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Thermochromic vanadium dioxide (VO2) can intelligently modulate the transmittance of indoor solar radiation to reduce the energy consumption of air conditioning in buildings. Nevertheless, it remains a great challenge to simultaneously improve the luminous transmittance (Tlum) and solar modulation ability (ΔTsol) of VO2. In this study, a novel approach is employed utilizing a coordination compound to finely tune the growth of a VO2 based composite film, yielding a hierarchical film comprising Zn2V2O7 nanoflakes and VO2@Zn2V2O7 core-shell nanoparticles. Remarkably, the resulting composite films showcase exceptional optical performance, achieving a Tlum of up to 73.0% and ΔTsol of 15.7%. These outcomes are attributed to the antireflection properties inherent in the nanoflake structure and the localized surface plasmon resonance of well-dispersed VO2 nanoparticles. In addition, the Zn2V2O7-VO2 film demonstrates remarkable environmental durability, retaining 90% of its initial ΔTsol even after undergoing aging at 100 °C under 50% relative humidity for a substantial period of 30 days - a durability equivalent to ≈20 years under ambient conditions. This work not only achieves a harmonious balance between Tlum and ΔTsol but also introduces a promising avenue for the design of distinctive composite nanostructures.
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High energy density and intrinsic safety are the central pursuits in developing rechargeable Zinc-ion batteries (ZIBs). The capacity and stability of nickel cobalt oxide (NCO) cathode are unsatisfactory because of its semiconductor character. Herein, we propose a built-in electric field (BEF) approach by synergizing cationic vacancies and ferroelectric spontaneous polarization on cathode side to facilitate electron adsorption and suppress zinc dendrite growth on the anode side. Concretely, NCO with cationic vacancies was constructed to expand lattice spacing for enhanced zinc-ion storage. Heterojunction with BEF leads to the Heterojunction//Zn cell exhibiting a capacity of 170.3â mAh g-1 at 400â mA g-1 and delivering a competitive capacity retention of 83.3 % over 3000 cycles at 2â A g-1 . We conclude the role of spontaneous polarization in suppressing zinc dendrite growth dynamics, which is conducive to developing high-capacity and high-safety batteries via tailoring defective materials with ferroelectric polarization on the cathode.
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Dendritas , Zinc , Cationes , ElectrodosRESUMEN
Factor VIII (FVIII) replacement products enable comprehensive care in hemophilia A. Treatment goals in severe hemophilia A are expanding beyond low annualized bleed rates to include long-term outcomes associated with high sustained FVIII levels. Endogenous von Willebrand factor (VWF) stabilizes and protects FVIII from degradation and clearance, but it also subjects FVIII to a half-life ceiling of â¼15 to 19 hours. Increasing recombinant FVIII (rFVIII) half-life further is ultimately dependent upon uncoupling rFVIII from endogenous VWF. We have developed a new class of FVIII replacement, rFVIIIFc-VWF-XTEN (BIVV001), that is physically decoupled from endogenous VWF and has enhanced pharmacokinetic properties compared with all previous FVIII products. BIVV001 was bioengineered as a unique fusion protein consisting of a VWF-D'D3 domain fused to rFVIII via immunoglobulin-G1 Fc domains and 2 XTEN polypeptides (Amunix Pharmaceuticals, Inc, Mountain View, CA). Plasma FVIII half-life after BIVV001 administration in mice and monkeys was 25 to 31 hours and 33 to 34 hours, respectively, representing a three- to fourfold increase in FVIII half-life. Our results showed that multifaceted protein engineering, far beyond a few amino acid substitutions, could significantly improve rFVIII pharmacokinetic properties while maintaining hemostatic function. BIVV001 is the first rFVIII with the potential to significantly change the treatment paradigm for severe hemophilia A by providing optimal protection against all bleed types, with less frequent doses. The protein engineering methods described herein can also be applied to other complex proteins.
