HA Molecules Research Articles

Disulfide-stabilized trimeric hemagglutinin ectodomains provide enhanced heterologous influenza protection

ABSTRACT Influenza virus infection poses a continual menace to public health. Here, we developed soluble trimeric HA ectodomain vaccines by establishing interprotomer disulfide bonds in the stem region, which effectively preserve the native antigenicity of stem epitopes. The stable trimeric H1 ectodomain proteins exhibited higher thermal stabilities in comparison with unmodified HAs and showed strong binding activities towards a panel of anti-stem cross-reactive antibodies that recognize either interprotomer or intraprotomer epitopes. Negative stain transmission electron microscopy (TEM) analysis revealed the stable trimer architecture of the interprotomer disulfide-stapled WA11#5, NC99#2, and FLD#1 proteins as well as the irregular aggregation of unmodified HA molecules. Immunizations of mice with those trimeric HA ectodomain vaccines formulated with incomplete Freund’s adjuvant elicited significantly more potent cross-neutralizing antibody responses and offered broader immuno-protection against lethal infections with heterologous influenza strains compared to unmodified HA proteins. Additionally, the findings of our study indicate that elevated levels of HA stem-specific antibody responses correlate with strengthened cross-protections. Our design strategy has proven effective in trimerizing HA ectodomains derived from both influenza A and B viruses, thereby providing a valuable reference for designing future influenza HA immunogens.

Hyaluronic Acid Nanoparticles with Parameters Required for In Vivo Applications: From Synthesis to Parametrization.

Hyaluronic acid is an excellent biocompatible material for in vivo applications. Its ability to bind CD44, a cell receptor involved in numerous biological processes, predetermines HA-based nanomaterials as unique carrier for therapeutic and theranostic applications. Although numerous methods for the synthesis of hyaluronic acid nanoparticles (HANPs) are available today, their low reproducibility and wide size distribution hinder the precise assessment of the effect on the organism. A robust and reproducible approach for producing HANPs that meet strict criteria for in vivo applications (e.g., to lung parenchyma) remains challenging. We designed and evaluated four protocols for the preparation of HANPs with those required parameters. The HA molecule was cross-linked by novel combinations of carbodiimide, and four different amine-containing compounds resulted in monodisperse HANPs with a low polydispersity index. By a complex postsynthetic characterization, we confirmed that the prepared HANPs meet the criteria for inhaled therapeutic delivery and other in vivo applications.

Modification and crosslinking strategies for hyaluronic acid-based hydrogel biomaterials.

Hyaluronic acid (HA) is an attractive extracellular matrix-derived polymer. The related HA-based hydrogels are emerging to be the hotspots in the cutting edge of biomaterials. The continuous sights concentrate on exploring modification methods and crosslinking strategies to promote the advancement of HA-based hydrogels with enhanced physical/chemical properties and enriched biological performance. Here, the advances on modification methods and crosslinking strategies for fabricating HA-based hydrogels with diverse capacities are summarized. Firstly, the modification reactions that occur on the active hydroxyl, carboxyl and N-acetyl groups of HA molecule are discussed. Next, the emphasis is put on various crosslinking strategies including physical crosslinking, covalent crosslinking and dynamic covalent crosslinking. Finally, we provide a general summary and give a critical viewpoint on the remaining challenges and the future development of HA-based hydrogels. It is hoped that this review can provide new proposals for the specific design of functional hydrogel biomaterials.

Developing hyaluronic acid-proline-ferric ion cross-linked film for efficient wound healing application

A novel cross-linked film dressing that can accelerate wound healing and guard against bacterial infection was presented in this work. The hyaluronic acid-proline-ferric ion (HA-Pro-Fe3+) film was successfully prepared by physically cross-linking method, which the carboxyl groups of the HA and Pro molecules should be in coordination with Fe3+. The HA-Pro-Fe3+ cross-linked film showed three-dimensional porous structure, appropriate water vapor permeability and swelling property, favorable cytocompatibility and hemocompatibility, antibacterial and antioxidative capability. The results of rat skin wound healing confirmed that HA-Pro-Fe3+ film could accelerate epithelial regeneration and collagen deposition, promote angiogenesis and significantly improve skin wound healing. Elisa analysis indicated that HA-Pro-Fe3+ material could down-regulate the expression of IL-6 and TNF-α, and up-regulate the level of TGF-β1 and VEGF. Given its biocompatibility, antibacterial ability, promotion of cell proliferation and angiogenesis, the wide application of HA-Pro-Fe3+ cross-linked film in wound repair would be anticipated.

