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MOLECULES · 2023 ·Vol. 28 ·期 6 ·2830 · IF 4.6

Bioactive C21 Steroidal Glycosides from Euphorbia kansui Promoted HepG2 Cell Apoptosis via the Degradation of ATP1A1 and Inhibited Macrophage Polarization under Co-Cultivation

Xiaoyi Feng,Jianchun Li,Hongmei Li,Xuanqin Chen,Dan Liu,Rongtao Li

Euphorbia kansuiis clinically used for the treatment of esophageal cancer, lung cancer, cancerous melanoma, asthma, pleural disorders, ascites, and pertussis, among other conditions. In this study, 12 steroids were obtained and identified fromE. kansui, and cynsaccatol L (5), which showed the best effects in terms of inhibiting the proliferation of HepG2 cells and the immune regulation of macrophages. Furthermore,5induced typical apoptotic characteristics in HepG2 cells, such as morphological changes and the caspase cascade, as well as inducing autophagy-dependent apoptosis via mitochondrial dysfunction and reactive oxygen species (ROS) accumulation. The antitumor mechanism of5might be related to promoting the endocytosis and degradation of ATP1A1 protein and then down-regulating the downstream AKT and ERK signaling pathways. Furthermore, the antiproliferation effect of5in co-cultivation with macrophages was investigated, which showed that5promoted the apoptosis of HepG2 cells by modulating the release of inflammatory cytokines, such as TNF-α and IFN-γ; regulating the M2-subtype polarization of macrophages; promoting the phagocytosis of macrophages. In conclusion,5exerted anti-proliferative effects by promoting the degradation of ATP1A1 and inhibiting the ATP1A1-AKT/ERK signaling pathway in HepG2. Furthermore, it regulated macrophage function in co-cultivation, thereby further exerting adjuvant anti-HepG2 activity.Keywords:Euphorbia kansui;antitumor;immunomodulatory;Na+, K+-ATPase;α1 subunit of NAK;dual antitumor activity

CAS / MDL: 67-68-5
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MATERIALS & DESIGN · 2023 · IF 8.4

Acceptor substitution engineering of BODIPY-based organic photosensitizers with aggregation-induced emission for organelle localization and photodynamic anticancer therapy

Chaojie Shen,Mintao Xie,Liying Pan,Binbin Wu,Wenxuan Zhang,Yuying Yuan,Yuan Chen,Yun-Yun Quan,Xiaoxia Ye,Zu-Sheng Huang

Photodynamic therapy (PDT) is a promising noninvasive treatment for cancer. Researchers have focused on improving the therapeutic effects of PDT in recent years. Subcellular organelles are the building blocks of cells, and their destruction can lead to cell dysfunction or even death. Photosensitizers (PSs) with precise organelle targeting capacity can not only kill cancer cells effectively but also help reduce PS dose, minimize side effects, and avoid drug resistance. Herein, four homologous luminogens with aggregation-induced emission (AIE) characteristics through acceptor substitution engineering are designed and synthesized to specifically anchor to mitochondria, cell membrane and lysosome through slight structural tweaks, and reactive oxygen species (ROS) are efficiently produced under light irradiation, which significantly enhance the therapy efficacy of PDT. Notably, biological studies have shown that membrane-targeted PS, TBVP exhibits more powerful therapeutic effects than other three PSs ( TBPy , TBPy-Bu and TBPy-TA ) at the same concentration. The highly effective anti-tumor activity of TBVP was evaluated successfully in vitro and in vivo . In addition, TBVP can promote cell autophagy to induce cell death. We thus believe the anchoring organelles approach described here represents an attractive therapeutic approach in photodynamic therapy.

