Latest ArticlesA visible light-promoted fast photochemical Wolff rearrangement was developed toward synthesis of α-substituted amides in continuous flow with the use of a photochemical oscillatory flow reactor (POFR). The control experiment indicates that a fast process of the Wolff rearrangement (<40 s) is involved. Notably, this protocol does not require excess use of any reactants, and the resulting α-substituted amides could be isolated by recrystallization in good to excellent yields.
Acute lung injury (ALI) was characterized by excessive reactive oxygen species (ROS) levels and inflammatory response in the lung. Scavenging ROS could inhibit the excessive inflammatory response, further treating ALI. Herein, we designed a novel nanozyme (P@Co) comprised of polydopamine (PDA) nanoparticles (NPs) loading with ultra-small Co, combining with near infrared (NIR) irradiation, which could efficiently scavenge intracellular ROS and suppress inflammatory responses against ALI. For lipopolysaccharide (LPS) induced macrophages, P@Co + NIR presented excellent antioxidant and anti-inflammatory capacities through lowering intracellular ROS levels, decreasing the expression levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) as well as inducing macrophage M2 directional polarization. Significantly, it displayed the outstanding activities of lowering acute lung inflammation, relieving diffuse alveolar damage, and up-regulating heat shock protein 70 (HSP70) expression, resulting in synergistic enhanced ALI therapy effect. It offers a novel strategy for the clinical treatment of ROS related diseases.
In recent years, biopharmaceuticals have witnessed remarkable advancements, transforming the landscape of therapeutic interventions. Biopharmaceuticals encompassing therapeutics generated through cutting-edge biotechnological methods have shown promising therapeutic outcomes. However, their clinical success hinges significantly on overcoming drug delivery challenges related to stability, intracellular delivery, immunogenicity, and pharmacokinetic properties. Herein, we provide an overview of various marketed macromolecules, including nucleic acids, and immunotherapeutic agents such as cytokines and monoclonal antibodies, as well as other therapeutic peptides/proteins like enzymes, hormones, and coagulation factors. Our primary focus is on elucidating the delivery challenges associated with these macromolecules and highlighting the pivotal role played by drug delivery platforms in the development of currently marketed products, offering valuable insights for both scientific research and the pharmaceutical industry.
It is of great significance to find safe and effective radiosensitizers. A primary investigation has been made on fisetin’s modification of radiation effect, but its radiosensitization and related mechanisms still need to be deeply clarified. Furthermore, fisetin with high hydrophobicity is difficult to dissolve in water, severely limiting its research and application. In this study, we fabricated a safe and soluble radiosensitizer fisetin micelle for precisely enhancing radiotherapy by inhibiting platelet-derived growth factor receptor-β (PDGFRβ)/signal transducer and activator of transcription 1 (STAT1)/signal transducer and activator of transcription 3 (STAT3)/B cell lymphoma 2 (Bcl-2) signaling pathway in the tumor. Systematic and detailed studies were performed to verify its radiosensitization effect in vitro and in vivo. On the cellular level, fisetin micelles selectively increased the radiosensitivity of tumor cells (CT26 and 4T1 cells) and had little effect on the sensitivity of normal mouse cells (L929 cells) to radiation. In the mouse models of colon and breast cancers, fisetin micelles showed an efficient radiosensitization capacity without apparent toxicity. Additionally, we first found that fisetin micelles played a radiotherapy sensitization role by inhibiting the PDGFRβ/STAT1/STAT3/Bcl-2 pathway activity. In general, this work not only confirmed that fisetin micelles precisely exhibit a radiosensitization effect in vitro and in vivo, but also profoundly explored its mechanisms underlying, to provide a theoretical and experimental basis for the clinical application of fisetin micelles.
Revealing the factors that affect the vibrational frequency of Stark probe at interface is a pre-requirement for evaluating the absolute interfacial electric field. Here using surface-enhanced infrared absorption (SEIRA) spectroscopy, attenuated total reflection (ATR) spectroscopy and molecular dynamics (MD), we reveal the assembled CN at gold nanofilm exhibits a reduced Stark tuning rate (STR) referring to the vibrational frequency shift in response to electric field comparing with the bulk which was regulated by the electron transfer between S and Au. These findings lead to a deeper understanding of the vibrational Stark effect at the interface and provide guidance for improving the interface electric field theory.
In this work, we employed a ring-opening strategy to develop a series of novel N-benzyl arylamide derivatives as tubulin polymerization inhibitors. Notably, 13n (MY-1388) exhibited remarkable antiproliferative potency on fifteen human cancer cell lines, with half maximal inhibitory concentration (IC50) values ranging from 8 nmol/L to 48 nmol/L. Furthermore, 13n effectively suppressed tubulin polymerization by targeting the colchicine-binding site (IC50 = 0.62 µmol/L). 13n also exhibited significant inhibition of cell colony formation, as well as displayed potent effects on inducing G2/M phase cell cycle arrest and promoting apoptosis. Importantly, 13n exhibited enhanced and adequate liver microsomal stability in human and rat liver microsomes, and also exhibited a moderate half-life (T1/2 = 0.938 h) in vivo. Meanwhile, 13n demonstrated effective antitumor effects in vivo in suppressing tumor growth in the MGC-803 xenograft model (tumor growth inhibition (TGI) value was 76.4% at the dosage of 30 mg kg−1 day−1) with a good safety profile. Collectively, these results revealed that 13n represents a promising tubulin polymerization inhibitor that deserves further investigation for its efficacy in treating gastric cancers.
