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1.
Carbohydr Polym ; 230: 115631, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31887916

RESUMO

Nano-fibrillated celluloses (NFCs) were separated from bleached softwood kraft pulp. Through the periodate oxidation method, 2,3-dialdehyde nano-fibrillated celluloses (DNFCs) with varied aldehyde content were prepared. The high aldehyde content, large specific surface area and high surface charge density of DNFCs benefited the adsorbing of Cu (II). The adsorption kinetics and isotherms presented good correlations with the Pseudo-second-order model and Freundlich model, respectively. Both physical and chemical adsorptions existed in the Cu (II) adsorption by DNFCs, while chemisorption was the rate-limiting step. The adsorption thermodynamic parameters Gibbs free energy change (ΔG), enthalpy change (ΔH) and entropy change (ΔS) were also investigated. This study provides theoretical support for applying DNFCs to remove metal ions from aqueous solutions.

2.
J Hand Surg Am ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31810540

RESUMO

PURPOSE: Finger pulp resurfacing is a challenging reconstructive problem. This article introduces sensory reconstruction of finger pulp defects using an innervated distally-based neurovascular flap raised from the dorsum of the thumb. METHODS: From May 2015 to May 2017, the innervated distally-based neurovascular flap was used in 36 patients. The mean age at surgery was 37 years (range, 18-61 years). All patients were assessed using the total active motion (TAM) scoring system of the American Society for Surgery of the Hand. The sensitivity of the flap was tested using static 2-point discrimination. RESULTS: Full flap survival was achieved in 35 cases. Partial necrosis at the distal margin of the flap was observed in 1 case. At the final follow-up (mean, 20 months; range, 18-23 months), the mean TAM of the thumb was 206° (range, 188°-238°), including 8 excellent and 28 good results. The mean TAM of fingers was 266° (range, 251°-282°), including 4 excellent and 32 good results. The mean value of static 2-point discrimination was 5 mm (range, 4-7 mm) in the flap, including 31 excellent and 5 good results. CONCLUSIONS: The innervated distally-based neurovascular flap raised from the dorsum of the thumb is a reliable alternative for sensory reconstruction of finger pulp defects. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

3.
Genes Dev ; 33(23-24): 1718-1738, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31727771

RESUMO

More than 90% of small cell lung cancers (SCLCs) harbor loss-of-function mutations in the tumor suppressor gene RB1 The canonical function of the RB1 gene product, pRB, is to repress the E2F transcription factor family, but pRB also functions to regulate cellular differentiation in part through its binding to the histone demethylase KDM5A (also known as RBP2 or JARID1A). We show that KDM5A promotes SCLC proliferation and SCLC's neuroendocrine differentiation phenotype in part by sustaining expression of the neuroendocrine transcription factor ASCL1. Mechanistically, we found that KDM5A sustains ASCL1 levels and neuroendocrine differentiation by repressing NOTCH2 and NOTCH target genes. To test the role of KDM5A in SCLC tumorigenesis in vivo, we developed a CRISPR/Cas9-based mouse model of SCLC by delivering an adenovirus (or an adeno-associated virus [AAV]) that expresses Cre recombinase and sgRNAs targeting Rb1, Tp53, and Rbl2 into the lungs of Lox-Stop-Lox Cas9 mice. Coinclusion of a KDM5A sgRNA decreased SCLC tumorigenesis and metastasis, and the SCLCs that formed despite the absence of KDM5A had higher NOTCH activity compared to KDM5A +/+ SCLCs. This work establishes a role for KDM5A in SCLC tumorigenesis and suggests that KDM5 inhibitors should be explored as treatments for SCLC.