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Factor VIII/metabolismo , Hemofilia A/terapia , Hemorragia/prevención & control , Proteínas Recombinantes de Fusión/administración & dosificación , Factor de von Willebrand/metabolismo , Animales , Factor VIII/genética , Hemofilia A/metabolismo , Hemofilia A/patología , Hemostasis , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Primates , Factor de von Willebrand/genéticaRESUMEN
Root-knot nematodes (Meloidogyne spp.) are obligate plant parasites that cause severe economic losses to agricultural crops worldwide. Because of serious health and environmental concerns related to the use of chemical nematicides, the development of efficient alternatives is of great importance. Biological control through exploiting the potential of rhizosphere microorganisms is currently accepted as an important approach for pest management in sustainable agriculture. In our research, during screening of rhizosphere bacteria against the root-knot nematodes Meloidogyne incognita, Ochrobactrum pseudogrignonense strain NC1 from the rhizosphere of healthy tomatoes showed strong nematode inhibition. A volatile nematicidal assay showed that the cell-free fermentation filtrate in the first-row wells of 12-well tissue culture plates caused M. incognita juvenile mortality in the second-row wells. Gas chromatography-mass spectrometry analysis revealed that dimethyl disulfide (DMDS) and benzaldehyde were the main volatile compounds produced by strain NC1. The nematicidal activity of these compounds indicated that the lethal concentration 50 against the M. incognita juveniles in the second-row wells and the fourth-row wells were 23.4 µmol/ml and 30.7 µmol/ml for DMDS and 4.7 µmol/ml and 15.2 µmol/ml for benzaldehyde, respectively. A greenhouse trial using O. pseudogrignonense strain NC1 provided management efficiencies of root-knot nematodes of 88 to 100% compared with the untreated control. This study demonstrated that nematode-induced root-gall suppression mediated by the bacterial volatiles DMDS and benzaldehyde presents a new opportunity for root-knot nematode management.
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Solanum lycopersicum , Tylenchoidea , Animales , Antinematodos/farmacología , Bacterias , Benzaldehídos , Solanum lycopersicum/microbiología , Tylenchoidea/fisiologíaRESUMEN
Anti-factor VIII (FVIII) antibodies is a major complication of FVIII replacement therapy for hemophilia A. We investigated the immune response to recombinant human factor VIII Fc (rFVIIIFc) in comparison to BDD-rFVIII and full-length rFVIII (FL-rFVIII) in hemophilia A mice. Repeated administration of therapeutically relevant doses of rFVIIIFc in these mice resulted in significantly lower antibody responses to rFVIII compared to BDD-rFVIII and FL-rFVIII and reduced antibody production upon subsequent challenge with high doses of rFVIIIFc. The induction of a tolerogenic response by rFVIIIFc was associated with higher percentage of regulatory T-cells, a lower percentage of pro-inflammatory splenic T-cells, and up-regulation of tolerogenic cytokines and markers. Disruption of Fc interactions with either FcRn or Fcγ receptors diminished tolerance induction, suggesting the involvement of these pathways. These results indicate that rFVIIIFc reduces immunogenicity and imparts tolerance to rFVIII demonstrating that recombinant therapeutic proteins may be modified to influence immunogenicity and facilitate tolerance.
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Factor VIII/inmunología , Hemofilia A/inmunología , Tolerancia Inmunológica/inmunología , Fragmentos Fc de Inmunoglobulinas/inmunología , Proteínas Recombinantes de Fusión/inmunología , Animales , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Factor VIII/farmacología , Citometría de Flujo , Humanos , Fragmentos Fc de Inmunoglobulinas/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Reacción en Cadena de la Polimerasa , Proteínas Recombinantes de Fusión/farmacología , Linfocitos T/inmunologíaRESUMEN
Despite proven benefits, prophylactic treatment for hemophilia A is hampered by the short half-life of factor VIII. A recombinant factor VIII-Fc fusion protein (rFVIIIFc) was constructed to determine the potential for reduced frequency of dosing. rFVIIIFc has an â¼ 2-fold longer half-life than rFVIII in hemophilia A (HemA) mice and dogs. The extension of rFVIIIFc half-life requires interaction of Fc with the neonatal Fc receptor (FcRn). In FcRn knockout mice, the extension of rFVIIIFc half-life is abrogated, and is restored in human FcRn transgenic mice. The Fc fusion has no impact on FVIII-specific activity. rFVIIIFc has comparable acute efficacy as rFVIII in treating tail clip injury in HemA mice, and fully corrects whole blood clotting time (WBCT) in HemA dogs immediately after dosing. Furthermore, consistent with prolonged half-life, rFVIIIFc shows 2-fold longer prophylactic efficacy in protecting HemA mice from tail vein transection bleeding induced 24-48 hours after dosing. In HemA dogs, rFVIIIFc also sustains partial correction of WBCT 1.5- to 2-fold longer than rFVIII. rFVIIIFc was well tolerated in both species. Thus, the rescue of FVIII by Fc fusion to provide prolonged protection presents a novel pathway for FVIII catabolism, and warrants further investigation.
