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Aptamers have been widely researched and applied in nanomedicine due to their programmable, activatable, and switchable properties. However, there are few reviews on aptamer-controlled stimuli-responsive drug delivery. This article highlights the mechanisms and advantages of aptamers in the construction of stimuli-responsive drug delivery systems. We summarize the assembly/reconfiguration mechanisms of aptamers in controlled release systems. The assembly and drug release strategies of drug delivery systems are illustrated. Specifically, we focus on the binding mechanisms to the target and the factors that induce/inhibit the binding to the stimuli, such as strand, pH, light, and temperature. The applications of aptamer-based stimuli-responsive drug release are elaborated. The challenges are discussed, and the future directions are proposed.

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In response to the escalating demand for flexible devices in applications such as wearables, sensors, and touch panels, there is a need for innovative fabrication approaches for devices made from nanomaterial-based inks. Subsequent to ink deposition, a pivotal stage in device manufacturing typically involves high-temperature sintering, posing challenges for heat-sensitive substrates. Nonthermal plasma jet sintering utilizing an atmospheric pressure dielectric barrier discharge (DBD) plasma jet enables sintering at room temperature and standard pressure, facilitating the sintering of printed nanoparticle films without compromising substrate or film surface integrity. However, determining optimal plasma jet sintering conditions can be challenging due to multiple processing variables with intricate interrelationships. This work employed Bayesian optimization (BO) and machine learning (ML) to identify optimal values for seven primary plasma jet sintering variables. Optimization yielded a 99.2% increase in the measured electrical conductivity for plasma jet-sintered indium tin oxide (ITO) films after five rounds of experiments. Moreover, the optimal sintering conditions achieved an electrical conductivity that was 81.4% of conventional furnace sintering at 300 °C, but was three times faster and with a peak substrate temperature below 47 °C. This result demonstrates the prospect of applying BO to optimize processing techniques for emerging low-temperature requirements.

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Chemoenzymatic strategies that combine synthetic and enzymatic transformations offer efficient approaches to yield target molecules, which have been increasingly employed in the synthesis of bioactive natural products. In the biosynthesis of macrocyclic nonribosomal peptides, polyketides, and their hybrids, thioesterase (TE) domains play a significant role in late-stage macrocyclization. These domains can accept mimics of native substrates in vitro and exhibit potential for use in total synthesis. This review summarizes the recent advances of TE domains in the chemoenzymatic synthesis for these natural products that aim to address the common issues in classical synthetic approaches and increase synthetic efficiencies, which have the potential to facilitate further pharmaceutical research.

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PURPOSE: Cervical cancer (CC) ranks the fourth among female malignancies and has become a dominating cause for tumor-associated death nowadays. More and more documents have proposed that long noncoding RNAs (lncRNAs), which emerge as pivotal biomarkers, actively participate in the regulation of human carcinomas. LncRNA ROR1-AS1 is a recently identified RNA that is highlighted for its crucial role in the biological processes of cancers. However, the role and molecular mechanism of ROR1-AS1 in CC have not been clarified yet. METHODS AND RESULTS: In the current study, RT-qPCR analysis uncovered that ROR1-AS1 expression was evidently upregulated in CC tissues and cell lines. Functional experiments (CCK-8, EdU, TUNEL, wound healing and Transwell assays as well as western blot analysis) revealed that knockdown of ROR1-AS1 markedly suppressed the malignant phenotypes of CC cells via decreasing cell viability, proliferation, migration, invasion and autography, and facilitating cell apoptosis. Subsequently, by performing luciferase reporter and RNA pulldown assays, miR-670-3p was identified to be sponged by ROR1-AS1. Additionally, STC2 was disclosed to be targeted by miR-670-3p in CC cells. Rescue assays illuminated that upregulation of STC2 counteracted ROR1-AS1 knockdown-induced suppression on CC cell growth. CONCLUSIONS: These data suggested that ROR1-AS1 contributed to the malignant properties of CC cells through sponging miR-670-3p and upregulating of STC2.

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Studies on the third-generation of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) targeting EGFRL858R/T790M mutant remain hotspots, specifically for non-small cell lung cancer (NSCLC). In the current study, a new series of EGFR-TKIs with thieno[3,2-d]pyrimidine derivatives(6a-6r) bearing quinolin-2(1H)-ones were designed and synthesized, through conformational constrained strategy from the third generation of EGFR-TKI olmutinib. In vitro structure-activity relationship (SAR) studies indicated that compounds 6a, 6l, 6m, 6n and 6o exhibited good selective inhibition to EGFRL858R/T790M (IC50 ≤ 250 nM) over wild type EGFR (IC50 > 10000 nM). The observed selectivity of compounds 6l and 6o was also proved by the computational molecular docking and the cellular thermal shift assay. These compounds had good growth inhibitory effect on the four tested cancer cell lines. Specifically, 6o could significantly inhibit the colony formation, wound healing and the expression of p-EGFR and its downstream p-ERK in EGFRL858R/T790M H1975 lung cancer cells. Our findings suggest that the thieno[3,2-d]pyrimidine compounds, especially 6l and 6o, can selectively target the mutant EGFRL858R/T790M in vitro and at cellular level and may serve as the lead compounds for generating new series of the third-generation EGFR-TKIs.

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