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1.
ACS Appl Mater Interfaces ; 16(14): 18008-18018, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38556992

RESUMO

Nanostructured electrode materials become a vital component for future electrode materials because of their short electron and ion transport distances for fast charge and discharge processes and sufficient space between particles for volume expansion. So, achieving a smaller size of the nanomaterial with stable structure and high electrode performance is always the pursuit. Herein, the hybrid electrode material system hydrogen-substituted graphdiyne (HsGDY)/Cu2O-quantum dots (QDs) composed of an active carbon substrate and vibrant metal oxide QD load was established by HsGDY and cuprous oxide. The HsGDY frame with conjugated structure not only delivers impressive capacity by a self-exchange mechanism but also characterizes a matrix to forge strong connections with numerous active Cu2O-QDs for the prevention of aggregation, leading to a homogeneous storage and transport of charge in a bulk material of crisscross structural pores. QD-based electrode materials would exhibit desired capacities by their large surface area, abundant active surface atoms, and the short diffusion pathway. The hybrid system of HsGDY/Cu2O-QDs delivers an ultrahigh capacity of 1230 mA h g-1 with loading density reaching up to 1 mg cm-2. In the meantime, the electrode exhibits a long cycle stability of over 8000 cycles. The synergistic effect endows the hybrid system electrode with an approximately theoretical energy density, suggesting the great potential of such carbon/QD hybrid material system applied for high-performance batteries.

2.
Science ; 383(6688): 1198-1204, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38484055

RESUMO

Printable mesoscopic perovskite solar cells (p-MPSCs) do not require the added hole-transport layer needed in traditional p-n junctions but have also exhibited lower power conversion efficiencies of about 19%. We performed device simulation and carrier dynamics analysis to design a p-MPSC with mesoporous layers of semiconducting titanium dioxide, insulating zirconium dioxide, and conducting carbon infiltrated with perovskite that enabled three-dimensional injection of photoexcited electrons into titanium dioxide for collection at a transparent conductor layer. Holes underwent long-distance diffusion toward the carbon back electrode, and this carrier separation reduced recombination at the back contact. Nonradiative recombination at the bulk titanium dioxide/perovskite interface was reduced by ammonium phosphate modification. The resulting p-MPSCs achieved a power conversion efficiency of 22.2% and maintained 97% of their initial efficiency after 750 hours of maximum power point tracking at 55 ± 5°C.

3.
Int J Biol Macromol ; 265(Pt 1): 130797, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38479662

RESUMO

In recent years, photocatalytic technology has been introduced to develop a new kind antimicrobial agents fighting antibiotic abusing and related drug resistance. The efforts have focused on non-precious metal photocatalysts along with green additives. In the present work, a novel bis-S heterojunctions based on the coupling of polysaccharide (CS) and bismuth-based MOF (CAU-17) s synthesized through a two-step method involving amidation reaction under mild conditions. The as prepared photocatalyst literally extended the light response to the near-infrared region. Owing to its double S-type heterostructure, the lifetime of the photocarriers is significantly prolonged and the redox capacity are enhanced. As a result, the as prepared photocatalyst indicated inhibition up to 99.9 % under 20 min of light exposure against Gram-positive (S. aureus) and Gram-negative (E. coli) bacteria as well as drug-resistant bacteria (MRSA). The outstanding photocatalytic performance is attributed to the effective charge separation and migration due to the unique double S heterostructure. Such a double S heterostructure was confirmed through transient photocurrent response, electrochemical impedance spectroscopy tests and electron spin resonance measurements. The present work provides a basis for the simple synthesis of high-performance heterojunction photocatalytic inhibitors, which extends the application of CAU-17 in environmental disinfection and wastewater purification.


Assuntos
Quitosana , Estruturas Metalorgânicas , Bismuto/química , Escherichia coli , Quitosana/farmacologia , Estruturas Metalorgânicas/farmacologia , Staphylococcus aureus , Catálise
4.
Proc Natl Acad Sci U S A ; 121(14): e2318777121, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38547057