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Factor VIII/farmacocinética , Hemofilia A/metabolismo , Antígenos de Histocompatibilidad Clase I/farmacología , Proteínas Recombinantes de Fusión/farmacocinética , Animales , Coagulantes/farmacocinética , Coagulantes/uso terapéutico , Modelos Animales de Enfermedad , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/metabolismo , Perros , Factor VIII/química , Factor VIII/genética , Factor VIII/uso terapéutico , Células HEK293 , Semivida , Hemofilia A/tratamiento farmacológico , Hemofilia A/patología , Antígenos de Histocompatibilidad Clase I/química , Antígenos de Histocompatibilidad Clase I/metabolismo , Antígenos de Histocompatibilidad Clase I/uso terapéutico , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Receptores Fc/química , Receptores Fc/metabolismo , Receptores Fc/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Tiempo de Coagulación de la Sangre TotalRESUMEN
Breast cancer is the most diagnosed malignancy in women globally, and drug resistance is among the major obstacles to effective breast cancer treatment. Emerging evidence indicates that photothermal therapy and ferroptosis are both promising therapeutic techniques for the treatment of drug-resistant breast tumors. In this study, we proposed a thermal/ferroptosis/magnetic resonance imaging (MRI) triple functional nanoparticle (I@P-ss-FRT) in which ferritin, an iron storage material with excellent cellular uptake capacity, was attached via disulfide bonds onto polydopamine coated iron oxide nanoparticle (I@P) as photothermal transduction agent and MRI probe. I@P-ss-FRT converted the near-infrared light (NIR) into localized heat which accelerated the release of ferrous ions from ferritin accomplished by glutathione reduction and subsequently induced ferroptosis. The drug-resistant cancer cell lines exhibited a more significant uptake of I@P-ss-FRT and sensitivity to PTT/ferroptosis compared with normal cancer cell lines. In vivo, I@P-ss-FRT plus NIR displayed the best tumor-killing potential with inhibitory rate of 83.46 %, along with a decline in GSH/GPX-4 content and an increase in lipid peroxides generation at tumor sites. Therefore, I@P-ss-FRT can be applied to combat drug-resistant breast cancer.
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Flare and multiple recurrences pose significant challenges in gouty arthritis. Traditional treatments provide temporary relief from inflammation but fail to promptly alleviate patient pain or effectively prevent subsequent recurrences. It should also be noted that both anti-inflammation and metabolism of uric acid are necessary for gouty arthritis, calling for therapeutic systems to achieve these two goals simultaneously. In this study, we propose a biomimetic integrated nanozyme, HMPB-Pt@MM, comprising platinum nanozyme and hollow Prussian blue. It demonstrates anti-inflammatory properties by eliminating reactive oxygen species and reducing infiltration of inflammatory macrophages. Additionally, it rapidly targets inflamed ankles through the camouflage of macrophage membranes. Furthermore, HMPB-Pt@MM exhibits urate oxidase-like capabilities, continuously metabolizing locally elevated uric acid concentrations, ultimately inhibiting multiple recurrences of gouty arthritis. In summary, HMPB-Pt@MM integrates ROS clearance with uric acid metabolism, offering a promising platform for the treatment of gouty arthritis.
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A long-acting factor VIII (FVIII) as a replacement therapy for hemophilia A would significantly improve treatment options for patients with hemophilia A. To develop a FVIII with an extended circulating half-life, but without a reduction in activity, we have engineered 23 FVIII variants with introduced surface-exposed cysteines to which a polyethylene glycol (PEG) polymer was specifically conjugated. Screening of variant expression level, PEGylation yield, and functional assay identified several conjugates retaining full in vitro coagulation activity and von Willebrand factor (VWF) binding.PEGylated FVIII variants exhibited improved pharmacokinetics in hemophilic mice and rabbits. In addition, pharmacokinetic studies in VWF knockout mice indicated that larger molecular weight PEG may substitute for VWF in protecting PEGylated FVIII from clearance in vivo. In bleeding models of hemophilic mice, PEGylated FVIII not only exhibited prolonged efficacy that is consistent with the improved pharmacokinetics but also showed efficacy in stopping acute bleeds comparable with that of unmodified rFVIII. In summary site-specifically PEGylated FVIII has the potential to be a long-acting prophylactic treatment while being fully efficacious for on-demand treatment for patients with hemophilia A.
