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1.
ACS Appl Mater Interfaces ; 15(33): 39625-39635, 2023 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-37428479

RESUMEN

The power conversion efficiencies (PCEs) of organic solar cells (OSCs) have risen dramatically since the introduction of the "Y-series" of non-fullerene acceptors. However, the demonstration of rapid scalable deposition techniques to deposit such systems is rare. Here, for the first time, we demonstrate the deposition of a Y-series-based system using ultrasonic spray coating─a technique with the potential for significantly faster deposition speeds than most traditional meniscus-based methods. Through the use of an air-knife to rapidly remove the casting solvent, we can overcome film reticulation, allowing the drying dynamics to be controlled without the use of solvent additives, heating the substrate, or heating the casting solution. The air-knife also facilitates the use of a non-halogenated, low-toxicity solvent, resulting in industrially relevant, spray-coated PM6:DTY6 devices with PCEs of up to 14.1%. We also highlight the obstacles for scalable coating of Y-series-based solar cells, in particular the influence of slower drying times on blend morphology and crystallinity. This work demonstrates the compatibility of ultrasonic spray coating, and use of an air-knife, with high-speed, roll-to-roll OSC manufacturing techniques.

2.
Adv Mater ; : e2209950, 2023 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-37001880

RESUMEN

Integrating photovoltaic devices onto the surface of carbon-fiber-reinforced polymer substrates should create materials with high mechanical strength that are also able to generate electrical power. Such devices are anticipated to find ready applications as structural, energy-harvesting systems in both the automotive and aeronautical sectors. Here, the fabrication of triple-cation perovskite n-i-p solar cells onto the surface of planarized carbon-fiber-reinforced polymer substrates is demonstrated, with devices utilizing a transparent top ITO contact. These devices also contain a "wrinkled" SiO2 interlayer placed between the device and substrate that alleviates thermally induced cracking of the bottom ITO layer. Devices are found to have a maximum stabilized power conversion efficiency of 14.5% and a specific power (power per weight) of 21.4 W g-1 (without encapsulation), making them highly suitable for mobile power applications.

3.
ACS Appl Mater Interfaces ; 15(5): 6312-6325, 2023 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-36701696

RESUMEN

Precision nanomedicine can be employed as an alternative to chemo- or radiotherapy to overcome challenges associated with the often narrow therapeutic window of traditional treatment approaches, while safely inducing effective, targeted antitumor responses. Herein, we report the formulation of a therapeutic nanocomposite comprising a hyaluronic acid (HA)-coated gold nanoframework (AuNF) delivery system and encapsulated IT848, a small molecule with potent antilymphoma and -myeloma properties that targets the transcriptional activity of nuclear factor kappa B (NF-κB). The porous AuNFs fabricated via a liposome-templated approach were loaded with IT848 and surface-functionalized with HA to formulate the nanotherapeutics that were able to efficiently deliver the payload with high specificity to myeloma and lymphoma cell lines in vitro. In vivo studies characterized biodistribution, pharmacokinetics, and safety of HA-AuNFs, and we demonstrated superior efficacy of HA-AuNF-formulated IT848 vs free IT848 in lymphoma mouse models. Both in vitro and in vivo results affirm that the AuNF system can be adopted for targeted cancer therapy, improving the drug safety profile, and enhancing its efficacy with minimal dosing. HA-AuNF-formulated IT848 therefore has strong potential for clinical translation.


Asunto(s)
Linfoma , Mieloma Múltiple , Nanopartículas , Ratones , Animales , Distribución Tisular , Oro , Sistemas de Liberación de Medicamentos/métodos , Linfoma/tratamiento farmacológico , Ácido Hialurónico/farmacología , Receptores de Hialuranos/metabolismo
4.
Mol Cancer Ther ; 21(12): 1798-1809, 2022 12 02.
Artículo en Inglés | MEDLINE | ID: mdl-36190955

