Latest ArticlesPoint mutations can be used as biomarkers to perform diagnosis for diseases. In this study, a nanorobot for low-abundance point mutation enrichment was constructed using DNA origami. The novel design achieved limits of detection of 0.1% and 1% for synthesized DNA samples and clinical gene samples, respectively. Resettability was a key property of this method, which also involved a simpler process, lower cost and shorter detection duration than traditional enrichment methods. This novel DNA nanorobot may enable the detection of tumor markers, potentially facilitating early cancer diagnosis.
A novel meroterpenoid, named meroterpenthiazole A (1), was isolated from the deep-sea-derived Penicillium allii-sativi. Its structure was established by extensive spectroscopic and computational methods. Meroterpenthiazole A bears a rare benzothiazole moiety in nature. Compound 1 significantly inhibited retinoid X receptor (RXR)-α transcriptional effect (KD = 12.3 µmol/L) through a novel binding mechanism.
The construction of all-carbon molecule frameworks remains challenging. Herein, we report a facile and efficient one-pot synthesis of a novel all-carbon stair containing dimerized pentalene core using inexpensive cyclopropyl alkyne catalyzed by in situ generated Cu(I) from the comproportionation reaction of Cu(II) salt and Cu powder under mild reaction conditions. The reaction proceeds via sequential acetylenic coupling, followed by cyclization and [2 + 2] cycloaddition to directly produce pentalene dimer, which is difficult to access by other established methods. Different mechanistic paths were studied for the pentalene formation using density functional theory, suggesting that the reaction also proceeds through acetylenic coupling followed by cyclization and [2 + 2] cycloaddition. Based on the activation energy barriers, Path 1 has the rate-determining step of 38.63 kcal/mol, which is the most thermodynamically preferred one among the four paths.
Neuroinflammation plays a significant role in inducing depression-like behavior. Tetrahedral DNA nanostructures (TDNs) are molecules that exhibit anti-inflammatory properties and can effectively penetrate the blood-brain barrier. Thus, researchers have hypothesized that TDNs regulate the secretion of proinflammatory cytokines and consequently alleviate depression-like behavior. To test this hypothesis, we investigated the effect of TDNs on the depression-like behavior of C57 mice induced by lipopolysaccharide (LPS). We performed open-field, tail suspension, and sucrose preference tests on LPS- and LPS/TDN-treated mice. The results indicated that the injection of TDNs into LPS-treated mice resulted in increased velocity, center zone duration, frequency to the center zone, and sucrose preference, and decreased immobility time. Immunofluorescence results indicated that peripheral administration of LPS in the mice activated inflammation, which culminated in distinct depression-like behavior. However, TDNs effectively alleviated the inflammation and depression-like behavior through the reduction of the expression levels of proinflammatory cytokines, such as interleukin-1β and tumor necrosis factor-α in the brain. Additionally, TDNs normalized the expression level of microglia cell activation markers, such as ionized calcium binding adaptor molecule 1, in the hippocampus of mice. These results indicated that TDNs attenuated the LPS-induced secretion of inflammatory factors and consequently alleviated depression-like behavior.
Since self-assembled peptide hydrogels can solve the problems such as low solubility, poor selectivity and serious adverse effects of traditional chemotherapy drugs, they have been widely used as carrier materials for drug delivery. In this study, we developed a novel and injectable drug delivery platform for the antitumor drug doxorubicin (DOX) using a pH-responsive ionic-complementary octapeptide FOE. This octapeptide could self-assemble into stable hydrogel under neutral conditions, while disassemble under the tumor microenvironment. Especially, at pH 5.8, its micromorphology displayed a transition from nanofibers to nanospheres with the change of secondary structure, which enhanced cellular uptake of DOX. In addition, FOE hydrogel serves as a smart drug reservoir by localized injection to achieve sustained drug release and improve antitumor efficacy. This octapeptide opens up new avenues for promoting the clinical translation of anticancer drugs on account of excellent injectable properties and economic benefits of simple and short sequence.