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CHEMISTRY-A EUROPEAN JOURNAL · 2023 ·Vol. 29 ·期 34 ·e202300454 · IF 4.3

Au Nanozyme Driven Cascading Catalysis in Tollens′ Reaction: An Insight of Glucose Oxidase-Like Mechanism

Henglong Xiang,Sijun Huang,Dongwei Zhu,Liqiang Yu,Rui Liu,Yi Guo,Li Xu

Graphical [Ag(NH 3 ) 2 ] + can be directly used as an electron acceptor for the oxidation of glucose by AuNPs to accelerate Tollens′ reaction, The formed Ag nanoparticles continued to act as a cascading catalyst to accelerate the reaction and indicator, which provides a possibility for the rapid colorimetric glucose detection. Au nanoparticles (NPs) have been proven to be excellent glucose oxidase (GOx) mimics, which can catalyze the electrons transform pathway from glucose to oxygen. This study confirmed AuNPs can accelerate the reaction between [Ag(NH 3 ) 2 ] + and glucose under alkaline conditions, which is also known as the Tollens′ reaction, and the possible mechanism was proposed. Here, [Ag(NH 3 ) 2 ] + instead of O 2 acted directedly as an electron acceptor during glucose oxidation catalyzed by AuNPs, accompanied by hydrogen transfer. The as-synthesized Ag nanoparticles can also catalyze this process, similar to AuNPs, via a unique cascading catalysis mechanism in the Tollens′ reaction. A simple and heatless glucose colorimetric assay can be established based on the plasmonic band of AgNPs with a liner range of 0.6–22.2 μM, and the limit of detection is 0.32 μM.

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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2023 · IF 9.9

The enhanced visible light driven photocatalytic activity of zinc porphyrin/g-C3N4 nanosheet for efficient bacterial infected wound healing

Hao Cheng,Niuniu Wang,Yongqiang Yang,Xiong Jiao,Peide Han,Wangping Duan,Di Huang,Meiwen An,Weiyi Chen,Xiaohong Yao,Xiangyu Zhang

Graphitic carbon nitride (g-C 3 N 4 ) has received much attention as a metal-free polymeric two-dimensional photocatalyst for antibiotic-free antibacterial application. However, the weak photocatalytic antibacterial activity of pure g-C 3 N 4 stimulated by visible light limits its applications. Herein, g-C 3 N 4 is modified with Zinc (II) meso -tetrakis (4-carboxyphenyl) porphyrin (ZnTCPP) by amidation reaction to enhance the utilization of visible light and reduce the recombination of electron-hole pairs. The composite (ZP/CN) is used to treat bacterial infection under visible light irradiation with a high efficacy of 99.99% within 10 min due to the enhanced photocatalytic activity. Ultraviolet photoelectron spectroscopy and density flooding theory calculations indicate the excellent electrical conductivity between the interface of ZnTCPP and g-C 3 N 4 . The formed built-in electric field is responsible for the high visible photocatalytic performance of ZP/CN. In vitro and in vivo tests have demonstrated that ZP/CN not only possesses excellent antibacterial activity upon visible light irradiation, but also facilitates the angiogenesis. In addition, ZP/CN also suppresses the inflammatory response. Therefore, this inorganic–organic material can serve as a promising platform for effective healing of bacteria-infected wounds.

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Advanced Materials Technologies · 2023 · IF 6.8

Microfluidic Continuous Modification of Magnetic Nanoparticles for Circulating Tumor Cell Capture and Isolation

Changqing Zhang,Jianwei Lin,Yunru Yu,Dawei Deng,Ying Yu,Dagan Zhang,Qifeng Zhong

Circulating Tumor Cells (CTCs) enrichment technology refers to medical approaches for capturing and isolating target tumor cells, which has drawn great attention owing to its applications in the clinic such as cancer diagnosis and prognosis. Magnetic nanoparticles have emerged as an important platform for CTCs capture and isolation. However, due to the inert surface nature, the molecular phenotype analysis of CTCs and identification sensitivity remain a huge challenge. Herein, an ultrasound-activated microfluidic method is presented for rapid basic modification of magnetic nanoparticles, laying the foundation for further covalently binding of functional groups to capture CTCs. In this work, Fe 3 O 4 @SiO 2 nanoparticles obtained from microfluidics are hybrid with folic acid for the capture and isolation of CTCs with folate receptors such as Hela cells. The usage of microfluidic technology to upgrade Fe 3 O 4 nanoparticles provides the possibility for improving the detective efficiency of rare cells associated with malignancies, which sheds new light on future clinical applications.

