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1.
PLoS Genet ; 19(12): e1011104, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38153934

RESUMO

Identifying causal variants from genome-wide association studies (GWAS) is challenging due to widespread linkage disequilibrium (LD) and the possible existence of multiple causal variants in the same genomic locus. Functional annotations of the genome may help to prioritize variants that are biologically relevant and thus improve fine-mapping of GWAS results. Classical fine-mapping methods conducting an exhaustive search of variant-level causal configurations have a high computational cost, especially when the underlying genetic architecture and LD patterns are complex. SuSiE provided an iterative Bayesian stepwise selection algorithm for efficient fine-mapping. In this work, we build connections between SuSiE and a paired mean field variational inference algorithm through the implementation of a sparse projection, and propose effective strategies for estimating hyperparameters and summarizing posterior probabilities. Moreover, we incorporate functional annotations into fine-mapping by jointly estimating enrichment weights to derive functionally-informed priors. We evaluate the performance of SparsePro through extensive simulations using resources from the UK Biobank. Compared to state-of-the-art methods, SparsePro achieved improved power for fine-mapping with reduced computation time. We demonstrate the utility of SparsePro through fine-mapping of five functional biomarkers of clinically relevant phenotypes. In summary, we have developed an efficient fine-mapping method for integrating summary statistics and functional annotations. Our method can have wide utility in understanding the genetics of complex traits and increasing the yield of functional follow-up studies of GWAS. SparsePro software is available on GitHub at https://github.com/zhwm/SparsePro.


Assuntos
Estudo de Associação Genômica Ampla , Software , Teorema de Bayes , Estudo de Associação Genômica Ampla/métodos , Desequilíbrio de Ligação , Algoritmos , Polimorfismo de Nucleotídeo Único/genética
2.
Bioinformatics ; 40(5)2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38688586

RESUMO

MOTIVATION: Colocalization analysis is commonly used to assess whether two or more traits share the same genetic signals identified in genome-wide association studies (GWAS), and is important for prioritizing targets for functional follow-up of GWAS results. Existing colocalization methods can have suboptimal performance when there are multiple causal variants in one genomic locus. RESULTS: We propose SharePro to extend the COLOC framework for colocalization analysis. SharePro integrates linkage disequilibrium (LD) modeling and colocalization assessment by grouping correlated variants into effect groups. With an efficient variational inference algorithm, posterior colocalization probabilities can be accurately estimated. In simulation studies, SharePro demonstrated increased power with a well-controlled false positive rate at a low computational cost. Compared to existing methods, SharePro provided stronger and more consistent colocalization evidence for known lipid-lowering drug target proteins and their corresponding lipid traits. Through an additional challenging case of the colocalization analysis of the circulating abundance of R-spondin 3 GWAS and estimated bone mineral density GWAS, we demonstrated the utility of SharePro in identifying biologically plausible colocalized signals. AVAILABILITY AND IMPLEMENTATION: SharePro for colocalization analysis is written in Python and openly available at https://github.com/zhwm/SharePro_coloc.


Assuntos
Algoritmos , Estudo de Associação Genômica Ampla , Desequilíbrio de Ligação , Estudo de Associação Genômica Ampla/métodos , Humanos , Software , Polimorfismo de Nucleotídeo Único , Densidade Óssea/genética
3.
Plant Biotechnol J ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38593377

