in nasal turbinate three days post-infection. Our findings demonstrated the potential of the lead compound for further preclinical investigation as a potential treatment for SARS-CoV-2.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Humans , Furin/pharmacology , Angiotensin-Converting Enzyme 2/chemistry , Pyrrolidinones/pharmacology , Antiviral Agents/pharmacology , Spike Glycoprotein, Coronavirus/metabolism , Virus Internalization
6.
Opt Express ; 20(13): 14090-9, 2012 Jun 18.
Article in English | MEDLINE | ID: mdl-22714473

ABSTRACT

We developed a four-channel photon counting based Stokes-polarimeter for spatial characterization of polarization effects in second harmonic generation (SHG). We have implemented a calibration technique allowing quantitative measurement of polarization parameters, such as the degree of polarization (DOP), degree of linear polarization (DOLP), degree of circular polarization (DOCP), as well as anisotropy from the acquired Stokes parameters. The technique is used as contrast mechanism to characterize the polarization properties from two potassium dihydrogen phosphate (KDP) micro-crystals and collagen type-I in SHG microscopy.


Subject(s)
Microscopy, Confocal/instrumentation , Scanning Laser Polarimetry/instrumentation , Equipment Design , Equipment Failure Analysis , Reproducibility of Results , Sensitivity and Specificity
7.
Sci Rep ; 11(1): 1929, 2021 Jan 21.
Article in English | MEDLINE | ID: mdl-33479432

ABSTRACT

The abnormal lattice expansion of commercial polypropylene (PP)/polyethylene (PE)/polypropylene (PP) separator in lithium-ion battery under different charging current densities was observed by in-situ X-ray diffraction. Significant lattice changes of both PP and PE were found during the low current density charging. The capacity fading and the resistance value of the cell measured at 0.025 C (5th retention, 92%) is unexpectedly larger than that at 1.0 C (5th retention, 97.3%) from the electrochemical impedance spectroscopic data. High-resolution scanning electron microscopy is employed to witness the pore changes of the trilayered membrane. Density functional theory calculations were used to investigate the mechanism responsible for the irregular results. The calculations revealed that the insertion of Li-ion and EC molecule into PP or PE are thermodynamically favourable process which might explain the anomalous significant lattice expansion during the low current density charging. Therefore, designing a new separator material with a more compact crystalline structure or surface modification to reduce the Li insertion during the battery operation is desirable.

8.
ACS Appl Mater Interfaces ; 12(36): 40296-40309, 2020 Sep 09.
Article in English | MEDLINE | ID: mdl-32841558

ABSTRACT

Polyoxometalates (POMs) have emerged as potential anode materials for lithium-ion batteries (LIBs) owing to their ability to transfer multiple electrons. Although POM anode materials exhibit notable results in LIBs, their energy-storage mechanisms have not been well-investigated. Here, we utilize various in operando and ex situ techniques to verify the charge-storage mechanisms of a Keplerate-type POM Na2K23{[(MoVI)MoVI5O21(H2O)3(KSO4)]12 [(VIVO)30(H2O)20(SO4)0.5]}·ca200H2O ({Mo72V30}) anode in LIBs. The {Mo72V30} anode provides a high reversible capacity of up to ∼1300 mA h g-1 without capacity fading for up to 100 cycles. The lithium-ion storage mechanism was studied systematically through in operando synchrotron X-ray absorption near-edge structure, ex situ X-ray diffraction, ex situ extended X-ray absorption fine structure, ex situ transmission electron microscopy, in operando synchrotron transmission X-ray microscopy, and in operando Raman spectroscopy. Based on the abovementioned results, we propose that the open hollow-ball structure of the {Mo72V30} molecular cluster serves as an electron/ion sponge that can store a large number of lithium ions and electrons reversibly via multiple and reversible redox reactions (Mo6+ ↔ Mo1+ and V5+/V4+↔ V1+) with fast lithium diffusion kinetics (DLi+: 10-9-10-10 cm2 s-1). No obvious volumetric expansion of the microsized {Mo72V30} particle is observed during the lithiation/delithiation process, which leads to high cycling stability. This study provides comprehensive analytical methods for understanding the lithium-ion storage mechanism of such complicated POMs, which is important for further studies of POM electrodes in energy-storage applications.

9.
J Nanosci Nanotechnol ; 9(5): 3084-91, 2009 May.
Article in English | MEDLINE | ID: mdl-19452973

ABSTRACT

The thermal and spectroscopic properties of polystyrene/(gold particles) (PS(SH)/Au) nanocomposite materials containing uniformly dispersed nanoparticles in a polymer matrix have been studied. The nanocomposite comprises the thiol-terminated polystyrene (PS(SH)) which was produced by capping a living polystyrene with ethylene sulfide and the nano-sized gold particles (AuNPs) which were in-situ formed in the presence of PS(SH). The PS(SH) was characterized by NMR and the bonding between thiols and AuNPs was verified by X-ray Photoelectron Spectroscopy. Based on the transmission electron microscopy and the UV-vis absorption spectra, PS(SH) with a lower molecular weight leads to the formation of bigger AuNPs. The T(D) of the nanocomposite (PS(SH)/Au) increases with an increase in the Au content and at a constant Au content the PS(SH) with a higher molecular weight affords PS(SH)/Au a higher T(D). While PS(SH)/Au has a higher T(g) than the corresponding pristine PS(SH), the difference reduces with an increase in Au content (i.e., a decrease in the PS(SH):Au weight ratio) because of the formation of larger AuNPs which provide a smaller total surface area for PS(SH) to anchor or to cover.

10.
Sci Rep ; 9(1): 1299, 2019 Feb 04.
Article in English | MEDLINE | ID: mdl-30718703

ABSTRACT

Artificial graphite (FSN) additive is employed as internal structural label for projecting cyclability of Si material native electrode in a mass ratio of Si/FSN = 1.0 in Li ion battery (LIB). Results of operando X-ray diffraction analysis on Si-FSN negative electrode in LIB demonstrate that one can evaluate the lithiation and delithiation affinity of active material by referring phase transition delay of graphite as affected by experimental splits in a formation process of LIB. We prove that a thin layer of surface amorphous structure and residual lattice strain are formed in Si by high energy ball-milling treatment. Those manipulations improve Li intercalation kinetics and thus enabling a capacity fading of less than 10% (from 1860 to 1650 mAhg-1) for Si negative electrode in 50 cycles. Of utmost importance, this study discloses a robust assessment for revealing mechanism on amorphous and strain related silicide formation and predicting cyclability of negative electrode by quantitative phase evolution rate of FSN additive in LIB.

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