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1.
Proc Natl Acad Sci U S A ; 121(28): e2314320121, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38954540

ABSTRACT

Liquid-phase electron microscopy (LP-EM) imaging has revolutionized our understanding of nanosynthesis and assembly. However, the current closed geometry limits its application for open systems. The ubiquitous physical process of the coffee-ring phenomenon that underpins materials and engineering science remains elusive at the nanoscale due to the lack of experimental tools. We introduce a quartz nanopipette liquid cell with a tunable dimension that requires only standard microscopes. Depending on the imaging condition, the open geometry of the nanopipette allows the imaging of evaporation-induced pattern formation, but it can also function as an ordinary closed-geometry liquid cell where evaporation is negligible despite the nano opening. The nano coffee-ring phenomenon was observed by tracking individual nanoparticles in an evaporating nanodroplet created from a thin liquid film by interfacial instability. Nanoflows drive the assembly and disruption of a ring pattern with the absence of particle-particle correlations. With surface effects, nanoflows override thermal fluctuations at tens of nanometers, in which nanoparticles displayed a "drunken man trajectory" and performed work at a value much smaller than kBT.

2.
ACS Appl Mater Interfaces ; 16(14): 18008-18018, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38556992

ABSTRACT

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.

3.
Science ; 383(6688): 1198-1204, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38484055

ABSTRACT

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.

4.
Proc Natl Acad Sci U S A ; 121(14): e2318777121, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38547057

ABSTRACT

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.
Int J Biol Macromol ; 265(Pt 1): 130797, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38479662

ABSTRACT

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.


Subject(s)
Chitosan , Metal-Organic Frameworks , Bismuth/chemistry , Escherichia coli , Chitosan/pharmacology , Metal-Organic Frameworks/pharmacology , Staphylococcus aureus , Catalysis
6.
Small ; 20(15): e2307184, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38012533

ABSTRACT

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.

7.
Small ; 20(5): e2304047, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37752779

ABSTRACT

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.


Subject(s)
Anti-Infective Agents , Hydrogels , Humans , Hydrogels/chemistry , Anti-Infective Agents/pharmacology , Bacteria , Bandages , Anti-Bacterial Agents/chemistry
8.
Anal Chem ; 96(2): 904-909, 2024 01 16.
Article in English | MEDLINE | ID: mdl-38158374

ABSTRACT

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.


Subject(s)
Oligonucleotides , Tandem Mass Spectrometry , Tandem Mass Spectrometry/methods , Oligonucleotides/chemistry , Liquid Chromatography-Mass Spectrometry , Molecular Weight , Drug Contamination , Chromatography, High Pressure Liquid/methods
9.
Blood ; 141(13): 1584-1596, 2023 03 30.
Article in English | MEDLINE | ID: mdl-36375120

ABSTRACT

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).


Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell , Humans , Agammaglobulinaemia Tyrosine Kinase , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/metabolism , Heterografts , Drug Resistance, Neoplasm , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/therapeutic use
10.
Fundam Res ; 2(2): 276-283, 2022 Mar.
Article in English | MEDLINE | ID: mdl-38933159

ABSTRACT

Highly crystalline perovskite films with large grains and few grain boundaries are conducive for efficient and stable perovskite solar cells. Current methods for preparing perovskite films are mostly based on a fast crystallization process, with rapid nucleation and insufficient growth. In this study, MAPbI3 perovskite with inhibited nucleation and promoted growth in the TiO2/ZrO2/carbon triple mesoscopic scaffold was crystallized by modulating the precursor and the crystallization process. N-methylformamide showed high solubility for both methylammonium iodide and PbI2 and hampered the formation of large colloids in the MAPbI3 precursor solution. Furthermore, methylammonium chloride was added to reduce large colloids, which are a possible source of nucleation sites. During the crystallization of MAPbI3, the solvent was removed at a slow controlled speed, to avoid rapid nucleation and provide sufficient time for crystal growth. As a result, highly oriented MAPbI3 crystals with suppressed non-radiative recombination and promoted charge transport were obtained in the triple mesoscopic layer with disordered pores. The corresponding hole-conductor-free, printable mesoscopic perovskite solar cells exhibited a highest power conversion efficiency of 18.82%. The device also exhibited promising long-term operational stability of 1000 h under continuous illumination at maximum power point at 55 ± 5 °C and damp-heat stability of 1340 h aging at 85 °C as well as 85% relative humidity.

11.
Chem Commun (Camb) ; 57(94): 12627-12630, 2021 Nov 25.
Article in English | MEDLINE | ID: mdl-34761762

ABSTRACT

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.


Subject(s)
Calixarenes/pharmacology , Peptides/metabolism , Biological Transport/drug effects , Calixarenes/chemistry , Drug Evaluation, Preclinical , Humans , Molecular Structure
12.
Nature ; 599(7886): 673-678, 2021 11.
Article in English | MEDLINE | ID: mdl-34732895

ABSTRACT

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.


