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EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS · 2022 · IF 5.589

Anchoring β-CD on simvastatin-loaded rHDL for selective cholesterol crystals dissolution and enhanced anti-inflammatory effects in macrophage/foam cells

Jianhua He,Xiaoju Zhou,Fengfei Xu,Hongliang He,Shuangyan Ma,Xinyue Liu,Mengyuan Zhang,Wenli Zhang,Jianping Liu

Macrophage/foam cells and cholesterol crystals (CCs) have been regarded as the central triggers of maladaptive inflammation in atherosclerotic plaque. Despite the tremendous progress of recombinant high-density lipoprotein (rHDL) serving for targeted drug delivery to alleviate inflammation in macrophage/foam cells, the active attempt to modulate/improve its CCs dissolution capacity remains poorly explored. The untreated CCs can seriously aggravate inflammation and threaten plaque stability. Based on the superb ability of β-cyclodextrin (β-CD) to bind CCs and promote cholesterol efflux, simvastatin-loaded discoidal-rHDL (ST-d-rHDL) anchored with β-CD (βCD-ST-d-rHDL) was constructed. We verified that βCD-ST-d-rHDL specifically bound and dissolved CCs extracellularly and intracellularly. Furthermore, anchoring β-CD onto the surface of ST-d-rHDL enhanced its cholesterol removal ability in RAW 264.7 cell-derived foam cells characterized by accelerated cholesterol efflux, reduced intracellular lipid deposition, and improved cell membrane fluidity/permeability. Finally, βCD-ST-d-rHDL exerted efficient drug delivery and effective anti-inflammatory effects in macrophage/foam cells. Collectively, anchoring β-CD onto the surface of ST-d-rHDL for selective CCs dissolution, accelerated cholesterol efflux, and improved drug delivery represents an effective strategy to enhance anti-inflammatory effects for the therapy of atherosclerosis.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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NEW JOURNAL OF CHEMISTRY · 2022 ·Vol. 46 ·期 17 ·7992-7998 · IF 3.925

A bisspiropyran fluorescent probe for the selective and rapid detection of cyanide anion in liqueurs

Ziqiang Zhou,Hongzhi Hu,Ling Xia,Gongke Li,Xiaohua Xiao

Cyanide anion (CN−) in diet may cause serious health risks, and hence it requires a sensitive, selective, and rapid detection method, particularly in on-site tests. In this study, a novel bisspiropyran (SP1) fluorescent probe has been designed and prepared for the selective and rapid detection of CN− in liqueurs. Containing two spiropyran units linked by an alkyl chain, the developed SP1 probe exhibited excellent photoluminescence properties and a specific fluorescence response towards CN−. Moreover, the sensing mechanism of SP1 to CN− was discussed in detail. Under the optimized analysis conditions, irradiated at 320 nm for 4 min after mixing with CN− and detection at 440 nm, a SP1 probe-based fluorescence method was established for CN− quantitation with a response range of 1.0–50.0 μmol L−1 (2.6 × 10−2–1.3 mg L−1), and the limit of detection was 0.21 μmol L−1 (5.5 × 10−3 mg L−1). Furthermore, this SP1 probe-based fluorescence method was applied to CN− detection in liqueurs, and the accuracy was proved by the satisfied recoveries of 91.5–102.5% with relative standard deviations less than 5.5% and the low relative error of 5.0% with the results using the standard ion chromatography method. This selective and rapid CN− detection method has a potential application in on-site tests of food safety.

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ACS Applied Materials & Interfaces · 2022 · IF 10.383

Charge-Reversible Pro-Ribonuclease Enveloped in Virus-like Synthetic Nanocapsules for Systemic Treatment of Intractable Glioma

