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1.
Biosens Bioelectron ; 195: 113661, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34592501

RESUMO

Aptamer-based dual recognition strategy, using dual aptamers or the cooperation of aptamers with other recognition elements, can better utilize the advantages of each recognition molecule and increase the design flexibility to effectively overcome the limitations of a single molecule recognition strategy, thereby improving the sensitivity and selectivity and facilitating the regulation of biological process. Hence, this review systematically tracks the construction and application of dual aptamers recognition strategy in the versatile detection of protein biomarkers, pathogenic microorganisms, cancer cells, and the treatment of some diseases and, more importantly, in functional regulation and imaging of cell-surface protein receptors. Then, the cooperation of aptamers with other recognition elements are briefly introduced. Potential challenges facing this field have been highlighted, aiming to expand bioanalytical applications of aptamer-based dual or multiple recognition strategies and meet the growing demand for precision medicine.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Biomarcadores , Proteínas
2.
Biomater Sci ; 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34726680

RESUMO

Mitochondria are crucial metabolic organelles involved in tumorigenesis and tumor progression, and the induction of abnormal mitochondria metabolism is recognized as a strategy with strong potential for the exploration of advanced tumor therapeutics. Herein, hierarchical manganese silicate nanoclusters modified with triphenylphosphonium (MSNAs-TPP) were designed and synthesized for mitochondria-targeted tumor theranostics. The as-prepared MSNAs-TPP retains considerable dimensional and structural stability in the neutral physiological environment, favoring its accumulation at the tumor site. More interestingly, MSNAs-TPP may disassemble in a responsive manner to an acidic tumor microenvironment into ultrasmall manganese silicate nanocapsules (∼6 nm), enabling deep tumor penetration and mitochondria targeting. When reaching the mitochondria, the nanocapsules effectively deplete mitochondrial glutathione (GSH), and simultaneously release catalytic Mn2+ ions to induce amplified oxidative stress in the structure with the enriched CO2 and H2O2 from mitochondria metabolism. As a result, MSNAs-TPP presents considerable antitumor effect without a clear side effect, both in vitro and in vivo. The study may provide an alternative concept in the development of intelligent nanotherapeutics for tumor treatment with high efficacy.

3.
Org Lett ; 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34784228

RESUMO

Under catalysis by chiral phosphine, an asymmetric isomerization/annulation cascade reaction of allylamines with allenoates was realized. A wide range of γ-substituted allenoates were tolerated to afford chiral pyrroline derivatives in high yields with excellent enantioselectivities. In the reaction, isomerization of readily available N-allylamines to reactive aliphatic imines through a 1,4-proton shift is a key step, which circumvents the isolation of highly unstable alkyl N-sulfonylimines.

4.
Front Immunol ; 12: 689866, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34737734

RESUMO

Rapid recruitment of neutrophils to an inflamed site is one of the hallmarks of an effective host defense mechanism. The main pathway through which this happens is by the innate immune response. Neutrophils, which play an important part in innate immune defense, migrate into lungs through the modulation actions of chemokines to execute a variety of pro-inflammatory functions. Despite the importance of chemokines in host immunity, little has been discussed on their roles in host immunity. A holistic understanding of neutrophil recruitment, pattern recognition pathways, the roles of chemokines and the pathophysiological roles of neutrophils in host immunity may allow for new approaches in the treatment of infectious and inflammatory disease of the lung. Herein, this review aims at highlighting some of the developments in lung neutrophil-immunity by focusing on the functions and roles of CXC/CC chemokines and pattern recognition receptors in neutrophil immunity during pulmonary inflammations. The pathophysiological roles of neutrophils in COVID-19 and thromboembolism have also been summarized. We finally summarized various neutrophil biomarkers that can be utilized as prognostic molecules in pulmonary inflammations and discussed various neutrophil-targeted therapies for neutrophil-driven pulmonary inflammatory diseases.


