Scientific Reports
·
2017
·Vol. 7
·期 1
·1-10
·
IF 4.259
Du Jianwei,Zhang Peng,Zhao Xiao,Wang Youxiang
Cucurbit[7]uril (CB[7]), a representative member of the host family cucurbit[n]uril, can host-guest interact with many guest molecules such as adamantane, viologen and naphthalene derivatives. This host-guest interaction provides an easy strategy in gene vector assembling. Furthermore, CB[7] can self-assemble on gold nanospheres (AuNSs). Herein, the combination of CB[7] and AuNSs provides both advantages of host-guest interaction and photo-thermal effect of AuNSs. In this study, polyethyleneimine (PEI) and polyethylene glycol (PEG) were separately interacted with CB[7] via host-guest interaction. Then by assembling on AuNSs, PEI and PEG were combined together to condense DNA into polyplexes as well as enhance circulation stability of the polyplexes. These gene vectors were found to have high cellular uptake efficiency and low cytotoxicity. Furthermore, the well distributed AuNSs in the polyplexes could transform light into heat under light exposure because of the photo-thermal effect. This was found to effectively promote the entry of gene into cytoplasm and highly enhanced gene transfection efficiency.
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INTERNATIONAL IMMUNOPHARMACOLOGY
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2024
·
IF 4.8
Feng-Ling Tang,Li-Wei Xie,Lin-Feng Tang,Hai-Yan Lu,Rui-Qiu Zhu,Di-Fan Wang,Ye Tian,Shang Cai,Ming Li
The small intestine exhibits remarkable sensitivity to ionizing radiation (IR), which significantly hampers the effectiveness of radiotherapy in the treatment of abdominal and pelvic tumors. Unfortunately, no effective medications are available to treat radiation-induced intestinal damage (RIID). Fraxin (7-hydroxy-6-methoxycoumarin 8-glucoside), is a coumarin derivative extracted from the Chinese herb Cortex Fraxini. Several studies have underscored the anti-inflammatory, antibacterial, antioxidant, and immunomodulatory properties of fraxin. However, the efficacy of fraxin at preventing or mitigating RIID remains unclear. Thus, the present study aimed to investigate the protective effects of fraxin against RIID in vitro and in vivo and to elucidate the underlying mechanisms. The study findings revealed that fraxin markedly ameliorated intestinal injuries induced by 13 Gy whole abdominal irradiation (WAI), which was accompanied by a significant increase in the population of Lgr5 + intestinal stem cells (ISCs) and Ki67 + progeny. Furthermore, fraxin mitigated WAI-induced intestinal barrier damage, and reduced oxidative stress and intestinal inflammation in mice. Transcriptome sequencing of fraxin-treated mice revealed upregulation of IL-22, a pleiotropic cytokine involved in regulating the function of intestinal epithelial cells. Moreover, in both human intestinal epithelial cells and ex vivo cultured mouse intestinal organoids, fraxin effectively ameliorated IR-induced damage by promoting the expression of IL-22. The radioprotective effects of fraxin were partially negated in the presence of an IL-22-neutralizing antibody. In summary, fraxin is demonstrated to possess the ability to alleviate RIID and maintain intestinal homeostasis , suggesting that fraxin might serve as a strategy for mitigating accidental radiation exposure- or radiotherapy-induced RIID.
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TOXICOLOGY
·
2024
·
IF 4.8
Yiren Xiong,Guoqiang Guo,Hongyi Xian,Zuqing Hu,Di Ouyang,Jiayi He,Shanshan He,Renyi Liu,Zhenjie Gao,Meilin Tang,Ying Chen,Suqin Tan,Xiaoqi Zhu,Abudumijiti Abulimiti,Sujin Zheng,Hehai Huang,Dalin Hu
Tributyltin chloride (TBTC) is a ubiquitous environmental pollutant with various adverse effects on human health. Exosomes are cell - derived signaling and substance transport vesicles. This investigation aimed to explore whether exosomes could impact the toxic effects caused by TBTC via their transport function. Cytotoxicity, DNA and chromosome damage caused by TBTC on MCF-7 cells were analyzed with CCK-8, flow cytometry, comet assay and micronucleus tests, respectively. Exosomal characterization and quantitative analysis were performed with ultracentrifugation, transmission electron microscope (TEM) and bicinchoninic acid (BCA) methods. TBTC content in exosomes was detected with Liquid Chromatography-Mass Spectrometry (LC-MS). The impacts of exosomal secretion on the toxic effects of TBTC were analyzed. Our data indicated that TBTC caused significant cytotoxicity, DNA and chromosome damage effects on MCF-7 cells, and a significantly increased exosomal secretion. Importantly, TBTC could be transported out of MCF-7 cells by exosomes. Further, when exosomal secretion was blocked with GW4869, the toxic effects of TBTC were significantly exacerbated. We concluded that TBTC promoted exosomal secretion, which in turn transported TBTC out of the source cells to alleviate its toxic effects. This investigation provided a novel insight into the role and mechanism of exosomal release under TBTC stress.