RESUMEN

Multiple myeloma is a plasma cell malignancy that is still largely incurable, despite considerable progress in recent years. NF-κB is a well-established therapeutic target in multiple myeloma, but none of the currently available treatment options offer direct, specific pharmacologic targeting of NF-κB transcriptional activity. Thus, we designed a novel direct NF-κB inhibitor (IT848) as a drug candidate with strong potential for clinical translation and conducted comprehensive in vitro and in vivo mechanistic studies in multiple myeloma cell lines, primary multiple myeloma cells, xenograft models, and immunocompetent mouse models of multiple myeloma. Here, we show that IT848 inhibits NF-κB activity through inhibition of DNA binding of all five NF-κB subunits. IT848 treatment of multiple myeloma cell lines and patient samples inhibited proliferation and induced caspase-dependent and independent apoptosis. In addition to direct NF-κB inhibitory effects, IT848 treatment altered the redox homeostasis of multiple myeloma cells through depletion of the reduced glutathione pool, selectively inducing oxidative stress in multiple myeloma but not in healthy cells. Multiple myeloma xenograft studies confirmed the efficacy of IT848 as single agent and in combination with bortezomib. Furthermore, IT848 significantly improved survival when combined with programmed death protein 1 inhibition, and correlative immune studies revealed that this clinical benefit was associated with suppression of regulatory T-cell infiltration of the bone marrow microenvironment. In conclusion, IT848 is a potent direct NF-κB inhibitor and inducer of oxidative stress specifically in tumor cells, displaying significant activity against multiple myeloma cells in vitro and in vivo, both as monotherapy as well as in combination with bortezomib or immune checkpoint blockade.


Asunto(s)
Mieloma Múltiple , Ratones , Animales , Humanos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/genética , Mieloma Múltiple/metabolismo , FN-kappa B/metabolismo , Bortezomib/farmacología , Bortezomib/uso terapéutico , Microambiente Tumoral , Apoptosis , Proteínas I-kappa B/metabolismo , Oxidación-Reducción , ADN/metabolismo , Línea Celular Tumoral
5.
ACS Appl Mater Interfaces ; 14(33): 37587-37594, 2022 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-35920712

RESUMEN

Spray coating is an industrially mature technique used to deposit thin films that combines high throughput with the ability to coat nonplanar surfaces. Here, we explore the use of ultrasonic spray coating to fabricate perovskite solar cells (PSCs) over rigid, nonplanar surfaces without problems caused by solution dewetting and subsequent "run-off". Encouragingly, we find that PSCs can be spray-coated using our processes onto glass substrates held at angles of inclination up to 45° away from the horizontal, with such devices having comparable power conversion efficiencies (up to 18.3%) to those spray-cast onto horizontal substrates. Having established that our process can be used to create PSCs on surfaces that are not horizontal, we fabricate devices over a convex glass substrate, with devices having a maximum power conversion efficiency of 12.5%. To our best knowledge, this study represents the first demonstration of a rigid, curved perovskite solar cell. The integration of perovskite photovoltaics onto curved surfaces will likely find direct applications in the aerospace and automotive sectors.

6.
Adv Sci (Weinh) ; 9(14): e2104848, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35142096

RESUMEN

Self-assembled monolayers (SAMs) are becoming widely utilized as hole-selective layers in high-performance p-i-n architecture perovskite solar cells. Ultrasonic spray coating and airbrush coating are demonstrated here as effective methods to deposit MeO-2PACz; a carbazole-based SAM. Potential dewetting of hybrid perovskite precursor solutions from this layer is overcome using optimized solvent rinsing protocols. The use of air-knife gas-quenching is then explored to rapidly remove the volatile solvent from an MAPbI3 precursor film spray-coated onto an MeO-2PACz SAM, allowing fabrication of p-i-n devices with power conversion efficiencies in excess of 20%, with all other layers thermally evaporated. This combination of deposition techniques is consistent with a rapid, roll-to-roll manufacturing process for the fabrication of large-area solar cells.