RESUMO

Fusarium head blight (FHB) and the presence of mycotoxin deoxynivalenol (DON) pose serious threats to wheat production and food safety worldwide. DON, as a virulence factor, is crucial for the spread of FHB pathogens on plants. However, germplasm resources that are naturally resistant to DON and DON-producing FHB pathogens are inadequate in plants. Here, detoxifying bacteria genes responsible for DON epimerization were used to enhance the resistance of wheat to mycotoxin DON and FHB pathogens. We characterized the complete pathway and molecular basis leading to the thorough detoxification of DON via epimerization through two sequential reactions in the detoxifying bacterium Devosia sp. D6-9. Epimerization efficiently eliminates the phytotoxicity of DON and neutralizes the effects of DON as a virulence factor. Notably, co-expressing of the genes encoding quinoprotein dehydrogenase (QDDH) for DON oxidation in the first reaction step, and aldo-keto reductase AKR13B2 for 3-keto-DON reduction in the second reaction step significantly reduced the accumulation of DON as virulence factor in wheat after the infection of pathogenic Fusarium, and accordingly conferred increased disease resistance to FHB by restricting the spread of pathogenic Fusarium in the transgenic plants. Stable and improved resistance was observed in greenhouse and field conditions over multiple generations. This successful approach presents a promising avenue for enhancing FHB resistance in crops and reducing mycotoxin contents in grains through detoxification of the virulence factor DON by exogenous resistance genes from microbes.

4.
Nano Lett ; 23(23): 10871-10878, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-37955520

RESUMO

Plasmon-enhanced electrochemistry (PEEC) has been observed to facilitate energy conversion systems by converting light energy to chemical energy. However, comprehensively understanding the PEEC mechanism remains challenging due to the predominant use of ensemble-based methodologies on macroscopic electrodes, which fails to measure electron-transfer kinetics due to constraints from mass transport and the averaging effect. In this study, we have employed nanoparticle impact electrochemistry (NIE), a newly developed electroanalytical technique capable of measuring electrochemical dynamics at a single-nanoparticle level under optimal mass transport conditions, along with microscopic electron-transfer theory for data interpretation. By investigating the plasmon enhanced hydrogen evolution reaction (HER) at individual silver nanoparticles (AgNPs), we have clearly revealed the previously unknown influence of solvent effects within the PEEC mechanism. This finding suggests an additional approach to optimize plasmon-assisted electrocatalysis and electrosynthesis systems.

5.
Telemed J E Health ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38920002

RESUMO

Background: Given the growing population of older adults globally, e-Health plays an indispensable role in the chronic disease management of multimorbidity. However, qualitative evidence that synthesizes the experiences of older adults with multimorbidity using e-Health service is currently lacking. The objective was to explore the experiences and perceptions of e-Health care in community-based settings among the older adults with multimorbidity. Methods: Seven electronic databases including PubMed, The Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Embase, Web of Science, China National Knowledge Infrastructure, and Chinese BioMedical Literature were searched, and the search was limited to studies from inception to September 1, 2023. Screening, data extraction, and quality appraisal were conducted independently by two reviewers. Thomas and Harden's thematic synthesis methodology was applied to synthesize the original themes. The methodological quality of included studies was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research, and the confidence of synthesized themes was evaluated by the Confidence in the Evidence from Reviews of Qualitative Research approaches. Results: Ten studies with moderate methodological quality met eligibility criteria and were included finally. Studies were conducted in four countries with 235 participants who were living with multiple chronic conditions. Among the 10 included studies, 37 credible findings were extracted and interpreted into 3 synthesized themes and 12 subthemes: (1) advantages and benefits perceived during e-Health service, (2) multidimensional challenges and negative experience posed by e-Health service, and (3) preferences, suggestions, and expectations for future e-Health improvement. The confidence in the majority of the three final synthesized themes was rated between "low" and "moderate" scales. Conclusions: The findings of this study provide new insights into implementing tailored e-Health care for older adults with multimorbidity. Further research should emphasize on realizing the potential value of e-Health service based on users' needs and perspectives to promote age-friendliness in geriatric practice.

6.
Molecules ; 29(6)2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38542935

RESUMO

The phase, mechanical properties, corrosion resistance, hydrophobicity, and interfacial contact resistance of Hastelloy X were investigated to evaluate its performance in proton exchange membrane fuel cells (PEMFCs). For comparison, the corresponding performance of 304 stainless steel (304SS) was also tested. Hastelloy X exhibited a single-phase face-centered cubic structure with a yield strength of 445.5 MPa and a hardness of 262.7 HV. Both Hastelloy X and 304SS exhibited poor hydrophobicity because the water contact angles were all below 80°. In a simulated PEMFC working environment (0.5 M H2SO4 + 2 ppm HF, 80 °C, H2), Hastelloy X exhibited better corrosion resistance than 304SS. At 140 N·cm-2, the interfacial contact resistance of Hastelloy X can reach as low as 7.4 mΩ·cm2. Considering its overall performance, Hastelloy X has better potential application than 304SS as bipolar plate material in PEMFCs.