Hongyan Cui,Liuwei Zhang,Shuang Zeng,Yu Wang,Zhen Li,Jingyun Wang,Qixian Chen

We have tailored multifaceted chemistries into the manufacture of artificial virus-like delivery vehicles mimicking viral “intelligent” transportation pathways through sequential biological barriers; these vehicles can acquire the ability to dynamically “program transfer” to their target sites. To accomplish this, we created anionic pro-proteins, which facilitate charge reversal when subject to acidic endosomal pH; in this way, carboxylation reactions are performed on proteins with amine-reactive cis-aconitic anhydride. Electrostatic associations then initiate the envelopment of these pro-proteins into multilayered nanoarchitectural vehicles composed of multiple-segmental block copolycationic cyclic Arg-Gly-Asp (RGD)-poly(ethylene glycol)(PEG)-GPLGVRG-polylysine(thiol). Therefore, upon the pro-proteins’ initial binding to the tumors via the protruding RGD ligands, the bio-inert PEG surroundings are detached through the enzymolysis of the intermediate GPLGVRG linkage by tumor-enriched matrix metalloproteinases, unveiling the cationic polylysine palisade and imparting intimate affinities to the anionic cytomembranes of the targeted tumors. Essentially, through their active endocytosis into the subcellular endosomal compartments, the pro-proteins are made capable of retrieving the original amine groups through a charge reversal decarboxylation process, consequently eliciting augmented charge densities (charge nonstoichiometric protein@polylysine(disulfide)) to disrupt the anionic endosomal membranes to facilitate translocation into the cytosol. Eventually, the active protein payloads can be liberated from nonstoichiometric protein@polylysine(thiol) by the disassembly of polylysine palisade upon the cleavage of disulfide crosslinking in response to the very high level of glutathione in the cytosol, thereby contributing toward extreme cytotoxic potency. Hence, our elaborated virus-mimicking platform has demonstrated potent antitumor efficacy through the systemic administration of ribonucleases, which will consequently lead to an innovative new therapeutic method by which proteins could reach intracellular targets.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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MOLECULES · 2022 ·Vol. 27 ·期 11 ·3582 · IF 4.927

Application of Dual-Enhanced Surface-Enhanced Raman Scattering Probe Technology in the Diagnosis of Tumor Cells in Vitro

Yinping Zhao,Yawei Kong,Liwen Chen,Han Sheng,Yiyan Fei,Lan Mi,Bei Li,Jiong Ma

With the development of precision medicine, antigen/antibody-targeted therapy has brought great hope to tumor patients; however, the migration of tumor cells, especially a small number of cells flowing into blood or other tissues, remains a clinical challenge. In particular, it is difficult to use functional gold nanomaterials for targeted clinical tumor diagnosis while simultaneously obtaining stable and highly sensitive Raman signals. Therefore, we developed a detection method for functional Au Nanostars (AuNSs) with dual signal enhancement that can specifically track location and obtain high-intensity surface-enhanced Raman scattering (SERS) signals. First, AuNSs with specific optical properties were synthesized and functionalized. The Raman dye 4-mercapto-hydroxybenzoic acid and polyethylene glycol were coupled with the tumor marker, epidermal growth factor receptor, to obtain the targeted SERS probes. In addition, a detection chip was prepared for Raman detection with physical enhancement, exhibiting a 40-times higher signal intensity than that of quartz glass. This study combines physical enhancement and SERS enhancement technologies to achieve dual enhancement, enabling the detection of a highly sensitive and stable Raman signal; this has potential clinical value for antigen/antibody-targeted tumor diagnosis and treatment.Keywords:SERS probe;dual enhancement;stable and highly sensitive;Raman signals;A549 cell

✓ 已验证 产品关联 DOI PubMed 高影响因子
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CHEMICAL ENGINEERING JOURNAL · 2022 · IF 16.744

Bridging environmental and biological monitoring: Constructing platform for hexavalent chromium detection and cancer-cells screening based on red fluorescent carbonized polymer dots

Xin Wang,Jinshuang Hu,Boxuan Yao,Hua Wei,Caiyun Zhang,Jiarui Zhou,Jian Liu,Shenghong Yang

Intensive research on biocompatible carbon-based fluorescent nanomaterials provides a brand-new platform for environmental and biological monitoring, but its applicability is limited by the single signal response, unfriendly synthesis route, or rare red fluorescence performance. In this study, we designed and prepared a new type of high-efficiency red fluorescent carbonized polymer dots (R-PDs) through rationally preferred raw materials. The proposed R-PDs with colorimetric and fluorescent dual-signal response to hexavalent chromium (Cr(VI)) can be obtained easily by hydrothermal treatment of o-hydroxybenzoic acid and p-phenylenediamine. A high-throughput smartphone-mediated scanometric analysis platform was constructed based on sensitive gray change, which was further applied for the rapid, simple, and low-cost detection of Cr(VI) in real environmental water. The fluorescent analysis mode exhibits high sensitivity with the limit of detection 20 nM, thereby realizing the Cr(VI) imaging in living cells and aquatic species. More importantly, R-PDs exhibited excellent nucleolus targeting capacity by virtue of their inherent high nitrogen content, thus successfully screening normal and cancerous cells. Encouraged by the simplicity of synthesis and availability of constructed analysis platform, the proposed R-PDs has great potential applications in environmental monitoring, biosensing and biomedical.