Assuntos
Imunidade Inata/imunologia , Neutrófilos/imunologia , Pneumonia/imunologia , Biomarcadores/sangue , COVID-19/imunologia , Degranulação Celular/imunologia , Quimiocinas/imunologia , Ensaios Clínicos como Assunto , Armadilhas Extracelulares/imunologia , Humanos , Integrinas/imunologia , Pulmão/imunologia , Pulmão/patologia , Neutrófilos/efeitos dos fármacos , Pneumonia/diagnóstico , Pneumonia/tratamento farmacológico , Receptores de Reconhecimento de Padrão/imunologia , Explosão Respiratória/imunologia , SARS-CoV-2 , Tromboembolia/imunologia
5.
Anal Chem ; 93(45): 15200-15208, 2021 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-34723514

RESUMO

Exosome concentration and exosomal proteins are regarded as promising cancer biomarkers. Herein, a waxberry-like magnetic bead (magnetic-nanowaxberry) which has huge surface area and strong affinity was synthesized to couple with aptamer for exosome capture and recovery. Subsequently, we developed a fluorescent assay for the sensitive, accurate, and simultaneous quantification of exosome and cancer-related exosomal proteins [epidermal growth factor receptor (EGFR) and epithelial cell adhesion molecule (EpCAM)] by using triple-colored probes to recognize EGFR and EpCAM or spontaneously anchor to the lipid bilayer. In this design, the interference of soluble proteins can be avoided due to the dual recognition strategy. Moreover, the lipid-based quantification of exosome concentration can improve the accuracy. Besides, the simultaneous detection mode can save samples and simplify the operation steps. Consequently, the assay shows high sensitivity (the limits of detection are down to 0.96 pg/mL for EGFR, 0.19 pg/mL for EpCAM, and 2.4 × 104 particles/µL for exosome), high specificity, and satisfactory accuracy. More importantly, this technique is successfully used to analyze exosomes in plasma to distinguish cancer patients from healthy individuals. To improve the diagnostic efficacy, the deep learning was used to exploit the potential pattern hidden in data obtained by the proposed method. Also, the accuracy for the intelligent diagnosis of cancer can achieve 96.0%. This study provides a new avenue for developing new biosensors for exosome analysis and intelligent disease diagnosis.


Assuntos
Técnicas Biossensoriais , Exossomos , Neoplasias , Biomarcadores Tumorais , Humanos , Fenômenos Magnéticos
6.
Front Pharmacol ; 12: 597907, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803661

RESUMO

Background: Carbapenemase-producing Klebsiella pneumoniae (CpKP) has been implicated as an increasing threat to public health. CpKP is a ubiquitous, opportunistic pathogen that causes both hospital and community acquired infections. This organism hydrolyzes carbapenems and other ß-lactams and thus, leading to multiple resistance to these antibiotics. Despite the difficult to treat nature of infections caused by CpKP, little has been discussed on the mortality, clinical response and microbiological success rates associated with various antibiotic regimen against CpKP. This meta-analysis was designed to fill the paucity of information on the clinical impact of various antibiotic therapeutic regimens among patients infected with CpKP. Materials and Methods: Literature in most English databases such as Medline through PubMed, Google Scholar, Web of Science, Cochrane Library and EMBASE, were searched for most studies published between the years 2015-2020. Data were analyzed using the R studio 2.15.2 statistical software program (metaphor and meta Package, Version 2) by random-effects (DerSimonian and Laird) model. Results: Twenty-one (21) studies including 2841 patients who had been infected with CpKP were analysed. The overall mortality rate was 32.2% (95%CI = 26.23-38.87; I 2 = 89%; p-value ≤ 0.01, Number of patients = 2716). Pooled clinical and microbiological success rates were 67.6% (95%CI = 58.35-75.64, I 2 = 22%, p-value = 0.25, Number of patients = 171) and 74.9% (95%CI = 59.02-86.09, I 2 = 53%, p-value = 0.05, Number of patients = 121), respectively. CpKP infected patients treated with combination therapy are less likely to die as compared to those treated with monotherapy (OR = 0.55, 95%CI = 0.35-0.87, p-value = 0.01, Number of patients = 1,475). No significant difference existed between the mortality rate among 60years and above patients vs below 60years (OR = 0.84, 95%CI = 0.28-2.57, p-value = 0.76, 6 studies, Number of patients = 1,688), and among patients treated with triple therapy vs. double therapy (OR = 0.50, 95%CI = 0.21-1.22, p-value = 0.13, 2 studies, Number of patients = 102). When compared with aminoglycoside-sparing therapies, aminoglycoside-containing therapies had positive significant outcomes on both mortality and microbiological success rates. Conclusion: New effective therapies are urgently needed to help fight infections caused by this organism. The effective use of various therapeutic options and the strict implementation of infection control measures are of utmost importance in order to prevent infections caused by CpKP. Strict national or international implementation of infection control measures and treatment guidelines will help improve healthcare, and equip governments and communities to respond to and prevent the spread of infectious diseases caused by CpKP.

