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1.
Anal Chim Acta ; 1157: 338377, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33832590

RESUMO

In this fundamental research, we found that homo-oligo based dsDNA holds potential electrochemical characteristics in comparison to hetero-oligo based dsDNA which can be exploited in voltammetric and impedimetric biosensors. We prepared a homo-oligo based dsDNA from 20 deoxyribonucleotides of adenine, guanine, cytosine, and thymine (A20, G20, C20, and T20 respectively) and a hetero-oligo based dsDNA from two partially complementary oligos (5'-TTT TTT CAT CTA TCA ACA TCA GTC TGA TAA GCT ATA GAA GC-3' and 5'-TTT TTT ATA GCT TTG ATA GA-3'. Electrochemical impedance spectroscopy in 1 mM 0.1 M K3[Fe(CN)6]/KCl showed that Au working electrode modified with hetero-oligo based dsDNA (Au/hetero-oligo-dsDNA) was more resistive toward charge transfer of Fe(CN)63-/4- compared to Au working electrode modified with homo-oligo based dsDNA (Au/homo-oligo-dsDNA). Additionally, cyclic voltammetry and linear sweep voltammetry showed that Au/homo-oligo-dsDNA produced quantifiable anodic and cathodic peak currents which were not observed for Au/hetero-oligo-dsDNA. Nyquist and Bode plots derived from electrochemical impedance spectroscopy on three different electroactive areas (0.0705, 0.0747 and 0.0837 cm2) of Au working electrode showed no significant change in the capacitive behavior of Au/homo-oligo-dsDNA and Au/hetero-oligo-dsDNA in a linear range of frequency (10-100 Hz).

2.
Gastroenterology ; 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33819483

RESUMO

BACKGROUND & AIMS: Sulfation is a conjugation reaction essential for numerous biochemical and cellular functions in mammals. The 3'-phosphoadenosine 5'-phosphosulfate (PAPS) synthase 2 (PAPSS2) is the key enzyme to generate PAPS, which is the universal sulfonate donor for all sulfation reactions. The goal of this study is to determine whether and how PAPSS2 plays a role in colitis and colonic carcinogenesis. METHODS: Tissue arrays of human colon cancer specimens, gene expression data, and clinical features of cancer patients were analyzed. Intestinal-specific Papss2 knockout mice (Papss2ΔIE) were created and subjected to dextran sodium sulfate (DSS)-induced colitis, and colonic carcinogenesis induced by combined treatment of azoxymethane (AOM) and DSS, or AOM alone. RESULTS: The expression of PAPSS2 is decreased in the colon cancers of mice and humans. The lower expression of PAPSS2 in colon cancer patients is correlated with worse survival. Papss2ΔIE mice showed heightened sensitivity to colitis and colon cancer by damaging the intestinal mucosal barrier, increasing intestinal permeability and bacteria infiltration, and worsening the intestinal tumor microenvironment. Mechanistically, the Papss2ΔIE mice exhibited reduced intestinal sulfomucin content. Metabolomic analyses revealed the accumulation of bile acids including the farnesoid X receptor (FXR) antagonist bile acid tauro-ß-muricholic acid (T-ß-MCA), and deficiency in the formation of bile acid-sulfates in the colon of Papss2ΔIE mice. CONCLUSIONS: We have uncovered an important role of PAPSS2-mediated sulfation in colitis and colonic carcinogenesis. Intestinal sulfation may represent a potential diagnostic marker, and PAPSS2 may serve as a potential therapeutic target for inflammatory bowel disease and colon cancer.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33821612