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ACS Applied Polymer Materials · 2022 · IF 4.855

Co2+-Mediated Hydrogels with Enhanced Mechanical Properties for Flexible Sensing

Shuai-Jun Guo,Hao-Yun Chang,Meng-Jia Xu,Chen-Xu Wang,Hua Wei,Dong-Dong Li,Jing Chen,Yang Zhou,Yi Liu

Flexible artificial skin sensors have been a hot research topic over the past 20 years due to their remarkable prospects in the fabrication of smart wearable devices. Normally, electronic skin sensors transmit signals via stretchy electrical conductors, and the manufacturing processes are more complicated, involving multiple steps. For the first time, this work reports a facile one-step fabrication of poly(sodium methacrylate-co-vinylimidazole)-Co2+ hydrogels with high mechanical strength, good elasticity, and excellent sensitivity that can be used as ionic skins (I-skins). In addition, mechanical analysis indicates that the designed hydrogels have enhanced strain and tensile strength due to hydrogen bonding and metal–ligand bonding interactions, and these two types of dynamic noncovalent interactions are explored in detail. Simultaneously, the developed hydrogels also display superior conductivity and self-healing qualities with restored sensing properties. Furthermore, the proposed hydrogel with good sensitivity and stable strain range is suitable to fabricate a wearable strain sensor, and this hydrogel sensor was demonstrated to be effective in monitoring human motion, including joint flexion, pulse, vocal cord vibration, and respiration. In addition, a pressure distribution sensor array was developed by this hydrogel and was used to construct the model of plantar pressure distribution in normal subjects and flatfoot patients, offering a strategy for the early detection and clinical diagnosis of numerous foot-related disorders. Hence, this research may offer a promising approach for generating biocompatible hydrogels with integrated mechanical characteristics, and these hydrogels present development potentials in multifunctional ionic skins.

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HIGH PERFORMANCE POLYMERS · 2022 · IF 1.73

Preparation and characterization of a low viscosity epoxy resin derived from m-divinylbenzene

Xiankun Wu,Chang-an Xu,Mangeng Lu,Xiaole Zheng,Yingjie Zhan,Bifang Chen,Kunxin Wang,Huifa Meng

To explore thermal and mechanical properties of epoxy material, difunctional aromatic epoxy--divinylbenzene dioxide (DVBDO) had been synthesized by epoxidizing divinylbenzene, using the metal acetylacetone compound grafted Fe3O4 particles as the catalyst. The catalyet had high conversion and epoxy selectivity and could be recyclable. Then the polymerization of DVBDO with different diamine curing agents were reported. The structure and viscosity of DVBDO were firstly characterized. Because it had low molecular weight and viscosity, DVBDO had excellent liquidity and formability. Subsequently to clarify the properties of epoxy thermosets, experiments to determine thermal and mechanical performances were carried out, such as differential scanning calorimetry (DSC), thermal gravimetric (TGA), dynamic mechanical analysis (DMA) and tensile test. It could be observed that the thermoset polymers using DVBDO as epoxy matrix had excellent thermal (Tg was about 201°C) and mechanical properties (tensile strength was 131.99Mpa). Possibly considering that this kind of thermoset polymers had higher rigidity and crosslink density. In conclusion, a new type of one-component liquid epoxy encapsulant material with low viscosity, good filling fluidity, strong heat resistance and excellent storage performance had been developed.

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BIOMEDICINE & PHARMACOTHERAPY · 2022 · IF 7.419

Hypouricemic effect of 2,4-dihydroxybenzoic acid methyl ester in hyperuricemic mice through inhibiting XOD and down-regulating URAT1

Tianqiao Yong,Danling Liang,Chun Xiao,Longhua Huang,Shaodan Chen,Yizhen Xie,Xiong Gao,Qingping Wu,Huiping Hu,Xiangmin Li,Yuancao Liu,Manjun Cai