Essential Role of Forest Fires in Humic Acids Structure and Composition Alteration

Pyrogenic components of soil organic matter are practically not taken into account when assessing the implications of global climate changes on the SOM sequestration rate and its stability. In this regard, both the amount and structural stability of SOM were investigated for postpyrogenic forest–steppe environments. Mature unaffected by fire Psamment Entisols were investigated in comparison with same soil strongly affected by surface and crown fires in 2010 in Tolyatti city. This article discusses postpyrogenic succession when comparing the results of field works in 2010 with 2020. The elemental composition of humic acids as well as 13C NMR spectra were investigated for the studied humic acids. Moreover, for the first time ever, integrated indicators of HAs’ molecular composition were presented for postpyrogenic soils. The data obtained showed that there are significant changes in the structural organization of organic matter as a result of forest fires. A simultaneous decrease in the H/C and O/C atomic ratios was identified as a result of fire, which indicates a slight loss of oxygen-containing functional groups, while the aromaticity degree of molecules increases. An increase in the content of oxygen-containing groups in the HA molecules was shown for 10 years after the fires, which was accompanied by the oxidation of the HA molecule with the same increase in the aromaticity degree of the HA molecule. The HA molecules of 2020 turned out to be more resistant to environmental factors compared to analogues in 2010. As a result of fires, the aromaticity degree of HAs molecules significantly increases.

On the Mechanism of Selective Chemical Exchange of Bacteriopheophytins in the Reaction Centers of Rhodobacter sphaeroides R-26.

To elucidate the mechanism of site-selective chemical replacement of chromophores in the reaction centers (RCs) of photosynthetic bacteria by external pigments, we investigated how the efficiency of incorporation of plant pheophytin a (Pheo) into the binding sites for bacteriopheophytin a molecules (BPheo) in the isolated Rhodobacter sphaeroides R-26 RCs depended on the incubation medium temperature, Pheo aggregation state, and the presence of organic solvent (acetone). When Pheo was in a form of monomers in free detergent micelles in a water-detergent incubation medium, the degree of selective replacement of photochemically inactive BPheo HB molecules upon incubation of the RC/Pheo mixture at 5°C was ~15%. The exchange efficiency increased to 40% upon incubation at 25°C and reached 100% at the same temperature when 10% acetone was added to the incubation medium. At both 5 and 25°C, the degree of pigment exchange increased approximately twice, when a mixture of Pheo monomers and dimers in the presence of 10% acetone was used as the incubation medium. The removal of acetone from this medium with the preservation of pigment forms led to a significant decrease in the efficiency of Pheo incorporation. The effect of acetone on the pigment exchange was also observed at an elevated incubation temperature (43.5°C), when functionally active BPheo HA molecules were partially replaced. The results are discussed in terms of the mechanism according to which (i) the temperature-dependent internal movements of the RC protein facilitate the release of the BPheo molecule from the binding site with simultaneous insertion of the Pheo molecule into the same site in a coupled process, (ii) the role of temperature largely depends on the steric accessibility of binding pockets in the RC protein, (iii) the incorporation of Pheo occurs from a pool of monomeric molecules included in the RC-detergent micelles, and (iv) the presence of acetone in the incubation medium facilitates the exchange of Pheo monomers between micelles in the solution and the detergent belt of the RC complex.

Molecular Dynamics Investigation of Hyaluronan in Biolubrication.

Aqueous solution of strongly hydrophilic biopolymers is known to exhibit excellent lubrication properties in biological systems, such as the synovial fluid in human joints. Several mechanisms have been proposed on the biolubrication of joints, such as the boundary lubrication and the fluid exudation lubrication. In these models, mechanical properties of synovial fluid containing biopolymers are essential. To examine the role of such biopolymers in lubrication, a series of molecular dynamics simulations with an all-atom classical force field model were conducted for aqueous solutions of hyaluronan (hyaluronic acid, HA) under constant shear. After equilibrating the system, the Lees-Edwards boundary condition was imposed, with which a steady state of uniform shear flow was realized. Comparison of HA systems with hydrocarbon (pentadecane, PD) solutions of similar mass concentration indicates that the viscosity of HA solutions is slightly larger in general than that of PDs, due to the strong hydration of HA molecules. Effects of added electrolyte (NaCl) were also discussed in terms of hydration. These findings suggest the role of HA in biolubirication as a load-supporting component, with its flexible character and strong hydration structure.

