Development of AAV-delivered broadly neutralizing anti-human ACE2 antibodies against SARS-CoV-2 variants.

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.

Propagation of Information About Preexposure Prophylaxis (PrEP) for HIV Prevention Through Twitter.

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.

Revealing molecular structure and orientation with Stokes vector resolved second harmonic generation microscopy.

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.

Construction of dual Z-scheme Ag3VO4-BiVO4/InVO4 photocatalysts using vanadium source from spent catalysts for contaminated water treatment and bacterial inactivation.

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.

Synthesis, evaluation, and mechanism of 1-(4-(arylethylenylcarbonyl)phenyl)-4-carboxy-2-pyrrolidinones as potent reversible SARS-CoV-2 entry inhibitors.

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.

Polarization-resolved second harmonic generation microscopy with a four-channel Stokes-polarimeter.

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.

Preferential lattice expansion of polypropylene in a trilayer polypropylene/polyethylene/polypropylene microporous separator in Li-ion batteries.

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.

In Operando X-ray Studies of High-Performance Lithium-Ion Storage in Keplerate-Type Polyoxometalate Anodes.

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.

Thermal and spectroscopic properties of polystyrene/gold nanocomposite containing well-dispersed gold nanoparticles.

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.

Cyclability evaluation on Si based Negative Electrode in Lithium ion Battery by Graphite Phase Evolution: an operando X-ray diffraction study.

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.

A new type of gasochromic material: conducting polymers with catalytic nanoparticles.

We report the first observation of gasochromism for a material based on a thin film of polyaniline:polystyrene sulfonate/platinum nanoparticles (PANI:PSS/PtNPs). This novel material displayed a significant colour change, from green to pale yellow, when exposed to hydrogen. Our results show that the PtNPs trigger a reductive reaction on the polymer surface. This new mechanism dramatically expands the selection of available gasochromic materials.

Heterogeneous Cu-Pd binary interface boosts stability and mass activity of atomic Pt clusters in the oxygen reduction reaction.

A ternary metallic CuPdPt nanocatalyst (NC) is synthesized using a wet chemical reduction method, which is sequentially designed, in the presence of acid treated carbon nanotubes. This NC is a nanocrystal with a configuration of a Cu@Pd core and atomic Pt clusters (∼9 wt%) on the top (Cu@Pd/Pt). A residual current of 92.6%, 5.2 times higher than that of commercial Pt catalysts (at 0.85 V vs. RHE), is retained after 40 000 cycles of an accelerated degradation test (ADT). Atomic and electronic structure analyses show that such exclusive stability mainly results from electron localization at Pt clusters in heterogeneous interfaces of the Cu-Pd core. Most importantly, we develop a robust ternary NC, which shows outstanding MA, superior chemical durability, and ∼90 wt% lower Pt loading than commercial Pt NCs in the oxygen reduction reaction.

Printed Multicolor High-Contrast Electrochromic Devices.

In this study, electrochemical responses of inkjet-printed multicolored electrochromic devices (ECD) were studied to evaluate the feasibility of presenting multiple colors in one ECD. Metallo-supramolecular polymers (MEPE) solutions with two primary colors were inkjet-printed on flexible electrodes. By digitally controlling print dosages of each species, the colors of the printed EC thin film patterns can be adjusted directly without premixing or synthesizing new materials. The printed EC thin films were then laminated with a solid transparent thin film electrolyte and a transparent conductive thin film to form an ECD. After applying a dc voltage, the printed ECDs exhibited great contrast with a transmittance change (ΔT) of 40.1% and a high coloration efficiency of 445 cm(2) C(-1) within a short darkening time of 2 s. The flexible ECDs also showed the same darkening time of 2 s and still had a high ΔT of 30.1% under bending condition. This study demonstrated the feasibility to fabricate display devices with different color setups by an all-solution process and can be further extended to other types of displays.

Three-dimensional Fe(II)-based metallo-supramolecular polymers with electrochromic properties of quick switching, large contrast, and high coloration efficiency.