In this paper, we reported the hypouricemic effect of 2,4-dihydroxybenzoic acid methyl ester (DAE), a component of Ganoderma applanatum , in hyperuricemic mice through inhibiting XOD and down-regulating URAT1. Computationally, DAE showed a high similarity to allopurinol and depicted a high affinity in docking to XOD. In vitro , DAE exhibited an inhibitory effect against XOD. Importantly, DAE demonstrated a remarkable hypouricemic effect, decreasing serum uric acids (SUAs) of hyperuricemic mice (407 ± 31 μmol/L) to 195 ± 23, 145 ± 33 and 134 ± 16 μmol/L ( P  < 0.01) at the doses of 20, 40, and 80 mg/kg with a dose-dependent manner and showing efficacies at 54–68 %, which were close to the efficacies of allopurinol (61 %) and benzbromarone (57 %). DAE depicted higher and negatively dose-independent urinary uric acids in comparison with that of the hyperuricemic control, implying DAE exerted an uricosuric effect and also a reduction effect on uric acid production. Unlike toxic allopurinol and benzbromarone, no general toxicity on body weights and no negative influence on liver, kidney, spleen and thymus were observed for DAE. Mechanistically, DAE inhibited XOD activities in vivo . Moreover, DAE up-regulated OAT1 and down-regulated GLUT9, URAT1 and CNT2. Overall, DAE may present a hypouricemic effect through inhibiting XOD and up-regulating OAT1 and down-regulating GLUT9, URAT1 and CNT2. This work provided novel insights into the hypouricemic effect of DAE and G. applanatum.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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PHARMACOLOGICAL RESEARCH · 2022 · IF 10.334

Biomimetic micelles to accurately regulate the inflammatory microenvironment for glomerulonephritis treatment

Huijuan Zhang,Qingqing He,Jingjing Wang,Yaping Wang,Xiangyang Xuan,Mingli Sui,Zhenzhong Zhang,Lin Hou

Glomerulonephritis is a key factor in leading to end-stage renal disease. Mesangial cell proliferation and macrophage infiltration are two prominent features linked in a vicious circle mechanism for glomerulonephritis progression. Herein, a novel biomimetic pH-sensitive nanomicelle (MM/HA-DXM) was constructed to synergize hyaluronic acid (HA)-activated macrophage phenotypic remodeling and dexamethasone (DXM)-mediated mesangial cell killing for precise treatment of glomerulonephritis. Owing to the camouflaged coating with endogenous macrophage membrane (MM), MM/HA-DXM could escape from RES phagocytosis and then be recruited to inflammatory glomerulus by active homing effect. Afterwards, HA-DXM nanomicelles ruptured in response to the weakly acidic glomerulonephritis microenvironment, to locally release HA and DXM . On the one hand, DXM can inhibit the abnormal proliferation of mesangial cells. On the other hand, HA transformed pro-inflammatory M1 macrophages into anti-inflammatory M2 phenotype to improve the glomerular inflammatory microenvironment. In doxorubicin-induced glomerulonephritis models, results revealed that MM/HA-DXM could specifically “homing” to inflammatory renal tissue with 4.33-fold improvement in targeting performance. In addition, in vivo pharmacodynamic results proved that after treatment with MM/HA-DXM, the proteinuria level decreased to 2.33 times, as compared with that of control group, demonstrating a superior therapeutic effect on glomerulonephritis via this collaborative two-pronged anti-inflammatory therapy strategy.

CAS / MDL: 23491-52-3 93572-42-0
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Acta Biomaterialia · 2022 · IF 10.633

Enhanced treatment of cerebral ischemia–Reperfusion injury by intelligent nanocarriers through the regulation of neurovascular units

Hongdan Lu,Shengnan Li,Dongwei Dai,Qi Zhang,Zhiyi Min,Chuanzhou Yang,Shanbo Sun,Lu Ye,Chuanhui Teng,Xiang Cao,Haoyuan Yin,Lingyan Lv,Wei Lv,Hongliang Xin

