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In this paper, a mild strategy for the oxidative cleavage of carbon-carbon bonds catalyzed by Lewis acid was developed in air condition at room temperature. Under such conditions, the bis-carbonyl compounds 3 were directly afforded from the reaction of D-ribose tosylate 1 and aniline in excellent yields through the oxidative cleavage of the key intermediate iminium-ion A and its tautomer enamine B. A series of N-arylated lactam-type iminosugars 5 were then successfully obtained by removing the isopropylidene group from 3 with the aid of the condensation agent DCC. Additionally, reduction of A and the removal of the isopropylidene group could provide N-arylated iminosugars 4. This strategy enables the oxidative cleavage of carbon-carbon bonds under mild conditions and facilitates the synthesis of the novel iminosugars with potent biological activity.
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An efficient and convenient strategy has been successfully developed for the preparation of novel furantetrahydroquinoline derivatives using d/l-ribose with a 2,3-O-isopropylidene group through the aza-Diels-Alder mechanism. This method has high atom and step economy, high stereoselectivity, and gram-scale synthesis (yield 67%).
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All pesticides are toxic by nature and pose short- or long-term safety risks to human or the environment, especially when they were used extensively and absence of safety measures. As a new insecticidal active compound with a novel mechanism of action, there is a serious inadequate of information on the hydrolytic behavior of broflanilide in the aqueous environment, as well as its degradation pattern in agricultural soils. In particular, the effects of temperature and pH of the aqueous environment on its hydrolytic behaviors and the dissipation pattern in different types of agricultural soils were still in a dark box. And the further understanding and insights into this insecticidal active ingredient were being deeply conditioned by these doubts. The hydrolysis behavior of broflanilide and the dissipation pattern in soil were systematically investigated by constructing hydrolysis systems with different temperatures and pH values, and conducting spiking experiments in different types of agricultural soil in the laboratory. The obtained results showed that the longest hydrolysis half-life of 10 mg/L broflanilide at 25 °C was 43.32 h (in pH 4.0 buffer), while it was only 12.84 h in pH 9.0 buffer. In pH 7.0 buffer, the hydrolysis rate of broflanilide exhibited a significant temperature dependence, as shown by the fact that for every 10 °C increase in the system temperature, the corresponding hydrolysis rate will increase about 1.5 times. The dissipation experiments in soils showed that broflanilide was most rapidly dissipated in fluvo-aquic soil (half-life of 1.94 days), followed by lime concretion black soil (half-life of 2.53 days) and cinnamon soil (half-life of 3.11 days), and slower in paddy soil (half-life of 4.03 days). It was indicated that broflanilide was a readily degradable pesticide in both aqueous environment and agricultural soil, and it was significantly affected by the temperature and pH of the system.
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Inseticidas , Praguicidas , Poluentes do Solo , Humanos , Solo/química , Hidrólise , Agricultura , Água , Poluentes do Solo/análiseRESUMO
Recently, gene therapy has become a subject of considerable research and has been widely evaluated in various disease models. Though it is considered as a stand-alone agent for COVID-19 vaccination, gene therapy is still suffering from the following drawbacks during its translation from the bench to the bedside: the high sensitivity of exogenous nucleic acids to enzymatic degradation; the severe side effects induced either by exogenous nucleic acids or components in the formulation; and the difficulty to cross the barriers before reaching the therapeutic target. Therefore, for the successful application of gene therapy, a safe and reliable transport vector is urgently needed. Extracellular vesicles (EVs) are the ideal candidate for the delivery of gene drugs owing to their low immunogenicity, good biocompatibility and low toxicity. To better understand the properties of EVs and their advantages as gene drug delivery vehicles, this review covers from the origin of EVs to the methods of EVs generation, as well as the common methods of isolation and purification in research, with their pros and cons discussed. Meanwhile, the engineering of EVs for gene drugs is also highlighted. In addition, this paper also presents the progress in the EVs-mediated delivery of microRNAs, small interfering RNAs, messenger RNAs, plasmids, and antisense oligonucleotides. We believe this review will provide a theoretical basis for the development of gene drugs.