A series of Fe(II)-based metallo-supramolecular polymers with three-dimensional (3-D) structures were synthesized by the stepwise complexation of an Fe(II) salt with different ratios of a linear bis(terpyridine) ligand and a branched tris(terpyridine) ligand. Atomic force microscopy images of the polymer films showed a drastic change in the surface morphology upon varying the amount of the branched ligand. The surface of a designed 3-D construction film showed a highly porous structure (pore size: approximately 30-50 nm in diameter), probably due to the formation of a hyperbranched polymer structure. All the 3-D polymers had a blue color based on the metal-to-ligand charge-transfer (MLCT) absorption and exhibited excellent electrochromic properties. The most highly porous 3-D-structured film showed the best electrochromic performance; as compared with a 1-D linear polymer, the switching times were improved 38.7% for the coloring (0.31 → 0.19 s) and 37.9% for the bleaching (0.58 → 0.36 s). The transmittance change (ΔT) increased 21.8% (41.6 → 50.7%). Also, the coloration efficiency (η) was enhanced 45.3% (263.8 → 383.4 cm(2) C(-1)). The redox in the 3-D film was diffusion-controlled, as supported by the linear relationship between the current and square root of the scan rate. It is considered that the porous structure of the 3-D polymer films contributed to smooth ionic transfer during the redox and to the improved electrochromic properties.

Origami paper-based fluidic batteries for portable electrophoretic devices.

A manufacturing approach for paper-based fluidic batteries was developed based on the origami principle (three-dimension paper folding). Microfluidic channels were first created on a filter paper by a wax-printing method. Copper and aluminium sheets were then glued onto the paper as electrodes for the redox reaction. After the addition of copper sulphate and aluminium chloride, commonly available cellophane paper was attached as a membrane to separate the two electrodes. The resulting planar paper sheets were then folded into three-dimensional structures and compiled as a single battery with glue. The two half reactions (Al/Al(3+) and Cu/Cu(2+)) in the folded batteries provided an open-circuit potential from 0.82 V (one cell) to 5.0 V (eight cells in series) depending on the origami design. The prepared battery can provide a stable current of 500 µA and can light a regular LED for more than 65 min. These paper-based fluidic batteries in a set can also be compiled into a portable power bank to provide electric power for many electric or biomedical applications, such as LED lights and electrophoretic devices, as we report here.

Tunable electrofluorochromic device from electrochemically controlled complementary fluorescent conjugated polymer films.

The fluorescent behavior of the electrofluorochromic devices (Type I) of greenish-yellow emitting P1 and blue emitting P2 can be reversibly switched between the nonfluorescent (oxidized) state and the fluorescent (neutral) state with a superb on/off ratio of 23.8 and 21.9, respectively. Moreover, a tunable electrofluorochromic device (Type II) based on two P1 and P2 polymeric layers that are coated individually on two independent ITO electrodes shows switchable blue-white-(greenish-yellow) multifluorescence states.

Rutile-type (Ti,Sn)O2 nanorods as efficient anode materials toward its lithium storage capabilities.

A series of rutile-type (Ti,Sn)O2 solid solutions with nanorod architecture were successfully synthesized in this study by varying their calcination temperatures of tin-modified titanium dioxide (Sn/TiO2) nanocomposites under a nitrogen atmosphere. During the delithiation process, the (Ti,Sn)O2 nanorods obtained at 500 °C delivered a specific capacity of about 300 mA h g(-1) and showed minimal capacity fading even at a high current density of 3 A g(-1).

Fluorescence lifetime imaging of alterations to cellular metabolism by domain 2 of the hepatitis C virus core protein.