Characteristics of humic acids isolated from burned and unburned topsoils in sub-boreal Scotch pine forests by 13C-NMR spectroscopy

Postpyrogenic soil dynamics is an informative tool for studying soil elementary processes in extreme temperature conditions and for predicting short time environmental changes in conditions of catastrophic landscape changes. Soil organic matter (SOM) system evolution is the most rapid process of postpyrogenic soil development. In this relation, the focus on humus structure is important for understanding these important dynamics. Soil restoration after spontaneous forest fires near Togljatty City (Samara Region, Russia) was abandoned in 2010 and further monitoring over the next ten years was organised to evaluate the speed of humus accumulation dynamics. The aim of this study was to apply the 13C-NMR (nuclear magnetic resonance) spectroscopy to analyse the effect of forest fires on SOM degradation in Scotch pine forests on Psamment Entisols of the fragmented steppe in the Samara Region. Three key soil plots were studied for estimating SOM quality changes under the forest fire effect: surface forest fire, crown forest fire and control, i.e. 18 soil samples of top soil horizons were analysed in three replicates. The data obtained indicate that the humus molecular composition was substantially affected by the wildfires. Investigation of the humic acids’ (HAs) molecular structure by 13C-NMR showed a relative increase in aromatic compounds and decrease in aliphatic ones. The aromaticity degree of HA molecules increases in 5.7 and 3.8 times in cases of surface and crown forest fires, correspondingly. In general, crown and surface fires plots are not very different in terms of 13C-NMR spectra of HAs (p = 0.34); however, HAs of control plot have essential differences from pyrogenic ones (p < 0.05). 13C NMR spectra have shown a change in the proportion of oxygen-containing functional groups as well. One of the most important effects observed in wildfire-affected SOM is that the proportion of lignin-like structures increases as a concomitant effect of depletion of C,H-alkyl groups, especially in the case of crown fires.

Bioanalytics for Influenza Virus-Like Particle Characterization and Process Monitoring.

Virus-like particles (VLPs) are excellent platforms for the development of influenza vaccine candidates. Nonetheless, their characterization is challenging due to VLPs’ unique biophysical and biochemical properties. To cope with such complexity, multiple analytical techniques have been developed to date (e.g., single-particle analysis, thermal stability, or quantification assays), most of which are rarely used or have been successfully demonstrated for being applicable for virus particle characterization. In this study, several biophysical and biochemical methods have been evaluated for thorough characterization of monovalent and pentavalent influenza VLPs from diverse groups (A and B) and subtypes (H1 and H3) produced in insect cells using the baculovirus expression vector system (IC-BEVS). Particle size distribution and purity profiles were monitored during the purification process using two complementary technologies — nanoparticle tracking analysis (NTA) and tunable resistive pulse sensing (TRPS). VLP surface charge at the selected process pH was also assessed by this last technique. The morphology of the VLP (size, shape, and presence of hemagglutinin spikes) was evaluated using transmission electron microscopy. Circular dichroism was used to assess VLPs’ thermal stability. Total protein, DNA, and baculovirus content were also assessed. All VLPs analyzed exhibited similar size ranges (90–115 nm for NTA and 129–141 nm for TRPS), surface charges (average of −20.4 mV), and morphology (pleomorphic particles resembling influenza virus) exhibiting the presence of HA molecules (spikes) uniformly displayed on M1 protein scaffold. Our data shows that HA titers and purification efficiency in terms of impurity removal and thermal stability were observed to be particle dependent. This study shows robustness and generic applicability of the tools and methods evaluated, independent of VLP valency and group/subtype. Thus, they are most valuable to assist process development and enhance product characterization.