RESUMO

A concept of solar energy convertible zinc-air battery (SZAB) is demonstrated through rational design of an electrode coupled with multifunction. The multifunctional electrode is fabricated using nitrogen-substituted graphdiyne (N-GDY) with large π-conjugated carbonous network, which can work as photoresponsive bifunctional electrocatalyst, enabling a sunlight-promoted process through efficient injection of photoelectrons into the conduction band of N-GDY. SZAB enables direct conversion and storage of solar energy during the charging process. Such a battery exhibits a lowered charge voltage under illumination, corresponding to a high energy efficiency of 90.4% and electric energy saving of 30.3%. The battery can display a power conversion efficiency as high as 1.02%. Density functional theory calculations reveal that the photopromoted oxygen evolution reaction kinetics originates from the transition from the alkyne bonds to double bonds caused by the transfer of excited electrons, which changes the position of highest occupied molecular orbital and lowest unoccupied molecular orbital, thus greatly promoting the formation of intermediates to the conversion process. Our findings provide conceptual and experimental confirmation that batteries are charged directly from solar energy without the external solar cells, providing a way to manufacture future energy devices.

5.
Small ; 20(15): e2307184, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38012533

RESUMO

Aqueous zinc-ion hybrid capacitors (ZIHCs), as ideal candidates for high energy-power supply systems, are restricted by unsatisfied energy density and poor cycling durability for further applications. The construction of a surface-functionalized carbon cathode is an effective strategy for improving the performance of ZIHCs. Herein, a high-performance ZIHC is achieved using oxygen-rich hierarchically porous carbon rods (MDPC-X) prepared by the pyrolysis of a metal-organic framework (MOF) assisted by KOH activation. The MDPC-X samples displayed high electric double-layer capacitance (EDLC) and pseudocapacitance owing to their oxygen-rich surfaces, abundant electroactive sites, and short ions/electron transfer lengths. The surface oxygen functional groups for the reversible chemical adsorption/desorption of Zn2+ are identified using ex situ X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). Consequently, the as-assembled ZIHC exhibited a high capacity of 323.4 F g-1 (161.7 mA h g-1) at 0.5 A g-1 and a retention of 147 F g-1 (73.5 mA h g-1) at an ultrahigh current density of 50 A g-1, corresponding to high energy and power densities of 145.5 W h kg-1 and 45 kW kg-1, respectively. Furthermore, an excellent cycling life with 96.5% of capacity retention is also maintained after 10 000 cycles at 10 A g-1, demonstrating its promising potential for applications.

6.
Small ; 20(5): e2304047, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37752779

RESUMO

Microbial infections based on drug-resistant pathogenic organisms following surgery or trauma and uncontrolled bleeding are the main causes of increased mortality from trauma worldwide. The prevalence of drug-resistant pathogens has led to a significant increase in medical costs and poses a great threat to the normal life of people. This is an important issue in the field of biomedicine, and the emergence of new antimicrobial materials hydrogels holds great promise for solving this problem. Hydrogel is an important material with good biocompatibility, water absorption, oxygen permeability, adhesion, degradation, self-healing, corrosion resistance, and controlled release of drugs as well as structural diversity. Bacteria-disturbing hydrogels have important applications in the direction of surgical treatment, wound dressing, medical device coating, and tissue engineering. This paper reviews the classification of antimicrobial hydrogels, the current status of research, and the potential of antimicrobial hydrogels for one application in biomedicine, and analyzes the current research of hydrogels in biomedical applications from five aspects: metal-loaded hydrogels, drug-loaded hydrogels, carbon-material-loaded hydrogels, hydrogels with fixed antimicrobial activity and biological antimicrobial hydrogels, and provides an outlook on the high antimicrobial activity, biodegradability, biocompatibility, injectability, clinical applicability and future development prospects of hydrogels in this field.


Assuntos
Anti-Infecciosos , Hidrogéis , Humanos , Hidrogéis/química , Anti-Infecciosos/farmacologia , Bactérias , Bandagens , Antibacterianos/química
7.
Anal Chem ; 96(2): 904-909, 2024 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-38158374

