Aptamers are oligonucleotide sequences with a length of about 25–80 bases which have abilities to bind to specific target molecules that rival those of monoclonal antibodies. They are attracting ...great attention in diverse clinical translations on account of their various advantages, including prolonged storage life, little batch-to-batch differences, very low immunogenicity, and feasibility of chemical modifications for enhancing stability, prolonging the half-life in serum, and targeted delivery. In this Review, we demonstrate the emerging aptamer discovery technologies in developing advanced techniques for producing aptamers with high performance consistently and efficiently as well as requiring less cost and resources but offering a great chance of success. Further, the diverse modifications of aptamers for therapeutic applications including therapeutic agents, aptamer–drug conjugates, and targeted delivery materials are comprehensively summarized.
•Ultrasound can initiate polymerization above the threshold.•Ultrasonic time for ultrasonic initiation polymerization also has an optimal value.•Ultrasound-induced methdod is better than in-situ ...polymerization.
The two-dimensional material graphene has many excellent physicochemical properties such as large specific surface area, high electron migration rate, good chemical properties, good thermal conductivity, high elastic modulus and mechanical strength that make it very valuable for theoretical research and application in the preparation of graphene/polymer composites. In this paper, the effects of ultrasonic intensity and reaction time on the molecular weight and yield of PMMA under supercritical CO2 conditions were investigated. It was found that there are threshold and optimal values of ultrasonic intensity for initiating the reaction in supercritical CO2 system. The threshold value is 150 W/cm2 and the optimal ultrasonic intensity value is 225 W/cm2. There is also an optimal value of ultrasonic initiation time for ultrasonic initiation polymerization. Combining the reaction yield and the molecular weight of the product, 2 h of ultrasonic initiation is a suitable initiation reaction time. Based on the synthesis of PMMA by ultrasonic excitation, the preparation of Graphene/PMMA composites by ultrasound assistance was also investigated. The TG and DTG characterization of PMMA and complex materials prepared by ultrasonic excitation showed that the radicals generated by ultrasonic excitation were uniformly distributed and did not generate unsaturated double bonded polymers. The electrical conductivity of the Graphene/PMMA composites prepared by ultrasonic excitation at a graphene content of 1 wt% increased to 1.13 × 10-1 S/cm, which is better than that of the Graphene/PMMA prepared by in situ polymerization. This may be attributed to the ultrasound-assisted supercritical CO2 fluid action that resulted in a more uniform distribution of Graphene mixed with PMMA in the prepared composites. Therefore, it is of important practical significance for the preparation of Graphene/PMMA composites by ultrasound-induced polymerization.
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.
Fibrosis can develop in most organs and causes organ failure. The most common type of lung fibrosis is known as idiopathic pulmonary fibrosis, in which fibrosis starts at the lung periphery and then ...progresses toward the lung center, eventually causing respiratory failure. Little is known about the mechanisms underlying the pathogenesis and periphery-to-center progression of the disease. Here we discovered that loss of Cdc42 function in alveolar stem cells (AT2 cells) causes periphery-to-center progressive lung fibrosis. We further show that Cdc42-null AT2 cells in both post-pneumonectomy and untreated aged mice cannot regenerate new alveoli, resulting in sustained exposure of AT2 cells to elevated mechanical tension. We demonstrate that elevated mechanical tension activates a TGF-β signaling loop in AT2 cells, which drives the periphery-to-center progression of lung fibrosis. Our study establishes a direct mechanistic link between impaired alveolar regeneration, mechanical tension, and progressive lung fibrosis.
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•Impaired alveolar regeneration results in sustained elevated tension on alveoli•Elevated mechanical tension activates a TGF-β signaling loop in AT2 cells•The impacts of mechanical tension on alveoli are not uniformly distributed•Mechanical tension-activated TGF-β signaling is essential for fibrosis progression
By investigating links between impaired alveolar regeneration and progressive pulmonary fibrosis, Wu et al. found that the periphery-to-center progression of the most common type of lung fibrosis is driven by sustained elevated mechanical tension that activates a TGF-β signaling loop in alveolar stem cells.
Fig. 4 shows that the LA has been absorbed in the pores and on the surface of EP, and the edge of EP turns smooth and round. The porous structures of the EP provided the mechanical strength for the ...whole composites and prevented the seepage of the melted fatty acids and results in the excellent stability during durability test. due to the effects of capillary and surface tension force between the components of the composites.
•The best weight ratio of LA was 70%.•LA can be quite evenly dispersed in the porous skeleton of EP.•Physical interaction existing between the expanded perlite and the LA makes PCMs stable.
