Latest ArticlesTerminal deoxynucleotidyl transferase (TdT) has been characterized as template-independent polymerase using single-stranded DNA (ssDNA) as primers to generate random oligonucleotides. However, the extension performance of TdT to single-stranded RNA (ssRNA) is vague. By systematically comparing and contrasting the performance of TdT-catalyzed ssDNA and ssRNA extension, it is indicated that the catalytic efficiency of ssRNA as primers was about 3 times lower than ssDNA as primers. Collectively, it is believed that understanding the catalytic performance of TdT will help to design the strategy to synthesize chimeric DNA on 3′-OH of ssRNA, which becomes invaluable.
Polycyclic aromatic hydrocarbons (PAHs), are regarded as molecular fragments of graphene and are facilely available through chemical synthesis. Recently, it is found collective charge density oscillations with strong induced electromagnetic field display in PAH derivatives. This phenomenon, analogue to plasmonic excitation in metal, called molecular plasmonics, arise the significant interest of physicists. Instead of discussing its rich physics, this work aims at the application of molecular plasmon-like excitations in electrochromics and optoelectronics. We found that the energy and the intensity of plasmonic-like oscillation could be largely tuned by increasing the conjugation size along both the longitude/transverse axis in PAHs. Besides, the dimeric PAH demonstrates the possibility that molecular plasmonics could be designed using PAHs as building blocks for integration into larger molecular systems. Moreover, this work straightforwardly extends the molecular plasmonic-like property from CH composed PAHs to much more versatile planar conjugation systems with heteroatoms, achieving transferring between p-type and n-type organic semiconductors. Therefore, with the natural abundance, low cost, easily chemical synthesis of PAH derivatives, we believe this work paves the way for the application of molecular plasmonic-like properties in optoelectronics.
Designing a multifunctional scaffold with osteogenic and angiogenic properties holds promise for ideal bone regeneration. Innovative scaffold was here constructed by immobilizing exosomes derived from human bone mesenchymal stem cells (hBMSCs) onto porous polymer meshes which developed by PLGA and Cu-based MOF (PLGA/CuBDC@Exo). The synthesized exosome-laden scaffold capable of providing a dual cooperative controllable release of bioactive copper ions and exosomes that promote osteogenesis and angiogenesis, thereby achieving cell-free bone regeneration. In vitro assay revealed the composite stent not only substantially upregulated the expression of osteogenic-related proteins (ALP, Runx2, Ocn) and VEGF in hBMSCs, but promoted the migration and tube formation of the human umbilical vein endothelial cells (HUVECs). In vivo evaluation further confirmed this scaffold dramatically stimulated bone regeneration and angiogenesis in critical-sized defects in rats. Altogether, this composite scaffold carrying therapeutic exosomes had an osteogenic-angiogenic coupling effect and offered a new idea for cell-free bone tissue engineering.
An efficient palladium-catalyzed electrooxidation C–H acylation reaction of N-nitrosoanilines with α-oxocarboxylic acids was developed. The anodic oxidation of the Pd(Ⅱ) intermediate was found to be the key to complete the reaction. In this case, the N-nitroso group was observed to be an effective directing group for C–H activation reaction. Moreover, the synthetic transformation of derivatives of natural products (L-menthol, dehydroepiandrosterone, and pregnenolone) was successfully realized. Finally, flow electrochemical synthesis of some substrates was achieved.
The development of deep-red emitting lead-free metal-halide perovskites with high photoluminescence quantum yields (PLQYs) and outstanding stability remains a major challenge for displays and deep-tissue bioimaging. In this work, we report a facile and convenient solvothermal method to synthesize metal halides Cs2ZnX4 (X = Cl, Br) that however is PL innert at room temperature. Upon composition engineering utilizing Sn2+ as the dopant, the resulting Cs2ZnCl4: Sn not only emits strong deep-red PL peaked at 700 nm with the highest 99.4% PLQY among the similar materials so far, but also exhibits excellent structure stability in air (PLQY remains 96% after one year exposure to the atmosphere). Detailed experimental characterizations and theoretical calculations reveal that the deep-red emission stems from self-trapped excitons induced by the Sn2+ dopant. Particularly, triplet emission (3P2→1S0) from Sn-5s2 orbitals has been observed at low temperature due to the break of parity-forbidden transition. This work provides an important guidance for the development of deep-red light-emitting materials with low price, high efficiency and excellent stability.
Decades have passed since the first nanoparticles-base medicine was approved for human cancer treatment, and the research and development of nanoparticles for drug delivery are always undergoing. Nowadays, the significant advances complicate nanoparticles' branches, including liposomes, solid lipid nanoparticles, inorganic nanoparticles, micelles, nanovaccines and nano-antibodies, etc. These nanoparticles show numerous capabilities in treatment and diagnosis of stubborn diseases like cancer and neurodegenerative diseases, emerging as novel drug carriers or therapeutic agents in future. In this review, the complicated branches of nanoparticles are classified and summarized, with their property and functions concluded. Besides, there are also some delivery strategies that make nanoparticles smarter and more efficient in drug delivery, and frontiers in these strategies are also summarized in this review. Except these excellent works in newly-produced drug delivery nanoparticles, some points of view and future expectations are made in the end.
