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1.
Nano Lett ; 24(29): 9017-9026, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39007530

RESUMO

The development of in situ tumor vaccines offers promising prospects for cancer treatment. Nonetheless, the generation of plenary autologous antigens in vivo and their codelivery to DC cells along with adjuvants remains a significant challenge. Herein, we developed an in situ tumor vaccine using a supramolecular nanoparticle/hydrogel composite (ANPMTO/ALCD) and a deformable nanoadjuvant (PPER848). The ANPMTO/ALCD composite consisted of ß-cyclodextrin-decorated alginate (Alg-g-CD) and MTO-encapsulated adamantane-decorated nanoparticles (ANPMTO) through supramolecular interaction, facilitating the long-term and sustained production of plenary autologous antigens, particularly under a 660 nm laser. Simultaneously, the produced autologous antigens were effectively captured by nanoadjuvant PPER848 and subsequently transported to lymph nodes and DC cells, benefiting from its optimized size and deformability. This in situ tumor vaccine can trigger a robust antitumor immune response and demonstrate significant therapeutic efficacy in inhibiting tumor growth, suppressing tumor metastasis, and preventing postoperative recurrence, offering a straightforward approach to programming in situ tumor vaccines.


Assuntos
Adjuvantes Imunológicos , Vacinas Anticâncer , Imunoterapia , Nanopartículas , Vacinas Anticâncer/química , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/uso terapêutico , Animais , Camundongos , Imunoterapia/métodos , Nanopartículas/química , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/uso terapêutico , Adjuvantes Imunológicos/farmacologia , Hidrogéis/química , Humanos , Linhagem Celular Tumoral , Células Dendríticas/imunologia , beta-Ciclodextrinas/química , Neoplasias/terapia , Neoplasias/imunologia , Alginatos/química , Adamantano/química , Adamantano/uso terapêutico
2.
Analyst ; 149(8): 2291-2298, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38511612

RESUMO

Building a high-performance sensing platform is the key to developing sensitive sensors. Herein, a highly sensitive self-powered electrochemical sensor (SPES) was constructed using a WO3·H2O film as the cathode prepared by a hydrothermal method and Zn as the anode, and it could be applied to sensitive detection of microcystin (MC-RR). The WO3·H2O film with a larger specific surface area could boost the oxygen reduction reaction (ORR), which could achieve signal amplification and significantly increase the sensitivity of the sensors. Under the optimal conditions, there was a good linear relationship between the increased electrical power density and the logarithm of MC-RR concentration with a detection limit of 1.31 × 10-15 M (S/N = 3). This method had good anti-interference ability and stability when applied to the determination of MC-RR content in actual samples, which could boost the potential application of electrochemical sensors in the field of environmental monitoring.

3.
Environ Res ; 258: 119453, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38909951

RESUMO

Thermophilic anaerobic digestion (AD) of animal manure offers various environmental benefits but the process requires a microbial community acclimatized to high ammonia. In current study, a lab-scale continuous stirred tank reactor (CSTR) fed with chicken manure was operated under thermophilic condition for 450 days in total. Results showed that the volumetric methane production decreased from 445 to 328 and sharply declined to 153 mL L-1·d-1 with feeding total solid (TS) step increased from 5% to 7.5% and 10%, respectively. While, after a long-term stop feeding for 80 days, highly disturbed reactor was able to recover methane generation to 739 mL L-1·d-1 at feeding TS of 10%. Isotope analysis indicted acetate converted to methane through the syntrophic acetate oxidation and hydrogenotrophic methanogenesis (SAO-HM) pathway increased from 33% to 63% as the concentration of ammonium increased from 2493 to 6258 mg L-1. Significant different in the genome expression of the SAO bacterial from 0.09% to 1.23%, combining with main hydrogenotrophic partners (Methanoculleus spp. and Methanothermobacter spp.) contented of 2.1% and 99.9% during inhibitory and recovery stages, respectively. The highly expressed KEGG pathway in level 3 (enzyme genes) for the Recovery sludge combining with the extraordinary high abundance of genera Halocella sp. suggested that Halocella sp. might be a highly efficient hydrolytic and acidogenic microorganism and enhance the process of SAO during carbon metabolic flow to methane. This report will be a basis for further study of AD studies on high nitrogen content of poultry manure.