7.
Clin Gerontol ; : 1-19, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38324289

RESUMO

OBJECTIVES: To examine the effectiveness of mindfulness-based interventions (MBIs) on psychological symptoms, motor symptoms, and quality of life in patients with Parkinson's disease (PD). METHODS: Published studies in Chinese and English languages, conducted from inception to March 2023, were identified by searching PubMed, Web of Science, Cochrane Library, CINAHL, PsycINFO, and two Chinese electronic databases. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines. RESULTS: Twelve studies were selected for quantitative syntheses. The impact of MBIs on reducing depression and anxiety, and improving mindfulness and quality of life in PD patients was statistically significant compared to the control group. However, no statistically significant effect on motor symptoms was observed. Subgroup analysis indicated that participants from Asia, those who received face-to-face sessions, and those whose sessions lasted 1.5 hours showed a more positive effect than other subgroups. CONCLUSIONS: Patients with PD may benefit from MBIs to improve psychological symptoms and quality of life. MBIs represent a pivotal non-pharmacological therapeutic approach in clinical practice. CLINICAL IMPLICATIONS: MBIs confer positive improvements in psychological well-being and quality of life in PD patients. However, it remains challenging to conclusively determine their efficacy in addressing motor symptoms.

8.
Anal Chem ; 95(14): 6098-6106, 2023 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-36972326

RESUMO

ß-Lactamase (Bla) produced by bacteria to resist ß-lactam antibiotics is a serious public health threat. Developing efficient diagnostic protocols for drug-resistant bacteria is of great significance. In this work, based on gas molecules in bacteria, a novel research strategy was proposed to develop a gas molecule-based probe by grafting 2-methyl-3-mercaptofuran (MF) onto cephalosporin intermediates via a nucleophilic substitution reaction. The probe can release the corresponding MF by reacting with Bla. The released MF, as a marker of drug-resistant bacteria, was analyzed by headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry. The Bla concentration as low as 0.2 nM can be easily observed, providing an efficient method for detecting enzyme activity and screening drug-resistant strains in vivo. Importantly, the method is universal, and probes with different properties can be prepared by changing different substrates to further identify different types of bacteria, thereby broadening the research methods and ideas for monitoring physiological processes.


Assuntos
Antibacterianos , beta-Lactamases , Antibacterianos/farmacologia , Antibacterianos/análise , beta-Lactamases/análise , Espectrometria de Massas em Tandem , Bactérias , Monobactamas/análise , Cromatografia Gasosa-Espectrometria de Massas
9.
Analyst ; 148(11): 2527-2535, 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37140019

RESUMO

An efficient and stable fiber coating is of great importance for solid-phase microextraction (SPME). In this study, carboxylated mesoporous carbon hollow spheres (MCHS-COOH) were developed as an efficient SPME coating of polar aromatic amines (AAs) for the first time. The MCHS-COOH coating material with high specific surface area (1182.32 m2 g-1), large pore size (10.14 nm), and rich oxygen-containing groups was fabricated via a facile H2O2 post-treatment. The as-prepared MCHS-COOH-coated fiber exhibited fast adsorption rate and excellent extraction properties, mainly due to its π-π interactions, hollow structure, and abundant affinity sites (carboxyl groups). Subsequently, coupled with gas chromatography-tandem mass spectrometry (GC-MS/MS), a sensitive method with low limits of detection (0.08-2.0 ng L-1), a wide linear range (0.3-500.0 ng L-1), and good repeatability (2.0-8.8%, n = 6) was developed for the analysis of AAs. The developed method was validated against three river water samples, with satisfactory relative recoveries being obtained. The above results demonstrated that the prepared MCHS-COOH-coated fiber exhibited good adsorption capacity, suggesting a promising application to monitor trace polar compounds in real environment.