7.
Sci Rep ; 11(1): 20879, 2021 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-34686707

RESUMEN

We have developed a simplified approach to fabricate high-reflectivity mirrors suitable for applications in a strongly-coupled organic-semiconductor microcavity. Such mirrors are based on a small number of quarter-wave dielectric pairs deposited on top of a thick silver film that combine high reflectivity and broad reflectivity bandwidth. Using this approach, we construct a microcavity containing the molecular dye BODIPY-Br in which the bottom cavity mirror is composed of a silver layer coated by a SiO2 and a Nb2O5 film, and show that this cavity undergoes polariton condensation at a similar threshold to that of a control cavity whose bottom mirror consists of ten quarter-wave dielectric pairs. We observe, however, that the roughness of the hybrid mirror-caused by limited adhesion between the silver and the dielectric pair-apparently prevents complete collapse of the population to the ground polariton state above the condensation threshold.

8.
ChemSusChem ; 14(12): 2486, 2021 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-34050608

RESUMEN

Invited for this month's cover is the group of David Lidzey at the University of Sheffield. The image shows a futuristic view of large-scale perovskite solar cell (PSC) manufacture. This includes a high-volume roll-to-roll printing facility and cold-storage of PSC precursor solutions in large industrial fridges. The Full Paper itself is available at 10.1002/cssc.202100332.

9.
ChemSusChem ; 14(12): 2537-2546, 2021 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-33872471

RESUMEN

The development of stable perovskite precursor solutions is critical if solution-processable perovskite solar cells (PSCs) are to be practically manufacturable. Ideally, such precursors should combine high solution stability without using chemical additives that might compromise PSC performance. Here, it was shown that the shelf-life of high-performing perovskite precursors could be greatly improved by storing solutions at low-temperature without the need to alter chemical composition. Devices fabricated from solutions stored for 31 days at 4 °C achieved a champion power conversion efficiency (PCE) of 18.6 % (97 % of original PCE). The choice of precursor solvent also impacted solution shelf-life, with DMSO-based solutions having enhanced solution stability compared to those including DMF. The compositions of aged precursors were explored using NMR spectroscopy, and films made from these solutions were analysed using X-ray diffraction. It was concluded that the improvement in precursor solution stability is directly linked to the suppression of an addition-elimination reaction and the preservation of higher amounts of methylammonium within solution.

10.
ACS Appl Energy Mater ; 3(6): 5552-5562, 2020 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-32596647

RESUMEN

The development of scalable deposition methods for perovskite solar cell materials is critical to enable the commercialization of this nascent technology. Herein, we investigate the use and processing of nanoparticle SnO2 films as electron transport layers in perovskite solar cells and develop deposition methods for ultrasonic spray coating and slot-die coating, leading to photovoltaic device efficiencies over 19%. The effects of postprocessing treatments (thermal annealing, UV ozone, and O2 plasma) are then probed using structural and spectroscopic techniques to characterize the nature of the np-SnO2/perovskite interface. We show that a brief "hot air flow" method can be used to replace extended thermal annealing, confirming that this approach is compatible with high-throughput processing. Our results highlight the importance of interface management to minimize nonradiative losses and provide a deeper understanding of the processing requirements for large-area deposition of nanoparticle metal oxides.

11.
J Virol ; 93(24)2019 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-31578292

RESUMEN

Interferons (IFNs) induce the expression of interferon-stimulated genes (ISGs), many of which are responsible for the cellular antiviral state in which the replication of numerous viruses is blocked. How the majority of individual ISGs inhibit the replication of particular viruses is unknown. We conducted a loss-of-function screen to identify genes required for the activity of alpha interferon (IFN-α) against vesicular stomatitis virus, Indiana serotype (VSVIND), a prototype negative-strand RNA virus. Our screen revealed that TRIM69, a member of the tripartite motif (TRIM) family of proteins, is a VSVIND inhibitor. TRIM69 potently inhibited VSVIND replication through a previously undescribed transcriptional inhibition mechanism. Specifically, TRIM69 physically associates with the VSVIND phosphoprotein (P), requiring a specific peptide target sequence encoded therein. P is a cofactor for the viral polymerase and is required for viral RNA synthesis, as well as the assembly of replication compartments. By targeting P, TRIM69 inhibits pioneer transcription of the incoming virion-associated minus-strand RNA, thereby preventing the synthesis of viral mRNAs, and consequently impedes all downstream events in the VSVIND replication cycle. Unlike some TRIM proteins, TRIM69 does not inhibit viral replication by inducing degradation of target viral proteins. Rather, higher-order TRIM69 multimerization is required for its antiviral activity, suggesting that TRIM69 functions by sequestration or anatomical disruption of the viral machinery required for VSVIND RNA synthesis.IMPORTANCE Interferons are important antiviral cytokines that work by inducing hundreds of host genes whose products inhibit the replication of many viruses. While the antiviral activity of interferon has long been known, the identities and mechanisms of action of most interferon-induced antiviral proteins remain to be discovered. We identified gene products that are important for the antiviral activity of interferon against vesicular stomatitis virus (VSV), a model virus that whose genome consists of a single RNA molecule with negative-sense polarity. We found that a particular antiviral protein, TRIM69, functions by a previously undescribed molecular mechanism. Specifically, TRIM69 interacts with and inhibits the function of a particular phosphoprotein (P) component of the viral transcription machinery, preventing the synthesis of viral messenger RNAs.


