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MOLECULES · 2022 ·Vol. 27 ·期 14 ·4535 · IF 4.927

Engineered 3D-Printed Polyvinyl Alcohol Scaffolds Incorporating β-Tricalcium Phosphate and Icariin Induce Bone Regeneration in Rat Skull Defect Model

Zhimin Xu,Yidan Sun,Huanyan Dai,Yujie Ma,Han Bing

The skull defects are challenging to self-heal, and autologous bone graft repair has numerous drawbacks. The scaffolds for the rapid and effective repair of skull defects have become an important research topic. In this study, polyvinyl alcohol (PVA)/β-tricalcium phosphate(β-TCP) composite scaffolds containing icariin (ICA) were prepared through direct-ink three-dimensional (3D) printing technology. β-TCP in the composite scaffold had osteoconductive capability, and the ICA molecule had osteoinductive capacity. The β-TCP and ICA components in the composite scaffold can enhance the capability to repair skull defects. We show that ICA exhibited a slow-release behaviour within 80 days. This behaviour helped the scaffold to continuously stimulate the formation of new bone. The results of in vitro cell compatibility experiments showed that the addition of ICA molecules contributed to the adhesion and proliferation of MC-3T3-E1 cells. The level of alkaline phosphatase secretion demonstrated that the slow release of ICA can promote the osteogenic differentiation of MC-3T3-E1 cells. The introduction of ICA molecules accelerated the in situ bone regeneration in in vivo. It is concluded that the 3D-printed PVA scaffold with β-TCP and ICA has a wide range of potential applications in the field of skull defect treatment.Keywords:three-dimensional printing;polyvinyl alcohol;icariin;β-tricalcium phosphate;skull base defects

CAS / MDL: 7758-87-4
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Journal of Water Process Engineering · 2022 · IF 7.34

Construction of dual-functional membrane with novel structured β-cyclodextrin hybridization for simultaneous oily wastewater separation and hazardous aromatics removal

Chengdong Guan,Fang Xu,Yanlin Li,Lijun Zhu,Daohong Xia

During the separation of water-insoluble oil droplets in the oily wastewater by the membrane treatment process, the simultaneous removal of organic pollutants dissolved in the aqueous phase remains a challenge. Herein, we demonstrate an effective strategy for preparing dual-functional membranes with hybridization of novel β-cyclodextrin (β-CD) derivatives to achieve complete cleansing of oily sewage. Alkylenedioxy bridged bis(p-difluoro-p-dicyano) phenyl substituted β-CDs (R 3 -2T-2β-CD and R 6 -2T-2β-CD) are first synthesized and incorporated into three frequently used membranes (polyethersulfone (PES), poly( p -phenylene terephthalamide) (PPTA) and poly( m -phenylene isophthalamide) (PMIA)) casting solutions to fabricate hybrid membranes, respectively. The hydrophilicity of the prepared membrane can be improved greatly for the separation of oil-in-water emulsions. The PMIA/R 3 -2T-2β-CD membrane exhibited pure water permeances over 760.50 L·m −2 ·h −1 ·bar −1 with separation efficiency of the tween 80 stabilized diesel-in-water emulsion above 98.62% under cross-flow filtration. Significantly, the hybrid membranes could concurrently remove naphthalene and methylene blue dissolved in water during oil-in-water separation. This study proves the application potential of cyclodextrins in designing membrane materials and these one-step hybrid membranes can thoroughly decontaminate oil-in-water emulsions by eliminating the dissolved polycyclic aromatic molecules.

CAS / MDL: 584-08-7 504-63-2
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SENSORS AND ACTUATORS B-CHEMICAL · 2022 · IF 9.221

Self-assembled β-galactosidase on T4 phage capsid through affinity binding with enhanced activity and stability for rapid bacteria detection

Jingjing Xu,Qiaoli Yang,Pei Wang,Dan Wu,Xiaohan Yang,Wei Chen,Song Gao,Shenqi Wang

Due to the highly efficient and specific catalysis , enzymes have been extensively applied in various fields. In the development of enzyme-based sensing devices, the immobilization of enzyme is critical for achieving superior performance which is drastically dependent on enzyme stability and activity. In this study, we construct and assemble the beta-galactosidase( β -gal)-Soc fusion proteins onto biologically produced nanoparticle – T4 phage in vitro as a specific sensing probe for the rapid colorimetric detection of Escherichia coli K12. The stability and substrate affinity of β -gal assembled on T4 phage were largely enhanced in comparison with that of free β -gal due to this affinity-based immobilization, and the assay based on this β -gal T4 phage was able to quantify bacteria at concentration of 10 3 cfu mL −1 in drink water within 2 h. This affinity binding based enzyme immobilization strategy employed T4 bacteriophage capsid as the supporting nanoparticle and exhibited enhanced enzyme activity and stability which are highly favored for the future development of sensing applications.