RESUMO

Analyzing coeluting impurities with similar masses in synthetic oligonucleotides by liquid chromatography-mass spectrometry (LC-MS) poses challenges due to inadequate separation in either dimension. Herein, we present a direct method employing fully resolved isotopic envelopes, enabled by high resolution mass spectrometry (HRMS), to identify and quantify isobaric impurity ions resulting from the deletion or addition of a uracil (U) or cytosine (C) nucleotide from or to the full-length sequence. These impurities may each encompass multiple sequence variants arising from various deletion or addition sites. The method utilizes a full or targeted MS analysis to measure accurate isotopic distributions that are chemical formula dependent but nucleotide sequence independent. This characteristic enables the quantification of isobaric impurity ions involving sequence variants, a capability typically unavailable in sequence-dependent MS/MS methods. Notably, this approach does not rely on standard curves to determine isobaric impurity compositions in test samples; instead, it utilizes the individual isotopic distributions measured for each impurity standard. Moreover, in cases where specific impurity standards are unavailable, the measured isotopic distributions can be adequately replaced with the theoretical distributions (calculated based on chemical formulas of standards) adjusted using experiment-specific correction factors. In summary, this streamlined approach overcomes the limitations of LC-MS analysis for coeluting isobaric impurity ions, offering a promising solution for the in-depth profiling of complex impurity mixtures in synthetic oligonucleotide therapeutics.


Assuntos
Oligonucleotídeos , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Oligonucleotídeos/química , Espectrometria de Massa com Cromatografia Líquida , Peso Molecular , Contaminação de Medicamentos , Cromatografia Líquida de Alta Pressão/métodos
8.
Blood ; 141(13): 1584-1596, 2023 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-36375120

RESUMO

Bruton tyrosine kinase (BTK) is essential for B-cell receptor (BCR) signaling, a driver of chronic lymphocytic leukemia (CLL). Covalent inhibitors bind C481 in the active site of BTK and have become a preferred CLL therapy. Disease progression on covalent BTK inhibitors is commonly associated with C481 mutations. Here, we investigated a targeted protein degrader, NRX-0492, that links a noncovalent BTK-binding domain to cereblon, an adaptor protein of the E3 ubiquitin ligase complex. NRX-0492 selectively catalyzes ubiquitylation and proteasomal degradation of BTK. In primary CLL cells, NRX-0492 induced rapid and sustained degradation of both wild-type and C481 mutant BTK at half maximal degradation concentration (DC50) of ≤0.2 nM and DC90 of ≤0.5 nM, respectively. Sustained degrader activity was maintained for at least 24 hours after washout and was equally observed in high-risk (deletion 17p) and standard-risk (deletion 13q only) CLL subtypes. In in vitro testing against treatment-naïve CLL samples, NRX-0492 was as effective as ibrutinib at inhibiting BCR-mediated signaling, transcriptional programs, and chemokine secretion. In patient-derived xenografts, orally administered NRX-0492 induced BTK degradation and inhibited activation and proliferation of CLL cells in blood and spleen and remained efficacious against primary C481S mutant CLL cells collected from a patient progressing on ibrutinib. Oral bioavailability, >90% degradation of BTK at subnanomolar concentrations, and sustained pharmacodynamic effects after drug clearance make this class of targeted protein degraders uniquely suitable for clinical translation, in particular as a strategy to overcome BTK inhibitor resistance. Clinical studies testing this approach have been initiated (NCT04830137, NCT05131022).


Assuntos
Leucemia Linfocítica Crônica de Células B , Humanos , Tirosina Quinase da Agamaglobulinemia , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/metabolismo , Xenoenxertos , Resistencia a Medicamentos Antineoplásicos , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico
9.
Chem Commun (Camb) ; 57(94): 12627-12630, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34761762

RESUMO

Calixarenes are reportedly excellent activators that can remarkably improve the transport efficiencies of cell penetrating peptides. We employed eight calixarenes to systematically study the influence of structure on activation efficiency, which revealed that the scaffold, head group, and alkyl chain are all significant factors for activation efficiency by affecting affinities with the peptide and membrane.


Assuntos
Calixarenos/farmacologia , Peptídeos/metabolismo , Transporte Biológico/efeitos dos fármacos , Calixarenos/química , Avaliação Pré-Clínica de Medicamentos , Humanos , Estrutura Molecular
10.
Nature ; 599(7886): 673-678, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34732895