RESUMO

A fundamental challenge, particularly, in surface-enhanced Raman scattering (SERS) analysis is the detection of analytes that are distant from the sensing surface. To tackle this challenge, we herein report a long-range SERS (LR-SERS) substrate supporting an extension of electric field afforded by long-range surface plasmon resonance (LRSPR) excited in symmetrical dielectric environments. The LR-SERS substrate has a sandwich configuration with a triangle-shaped gold nanohole array embedded between two dielectrics with similar refractive indices (i.e., MgF2 and water). The finite-difference time-domain simulation was applied to guide the design of the LR-SERS substrate, which was engineered to have a wavelength-matched LRSPR with 785 nm excitation. The simulations predict that the LR-SERS substrate exhibits great SERS enhancement at distances of more than 10 nm beyond its top surface, and the enhancement factor (EF) has been improved by three orders of magnitude on LR-SERS substrates compared to that on conventional substrates. The experimental results show good agreement with the simulations, an EF of 4.1 × 105 remains available at 22 nm above the LR-SERS substrate surface. The LR-SERS substrate was further applied as a sensing platform to detect microRNA (miRNA) let-7a coupled with a hybridization chain reaction (HCR) strategy. The developed sensor displays a wide linear range from 10 aM to 1 nM and an ultralow detection limit of 8.5 aM, making it the most sensitive among the current detection strategies for miRNAs based on the SERS-HCR combination to the best of our knowledge.

4.
Protein Cell ; 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33675514

RESUMO

Rice stripe virus (RSV) transmitted by the small brown planthopper causes severe rice yield losses in Asian countries. Although viral nuclear entry promotes viral replication in host cells, whether this phenomenon occurs in vector cells remains unknown. Therefore, in this study, we systematically evaluated the presence and roles of RSV in the nuclei of vector insect cells. We observed that the nucleocapsid protein (NP) and viral genomic RNAs were partially transported into vector cell nuclei by utilizing the importin α nuclear transport system. When blocking NP nuclear localization, cytoplasmic RSV accumulation significantly increased. In the vector cell nuclei, NP bound the transcription factor YY1 and affected its positive regulation to FAIM. Subsequently, decreased FAIM expression triggered an antiviral caspase-dependent apoptotic reaction. Our results reveal that viral nuclear entry induces completely different immune effects in vector and host cells, providing new insights into the balance between viral load and the immunity pressure in vector insects.

5.
Redox Biol ; 41: 101904, 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33706169

RESUMO

Protein S-nitrosylation is a reversible protein modification implicated in both physiological and pathophysiological regulation of protein function. However, the relationship between dysregulated S-nitrosylation homeostasis and diabetic vascular complications remains incompletely understood. Here, we demonstrate that basic fibroblast growth factor (bFGF) is a key regulatory link between S-nitrosylation homeostasis and inflammation, and alleviated endothelial dysfunction and angiogenic defects in diabetes. Subjecting human umbilical vein endothelial cells (HUVECs) to hyperglycemia and hyperlipidemia significantly decreased endogenous S-nitrosylated proteins, including S-nitrosylation of inhibitor kappa B kinase ß (IKKßC179) and transcription factor p65 (p65C38), which was alleviated by bFGF co-treatment. Pretreatment with carboxy-PTIO (c-PTIO), a nitric oxide scavenger, abolished bFGF-mediated S-nitrosylation increase and endothelial protection. Meanwhile, nitrosylation-resistant IKKßC179S and p65C38S mutants exacerbated endothelial dysfunction in db/db mice, and in cultured HUVECs subjected to hyperglycemia and hyperlipidemia. Mechanistically, bFGF-mediated increase of S-nitrosylated IKKß and p65 was attributed to synergistic effects of increased endothelial nitric oxide synthase (eNOS) and thioredoxin (Trx) activity. Taken together, the endothelial protective effect of bFGF under hyperglycemia and hyperlipidemia can be partially attributed to its role in suppressing inflammation via the S-nitrosylation pathway.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33751758

RESUMO

Abnormal tumor microenvironment (TME) facilitates tumor proliferation and metastasis and establishes physiological barriers for effective transport of therapeutics inside the tumor, posing great challenges for cancer treatment. We designed a core-satellite size transformable nanoframework (denoted as T-PFRT) that can synchronously adapt to and remold TME for augmenting photodynamic therapy to inhibit tumor growth and prevent tumor metastasis. Upon matrix metalloproteinase 2 (MMP2)-responsive dissociation of the nanoframework in TME, the core structure loaded with TGFß signaling pathway inhibitor and oxygen-carrying hemoglobin aims to stroma remodeling and hypoxia relief, allowing photosensitizer-encapsulated satellite particles to penetrate to deep-seated tumor for oxygen-fueled photodynamic therapy. T-PFRT could overcome the stroma and hypoxia barriers for delivering therapeutics and gain excellent therapeutic outcomes in the treatment of primary and metastatic tumors.