4.
Mikrochim Acta ; 191(7): 379, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38856817

RESUMO

A novel high-precision aptasensor of microcystin-RR (MC-RR) is developed based on a ratiometric self-powered photoelectrochemical platform. In detail, the defective MoS2/Ti3C2 nanocomposite with good photoelectric activity was designed to serve as the photoanode of the sensor for enhancing the signal and improving the detection sensitivity. In order to effectively eliminate external interferences, the key point of this ratiometric device is the introduction of the spatial-resolved technique, which includes the detection section and the reference section, generating reference signals and response signals, respectively. Moreover, output power was used as the detection signal, instead of the traditional photocurrent or photovoltage. Further, potassium persulfate was introduced as electron acceptor, which was beneficial for improving the electron transport efficiency, hindering electron-hole recombination, and significantly promoting the performance of the sensor. Finally, aptamer was adopted as recognition element to capture MC-RR molecules. The prepared sensor had a linear range from 10-12 to 10-6 M, and the detection limit was 5.6 × 10-13 M (S/N = 3). It has good precision, selectivity, and sensitivity, which shows great prospects in the on-site accurate analysis of samples with high energy output in the self-powered sensing field.

5.
Anal Chem ; 95(34): 12595-12599, 2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37522904

RESUMO

Self-powered electrochemical sensors, which can function without external electricity, are incredibly valuable in the realm of sensing. However, most of the present testing methods are normally confined to high environmental requirements, restricted lighting conditions, and temperature differences. Herein, an innovative self-powered electrochemical sensor was successfully developed based on hydrovoltaic effect coupling with capacitor amplification. Due to the combined merits from the two-dimensional transition metal carbides and nitrides (MXene)-polyaniline (PANI) with high surface potential and good hydrophilicity, and the capacitor amplification strategy, the device could harvest electric energy from water evaporation and displayed a high short circuit current value. Under optimal conditions, the proposed self-powered electrochemical sensor presented excellent sensitivity and high specificity for enrofloxacin (ENR) detection in the concentration range from 1 fM to 1 nM with a detection limit of 0.585 fM. Such a proposed sensor also has the advantages of environmental friendliness and ease of use, which is an ideal choice for accurately and precisely detecting ENR in real samples. The mode of such electrochemical detection outlined in this technical note implements a breakthrough in designing self-powered electrochemical sensors, providing a rational basis for development of a diversified sensing platform.

6.
Pharm Res ; 40(1): 145-156, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36002611

RESUMO

PURPOSE: Hepatitis B virus (HBV) infection is such a global health problem that hundreds of millions of people are HBV carriers. Current anti-viral agents can inhibit HBV replication, but can hardly eradicate HBV. Cytosine-phosphate-guanosine (CpG) oligodeoxynucleotides (ODNs) are an adjuvant that can activate plasmacytoid dendritic cells (pDCs) and conventional dendritic cells (cDCs) to induce therapeutic immunity for HBV eradication. However, efficient delivery of CpG ODNs into pDCs and cDCs remains a challenge. In this study, we constructed a series of cationic lipid-assisted nanoparticles (CLANs) using different cationic lipids to screen an optimal nanoparticle for delivering CpG ODNs into pDCs and cDCs. METHODS: We constructed different CLANCpG using six cationic lipids and analyzed the cellular uptake of different CLANCpG by pDCs and cDCs in vitro and in vivo, and further analyzed the efficiency of different CLANCpG for activating pDCs and cDCs in both wild type mice and HBV-carrier mice. RESULTS: We found that CLAN fabricated with 1,2-Dioleoyl-3-trimethylammonium propane (DOTAP) showed the highest efficiency for delivering CpG ODNs into pDCs and cDCs, resulting in strong therapeutic immunity in HBV-carrier mice. By using CLANCpG as an immune adjuvant in combination with the injection of recombinant hepatitis B surface antigen (rHBsAg), HBV was successfully eradicated and the chronic liver inflammation in HBV-carrier mice was reduced. CONCLUSION: We screened an optimized CLAN fabricated with DOTAP for efficient delivery of CpG ODNs to pDCs and cDCs, which can act as a therapeutic vaccine adjuvant for treating HBV infection.