7.
Mikrochim Acta ; 188(11): 405, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34731318

RESUMO

With polyacrylonitrile nanofibers mat (PAN NFsM) as a template, molecularly imprinted resin/polydopamine nanofibers mat (MIR/PDA NFsM) was synthesized for the extraction of sulfonamides (SAs) in water. The specific surface area and pore volume were increased obviously due to the functionalization of MIR. The adsorption efficiencies of MIR/PDA NFsM under optimized conditions for SAs were 92.3-99.3%. Possible adsorption mechanisms of imprinting recognition and hydrogen bond interactions were also put forward. Compared with MIR particles, the MIR/PDA NFsM exhibited much superior adsorption performance. Particularly, the outstanding mass transfer efficiency of MIR/PDA NFsM was much higher than the other reported adsorbents for SAs. Finally, a new method based on the solid-phase extraction (SPE) of MIR/PDA NFsM was successfully developed for the detection of five SAs in environmental water with HPLC-MS/MS and applied to the analysis of actual samples. Under the selected conditions, the enrichment factors of MIR/PDA NFsM of SCP, SMT, SMZ, SMR, and SMX were between 23.0 and 25.0. Low detection limits (0.26-0.76 ng L-1), broad linear range (1.0 ng L-1 to 10.0 µg L-1), and satisfactory recoveries (82.8-115.6%) and precisions (RSDs < 7.2%) were obtained. Moreover, the excellent reusability properties and storage stability endowed MIR/PDA NFsM with great value for practical applications.

8.
J Nanobiotechnology ; 19(1): 358, 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34736483

RESUMO

Sonodynamic therapy (SDT), presenting spatial and temporal control of ROS generation triggered by ultrasound field, has attracted considerable attention in tumor treatment. However, its therapeutic efficacy is severely hindered by the intrinsic hypoxia of solid tumor and the lack of smart design in material band structure. Here in study, fine α-Fe2O3 nanoparticles armored with Pt nanocrystals (α-Fe2O3@Pt) was investigated as an alternative SDT agent with ingenious bandgap and structural design. The Schottky barrier, due to its unique heterostructure, suppresses the recombination of sono-induced electrons and holes, enabling superior ROS generation. More importantly, the composite nanoparticles may effectively trigger a reoxygenation phenomenon to supply sufficient content of oxygen, favoring the ROS induction under the hypoxic condition and its extra role played for ultrasound imaging. In consequence, α-Fe2O3@Pt appears to enable effective tumor inhibition with imaging guidance, both in vitro and in vivo. This study has therefore demonstrated a highly potential platform for ultrasound-driven tumor theranostic, which may spark a series of further explorations in therapeutic systems with more rational material design.

9.
Org Lett ; 23(20): 7703-7707, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34605654

RESUMO

The δ-sulfonamido-substituted enones were employed as phosphine acceptor in phosphine-catalyzed (4 + 2) annulation of 1,1-dicyanoalkenes. They served as a four-membered synthon to react with 1,1-dicyanoalkenes under mild reaction conditions, producing piperidine derivatives in moderate to excellent yields with good to excellent diastereoselectivities.

10.
Mikrochim Acta ; 188(11): 397, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34716495

RESUMO

A simple nanoplatform based on molybdenum disulfide (MoS2) nanosheets, a fluorescence quencher (signal off), and a hybridization chain reaction (HCR) signal amplification (signal on) used for the enzyme-free, label-free, and low-background signal quantification of microRNA-21 in plasma exosome is reported. According to the sequence of microRNA-21, carboxy-fluorescein (FAM)-labeled hybridization probe 1 (FAM-H1) and hybridization probes 2 (FAM-H2) were designed with excitation maxima at 488 nm and emission maxima at 518 nm. MoS2 nanosheets could adsorb FAM-H1 and FAM-H2 and quenched their fluorescence signals to reduce the background signal. However, HCR was triggered when microRNA-21 was present. Consequently, HCR products containing a large number of FAM fluorophores can emit a strong fluorescence at 518 nm and could realize the detection of microRNA-21 as low as 6 pmol/L and had a wide linear relation of 0.01-25 nmol/L. This assay has the ability of single-base mismatch recognition and could identify microRNA-21 with high specificity. Most importantly, this approach was successfully applied to the detection of plasma exosomal microRNA-21 in patients with lung cancer, and it is proposed that other targets can also be detected by changing the FAM-H1 and FAM-H2 corresponding to the target sequence. Thus, a novel, hands-on strategy for liquid biopsy was proposed and has a potential application value in the early diagnosis of lung cancer.