RESUMO

Immune exclusion predicts poor patient outcomes in multiple malignancies, including triple-negative breast cancer (TNBC)1. The extracellular matrix (ECM) contributes to immune exclusion2. However, strategies to reduce ECM abundance are largely ineffective or generate undesired outcomes3,4. Here we show that discoidin domain receptor 1 (DDR1), a collagen receptor with tyrosine kinase activity5, instigates immune exclusion by promoting collagen fibre alignment. Ablation of Ddr1 in tumours promotes the intratumoral penetration of T cells and obliterates tumour growth in mouse models of TNBC. Supporting this finding, in human TNBC the expression of DDR1 negatively correlates with the intratumoral abundance of anti-tumour T cells. The DDR1 extracellular domain (DDR1-ECD), but not its intracellular kinase domain, is required for immune exclusion. Membrane-untethered DDR1-ECD is sufficient to rescue the growth of Ddr1-knockout tumours in immunocompetent hosts. Mechanistically, the binding of DDR1-ECD to collagen enforces aligned collagen fibres and obstructs immune infiltration. ECD-neutralizing antibodies disrupt collagen fibre alignment, mitigate immune exclusion and inhibit tumour growth in immunocompetent hosts. Together, our findings identify a mechanism for immune exclusion and suggest an immunotherapeutic target for increasing immune accessibility through reconfiguration of the tumour ECM.


Assuntos
Colágeno/metabolismo , Receptor com Domínio Discoidina 1/metabolismo , Matriz Extracelular/metabolismo , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/metabolismo , Evasão Tumoral , Animais , Linhagem Celular Tumoral , Receptor com Domínio Discoidina 1/antagonistas & inibidores , Receptor com Domínio Discoidina 1/deficiência , Receptor com Domínio Discoidina 1/genética , Modelos Animais de Doenças , Matriz Extracelular/imunologia , Feminino , Deleção de Genes , Técnicas de Inativação de Genes , Humanos , Imunocompetência/imunologia , Imunoterapia , Camundongos , Linfócitos T/citologia , Linfócitos T/imunologia , Neoplasias de Mama Triplo Negativas/terapia
11.
Food Sci Biotechnol ; 30(10): 1303-1312, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34691803

RESUMO

Analytical method which combines electronic tongue technique and chemometrics analysis is developed to discriminate oil types and predict oil quality. All the studied Camellia oil samples from pressing, n-hexane extraction and supercritical CO2 extraction (SCCE), were successfully identified by principal component analysis (PCA) and hierarchical cluster analysis (HCA). Furthermore, multi factor linear regression model (MLRM) was established to predict oil quality, which are indicated by acid value (AV) and peroxide value (POV). The practical potential of e-tongue for the discrimination and assessment of Camellia oils has shown promising application in the characterization of Camellia oils in the oil quality evaluation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-021-00973-1.

12.
J Immunother Cancer ; 9(4)2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33849925

RESUMO

BACKGROUND: Anti-programmed death-ligand 1 (αPD-L1) immunotherapy is approved to treat bladder cancer (BC) but is effective in <30% of patients. Interleukin (IL)-2/αIL-2 complexes (IL-2c) that preferentially target IL-2 receptor ß (CD122) augment CD8+ antitumor T cells known to improve αPD-L1 efficacy. We hypothesized that the tumor microenvironment, including local immune cells in primary versus metastatic BC, differentially affects immunotherapy responses and that IL-2c effects could differ from, and thus complement αPD-L1. METHODS: We studied mechanisms of IL-2c and αPD-L1 efficacy using PD-L1+ mouse BC cell lines MB49 and MBT-2 in orthotopic (bladder) and metastatic (lung) sites. RESULTS: IL-2c reduced orthotopic tumor burden and extended survival in MB49 and MBT-2 BC models, similar to αPD-L1. Using antibody-mediated cell depletions and genetically T cell-deficient mice, we unexpectedly found that CD8+ T cells were not necessary for IL-2c efficacy against tumors in bladder, whereas γδ T cells, not reported to contribute to αPD-L1 efficacy, were indispensable for IL-2c efficacy there. αPD-L1 responsiveness in bladder required conventional T cells as expected, but not γδ T cells, altogether defining distinct mechanisms for IL-2c and αPD-L1 efficacy. γδ T cells did not improve IL-2c treatment of subcutaneously challenged BC or orthotopic (peritoneal) ovarian cancer, consistent with tissue-specific and/or tumor-specific γδ T cell contributions to IL-2c efficacy. IL-2c significantly altered bladder intratumoral γδ T cell content, activation status, and specific γδ T cell subsets with antitumor or protumor effector functions. Neither IL-2c nor αPD-L1 alone treated lung metastatic MB49 or MBT-2 BC, but their combination improved survival in both models. Combination treatment efficacy in lungs required CD8+ T cells but not γδ T cells. CONCLUSIONS: Mechanistic insights into differential IL-2c and αPD-L1 treatment and tissue-dependent effects could help develop rational combination treatment strategies to improve treatment efficacy in distinct cancers. These studies also provide insights into γδ T cell contributions to immunotherapy in bladder and engagement of adaptive immunity by IL-2c plus αPD-L1 to treat refractory lung metastases.