Assuntos
Diferenciação Celular/genética , Células Neuroendócrinas/citologia , Receptores Notch/fisiologia , Proteína 2 de Ligação ao Retinoblastoma/metabolismo , Transdução de Sinais/genética , Carcinoma de Pequenas Células do Pulmão/enzimologia , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Linhagem Celular , Transformação Celular Neoplásica/genética , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica/genética , Histona Desmetilases/metabolismo , Humanos , Técnicas In Vitro , Camundongos , Células Neuroendócrinas/patologia , Carcinoma de Pequenas Células do Pulmão/fisiopatologia
4.
ACS Appl Mater Interfaces ; 11(42): 39088-39099, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31566951

RESUMO

To date, various electronic devices have been strategically fabricated, and simultaneous realization of high electrical conductivity, sensing property, and heat-conducting property by a simple, efficient, and accurate approach is significant but still challenging. Here, cellulosic fiber supported 3D interconnected silver nanowire (AgNW) networks with hierarchical structures are rationally designed to achieve excellent electrical conductivity and superior thermal dispersion capability. In particular, thermal annealing at the junctions enables both phonon and electron transfer as well as impedes interfacial slippage. In the current study, the AgNW/cellulosic paper with the low Ag content (1.55 wt %) exhibits a low sheet resistance of 0.51 Ω sq-1. More importantly, the AgNW/cellulosic paper-based flexible strain sensor has been reasonably developed, which can be applied to monitor various microstructural changes and human motions with high sensitivity and robust stability (fast response/relaxation time of ∼100 ms and high stability >2000 bending-stretching cycles). The AgNW/cellulosic paper-based device also displays efficient thermal dispersion property, which offers exciting opportunities for thermal management application. Furthermore, the obtained hybrid paper exhibits superior heat dispersion capacity for thermal management devices. Overall, uniform dispersion and 3D interconnected junctions of AgNW among the fibers inside the cellulosic papers lead to the combination of high mechanical strength, highly efficient electrical conductivity, and ultrahigh heat dispersion property. The AgNW/cellulosic paper has promising potentials in the flexible and wearable sensing elements, thermal management materials, and artificial intelligence devices.

5.
Biosens Bioelectron ; 143: 111627, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31476601

RESUMO

In traditional electrochemiluminescence (ECL) analysis, gold nanomaterials are commonly used as a tool for signal amplification and linking antibodies due to their good electrical conductivity and biocompatibility. Here, we found that multitipped gold nanoparticles-gold nanoflowers (AuNFs) as coreactant accelerator have good catalytic activity for the reduction of dissolved oxygen (O2) to hydrogen peroxide (H2O2) using tris (hydroxymethyl) aminomethane (Tris) as electron donor. Based on this, a new enzyme-free and label-free ECL immunosensor have been constructed for the detection of α-fetoprotein (AFP). In this system, due to the unique geometric and spatial effects of AuNFs, the dissolved O2 as endogenous coreactant was catalyzed by AuNFs to produce H2O2 using Tris as an electron donor. The in situ generated H2O2 can more efficiently produce various electrogenerated reactive oxygen species (ROSs) as the important intermediates on the electrode surface. Then, oxidation of luminol reacts with ROSs significantly amplifies the luminol ECL signal. Under optimal experimental conditions, the proposed ECL immunosensor was able to detect the AFP concentration from 0.01 to 100 ng mL-1, with a low detection limit of 3.4 pg mL-1 (S/N = 3). In addition, the prepared ITO-based sensor is similar to a micro-test chip and convenient to use, thus making it suitable for clinical use as a disposable device in point-of-care tests (POCTs).


Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , alfa-Fetoproteínas/isolamento & purificação , Glucose Oxidase/química , Ouro/química , Grafite/química , Humanos , Peróxido de Hidrogênio/química , Medições Luminescentes , Luminol/química , Nanopartículas Metálicas/química , alfa-Fetoproteínas/química
6.
Carbohydr Polym ; 223: 115052, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31427013

RESUMO

Enzymatic pretreatment as an eco-friendly strategy has offered potential benefits in disintegrating cellulosic fibers into fibrils but limited by its high price. In this study, endoglucanase recycling was investigated in order to reduce endoglucanase expanses. Significant DP reduction can be achieved from 50.88% to 76.96% only by recycling liquid which included free endoglucanase. In the presence of fresh endoglucanase, no more pronounced reduction of DP was observed in all recycling rounds attributing to competitive adsorption between fresh and recycled endoglucanase. Fresh endoglucanase preferentially occupied active sites on cellulose surface, hydrolyzed amorphous region, and followed by degrading fibrils to saccharides together with recycled endoglucanase. This hypothesis was evidenced by increase of saccharides concentration when fresh endoglucanase was added. This study aims to provide theoretical support to decrease endoglucanase cost for deconstruction of fibers to fibrils in industrial manufacture.


