Polymeric Nanoparticles with a Glutathione‐Sensitive Heterodimeric Multifunctional Prodrug for In Vivo Drug Monitoring and Synergistic Cancer Therapy

Polymeric micelle‐based drug delivery systems have dramatically improved the delivery of small molecular drugs, yet multiple challenges remain to be overcome. A polymeric nanomedicine has now been engineered that possesses an ultrahigh loading (59 %) of a glutathione (GSH)‐sensitive heterodimeric multifunctional prodrug (HDMP) to effectively co‐deliver two synergistic drugs to tumors. An HDMP comprising of chemotherapeutic camptothecin (CPT) and photosensitizer 2‐(1‐hexyloxyethyl)‐2‐devinyl pyropheophorbide‐α (HPPH) was conjugated via a GSH‐cleavable linkage. The intrinsic fluorogenicity and label‐free radio‐chelation (⁶⁴Cu) of HPPH enabled direct drug monitoring by fluorescence imaging and positron emission tomography (PET). Through quantitative PET imaging, HDMP significantly improves drug delivery to tumors. The high synergistic therapeutic efficacy of HDMP‐loaded NPs highlights the rational design of HDMP, and presents exciting opportunities for polymer NP‐based drug delivery.     

Simultaneous Fenton‐like Ion Delivery and Glutathione Depletion by MnO2‐Based Nanoagent to Enhance Chemodynamic Therapy

Chemodynamic therapy (CDT) utilizes iron‐initiated Fenton chemistry to destroy tumor cells by converting endogenous H₂O₂ into the highly toxic hydroxyl radical (^.OH). There is a paucity of Fenton‐like metal‐based CDT agents. Intracellular glutathione (GSH) with ^.OH scavenging ability greatly reduces CDT efficacy. A self‐reinforcing CDT nanoagent based on MnO₂ is reported that has both Fenton‐like Mn²⁺ delivery and GSH depletion properties. In the presence of HCO₃^?, which is abundant in the physiological medium, Mn²⁺ exerts Fenton‐like activity to generate ^.OH from H₂O₂. Upon uptake of MnO₂‐coated mesoporous silica nanoparticles (MS@MnO₂ NPs) by cancer cells, the MnO₂ shell undergoes a redox reaction with GSH to form glutathione disulfide and Mn²⁺, resulting in GSH depletion‐enhanced CDT. This, together with the GSH‐activated MRI contrast effect and dissociation of MnO₂, allows MS@MnO₂ NPs to achieve MRI‐monitored chemo–chemodynamic combination therapy.     

Electrochemical recognition for tryptophan enantiomers based on 3, 4, 9, 10-perylenetetracarboxylic acid–chitosan composite film

A novel and simple chiral sensing platform had been successfully fabricated by means of amidation reaction between 3, 4, 9, 10-perylenetetracarboxylic acid (PTCA) and chitosan (CS) to form 3, 4, 9, 10-perylenetetracarboxylic acid–chitosan (PTCA–CS) composite film. Since CS has chiral center and PTCA has excellent electrical conductivity, the PTCA–CS composite modified glassy carbon electrode (PTCA–CS/GCE) could be treated as an effective electrochemical chiral sensor and applied for chiral discrimination of tryptophan (Trp) enantiomers theoretically. PTCA–CS composite was characterized by Fourier transform infrared (FTIR) spectroscopy and cyclic voltammetry (CV). When the prepared chiral sensing interface interacted with tryptophan isomers, a higher selectivity was received from D-Trp by differential pulse voltammetry (DPV). It indicated that the PTCA–CS/GCE can be treated as an electrochemical chiral sensor for the discrimination of Trp enantiomers. Further study demonstrated that the peak currents were linearly increased with the increasing percentage of L-Trp of Trp racemic mixture. Furthermore, the enantioselective interaction of the PTCA–CS/GCE was systematically studied by other experimental factors, such as the incubation time and acidity.     

Site‐Selective O‐Arylation of Glycosides

Direct and site‐selective O‐arylation of carbohydrates has been a challenge in synthesis. Herein we report a method based on copper‐catalyzed O‐arylation to address this challenge. Proper choice of the ancillary ligand on copper is critical for the efficiency and site selectivity of this transformation. This method features mild conditions, tolerates various functional groups, and demonstrates broad substrate scope.     