Assuntos
Hepatite B , Nanopartículas , Camundongos , Animais , Vírus da Hepatite B , Oligodesoxirribonucleotídeos/farmacologia , Fosfatos , Citosina , Guanosina , Hepatite B/tratamento farmacológico , Ácidos Graxos Monoinsaturados , Adjuvantes Imunológicos/uso terapêutico , Células Dendríticas
7.
Analyst ; 148(20): 5060-5069, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37668261

RESUMO

A photo-driven self-powered aptasensor was constructed based on a matching capacitor and the ZnIn2S4/Ti3C2 heterojunction as the photoanode and Cu2O as the photocathode in a dual-photoelectrode sensing matrix for multiple signal amplification for the ultrasensitive detection of microcystin-RR (MC-RR). The introduction of Ti3C2 MXene nanosheets on the photoanode surface can not only accelerate the transfer and separation of photoinduced electron/hole pairs, thus enhancing the output signal of the photo-driven self-powered system, but also provide a larger specific surface area for the immobilization of the bio-recognition unit aptamer. More importantly, for a portable and miniaturized device, a micro-workstation with the size of a universal serial bus (USB) disk and a novel short-circuit current access was proposed to capture the instantaneous output electrical signal for real-time data tracking. In such a way, a sensitivity of 2.7 mA pM-1 was achieved when the matching capacitor was integrated into the self-powered system, which was 22 times that without a capacitor. After the interaction between MC-RR and the corresponding aptamer, a 'signal-off' detection configuration was formed via the steric hindrance effect. Therefore, such a multiple signal amplification system realized the ultrasensitive and selective determination of MC-RR successfully. Under optimal conditions, the linear range of the self-powered aptasensor was 0.1 to 100 pM and the detection limit was 0.033 pM (S/N = 3). The aptasensor was applied to the detection of MC-RR in fish, exhibiting good reproducibility (≈3.88%), paving the way for detecting microcystins in real-life samples.

8.
Int Heart J ; 64(3): 374-385, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37258114

RESUMO

Acute viral myocarditis is a serious complication of viral infectious diseases, including coronavirus disease 2019 (COVID-19). To better understand the pathogenesis of acute viral myocarditis, we retrospectively analyzed the incidence and prognostic significance of hypocalcemia among patients with acute myocarditis, most of whom were considered to have acute viral myocarditis. We retrospectively reviewed the demographic and clinical data of patients with clinically confirmed acute myocarditis treated in our hospital over a 13-year period from 2006 to 2019, including laboratory results, cardiac imaging findings, and clinical outcomes. These data were compared between lower, middle, and higher calcium groups depending on the minimum calcium level measured during hospitalization. Among the 288 patients with acute myocarditis included, the hypocalcemia group (lower calcium group) had poorer clinical and laboratory results, received more medications and device support, and experienced poorer outcomes, including heart failure, arrhythmias, and death. Specifically, the left ventricular ejection fraction was significantly lower, and the length of hospital stay was significantly longer in the hypocalcemia group than in the other two groups. Furthermore, the incidence rates of atrioventricular block, ventricular tachycardia/ventricular fibrillation, cardiogenic shock, and mortality were significantly higher in the hypocalcemia group. Multivariate Cox regression analysis identified hypocalcemia as an independent risk factor for 30-day mortality in patients with acute myocarditis. In conclusion, the clinical evidence provided by the present study indicates that hypocalcemia is a risk factor for poorer outcomes in patients with acute myocarditis that should be considered carefully in the diagnosis and treatment of these patients.


Assuntos
COVID-19 , Hipocalcemia , Miocardite , Humanos , Volume Sistólico , Hipocalcemia/epidemiologia , Hipocalcemia/complicações , Cálcio , Função Ventricular Esquerda , Miocardite/complicações , Miocardite/diagnóstico , Estudos Retrospectivos , COVID-19/complicações , Prognóstico , Arritmias Cardíacas/etiologia , Fibrilação Ventricular , Doença Aguda
9.
J Phys Chem A ; 126(3): 453-461, 2022 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-35023742

RESUMO

A joint experimental and theoretical investigation of the valence shell excitations of carbon tetrachloride has been performed by fast electron scattering and time dependent density functional theory calculations. At a collision energy of 1.5 keV and an energy resolution of about 70 meV, the dipole-forbidden transition of a1σ* ← 2t1 has been clearly observed at large momentum transfers, and its excitation energy of 6.15 eV and line width of 0.72 eV have been determined. Two new features are also recognized at 9.97 and 10.26 eV. The generalized oscillator strengths of the excited states at 5-11.3 eV have been determined from the measured spectra. The calculated generalized oscillator strength of the a1σ* ← 2t1 transition with the vibronic effect shows better agreement with the experiment, and the vibronic effect also accounts for its nonzero intensity at zero squared momentum transfer. The optical oscillator strengths of the valence shell excitations have also been obtained by extrapolating the generalized oscillator strengths to the limit of zero squared momentum transfer. The integral cross sections have been systematically determined from the threshold to 5000 eV by means of the BE-scaling method. The present oscillator strengths and cross sections provide the fundamental data of carbon tetrachloride and have important applications in photochemical modeling for atmospheric physics.