The reuse of nano-TiO2 under different concentration of CO32– using coagulation process and its photocatalytic ability in treatment of methyl orange

• Al-based coagulants can effectively separate nano-TiO 2 . • Flocs formed by different coagulants can degrade methyl orange. • AT 2 achieved high degradation efficiency under UV irradiation. • It proposes a new perspective on recycling coagulated flocs for sewage treatment. Photocatalysis is highly efficient for the treatment of dyeing wastewater. However, the wastewater still contains a large amount of nano-TiO 2 after photocatalysis. In order to reduce the cost of nano-TiO 2 , different coagulants were used to improve the solid/liquid separation efficiency. At the same time, the reuse of flocs has raised increasing attention after coagulation. In this study, we report on the recycling of flocs for the production of AlCl 3 and TiO 2 formed flocs (AT 1 ) and Al 13 and TiO 2 formed flocs (AT 2 ) through a simple calcination process. Results indicated the flocs formation processes under different concentration of CO 3 2– were Al species distribution and coagulant dosage dependent. Without HA molecules, the reaction between Al-based coagulants and CO 3 2– are the controlling steps in the coagulation process, and Al a and Al b species had different reaction processes. The influence of HA molecules was also studied, and the HA-Al aggregates which could bridge the TiO 2 nanoparticles, and thus induce sweep flocculation. Consequently, highly enhanced aggregation rate, due to the heteroaggregation between these aggregates and TiO 2 was observed. After calcination, the AT 2 -10 and AT 2 -20 (CO 3 2– : 10, 20 mmol/L) with petal-like structures (mesoporous), relatively high specific surface areas, i.e. 83.98 m 2 /g and 78.38 m 2 /g and high photocatalytic degradation, i.e. 72.79%, 67.78% (compared to nano-TiO 2 , AT 1 -10 and AT 1 -20), were obtained. Additionally, oxygen vacancy (OV) was generated on the surface of the recycled AT 2 -10 and AT 2 -20, which display strong photocatalytic performance for the degradation of MO greater than 65%, under ultraviolet (UV) irradiation and without any sacrificial reagents. This study proposes a new perspective on recycling coagulated flocs for practical application in wastewater treatment.

Enhancement of the electron transfer and ion transport phenomena in microbial fuel cells containing humic acid-modified bioanodes

Although microbial fuel cells (MFCs) are an attractive alternative to environmental remediation and power generation, there are still significant limitations related to power density and coulombic efficiency. Previous works have shown that the addition of humic acids (HA, a type of organic matter contained in soils and composting-by-products), improves the fuel to electricity conversion at the porous bioanodes (ba)|anolyte junction. In this work, MFCs having HA-modified bioanodes (MFC/baHA) were prepared and electrochemically analyzed utilizing discharge curves (cell potential vs current density plots) and electrochemical impedance spectroscopy (EIS). This investigation was motivated by looking for a deeper understanding of the functional effects of HA molecules on the operation of baHA-containing Microbial Fuel Cells (MFC/baHA). Our results revealed that the modification of bioanodes with HA molecules decreases the activation energy of the acetate ion oxidation, increasing by a factor of three the consumption rate of this fuel at the baHA|anolyte interface, and enhancing the diffusive transport of these ions through the pores of the baHA permeated by the anolyte.

Human antibody recognition of H7N9 influenza virus HA following natural infection.

Avian H7N9 influenza viruses cause sporadic outbreaks of human infections and threaten to cause a major pandemic. The breadth of B cell responses to natural infection and the dominant antigenic sites recognized during first exposure to H7 HA following infection are incompletely understood. Here, we studied the B cell response to H7 HA of 2 individuals who had recovered from natural H7N9 virus infection. We used competition binding, hydrogen-deuterium mass spectrometry, and single-particle negative stain electron microscopy to identify the patterns of molecular recognition of the antibody responses to H7 HA. We found that circulating H7-reactive B cells recognized a diverse antigenic landscape on the HA molecule, including HA head domain epitopes in antigenic sites A and B and in the trimer interface-II region and epitopes in the stem region. Most H7 antibodies exhibited little heterosubtypic breadth, but many recognized a wide diversity of unrelated H7 strains. We tested the antibodies for functional activity and identified clones with diverse patterns of inhibition, including neutralizing, hemagglutination- or egress-inhibiting, or HA trimer–disrupting activities. Thus, the human B cell response to primary H7 natural infection is diverse, highly functional, and broad for recognition of diverse H7 strains.