Subject(s)
Collagen/metabolism , Discoidin Domain Receptor 1/metabolism , Extracellular Matrix/metabolism , Triple Negative Breast Neoplasms/immunology , Triple Negative Breast Neoplasms/metabolism , Tumor Escape , Animals , Cell Line, Tumor , Discoidin Domain Receptor 1/antagonists & inhibitors , Discoidin Domain Receptor 1/deficiency , Discoidin Domain Receptor 1/genetics , Disease Models, Animal , Extracellular Matrix/immunology , Female , Gene Deletion , Gene Knockout Techniques , Humans , Immunocompetence/immunology , Immunotherapy , Mice , T-Lymphocytes/cytology , T-Lymphocytes/immunology , Triple Negative Breast Neoplasms/therapy
13.
Food Sci Biotechnol ; 30(10): 1303-1312, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34691803

ABSTRACT

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.

14.
J Immunother Cancer ; 9(4)2021 04.
Article in English | MEDLINE | ID: mdl-33849925

ABSTRACT

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.


Subject(s)
B7-H1 Antigen/antagonists & inhibitors , Immune Checkpoint Inhibitors/pharmacology , Interleukin-2 Receptor beta Subunit/agonists , Interleukin-2/pharmacology , Intraepithelial Lymphocytes/drug effects , Lung Neoplasms/drug therapy , Urinary Bladder Neoplasms/drug therapy , Animals , Antineoplastic Combined Chemotherapy Protocols/pharmacology , B7-H1 Antigen/immunology , B7-H1 Antigen/metabolism , Cell Line, Tumor , Interleukin-2 Receptor beta Subunit/immunology , Interleukin-2 Receptor beta Subunit/metabolism , Intraepithelial Lymphocytes/immunology , Intraepithelial Lymphocytes/metabolism , Lung Neoplasms/immunology , Lung Neoplasms/metabolism , Lung Neoplasms/secondary , Male , Mice , Mice, Inbred C3H , Mice, Inbred C57BL , Mice, Transgenic , Molecular Targeted Therapy , Signal Transduction , Tumor Burden/drug effects , Tumor Microenvironment , Urinary Bladder Neoplasms/immunology , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/pathology
15.
J Inorg Biochem ; 220: 111456, 2021 07.
Article in English | MEDLINE | ID: mdl-33857698

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents/pharmacology , Nanocomposites/chemistry , Quantum Dots/chemistry , Anti-Bacterial Agents/chemistry , Carbon/chemistry , Cell Membrane/drug effects , Chitosan/chemistry , Chitosan/pharmacology , Escherichia coli/drug effects , Methicillin-Resistant Staphylococcus aureus/drug effects , Microbial Sensitivity Tests , Silver Compounds/chemistry , Silver Compounds/pharmacology
16.
Cancer Med ; 10(6): 2137-2152, 2021 03.
Article in English | MEDLINE | ID: mdl-33626233

ABSTRACT

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.


Subject(s)
Autophagy/physiology , B7-H1 Antigen/metabolism , Mechanistic Target of Rapamycin Complex 1/metabolism , Urinary Bladder Neoplasms/metabolism , Animals , Antibiotics, Antineoplastic/therapeutic use , Autophagy/drug effects , Cell Line, Tumor , Cell Proliferation , Chloroquine/pharmacology , Cisplatin/therapeutic use , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Drug Resistance, Neoplasm , Female , Gene Expression , Humans , Mechanistic Target of Rapamycin Complex 1/antagonists & inhibitors , Melanoma/metabolism , Melanoma/physiopathology , Mice , Mice, Inbred C57BL , Mice, Inbred NOD , Mice, SCID , Neoplasm Metastasis , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/physiopathology , Phosphorylation , Proto-Oncogene Proteins c-akt/metabolism , Sirolimus/therapeutic use , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/immunology , Gemcitabine
17.
Nano Lett ; 20(11): 8178-8184, 2020 Nov 11.
Article in English | MEDLINE | ID: mdl-33125246

ABSTRACT

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.

18.
AAPS PharmSciTech ; 21(3): 116, 2020 Apr 15.
Article in English | MEDLINE | ID: mdl-32296974

ABSTRACT

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.


Subject(s)
Magnetic Resonance Spectroscopy/methods , Polymers/analysis , Polymers/chemistry
19.
Neurochem Res ; 45(5): 1130-1141, 2020 May.
Article in English | MEDLINE | ID: mdl-32080784

ABSTRACT

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.


Subject(s)
Alzheimer Disease/drug therapy , Berberine/administration & dosage , Brain/drug effects , Cognition/drug effects , Curcumin/administration & dosage , Oxidative Stress/drug effects , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Amyloid Precursor Protein Secretases/antagonists & inhibitors , Amyloid Precursor Protein Secretases/biosynthesis , Amyloid beta-Peptides/antagonists & inhibitors , Amyloid beta-Peptides/biosynthesis , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Aspartic Acid Endopeptidases/antagonists & inhibitors , Aspartic Acid Endopeptidases/biosynthesis , Brain/metabolism , Cognition/physiology , Drug Synergism , Female , Male , Mice , Mice, Transgenic , Oxidative Stress/physiology , Peptide Fragments/antagonists & inhibitors , Peptide Fragments/biosynthesis
20.
J Phys Chem Lett ; 10(21): 6865-6872, 2019 Nov 07.
Article in English | MEDLINE | ID: mdl-31599595

ABSTRACT

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.

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