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INORGANIC CHEMISTRY
·
2024
·
IF 4.3
Ziyan Lv,Rukang Li
A new noncentrosymmetric crystal Na12(NbO)3(PO4)7 was successfully synthesized in the niobium phosphate system. Its structure characterizes isolated and highly distorted NbO6 octahedra joining with isolated PO4 groups to form a unit of a (Nb6P6O12) hexagonal star by sharing O atoms. In (Nb6P6O12) hexagonal stars, all Nb and P atoms are in a hexagonal star-like arrangement and all Na atoms are also in a hexagonal star-like arrangement, except for Na(3) and Na(10) atoms. Notably, it exhibits a strong phase-matched second harmonic response: 3 × KDP, which is rare in known niobium phosphate systems. Meanwhile, it also has a wide optically transparent window (0.29–4.44 μm) and a high laser-induced damage threshold (3.5 GW/cm2). More importantly, Na12(NbO)3(PO4)7 is a congruent melting compound that has the potential to be grown into large-sized single crystals by the Czochralski method. These excellent properties make it a promising candidate as a mid-infrared nonlinear optical crystal.
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Journal of Environmental Chemical Engineering
·
2025
·
IF 7.2
Yang Gao,Yuyang Wang,Yanlin Jiang,Chaojie Bai,Zuoqun Zhang,Yawen Zhao,Congjie Gao,Lixin Xue
To improve interface compatibility between ZIF-7 particles (PTs) and polyamide (PA) and reverse osmosis (RO) performance of thin film nano-composite (TFN) membranes, ZIF-7-NH 2 (x) particles (PTs) with different levels of -NH 2 substitution were synthesized by reacting Zn(NO 3 ) 2 with mixed ligand under different preparation conditions. The impact of their residual surface functional groups (SFGs) on the formation of inter-phase covalent bonds (ICBs) in PA separating layers were investigated relating to the inter-phase compatibility and salt rejection performance of the formed composite RO membranes. Doping ZIF-7-NH 2 PTs with ICBs could avoid the expansion of PA in acidic condition. Surprisingly high chemical stability was observed for ZIF-7-NH 2 PTs wrapped in the PA separating layers in TN membranes in the pH range of 2–13. TN(50)-0.15 membranes with strong ICBs showed 3 times higher water flux of 76 L·m −2 ·h −1 under 5.5 MPa at a high salt rejection of 98.7 %.
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Food Bioscience
·
2024
·
IF 4.8
Siyi Song,Shuqi He,Qianxia Lin,Huoxi Jin
Hypertension significantly contributes to adverse cardiovascular outcomes. Our investigation was designed to evaluate the effects of supplementation with collagen peptide (LR-7) and taurine (Tau) on cardiovascular impairment in hypertensive mice induced by an 8% high-salt (HS) diet. Compared to administration of LR-7 (200 μmol/kg) or Tau (200 μmol/kg) alone, the combined treatment of LR-7 (100 μmol/kg) and Tau (100 μmol/kg) exhibited the strongest inhibition of systolic blood pressure elevation, aortic intimal thickening, reduction in myocardial fiber density, and myocardial fibrosis in HS-induced hypertensive mice. Furthermore, the treatment with LR-7+Tau significantly ameliorated the levels of cardiac adhesion factor (intercellular adhesion molecule 1), antioxidant enzymes (catalase and glutathione peroxidase), and inflammatory markers (interleukin-6, interleukin-1β, and nuclear factor kappa-B) in hypertensive mice compared to either LR-7 or Tau alone. To uncover the underlying mechanisms, the calpain 1/junctophilin-2 (JP2) pathway in cardiac tissue was investigated. Our findings revealed that LR-7+Tau treatment reversed the abnormal expression of calpain 1 and JP2 proteins in cardiac tissue. Additionally, it upregulated the endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (p-eNOS) levels in the heart. In summary, LR-7 and Tau collectively exerted a cardiovascular protective effect in HS diet-induced hypertensive mice, demonstrating synergistic efficacy.