CAS / MDL: 25952-53-8 6066-82-6
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JOURNAL OF SEPARATION SCIENCE · 2022 ·Vol. 45 ·期 9 ·1493-1501 · IF 3.614

β-Ketoenamine-linked covalent organic framework absorbent for online micro-solid phase extraction of trace levels bisphenols in plastic samples

Chengjiang Zhang,Hongmei Yuan,Zeyi Lu,Yuhuang Li,Lirong Zhao,Zhuomin Zhang,Gongke Li

Covalent organic frameworks with tunable porous crystallinity and outstanding stability have exhibited fascinating pretreatment performance as ideal extraction media. Herein, the β-ketoenamine-linked TpPa-1 synthesized by 1,3,5-triformylphloroglucinol and paraphenylenediamine was employed as the absorbent for online micro-solid phase extraction of trace bisphenols combined with high-performance liquid chromatography detection. A series of characterizations indicated that the TpPa-1 possessed large surface areas, high stability, and hydrophobicity. The main experimental parameters affecting the extraction efficiency were optimized in detail. Compared with four commercial sorbents, the TpPa-1 exhibited superior enrichment capacity for extracting bisphenols. Under the optimum conditions, the established method demonstrated a wide linear range and high sensitivity with the limit of detection ranging from 0.05–0.06 μg/L. Furthermore, the developed method was successfully applied to determine bisphenols in plastic samples. Bisphenol A was actually detected in a transparent box with a concentration of 0.31 μg/g, and the recoveries of the four bisphenols in the plastic samples were 80.5–116% with the relative standard deviation less than 9.2%. Such performance was attributed to recognition affinity, including the π-π affinity, hydrophobic effect, and hydrogen bond. These results demonstrated that TpPa-1 possessed great potential to be an excellent pretreatment medium for online separation and analysis of trace analytes in complex samples.

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ENVIRONMENTAL POLLUTION · 2023 · IF 8.9

MiR-133b as a crucial regulator of TCS-induced cardiotoxicity via activating β-adrenergic receptor signaling pathway in zebrafish embryos

Xiancheng Wan,Huili Wang,Qiuhui Qian,Jin Yan

As a commonly used antibacterial agent in daily consumer products, triclosan (TCS) has attracted significant attention due to its potential environmental risks. In this study, we investigated the toxic effects of TCS exposure (1.4 μM) on heart development in zebrafish embryos. Our findings revealed that TCS exposure caused significant cardiac dysfunction, characterized by pericardial edema, malformations in the heart structure, and a slow heart rate. Additionally, TCS exposure induced oxidative damage and abnormal apoptosis in heart cells through the up-regulation of β-adrenergic receptor (β-AR) signaling pathway genes ( adrb1 , adrb2a , arrb2b ), similar to the effects induced by β-AR agonists. Notably, the adverse effects of TCS exposure were alleviated by β-AR antagonists. Using high-throughput transcriptome miRNA sequencing and targeted miRNA screening, we focused on miR-133b, which targets adrb1 and was down-regulated by TCS exposure, as a potential contributor to TCS-induced cardiotoxicity. Inhibition of miR-133b produced similar toxic effects as TCS exposure, while overexpression of miR-133b down-regulated the β-AR signaling pathway and rescued heart defects caused by TCS. In summary, our findings provide new insights into the mechanisms underlying the cardiotoxic effects of TCS. We suggest that targeting the β-AR pathway and miR-133b may be effective strategies for pharmacotherapy in cardiotoxicity induced by environmental pollutants such as TCS.