Hepatitis C virus (HCV) co-opts hepatic lipid pathways to facilitate its pathogenesis. The virus alters cellular lipid biosynthesis and trafficking, and causes an accumulation of lipid droplets (LDs) that gives rise to hepatic steatosis. Little is known about how these changes are controlled at the molecular level, and how they are related to the underlying metabolic states of the infected cell. The HCV core protein has previously been shown to independently induce alterations in hepatic lipid homeostasis. Herein, we demonstrate, using coherent anti-Stokes Raman scattering (CARS) microscopy, that expression of domain 2 of the HCV core protein (D2) fused to GFP is sufficient to induce an accumulation of larger lipid droplets (LDs) in the perinuclear region. Additionally, we performed fluorescence lifetime imaging of endogenous reduced nicotinamide adenine dinucleotides [NAD(P)H], a key coenzyme in cellular metabolic processes, to monitor changes in the cofactor's abundance and conformational state in D2-GFP transfected cells. When expressed in Huh-7 human hepatoma cells, we observed that the D2-GFP induced accumulation of LDs correlated with an increase in total NAD(P)H fluorescence and an increase in the ratio of free to bound NAD(P)H. This is consistent with an approximate 10 fold increase in cellular NAD(P)H levels. Furthermore, the lifetimes of bound and free NAD(P)H were both significantly reduced--indicating viral protein-induced alterations in the cofactors' binding and microenvironment. Interestingly, the D2-expressing cells showed a more diffuse localization of NAD(P)H fluorescence signal, consistent with an accumulation of the co-factor outside the mitochondria. These observations suggest that HCV causes a shift of metabolic control away from the use of the coenzyme in mitochondrial electron transport and towards glycolysis, lipid biosynthesis, and building of new biomass. Overall, our findings demonstrate that HCV induced alterations in hepatic metabolism is tightly linked to alterations in NAD(P)H functional states.

One-pot synthesis of poly (3,4-ethylenedioxythiophene)-Pt nanoparticle composite and its application to electrochemical H2O2 sensor.

Poly(3,4-ethylenedioxythiophene)-Pt nanoparticle composite was synthesized in one-pot fashion using a photo-assisted chemical method, and its electrocatalytic properties toward hydrogen peroxide (H2O2) was investigated. Under UV irradiation, the rates of the oxidative polymerization of EDOT monomer along with the reduction of Pt4+ ions were accelerated. In addition, the morphology of PtNPs was also greatly influenced by the UV irradiation; the size of PtNPs was reduced under UV irradiation, which can be attributed to the faster nucleation rate. The immobilized PtNPs showed excellent electrocatalytic activities towards the electroreduction of hydrogen peroxide. The resultant amperometric sensor showed enhanced sensitivity for the detection of H2O2 as compared to that without PtNPs, i.e., only with a layer of PEDOT. Amperometric determination of H2O2 at -0.55 V gave a limit of detection of 1.6 µM (S / N = 3) and a sensitivity of 19.29 mA cm-2 M-1 up to 6 mM, with a response time (steady state, t95) of 30 to 40 s. Energy dispersive X-ray analysis, transmission electron microscopic image, cyclic voltammetry (CV), and scanning electron microscopic images were utilized to characterize the modified electrode. Sensing properties of the modified electrode were studied both by CV and amperometric analysis.

Modification of glassy carbon electrode with a polymer/mediator composite and its application for the electrochemical detection of iodate.

A modified glassy carbon electrode was prepared by depositing a composite of polymer and mediator on a glassy carbon electrode (GCE). The mediator, flavin adenine dinucleotide (FAD) and the polymer, poly(3,4-ethylenedioxythiophene) (PEDOT) were electrochemically deposited as a composite on the GCE by applying cyclic voltammetry (CV). This modified electrode is hereafter designated as GCE/PEDOT/FAD. FAD was found to significantly enhance the growth of PEDOT. Electrochemical quartz crystal microbalance (EQCM) analysis was performed to study the mass changes in the electrode during the electrodeposition of PEDOT, with and without the addition of FAD. The optimal cycle number for preparing the modified electrode was determined to be 9, and the corresponding surface coverage of FAD (Γ(FAD)) was ca. 5.11×10(-10)mol cm(-2). The amperometric detection of iodate was performed in a 100 mM buffer solution (pH 1.5). The GCE/PEDOT/FAD showed a sensitivity of 0.78 µA µM(-1) cm(-2), a linear range of 4-140 µM, and a limit of detection of 0.16 µM for iodate. The interference effects of 250-fold Na(+), Mg(2+), Ca(2+), Zn(2+), Fe(2+), Cl(-), NO(3)(-), I(-), SO(4)(2-) and SO(3)(2-), with reference to the concentration of iodate were negligible. The long-term stability of GCE/PEDOT/FAD was also investigated. The GCE/PEDOT/FAD electrode retained 82% of its initial amperometric response to iodate after 7 days. The GCE/PEDOT/FAD was also applied to determine iodate in a commercial salt.