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SEPARATION AND PURIFICATION TECHNOLOGY
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2024
·
IF 8.1
Ming Sun,Yuqiao Jiang,Qinhua Qu,Jingya Yang,Linyan Cheng,Cheng Fang,Hongping Li,Jing Ding,Hui Wan,Guofeng Guan
The preparation of cyclic carbonates via CO 2 cycloaddition reaction was crucial for the lithium industry. Herein, a series of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) based hyper-crosslinked ionic polymers with different ionic site densities were prepared by simultaneously Friedel-Crafts alkylation and quaternization reactions. The obtained P[DBU]DCX(1:1) with a high ionic site density (1.45 mmol‧g −1 ), prepared by the equimolar ratio of 1,8-diazabicyclo[5.4.0]undec-7-ene and α,α′-dichloro-p-xylene, exhibiting excellent catalytic performance with a chloropropylene carbonate (CPC) yield of 98.8 % and selectivity of 99.3 % at atmospheric pressure. Meanwhile, the conversion capacity was comparable with other catalysts. Moreover, the CO 2 cycloaddition reaction over P[DBU]DCX(1:1) catalyst followed pseudo-first-order kinetics, and the activation energy ( Ea ) was obtained to be 28.7 kJ/mol by performing kinetic experiments at different temperatures. In addition, it also had a good reusability and universality for different epoxides. The synergistic effects of abundant quaternary nitrogen cations derived from DBU and chlorine anions on the activation of CO 2 and epoxide were explored based on density functional theory calculation. This study offers a new approach for the design and application of hyper-crosslinked ionic polymers for efficient CO 2 conversion at atmospheric pressure.
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RSC Advances
·
2015
·Vol. 5
·期 19
·14858-14870
·
IF 3.84
Qingqing Yang,Lian Li,Xi Zhu,Wei Sun,Zhou Zhou,Yuan Huang
Thanks to the enhanced cancer cell affinity, modification of polymeric drug carriers with an active targeting ligand has been one of the most effective strategies to achieve better therapeutic efficacy. However, hydrophobic ligands (e.g. folate), when conjugated to hydrophilic carriers, encounter the problem of reduced targeting effectiveness due to the fact that the ligand may be buried inside the carrier. In the present study, we studied the impact of the hydrophilic polymer structure on the targeting efficiency of the conjugated folate (FA). After modification with folate, the linear N-(2-hydroxypropyl)-methacrylamide (HPMA) polymer (P-FA, 27.3 kDa) exhibited a neutral surface charge (1.5 mV), while the graft HPMA polymer (GP-FA, 117.4 kDa) possessed a mild negative charge (−7.2 mV), which suggests different exposure levels of negatively charged folate on the surface of P-FA and GP-FA. Notably, on folate receptor positive MCF-7 cells, P-FA exhibited comparable cell uptake with the unmodified linear polymer, whereas GP-FA resulted in 2-fold higher cell internalization over the untargeted graft polymer. Meanwhile, the involvement of folate receptor mediated endocytosis and augmented folate binding affinity of GP-FA were observed in comparison with P-FA. Moreover, GP-FA exhibited significantly enhanced tumor accumulation relative to GP, while marginally improved tumor accumulation was observed for P-FA compared with P. In summary, the structure of the hydrophilic polymer plays a vital role in the targeting efficiency of the conjugated hydrophobic ligand.