In this work, a simple gold nanoparticles (AuNPs) based colorimetric biosensor was developed for chlorpyrifos (Chl) detection using an aptamer as the capture probe. The Chl-aptamer with low dissociation constant (Kd) of 58.59 ± 6.08 nmol/L was selected by ssDNA library immobilized systematic evolution of ligands by enrichment (SELEX). In the absence of Chl, the Chl-aptamer acted as the stabilizer for AuNPs in salt solution. In the presence of Chl, the highly specific Chl-aptamer bound with Chl targets immediately, thus a self-aggregation of AuNPs induced by salt was displayed. The fabricated colorimetric aptasensor exhibited an excellent sensitivity for Chl detection with the LOD as low as 14.46 nmol/L. In addition, the aptasensor was applied to test Chl in tap water, cucumber and cabbage samples, the excellent recoveries with acceptable RSD values below 5% demonstrated that the method can be considered as a promising tool for simple, rapid Chl detection.
Dual specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) is an evolutionarily conserved protein kinase belonging to the CMGC kinase family, which is closely related to Down syndrome (DS) and Alzheimer's disease (AD). In recent years, not only the treatment of diabetes, but also the treatment of cancer gradually focuses on targeting DYRK1A. Therefore, a series of DYRK1A inhibitors have been developed to treat relevant diseases and clarify their treatment mechanism furtherly. DYRK1A inhibitors are mainly divided into natural products and synthetic compounds. Among them, harmine is an excellent DYRK1A inhibitor. Therefore, the synthetic DYRK1A inhibitors are mainly based on harmine, which greatly enriches the structure and quantity of DYRK1A inhibitors. The interaction between the inhibitors and the DYRK1A protein has a guiding significance in predicting the activity of the inhibitors, and plays an irreplaceable role in the design of the compounds. This paper mainly reviews DYRK1A inhibitors found in recent years and their structure-activity relationship, looking forward to providing a theoretical basis for the development of DYRK1A inhibitors.
The development of green and convenient methods for C–S bond formation has received significant attention because C–S bond widely occurs in many important pharmaceutical and biological compounds. Recently, visible-light photoredox catalysis has been established as an efficient and general tool for the construction of C–C and C-heteroatom bonds. In this review, we have focused on the research on recent advances in C–S bond formation via visible-light photoredox catalysis, and the growing opportunities they present to the construction of complex chemical scaffolds for applications encompassing bioactive molecules synthesis, synthetic methodology development, and sulfur-containing drugs. We hope that this review will provide chemists with a synthetic tool that will open the door to further development of organsulfur chemistry
Photodynamic therapy (PDT) has been widely investigated for cancer therapy. The intracellular accumulation of reactive oxygen species (ROS)-damaged protein facilitates tumor cell apoptosis. However, there is growing evidence that the ubiquitin-proteasome pathway (UPP) significantly impedes PDT by preventing the enrichment of ROS-damaged proteins in tumor cells. To tackle this challenge, we report a facile dual-drug nanoassembly based on the discovery of an interesting co-assembly of bortezomib (BTZ, a proteasome inhibitor) and pyropheophorbide a (PPa) for proteasome inhibition-mediated PDT sensitization. The precisely engineered nanoassembly with the optimal dose ratio of BTZ and PPa demonstrates multiple advantages, including simple fabrication, high drug co-loading efficiency, flexible dose adjustment, good colloidal stability, long systemic circulation, favorable tumor-specific accumulation, as well as significant enrichment of ROS-damaged proteins in tumor cells. As a result, the cooperative nanoassembly exhibits potent synergistic antitumor activity in vivo. This study provides a novel dual-drug engineering modality for multimodal cancer treatment.
miRNA, which is a common non-coding RNA, can target various mRNAs to regulate their physiological activities. Therefore, miRNAs play an important role in various physiological and pathological processes, and so they have been proposed as a powerful tool to treat different diseases efficiently. However, the characteristic of miRNA degradation in vivo limits its further clinical application. Exosomes have the advantage of crossing the biological barrier and achieving long-distance communication with cells, so they are excellent vectors for miRNAs. By studying the biogenesis of exosomes, the way for loading miRNAs, the mechanism of targeting, and disease occurrence and development, it is confirmed that exosomes can enrich specific endogenous miRNAs and regulate a variety of physiological activities, such as promoting cancer cell apoptosis, regulating lipid metabolism and promoting angiogenesis. It is shown that exosomes loaded with miRNAs have good performance in the fields of cancer, neurodegenerative diseases, cardiovascular disease treatment, and regenerative medicine. In this paper, the application and research progress of exosomes carrying miRNA in the above fields are systematically described.
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