X-ray scintillation in lead-free double perovskite crystals

Metal halide perovskites have shown great performance for various applications,including solar cells,light emitting diodes,and radiation detectors,but they still suffer from the toxicity of lead and instability.Here we report the use of lanthanide series as trivalent metals to obtain low toxicity and highly stable double perovskites(Cs_2NaLnCl_6,Ln=Tb or Eu)with high scintillation light yield.The crystals exhibit typical f-f transitions of lanthanide cations,while Cs_2NaTbCl_6exhibits strong green photoluminescence,and Cs_2NaEuCl_6exhibits red photoluminescence.Under X-ray radiations,the light yield of Cs_2NaTbCl_6reaches46600 photons MeV~(-1),much higher than that of the commercially used(Lu,Y)_2SiO_5:Ce~(3+)crystals(LYSO,28500 photons MeV~(-1)),and previously reported lead-based perovskites(14000 photons MeV~(-1)).As a new member of lead-free perovskites,lanthanide-based double perovskites open up a new route toward radiation detections and potential medical imaging.     

Acid‐Induced Shift of Intramolecular Hydrogen Bonding Responsible for Excited‐State Intramolecular Proton Transfer

The significant progress recently achieved in designing smart acid‐responsive materials based on intramolecular charge transfer inspired us to utilize excited‐state intramolecular proton transfer (ESIPT) for developing a turn‐on acid‐responsive fluorescent system with an exceedingly large Stokes shift. Two ESIPT‐active fluorophores, 2‐(2‐hydroxyphenyl)pyridine (HPP) and 2‐(2‐hydroxyphenyl)benzothiazole (HBT), were fused into a novel dye (HBT‐HPP) fluorescent only in the protonated state. Moreover, we also synthesized three structurally relevant control compounds to compare their steady‐state fluorescence spectra and optimized geometric structures in neutral and acidic media. The results suggest that the fluorescence turn‐on was caused by the acid‐induced shift of the ESIPT‐responsible intramolecular hydrogen bond from the HPP to HBT moiety. This work presents a systematic comparison of the emission efficiencies and basicity of HBT and HPP for the first time, thereby utilizing their differences to construct an acid‐responsive smart organic fluorescent material. As a practical application, red fluorescent letters can be written using the acid as an ink on polymer film.     

Grayanane diterpenoids with diverse bioactivities from the roots of Pieris formosa

During our continuing study on the roots of Pieris formosa, twelve new grayanane diterpenoids (1–12), together with eight known compounds (13–20), were obtained. Their structures with absolute configurations were characterized by a series of spectroscopic methods and X-ray diffraction. Compounds 1, 2, 4–5, 7–8, 14, and 19 exhibited significant analgesic activity in an acetic acid-induced writhing test. In particular, 7 and 14 were found to be 5 times more potent than morphine in the acetic acid-induced writhing test model. Compounds 1, 4, 9, 13, and 18 showed antifeedant activity against Plutella xylostella at 0.5 mg/mL. Compound 4 exhibited a 38.3% inhibitory effect against the KCNQ2 potassium channel at a concentration of 10 μM.     

一类常微分方程在奇点处解的符号算法

借助于常微分方程(或微分算子)的牛顿多边形,本文给出了一类常微分方程在奇点处解的符号算法。此算法能使我们得到方程在奇点处的精确解。     

豫北大天鹅越冬生态习性的研究

论述豫北黄河故道湿地鸟类自然保扩区天鹅越冬情况，通过多年野外观察和研究，基本弄清了该保护区大天鹅的越冬生态习性、食性及数量分布，并提出了保护性建议。     

用ispLSI实现一个四位二进制计数器

ｉｓｐＬＳＩ是Ｌａｔｔｉｃｅ公司生产的一种ＰＬＤ器件，它的优点是不需要编辑器可以直接在系统上编程。本文对ｉｓｐＬＳＩ的开发系统ＰＤＳ的ｉｓｐＬＳＩ器件内部结构进行了分析，说明如何使用ＰＤＳ软件来设计器件，并用ｉｓｐＬＳＩ实现一个四位二进制的计数器。