Asunto(s)
Interferón-alfa/farmacología , Proteínas de Motivos Tripartitos/antagonistas & inhibidores , Ubiquitina-Proteína Ligasas/antagonistas & inhibidores , Virus de la Estomatitis Vesicular Indiana/efectos de los fármacos , Vesiculovirus/efectos de los fármacos , Replicación Viral/efectos de los fármacos , Antivirales/farmacología , Línea Celular , Citocinas/farmacología , Humanos , Modelos Moleculares , Fosfoproteínas/genética , Conformación Proteica , Dominios Proteicos , ARN Mensajero/metabolismo , ARN Viral/biosíntesis , Proteínas de Motivos Tripartitos/química , Ubiquitina-Proteína Ligasas/química , Estomatitis Vesicular/virología , Virus de la Estomatitis Vesicular Indiana/genética , Vesiculovirus/genética , Proteínas Virales
12.
Elife ; 82019 10 23.
Artículo en Inglés | MEDLINE | ID: mdl-31644426

RESUMEN

Numerous challenges have impeded HIV-1 vaccine development. Among these is the lack of a convenient small animal model in which to study antibody elicitation and efficacy. We describe a chimeric Rhabdo-Immunodeficiency virus (RhIV) murine model that recapitulates key features of HIV-1 entry, tropism and antibody sensitivity. RhIVs are based on vesicular stomatitis viruses (VSV), but viral entry is mediated by HIV-1 Env proteins from diverse HIV-1 strains. RhIV infection of transgenic mice expressing human CD4 and CCR5, exclusively on mouse CD4+ cells, at levels mimicking those on human CD4+ T-cells, resulted in acute, resolving viremia and CD4+ T-cell depletion. RhIV infection elicited protective immunity, and antibodies to HIV-1 Env that were primarily non-neutralizing and had modest protective efficacy following passive transfer. The RhIV model enables the convenient in vivo study of HIV-1 Env-receptor interactions, antiviral activity of antibodies and humoral responses against HIV-1 Env, in a genetically manipulatable host.


Asunto(s)
Anticuerpos Antivirales/biosíntesis , Linfocitos T CD4-Positivos/inmunología , VIH-1/genética , Virus Reordenados/genética , Vesiculovirus/genética , Productos del Gen env del Virus de la Inmunodeficiencia Humana/genética , Animales , Especificidad de Anticuerpos , Antígenos CD4/genética , Antígenos CD4/inmunología , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/virología , Modelos Animales de Enfermedad , Efecto Fundador , Expresión Génica , Infecciones por VIH/genética , Infecciones por VIH/inmunología , Infecciones por VIH/virología , VIH-1/inmunología , Humanos , Ratones , Ratones Transgénicos , Virus Reordenados/inmunología , Receptores CCR5/genética , Receptores CCR5/inmunología , Vesiculovirus/inmunología , Tropismo Viral/genética , Tropismo Viral/inmunología , Internalización del Virus , Productos del Gen env del Virus de la Inmunodeficiencia Humana/inmunología
13.
Elife ; 72018 08 22.
Artículo en Inglés | MEDLINE | ID: mdl-30132758