10.
J Fluoresc ; 33(6): 2119-2129, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37040002

RESUMO

Two new 3D metal-organic frameworks (MOFs) ZZUT1 and ZZUT2 were prepared through the reaction of tris-(4-carboxylphenyl) phosphineoxide (H3TPO) ligand with nitrate of neodymium and praseodymium by solvothermal method. The structure, fluorescence and photocatalytic properties of ZZUT1 and ZZUT2 were studied. The crystalline structure of two 3D Ln(III)-MOFs both exhibit triclinic system and P-1 space group. The results of fluorescence analysis showed that two 3D Ln(III)-MOFs could selectively recognize acetone molecule through the fluorescence quenching mechanism. Meanwhile, ZZUT1 and ZZUT2 showed good adsorption and degradation ability on organic dye methylene blue (MB) in photocatalytic condition, and the degradation efficiency can reach to more than 90%.

11.
Nano Lett ; 22(17): 7028-7033, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-35856652

RESUMO

The large-scale application of direct ethanol fuel cells has long been obstructed by the sluggish ethanol oxidation reaction at the anode. Current wisdom for designing and fabricating EOR electrocatalysts has been focused on crystalline materials, which result in only limited improvement in catalytic efficiency. Here, we report the amorphous PdCu (a-PdCu) nanomaterials as superior EOR electrocatalysts. The amorphization of PdCu catalysts can significantly facilitate the C-C bond cleavage, which thereby affords a C1 path faradic efficiency as high as 69.6%. Further tailoring the size and shape of a-PdCu nanocatalysts through the delicate kinetic control can result in a maximized mass activity up to 15.25 A/mgPd, outperforming most reported catalysts. Notably, accelerated durability tests indicate that both the isotropic structure and one-dimensional shape can dramatically enhance the catalytic durability of the catalysts. This work provides valuable guidance for the rational design and fabrication of amorphous noble metal-based electrocatalysts for fuel cells.

12.
Molecules ; 28(18)2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37764493

RESUMO

The FeCrMoSi amorphous coatings were fabricated on the surface of a 304 stainless steel (SS) base material using atmospheric plasma spraying. A comprehensive investigation was carried out to evaluate the structure, morphology, adhesion to base material, hardness, hydrophobicity, interfacial contact resistance, and corrosion resistance of the coatings. The results show a remarkable hardness of 1180.1 HV, a strong bond strength of up to 64.3 N/mm2, and excellent hydrophobicity with a water contact angle reaching 141.2°. Additionally, in an acidic environment with fluoride ions (0.5 M H2SO4 + 2 ppm HF, 80 °C), the FeCrMoSi amorphous coating demonstrated superior corrosion resistance compared with 304 SS while maintaining similar electroconductibility. Detailed analysis of the structural characteristics and corrosion resistance of FeCrMoSi amorphous coatings provided valuable insights into their mechanics. These promising results signify a bright future for FeCrMoSi amorphous coatings in various industrial sectors, including transportation, petroleum, and electric power industries.

13.
Angew Chem Int Ed Engl ; 61(8): e202115819, 2022 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-34890086

RESUMO

The structure-function relationship of plasmon-enhanced electrochemistry (PEEC) is of great importance for the design of efficient PEEC catalysts, but is rarely investigated at single nanoparticle level for the lack of an efficient nanoscale methodology. Herein, we report the utilization of nanoparticle impact electrochemistry to allow single nanoparticle PEEC, where the effect of incident light on the plasmonic Ag/Au nanoparticles for accelerating cobalt metal-organic framework nanosheets (Co-MOFNs) catalyzed hydrogen evolution reaction (HER) is systematically explored. It is found that the plasmon-excited hot carrier injection can lower the reaction activation energy, resulting in a much promoted reaction probability and the integral charge generated from individual collisions. Besides, a plasmonic nanoparticle filtering method is established to effectively distinguish different plasmonic nanoparticles. This work provides a unique view in understanding the intrinsic physicochemical properties for PEEC at the nano-confined domains.