10.
Analyst ; 146(20): 6220-6227, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34523620

RESUMO

In this work, a novel visible light-driven self-powered photoelectrochemical (PEC) platform was designed based on 3D N-doped graphene hydrogel/hematite nanocomposites (NGH/Fe2O3) via a facile one-pot hydrothermal route. The coupling NGH with Fe2O3 could generate a Schottky junction, which promoted the separation of charges. Moreover, Mott-Schottky measurements validated that the carrier concentration achieved by NGH/Fe2O3 was about 3.4 × 103 times in comparison to that of pure Fe2O3, which was beneficial for efficient charge transfer. Owing to the carrier density effect and Schottky junction, the photocurrent of the as-fabricated NGH/Fe2O3 nanocomposites was 6.9-fold higher than that of pure Fe2O3. On the basis of such excellent Schottky junctions, an ultrasensitive visible light-induced self-powered PEC aptasensor was developed using a Microcystin-LR (MC-LR) aptamer. The as-fabricated PEC aptasensor displayed good analytical performance toward MC-LR detection in terms of wide linear range (1 pM-5 nM), low detection limit (0.23 pM, S/N = 3), excellent selectivity and high stability. This new strategy can provide a way for regulating nanostructures for more sensitive PEC sensors by increasing the carrier density.


Assuntos
Técnicas Biossensoriais , Grafite , Técnicas Eletroquímicas , Compostos Férricos , Hidrogéis , Luz , Limite de Detecção , Toxinas Marinhas , Microcistinas
11.
Anal Bioanal Chem ; 413(21): 5373-5382, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34264374

RESUMO

Low-cost and resource-rich non-noble metal plasmonic materials have attracted tremendous attention as potential substitutes for plasmonic noble metals. Herein, 3D nitrogen-doped graphene hydrogels (NGH) decorated with Ti3+ self-doped 1D rod-shaped titanium dioxide nanorods (TiO2-x NR), 10-25 nm in size, were prepared by a facile one-step method. It was found that the as-fabricated TiO2-x NR/NGH showed a synergistic effect, displaying enhanced photoelectrochemical (PEC) activity by controlling the nanoscale architecture and improving the electronic properties, while also producing abundant oxygen vacancies, which extended the light harvesting and suppressed the recombination of electron-hole pairs induced by the non-noble metal surface plasmon resonance (SPR) effect. In particular, the transient-state photocurrent intensity of the TiO2-x NR/NGH composites was 5.1 times as high as that of pure TiO2. Therefore, the TiO2-x NR/NGH composites could serve as a substrate material for PEC sensing, providing a good basis for selective and sensitive detection of chlorpyrifos. Under optimal conditions, the constructed PEC sensor was found to have several advantages including a broad linear range (0.05 ng/mL-0.5 µg/mL), low detection limit (0.017 ng/mL), and considerable stability, demonstrating that the sensor may offer a promising route in the field of environmental analysis.