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Coagulantes/farmacocinética , Factor VIII/farmacocinética , Hemofilia A/tratamiento farmacológico , Polietilenglicoles/farmacocinética , Animales , Western Blotting , Coagulantes/administración & dosificación , Coagulantes/química , Preparaciones de Acción Retardada , Electroforesis en Gel de Poliacrilamida , Factor VIII/administración & dosificación , Factor VIII/química , Semivida , Ratones , Ratones Noqueados , Mutagénesis Sitio-Dirigida , Polietilenglicoles/administración & dosificación , Polietilenglicoles/química , Conejos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
Controllable synthesis of MOFs with desired structures is of great significance to deepen the understanding of the crystal nucleation-growth mechanism and deliver unique structural features to their derived metal oxides with target catalytic applications. In this study, NH2-Ce-BDC with morphology similar to a second-order magic cube (mc) is facile synthesized via H+ mediation in nucleation and growth stages. The pertinent variables that can greatly influence the formation of magic cube-like structures (MCS) were investigated, in which the concentric diffusion field was found to be one of the key factors. Upon calcination, the derived CeO2 inherits unique gullies and grooves located on the pristine MOFs surface, which is quite useful for atomic layer deposition (ALD) of platinum (Pt) nanoparticles because of strong interaction with MOF-derived CeO2 (mc-CeO2). XPS, H2-TPR, Raman, and in situ DRIFTS characterization results show that there is a stronger interaction between Pt and mc-CeO2 in mc-Pt/CeO2 compared with c-Pt/CeO2 that is derived from the well-developed cubic Ce-MOFs. Furthermore, Pt2+ ions, hydroxyl oxygen, and oxygen defects in mc-Pt/CeO2 account highly for exemplary catalytic activity toward HCHO oxidation.
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Liver gene therapy with adeno-associated viral (AAV) vectors delivering clotting factor transgenes into hepatocytes has shown multiyear therapeutic benefit in adults with hemophilia. However, the mostly episomal nature of AAV vectors challenges their application to young pediatric patients. We developed lentiviral vectors, which integrate in the host cell genome, that achieve efficient liver gene transfer in mice, dogs and non-human primates, by intravenous delivery. Here we first compare engineered coagulation factor VIII transgenes and show that codon-usage optimization improved expression 10-20-fold in hemophilia A mice and that inclusion of an unstructured XTEN peptide, known to increase the half-life of the payload protein, provided an additional >10-fold increase in overall factor VIII output in mice and non-human primates. Stable nearly life-long normal and above-normal factor VIII activity was achieved in hemophilia A mouse models. Overall, we show long-term factor VIII activity and restoration of hemostasis, by lentiviral gene therapy to hemophilia A mice and normal-range factor VIII activity in non-human primate, paving the way for potential clinical application.
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Hemofilia A , Animales , Niño , Perros , Factor VIII/genética , Terapia Genética , Vectores Genéticos/genética , Hemofilia A/genética , Hemofilia A/terapia , Humanos , Hígado/metabolismo , Ratones , Primates/genéticaRESUMEN
Recombinant FVIII formulated in PEG-ylated liposomes (rFVIII-PEG-Lip) was reported to increase the bleed-free days from 7 to 13 days (at 35 IU/kg rFVIII) in severe hemophilia A patients. To understand the underlying mechanism, we sought to recapitulate its efficacy in hemophilia A mice. Animals treated with rFVIII-PEG-Lip achieved approximately 30% higher survival relative to rFVIII after tail vein transection inflicted 24 hours after dosing. The efficacy of rFVIII-PEG-Lip represents an approximately 2.5-fold higher "apparent" FVIII activity, which is not accounted for by its modestly increased (13%) half-life. The enhanced efficacy requires complex formation between rFVIII and PEG-Lip before the administration. Furthermore, PEG-Lip associates with the majority of platelets and monocytes in vivo, and results in increased P-selectin surface expression on platelets in response to collagen. Rotational thromboelastometry (ROTEM) analysis of whole blood from rFVIII-PEG-Lip-treated animals at 5 minutes up to 72 hours after dosing recapitulated the 2- to 3-fold higher apparent FVIII activity. The enhanced procoagulant activity is fully retained in plasma unless microparticles are removed by ultracentrifugation. Taken together, the efficacy of rFVIII-PEG-Lip is mediated mainly by its sensitization of platelets and the generation of procoagulant microparticles that may express sustained high-affinity receptors for FVIII.