14.
Anal Chem ; 92(8): 6094-6102, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32233361

RESUMO

Efficient energy transfer is a promising strategy in overcoming the inherent limits of a narrow band and weak absorption of lanthanide ions due to the nature of 4f-4f transitions. Herein, we introduce a nanoparticle-sensitized nanoparticle system where a near-infrared-emitting quantum dot (QD) is used as a sensitizer with broadband photon absorption for a lanthanide-doped nanoparticle (LNP) to generate second near-infrared (NIR-II) emission. The NIR-II luminescence of Er3+-doped LNP by Ag2S QD sensitization displays an enhancement of ∼17-fold in intensity and ∼10-fold in brightness over bare LNP because of increased absorptivity and overall broadening of the absorption spectrum of LNP. Furthermore, a QD-sensitized LNP system exhibits excellent photostability and is able to improve the signal-to-noise ratio of tumor NIR-II imaging via in situ cross-linking of QD and LNP. The QD-sensitized LNP system for luminescence enhancement opens a potential avenue for efficient energy transfer in complex nanoparticle-nanoparticle systems.

15.
Anal Chem ; 92(8): 6111-6120, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32216270

RESUMO

Fluorescence (FL) imaging in the second near-infrared window (NIR-II, 1000-1700 nm) has emerged as a promising bioimaging modality that enables noninvasive visualization of deep tissue with an unprecedented resolution. However, there is a paucity of studies on high-quality responsive NIR-II FL molecules. Herein we report a novel activated NIR-II FL molecule, 4,7-bis(5-(4-(diphenylamine)phenyl)-2-thiophene) [1,2,5]selenadiazolo[3,4-f]benzo[c][1,2,5]thiadiazole (SeTT), which exhibits fast and specific responsive capability to hypochlorous acid (HClO). To obtain the NIR-II ratiometric nanoprobe, SeTT was encapsulated on the surface of Er3+-doped down-conversion nanoparticles (DCNP), achieving the DCNP@SeTT nanoprobe. With a single 980 nm laser excitation, the ratiometric FL signal of SeTT at 1150 nm and DCNP at 1550 nm (I1150 nm/I1550 nm) was linearly correlated with the concentration of HClO with a detection limit of 0.4 µM. The ratiometric nanoprobe was successfully investigated for variations in HClO concentration in the tumor progression, visualization of anatomical structures of the peritoneal cavity in the mice model with inflammation, and quantitative detection of the HClO concentration in a rabbit model of osteoarthritis, achieving a fast response and high selectivity for the detection of HClO. The NIR-II-responsive nanoprobe can serve as a promising and effective tool for highly sensitive monitoring and imaging of HClO in living systems.


Assuntos
Corantes Fluorescentes/química , Ácido Hipocloroso/análise , Lasers , Imagem Óptica , Animais , Artrite/diagnóstico por imagem , Linhagem Celular Tumoral , Feminino , Raios Infravermelhos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Estrutura Molecular , Tamanho da Partícula , Peritonite/diagnóstico por imagem , Células RAW 264.7 , Coelhos , Propriedades de Superfície
16.
Analyst ; 145(17): 5925-5932, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32692339