12.
Nutr Metab Cardiovasc Dis ; 31(8): 2458-2470, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34090773

RESUMO

BACKGROUND AND AIMS: Insufficient dietary fiber (DF) intake is associated with increased blood pressure (BP) and the mode of action is unclear. The intake of DF supplements by participants in previous interventional studies was still far below the amount recommended by the World Health Organization. Therefore, this study aims to explore the effect of supplementing relatively sufficient DF on BP and gut microbiota in patients with essential hypertension (HTN). METHODS AND RESULTS: Fifty participants who met the inclusion criteria were randomly divided into the DF group (n = 25) and control group (n = 25). All the participants received education on regular dietary guidance for HTN. In addition to dietary guidance, one bag of oat bran (30 g/d) supplement (containing DF 8.9 g) was delivered to the DF group. The office BP (oBP), 24 h ambulatory blood pressure, and gut microbiota were measured at baseline and third month. After intervention, the office systolic blood pressure (oSBP; P < 0.001) and office diastolic blood pressure (oDBP; P < 0.028) in the DF group were lower than those in the control group. Similarly, the changes in 24hmaxSBP (P = 0.002), 24hmaxDBP (P = 0.001), 24haveSBP (P < 0.007), and 24haveDBP (P = 0.008) were greater in the DF group than in the control group. The use of antihypertensive drugs in the DF group was significantly reduced (P = 0.021). The ß diversity, including Jaccard (P = 0.008) and Bray-Curtis distance (P = 0.004), showed significant differences (P < 0.05) between two groups by the third month. The changes of Bifidobacterium (P = 0.019) and Spirillum (P = 0.006) in the DF group were significant. CONCLUSIONS: Increased DF (oat bran) supplement improved BP, reduced the amount of antihypertensive drugs, and modulated the gut microbiota. TRIAL REGISTRATION NUMBER: ChiCTR1900024055.


Assuntos
Avena , Bifidobacterium/crescimento & desenvolvimento , Pressão Sanguínea , Fibras na Dieta/administração & dosagem , Grão Comestível , Hipertensão Essencial/dietoterapia , Microbioma Gastrointestinal , Spirillum/crescimento & desenvolvimento , Adulto , Monitorização Ambulatorial da Pressão Arterial , China , Disbiose , Hipertensão Essencial/diagnóstico , Hipertensão Essencial/microbiologia , Hipertensão Essencial/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Nutritivo , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
13.
J Phys Chem A ; 124(52): 10997-11005, 2020 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-33347306

RESUMO

The valence-shell excitations of hydrogen sulfide have been studied by fast electron impact at a collision energy of 1.5 keV and an energy resolution of about 70 meV. By analyzing the variations of intensity and shape of the feature in the range of 5.0-7.5 eV at different scattering angles, the excitation energy of 5.85 ± 0.01 eV and the line width of 0.80 ± 0.01 eV of the 3b21A2 state have been determined. The generalized oscillator strengths of the valence-shell excitations in the energy range of 5.0-9.2 eV of hydrogen sulfide have been determined from the measured spectra. The corresponding optical oscillator strengths have been obtained by extrapolating the generalized oscillator strengths to the limit of zero squared momentum transfer. The integral cross sections have also been systematically determined from the threshold to 5000 eV by means of the BE-scaling method. The presently obtained oscillator strengths and integral cross sections have significant applications in the studies of planetary atmospheres and interstellar gases.

14.
Anal Chem ; 91(3): 1728-1732, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30640442

RESUMO

To further heighten solar-energy utilization efficiency could be significantly meaningful for developing useful photoelectric devices. Here, by integrating the nitrogen-doped graphene-BiOBr (NG-BiOBr) nanocomposites as a photocathode with titanium dioxide (TiO2) nanoparticles as a photoanode synchronously, a dual-photoelectrode internally driven self-powered sensing platform was fabricated, which can work without an external energy input except for light illumination. In this design, the microcystin-LR (MC-LR) molecules function as the fuel and model analyte as well. Avoiding the use of the costly cathode, this is the first example of the integration of a dual photoresponsive electrode into a photofuel cell for self-powered sensing and paves a luciferous way for efficient multidimension energy conversion. Besides, in order to investigate the detailed sensing process of the self-powered system, the Nyquist curves of the interface are studied between the dual-photoelectrode before and after adding the target MC-LR. The results demonstrated that the photoanode TiO2 contributed to the oxidation of MC-LR under photoirradiation rather than the photocathode. This work not only provides an appealing idea to construct the sensitive and easy-to-use assays of microcystins but also exhibits a successful prototype of a portable and on-site sensor.


Assuntos
Técnicas Eletroquímicas/métodos , Microcistinas/análise , Energia Solar , Bismuto/química , Técnicas Eletroquímicas/instrumentação , Eletrodos , Grafite/química , Grafite/efeitos da radiação , Luz , Limite de Detecção , Toxinas Marinhas , Nanopartículas Metálicas/química , Nanopartículas Metálicas/efeitos da radiação , Nanocompostos/química , Nanocompostos/efeitos da radiação , Nitrogênio/química , Nitrogênio/efeitos da radiação , Lagoas/análise , Titânio/química , Titânio/efeitos da radiação , Poluentes Químicos da Água/análise
15.
Phys Chem Chem Phys ; 21(31): 17433-17440, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31360966