Assuntos
Antígeno B7-H1/antagonistas & inibidores , Inibidores de Checkpoint Imunológico/farmacologia , Subunidade beta de Receptor de Interleucina-2/agonistas , Interleucina-2/farmacologia , Linfócitos Intraepiteliais/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Antígeno B7-H1/imunologia , Antígeno B7-H1/metabolismo , Linhagem Celular Tumoral , Subunidade beta de Receptor de Interleucina-2/imunologia , Subunidade beta de Receptor de Interleucina-2/metabolismo , Linfócitos Intraepiteliais/imunologia , Linfócitos Intraepiteliais/metabolismo , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Terapia de Alvo Molecular , Transdução de Sinais , Carga Tumoral/efeitos dos fármacos , Microambiente Tumoral , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia
13.
J Inorg Biochem ; 220: 111456, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33857698

RESUMO

The present study attempted to synthesize carbon quantum dots (CQDs) through Aldol polymerization reaction, wherein acetone was used as the carbon source. A nano composite CQDs/Ag2S/CS was developed by loading as prepared CQDs and Ag2S nanoparticles on a chitosan substrate (CS). An in-situation growth of nanocomposites was adopted to study their antibacterial properties. Staphylococcus aureus (Gram-positive), Escherichia coli (Gram-negative) and methicillin-resistant Staphylococcus aureus were selected as the model bacteria. The CQDs/Ag2S/CS nanocomposites exhibited excellent inhibition not only against common pathogenic bacteria, but also those well-known drug-resistant bacteria. Moreover, compared to traditional antibiotics, the as prepared nanocomposites in the present work do not likely cause bacterial drug resistance, which make them a potential candidate for a new type of clinically applicable antibiotics.


Assuntos
Antibacterianos/farmacologia , Nanocompostos/química , Pontos Quânticos/química , Antibacterianos/química , Carbono/química , Membrana Celular/efeitos dos fármacos , Quitosana/química , Quitosana/farmacologia , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Compostos de Prata/química , Compostos de Prata/farmacologia
14.
Cancer Med ; 10(6): 2137-2152, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33626233

RESUMO

Tumor cell-intrinsic programmed death-ligand 1 (PD-L1) signals mediate immunopathologic effects in breast, colon, and ovarian cancers and in melanomas, but bladder cancer (BC) effects are unreported. We show here that BC cell-intrinsic PD-L1 signals in mouse MB49 and human RT4, UM-UC3, and UM-UC-14 BC cells regulate important pathologic pathways and processes, including effects not reported in other cancers. α-PD-L1 antibodies reduced BC cell proliferation in vitro, demonstrating direct signaling effects. BC cell-intrinsic PD-L1 promoted mammalian target of rapamycin complex 1 (mTORC1) signals in vitro and augmented in vivo immune-independent cell growth and metastatic cancer spread, similar to effects we reported in melanoma and ovarian cancer. BC cell-intrinsic PD-L1 signals also promoted basal and stress-induced autophagy, whereas these signals inhibited autophagy in melanoma and ovarian cancer cells. BC cell-intrinsic PD-L1 also mediated chemotherapy resistance to the commonly used BC chemotherapy agents cis-platinum and gemcitabine and to the mTORC1 inhibitor, rapamycin. Thus, BC cell-intrinsic PD-L1 signals regulate important virulence and treatment resistance pathways that suggest novel, actionable treatment targets meriting additional studies. As a proof-of-concept, we showed that the autophagy inhibitor chloroquine improved cis-platinum treatment efficacy in vivo, with greater efficacy in PD-L1 null versus PD-L1-replete BC.