RESUMO

Sorbents with high surface utilization and good dispersibility are of great importance for the extraction performance of magnetic solid-phase extraction (MSPE). In this study, a fish scale-like magnetic nanomaterial (Co@Co3O4/OCN) was synthesized, which can be used as a highly efficient MSPE sorbent due to its strong magnetism, special morphology, doping of N element, numerous micro-mesopore cavities and organic functional groups (hydroxyl and carboxyl). Furthermore, a Co@Co3O4/OCN-based MSPE method for monitoring the changes in the levels of three auxins (indole-3-acetic acid, indole-3-propionic acid and 3-indole butyric acid) was successfully established. Wide linear ranges (1.0-1000.0 pg mL-1) with good correlation coefficients (R > 0.9992), low limits of detection (LODs, 0.2-4.0 pg mL-1) and satisfactory repeatability (RSD ≤5.9%, n = 3) were obtained. Using the developed method, various growth parts and different growth periods of plants under Cd stress were monitored. The results showed that auxins in various parts of plants showed differential response under Cd stress, and there was a threshold for the changes in auxin levels against Cd stress. This indicates that the developed fish scale-like Co@Co3O4/OCN nanomaterial has a good application prospect for enriching small molecular targets containing hydroxyl and carboxyl groups.

17.
BMC Bioinformatics ; 20(1): 352, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31226925

RESUMO

BACKGROUND: Third-generation sequencing platforms, such as PacBio sequencing, have been developed rapidly in recent years. PacBio sequencing generates much longer reads than the second-generation sequencing (or the next generation sequencing, NGS) technologies and it has unique sequencing error patterns. An effective read simulator is essential to evaluate and promote the development of new bioinformatics tools for PacBio sequencing data analysis. RESULTS: We developed a new PacBio Sequencing Simulator (PaSS). It can learn sequence patterns from PacBio sequencing data currently available. In addition to the distribution of read lengths and error rates, we included a context-specific sequencing error model. Compared to existing PacBio sequencing simulators such as PBSIM, LongISLND and NPBSS, PaSS performed better in many aspects. Assembly tests also suggest that reads simulated by PaSS are the most similar to experimental sequencing data. CONCLUSION: PaSS is an effective sequence simulator for PacBio sequencing. It will facilitate the evaluation and development of new analysis tools for the third-generation sequencing data.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala/métodos , Análise de Sequência de DNA , Software , Animais , Arabidopsis/genética , Caenorhabditis elegans/genética , Simulação por Computador , Escherichia coli/genética
18.
Immunol Cell Biol ; 97(8): 714-725, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30977930

RESUMO

Acute rejection is the major determinant for the long-term survival of donor liver after liver transplantation (LT). The aim of this study was to examine the therapeutic potential of interleukin (IL)-10-FasL-overexpressing immature dendritic cells (imDCs) to induce local immunosuppression in liver grafts. imDCs derived from donors were transduced by lentiviral vectors expressing human IL-10 and/or Fas ligand (FasL) gene(s), and the expression of surface molecules and the ability to induce T-cell proliferation were measured. imDCs were intraperitoneally injected into recipient rats as a model of LT to examine the rejection grade [Banff rejection activity index (RAI)], liver functions [Alanine aminotransferase, Aspartate aminotransferase (AST) and total bilirubin (TBIL)] and post-transplant survival. IL-10 and FasL co-transduction of imDCs induced a greater reduction in CD80, CD86 and major histocompatibility complex class II (MHC II) expression, as well as T-cell proliferation, but increased levels of IL-10 and FasL in culture supernatants compared with mono-transduced or untransduced imDCs (P < 0.05). The infusion of co-transduced imDCs in LT recipients reduced RAI scores, decreased plasma AST and TBIL, and prolonged survival compared with mono-transduced or untransduced imDC-treated liver allografts. These findings demonstrated that the transfusion of IL-10-FasL/imDCs enhanced immune tolerance and prolonged the survival of liver allografts after LT. The immunomodulatory activity of IL-10- and FasL-modified imDCs might be a new therapeutic approach to prevent organ rejection in clinical transplantation.