RESUMO

The oscillator strengths and integral cross sections of the valence-shell excitations of HCl have significant applications in the studies of planetary atmospheres and interstellar gases. In the present work, the generalized oscillator strengths of the valence-shell excitations of HCl have been measured at an incident electron energy of 1500 eV and an energy resolution of 70 meV, and their momentum transfer dependence behaviors have been elucidated. It is observed that the generalized oscillator strength ratios of the b3Π1(ν' = 0) state to the C1Π(ν' = 0) state are a constant and independent of the squared momentum transfer, and this typical behavior in the momentum space is explained by the intraconfiguration mixing of the b3Π1 and C1Π states due to the spin-orbital interaction. The optical oscillator strengths of the valence-shell excitations have been obtained by extrapolating the generalized oscillator strengths to the limit of zero squared momentum transfer. The present optical oscillator strengths give an independent cross-check to the previous experimental and theoretical results, and it is found that most of the photoabsorption measurements are limited by the line saturation effect. The integral cross sections of the valence-shell excitations of HCl have been obtained systematically from the threshold to 5000 eV with the aid of the BE-scaling method.

16.
J Chem Phys ; 150(6): 064311, 2019 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-30770016

RESUMO

The vibrationally resolved generalized oscillator strengths of the first and strongest singlet excitation ÃA2″1← X̃1A1 of ammonia have been determined at an impact electron energy of 1500 eV with an energy resolution of 80 meV. The comprehensive comparison of the present results with the previous experimental and theoretical ones shows that the high-energy limit, where the first Born approximation holds, has been reached at an impact electron energy of 1500 eV in K2 < 1 a.u., while it is still not satisfied in the K2 > 1 a.u. even at 1500 eV. It is also observed that the minimum position of the generalized oscillator strength of the vibronic state shifts toward the larger squared momentum transfer with the increasing vibrational quantum number. By extrapolating the generalized oscillator strength to the zero momentum transfer, the optical oscillator strength of the ÃA2″1 state has been obtained, which gives an independent cross check to the previous results. The integral cross sections of the ÃA2″1 state have been obtained systematically from the threshold to 5000 eV with the aid of the BE-scaling method.

17.
Proc Natl Acad Sci U S A ; 113(15): 4164-9, 2016 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-27035960

RESUMO

A principal goal of cancer nanomedicine is to deliver therapeutics effectively to cancer cells within solid tumors. However, there are a series of biological barriers that impede nanomedicine from reaching target cells. Here, we report a stimuli-responsive clustered nanoparticle to systematically overcome these multiple barriers by sequentially responding to the endogenous attributes of the tumor microenvironment. The smart polymeric clustered nanoparticle (iCluster) has an initial size of ∼100 nm, which is favorable for long blood circulation and high propensity of extravasation through tumor vascular fenestrations. Once iCluster accumulates at tumor sites, the intrinsic tumor extracellular acidity would trigger the discharge of platinum prodrug-conjugated poly(amidoamine) dendrimers (diameter ∼5 nm). Such a structural alteration greatly facilitates tumor penetration and cell internalization of the therapeutics. The internalized dendrimer prodrugs are further reduced intracellularly to release cisplatin to kill cancer cells. The superior in vivo antitumor activities of iCluster are validated in varying intractable tumor models including poorly permeable pancreatic cancer, drug-resistant cancer, and metastatic cancer, demonstrating its versatility and broad applicability.


Assuntos
Antineoplásicos/uso terapêutico , Nanopartículas , Neoplasias/tratamento farmacológico , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Apoptose , Linhagem Celular Tumoral , Humanos , Metástase Neoplásica , Neoplasias/patologia , Esferoides Celulares
18.
Anal Chem ; 90(5): 3615-3620, 2018 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-29397697