CAS / MDL: 29122-68-7 7683-59-2
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EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY · 2023 · IF 6.7

A novel multifunctional mitochondrion-targeting NIR fluorophore probe inhibits tumour proliferation and metastasis through the PPARγ/ROS/β-catenin pathway

Jianv Wang,Jing Jia,Qingqing He,Yang Xu,Hongye Liao,Xia Xiong,Li Liu,Changzhen Sun

Recent advancements in tumour-targeted therapies and immunotherapy offer hope to patients with various malignancies. However, the uncontrolled growth and metastatic infiltration of malignant tumours remain a huge therapeutic challenge. Therefore, this study aimed to develop an integrated multifunctional diagnostic and treatment reagent IR-251 that can not only be used for tumour imaging but also to inhibit tumour growth and metastasis. Besides, our results showed that IR-251 targeted and damaged the mitochondria in cancer cells via organic anion-transporting polypeptides . Mechanistically, IR-251 induced ROS overproduction by inhibiting PPARγ and then inhibiting the β-catenin signalling pathway and downstream protein molecules related to the cell cycle and metastasis. Moreover, the excellent anti-tumour proliferation and metastasis ability of IR-251 were verified in vitro/in vivo . And histochemistry staining revealed that IR-251 inhibited tumour proliferation and metastasis, which showed no significant side effect. In conclusion, this novel, multifunctional, mitochondria-targeting near-infrared fluorophore probe IR-251 has great potential in achieving accurate tumour imaging and inhibiting tumour proliferation and metastasis, and the underlying mechanism of action of IR-251 is mainly via the PPARγ/ROS/β-catenin pathway.

CAS / MDL: 144-62-7 122320-73-4
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CANCER LETTERS · 2023 · IF 9.7

A multi-functional nano-system combining PI3K-110α/β inhibitor overcomes P-glycoprotein mediated MDR and improves anti-cancer efficiency

Ruikun Lin,Lei Zhang,Biwei Ye,Yanan Wang,Yi-Dong Li,Hsu Jason,Wenzhen Liu,Ping Hu,Jincan Chen,Zhe-Sheng Chen,Zhuo Chen

P-glycoprotein (P-gp/ABCB1)-mediated multidrug resistance (MDR) in cancers severely limit chemotherapeutic efficacy. We recently reported that phosphatidylinositol-3-kinase (PI3K) 110α and 110β subunits can be novel targets for reversal of P-gp mediated MDR in cancers, and BAY-1082439 as an inhibitor specific for PI3K 110α and 110β subunits could reverse P-gp-mediated MDR by downregulating P-gp expression in cancer cells. However, BAY-1082439 has very low solubility, short half-life and high in-vivo clearance rate. Till now, nano-system with the functions to target PI3K P110α and P110β and reverse P-gp mediated MDR in cancers has not been reported. In our study, a tumor targeting drug delivery nano-system PBDF was established, which comprised doxorubicin (DOX) and BAY-1082439 respectively encapsulated by biodegradable PLGA-SH nanoparticles (NPs) that were grafted to gold nanorods (Au NRs) modified with FA-PEG-SH, to enhance the efficacy to reverse P-gp mediated MDR and to target tumor cells, further, to enhance the efficiency to inhibit MDR tumors overexpressing P-gp. In-vitro experiments indicated that PBDF NPs greatly enhanced uptake of DOX, improved the activity to reverse MDR, inhibited the cell proliferation, and induced S-phase arrest and apoptosis in KB-C2 cells, as compared with free DOX combining free BAY-1082439. In-vivo experiments further demonstrated that PBDF NPs improved the anti-tumor ability of DOX and inhibited development of KB-C2 tumors. Notably, the metastasis of KB-C2 cells in livers and lungs of nude mice were inhibited by treatment with PBDF NPs, which showed no obvious in-vitro or in-vivo toxicity.