In this study, a form-stable lauric acid/expanded perlite (LA/EP) composite was prepared by absorbing paraffin into porous networks of expanded perlite. The form-stable composite was characterized by using Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), Scanning electron microscope (SEM) techniques, durability and leakage test. Leakage test results showed that optimum and maximum mass fraction of LA contained in the composite without leakage is 70wt.%. The FT-IR results revealed that there were physical interactions between the expanded perlite and the lauric acid. In addition, SEM images showed that LA can be quite evenly dispersed in the porous skeleton of EP. The melting temperature and latent heat of the form-stable EP/PA composite containing 70wt.% lauric acid were determined as 43.2°C and 105.58J/g, presenting its suitable phase transition temperature, sufficient latent heat, good thermal stability for application as composite phase change materials (PCMs). The durability test showed that the leakage problems of PCMs composite can be greatly prevented because of the interaction between the expanded perlite and the LA. All the results suggested that the form-stable EP/PA composite has great potential in building applications for thermal energy storage.
A kind of nitrogen doped carbon dots (NCDs) with excellent stable luminescence performance was prepared by pyrolysis using ethanolamine as precursor. By simply mixing solution of NCDs and ...calcein-Eu3+, a ratio fluorometric probe with carbon dots as "internal reference" and calcein-Eu3+ as recognition group was constructed for ATP detection. The fluorescence of the calcein can be selectively quenched by Eu3+, and can be restored when ATP was added because Eu3+ ions exhibit higher affinity to the oxygen-donor atoms originated from phosphates than that from carboxylate groups. Meanwhile, fluorescence of NCDs was not affected by Eu3+, calcein or ATP. By adding NCDs as "internal reference" in the above system, a new ratiometric strategy for detecting ATP was conducted. The dynamic linear range for ATP detection was 5.0 × 10−8 mol L−1~ 2.0 × 10−6 mol L−1, and the detection limit was 2.0 × 10−8 mol L−1.The method was successfully applied to detecting ATP in adenosine disodium triphosphate injection. Compared with calcein- Eu3+ probe without NCDs as reference, the ratio fluorometric probe effectively reduced interference and improved the accuracy and sensitivity.
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•The NCDs has excellent stable luminescence.•A ratio fluorometric ATP probe was constructed by mixing solution of NCDs and calcein-Eu3+.•Fluorescence of calcein quenched by Eu3+ and restored by ATP while fluorescence of NCDs was not affected.•The ratio fluorometric probe reduced interference and improved the accuracy and sensitivity.
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•"One-enzyme double catalysis" strategy for functionalizing wool was developed.•Laccase/TEMPO mediated oxidization and multi-crosslink between chitosan and wool.•The enzymatic ...mechanism between chitosan and wool was studied using their models.•Anti-felting property, wettability and dyeability of wool were greatly improved.
Chitosan is considered as a green additive with broad application prospects due to its advantages like biodegradability and antibacterial ability. Herein, we proposed an effective chitosan grafting approach via "one-enzyme double catalysis" strategy which aimed at functionalizing wool fibers to achieve bidirectionally multiple covalent crosslinking between chitosan and wool by laccase/2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) mediated oxidization. The mechanism was studied using models of wool and chitosan in terms of UV, FTIR, GPC and MALDI-TOF MS. Meanwhile, the structure and morphology of wool fiber grafted with chitosan were characterized by ATR-FTIR and SEM. Compared with untreated wool, this efficient method can significantly improve the dimensional stability to felting (2.53 %), wettability and dyeability of wool fabric, and can also compensate for the strength loss caused by the pretreatment. The present work provides a useful path for the enzymatic modification of keratin-containing fibers like wool using chitosan and other natural biopolymers with similar structure.
An indoxyl‐based strategy for the synthesis of indolines and indolenines via unprecedented aza‐pinacol and aza‐semipinacol rearrangements was developed. This method provides direct access to the core ...structures of several classes of indole alkaloids. The synthetic utility was demonstrated by the divergent synthesis of an array of functionalized polycyclic structures from a common intermediate and the formal total synthesis of the indoline natural product minfiensine. The reversed reactivity of indoxyl as a building block compared to that of indole offers a conceptually distinct disconnection strategy for indoline‐ and indolenine‐containing heterocycles and natural products.
Making other arrangements: The chemical synthesis of a diverse range of functionalized indolines/indolenines and the formal total synthesis of the indoline natural product minfiensine were achieved by using an indoxyl‐based strategy that proceeds via unprecedented aza‐pinacol rearrangements. This method provides direct access to the core structures of several classes of indole alkaloids by employing conceptually distinct bond disconnections.
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