7.
Environ Sci Technol ; 55(6): 3453-3464, 2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33722002

RESUMO

Environmental Science & Technology (ES&T) has served a leadership role in reporting advanced and significant research findings for decades and accumulated tremendous amount of high-quality literature. In this study, we developed tailored text mining methods and analyzed 29 188 papers published in ES&T from 2000 to 2019, and we performed data-driven analyses to reveal some critical information and guidance on what has been published, what topical changes have evolved, and what are the areas that deserve additional attention. While top research keywords remained stable (water, sorption, soil, emiss, oxid, exposur), the trending up and emerging keywords showed clear shift over the years. Keywords related to nanobased materials (nanoparticl, nanomateri, carbon nanotub), climate and energy (climat, ch4, greenhouse gas emiss, mitig, energi), and health (exposur, health, ingest) demonstrated the strongest uptrend in the past 10 years, while plastics and PFAS were among clear emerging topics in the past 5 years. Co-occurrence analysis showed distinct associations between media (water, soil, air, sediment), chemicals (pcb, humic subst, particulate matt), processes (sorption, remov, degrad), and properties (kinet, mechan, speciat). Furthermore, a rule-based classification deciphered trends, distributions, and interconnections of articles based on either monodomains (air, soil, solid waste, water, and wastewater) or multidomains. It found water and wastewater cross-discipline articles tended to have higher citation values, while air domain tended to stand alone. Water and air monodomains consistently increased their shares in publications (together 56.3% in 2019), while shares of soil studies gradually declined. This study provides new data-driven methods on literature mining and offers unique insights on environmental research landscape and opportunities.

8.
Toxicol Sci ; 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33629115

RESUMO

Liver-related diseases including drug-induced liver injury are becoming increasingly prominent in AIDS patients. Cobicistat (COBI) is the backbone of multiple regimens for antiretroviral therapy. The current work investigated the mechanisms of adverse drug-drug interactions associated with COBI that lead to liver damage. For individuals co-infected with HIV and tuberculosis (TB), the World Health Organization recommends the initiation of TB treatment followed by antiretroviral therapy. Rifampicin (RIF), a first line anti-TB drug, is a human specific activator of pregnane X receptor (PXR). Using PXR-humanized mice, we found that RIF-mediated PXR activation potentiates COBI hepatotoxicity. In contrast, rifabutin, a PXR-neutral analog of RIF, has no impact on COBI hepatotoxicity. Because of the crosstalk between PXR and the constitutive androstane receptor (CAR), the role of CAR in COBI hepatotoxicity was also investigated. Similar to PXR, ligand-dependent activation of CAR also potentiates COBI hepatotoxicity. Our further studies illustrated that PXR and CAR modulate COBI hepatotoxicity through the CYP3A4-dependent pathways. In summary, the current work determined PXR and CAR as key modulators of COBI hepatotoxicity. Given the fact that many prescription drugs and herbal supplements can activate PXR and CAR, these two receptors should be considered as targets to prevent COBI hepatotoxicity in the clinic.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33630146