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Factor VIII/administración & dosificación , Hemofilia A/tratamiento farmacológico , Polietilenglicoles/administración & dosificación , Animales , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Factor VIII/metabolismo , Semivida , Hemofilia A/mortalidad , Hemofilia A/patología , Liposomas , Sustancias Macromoleculares/administración & dosificación , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Polietilenglicoles/química , Polietilenglicoles/metabolismo , Unión Proteica , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/metabolismo , Especificidad por Sustrato , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Plastics are widely used in daily life. Due to poor management and disposal, about 80% of plastic wastes were buried in landfills and eventually became land and ocean waste, causing serious environmental pollution. Recycling plastics is a desirable approach, but not applicable for most of the plastic waste. Microbial degradation offers an environmentally friendly way to degrade the plastic wastes, and this review summarizes the potential microbes, enzymes, and the underpinning mechanisms for degrading six most commonly used plastics including polyethylene terephthalate, polyethylene, polyvinyl chloride, polypropylene, polystyrene and polyurethane. The challenges and future perspectives on microbial degradation of plastics were proposed.
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Plásticos , Reciclaje , Biodegradación Ambiental , PoliuretanosRESUMEN
The development of neutralizing antibodies (inhibitors) against factor VIII (FVIII) is a major complication of hemophilia A treatment. The sole clinical therapy to restore FVIII tolerance in patients with inhibitors remains immune tolerance induction (ITI) which is expensive, difficult to administer and not always successful. Although not fully understood, the mechanism of ITI is thought to rely on inhibition of FVIII-specific B cells (1). Its efficacy might therefore be improved through more aggressive B cell suppression. FcγRIIB is an inhibitory Fc receptor that down-regulates B cell signaling when cross-linked with the B cell receptor (BCR). We sought to investigate if recombinant FVIII Fc (rFVIIIFc), an Fc fusion molecule composed of FVIII and the Fc region of immunoglobulin G1 (IgG1) (2), is able to inhibit B cell activation more readily than FVIII. rFVIIIFc was able to bind FVIII-exposed and naïve B cells from hemophilia A mice as well as a FVIII-specific murine B cell hybridoma line (413 cells). An anti-FcγRIIB antibody and FVIII inhibited binding, suggesting that rFVIIIFc is able to interact with both FcγRIIB and the BCR. Furthermore, incubation of B cells from FVIII-exposed mice and 413 cells with rFVIIIFc resulted in increased phosphorylation of SH-2 containing inositol 5-phosphatase (SHIP) when compared to FVIII. B cells from FVIII-exposed hemophilia A mice also exhibited decreased extracellular signal-regulated kinase (ERK) phosphorylation when exposed to rFVIIIFc. These differences were absent in B cells from naïve, non-FVIII exposed hemophilic mice suggesting an antigen-dependent effect. Finally, rFVIIIFc was able to inhibit B cell calcium flux induced by anti-Ig F(ab)2. Our results therefore indicate that rFVIIIFc is able to crosslink FcγRIIB and the BCR of FVIII-specific B cells, causing inhibitory signaling in these cells.
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Linfocitos B/inmunología , Factor VIII/inmunología , Activación de Linfocitos/inmunología , Receptores Fc/inmunología , Receptores de IgG/efectos de los fármacos , Proteínas Recombinantes de Fusión/farmacología , Animales , Linfocitos B/efectos de los fármacos , Hemofilia A , Fragmentos Fc de Inmunoglobulinas/inmunología , Activación de Linfocitos/efectos de los fármacos , Ratones , Receptores de IgG/inmunología , Proteínas Recombinantes de Fusión/inmunologíaRESUMEN
All-solid-sate Al-air batteries with features of high theoretical energy density, low cost, and environmental-friendliness are promising as power sources for next-generation flexible and wearable electronics. However, the sluggish oxygen reduction reaction (ORR) and poor interfacial contact in air cathodes cause unsatisfied performance. Herein, a free-standing Co3 Fe7 nanoalloy and Co5.47 N encapsulated in 3D nitrogen-doped carbon foam (Co3 Fe7 @Co5.47 N/NCF) is prepared as an additive-free and integrated air cathode for flexible Al-air batteries in both alkaline and neutral electrolytes. The Co3 Fe7 @Co5.47 N/NCF outperforms commercial platinum/carbon (Pt/C) toward ORR with an onset potential of 1.02 V and a positive half-wave potential of 0.92 V in an alkaline electrolyte (0.59 V in sodium chloride solution), which is ascribed to the unique interfacial structure between Co3 Fe7 and Co5.47 N supported by 3D N-doped carbon foam to facilitate fast electron and mass transfer. The high ORR performance is also supported by in-situ electrochemical Raman spectra and density functional theory calculation. Furthermore, the fabricated Al-air battery displays good flexibility and delivers a power density of 199.6 mW cm-2 , and the binder-free and integrated cathode shows better discharge performance than the traditionally slurry casting cathode. This work demonstrates a facile and efficient approach to develop integrated air cathode for metal-air batteries.