Assuntos
Celulase/química , Celulose/química , Adsorção , Química Verde/métodos , Hidrólise , Peso Molecular , Reciclagem
7.
Biosens Bioelectron ; 133: 125-132, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30921628

RESUMO

Herein, novel photoactive materials, MOF-derived porous hollow carbon nanobubbles@ZnCdS multi-shelled dodecahedral cages (C@ZnCdS MSDCs), were synthesized via continuous chemical etching, sulfurization, cation-exchange and calcination strategies. Due to the synergistic effect between the porous shells and the carbon-layer coating, C@ZnCdS MSDCs displayed superior photoelectrochemical (PEC) performance. The synthesized C@ZnCdS MSDCs were assembled onto TiO2 modified ITO electrodes to form a type-II heterostructures. Then, Au nanoparticles (NPs) were deposited on the surface of ITO/TiO2/C@ZnCdS MSDCs. Benefiting from the unique structure and performance merits of photoactive materials, a label-free PEC sensing platform based on ITO/TiO2/C@ZnCdS MSDCs/Au was successfully constructed for CEA detection. Under optimal conditions, the PEC biosensor exhibited a wide linear range (0.00005-500 ng mL-1) and low detection limit (2.28 fg mL-1). The proposed PEC biosensor also showed good stability, specificity, reproducibility and acceptability in human serum. The prepared C@ZnCdS MSDCs would be a promising photoactive material for PEC biosensors. Most importantly, this work opens up new horizons for the application of MOFs-derived hollow carbon materials in sensing.


Assuntos
Técnicas Biossensoriais , Antígeno Carcinoembrionário/isolamento & purificação , Técnicas Eletroquímicas , Nanopartículas Metálicas/química , Cádmio/química , Antígeno Carcinoembrionário/sangue , Ouro/química , Humanos , Luz , Limite de Detecção , Porosidade , Titânio/química , Zinco/química
8.
Bioresour Technol ; 282: 228-235, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30870688

RESUMO

Camellia Oleifera Shell (COS) is a kind of renewable lignocellulose resource and contains abundant hemicelluloses. In this work, the hemicelluloses in COS were extracted by alkali treatment and precipitated by ethanol with different concentration. Thermal pyrolysis kinetics of COS hemicelluloses were investigated using a thermogravimetric analyzer at the heating rates of 5, 10, and 20 °C/min based on Coats-Redfern, Flynn-Wall-Ozawa (FWO), and Kissinger-Akahira-Sunose (KAS) model. The results showed that the best fitting thermal pyrolysis mechanism of COS hemicelluloses was one-dimensional diffusion reaction analyzed by Coats-Redfern model. The activation energies of COS hemicelluloses ranged from 175.07 to 247.87 kJ·mol-1 and from 174.74 to 252.50 kJ·mol-1 calculated by FWO and KAS, respectively. The thermal stabilities of COS hemicelluloses were enhanced with the precipitated ethanol concentration increasing, and reflected by thermodynamic parameters ΔH, ΔG and ΔS. This study may provide basic theoretical supports for the thermochemical conversion of COS hemicelluloses.


Assuntos
Camellia/química , Polissacarídeos/química , Cinética , Polissacarídeos/isolamento & purificação , Pirólise , Termodinâmica
9.
Sci Total Environ ; 661: 63-74, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30665133