Solid-state batteries (SSBs) with high-capacity Si anodes have been regarded as one of the most promising candidates to meet the large scale energy storage and electrical vehicles due to its intrinsic safety and potential high energy density. However, Si suffers from poor electrical conductivity and huge volume change and particles fracture during lithiaiotn and delithiation, which induces low practical energy density. In addition, the SSBs are often operated at high temperature due to the poor physical contact and huge resistance between Si and solid-state electrolyte (SSE). To improve the bulk electronic/ionic conductivity of Si and its interfacial compatibility with SSE, herein, a binder free and self-supporting Si/C film was developed. The monolithic carbon not only enhance the electric conductivity but also release huge stress during lithiation and delithiation. In addition, paired with the flexible and soft poly(vinylidene fluoride)-co-hexafluoropropylene (PVDF-HFP) and Li1.3Al0.3Ti1.7(PO4)3 (LATP) solid-state electrolyte, a LiF-rich and electrochemical stable solid-electrolyte interphase (SEI) layer is in-situ engineered. The fast bulk and interfacial ionic transportation as well as the mechanical integrity of MSi enable high performance SSBs at room temperature. As a result, high specific capacity of 2137 mAh/g with an initial Coulombic efficiency of 83.2% is obtained at a rate of 0.5 A/g. Even at a high rate of 3 A/g, the specific capacity is 1793 mAh/g. At a rate of 1 A/g, the Si/C anode delivers a long cycling performance over 500 cycles while maintains a capacity of 1135 mAh/g. This work provides a new strategy that combines charge transfer kinetics and interfacial chemistry design toward high energy density Si-based SSBs.
Ultrasensitive detection of nucleic acids is of great significance for precision medicine. Digital polymerase chain reaction (dPCR) is the most sensitive method but requires sophisticated and expensive instruments and a long reaction time. Digital PCR-free technologies, which mean the digital assay not relying on thermal cycling to amplify the signal for quantitative detection of nucleic acids at the single-molecule level, include the digital isothermal amplification techniques (dIATs) and the digital clustered regularly interspaced short palindromic repeats (CRISPR) technologies. They combine the advantages of dPCR and IATs, which could be fast and simple, enabling absolute quantification of nucleic acids at a single-molecule level with minimum instrument, representing the next-generation molecular diagnostic technology. Herein, we systematically summarized the strategies and applications of various dIATs, including the digital loop-mediated isothermal amplification (dLAMP), the digital recombinase polymerase amplification (dRPA), the digital rolling circle amplification (dRCA), the digital nucleic acid sequence-based amplification (dNASBA) and the digital multiple displacement amplification (dMDA), and evaluated the pros and cons of each method. The emerging digital CRISPR technologies, including the detection mechanism of CRISPR and the various strategies for signal amplification, are also introduced comprehensively in this review. The current challenges as well as the future perspectives of the digital PCR-free technology were discussed.
Imaging detection of interlinked dual proteases is imperative for precise tumor imaging, which remains challenging due to limited modification position of specific substrate and possible steric hindrance. Herein, we have developed a unimolecular chemiluminescent probe (LGP-CL) tandemly activated by two proteases interlinked with liver cancer to achieve precise tumor imaging. Probe LGP-CL consists of a phenoxy-dioxetane scaffold caged by a tripeptide substrate (LGP, leucine-glycine-proline) as the sensing layer, which can be cleaved sequentially by aminopeptidase N (APN) and dipeptidyl peptidase Ⅳ (DPPIV) to turn on a strong chemiluminescent signal, and silenced by specific inhibitor of each enzyme, which accounts for an integrated logic gate (AND, OR and INHIBIT). The successful cleavage of dual proteases on the metabolic site depends on the proper structure of the tripeptide substrate, as confirmed by two probes design. Probe LGP-CL (LGP as the substrate) enables the excellent "dual-lock-dual-key" fit with a 382-fold enhancement of chemiluminescent emission while no obvious signal is observed by using GPL-CL (GPL as the substrate). By virtue of its rapid response (several minutes), high sensitivity and good cell viability, probe LGP-CL has been utilized to evaluate upregulated levels of proteases in vitro and in living systems, especially to distinguish liver tumor cells (HepG2) from others (LO2, MCF-7, MCF-10a and RAW264.7). Overall, the newly developed CL probe may facilitate rapid investigation into the role played by proteases in liver diseases, enabling timely selection appropriate treatment. Therefore, our work not only sheds light on the rational design of optical probes for dual protease imaging, but provides a promising tool for clinical diagnosis and even drug discovery.
Metal-organic frameworks (MOFs) attract broad interests in mercury (Hg) ion adsorption field, while unreasonable distribution of active groups commonly restricts their utilization efficiency. In this work, we constructed a new MOF (TYUST-6) with dense thiol-rich traps in the 1D pore wall. This accessible channel and rational distribution of thiols allow the smooth diffusion of Hg ions and thereby result in a high Langmuir adsorption capacity of 1347.6 mg/g, almost reaching the theoretical maximum (1444.3 mg/g). Adsorption equilibrium needs 10 and 30 min at the initial concentrations of 10 and 100 mg/L, respectively. Common co-existing ions and solution pH show almost negligible interferences on the adsorption, and adsorbent regeneration can be well achieved. Combining experimental characterizations and theoretical calculations, the thiol groups in the pore wall are proved to be the dominant interaction sites. Thus, this work reports a novel high-capacity adsorbent for Hg2+, and proposes a feasible guideline for designing effective adsorbents.
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