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Vesículas Extracelulares , Ácidos Nucleicos , Humanos , Preparações Farmacêuticas , Vacinas contra COVID-19/metabolismo , Vesículas Extracelulares/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Terapia Genética , Ácidos Nucleicos/metabolismoRESUMO
This paper presents the data collection method and introduces the dataset about consumers' consider-then-choose behaviors in the household vacuum cleaner market. First, we designed a questionnaire that collected participants' consideration and choice data, social network data, demographic information, and preferences for product features. In addition, we obtained data on vacuum cleaner product features through web scraping from online shopping websites. After data cleaning and processing, the resulting dataset enables investigation into customer preferences in two stages, namely the consideration and choice stages and the impact of social influence on the two-stage decision-making process. This dataset is unique as it is the first of its kind to collect both customers' revealed preferences in a two-stage decision-making process and their ego social networks. This enables the modeling of customer preferences while accounting for social influence. The published survey questionnaire can be used as a template to collect data on other products in support of customer preferences modeling and the design for market systems.
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Three-dimensional (3D) graphene oxide (GO)-based aerogels, GO and 4-methyl-5-thiazoleethanol (MTZE) composites, were prepared by a facile hydrothermal method. Due to the hydrogen bonding and π-π stacking interactions, the produced 3D GO-MTZE composites possessed large cylindrical structures. The morphologies, composition, and chemical states of 3D GO-MTZE3:1 composite were characterized by Fourier transform infrared (FT-IR) spectroscopy, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and N2 adsorption-desorption isotherms based on the Brunauer-Emmett-Teller (BET) method. The existence of nitrogen (N)-containing heterocyclic system and oxygen (O)-containing branched chain of MTZE contributed to the formation of 3D structures, while the complexation effect of heterocyclic sulfur (S)- and N-containing functional groups of MTZE for metal cations dominated the adsorption performance of 3D GO-MTZE3:1 composite, which could selectively adsorb copper ions (Cu2+). In addition, the better hydrophobic property of 3D GO-MTZE3:1 composite facilitates its facile recycling from aqueous solution after adsorption. The adsorption data of 3D GO-MTZE3:1 composite toward Cu2+ fitted well (R2 = 0.9996) with the linear pseudo-second-order kinetic model, giving an equilibrium rate constant (k2) of 0.0187 g mg-1 min-1. The linear Langmuir isothermal model could more accurately describe the experimental data, indicating the adsorption process is mainly dominated by the complexation interactions between MTZE and Cu2+. The thermodynamic parameters of ΔG° (< 0), ΔH° (> 0), and ΔS° (> 0) further indicate that the adsorption is a spontaneous and endothermic, confirming that the complexation between Cu2+ and 3D GO-MTZE3:1 composite occurs. Due to its high selectivity for Cu2+, good hydrophobicity, and excellent stability, the developed 3D GO-MTZE3:1 composite possesses might be promisingly used in the aqueous selective enrichment/removal of Cu2+.
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Cobre , Grafite , Adsorção , Cobre/química , Grafite/química , Poluentes Químicos da Água/química , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Exosomes (Exos) as drug delivery vehicles have been widely used for cancer immunotherapy owing to their good biocompatibility, low toxicity, and low immunogenicity. Some Exos-based cancer immunotherapy strategies such as tuning of immunosuppressive tumor microenvironment, immune checkpoint blockades, and cancer vaccines have also been investigated in recent years, which all showed excellent therapeutic effects for malignant tumor. Furthermore, some Exos-based drug delivery systems (DDSs) for cancer immunotherapy have also undergone clinic trails, indicating that Exos are a promising drug delivery carrier. In this review, in order to promote the development of Exos-based DDSs in cancer immunotherapy, the biogenesis and composition of Exos, and Exos as drug delivery vehicles for cancer immunotherapy are summarized. Meanwhile, their clinical translation and challenges are also discussed. We hope this review will provide a good guidance for Exos as drug delivery vehicles for cancer immunotherapy.