Cu2-xS nanostructures have been intensively studied as outstanding chemodynamic therapy (CDT) and good photothermal therapy (PTT) antibacterial agents due to their highly efficient Cu(Ⅰ)-initiated Fenton-like catalytic activity and good photothermal conversion property. However, they still suffer from shortage of Cu(Ⅰ) supply in the long-term and comparatively low inherent photothermal conversion efficiency. Herein, we constructed a self-enhanced synergistic PTT/CDT nanoplatform (Cu1.94S@MPN) by coating Cu1.94S nanoparticles with Fe(Ⅲ)/tannic acid based metal-polyphenol networks (MPN). Activated by the acidic bacterial infection microenvironment, Cu1.94S@MPN could be decomposed to continuously release Cu(Ⅱ), Fe(Ⅲ) ions and tannic acid. As the result of tannic acid-involved Cu and Fe redox cycling, Cu(Ⅰ)/Fe(Ⅱ)-rich CDT could be achieved through the highly accelerated catalytic Fenton/Fenton-like reactions. More importantly, experimental results demonstrated that Cu1.94S@MPN exhibited both excellent photothermal antibacterial and photothermal-enhanced CDT properties to eradicate bacteria in vitro and in vivo. Overall, this novel nanotherapeutics has great potential to become a clinic candidate for anti-infective therapy in future.
Heat shock protein 90 (Hsp90) is an appealing anticancer drug target that provoked a tremendous wave of investigations. Geldanamycin (GA) is the first identified Hsp90 inhibitor that exhibited potent anti-cancer activity, but the off-target toxicity associated with the benzoquinone moiety hampered its clinical application. Until now, structure optimization of GA is still in need to fully exploit the therapeutic value of Hsp90. Due to the structural complexity and synthetic challenge of this compound family, conventional optimization is bound to be costly but high efficiency is expected to be reachable by combining the art of rational design and total synthesis. Described in this paper is our first attempt at this approach aiming at rational modification of the C6-position of GA. The binding affinities towards Hsp90 of compound 1 (C6-ethyl) and 2 (C6-methyl) were designed and predicted by using Discovery Studio. These compounds were synthesized and further subjected to a thorough in vitro biological evaluation. We found that compounds 1 and 2 bind to Hsp90 protein with the IC50 of 34.26 nmol/L and 163.7 nmol/L, respectively. Both compounds showed broad-spectrum antitumor effects. Replacing by ethyl, compound 1 exhibited more potent bioactivity than positive control GA, such as in G2/M cell cycle arrest, cell apoptosis and client proteins degradations. The results firstly indicated that the docking study is able to provide a precise prediction of Hsp90 affinities of GA analogues, and the C6 substituent of GA is not erasable without affecting its biological activity.
Vercytochalasins A (1) and B (2), two biosynthetically related cytochalasins featuring novel structure and substituents, were isolated from the endozoic fungus Curvularia verruculosa which was associated with the deep-sea squat lobster Shinkaia crosnieri collected from the cold seep environment in South China sea. Their structures were elucidated by detailed interpretation of NMR spectroscopic and mass spectrometric data. The absolute configurations were confirmed by NOESY experiments as well as by DP4+ and ECD calculations. Differed from common cytochalasins, compound 1 is an uncommon secocytochalasin featuring the ester group cleaved between C-9 and C-23, and incorporating an additional oxygenated C4 unit which coupled with C-20 and C-22 to form a new substituted cyclohexenone moiety, while compound 2 contains an unusual 2‑hydroxy-3-oxobutan-2-yl unit at C-22. Both compounds are distinctive from the commonly described cytochalasins. Compound 1 exhibited potent activity against angiotensin-Ⅰ-converting enzyme (ACE) whereas compound 2 showed antibacterial activity. Molecular docking simulations were performed to explore the intermolecular interaction of compounds 1 and 2 with ACE.
The hyperplasia and destruction of synovial tissue have an important impact on the development of rheumatoid arthritis (RA), the abnormal proliferation and migration of synovial fibroblast in synovial tissue is similar to tumor cells. Targeting anomalous synovial fibroblast and designing a high bioavailability nano drug delivery system can reduce the dosage for the treatment of rheumatoid arthritis and it is of great significance to reduce toxic and side effects and improve curative effect. In this experiment, the nobiletin-loaded tetrahedral framework nucleic acids cargo tank was established, carrying anti-inflammatory small molecule monomer drug nobiletin with minimal bioavailability. Both in vitro cell experiments and in vivo animal studies proved the nano cargo tank enhance the role of nobiletin in reducing the invasiveness of pathological synovial fibroblast and promote their apoptosis, effectively alleviate the disease development of rheumatoid arthritis.
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