研究领域:
药学
·
聚合物化学
·
癌症研究
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JOURNAL OF ALLOYS AND COMPOUNDS
·
2022
·
IF 6.371
Xiyuan Tao,Li Yang,Jiali Liu,Zihao Zang,Peng Zeng,Changfei Zou,Lingguang Yi,Xiaoyi Chen,Xiaolin Liu,Xianyou Wang
Garnet-type Li 7 La 3 Zr 2 O 12 (LLZO) is a promising solid-state electrolyte (SSE) for next generation lithium batteries due to its high Li + conductivity and stability against lithium metal, especially the Li 7−3x Ga x La 3 Zr 2 O 12 (Ga-LLZO) is most valuable because of its high ionic conductivity (> 1 ×10 −3 S cm −1 ). However, it is difficult to prepare high-quality Ga-LLZO by the traditional air ambient sintering. Herein, we develop a simple and efficient rapid ultra-high-temperature sintering (RUHTS) method to prepare high-conductivity Ga-LLZO ceramic SSE. It has been found that the as-prepared Ga-LLZO ceramic SSE with the composition of Li 6.25 Ga 0.25 La 3 Zr 2 O 12 exhibits high relative density of 99%, good ionic conductivity of 1.48 × 10 −3 S cm −1 and large critical current density of 0.5 mA cm −2 after sintering at 1200 °C for 2 min. In addition, the Ga-LLZO SSE shows good electrochemical stability and interfacial compatibility against Li metal. The assembled Li-Li symmetric cell represents a small interfacial impedance of 37 Ω cm 2 . In the same time, the Li/Ga-LLZO/LE+LMNCO full battery has a total impedance of 205 Ω cm 2 , and can deliver a first discharge capacity of 235.1 mAh g −1 at 0.5 C, and the capacity retention rate is 88.3% after 100 cycles. This indicates that the as-prepared Ga-LLZO has good application prospect in the Li-metal solid-state batteries (LMSSBs). Moreover, this method does not require the use of mother powder during preparation process, which will effectively reduce the waste of raw materials, save manufacture costs and be beneficial to quantity production of Ga-LLZO ceramic electrolyte.
研究领域:
材料科学
·
电化学
·
电池技术
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PHYTOMEDICINE
·
2021
·
IF 5.34
Lei Yu,Shuang Han,Lang Lang,Hui Song,CaiYun Zhang,Lin Dong,ShaoHua Jia,Ying Zhang,Di Xiao,Jun Liu,Ying Xu,XiaoPo Zhang
Background DNA topoisomerase (Topo) inhibition plays key role in breast cancer treatment. Stephania hainanensis H. S. Lo et Y. Tsoong ( S. hainanensis ), a Li nationality plant that has abundant aporphine alkaloids , can inhibit Topo. Purpose To identify a dual Topo inhibitor , a deep and systematic study of active aporphine alkaloids in S. hainanensis and their mechanisms of inhibiting breast cancer proliferation and Topo activity are essential. Study design This study aimed to assess the anti-breast cancer and Topo inhibitory activities of oxocrebanine and explore the underlying mechanisms. Methods The growth inhibitory activities of 12 compounds in S. hainanensis were screened by MTT assay in MCF-7, SGC-7901, HepG-2 cells, and compared with the effects on human normal mammary epithelial MCF-10A cells as non cancer control cells. The Topo inhibitory activity was assessed by DNA relaxation and unwinding assays, kDNA decatenation assay and western blot . Cell cycle and autophagy analyses were carried out with flow cytometry and staining. Acridine orange staining and α-tubulin morphology were observed by fluorescence microscopy . Western blot was used to examine microtubule assembly dynamics and the expression levels of key proteins associated with DNA damage, autophagy and mitotic arrest . Results Oxocrebanine was the anti-breast cancer active alkaloid in S. hainanensis . It exhibited the best inhibitory effect on MCF-7 cells with an IC 50 of 16.66 μmol/l, and had only weak effect on the proliferation of MCF-10A cells. Oxocrebanine inhibited Topo I and II α in a cell-free system and in MCF-7 cells. The DNA unwinding assay suggested that oxocrebanine intercalated with DNA as a catalytic inhibitor. Oxocrebanine regulated the levels of Topo I and IIα and DNA damage-related proteins. Oxocrebanine led to the mitotic arrest, and these effects occurred through both p53-dependent and p53-independent pathways. Oxocrebanine induced autophagy, abnormal α-tubulin morphology and stimulated enhanced microtubule dynamics. Conclusion Oxocrebanine was the anti-breast cancer active aporphine alkaloid in S. hainanensis . Oxocrebanine was a Topo I/IIα dual inhibitor, catalytic inhibitor and DNA intercalator . Oxocrebanine caused DNA damage, autophagy, and mitotic arrest in MCF-7 cells. Oxocrebanine also disrupted tubulin polymerization. Accordingly, oxocrebanine held a great potential for development as a novel dual Topo inhibitor for effective breast cancer treatment.