Assuntos
Autofagia/fisiologia , Antígeno B7-H1/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Animais , Antibióticos Antineoplásicos/uso terapêutico , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células , Cloroquina/farmacologia , Cisplatino/uso terapêutico , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Feminino , Expressão Gênica , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/antagonistas & inibidores , Melanoma/metabolismo , Melanoma/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos SCID , Metástase Neoplásica , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/fisiopatologia , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sirolimo/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/imunologia , Gencitabina
15.
Nano Lett ; 20(11): 8178-8184, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33125246

RESUMO

Stable electron transport materials (ETMs) with fewer surface defects and proper energy level alignments with halide perovskite active layers are required for efficient perovskite solar cells (PSCs) with long-term durability. Here, two-dimensional van der Waals mixed valence tin oxides Sn2O3 and Sn3O4 are controllably synthesized and applied as ETMs for planar PSCs. The synthesized Sn2O3 and Sn3O4 have size of 5-20 nm and disperse well in water as stable colloids for months. Both Sn2O3 and Sn3O4 exhibit typical n-type semiconductor energy band structures, low trap density, and suitable energy level alignments with halide perovskites. Steady-state power conversion efficiencies (PCEs) of 22.36% and 21.83% are obtained for Sn2O3-based and Sn3O4-based planar PSCs. In addition, the half cells without hole transport materials and back electrodes show good UV-stability with average PCE of 99.0% and 95.7% for Sn2O3-based and Sn3O4-based devices remaining after 1000 h of ultraviolet soaking with an intensity of 70 mW cm-2.

16.
AAPS PharmSciTech ; 21(3): 116, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32296974

RESUMO

Although extensive precautions are taken to limit batch-to-batch variation in pharmaceutical manufacturing, differences between lots may still exist, particularly in complex formulations. When polymerization is used in the production process, the potential for varying chain lengths and incorporation of different monomers increases the likelihood of batch-to-batch variation. This poses a significant challenge for demonstrating active pharmaceutical ingredient (API) sameness between the innovator and generic drug under development. Therefore, the ability to accurately analyze and quantify the relative amounts of active ingredients present in a formulated product is critically important. Solid-state nuclear magnetic resonance (SSNMR) spectroscopy was used to identify, quantify, and compare the relative amounts of the three polymer groups in the amorphous block copolymer drug, patiromer (Veltassa®). Techniques such as cross polarization (CP) and magic angle spinning were used to quantify each polymer group while the importance of understanding CP dynamics to obtain quantitative data was also addressed. It was found that the magnetization transfer rate and chemical shift anisotropy for different functional groups present in patiromer play a large role when optimizing parameters for spectral acquisition. Once accounted for, the average patiromer lot contained 90.9%, 7.6%, and 1.5% carboxylate, aromatic, and aliphatic blocks, respectively, with little lot-to-lot variation between different dosage strengths and expiration dates. SSNMR proved to be a sensitive analytical technique for evaluating and quantifying different monomer groups present in patiromer. This procedure may serve as a guide for similar quantitation studies on complex drug products and for demonstrating API sameness during generic drug development.


Assuntos
Espectroscopia de Ressonância Magnética/métodos , Polímeros/análise , Polímeros/química
17.
Neurochem Res ; 45(5): 1130-1141, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32080784

RESUMO

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, and no effective therapies have been found to prevent or cure AD to date. Berberine and curcumin are extracts from traditional Chinese herbs that have a long history of clinical benefits for AD. Here, using a transgenic AD mouse model, we found that the combined berberine and curcumin treatment had a much better effect on improving the cognitive function of mice than the single-drug treatment, suggesting synergic effects of the combined berberine and curcumin treatment. In addition, we found that the combined berberine and curcumin treatment had significant synergic effects on reducing soluble amyloid-ß-peptide(1-42) production. Furthermore, the combination treatment also had remarkable synergic effects on decreasing inflammatory responses and oxidative stress in both the cortex and hippocampus of AD mice. We also found that the combination treatment performed much better than the single drugs in reducing the APP and BACE1 levels and increasing AMPKα phosphorylation and cell autophagy, which might be the underlying mechanism of the synergic effects. Taken together, the result of this study reveal the synergic effects and potential underlying mechanisms of the combined berberine and curcumin treatment in improving the symptoms of AD in mice. This study sheds light on a new strategy for exploring new phytotherapies for AD and also emphasizes that more research should focus on the synergic effects of herbal drugs in the future.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Berberina/administração & dosagem , Encéfalo/efeitos dos fármacos , Cognição/efeitos dos fármacos , Curcumina/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Secretases da Proteína Precursora do Amiloide/biossíntese , Peptídeos beta-Amiloides/antagonistas & inibidores , Peptídeos beta-Amiloides/biossíntese , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Ácido Aspártico Endopeptidases/antagonistas & inibidores , Ácido Aspártico Endopeptidases/biossíntese , Encéfalo/metabolismo , Cognição/fisiologia , Sinergismo Farmacológico , Feminino , Masculino , Camundongos , Camundongos Transgênicos , Estresse Oxidativo/fisiologia , Fragmentos de Peptídeos/antagonistas & inibidores , Fragmentos de Peptídeos/biossíntese
18.
J Phys Chem Lett ; 10(21): 6865-6872, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31599595