RESUMO

Many rivers are facing human-induced system regime shifts that have great environmental, ecological and social implications, necessitating an increasing need to quantify the human influence on sediment properties and their impacts on the source-to-sink system of marginal seas. The Huanghe and Changjiang Rivers have experienced a dramatic reduction in sediment flux in recent decades, typifying the human influence on sediment properties of global large rivers. Sediment samples from the two rivers were analyzed to obtain grain size, magnetic and geochemical data. The results show a large difference in sediment properties between pre- and post-dam periods. We applied a discrepancy factor to re-examine the magnetic and geochemical tracers that were previously used in the two rivers. The discrepancy factors of most magnetic and geochemical tracers in the mud-sized sediments of the two rivers increased by an average of about 109% after dam construction. This suggests that human-induced changes in sediment properties have greatly improved the discriminatory ability between the sediments from the two rivers. The results also raise the uncertainty of using previous tracers to distinguish between sediments from the two rivers after damming. Furthermore, significant changes in sediment properties that happened in a relatively short time may provide future geological time markers for sedimentary records with a temporal resolution of 100-101 years. For marine environments, an approach for identifying sediment sources based on multiple independent optimum tracers is also proposed, with composite magnetic (SIRM vs. HIRM) and geochemical (Na2O vs. Zn) tracers being considered. The results of this work can advance our knowledge of how human activities alter river systems, and identify a sustainable development model under system regime shifts for areas of high-intensity human activity.

10.
Carbohydr Polym ; 207: 44-51, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30600026

RESUMO

Hornification are usually occurred in cellulosic fibers and even in nanocellulose fibrils during dehydration process but their mesoscopic structural changes is not fully understood. Here we investigated the structural features of cellulose nanocrystals (CNCs) and cellulose nanofibrils (CNF) with different solid content. In order to avoid the effect of drying, liquid AFM mode was carried out in this work. The different water contents of nanocellulose were quantified by Differential Scanning Calorimetry (DSC). We showed evidence of extreme growth in radial direction in the redispersed nanocelluloses, analyzed by statistics of contours from microscopy images. The amount of free water, freezing bound water, and non-freezing bound water decreased gradually during water evaporation and were completely removed in sequence. In addition, the hydroxyl accessibility of both redispersed CNCs and CNF were reduced by 83.33% and 81.96% via evaluating the uptake of fluorescent dyes.


Assuntos
Celulose/química , Dessecação , Nanofibras/química , Nanopartículas/química , Água/química , Coloides/química , Ligações de Hidrogênio , Pinus/química , Eletricidade Estática
11.
PLoS Genet ; 14(9): e1007679, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30256787

RESUMO

The mechanistic target of rapamycin (mTOR) is an established therapeutic target in renal cell carcinoma (RCC). Mechanisms of secondary resistance to rapalog therapy in RCC have not been studied previously. We identified six patients with metastatic RCC who initially responded to mTOR inhibitor therapy and then progressed, and had pre-treatment and post-treatment tumor samples available for analysis. We performed deep whole exome sequencing on the paired tumor samples and a blood sample. Sequence data was analyzed using Mutect, CapSeg, Absolute, and Phylogic to identify mutations, copy number changes, and their changes over time. We also performed in vitro functional assays on PBRM1 in RCC cell lines. Five patients had clear cell and one had chromophobe RCC. 434 somatic mutations in 416 genes were identified in the 12 tumor samples. 201 (46%) of mutations were clonal in both samples while 129 (30%) were acquired in the post-treatment samples. Tumor heterogeneity or sampling issues are likely to account for some mutations that were acquired in the post-treatment samples. Three samples had mutations in TSC1; one in PTEN; and none in MTOR. PBRM1 was the only gene in which mutations were acquired in more than one post-treatment sample. We examined the effect of PBRM1 loss in multiple RCC cell lines, and could not identify any effect on rapalog sensitivity in in vitro culture assays. We conclude that mTOR pathway gene mutations did not contribute to rapalog resistance development in these six patients with advanced RCC. Furthermore, mechanisms of resistance to rapalogs in RCC remain unclear and our results suggest that PBRM1 loss may contribute to sensitivity through complex transcriptional effects.