Monoclonal antibodies to hemagglutinin of influenza A/H7N3 virus (Orthomyxoviridae: Alphainfluenzavirus: Influenza A virus)

Variants of influenza virus A/H7 have the same high pandemic potential as A/H5. However, the information about the antigenic structure of H7 hemagglutinin (НА) is considerably inferior in quantitative terms to similar data for H5 НА.The aims of the study were development and characterization of the monoclonal antibodies (MAbs) panel for HA subtype H7 of the influenza A virus. Viruses were accumulated in 10-day-old chicken embryos. Purification and concentration of the virus, determination of protein concentration, preparation of MAbs and ascitic fluids, hemagglutination and hemagglutination inhibition (HI) tests, assessment of antibodies' activity in indirect enzyme-linked immunosorbent assay (ELISA), as well as determination of MAbs isotypes and neutralization reaction (NR) were carried out by standard methods. The obtained MAbs to А/mallard/Netherlands/12/2000 (H7N3) strain were studied in HI test with a set of strains of different years of isolation belonging to different evolutionary groups. MAbs had a reduced reactivity compared to the immunogen-virus for all the studied strains. Cross-interaction of MAbs 9E11 and 9G12 in HI test with influenza A/H15 virus has been observed. Influenza A agent with H7 HA variant could serve as a potential cause of a future pandemic. Development of the MAbs panel for subtype H7 HA is an urgent task for both veterinary medicine and public health. The obtained MAbs can be used not only for epitope mapping of the H7 HA molecule (currently insufficiently studied) and as reagents for diagnostic assays, but also for determining common («universal») epitopes in HA of different strains of this subtype.

Humus is a guarantor of the stability of agroecosystems

The paper studies the processes of transformation of the molecular structure of humic (HA) and fulvic acids (FA) of leached chernozem under the influence of fertilizers and meliorant. The research was carried out under the conditions of many years of stationary experiment of the Department of Agrochemistry, Soil Science and Agroecology of the FSBEI HE Voronezh SAU. Samples of leached low-humus thin heavy-loamy chernozem were analyzed. The isolated and purified preparations of HA and FA were studied on a SM2203 spectrofluorimeter in the ultraviolet and visible ranges. The paper also presents the results of determining the most important physical and chemical properties of soil variants using various fertilizer and meliorant systems. Limed variants have optimal indicators. Based on the analysis, it can be assumed that the FA molecules of the variant with a double dose of mineral fertilizers on the background of manure differ in a developed aliphatic part, have many auxochromic substituents. HA of the same variant are characterized by a high condensation of nuclear structures. The HA and FA molecules of the variant with the joint application of fertilizers and meliorant have a more complex structure of the nuclear and peripheral parts. According to the results of calculations of extinction coefficients, it was found that liming contributes to the accumulation of more mature forms of humic acids.

Synthesis of hyaluronated poly(exo-7-oxabicyclo[2.2.1]hept-5-en-2,3-dicarboxylic anhydride) brushes via a combination of surface-initiated ring-opening metathesis polymerization and thiol-ene click reaction

Well-defined hyaluronated poly(exo-7-oxabicyclo[2.2.1]hept-5-en-2,3-dicarboxylic anhydride) [poly(EHDA)-HA] brushes on the hydroxyl-terminated silicon (Si–OH) surface were prepared through the combination of surface-initiated ring-opening metathesis polymerization (ROMP) and thiol-ene click reaction. This process was realized in four successive steps: (i) formation of self-assembled monolayer of (3-aminopropyl) triethoxysilane on the Si–OH surface (Si-APTES), (ii) bonding of EHDA monomer to the Si-APTES surface, (iii) synthesis of poly(EHDA) brushes via surface-initiated ROMP and (iv) coupling of thiolated hyaluronic acid (Th-HA) to poly(EHDA) chains via thiol-ene click reaction. Surface wettability, surface morphology and chemical compositions of poly(EHDA)-HA brushes were characterized by contact angle measurements, atomic force, microscopy and X-ray photoelectron spectroscopy, respectively. Grafting density (σ, chains nm−2) and average distance between grafting points (D, nm) of the poly(EHDA) brushes were measured to be 0.50 chains nm−2 and 1.65 nm, independent of the [catalyst]/[monomer] ratios, which indicated that high grafting was created on the silicon substrate. However, low amounts of HA molecules were bonded to poly(EHDA) chains due to the high volume of Th-HA chains creating some steric hindrances. Biocompatible property of the poly(EHDA)-HA brushes are useful candidate for making advanced biological devices to control the behavior of biomolecules on surfaces.

Probabilistic Optically-Selective Single-molecule Imaging Based Localization Encoded (POSSIBLE) microscopy for ultra-superresolution imaging.