RESUMO

Solution-processable organic-inorganic perovskite solar cells have attracted much attention in the past few years. Energy level alignment is of great importance for improving the performance of perovskite solar cells because it strongly influences charge separation and recombination. In this report, we introduce three amide additives, namely, formamide, acetamide, and urea, into the MAPbI3 perovskite by mixing them directly in perovskite precursor solutions. The Fermi level of MAPbI3 shifts from -4.36 eV to -4.63, -4.65, and -4.61 eV, respectively, upon addition of these additives. The charge transfer between perovskite and mp-TiO2 is found to be promoted as determined via TRPL spectra, and recombination in the perovskite is suppressed. As a result, the built-in electric field (Vbi) of the printable, hole-conductor-free mesoscopic perovskite solar cells based on these perovskites with amide additives is enhanced and a peak power conversion efficiency of 15.57% is obtained.

19.
J Cancer Res Ther ; 14(Supplement): S1004-S1011, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30539837

RESUMO

BACKGROUND: Cancer stem cells (CSCs) are responsible for tumor relapse after chemotherapy and radiotherapy in non-small cell lung cancer (NSCLC). The aim of this study is to explore the profile and role of microRNA (miRNA) in CSC of NSCLC. MATERIALS AND METHODS: We studied the expression of stem cell marker in side population cells and serum-free cultured spheres of NSCLC. We identified that CD133+ CD34- cells are NSCLC stem cell. We isolated CD133+ CD34- cells and CD133- CD34+ cells with MicroBead Kit. We verified that H1650 CD133+ CD34- cells have CSC characteristics with doxorubicin, radiation, and xenograft. We studied miRNA expression profile in H1650 and HCC827 CD133+ CD34- cells with microarray analysis. We detected proliferation, migration, and invasion with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, scratch test, and Transwell chamber invasion assay, respectively. RESULTS: CD133 and CD34 are CSC markers in H1650. We demonstrated that H1650 CD133+ CD34- cells have CSC characteristics and found that miR-27a was highly expressed in H1650 CD133+ CD34- cells. In addition, we showed that miR-27a regulates proliferation, migration, and invasion in H1650 cell line and demonstrated that miR-27a expression was positively related to epidermal growth factor receptor in NSCLC cell lines. CONCLUSIONS: CD133+ CD34- is a CSC marker in H1650. miR-27a is highly expressed in H1650 CSCs and regulates cancer development in H1650. miR-27a may be a potential target for NSCLC therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , MicroRNAs/metabolismo , Células-Tronco Neoplásicas/metabolismo , Antígeno AC133/metabolismo , Animais , Antígenos CD34/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Doxorrubicina/farmacologia , Receptores ErbB/genética , Receptores ErbB/metabolismo , Humanos , Neoplasias Pulmonares/patologia , Camundongos SCID , Invasividade Neoplásica/genética , Células-Tronco Neoplásicas/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Oncoimmunology ; 7(11): e1500107, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30393583

RESUMO

Programmed death-ligand 1 (PD-L1) and its receptor programmed cell death protein 1 (PD-1) modulate antitumor immunity and are major targets of checkpoint blockade immunotherapy. However, clinical trials of anti-PD-L1 and anti-PD-1 antibodies in breast cancer demonstrate only modest efficacy. Furthermore, specific PD-L1 contributions in various tissue and cell compartments to antitumor immunity remain incompletely elucidated. Here we show that PD-L1 expression is markedly elevated in mature adipocytes versus preadipocytes. Adipocyte PD-L1 prevents anti-PD-L1 antibody from activating important antitumor functions of CD8+ T cells in vitro. Adipocyte PD-L1 ablation obliterates, whereas forced preadipocyte PD-L1 expression confers, these inhibitory effects. Pharmacologic inhibition of adipogenesis selectively reduces PD-L1 expression in mouse adipose tissue and enhances the antitumor efficacy of anti-PD-L1 or anti-PD-1 antibodies in syngeneic mammary tumor models. Our findings provide a previously unappreciated approach to bolster anticancer immunotherapy efficacy and suggest a mechanism for the role of adipose tissue in breast cancer progression.

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