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Exossomos , Neoplasias , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Portadores de Fármacos , Imunoterapia , Neoplasias/terapiaRESUMO
Hydrological characteristics since the Little Ice Age (LIA) could provide a good reference for current climate analysis and future climate prediction. However, the hydrological variation since the LIA and its driving mechanisms in Northeast Asia remain unclear, which has severely restricted our understanding on the past, present and future hydroclimate changes in these regions. Here we reconstruct the hydrological dynamics over the past 700 years using samples from the Hani peatland a subalpine peatland of Changbai Mountains to reveal these issues. The analytical results from plant macrofossil and grain-size of the HN-1 core and the integrated moisture/precipitation records across the entire Northeast Asia indicate that the hydrological environments in Northeast Asia were wetter conditions during the period of 1300-1700 AD, dry conditions during the period of 1700-1850 AD, and wet conditions during the period of 1850-2018 AD, respectively. The possible driving mechanisms for the hydrological variations in Northeast Asia since the LIA can be divided into three models. La Niña-like conditions induced wetter conditions in Northeast Asia from 1300 to 1700 AD. From 1700 to 1850 AD, strong volcanic aerosol effects superimposed on weaker La Niña-like conditions, resulting in dry conditions in Northeast Asia. However, El Niño-like conditions induced wet conditions in Northeast Asia from 1850 to 2018 AD. These driving models suggest that the teleconnected influence of solar activity/sunspot could control the hydrological dynamics in Northeast Asia on a decadal-centennial scale through the ENSO activities and Walker Circulation changes since the LIA. Based on the periodicity relationship between hydrological conditions and sunspot, it can be predicted that the moisutre conditions in Northeast Asia would gradually decrease from 2030 to 2085 AD, and gradually increase from 2085 to 2140 AD.
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Ketoprofen, a non-steroidal anti-inflammatory drug, can effectively relieve pain associated with arthritis, and microRNA-124 (miR-124) can inhibit the progression of the disease. In this study, poly (cyclohexane-1,4-diylacetone dimethylene ketal) (PCADK) nanoparticles (NPs) co-loaded with ketoprofen and miR-124 were successfully prepared using an emulsified solvent evaporation method. The co-loaded NPs exhibited a mean particle diameter of 160 nm. The acid sensitivity of the NPs was determined through in vitro release experiments. An adjuvant-induced arthritis rat model of arthritis was established for evaluating the pharmacodynamics of the NPs through clinical scoring and degree of swelling. The PCADK NPs exhibited more potent pharmacodynamic effects owing to the acid-sensitive properties of the carrier materials, compared with Poly (lactic-co-glycolic acid) (PLGA) NPs. Furthermore, PCADK co-loaded NPs exhibited superior anti-inflammatory effects compared to NPs loaded with either miR-124 or ketoprofen alone. In conclusion, co-delivery of ketoprofen and miR-124 through NPs is a promising strategy for the treatment of arthritis.