研究领域:
癌症研究
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药理学
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分子生物学
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植物化学
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细胞生物学
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BIOLOGICAL PROCEDURES ONLINE
·
2022
·Vol. 24
·期 1
·1-16
·
IF 7.717
Mei Jie,Cai Yun,Xu Rui,Yu Xinqian,Han Xu,Weng Miaomiao,Chen Lingyan,Ma Tao,Gao Tianshu,Gao Fei,Xia Tiansong,Zhu Yichao,Zhang Yan
Background Angiotensin-converting enzyme 2 (ACE2) is known as a tumor suppressor and lowly expressed in most cancers. The expression pattern and role of ACE2 in breast cancer (BC) have not been deeply elucidated. Methods A systematic pan-cancer analysis was conducted to assess the expression pattern and immunological role of ACE2 based on RNA-sequencing (RNA-seq) data downloaded from The Cancer Genome Atlas (TCGA). The correlation of ACE2 expression and immunological characteristics in the BC tumor microenvironment (TME) was evaluated. The role of ACE2 in predicting the response to therapeutic options was estimated. Moreover, the pharmacodynamic effect of angiotensin-(1–7) (Ang-1–7), the product of ACE2, on chemotherapy and immunotherapy was evaluated on the BALB/c mouse BC model. In addition, the plasma samples from BC patients receiving neoadjuvant chemotherapy were collected and subjected to the correlation analysis of the expression level of Ang-1–7 and the response to neoadjuvant chemotherapy. Results ACE2 was lowly expressed in BC tissues compared with that in adjacent tissues. Interestingly, ACE2 was shown the highest correlation with immunomodulators, tumor-infiltrating immune cells (TIICs), cancer immunity cycles, immune checkpoints, and tumor mutation burden (TMB) in BC. In addition, a high level of ACE2 indicated a low response to endocrine therapy and a high response to chemotherapy, anti-ERBB therapy, antiangiogenic therapy and immunotherapy. In the mouse model, Ang-1–7 sensitized mouse BC to the chemotherapy and anti-PD-1 immunotherapy, which revealed its significant anti-tumor effect. Moreover, a high plasma level of Ang-1–7 was associated with a better response to neoadjuvant chemotherapy. Conclusions ACE2 identifies immuno-hot tumors in BC, and its enzymatic product Ang-1–7 sensitizes BC to the chemotherapy and immunotherapy by remodeling the TME.
研究领域:
肿瘤学
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免疫学
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分子生物学
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药理学
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JOURNAL OF MEDICINAL CHEMISTRY
·
2026
·
IF 7.3
Han Wang,Weiming Liao,Yunzhe Li,Aiping Guo,Zhenyu Liu,Xinyu Guo,Kexin Wang,Yulin Zheng,Zihan Wang,Wei Wang,Xiaowei Wang,Liangren Zhang,Qi Sun,Zhuo Huang
Activation of extrasynaptic δ-GABAARs represents a promising strategy for rapid-acting antidepressant therapy in major depressive disorder (MDD). Here, we report the discovery and pharmacological characterization of a novel series of thiazolo[4,5-d]pyrimidin-7(6H)-one derivatives as potent positive allosteric modulators selective for δ-GABAARs. Systematic SAR exploration identified compound 12i as a lead candidate, which demonstrated high potency on the extrasynaptic receptor subtype (α4β3δ: 950% current enhancement at 10 μM, EC50 = 0.8 μM) while maintaining favorable modulation of synaptic subtypes. In vivo, 12i exerted rapid-acting antidepressant effects in both the mouse tail suspension test and the chronic restraint stress-induced depression model, with no addictive behaviors observed. These effects were completely abolished in δ-subunit knockout mice, confirming target engagement. Furthermore, 12i significantly enhanced NREM sleep in a p-chlorophenylalanine-induced insomnia model, highlighting potential dual efficacy in MDD with comorbid sleep disturbance. Collectively, these findings position 12i as a promising clinical candidate for next-generation rapid-acting antidepressant therapy.
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