11.
IEEE Trans Image Process ; 30: 8059-8074, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34534087

RESUMO

We propose a new model for no-reference video quality assessment (VQA). Our approach uses a new idea of highly-localized space-time (ST) slices called Space-Time Chips (ST Chips). ST Chips are localized cuts of video data along directions that implicitly capture motion. We use perceptually-motivated bandpass and normalization models to first process the video data, and then select oriented ST Chips based on how closely they fit parametric models of natural video statistics. We show that the parameters that describe these statistics can be used to reliably predict the quality of videos, without the need for a reference video. The proposed method implicitly models ST video naturalness, and deviations from naturalness. We train and test our model on several large VQA databases, and show that our model achieves state-of-the-art performance at reduced cost, without requiring motion computation.

12.
Chin Med J (Engl) ; 134(14): 1687-1694, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34397595

RESUMO

BACKGROUND: Computed tomography images are easy to misjudge because of their complexity, especially images of solitary pulmonary nodules, of which diagnosis as benign or malignant is extremely important in lung cancer treatment. Therefore, there is an urgent need for a more effective strategy in lung cancer diagnosis. In our study, we aimed to externally validate and revise the Mayo model, and a new model was established. METHODS: A total of 1450 patients from three centers with solitary pulmonary nodules who underwent surgery were included in the study and were divided into training, internal validation, and external validation sets (n = 849, 365, and 236, respectively). External verification and recalibration of the Mayo model and establishment of new logistic regression model were performed on the training set. Overall performance of each model was evaluated using area under receiver operating characteristic curve (AUC). Finally, the model validation was completed on the validation data set. RESULTS: The AUC of the Mayo model on the training set was 0.653 (95% confidence interval [CI]: 0.613-0.694). After re-estimation of the coefficients of all covariates included in the original Mayo model, the revised Mayo model achieved an AUC of 0.671 (95% CI: 0.635-0.706). We then developed a new model that achieved a higher AUC of 0.891 (95% CI: 0.865-0.917). It had an AUC of 0.888 (95% CI: 0.842-0.934) on the internal validation set, which was significantly higher than that of the revised Mayo model (AUC: 0.577, 95% CI: 0.509-0.646) and the Mayo model (AUC: 0.609, 95% CI, 0.544-0.675) (P < 0.001). The AUC of the new model was 0.876 (95% CI: 0.831-0.920) on the external verification set, which was higher than the corresponding value of the Mayo model (AUC: 0.705, 95% CI: 0.639-0.772) and revised Mayo model (AUC: 0.706, 95% CI: 0.640-0.772) (P < 0.001). Then the prediction model was presented as a nomogram, which is easier to generalize. CONCLUSIONS: After external verification and recalibration of the Mayo model, the results show that they are not suitable for the prediction of malignant pulmonary nodules in the Chinese population. Therefore, a new model was established by a backward stepwise process. The new model was constructed to rapidly discriminate benign from malignant pulmonary nodules, which could achieve accurate diagnosis of potential patients with lung cancer.


Assuntos
Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Nódulo Pulmonar Solitário , Humanos , Pulmão , Neoplasias Pulmonares/diagnóstico por imagem , Medição de Risco , Nódulo Pulmonar Solitário/diagnóstico por imagem , Tomografia Computadorizada por Raios X
14.
Org Lett ; 23(17): 6780-6783, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34432980

RESUMO

An efficient K2CO3-catalyzed 1,4-addition/intramolecular cyclization/aromatization reaction of aurone-derived 1-azadienes with trisubstituted allenoates has been developed, giving a series of benzofuro[3,2-b]pyridines in moderate to excellent yields. The reaction proceeded efficiently under an air atmosphere without the use of transition metal catalysts. This protocol provides a concise approach to benzofuro[3,2-b]pyridines.

15.
Org Lett ; 23(14): 5571-5575, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34232667

RESUMO

A phosphine-catalyzed cascade annulation of Morita-Baylis-Hillman (MBH) carbonates and diazenes was achieved, giving tetrahydropyrazole-fused heterocycles bearing two five-membered rings in moderate to excellent yields. The reaction underwent an unprecedented reaction mode of MBH carbonates, in which two molecules of MBH carbonates were fully merged into the ring system.

16.
Chem Commun (Camb) ; 57(65): 8059-8062, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34296236

RESUMO

In this paper, an asymmetric allylic alkylation of easily available azomethine ylides with Morita-Baylis-Hillman (MBH) carbonates through a copper (i)/Lewis base cooperative catalysis strategy has been realized. The co-catalyzed asymmetric allylic alkylation provided the corresponding amino acid derivatives in up to 90% yields with up to 99% ee as well as good to excellent regioselectivity.