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Artrite Reumatoide , Cetoprofeno , MicroRNAs , Nanopartículas , Animais , Artrite Reumatoide/tratamento farmacológico , Portadores de Fármacos/uso terapêutico , Cetoprofeno/uso terapêutico , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , RatosRESUMO
Myeloid cell leukemia-1 (Mcl-1), a member of the Bcl-2 anti-apoptotic family, is overexpressed in the synovial macrophages of patients with rheumatoid arthritis (RA). Small interfering RNA (siRNA) Mcl-1 can induce macrophage apoptosis in the joints and is a potential therapeutic target of RA. Nevertheless, the application of siRNA is limited owing to its instability and susceptibility to degradation in vivo. To address these shortcomings, we developed composite microspheres (MPs) loaded with hyaluronic acid (HA)-chitosan (CS) nanoparticles (NPs). First, we synthesized HA-CS/siRNA NPs (HCNPs) using ionotropic gelation process. Then, HCNPs, as an internal aqueous phase, were loaded into poly (D, L-lactide-co-glycolide) (PLGA) and poly (cyclohexane-1,4-diyl acetone dimethylene ketal) (PCADK) MPs using the double emulsion method. The NPs-in-MPs (NiMPs) composite system provided sustained release of NPs, protected siRNA against nuclease degradation in the serum, and could readily cross the cellular membrane. In addition, we evaluated the advantages of NiMPs in an adjuvant-induced arthritis rat model. Our experimental results demonstrate that NiMPs have greater pharmacodynamic effects than common MPs. Meanwhile, compared with HCNPs, NiMPs reduced the frequency of drug administration. Therefore, NiMPs are a promising and novel siRNA delivery vehicle for RA therapy.
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Artrite Reumatoide , Quitosana , Nanopartículas , Animais , Artrite Reumatoide/tratamento farmacológico , Humanos , Ácido Hialurônico , Microesferas , RNA Interferente Pequeno , RatosRESUMO
The co-delivery of nanoparticles encapsulating gene therapies and chemotherapeutic drugs can achieve synergistic treatment and reduce side effects in normal tissues relative to the systemic use of single drug delivery. Activated macrophages play a fundamental role in the pathogenesis of rheumatoid arthritis (RA). Hyaluronic acid (HA), a natural polysaccharide, is a specific ligand for CD44 that is overexpressed on the surface of activated macrophages. In this study, HA-coated pH-responsive nanoparticles loaded with MCL-1 small interfering RNA (siRNA) and dexamethasone (HNPs/MD) were developed for RA treatment. The HNPs/MD had a mean particle size of 117.07 ± 2.21 nm and zeta potential of 15.53 ± 1.06 mV. The release rates of both MCL-1 siRNA and dexamethasone from the HNPs/MD at pH 4.5 and 6.0 were higher than those at pH 7.4, indicating that the nanoparticles were acid-sensitive. Cytotoxicity assays showed that compared with single drug loaded nanoparticles, the HNPs/MD showed higher cytotoxicity to activated macrophages. The superior therapeutic effect of HNPs/MD was demonstrated in an adjuvant-induced arthritis rat model. These findings indicate that pH-sensitive and HA-targeting co-delivery nanoparticles provide a new direction for the therapy of RA.
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Anti-Inflamatórios/administração & dosagem , Artrite Experimental/terapia , Dexametasona/administração & dosagem , Proteína de Sequência 1 de Leucemia de Células Mieloides/administração & dosagem , Nanopartículas/administração & dosagem , RNA Interferente Pequeno/administração & dosagem , Células 3T3 , Animais , Artrite Experimental/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Sistemas de Liberação de Medicamentos/métodos , Técnicas de Transferência de Genes , Masculino , Camundongos , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , Células PC12 , Células RAW 264.7 , RNA Interferente Pequeno/genética , Ratos , Ratos Sprague-DawleyRESUMO
A series of thiophene derivatives were synthesized by functionalization of 2,3-fused thiophene scaffolds. Their cytotoxicity was assessed against HeLa and Hep G2 cells. Compound 480 was identified as a promising candidate because of its low IC50 in HeLa (12.61 µg/mL) and Hep G2 (33.42 µg/mL) cells. The drug was loaded into folic acid (FA)-coated nanoparticles (NPs) to address its poor water solubility and to improve its selectivity for cancer cells. Compound 480 was shown to induce apoptosis by changes in mitochondrial membrane potential (ΔΨm) and the reactive oxygen species level. Furthermore, FA-modified NPs enhanced uptake capacity compared to unmodified controls by flow cytometry. This drug delivered in folate nanocarriers is promising for the treatment of cancers.