RESUMO

PURPOSE: This study retrospectively investigated the clinical utility of 2-deoxy-18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) and circulating tumor cells (CTCs) in the diagnosis and prognosis of treatment-naive patients with non-small-cell lung cancer (NSCLC). METHODS: The blood samples of treatment-naive patients with NSCLC were collected for CTCs detection, and the tumor metabolic parameters of 18F-FDG PET/CT, including maximum standard uptake value (SUVmax), metabolic tumor volume of primary lesion (MTV-P) and combination of primary lesion and metastases (MTV-C), and total lesion glycolysis of primary lesion (TLG-P) and combination of primary lesion and metastases (TLG-C), were analyzed. Age, sex, smoking, serum tumor markers, tumor size, location, TNM stage, and genetic mutations were also reviewed. Moreover, progression-free survival (PFS) and overall survival (OS) of these patients were analyzed. RESULTS: A total of 309 patients with NSCLC (200 men, 109 women; mean age: 61 ± 9 years) were enrolled in this study, including 217 patients with adenocarcinoma and 92 with squamous cell carcinoma. Of the 309 cases, 11 were misdiagnosed with benign diseases by 18F-FDG PET/CT. CTCs positivity was detected in 234 cases. The sensitivity of 18F-FDG PET/CT and CTCs in NSCLC were 96.4% and 75.7%, respectively. SUVmax, MTV-P, TLG-P, MTV-C, TLG-C, tumor size, and serum CYFRA211 levels were significantly higher in CTCs positive group than negative group; and advanced TNM stage, squamous cell carcinoma, and EGFR wild type presented higher CTCs positivity. Multivariate logistic regression analysis revealed that SUVmax was significantly associated with CTCs positivity. Multivariate cox regression analysis showed that TLG-P, TLG-C, and CTCs were independent predictors of PFS in patients with NSCLC, and TLG-C and CTCs were independent predictors of OS. CONCLUSIONS: 18F-FDG PET/CT was superior to CTCs in the diagnosis of treatment-naive patients with NSCLC. The levels of CTCs in the peripheral blood were associated with tumor glucose metabolism in NSCLC. Metabolic parameters of 18F-FDG PET/CT and CTCs could separately predict the outcomes of treatment-naive patients with NSCLC.

10.
Nat Commun ; 12(1): 781, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536416

RESUMO

After complete spinal cord injuries (SCI), spinal segments below the lesion maintain inter-segmental communication via the intraspinal propriospinal network. However, it is unknown whether selective manipulation of these circuits can restore locomotor function in the absence of brain-derived inputs. By taking advantage of the compromised blood-spinal cord barrier following SCI, we optimized a set of procedures in which AAV9 vectors administered via the tail vein efficiently transduce neurons in lesion-adjacent spinal segments after a thoracic crush injury in adult mice. With this method, we used chemogenetic actuators to alter the excitability of propriospinal neurons in the thoracic cord of the adult mice with a complete thoracic crush injury. We showed that activating these thoracic neurons enables consistent and significant hindlimb stepping improvement, whereas direct manipulations of the neurons in the lumbar spinal cord led to muscle spasms without meaningful locomotion. Strikingly, manipulating either excitatory or inhibitory propriospinal neurons in the thoracic levels leads to distinct behavioural outcomes, with preferential effects on standing or stepping, two key elements of the locomotor function. These results demonstrate a strategy of engaging thoracic propriospinal neurons to improve hindlimb function and provide insights into optimizing neuromodulation-based strategies for treating SCI.


Assuntos
Dependovirus/genética , Membro Posterior/fisiopatologia , Locomoção/fisiologia , Neurônios/metabolismo , Traumatismos da Medula Espinal/fisiopatologia , Animais , Antipsicóticos/administração & dosagem , Clozapina/administração & dosagem , Clozapina/análogos & derivados , Vetores Genéticos/genética , Membro Posterior/inervação , Locomoção/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/terapia
11.
Chem Commun (Camb) ; 57(17): 2168-2171, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33524085

RESUMO

Catalytic route electrochemiluminescence (ECL) microscopy enables imaging upper cell membranes with freely diffusing Ru(bpy)32+ as the emitter and nitrogen-doped carbon dots as the nano-coreactants and labels. This strategy provides a vertical resolution when studying the ECL profiles at different heights and realizes the ECL imaging of the externalized phosphatidylserine.

