A novel and practical fluoroalkyl radical-initiated cascade reaction was developed to access diverse 2-fluoroalkylbenzothiazoles by reacting various fluoroalkyl radical sources, including ...perfluoroalkyl iodide (IC n F2n+1, n = 3–8, 10), ICF(CF3)2, ICF2COOEt, ICF2CF2Cl, or ICF2CF2Br, tetramethylethane-1,2-diamine (TMEDA), and 2-isocyanoaryl thioethers in tetrahydrofuran under nitrogen atmosphere and blue-light irradiation conditions. Furthermore, this one-pot protocol could well be expanded to access various 2-fluoroalkylbenzoselenazoles starting from (2-isocyanophenyl)(methyl)selane, perfluoroalkyl iodides (IC n F2n+1, n = 3–8) or ICF2COOEt and TMEDA.
The transcription factor MYC is deregulated in almost all human cancers, especially in aggressive lymphomas, through chromosomal translocation, amplification, and transcription hyperactivation. Here, ...we report that high expression of tribbles homologue 3 (TRIB3) positively correlates with elevated MYC expression in lymphoma specimens; TRIB3 deletion attenuates the initiation and progression of MYC-driven lymphoma by reducing MYC expression. Mechanistically, TRIB3 interacts with MYC to suppress E3 ubiquitin ligase UBE3B-mediated MYC ubiquitination and degradation, which enhances MYC transcriptional activity, causing high proliferation and self-renewal of lymphoma cells. Use of a peptide to disturb the TRIB3-MYC interaction together with doxorubicin reduces the tumor burden in Myc
mice and patient-derived xenografts. The pathophysiological relevance of UBE3B, TRIB3 and MYC is further demonstrated in human lymphoma. Our study highlights a key mechanism for controlling MYC expression and a potential therapeutic option for treating lymphomas with high TRIB3-MYC expression.
Adsorption is a widely applied technique in producing high‐purity chemicals with advantages of low energy consumption, high selectivity, and mild operating conditions. However, traditional adsorbents ...have inflexible properties and suffer from the trade‐off between selective adsorption and efficient desorption. Recently, the emerging photoresponsive adsorbents have provided new avenues for adsorption techniques. Active sites of photoresponsive adsorbents can be regulated through steric hindrance or tunable adsorbent‐adsorbate interactions. Therefore, variation in adsorptive capacity is able to readily achieve through photomodulation, and the corresponding adsorption/desorption cycles are energy‐saving. This concept mainly summarizes recent efforts on the fabrication and application of photoresponsive adsorbents with tunable active sites. Also, the future opportunities and critical challenges of photoregulation on adsorptive sites are presented.
Photomodulation on adsorptive sites is an emerging strategy to achieve selective adsorption and efficient desorption. Compared with traditional adsorption techniques, active sites of photoresponsive adsorbents can be flexibly regulated by light irradiation based on the demands of adsorption process. This concept summarizes recent advances in this field and highlights the exquisite strategies of photoregulation on active sites.
Special delivery! An aptamer-directed anticancer drug was molecularly engineered to be delivered to target cells for efficient therapeutic application. The covalent conjugation of drug and aptamer ...creates alternative opportunities for targeted therapy, as multiple yet specific aptamers can be "generated" relatively easily by cell-SELEX for any target cells; this demonstrates the full potential of cell-SELEX as a molecular discovery tool for biomedical studies and drug development.The conjugation of antitumor drugs to targeting reagents such as antibodies is a promising method that can increase the efficacy of chemotherapy and reduce the overall toxicity of the drugs. In this study, we covalently link the antitumor agent doxorubicin (Dox) to the DNA aptamer sgc8c, which was selected by the cell-SELEX method. In doing so, we expected that this sgc8c-Dox conjugate would specifically kill the target CCRF-CEM (T-cell acute lymphoblastic leukemia, T-cell ALL) cells, but with minimal toxicity towards nontarget cells. The results demonstrated that the sgc8c-Dox conjugate possesses many of the properties of the sgc8c aptamer, including high binding affinity (Kd=2.0±0.2 nM) and the capability to be efficiently internalized by target cells. Moreover, due to the specific conjugation method, the acid-labile linkage connecting the sgc8c-Dox conjugate can be cleaved inside the acidic endosomal environment. Cell viability tests demonstrate that the sgc8c-Dox conjugates not only possess potency similar to unconjugated Dox, but also have the required molecular specificity that is lacking in most current targeted drug delivery strategies. Furthermore, we found that nonspecific uptake of membrane-permeable Dox to nontarget cell lines could also be inhibited by linking the drug with the aptamer; thus, the conjugates are selective for cells that express higher amounts of target proteins. Compared to the less effective Dox-immunoconjugates, these sgc8c-Dox conjugates make targeted chemotherapy more feasible with drugs having various potencies. When combined with the large number of recently created DNA aptamers that specifically target a wide variety of cancer cells, this drug-aptoconjugation method will have broad implications for targeted drug delivery.