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Nano Today · 2023 · IF 17.4

Radiation-enhanced self-cascade catalytic Ti3C2Tx-based platform enables controlled release of trans-resveratrol for synergistic radiosensitization against metastasis of orthotopic breast cancer

Xianyu Zhu,Wenqi Zhang,Huandong Xiang,Qingchao Chang,Ruixue Liu,Yilong Wan,Ruiting Zhang,Feng Zhao,Yongxing She,Hui Yuan,Jigang Yang,Qiqiang Li,Shanshan Wang,Liang Yan

Synergistic radiosensitization of cancer cells by metal-based nanomaterials and natural products is a forward-looking alternative for radiotherapy enhancement while inhibiting tumor metastasis. This work explores a phase change material (PCM)-gated Ti 3 C 2 T x nanosheet as a photothermal-responsive drug delivery system for loading natural trans -resveratrol (RSV), aiming at such synergistic radiosensitization in a controlled manner. This system can improve the biodispersity of RSV in the physiological solutions and inhibit the radiation-enhanced enzymatic activity of Ti 3 C 2 T x nanosheets to a large extent. Upon 808 nm near infrared light illimitation, Ti 3 C 2 T x -mediated photothermal heating makes the loaded PCM to be melted, resulting in the controlled release of RSV and simultaneous recovery of radiation-enhanced enzymatic activity of Ti 3 C 2 T x nanosheets. By further irradiating with X-ray, Ti 3 C 2 T x nanosheets is responsible for enhanced catalytic decomposition of H 2 O 2 to highly toxic hydroxyl radical as well as the consumption of intracellular glutathione . Both in vitro and in vivo studies demonstrate that those excess radical oxygen species can synergize with the released RSV to induce cancer cell death by apoptosis/ferroptosis hybrid pathway, fully inhibiting growth and metastasis of orthotopic breast cancer. These results reveal that the combination of PCM-gated Ti 3 C 2 T x nanosheets with RSV is capable of fabricating the photothermal-responsive theranostic systems and aiding the confinement of synergistic radiosensitization exclusively in the cancer cells for radiotherapy enhancement against tumor metastasis.

CAS / MDL: 69-78-3
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NEW JOURNAL OF CHEMISTRY · 2023 ·Vol. 47 ·期 17 ·7957-7960 · IF 3.3

Selective hydrogenolysis of agricultural straw-based cellulose to propylene glycol and acetol over acidic WOx/ZrO2

Zhicheng Luo,Zhiguo Zhu,Lupeng Han,Rui Xiao,Dawang Chu

WOx/ZrO2 is effective in the hydrogenolysis of cellulose to C3 products but the active sites on the W–Zr interfaces are hardly controlled. Herein, we prepared WOx/ZrO2 catalysts with active WOx species by simply varying the reduction temperatures, which selectively achieved C3 alcohol formation. A series of characterizations showed that increased reduction temperatures (400–600 °C) led to the formation of more dispersed WOx, while higher reduction temperatures (>600 °C) contributed to producing aggregated WO3 and W2C. At 600 °C, the dispersity of WOx peaked with a W5+/∑Wn+ ratio of 19%, providing abundant Lewis acid sites and oxygen vacancies (Vo), which were the active sites for glucose isomerization to fructose and C–C cleavage of fructose. A selectivity of 48% for C3 alcohols was obtained over the optimized WOx/ZrO2(600 °C) + Ru/AC catalyst.

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AAPS PHARMSCITECH · 2023 ·Vol. 24 ·期 4 ·1-18 · IF 3.3

Microfluidic Generation of Near-Infrared Photothermal Vitexin/ICG Liposome with Amplified Photodynamic Therapy

Cao Xia,Liu Qi,Adu-Frimpong Michael,Shi Wenwan,liu Kai,Deng Tianwen,Yuan Hui,Weng Xuedi,Gao Yihong,Yu Qingtong,Deng Wenwen,Yu Jiangnan,Wang Qilong,Xiao Gao,Xu Ximing