RESUMEN

The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor whose activation induces the expression of numerous genes, with many effects on cells. However, AhR activation is not known to affect the replication of viruses. We show that AhR activation in macrophages causes a block to HIV-1 and HSV-1 replication. We find that AhR activation transcriptionally represses cyclin-dependent kinase (CDK)1/2 and their associated cyclins, thereby reducing SAMHD1 phosphorylation, cellular dNTP levels and both HIV-1 and HSV-1 replication. Remarkably, a different antiviral stimulus, interferon gamma (IFN-γ), that induces a largely non-overlapping set of genes, also transcriptionally represses CDK1, CDK2 and their associated cyclins, resulting in similar dNTP depletion and antiviral effects. Concordantly, the SIV Vpx protein provides complete and partial resistance to the antiviral effects of AhR and IFN-γ, respectively. Thus, distinct antiviral signaling pathways converge on CDK/cyclin repression, causing inhibition of viral DNA synthesis and replication.


Asunto(s)
Antivirales/metabolismo , Interferón gamma/metabolismo , Receptores de Hidrocarburo de Aril/metabolismo , Transcripción Genética , Animales , Ciclo Celular , Línea Celular Tumoral , Quinasas Ciclina-Dependientes/genética , Quinasas Ciclina-Dependientes/metabolismo , Ciclinas/genética , Ciclinas/metabolismo , Regulación de la Expresión Génica , VIH-1/fisiología , Humanos , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Activación de Macrófagos , Macrófagos/metabolismo , Macrófagos/virología , Modelos Biológicos , Nucleótidos/metabolismo , Fosforilación , Estabilidad del ARN/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteína 1 que Contiene Dominios SAM y HD/metabolismo , Factor de Transcripción STAT1/metabolismo , Síndrome de Inmunodeficiencia Adquirida del Simio/patología , Síndrome de Inmunodeficiencia Adquirida del Simio/virología , Proteínas Reguladoras y Accesorias Virales/metabolismo , Replicación Viral/fisiología
14.
Blood Cells Mol Dis ; 54(3): 234-41, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25703685

RESUMEN

Primary myelofibrosis (PMF) is characterized by megakaryocyte hyperplasia, dysplasia and death with progressive reticulin/collagen fibrosis in marrow and hematopoiesis in extramedullary sites. The mechanism of fibrosis was investigated by comparing TGF-ß1 signaling of marrow and spleen of patients with PMF and of non-diseased individuals. Expression of 39 (23 up-regulated and 16 down-regulated) and 38 (8 up-regulated and 30 down-regulated) TGF-ß1 signaling genes was altered in the marrow and spleen of PMF patients, respectively. Abnormalities included genes of TGF-ß1 signaling, cell cycling and abnormal in chronic myeloid leukemia (EVI1 and p21(CIP)) (both marrow and spleen) and Hedgehog (marrow only) and p53 (spleen only) signaling. Pathway analyses of these alterations predict an increased osteoblast differentiation, ineffective hematopoiesis and fibrosis driven by non-canonical TGF-ß1 signaling in marrow and increased proliferation and defective DNA repair in spleen. Since activation of non-canonical TGF-ß1 signaling is associated with fibrosis in autoimmune diseases, the hypothesis that fibrosis in PMF results from an autoimmune process triggered by dead megakaryocytes was tested by determining that PMF patients expressed plasma levels of mitochondrial DNA and anti-mitochondrial antibodies greater than normal controls. These data identify autoimmunity as a possible cause of marrow fibrosis in PMF.


Asunto(s)
Autoinmunidad , Médula Ósea/patología , Mielofibrosis Primaria/inmunología , Transducción de Señal , Factor de Crecimiento Transformador beta1/inmunología , Adulto , Animales , Médula Ósea/inmunología , Femenino , Humanos , Inflamación/inmunología , Inflamación/patología , Masculino , Megacariocitos/inmunología , Megacariocitos/patología , Ratones , Mielofibrosis Primaria/patología , Bazo/inmunología , Bazo/patología
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