A simple and efficient decarboxylative radical addition/cyclization strategy was developed, by which a wide range of benzimidazo2,1-aisoquinoline-6(5H)-ones were prepared in one-pot via reaction of ...functionalized 2-arylbenzoimidazoles and carboxylic acids in the presence of K2S2O8/AgNO3 under mild reaction conditions.
A significant advance toward achieving practical applications of graphene as a two-dimensional material in nanoelectronics would be provided by successful synthesis of both n-type and p-type doped ...graphene. However, reliable doping and a thorough understanding of carrier transport in the presence of charged impurities governed by ionized donors or acceptors in the graphene lattice are still lacking. Here we report experimental realization of few-layer nitrogen-doped (N-doped) graphene sheets by chemical vapor deposition of organic molecule 1,3,5-triazine on Cu metal catalyst. When reducing the growth temperature, the atomic percentage of nitrogen doping is raised from 2.1% to 5.6%. With increasing doping concentration, N-doped graphene sheet exhibits a crossover from p-type to n-type behavior accompanied by a strong enhancement of electron–hole transport asymmetry, manifesting the influence of incorporated nitrogen impurities. In addition, by analyzing the data of X-ray photoelectron spectroscopy, Raman spectroscopy, and electrical measurements, we show that pyridinic and pyrrolic N impurities play an important role in determining the transport behavior of carriers in our N-doped graphene sheets.
Post-operative thirst is common and may cause intense patient discomfort. The aims of this retrospective study conducted in a high-volume post-anesthesia care unit (PACU) were as follows: (1) to ...examine the prevalence of moderate-to-severe post-operative thirst-defined as a numerical rating scale (NRS) score of 4 or higher, (2) to identify the main risk factors for moderate-to-severe post-operative thirst, and (3) to maximize the efficacy and safety of thirst management through a quality improvement program. During a 1-month quality improvement program conducted in August 2018, a total of 1211 adult patients admitted to our PACU were examined. Moderate-to-severe thirst was identified in 675 cases (55.8%). The use of glycopyrrolate during anesthesia was associated with moderate-to-severe thirst (71.7% versus 66.4%, respectively, p = 0.047; adjusted odds ratio: 1.46, p = 0.013). Following a safety assessment, ice cubes, room temperature water, or an oral moisturizer were offered to patients. A generalized estimating equation model revealed that ice cubes were the most effective means for thirst management-resulting in an estimated thirst intensity reduction of 0.93 NRS points at each 15-min interval assessment (p < 0.001)-followed by room temperature water (- 0.92/time-point, p < 0.001) and the oral moisturizer (- 0.60/time-point; p < 0.001). Patient satisfaction (rated from 1 definitely dissatisfied to 5 very satisfied) followed a similar pattern (ice cubes: 4.22 ± 0.58; room temperature water: 4.08 ± 0.55; oral moisturizer: 3.90 ± 0.55, p < 0.001). The use of glycopyrrolate-an anticholinergic agent that reduces salivary secretion-was the main independent risk factor for moderate-to-severe post-operative thirst. Our findings may provide clues towards an optimized management of thirst in the immediate post-operative period.
In the synthesis of dimethyl carbonate (DMC) by transesterification, CH
3
ONa has been commonly applied as a homogeneous catalyst due to its high catalytic activity, but its stability is ...unsatisfactory. Here, by studying the influence of ionic liquid base strength on transesterification, we prepared an organic base catalyst, potassium imidazole (KIm), with high catalytic activity and stability, which solved the problem of catalyst deactivation in transesterification. The results showed that when KIm was used in the synthesis of DMC from propylene carbonate (PC) and methanol (MeOH), the chemical equilibrium could be reached within 3 minutes and the yield of DMC reached 73.03%, indicating that KIm performed better in transesterification than the majority of previously reported catalysts. In addition, the activity of the catalyst had hardly decreased after ten cycles of reaction, which can well meet the requirements of industrial production.
A novel type of homogeneous catalyst KIm was developed and applied to the reaction of PC and MeOH to synthesize DMC.
An effective radical cascade cyclization strategy was developed, by which a wide range of 2-phosphoryl-substituted quinoxalines were prepared in one pot via reaction of ortho-diisocyanoarenes with ...diarylphosphine oxides in the presence of AgNO3 under mild reaction conditions.
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