Reperfusion injury is one of the major causes of disability and death caused by ischemic stroke, and drug development focuses mainly on single neuron protection. However, different kinds of cells in the neurovascular units (NVUs), including neurons, microglia and vascular endothelial cells, are pathologically changed after cerebral ischemia–reperfusion injury, resulting in an urgent need to develop a drug delivery system to comprehensively protect the kinds of cells involved in the NVU. Herein, we have constructed a c(RGDyK) peptide modified, NF-κB inhibitor caffeic acid phenethyl ester (CAPE)-loaded and reactive nitrogen species (RNS) stimuli-responsive liposomal nanocarrier (R-Lipo-CAPE) to target ischemic lesions and then remodel the NVU to reduce the progression of cerebral ischemia–reperfusion injury. The R-Lipo-CAPE liposomes were approximately 170 nm with a zeta potential of -30.8 ± 0.2 mV. The in vitro CAPE release behavior from R-Lipo-CAPE showed an RNS-dependent pattern. For in vivo studies, transient middle cerebral artery occlusion/reperfusion (MCAO) model mice treated with R-Lipo-CAPE had the least neurological impairment and decreased brain tissue damage, with an infarct area of 13%, compared with those treated with saline of 53% or free CAPE of 38%. Furthermore, microglia in the ischemic brain were polarized to the tissue-repairing M2 phenotype after R-Lipo-CAPE treatment. In addition, R-Lipo-CAPE-treated mice displayed a prominent down-regulated expression of MMP-9 and restored expression of the tight junction protein claudin-5. This proof-of-concept indicates that R-Lipo-CAPE is a promising nanomedicine for the treatment of cerebral ischemia–reperfusion injury through the regulation of neurovascular units. Statement of significance Based on the complex mechanism and difficulty in treatment of cerebral ischemia-reperfusion injury, the overall regulation of neurovascular unit has become an extremely important target. However, little nanomedicine has been directed to remodel the neurovascular units in targeted cerebral ischemia-reperfusion injury therapy. Here, c(RGDyK) peptide modified reactive nitrogen species (RNS) stimuli-responsive liposomal nanocarrier loaded with a NF-κB inhibitor (CAPE), was designed to simultaneously regulate various cells in the microenvironment of cerebral ischemia-reperfusion injury to remodel the neurovascular units. Our in vitro and in vivo data showed that the intelligent nanocarrier exerted the ability of pathological signal stimuli-responsive drug release, cerebral ischemia-reperfusion injury site targeting and neurovascular units remodeling through reducing neuron apoptosis , regulating microglia polarization and repairing vascular endothelial cell. Overall, the intelligent liposomal drug delivery system was a promising and safe nanomedicine in the perspective of cerebral ischemia-reperfusion injury treatment.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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ANALYTICAL CHEMISTRY · 2022 · IF 8.008

All-in-One Luminescent Lanthanide Coordination Polymer Nanoprobe for Facile Detection of Protein Kinase Activity

Baoxia Liu,Yaoyao Zhang,Yuanqiang Hao,Xu Zhu,Yintang Zhang,Yanli Zhou,Hongliang Tan,Maotian Xu

This study developed a novel luminescent assay for kinase activity using metal–organic coordination polymer nanoparticles (Tb/ATP-Zn) as the probe. Tb/ATP-Zn, self-assembled by adenosine triphosphate (ATP), Zn2+, and Tb3+, is non-luminescent. Protein kinase A (PKA) can catalyze the transformation of ATP within Tb/ATP-Zn nanoparticles to adenosine diphosphate (ADP), which in turn effectively sensitizes the luminescence of Tb3+. Based on this mechanism, Tb/ATP-Zn can realize the facile luminescent “turn-on” sensing of protein kinase activity without the use of external ATP and substrate peptide. Under optimized conditions, the fluorescence intensities of Tb/ATP-Zn at 550 nm are linear with the PKA activity within a range of 0.3–1.5 U·μL–1. The LOD (S/N = 3) of this method is down to 0.001 U·μL–1. The presented assay also features high selectivity, long-term stability, fast response, and convenient operation. Furthermore, Tb/ATP-Zn was successfully employed for monitoring PKA activity in cell lysis solutions. Probe Tb/ATP-Zn is thus expectable to be a powerful tool for the practical study of PKA in relevant biological events.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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Heritage Science · 2022 ·Vol. 10 ·期 1 ·1-12 · IF 2.843

Bronze preservation by using composite hydrogel coating-loaded corrosion inhibitors

Zhou Sheng,Zhao Zongshen,Mao Heyi,Wang Lei,Chen Junyin,Chen Jiachang,Huang Xia

Bronze has been used for various applications since ancient times, and therefore, its preservation is critical. However, preserving bronze is challenging. The traditional inhibitor sealing method is limited by its toxicity and sealing effects. In this study, a benzotriazole (BTA) inhibitor loaded with a composite hydrogel of sodium alginate and cyclic-peptide-grafted β-cyclodextrin was prepared. The chemical structure of the components of the composite hydrogel coating was characterized through Fourier-transform infrared spectroscopy. The microstructure of the coating on bronzeware was characterized through scanning electronic microscopy. The thermal analysis of the composite hydrogel coating confirmed that BTA was introduced successfully into the composite hydrogel, and the coating exhibited the liquid crystalline property because of the mesogenic unit—cyclic peptide. Electrochemical impedance spectroscopy revealed that the modified β-cyclodextrin-loaded benzotriazole considerably improved the corrosion resistance. In a certain range, the higher was the BTA-loaded Cyc-g-β-CD ratio, the stronger was the protective effect of the gel coating. In conclusion, corrosion inhibitors can considerably improve the corrosion resistance of gel coatings.

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