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Liver-directed gene therapy for the coagulation disorder hemophilia showed safe and effective results in clinical trials using adeno-associated viral vectors to replace a functional coagulation factor, although some unmet needs remain. Lentiviral vectors (LVs) may address some of these hurdles because of their potential for stable expression and the low prevalence of preexisting viral immunity in humans. However, systemic LV administration to hemophilic dogs was associated to mild acute toxicity and low efficacy at the administered doses. Here, exploiting intravital microscopy and LV surface engineering, we report a major role of the human phagocytosis inhibitor CD47, incorporated into LV cell membrane, in protecting LVs from uptake by professional phagocytes and innate immune sensing, thus favoring biodistribution to hepatocytes after systemic administration. By enforcing high CD47 surface content, we generated phagocytosis-shielded LVs which, upon intravenous administration to nonhuman primates, showed selective liver and spleen targeting and enhanced hepatocyte gene transfer compared to parental LV, reaching supraphysiological activity of human coagulation factor IX, the protein encoded by the transgene, without signs of toxicity or clonal expansion of transduced cells.
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Terapia Genética , Vectores Genéticos/uso terapéutico , Lentivirus/genética , Hígado/patología , Fagocitosis , Animales , Antígeno CD47/metabolismo , Técnicas de Transferencia de Gen , Hepatocitos/metabolismo , Humanos , Tolerancia Inmunológica , Inmunidad Innata , Macrófagos del Hígado/metabolismo , Macaca , Ratones Endogámicos C57BL , Ratones Endogámicos NOD , Fagocitos/metabolismo , Distribución TisularRESUMEN
In previous studies, photocatalytic heterostructures between two components have usually been distributed randomly at the material's surface. It is significant and important to fabricate a selective heterostructure interface with more efficient charge separation and transfer. In this study, active pores were first investigated through competitive adsorption, degradation efficiency, and selective corrosion. It was found that selective adsorption-induced photosensitization along with active facets led to selective photocorrosion around the pores in ZnO nanosheets. Then, comparison between the properties of selectively and randomly distributed ZnO/CdS heterostructures is presented, namely, phase composition, morphology, pore size, absorbance, electronic band structure, photocurrent density, electrochemical impedance, and hydrogen evolution. Due to the Z-scheme, ZnO/CdS heterostructure selectively bound at the active pores, due to which more efficient charge separation and higher hydrogen evolution were achieved for ZnO/CdS-S. Thus, fabrication of selective heterostructure interface endows ZnO/CdS with more efficient hydrogen evolution.
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In this study, a series of hybrid nanostructured photocatalysts P25/(NH4)xWO3 nanocomposites with the average crystallite size of P25 and (NH4)xWO3 of the sample was calculated to be about 30 nm and 130 nm, were successfully synthesized via a simple one-step hydrothermal method. The as-obtained samples was characterized by transmission electron microscopy (TEM), which implies that the P25/(NH4)xWO3 nanocomposites are fabricated with favourable nanosizd interfacial. The XPS results confirmed that the obtained sample consists of mixed chemical valences of W5+ and W6+, the low-valance W5+ sites could be the origin of NIR absorption. As revealed by optical absorption results, P25/(NH4)xWO3 nanocomposites possess high optical absorption in the whole solar spectrum of 200-2500 nm. Benefiting from this unique photo-absorption property and the synergistic effect of P25 and (NH4)xWO3, broad spectrum response photocatalytic activities covering UV, visible and near infrared regions on degradation of Rhodamine B have been realized by P25/(NH4)xWO3 nanocomposites. Meanwhile, the stability of photocatalysts was examined by the XRD and XPS of the photocatalysts after the reaction. The results show that P25/(NH4)xWO3 photocatalysts has a brilliant application prospect in the energy utilization to solve deteriorating environmental issues.