Glioma, in which a malignant tumor cell occurs in neural mesenchymal cells, has a rapid progression and poor prognosis, which is still far from desirable in clinical treatments. We developed a lab-on-a-chip (LOC) device for the rapid and efficient preparation of vitexin/indocyanine green (ICG) liposomes. Vitexin could be released from liposome to kill cancer cell, which can potentially improve the glioma therapeutic effect and reduce the treatment time through synergistic photodynamic/photothermal therapies (PDT/PTT). The vitexin/ICG liposome was fabricated via LOC and its physicochemical property and release in vitro were evaluated. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and live/dead staining were used to examine the enhanced antitumor effect of vitexin/ICG liposome in cooperation with PDT/PTT, while the related mechanism was explored by flow cytometry and western blot. The results were as follows: (1) The prepared vitexin/ICG liposome was smaller in size, homogenous in particle size distribution with significant low polydispersity index (PDI), and enhanced cumulative release in vitro . (2) We found that the formulated liposome presented strong cancer cell inhibition and suppression of its migration in a dose-dependent manner. (3) Further mechanistic studies showed that liposome combined with near-infrared irradiation could significantly upregulate levels of B cell lymphoma 2-associated X (Bax) protein and decrease B cell lymphoma 2 (Bcl-2) at protein levels. The vitexin/ICG liposomes prepared based on a simple LOC platform can effectively enhance the solubility of insoluble drugs, and the combined effect of PTT/PDT can effectively increase their antitumor effect, which provides a simple and valid method for the clinical translation of liposomes. Graphical Abstract

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ANALYTICAL SCIENCES · 2023 ·Vol. 39 ·期 7 ·1097-1106 · IF 1.6

Construction of a ratiometric fluorescent sensing platform based on near-infrared carbon dots for organophosphorus pesticides detection

Xie Wenfei,Liu Jinrui,Qu Yunting,Du Fangkai

In this work, a convenient ratiometric fluorescent platform was designed to measure organophosphorus pesticides (OPs) based on acetylcholinesterase (AChE), acetylthiocholine (ATCh), manganese dioxide nanosheets (MnO 2 ), near-infrared carbon dots (RCDs) and o-phenylenediamine (OPD). In this platform, a direct oxidation of OPD by MnO 2 generated the luminescent product 2,3-diaminophenolazine (DAP) through intrinsic oxidase activity, while RCDs served as a fluorescent reference indicator. In the presence of AChE and ATCh, the enzymatic hydrolysate thiocholine (TCh) would reduce MnO 2 nanosheets to Mn 2+ , leading to the quenching of DAP fluorescence. On the other hand, OPs can inhibit the catabolism of ATCh by AChE thus acting as a recognizer of OPs. According to these reactions, OPs were quantitatively analyzed by the intensity ratio of fluorescence emitted from RCDs and DAP ( F 560 / F 676 ). The constructed platform can detect OPs with the range of 0.2–0.6 μM with a detection limit of 4.3 nM. Graphical abstract Figure A ratiometric fluorescent probe based on carbon dots was obtained and using it to determine the concentration of organophosphorus pesticides

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APL Bioengineering · 2023 ·Vol. 7 ·期 1 · IF 6

pH/thermal dual-responsive multifunctional drug delivery system for effective photoacoustic imaging-guided tumor chemo/photothermal therapy

Wang Jun,Wu YanYan,Liu Kai,Yang Weitao,Zeng Weiwei,Gao Xiaolong,Liu ShiYuan,Zhang Bingbo

The development of a combination of chemo/photothermal therapy could overcome the limitations of single-modality therapy and enhance therapeutic efficacy. In this study, a pH/thermal dual-responsive multifunctional drug delivery system with dual-drug loading and enhanced chemo/photothermal therapy is developed based on polydopamine-coated mesoporous silica-gold nanorods (PDA-AuNRs@MSN). Nanoscale mesoporous silica-gold nanorods encapsulating doxorubicin (DOX) are designed as a core and then modified by polydopamine. The PDA shell not only conjugates with another anticancer bortezomib (Btz) to form pH-sensitive bond through boronic acid and catechol but also acts as a gatekeeper to control the release of doxorubicin and enhance the photothermal effect. Such a nanocarrier not only acts as a contrast agent for PA imaging but also serves as a therapeutic agent for enhanced chemo/photothermal therapy. The DOX and Btz could be released in an on-demand mode under near-infrared light irradiation and acid environment. The tumor size and location could be observed via PA imaging after intravenous injection into 4T1-bearing mice. Compared with AuNRs@MSN, PDA-AuNRs@MSN exhibit an increased near-infrared (NIR) absorption at 808 nm and an enhanced photothermal effect. The integrated D/B-PDA-AuNRs@MSN nanoparticles show higher cell apoptosis and enhanced tumor treatment efficacy in vitro and in vivo in comparison with single chemotherapy or photothermal therapy. Combined together, D/B-PDA-AuNRs@MSN show pH/thermal-responsive controlled-release and synergistic chemo/photothermal therapy for tumor.