To be able to resolve molecular-clusters it is crucial to access vital information (such as, molecule density, cluster-size, and others) that are key in understanding disease progression and the underlying mechanism. Traditional single-molecule localization microscopy (SMLM) techniques use molecules of variable sizes (as determined by its localization precision (LP)) to reconstruct a super-resolution map. This results in an image with overlapping and superimposing PSFs (due to a wide size-spectrum of single-molecules) that undermine image resolution. Ideally, it should be possible to identify the brightest molecules (also termed as the fortunate molecules) to reconstruct ultra-superresolution map, provided sufficient statistics is available from the recorded data. Probabilistic Optically-Selective Single-molecule Imaging Based Localization Encoded (POSSIBLE) microscopy explores this possibility by introducing a narrow probability size-distribution of single-molecules (narrow size-spectrum about a predefined mean-size). The reconstruction begins by presetting the mean and variance of the narrow distribution function (Gaussian function). Subsequently, the dataset is processed and single-molecules are filtered by the Gaussian function to remove unfortunate molecules. The fortunate molecules thus retained are then mapped to reconstruct an ultra-superresolution map. In-principle, the POSSIBLE microscopy technique is capable of infinite resolution (resolution of the order of actual single-molecule size) provided enough fortunate molecules are experimentally detected. In short, bright molecules (with large emissivity) holds the key. Here, we demonstrate the POSSIBLE microscopy technique and reconstruct single-molecule images with an average PSF sizes of σ ± Δσ = 15 ± 10 nm, 30 ± 2 nm & 50 ± 2 nm. Results show better-resolved Dendra2-HA clusters with large cluster-density in transfected NIH3T3 fibroblast cells as compared to the traditional SMLM techniques. Cluster analysis indicates densely-packed HA molecules, HA-HA interaction, and a surge in the number of HA molecules per cluster post 24 Hrs of transfection. The study using POSSIBLE microscopy introduces new insights in influenza biology. We anticipate exciting applications in the multidisciplinary field of disease biology, oncology, and biomedical imaging.

Neutralizing epitope of the Fusion Protein of Respiratory Syncytial Virus Embedded in the HA Molecule of LAIV Virus is not Sufficient to Prevent RS Virus Pulmonary Replication but Ameliorates Lung Pathology following RSV Infection in Mice

Aims:To develop experimental bivalent vaccines against influenza and RSV using a cold-adapted LAIV backbone.Background:Respiratory syncytial virus (RSV) is a causative agent of bronchiolitis and pneumonia in young children, elderly and immunocompromised adults. No vaccine against RSV has been licensed to date for various reasons. One of the promising platforms for designing RSV vaccine is the use of live attenuated influenza vaccine (LAIV) viruses to deliver RSV epitopes to the respiratory mucosa.Objective:To generate recombinant LAIV viruses encoding a neutralizing epitope of the RSV fusion protein and assess their protective potential against both influenza and RSV infections in a mouse model.Methods:Reverse genetics methods were used to rescue recombinant LAIV+HA/RSV viruses expressing chimeric hemagglutinins encoding the RSV-F epitope at its N-terminus using two different flexible linkers. BALB/c mice were intranasally immunized with two doses of the recombinant viruses and then challenged with the influenza virus or RSV. The LAIV viral vector and formalin-inactivated RSV (FI-RSV) were included as control vaccines. Protection was assessed by the reduction of virus pulmonary titers. In addition, RSV-induced lung pathology was evaluated by histopathology studies.Results:Two rescued chimeric LAIV+HA/RSV viruses were identical to the LAIV vector in terms of replication capacityin vitroandin vivo. The RSV-F neutralizing epitope was successfully expressed only if inserted into the HA molecule via G-linker, but not A-linker. Both chimeric viruses induced high influenza-specific antibody levels and fully protected mice against a lethal influenza challenge virus. However, they induced weak anti-RSV antibody responses which did not prevent RS virus replication upon challenge, and only LAIV-HA+G-RSV variant protected mice against RSV-induced lung pathology.Conclusion:Although the designed LAIV-RSV chimeric viruses were unable to neutralize the RS virus pulmonary replication, the LAIV-HA+G-RSV reduced RSV-induced lung pathology and can be considered a promising bivalent vaccine against influenza and RSV infections and warrants its further development.