Assuntos
Células Dendríticas/transplante , Rejeição de Enxerto/prevenção & controle , Transplante de Fígado/efeitos adversos , Tolerância ao Transplante , Animais , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Modelos Animais de Doenças , Proteína Ligante Fas/genética , Proteína Ligante Fas/imunologia , Proteína Ligante Fas/metabolismo , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Humanos , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-10/metabolismo , Masculino , Ratos , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/metabolismo , Transplante Heterotópico/efeitos adversos
19.
Chembiochem ; 20(4): 561-567, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30304583

RESUMO

Live-cell imaging of cell-surface-associated proteolytic enzymes is crucial to understand their biological roles and functions in both physiological and pathological processes. However, the complexity of the cell membrane environment increases difficulties in specifically investigating targeted proteolytic activities within the microenvironment. Towards this end, a unique, photoremovable, furin-responsive peptide probe that can undergo spatiotemporal control through UV-light illumination has been designed and synthesized to aid in visualizing the activity of a cell-surface-associated protease enzyme, furin, in live cells. Prior to light irradiation, the photolabile moiety, 4,5-dimethoxy-2-nitrobenzyl, in the peptide sequence of the reporter will block furin-like enzymatic hydrolysis, and thus, no fluorescence will be observed. Upon simple light illumination, photolysis will occur, thereby revealing the uncaged peptide probe, which can undergo enzyme hydrolysis and lead to an increase in fluorescence signal; this allows the real-time imaging of endogenous cell-surface-associated furin-like enzyme function in living cells through precise spatial and temporal resolution.


Assuntos
Membrana Celular/metabolismo , Furina/metabolismo , Microscopia de Fluorescência , Linhagem Celular Tumoral , Corantes Fluorescentes/química , Humanos , Hidrólise , Nitrobenzenos/química , Peptídeos/química , Peptídeos/metabolismo , Raios Ultravioleta
20.
Bioconjug Chem ; 29(4): 928-938, 2018 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-29466856

RESUMO

Near-infrared (NIR) light-mediated photodynamic therapy (PDT), especially based on lanthanide-doped upconversion nanocrystals (UCNs), have been extensively investigated as a promising strategy for effective cellular ablation owing to their unique optical properties to convert NIR light excitation into multiple short-wavelength emissions. Despite the deep tissue penetration of NIR light in living systems, the therapeutic efficiency is greatly restricted by insufficient oxygen supply in hypoxic tumor microenvironment. Moreover, the coexistent tumor-associated macrophages (TAMs) play critical roles in tumor recurrence during the post-PDT period. Herein, we developed a unique photosensitizer-loaded UCNs nanoconjugate (PUN) by integrating manganese dioxide (MnO2) nanosheets and hyaluronic acid (HA) biopolymer to improve NIR light-mediated PDT efficacy through attenuating hypoxia status and synergistically reprogramming TAMs populations. After the reaction with overproduced H2O2 in acidic tumor microenvironment, the MnO2 nanosheets were degraded for the production of massive oxygen to greatly enhance the oxygen-dependent PDT efficiency upon 808 nm NIR light irradiation. More importantly, the bioinspired polymer HA could effectively reprogram the polarization of pro-tumor M2-type TAMs to anti-tumor M1-type macrophages to prevent tumor relapse after PDT treatment. Such promising results provided the great opportunities to achieve enhanced cellular ablation upon NIR light-mediated PDT treatment by attenuating hypoxic tumor microenvironment, and thus facilitated the rational design of new generations of nanoplatforms toward immunotherapy to inhibit tumor recurrence during post-PDT period.


Assuntos
Hipóxia/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Compostos de Manganês/uso terapêutico , Melanoma/tratamento farmacológico , Nanopartículas/uso terapêutico , Óxidos/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Microambiente Tumoral/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Ácido Hialurônico/química , Ácido Hialurônico/uso terapêutico , Hipóxia/metabolismo , Hipóxia/patologia , Raios Infravermelhos , Elementos da Série dos Lantanídeos/química , Elementos da Série dos Lantanídeos/uso terapêutico , Macrófagos/metabolismo , Macrófagos/patologia , Compostos de Manganês/química , Melanoma/metabolismo , Melanoma/patologia , Camundongos , Nanopartículas/química , Óxidos/química , Oxigênio/metabolismo , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Células RAW 264.7
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