17.
Org Lett ; 23(15): 5750-5754, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34286988

RESUMO

In this paper, we designed and synthesized a new type of cyclic carbonates, allenylethylene carbonates (AECs). With AECs as reactive precursors, we developed palladium-catalyzed (3+3) annulation of AECs with nitrile oxides. Various AECs worked well in this reaction under mild reaction conditions. A variety of 5,6-dihydro-1,4,2-dioxazine derivatives with allenyl quaternary stereocenters can be accessed in a facile manner in high yields (≤98%).

18.
Adv Mater ; 33(29): e2006836, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34096113

RESUMO

Macromolecular films are crucial functional materials widely used in the fields of mechanics, electronics, optoelectronics, and biology, due to their superior properties of chemical stability, small density, high flexibility, and solution-processing ability. Their electronic and mechanical properties, however, are typically much lower than those of crystalline materials, as the macromolecular films have no long-range structural ordering. The state-of-the-art for producing highly ordered macromolecular films is still facing a great challenge due to the complex interactions between adjacent macromolecules. Here, the growth of textured macromolecular films on a designed graphene/high-index copper (Cu) surface is demonstrated. This successful growth is driven by a patterned potential that originates from the different amounts of charge transfer between the graphene and Cu surfaces with, alternately, terraces and step edges. The textured films exhibit a remarkable improvement in remnant ferroelectric polarization and fracture strength. It is also demonstrated that this growth mechanism is universal for different macromolecules. As meter-scale graphene/high-index Cu substrates have recently become available, the results open a new regime for the production and applications of highly ordered macromolecular films with obvious merits of high production and low cost.

19.
Spectrochim Acta A Mol Biomol Spectrosc ; 261: 120020, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34119770

RESUMO

DNA (cytosine-5)-methyltransferase1 (DNMT1) is the most abundant DNA methyltransferase in somatic cells, and it plays an important role in the initiation, occurrence, and rehabilitation of tumors. Herein, we developed a novel strategy for the detection of the level of DNMT1 in human plasma using the self-assembled nucleic acid probe signal amplification technology. In this method, the DNMT1 monoclonal antibody (McAbDNMT1) was immobilized on carboxyl magnetic beads to form immunomagnetic beads and then captured DNMT1 specifically. After that, DNMT1 polyclonal antibody (PcAbDNMT1) and biotinylated sheep anti-rabbit IgG (sheep anti rabbit IgG-Biotin) were sequentially added into the system to react with DNMT1 and form biotinylated double antibody sandwich immunomagnetic beads. In the presence of the bridging medium streptavidin, the biotinylated double antibody sandwich immunomagnetic beads would form a complex with biotinylated poly-fluorescein (Biotin-poly FAM), and the fluorescence intensity of the complex was proportional to the concentration of DNMT1. Immunomagnetic beads can capture the target DNMT1 in the sample, and Biotin-poly FAM can realize signal amplification. Using these strategies, we got a linear range of the system for DNMT1 level detection was from 2 nmol/L to 200 nmol/L, and the limit of detection (LOD) was 0.05 nmol/L. The method was successfully applied for the determination of DNMT1 in human plasma with the recovery of 101.3-106.0%. Therefore, this method has the potential for the detection of DNMT1 level in clinical diagnosis.


Assuntos
Biotina , DNA , Animais , Fluoresceína , Limite de Detecção , Coelhos , Ovinos , Estreptavidina
20.
Small ; 17(29): e2007174, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34047052

RESUMO

Exosomes, a class of small extracellular vesicles (30-150 nm), are secreted by almost all types of cells into virtually all body fluids. These small vesicles are attracting increasing research attention owing to their potential for disease diagnosis and therapy. However, their inherent heterogeneity and the complexity of bio-fluids pose significant challenges for their isolation. Even the "gold standard," differential centrifugation, suffers from poor yields and is time-consuming. In this context, recent developments in microfluidic technologies have provided an ideal system for exosome extraction and these devices exhibit some fascinating properties such as high speeds, good portability, and low sample volumes. In this review, the focus is on the state-of-the-art microfluidic technologies for exosome isolation and highlight potential directions for future research and development by analyzing the challenges faced by the current strategies.


Assuntos
Exossomos , Vesículas Extracelulares , Transporte Biológico , Exossomos/metabolismo , Humanos , Microfluídica
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