RESUMO

Oxygen vacancy is an intrinsic defect in metal oxide semiconductors and has a crucial influence on their physicochemical and electronic properties. To boost the electrochemiluminescence (ECL) efficiency of the graphite-like carbon nitride (g-C3N4), the wet-chemical-calcination method was developed to introduce an oxygen vacancy in Eu-doped g-C3N4 nanostructures for the first time. The morphology and structure characterization suggest that the Eu element was present in the matrix of the europia (Eu2O3) clusters. Because of the effect of oxygen vacancy promoting catalytic activity, the doping of Eu caused a great positive shift of onset potential and large signal amplification in cathodic ECL signals compared with pure g-C3N4. Furthermore, a novel and ultrasensitive ECL aptasensor was realized with 17ß-estradiol (E2) as a prototype target by adsorption of E2 aptamer onto the Eu2O3-doped g-C3N4 (Eu2O3- g-C3N4) surface via van der Waals force. Given the specific recognition between aptamer and E2, the ECL signal decreased with the increasing concentration of E2, because the formation of E2-aptamer complex impeded the diffusion of luminophor molecules and the electrons approaching the surface of the electrode. Under the optimal cases, the as-prepared ECL aptasensor showed superior performances and also manifested outstanding selectivity toward E2. The present conceptual strategy offers a novel methodology to boost the sensitivity of the ECL sensor and promote the activity of ECL reagents.

19.
Nano Lett ; 17(5): 2871-2878, 2017 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-28375632

RESUMO

Precisely controlling the interaction of nanoparticles with biological systems (nanobio interactions) from the injection site to biological targets shows great potential for biomedical applications. Inspired by the ability of nanoparticles to alter their physicochemical properties according to different stimuli, we explored the tumor acidity and near-infrared (NIR) light activated transformable nanoparticle DATAT-NPIR&DOX. This nanoparticle consists of a tumor acidity-activated TAT [the TAT lysine residues' amines was modified with 2,3-dimethylmaleic anhydride (DA)], a flexible chain polyphosphoester core coencapsulated a NIR dye IR-780, and DOX (doxorubicin). The physicochemical properties of the nanoparticle can be controlled in a stepwise fashion using tumor acidity and NIR light, resulting in adjustable nanobio interactions. The resulting transformable nanoparticle DATAT-NPIR&DOX efficiently avoids the interaction with mononuclear phagocyte system (MPS) ("stealth" state) due to the masking of the TAT peptide during blood circulation. Once it has accumulated in the tumor tissues, DATAT-NPIR&DOX is reactivated by tumor acidity and transformed into the "recognize" state in order to promote interaction with tumor cells and enhance cellular internalization. Then, this nanoparticle is transformed into "attack" state under NIR irradiation, achieving the supersensitive DOX release from the flexible chain polyphosphoester core in order to increase the DOX-DNA interaction. This concept provides new avenues for the creation of transformable drug delivery systems that have the ability to control nanobio interactions.


Assuntos
Antineoplásicos/química , Adutos de DNA/química , Doxorrubicina/química , Corantes Fluorescentes/química , Produtos do Gene tat/química , Nanopartículas/química , Neoplasias/tratamento farmacológico , Oligopeptídeos/química , Animais , Antineoplásicos/administração & dosagem , Linhagem Celular Tumoral , Corantes/química , Adutos de DNA/administração & dosagem , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos , Produtos do Gene tat/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Indóis/química , Raios Infravermelhos , Camundongos , Nanopartículas/efeitos da radiação , Neoplasias/química , Neoplasias/diagnóstico por imagem , Tamanho da Partícula , Células RAW 264.7
20.
Anal Chem ; 89(8): 4525-4531, 2017 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-28337919

RESUMO

Deeply understanding the internal mechanism of the photoelectrohemical (PEC) process is conducive to fabricate high-performance PEC biosensors. In this work, we proposed a new insight toward an efficient charge-separation mechanism in high-performance PEC biosensors. Specifically, we disclosed that the lifetimes of photogenerated charge carriers of ultrathin MoS2 nanosheets could be prolonged by approximately millisecond time scales after a proper mole ratio of NGQDs were coupled, leading to the promoted charge separation and a giant photocurrent signal magnification. Benefiting from the dramatic signal amplification and the introduction of acetamiprid aptamer, subfemtomolar level detection of acetamiprid is achieved, which makes our strategy among the most sensitive electronic approaches for PEC-based monitoring of targets. This study was beneficial to further understand the charge-separation mechanism in PEC biosensing, which paved the way for the development of more efficient PEC biosensors.


Assuntos
Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais , Dissulfetos/química , Inseticidas/análise , Molibdênio/química , Nanoestruturas/química , Neonicotinoides/análise , Pontos Quânticos/química , Cucumis sativus/química , Cucumis sativus/metabolismo , Técnicas Eletroquímicas , Eletrodos , Ferricianetos/química , Grafite/química , Luz , Limite de Detecção , Solanum lycopersicum/química , Solanum lycopersicum/metabolismo , Nitrogênio/química
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