Assuntos
Antineoplásicos/farmacologia , Carcinoma de Células Renais/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Renais/tratamento farmacológico , Proteínas Nucleares/genética , Inibidores de Proteínas Quinases/farmacologia , Fatores de Transcrição/genética , Adulto , Idoso , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Progressão da Doença , Epigênese Genética , Everolimo/farmacologia , Everolimo/uso terapêutico , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Heterogeneidade Genética/efeitos dos fármacos , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Transdução de Sinais/genética , Sirolimo/análogos & derivados , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Sequenciamento Completo do Exoma
12.
Bioresour Technol ; 267: 426-430, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30032056

RESUMO

Enzymatic pretreatment has shown great potential in making the disintegration of cellulosic fibers to fibrils cost-effectively and environmental-friendly. In this study, an extensive commercial endoglucanase was used to pretreat cellulosic fibers for fibrillation. The pretreatment time and the enzyme dosage were optimized using response surface methodology. A 100% fiber recovery was obtained at endoglucanase usage of 9.0 mg/g (substrate) and pretreatment time of less than 3.0 h. A highly fibrillated and fractured surface of pretreated fibers was observed after 0.5 h of pretreatment compared to native fibers. Meanwhile, the progressive deconstruction of cellulosic fibers was occurred with the enzymatic pretreatment time increasing. The degree of deconstruction of fibers was evidenced by changes of the fiber microstructure, such as the inter-/intra-molecular H-bonds, the ß-1,4-glucosidic linkages, crystallinity and crystallite size. These discoveries provide new insights into a more efficient and economic pretreatment methods for the disintegration of fibrils from cellulosic fibers.


Assuntos
Celulase/metabolismo , Celulose/metabolismo , Carboidratos
13.
Talanta ; 188: 58-65, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30029416

RESUMO

In this study,we proposed a triangular silver nanosheets (Tri-SNSs)-layered, Chitosan (CS)-supported three-dimensional of reduced graphene oxide (3D-ERGO) electrochemiluminescence (ECL) biosensing platform using self-designed dual-Ru(bpy)32+ scDNA (Ru2-DNA) as capture probe for ECL biosensing of single-chain DNA (scDNA). Based on the different affinity with scDNA and double chain DNA (dcDNA), the biosensor is designed to recognize the target DNA (t-DNA), which leads to the desorption of a hybrid molecule from the surface of the biosensor, further removing the Ru2-DNA and inhibiting the ECL. Analytical results clearly showed that the electrochemical and ECL behaviors of proposed biosensing platform on the glassy carbon electrode (GCE) exhibited outstanding performance, which was due to large specific surface area, high carrier mobility and strong π-π non-covalent attraction toward single-chain DNA (scDNA) of the stable 3D platform, and ECL amplification of Tri-SNSs. Besides, based on such a system, this strategy can effectively identify full match and mismatched target DNA (M-DNA) with a wide concentration range beyond 7 orders of magnitude and detection limit down to 16.2 aM. Therefore, the 3D biosensing strategy shows potential for the application of bioassays.


Assuntos
Técnicas Biossensoriais/métodos , DNA de Cadeia Simples/análise , Técnicas Eletroquímicas/métodos , Grafite/química , Nanoestruturas/química , Prata/química , 2,2'-Dipiridil/análogos & derivados , 2,2'-Dipiridil/química , Quitosana/química , Complexos de Coordenação/química , DNA de Cadeia Simples/química , Eletrodos , Limite de Detecção , Luminescência , Medições Luminescentes/métodos , Hibridização de Ácido Nucleico , Óxidos/química , Reprodutibilidade dos Testes
14.
Mikrochim Acta ; 185(5): 263, 2018 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-29687401

RESUMO

A photoelectrochemical (PEC) aptasensor for the highly sensitive and specific detection of thrombin is described. This aptasensor is based on an indium tin oxide (ITO) support that is covered with carbon quantum dot (CQD)-sensitized TiO2 and acts as a photoactive matrix. The ITO/TiO2/CQD electrode was prepared by impregnation assembly. It displays an enhanced and steady photocurrent response under irradiation by visible light. A carboxyl-functionalized thrombin-binding aptamer was covalently immobilized on the modified ITO to obtain a PEC aptasensor whose photocurrent decreases with increasing concentration of thrombin. Under 420 nm irradiation at a bias voltage of 0 V, the aptasensor has a linear response in the 1.0 to 250 pM thrombin concentration range, with a 0.83 pM detection limit. Conceivably, this approach can be extended to numerous other PEC aptasensors for the detection of targets for which appropriate aptamers are available. Graphical abstract Schematic of a PEC aptasensor for thrombin. It is based on the use of CQD as the sensitizer, TiO2/CQDs as the photoactive matrix, and the thrombin aptamer as the recognition element.