12.
Nat Prod Res ; : 1-8, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33445960

RESUMO

To search for antifungal leads, the metabolites of an insect-derived fungus Fusarium lateritium ZMT01 were investigated, providing five sesquiterpenes (1-5), including new molecules microsphaeropsisins D and E (1 and 2). The evaluated antifungal activities in vitro which are higher than the positive control triadimefon include: 1 and 2 towards Fusarium oxysporum (MICs 50, 25 mg L-1; triadimefon 100 mg L-1); 1, 2, 4 and 5 towards Penicillium italicum (MICs 25, 12.5, 25, 25; triadimefon 50 mg L-1), 1, 2 and 4 towards Colletotrichum musae (MICs 25, 12.5, 25; triadimefon 80 mg L-1), 2 and 4 towards Fusarium graminearum (MICs 100, 100; triadimefon 150 mg L-1). The bioassay in vivo displayed that the banana anthracnose control effect of 2 (100 mg L-1) was also higher than that of triadimefon (Inhibition ratios 27.5 ± 2.5%, 55.3 ± 1.4%, 52.1 ± 1.3% for 2, 22.5 ± 2.1%, 47.2 ± 2.0%, 36.6 ± 2.2% for triadimefon at 4 d, 8 d and 12 d, respectively).

13.
J Mater Chem B ; 9(6): 1638-1646, 2021 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-33480952

RESUMO

Surface modification of exoelectrogens with photoelectric materials is a promising way for achieving photo-assisted microbial fuel cells (MFCs). However, the poor conductivity of most photoelectric materials inevitably hampers the electron transfer inside bacterial biofilms. Herein, by utilizing the electrostatic layer-by-layer assembly strategy, the conductive Au nanoparticles (NPs) and photo-responsive CdS NPs were alternatively modified onto the surface of Escherichia coli for photo-assisted bioanodes in MFCs. The CdS layer was found to protect the bacterial cells from light illumination-induced inactivation. When the CdS layer coexisted with an outer layer of Au NPs, the modification of the CdS layers can generate photocurrent without any loss of biocurrent, because the outer Au layer could serve as a conductive channel for the photoelectron and bioelectron transfer between each bacterium. But the increase of CdS layers failed to further improve the photocurrent, implying that the light was inaccessible to the inner CdS layer. This work brings a universal way to fabricate conductive and photo-responsive bacteria, which would deepen the application of cell-surface modification technology in photo-assisted MFCs.

14.
Adv Mater ; 33(7): e2007557, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33448035

RESUMO

Despite the critical breakthrough achieved by immune checkpoint blockade (ICB), the clinical benefits are usually restricted by inefficient infiltration of immune cells and immune-associated adverse effects. Noninvasive aerosol inhalation, as a definitive procedure for treatment of respiratory diseases, for ICB immunotherapy against lung metastasis, has not been realized to the best knowledge. Herein, an inhaled immunotherapeutic chitosan (CS)-antibody complex is developed for immunotherapy against lung cancer. In this system, CS is used as a carrier to assemble with anti-programmed cell death protein ligand 1 (aPD-L1) to enable efficient transmucosal delivery. Moreover, CS exhibits adjuvant effects to drive potent immune responses via activating the cyclic-di-GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. Interestingly, repeated inhalation of CS/aPD-L1 complex can effectively activate the immune system by promoting the infiltration of different immune cells especially CD8+ T cells around tumor lesions, and finally prolongs the survival of mice to 60 days. Thus, the work presents a unique aerosol inhalation delivery system for ICB antibody, which is promising for immunotherapy against lung metastasis without the concern of systemic toxicity.