Light-triggered NO-releasing nanoparticles for treating mice with liver fibrosis

Liver fibrosis, resulting from chronic liver damage and characterized by the accumulation of extracellular matrix (ECM) proteins, is a characteristic of most types of chronic liver diseases. The activation of hepatic stellate cells (HSC) is considered an essential pathological hallmark in liver fibrosis. Although nitric oxide (NO) can effectively induce HSC apoptosis, the systemic administration of NO is ineffective and may cause severe complications such as hypotension. To overcome this limitation, nanoparticles were designed to target HSCs and release NO locally under the exposure of near infrared light (NIR). To achieve this, upconversion nanoparticle (UCNP) cores were enveloped in mesoporous silica shells (UCNP@mSiO2), which were modified with hyaluronic acid (HA-UCNP@mSiO2) and Roussin’s black salt (RBS). HA molecules recognize and bind to CD44 proteins, which are overexpressed on activated HSCs. Under exposure to a 980-nm NIR laser, the UCNP cores convert the 980-nm wavelength into ultraviolet (UV) light, which then energizes the RBS (NO donors), resulting in an efficient release of NO inside of the HSCs. Once released, NO triggers HSC apoptosis and reverses the liver fibrosis. This targeted and controlled release method provides the theoretical and experimental basis for novel therapeutic approaches to treat hepatic fibrosis.

Extraction of Lanthanides(III) along with Thorium(IV) from Chloride Solutions by N,N-di(2-Ethylhexyl)-Diglycolamic Acid

ABSTRACT The extraction of Nd(III), Gd(III), and Er(III), which represent light, middle, and heavy lanthanides, respectively, from chloride solutions has been carried out by using N,N-di(2-ethylhexyl)-diglycolamic acid (HDEHDGA, HA) diluted in kerosene as the organic phase. The results from the slope analysis method indicate that the extraction of Ln(III) with HDEHDGA is mainly governed by the cation-exchange reaction mechanisms in the low pH region (pH 1.2–2.7). The obtained data reveal that the extracted species in the organic phase might be LnA3∙HA(1~2), which consist of a core of 1:3 LnA3 complex and one additional neutral HA molecule for light Ln(III) or two for heavy Ln(III) associated with the core in the outer coordination sphere. The dependency on the temperatures indicates that the extraction of Ln(III) with HDEHDGA is exothermic and is mainly driven by the exothermic enthalpies crossing the whole Ln(III) series. The extraction of the whole Ln(III) series (except for Pm(III)) and Th(IV) has also been evaluated. HDEHDGA provides remarkable extraction capability with considerable separation factors (SF) for adjacent light Ln(III) pairs (SFCe/La = 6.8, SFPr/Ce = 3.3, SFNd/Pr = 2.5, and SFSm/Nd = 3.5), but relatively poor selectivity for the adjacent heavy Ln(III) pairs. It also presents very good selectivity/extractability for Th(IV) over the light Ln(III) ions (SFTh/La = 1362 and SFTh/Ce = 200). These properties make HDEHDGA a promising extractant for separating Th(IV) from light Ln(III) ions and for separating light Ln(III) ions from each other, which coexist significantly in some Rare Earth (RE) minerals, especially monazite and bastnaesite.

Impacts of composite flocculant in coagulation/ultrafiltration hybrid process for treatment of humic acid water: the role of basicity

ABSTRACT The effects of the composite flocculant, polyaluminium chloride and poly dimethyldiallylammonium chloride (PACl-PDMDAAC) in comparison with PACl on coagulation efficiencies and membrane fouling in coagulation-ultrafiltration (C-UF) process were analysed, which was conducted in the conditions of different basicity (B) values and the presence of Mg2+. Results showed that PACl-PDMDAAC enhanced the ability of charge neutralization and absorption bridging, and improved the coagulation efficiency. When B value was 1.5, the flocculant hydrolyzed to form more Alb morphology and effectively removed HA molecules. The presence of Mg2+ could improve the coagulation performance through bridging ability. The results of the ultrafiltration test showed that the flux reduction for PACl was 70%, while the flux reduction for PACl-PDMDAAC was 60% in C-UF process. PACl-PDMDAAC could effectively reduce membrane fouling mainly by reducing strongly attached cake/gel layer. When B value was 1.5, the Alb content of the flocculant was higher and the ability of adsorption charge neutralization was strong, resulting in forming a stable cake layer. Therefore, the membrane fouling was the lightest. In addition, the presence of Mg2+ in raw water reduced the membrane fouling.