15.
J Hazard Mater ; 353: 151-157, 2018 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-29660701

RESUMO

Reduced graphite oxide (rGO) was incorporated into a metal organic framework (MOF) MIL-101(Cr) for the modification of carbon paste electrode. Taking advantages of the large surface area of MOF and the electrical conductivity of rGO, the resulted electrodes exhibited high sensitivity and reliability in the simultaneous electrochemical identification and quantification of catechol (CC) and hydroquinone (HQ). Specifically, in the mixture solution of catechol and hydroquinone (constant concentration of an analyte), the linear response ranges for catechol and hydroquinone were 10-1400 µM and 4-1000 µM, and detection limits were 4 µM and 0.66 µM (S/N = 3) for individual catechol and hydroquinone, respectively. Therefore, the relatively easy fabrication of modified CPE and its fascinating reliability towards HQ and CC detection may simulate more research interest in the applications of MIL-101(Cr)-rGO composites for electrochemical sensors.

16.
Carbohydr Polym ; 186: 73-81, 2018 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-29456011

RESUMO

In this work, we report a new characterization method using fluorescent cellulose nanofibrils to analyze retention and loss rates in the papermaking process. Cellulose nanofibrils (CNF) were isolated from chemical pulp by enzymatic pretreatment and used as a strengthening additive in sheet forming. The aim of this paper was to investigate its effects on flocculation, retention and loss rate and the physical and mechanical properties. CNF was subjected to fluorescent labeling with RBITC (Rhodamine B isothiocyanate), and the retention of fluorescent cellulose nanofibrils (FCNF) was analyzed by elemental analysis and fluorescence intensity. The retention and loss rate of the FCNF decreased with increasing the addition of FCNF. Laser Confocal Scanning Microscopy (LCSM) and Scanning Electron Microscope (SEM) images confirmed that FCNF can be evenly distributed in the paper. A thorough investigation of the relation between the retention rate and papersheet performance was conducted.


Assuntos
Celulose/química , Nanofibras/química , Microscopia Eletrônica de Varredura , Rodaminas/química , Resistência à Tração
17.
Science ; 359(6374): 411-418, 2018 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-29371462

RESUMO

Aerosol-cloud interactions remain the largest uncertainty in climate projections. Ultrafine aerosol particles smaller than 50 nanometers (UAP<50) can be abundant in the troposphere but are conventionally considered too small to affect cloud formation. Observational evidence and numerical simulations of deep convective clouds (DCCs) over the Amazon show that DCCs forming in a low-aerosol environment can develop very large vapor supersaturation because fast droplet coalescence reduces integrated droplet surface area and subsequent condensation. UAP<50 from pollution plumes that are ingested into such clouds can be activated to form additional cloud droplets on which excess supersaturation condenses and forms additional cloud water and latent heating, thus intensifying convective strength. This mechanism suggests a strong anthropogenic invigoration of DCCs in previously pristine regions of the world.

18.
Science ; 359(6377): 801-806, 2018 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-29301960

RESUMO

Immune checkpoint inhibitors targeting the programmed cell death 1 receptor (PD-1) improve survival in a subset of patients with clear cell renal cell carcinoma (ccRCC). To identify genomic alterations in ccRCC that correlate with response to anti-PD-1 monotherapy, we performed whole-exome sequencing of metastatic ccRCC from 35 patients. We found that clinical benefit was associated with loss-of-function mutations in the PBRM1 gene (P = 0.012), which encodes a subunit of the PBAF switch-sucrose nonfermentable (SWI/SNF) chromatin remodeling complex. We confirmed this finding in an independent validation cohort of 63 ccRCC patients treated with PD-1 or PD-L1 (PD-1 ligand) blockade therapy alone or in combination with anti-CTLA-4 (cytotoxic T lymphocyte-associated protein 4) therapies (P = 0.0071). Gene-expression analysis of PBAF-deficient ccRCC cell lines and PBRM1-deficient tumors revealed altered transcriptional output in JAK-STAT (Janus kinase-signal transducers and activators of transcription), hypoxia, and immune signaling pathways. PBRM1 loss in ccRCC may alter global tumor-cell expression profiles to influence responsiveness to immune checkpoint therapy.