CAS / MDL: 9002-89-5
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JOURNAL OF DISPERSION SCIENCE AND TECHNOLOGY · 2021 · IF 2.262

Facile preparation of tertiary amine grafted poly (α,β-L-aspartic acid) with zwitterionic property to limit nonspecific protein adsorption

Xiaojuan Wang,Hanqing Gu,Guolin Wu

A series of poly (amino acid) with zwitterionic character was prepared for surface coating to avoid protein adsorption, by modifying the poly (aspartic acid) side chain with tertiary amine groups. An interesting and facile procedure is described with starts with polysuccinic acid which is followed by ring-opening with amino functions and finally hydrolysis of the remaining succinic acid groups achieving the polyaspartic acid structure as backbone. The degree of cationic tertiary amino group was easily varied by the degree of ring-opening with amines. The materials show isoelectric point between pH 4 and 9, have a typical zwitterionic character, and can be used to coat negatively as well as positively charged surfaces, depending on composition. The protein adsorption behavior is thus pH dependent and was studied with various proteins mainly available in blood. The adsorption test proved that a significant reduction of protein adsorption could be found for fibrinogen and albumin, and this protein-repellent behavior is strongly dependent on the amount of the absorbed polymer (adsorbed at pH = 7.4). This is a nice additional contribution to polymers with zwitterionic character used as coating reducing nonspecific protein adsorption.

CAS / MDL: 109-55-7
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Frontiers in Pharmacology · 2021 · IF 5.811

Berberine Improves Irinotecan-Induced Intestinal Mucositis Without Impairing the Anti-colorectal Cancer Efficacy of Irinotecan by Inhibiting Bacterial β-glucuronidase

Yue Bei,Gao Ruiyang,Lv Cheng,Yu Zhilun,Wang Hao,Geng Xiaolong,Wang Zhengtao,Dou Wei

Irinotecan (CPT11), a broad-spectrum cytotoxic anticancer agent, induces a series of toxic side-effects. The most conspicuous side-effect is gastrointestinal mucositis, including nausea, vomiting, and diarrhea. A growing body of evidence indicates that bacteria β-glucuronidase (GUS), an enzyme expressed by intestinal microbiota, converts the inactive CPT11 metabolite SN38G to the active metabolite SN38 to ultimately induce intestinal mucositis. We sought to explore the potential efficacy and underlying mechanisms of berberine on CPT11-induced mucositis. Our study showed that berberine (50 mg/kg; i. g.) mitigated the CPT11-induced loss of mucosal architecture, ulceration, and neutrophil infiltration. Meanwhile, berberine improved mucosal barrier function by increasing the number of globlet cells, protecting trans-endothelial electrical resistance (TEER), reducing permeability and increasing tight junction proteins expression. LC-MS analysis showed that berberine decreased the content of SN38 in feces, which correlated with decreases in both GUS activity and GUS-producing bacteria. Further molecular docking and Lineweaver-Burk plots analyses suggested that berberine functions as a potential non-competitive inhibitor against GUS enzyme. Of note, berberine maintained the anti-tumor efficacy of CPT11 in a tumor xenograft model while abrogating the intestinal toxicity of CPT11. Overall, we identified for the first time the remission effects of berberine on intestinal mucositis induced by CPT11 without impairing the anti-colorectal cancer efficacy of CPT11 partially via inhibiting bacterial GUS enzyme.

CAS / MDL: 60842-46-8
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MATERIALS & DESIGN · 2021 · IF 7.991

Realization of polyurethane/epoxy interpenetrating polymer networks with a broad high-damping temperature range using β-cyclodextrins as chain extenders

Qiang Feng,Menglu Shen,Jiaming Zhu,Jiang Li,Jie Zhang,Shaoyun Guo

Damping materials, especially high-damping (loss factor (tanδ) > 0.5 and above) materials, are widely applied for suppressing vibration and controlling noise in industrial field, but achieving a high tanδ over a wide temperature range is a challenging task. Herein, we report a novel polyurethane (PU)/epoxy (EP) interpenetrating polymer network (IPN) damping material by using 21-hydroxyl β-cyclodextrins (β-CDs) as PU chain extenders. At a high ratio of hydroxyls to isocyanate groups, every β-CD underwent a different degree of chain expansion. Then these β-CDs grafting different numbers of PU chains generated different-size hard segments, thus increasing the species of motion units and widening the damping temperature range. The unreacted hydroxyls on β-CDs provided a large quantity of hydrogen bonding protons, which could form hydrogen bonds with urethane groups, thus facilitating an increase in the tanδ value. Therefore, PU/EP IPNs with a broad high-damping temperature range were successfully prepared. The results showed that PU/EP IPNs cured by β-CDs underwent a damping temperature range of 93.1 K (tanδ > 0.5), 82.4 K (tanδ > 0.7) and even 74.1 K (tanδ > 0.8), much better than the corresponding 32.9 K, 23.9 K and 20.5 K for traditional PU/EP IPNs cured by trihydroxyl trimethylolpropane (TMP).