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COLLOIDS AND SURFACES B-BIOINTERFACES · 2023 · IF 5.8

Fe-doped mesoporous silica catalyzes ascorbic acid oxidation for tumor-specific therapy in scaffold

Cijun Shuai,Xuan Chen,Chongxian He,Min Chen,Shuping Peng,Wenjing Yang

Ascorbic acid (AA) is a promising antitumor agent, yet its autooxidation is too slow which constrains the further application. Fortunately, the autoxidation process can be accelerated by transition metal catalysts , especially Fe 3+ ions. In this study, AA was loaded to Fe-doped mesoporous silica (designated as [email protected] 2 ), which was introduced into poly- L -lactic acid (PLLA) and then prepared into a scaffold. Mechanistically, [email protected] 2 degraded in acidic tumor microenvironment because excessive H + substituted Fe atoms in the iron silicate framework, releasing Fe 3+ and AA. The Fe 3+ boosted the pro-oxidation reaction of AA, generating numerous hydrogen peroxide (H 2 O 2 ) and Fe 2+ . Then, Fe 2+ reacted with H 2 O 2 to initiate Fenton reactions favoring hydroxyl radical generation, triggering oxidative damage on tumor cells to implement tumor-specific therapy. Results showed that the release amount of AA in acidic solution was about 3 times higher than that in neutral solution, which was attributed to the pH-dependency of the degradation of [email protected] 2 in scaffold. Furthermore, the scaffold generated numerous ascorbate radical intermediate and increased the H 2 O 2 concentration by 120.2%, demonstrating that Fe 3+ remarkably accelerated the oxidation rate of AA. Cell experimental results showed that the scaffold caused massive apoptosis of tumor cells, while no obvious cytotoxicity to normal cells, confirming the antitumor specificity of scaffold. This work paves a promising way to construct a biodegradable and catalytic scaffold, featuring effective tumor-specific therapy.

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FOOD AND CHEMICAL TOXICOLOGY · 2023 · IF 4.3

In vitro and in silico assessment of endocrine disrupting effects of food contaminants through pregnane X receptor

Yuan Liang,Qiuyan Jiang,Yiyao Gong,Yifan Yu,Haoyang Zou,Jingqi Zhao,Tiehua Zhang,Jie Zhang

As a promiscuous xenobiotic receptor, pregnane X receptor (PXR) has been confirmed to participate in numerous physiological process. In addition to the conventional estrogen/androgen receptor, PXR also serves as an alternative target for environmental chemical contaminants. In this work, the PXR-mediated endocrine disrupting effects of typical food contaminants were explored. Firstly, the time-resolved fluorescence resonance energy transfer assays confirmed the PXR binding affinities of 2,2′,4,4′,5,5′-hexachlorobiphenyl, bis(2-ethylhexyl) phthalate , dibutyl phthalate , chlorpyrifos , bisphenol A , and zearalenone , with IC50 values ranging from 1.88 to 4284.00 nM. Then their PXR agonist activities were assessed by PXR-mediated CYP3A4 reporter gene assays. Subsequently, the regulation of gene expressions of PXR and its targets CYP3A4 , UGT1A1 , and MDR1 by these compounds was further investigated. Intriguingly, all the tested compounds interfered with these gene expressions, confirming their endocrine disrupting effects via PXR-mediated signaling. The compound-PXR-LBD binding interactions were explored by molecular docking and molecular dynamics simulations to unravel the structural basis of their PXR binding capacities. The weak intermolecular interactions are key players in stabilizing these compound-PXR-LBD complexes. During the simulation process, 2,2′,4,4′,5,5′-hexachlorobiphenyl remained stable while the other 5 compounds underwent relatively severe disturbances. In conclusion, these food contaminants might exhibit endocrine disrupting effects via PXR.

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