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Additional therapeutic options are needed for patients with bleeding disorders such as hemophilia A, hemophilia B, severe von Willebrand disease, and other rare factor deficiencies. A novel approach to improve coagulation in such clotting disorders has been identified that, parodoxically, involves heparinlike sulfated polysaccharides. Select molecules of this broad class are largely devoid of anticoagulant activity and are here denoted Non-Anticoagulant Sulfated Polysaccharides (NASPs). A mechanism involving blockade of the extrinsic pathway downregulator, Tissue Factor Pathway Inhibitor (TFPI) by NASPs, was conceived as an approach for improving procoagulant behavior in hemophilic settings. A subset of NASPs, including pentosan polysulfate (PPS) and fucoidan inhibited both full-length and Kunitz 1 and 2 (K1K2) TFPI and, at concentrations from 4-500 nM, improved (i.e. accelerated) the clotting time of human hemophilia A and hemophilia B plasmas or plasma with reduced factor VII levels when tested in dilute prothrombin time (dPT) assays. Fucoidan did not reduce normal plasma APTT times implying specificity for extrinsic pathway control. Improved hemostasis in vivo was observed in mice with hemophilias A or B following low dose subcutaneous administration of PPS or fucoidan, or a combination of NASP plus factor supplement. Increased survival of factor deficient mice following a bleeding challenge was observed. Accordingly, administration of select NASP(s), via mechanism(s) not fully understood, represents a unique means of improving coagulation in bleeding disorders.
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Trastornos de la Coagulación Sanguínea/sangre , Coagulación Sanguínea/efectos de los fármacos , Coagulantes/farmacología , Polisacáridos/farmacología , Animales , Trastornos de la Coagulación Sanguínea/tratamiento farmacológico , Coagulantes/uso terapéutico , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Factor VIII/farmacología , Factor VIII/uso terapéutico , Hemofilia A/sangre , Hemofilia A/tratamiento farmacológico , Hemofilia B/sangre , Hemofilia B/tratamiento farmacológico , Humanos , Lipoproteínas/antagonistas & inhibidores , Ratones , Poliéster Pentosan Sulfúrico/farmacología , Poliéster Pentosan Sulfúrico/uso terapéutico , Polisacáridos/uso terapéutico , Tiempo de ProtrombinaRESUMEN
INTRODUCTION: Hemophilia B is an inherited X chromosome-linked disorder characterized by impaired blood clotting owing to the absence of functional coagulation factor IX. Due to the relatively short half-life of factor IX, patients with hemophilia B require frequent factor IX infusions to maintain prophylaxis. We have developed a recombinant factor IX (rFIX) fused to the Fc region of IgG (rFIXFc) with an extended half-life in animals and humans. MATERIALS AND METHODS: Procoagulant properties of rFIXFc and rFIX (BENEFIX®) were compared to determine the effect of the Fc region on rFIXFc hemostatic function. Specifically, we assessed rFIXFc activation, intermolecular interactions within the Xase complex, inactivation by antithrombin III (AT) and thrombin generation potential compared with rFIX. We also assessed the acute and prophylactic efficacy profiles of rFIXFc and rFIX in vivo in hemophilia B mouse bleeding models. RESULTS AND CONCLUSIONS: The activation by factor XIa or factor VIIa/tissue factor, inhibition by AT, interaction profiles with phospholipids, affinities for factor VIIIa within the context of the Xase complex, and thrombin generation profiles were similar for rFIXFc and rFIX. Xase complexes formed with either molecule exhibited similar kinetic profiles for factor Xa generation. In acute efficacy models, mice infused with rFIXFc or rFIX were equally protected from bleeding. However, in prophylactic efficacy models, protection from bleeding was maintained approximately three times longer in rFIXFc-dosed mice than in those given rFIX; this prolonged efficacy correlates with the previously observed half-life extension. We conclude that rFIXFc retains critical FIX procoagulant attributes and that the extension in rFIXFc half-life translates into prolonged efficacy in hemophilia B mice.