Aptamers are short DNA/RNA oligonucleotides capable of binding to target molecules with high affinity and specificity. The process of selecting an aptamer is called Systematic Evolution of Ligands by Exponential Enrichment (SELEX). Thanks to the inherit merits, aptamers have been used in a wide range of applications, including disease diagnosis, targeted delivery agents and therapeutic uses. To date, great achievements regarding the selection, modifications and application of aptamers have been made. However, few aptamer-based products have already successfully entered into clinical and industrial use. Besides, it is still a challenge to obtain aptamers with high affinity in a more efficient way. Thus, it is important to comprehensively review the current shortage and achievement of aptamer-related technology. In this review, we first present the limitations and notable advances of aptamer selection. Then, we compare the different methods used in the kinetic characterization of aptamers. We also discuss the impetus and developments of the clinical application of aptamers.
Paclitaxel (PTX) is among the most commonly used first-line drugs for cancer chemotherapy. However, its poor water solubility and indiscriminate distribution in normal tissues remain clinical challenges. Here we design and synthesize a highly water-soluble nucleolin aptamer-paclitaxel conjugate (NucA-PTX) that selectively delivers PTX to the tumor site. By connecting a tumor-targeting nucleolin aptamer (NucA) to the active hydroxyl group at 2′ position of PTX via a cathepsin B sensitive dipeptide bond, NucA-PTX remains stable and inactive in the circulation. NucA facilitates the uptake of the conjugated PTX specifically in tumor cells. Once inside cells, the dipeptide bond linker of NucA-PTX is cleaved by cathepsin B and then the conjugated PTX is released for action. The NucA modification assists the selective accumulation of the conjugated PTX in ovarian tumor tissue rather than normal tissues, and subsequently resulting in notably improved antitumor activity and reduced toxicity.
SummaryOut of 168 Arabidopsis accessions screened with isolates of Leptosphaeria maculans, one (An-1) showed clear disease symptoms. In order to identify additional components involved in containment of L. maculans in Arabidopsis, a screen for L. maculans-susceptible (lms) mutants was performed. Eleven lms mutants were isolated, which displayed differential susceptibility responses to L. maculans. lms1 was crossed with Columbia (Col-0) and Ws-0, and mapping data for both populations showed the highest linkage to a region on chromosome 2. Reduced levels of PR-1 and PDF1.2 expression were found in lms1 compared to wild-type plants 48 h after pathogen inoculation. In contrast, the lms1 mutant displayed upregulation of either marker gene upon chemical treatment, possibly as an effect of an altered ethylene (ET) response. To assess the contribution of different defence pathways, genotypes implicated in salicylic acid (SA) signalling plants expressing the bacterial salicylate hydroxylase (nahG) gene, non-expressor of PR1 (npr1 )-1 and phytoalexin-de®cient (pad4-1 ), jasmonic acid (JA) signalling (coronatine insensitive (coi )1-16, enhanced disease susceptibility (eds )8-1 and jasmonic acid resistant (jar)1-1 ) and ET signalling (eds4-1, ethylene insensitive (ein )2, ein3-1 and ethylene resistant (etr)1-1 ) were screened. All the genotypes screened were as resistant as wild-type plants, demonstrating the dispensability of the pathways in L. maculans resistance. When mutants implicated in cell death responses were assayed, responsive to antagonist 1 (ran1 )-1 exhibited a weak susceptible phenotype, whereas accelerated cell death (acd )1-20 showed a rapid lesion development. Camalexin is only partially responsible for L. maculans containment in Arabidopsis, as pad3-1 and enhanced susceptibility to Alternaria (esa )1 clearly showed a susceptible response while wild-type levels of camalexin were present in An-1 and lms1. The data presented point to the existence of multiple defence mechanisms controlling the containment of L. maculans in Arabidopsis.
The electro-reforming of polymer plastic waste and CO2 has the merits for producing value-added chemicals and alleviating environmental pollution. Herein, we report an electrocatalytic integrating strategy for efficient valorization of poly(ethylene terephthalate) (PET) plastic and CO2 to simultaneously produce formic acid at both anode and cathode. The NiCo2O4 electrocatalyst displays a high Faradaic efficiency of 90% for formic acid production, which indicates the excellent selectivity for PET hydrolysate oxidation. By coupling the PET hydrolysate oxidation reaction with the CO2 reduction reaction, the assembled electrolyzer exhibits a low cell voltage of 1.55 V to drive the integrated two half-reactions. Furthermore, a high Faradaic efficiency of 155% for formic acid can be achieved at a cell voltage of 1.90 V. This study suggests that electrocatalytic valorization of PET plastic coupling with CO2 reduction could be an energy-efficient and economically viable strategy to realize the production of value-added chemicals.
Summary1. Previous studies have demonstrated that poplar is sexually dimorphic in its responses to environmental stresses and provided evidence of sex-related differences in protein composition, gene transcription and morphological and physiological processes. However, sexual competition of poplar has not yet been studied. 2. We employed Populus cathayana males and females as a model to investigate intra-and intersexual competition under well-watered condition and drought stress. 3. Our results indicated that competition significantly affected sexual dimorphism of P. cathayana under different watering regimes. Sexual competition was environment-dependent and modified by drought. In females, drought intensified the negative effect of intrasexual competition. Similar resource utilization patterns of females may aggravate pressure for resources under drought stress. Under intersexual competition, females showed a greater competitive ability than males under well-watered condition, while males showed a slight competitive advantage under drought stress. Intersexual competition seems to alleviate the sexual dimorphism of P. cathayana in response to drought stress, as females increase fitness and males decrease fitness compared with intrasexual competition. 4. Sexual dimorphism in resource utilization patterns and niche segregation may contribute to sexual competition in a given environment. Sexual competition was found to affect competitive ability and fitness of both sexes, which may cause spatial segregation of sexes in P. cathyana populations.
Recurrent Neural Networks (RNNs) and their variants, such as Long-Short Term Memory (LSTM) networks, and Gated Recurrent Unit (GRU) networks, have achieved promising performance in sequential data modeling. The hidden layers in RNNs can be regarded as the memory units, which are helpful in storing information in sequential contexts. However, when dealing with high dimensional input data, such as video and text, the input-to-hidden linear transformation in RNNs brings high memory usage and huge computational cost. This makes the training of RNNs very difficult. To address this challenge, we propose a novel compact LSTM model, named as TR-LSTM, by utilizing the low-rank tensor ring decomposition (TRD) to reformulate the input-to-hidden transformation. Compared with other tensor decomposition methods, TR-LSTM is more stable. In addition, TR-LSTM can complete an end-to-end training and also provide a fundamental building block for RNNs in handling large input data. Experiments on real-world action recognition datasets have demonstrated the promising performance of the proposed TR-LSTM compared with the tensortrain LSTM and other state-of-the-art competitors.
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