Assuntos
Antígeno B7-H1/antagonistas & inibidores , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/terapia , Imunoterapia/métodos , Neoplasias Renais/genética , Neoplasias Renais/terapia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Antígeno CTLA-4/antagonistas & inibidores , Proteínas Cromossômicas não Histona/genética , Estudos de Coortes , Exoma/genética , Perfilação da Expressão Gênica , Genômica , Humanos , Mutação , Fatores de Transcrição/genética
19.
Mol Med Rep ; 17(3): 4074-4082, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29257305

RESUMO

Copper is a trace element which exerts an important role in neuronal functions. Excessive Cu exposure is associated with central nervous system dysfunction, including memory loss. The present study examined the effects of CuCl2 exposure on the spatial learning and memory of rats, and on metabolites in the hippocampus. A total of 60 male Sprague­Dawley rats (10 rats/group) were intraperitoneally injected with various doses (0, 0.5, 1.0, 2.0, 4.0 and 6.0 mg/kg) of CuCl2 three times every other day for 6 days. Rats administered with 1.0 ml/kg sterile saline were used as controls. A total of 2 days subsequent to the final injection, the rats were subjected to the Morris water maze (MWM) test, followed by proton magnetic resonance spectroscopy (1H­MRS). The rats were subsequently sacrificed, and their hippocampal tissues were processed for high performance liquid chromatography (HPLC). The MWM test demonstrated that the high­dose groups exhibited worse spatial learning and memory compared with the controls; however, the rats that received a relatively low dose (2.0 mg/kg) exhibited a decreased impairment. The 1H­MRS results revealed increased Glu, N­acetyl­L­aspartate (NAA)+N­acetylaspartylglutamate, phosphocreatine (PCr) and Cr+PCr levels in the hippocampus of the 2.0 mg/kg group. HPLC analysis revealed increased γ­aminobutyric acid and glutamate (Glu) levels in the 2.0 mg/kg group, and decreased Glu levels in the 6.0 mg/kg group. The results of the present study demonstrated a beneficial effect of short­term exposure to a relatively low dose of CuCl2 on spatial learning and memory, and the association of this effect with increased NAA and Glu levels in the hippocampus.


Assuntos
Cobre/farmacologia , Ácido Glutâmico/metabolismo , Hipocampo/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Animais , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Química Encefálica , Dipeptídeos/metabolismo , Relação Dose-Resposta a Droga , Hipocampo/química , Hipocampo/fisiologia , Masculino , Aprendizagem em Labirinto/fisiologia , Memória/fisiologia , Fosfocreatina/metabolismo , Espectroscopia de Prótons por Ressonância Magnética , Ratos , Ratos Sprague-Dawley , Ácido gama-Aminobutírico/metabolismo
20.
Carbohydr Polym ; 175: 105-112, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-28917845

RESUMO

Cellulose nanocrystals (CNCs) have excellent properties, such as reproducibility, low biodegradability and a large amount of reactive hydroxyl groups on the surface. This study focused on the labeling efficiency and fluorescent properties of the fluorescent labeling of CNCs by means of electrostatic adsorption and covalent bonding. The CNCs in the sample were approximately 94.76% successfully labeled with dyes, and the number of dye molecules adsorbed by per CNC was approximately 208 by electrostatic adsorption. For the sample covalently linked, the efficiency of the fluorescent labeling was 95.51%, and the number of dye molecules attached to per CNC was 1038. The quenching mode of the fluorescent CNCs was dynamic quenching. The fluorescence lifetime and quantum yield of the fluorescent CNCs increased by 1-2 times compared to the free dye. A thorough investigation of the relation between the binding mechanism and the fluorescent properties in fluorescent CNCs was conducted.

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