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JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY · 2017 · IF 3.225

The chemical speciation, spatial distribution and toxicity of mercury from Tibetan medicine Zuotai,β-HgS and HgCl2 in mouse kidney

Cen Li,Wei Xu,Shengqi Chu,Zhiyuan Zheng,Yuancan Xiao,Linshuai Li,Hongtai Bi,Lixin Wei

Zuotai , a famous Tibetan medicinal mixture containing β-HgS, has been used to combine with herbal remedies for treating diseases for more than 1 300 years. The target organ for inorganic mercury toxicity is generally considered to be the kidney. Therefore, it is crucial to reveal the chemical speciation , spatial distribution and potential nephrotoxicity of mercury from Zuotai in kidney. To date, this remains poorly understood. We used X-ray absorption spectroscopy (XAS) and micro X-ray fluorescence (μ-XRF) imaging based on synchrotron radiation to study mercury chemical forms and mercury special distribution in kidney after mice were treated orally with Zuotai , β-HgS or HgCl 2 . Meanwhile, the histopathology of kidney was observed. Mice exposed with Zuotai showed kidney with significant proportion of mercury ions bound to sulfydryl biomolecules (e.g. Cys-S-Hg-S-Cys) plus some of unknown species, but without methylmercury cysteine, which is the same as β-HgS and HgCl 2 . The mercury is mainly deposited in renal cortex in mouse treated with Zuotai , β-HgS or HgCl 2 , but with a low level of mercury in medulla. The total mercury in kidney of mice treated with HgCl 2 was much higher than that of β-HgS, and the later was higher than that of Zuotai . And, HgCl 2 cause severe impairments in mouse kidney, but that was not observed in the Zuotai and β-HgS groups. Meanwhile, the bio-metals (Ca, Zn, Fe and Cu) micro-distributions in kidney were also revealed. These findings elucidated the chemical nature, spatial distribution and toxicity difference of mercury from Zuotai , β-HgS and HgCl 2 in mouse kidney, and provide new insights into the appropriate methods for biological monitoring.

CAS / MDL: 7783-35-9 115-09-3
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BIOMACROMOLECULES · 2016 · IF 5.583

Polymersomes via Self-Assembly of Amphiphilic β-Cyclodextrin-Centered Triarm Star Polymers for Enhanced Oral Bioavailability of Water-Soluble Chemotherapeutics

Mengying Hu,Yurun Shen,Lu Zhang,Liyan Qiu

To date, improving oral bioavailability of water-soluble drugs with poor membrane permeability is still challenging. An example of this includes doxorubicin hydrochloride (DOX·HCl), a widely used chemotherapeutic. We therefore developed a novel DOX·HCl-loaded polymersome (Ps-DOX·HCl) self-assembled by amphiphilic β-cyclodextrin-centered triarm star polymer (mPEG2k-PLA3k)3-CD with the considerable drug loading capability. Using Madin-Darby canine kidney (MDCK) cells trans-well models, it was found that the cellular uptake and absorptive transport of DOX·HCl was significantly increased and the efflux was attenuated when delivered through polymersomes than free drugs. This phenomenon was further verified in mechanistic studies, which was attributed to the change in membrane transport pathway from paracellular route (free DOX·HCl) to active transcellular transport (drug-loaded polymersomes). Moreover, in vivo pharmacokinetic studies in mice demonstrated a significant increase in the oral bioavailability of Ps-DOX·HCl compared with free DOX·HCl (7.32-fold), as well as extended half-life (8.22-fold). This resulted in a substantial anticancer efficacy against mouse sarcoma 180 (S180) tumor in vivo. The cardiotoxicity, which is intrinsically induced by DOX·HCl, and toxicity toward gastrointestinal tissues were avoided according to histological studies. These findings indicate that (mPEG2k-PLA3k)3-CD copolymer displays great potential as a vehicle for the effective oral delivery of water-soluble drugs with low permeability.

CAS / MDL: 631-61-8
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