15.
ACS Appl Mater Interfaces ; 13(1): 135-147, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33356115

RESUMO

Plasmonically engineered nanomaterials based on Au-Ag for surface-enhanced Raman scattering (SERS)-based biomedicine is of great importance but is still far behind clinical needs because of the poor compatibility between sensitivity and safety. Here, robust plasmonically encoded Raman scattering nanoparticles, named Au core-Raman-active molecule-Ag shell-Au shell nanoparticles (CMSS NPs), were synthesized. The as-developed CMSS NPs possess a unique exterior ultrathin Au shell (∼2.2 nm thickness) that plays double key roles as an effective wrapping layer as well as a plasmonic enhancing layer, thereby showing not only extraordinary stability against oxidative damages and bioerosion but also outstanding SERS sensitivity because of the stronger in-built electromagnetic field, achieving a significant SERS enhancement factor of 3.3 × 108. The results confirm that the individual CMSS NPs show ultrahigh brightness, reproducibility, selectivity, and biocompatibility in single-cell Raman imaging. Moreover, ultrabright in vivo tumor imaging with 1 × 1 mm2 area can be quickly achieved within 35 s under open-air condition. Furthermore, by secondary plasmonic encoding, the CMSS NPs flexibly serve as nanobeacon to monitor single-cell autophagy with improved accuracy. The CMSS NPs are expected as versatile SERS probes that enable ultrabright, fast, and precise Raman-based bioimaging and clinical bioapplications.


Assuntos
Autofagia/fisiologia , Nanopartículas Metálicas/química , Neoplasias/diagnóstico por imagem , Análise Espectral Raman/métodos , Animais , Linhagem Celular Tumoral , Feminino , Ouro/química , Humanos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Estudo de Prova de Conceito , Reprodutibilidade dos Testes , Prata/química , Análise de Célula Única/métodos , Superóxidos/análise
16.
Environ Res ; 194: 110633, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33359459

RESUMO

Better municipal solid waste (MSW) management can help to address environmental concerns and supports economic and social development. Because MSW characteristics can change over time, management strategies should also evolve and be applied correspondingly. However, many previous studies have focused on MSW characterization or investigated specific management strategies for a target MSW. Few studies have assessed the spatial variations of MSW characteristics and socio-economic (SE) conditions as well as their associations. This study evaluated the feasibility of using an integrated unsupervised method (cluster analysis and cross-tabulation analysis) to explore these topics for MSW management. Results suggest that the integrated method can successfully help to reveal key information. Seven jointed MSW-SE scenarios were investigated based on 259 individual observations of Taiwan. Associations between MSW compositions and SE conditions were identified statistically significant for four MSW-SE scenarios. In general, the general SE type (SE1) is very likely to generate high food wastes and other combustible, low paper, wood, and rubber wastes (MSW1). The small island SE type (SE3) is more likely to produce high paper and low wood, rubber, textile, and other noncombustible wastes (MSW2). Overall, the method applied in this study could help to reveal statistical associations between MSW and SE, which can help decision-makers comprehend underlying facts and develop effective management strategies.

17.
Anal Chem ; 93(3): 1818-1825, 2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33372764

RESUMO

All-inorganic lead halide perovskites have become promising alternatives to traditional semiconductor electrochemiluminescence (ECL) emitters because of their appealing optoelectronic attributes, but major challenges remain in improving their stability and enhancing charge injection/transfer capacities. Herein, a self-sustaining suprastructure was constructed by successively loading aminated carbon dots (NCDs) and CsPbBr3 perovskite quantum dots (PeQDs) in situ into hierarchical zeolite imidazole framework-8 (HZIF-8). The elaborated architecture guarantees not only improved stability via the peripheral HZIF-8 protective barrier but also accelerated charge transport and efficient self-enhanced ECL between PeQDs and the surrounding NCDs in a confined structure. As a result, the ternary nanocomposite is endowed with greatly improved stability and ECL efficiency. Based on this ternary nanocomposite as an electrode substrate, a novel ECL sensing strategy is further proposed for the first time to evaluate T4 polynucleotide kinase activity and screen its inhibitors. This work opens an avenue for the advancement of perovskite-based ECL emitters as well as the development of corresponding applications in the ECL domain.


Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , Medições Luminescentes , Estruturas Metalorgânicas/química , Polinucleotídeo 5'-Hidroxiquinase/análise , Pontos Quânticos/química , Bacteriófago T4/enzimologia , Brometos/química , Carbono , Césio/química , Inibidores Enzimáticos/farmacologia , Chumbo/química , Estruturas Metalorgânicas/síntese química , Tamanho da Partícula , Polinucleotídeo 5'-Hidroxiquinase/antagonistas & inibidores , Polinucleotídeo 5'-Hidroxiquinase/metabolismo , Propriedades de Superfície
18.
Artigo em Inglês | MEDLINE | ID: mdl-33289255

RESUMO

Development of versatile nanotheranostic platforms that integrate both diagnostic and therapeutic functions have always been an intractable challenge in precise cancer treatment. Herein, an aptamer-tethered deoxyribonucleic acids-gold particle (Apt-DNA-Au) nanomachine has been developed for in situ imaging and targeted multimodal synergistic therapy of mammary carcinoma. Upon specifically internalized into MCF-7 cells, the tumor-related TK1 mRNA activates the Apt-DNA-Au nanomachine via DNA strand displacement cascades, resulting in the release of fluorophore and antisense DNA as well as the aggregation of AuNPs for in situ imaging, suppression of survivin expression and photothermal therapy, respectively. Meanwhile, the controlled released drugs are used for chemotherapy, while under the laser irradiation the loaded photosensitizer produces reactive oxygen species (ROS) for photodynamic therapy. The results confirm that the proposed Apt-DNA-Au nanomachine provides a powerful nanotheranostic platform for in situ imaging-guided combinatorial anticancer therapy.

19.
Nature ; 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33238290

RESUMO

The distal lung contains terminal bronchioles and alveoli that facilitate gas exchange. Three-dimensional in vitro human distal lung culture systems would strongly facilitate investigation of pathologies including interstitial lung disease, cancer, and SARS-CoV-2-associated COVID-19 pneumonia. We generated long-term feeder-free, chemically defined culture of distal lung progenitors as organoids derived from single adult human alveolar epithelial type II (AT2) or KRT5+ basal cells. AT2 organoids exhibited AT1 transdifferentiation potential while basal cell organoids developed lumens lined by differentiated club and ciliated cells. Single cell analysis of basal organoid KRT5+ cells revealed a distinct ITGA6+ITGB4+ mitotic population whose proliferation further segregated to a TNFRSF12Ahi subfraction comprising ~10% of KRT5+ basal cells, residing in clusters within terminal bronchioles and exhibiting enriched clonogenic organoid growth activity. Distal lung organoids were created with apical-out polarity to display ACE2 on the exposed external surface, facilitating SARS-CoV-2 infection of AT2 and basal cultures and identifying club cells as a novel target population. This long-term, feeder-free organoid culture of human distal lung, coupled with single cell analysis, identifies unsuspected basal cell functional heterogeneity and establishes a facile in vitro organoid model for human distal lung infections including COVID-19-associated pneumonia.

20.
Chemosphere ; : 128966, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33243573

RESUMO

Organic carbon (OC) and elemental carbon (EC) play important roles in various atmospheric processes and health effects. Predicting carbonaceous aerosols and identifying source contributions are important steps for further epidemiological study and formulating effective emission control policies. However, we are not aware of any study that examined predictions of OC and EC, and this work is also the first study that attempted to use machine learning and hyperparameter optimization method to predict concentrations of specific aerosol contaminants. This paper describes an investigation of the characteristics and sources of OC and EC in fine particulate matter (PM2.5) from 2005 to 2010 in the City of Taipei. Respective hourly average concentrations of OC and EC were 5.2 µg/m3 and 1.6 µg/m3. We observed obvious seasonal variation in OC but not in EC. Hourly and daily OC and EC concentrations were predicted using generalized additive model and grey wolf optimized multilayer perceptron model, which could explain up to about 80% of the total variation. Subsequent clustering suggests that traffic emission was the major contribution to OC, accounting for about 80% in the spring, 65% in the summer, and 90% in the fall and winter. In the Taipei area, local emissions were the dominant sources of OC and EC in all seasons, and long-range transport had a significant contribution to OC and in PM2.5 in spring.

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