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Journal of Materials Chemistry A · 2021 ·Vol. 9 ·期 8 ·4758-4769 · IF 12.732

Highly stretchable, non-flammable and notch-insensitive intrinsic self-healing solid-state polymer electrolyte for stable and safe flexible lithium batteries

Cheng Wang,RuiJing Li,Peng Chen,Yongsheng Fu,XinYan Ma,Tao Shen,Baojing Zhou,Ke Chen,JiaJun Fu,Xiaofang Bao,Wuwei Yan,Yong Yang

Solid-state polymer electrolytes (SPEs) with superior self-healing capacity are urgently required for next-generation flexible energy storage devices. Herein, a highly stretchable (extensibility > 4000% and stress > 130 kPa), non-flammable and notch-insensitive intrinsic self-healing solid-state polymer electrolyte (SHSPE) was prepared based on the combination of a poly(HFBM-co-SBMA) network, imidazole-based ionic liquid (EMI–TFSI) and LiTFSI. The incorporation of the imidazole cation and fluorine atom contributed to the formation of supramolecular bonds (ion–dipole interactions) inside the electrolyte framework, thus endowing SHSPE with prominent self-healing ability (recovery time < 60 min, 25 °C). Moreover, the density functional theory (DFT) calculations indicated that the large electrostatic attraction of SO3− towards Li+ liberated it from trapping in the ionic reservoir of TFSI− and EMI+, thereby resulting in a superior tLi+ (0.37). The electrochemical window of SHSPE achieved was 4.9 V vs. Li+/Li, which well satisfies the demand for safe lithium batteries. The optimized SHSPE3 presented excellent interfacial compatible property with a lithium electrode and record adhesion strength (weight loading > 200 g). The as-assembled Li/SHSPE3/LiFePO4 battery delivered a high discharge capacity of 144.8 mA h g−1 at 0.2C, and its capacity retention ratio reached 82% after 100 cycles with a coulombic efficiency of 97%. In particular, the mechanical properties and conductivity of SHSPE3 could fully recover after repeated damage, conferring the derived soft-pack battery excellent anti-fatigue capability. The use of intrinsic self-healing principles in the field of SPEs provides new insight for developing reliable and safe flexible electronic devices.

CAS / MDL: 90076-65-6 174899-82-2
研究领域: 材料科学 · 能源存储技术 · 化学工程
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SCIENCE OF THE TOTAL ENVIRONMENT · 2018 · IF 4.61

Exposure to acrylamide disrupts cardiomyocyte interactions during ventricular morphogenesis in zebrafish embryos

Mengmeng Huang,Fanghuan Zhu,Jingjing Jiao,Jun Wang,Yu Zhang

Acrylamide (AA), a ubiquitous chemical that is present in surrounding environment and baked or fried carbohydrate-rich food, has recently been linked to cardiac developmental toxicity. However, the toxicological role of AA exposure in the cardiac development remains largely unknown. Here we showed the cardiotoxicity of AA and its role in cardiomyocyte interactions in zebrafish embryos during ventricular morphogenesis. Using the embryo model of transgenic zebrafish Tg(Tp1:d2GFP ; myl7:mCherry) , we found AA interfered the dynamics of Notch signaling in the endocardium during early cardiogenesis. Prolonged exposure to AA thickened the chamber wall and prevented the trabeculae from extending into the lumen of ventricular chamber. As a result, AA reduced the ventricular shortening fraction and spatial dimension via excessively activating the Notch signal in myocardium during cardiac maturation. Moreover, exposure to AA inhibited the re-distribution of N ‑cadherin and failed to coordinate cardiomyocyte interactions between the myocardium layers due to the lack of delaminated cardiomyocytes. Therefore, AA-treated embryos exhibited subcellular pathological states including disarrayed myofibrils and abnormal morphology of mitochondria despite normal proliferation of cardiomyocytes. In addition, we found overexpression of some cardiac-specific transcription factors, such as hand2 and nkx2.5 , in hearts of AA-treated embryos compared with those in control group. Our study provided the evidence that the period of ventricular chamber morphogenesis might be a vulnerable window in zebrafish, and revealed new insights into how AA might exert cardiac developmental toxicity.

研究领域: 毒理学 · 发育生物学 · 心脏病学
✓ 已验证 DOI PubMed 高影响因子
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Reproductive Biology · 2023 · IF 2.1

Gastrodin protects porcine sertoli cells from zearalenone-induced abnormal secretion of glial cell line-derived neurotrophic factor through the NOTCH signaling pathway

Yulu Cao,Jingjing Wang,Xiaoxiao Li,Biyun Liu,Chongjun Li,Yijin Sun,Kang Zou

Zearalenone (ZEA) is a prevalent mycotoxin found in moldy diets and is associated with reproductive dysfunction. However, the molecular underpinning of ZEA in impairment of spermatogenesis remains largely unknown. To unveil the toxic mechanism of ZEA, we established a co-culture model using porcine Sertoli cells and porcine spermatogonial stem cells (pSSCs) to investigate the impact of ZEA on these cell types and their associated signaling pathways . Our findings showed that low concentration of ZEA inhibited cell apoptosis , while high concentration induced cell apoptosis. Furthermore, the expression levels of Wilms’ tumor 1 (WT1), proliferating cell nuclear antigen (PCNA) and glial cell line-derived neurotrophic factor (GDNF) were significantly decreased in ZEA treatment group, while concurrently upregulating the transcriptional levels of the NOTCH signaling pathway target genes HES1 and HEY1 . The addition of the NOTCH signaling pathway inhibitor DAPT (GSI-IX) alleviated the damage to porcine Sertoli cells caused by ZEA. Gastrodin (GAS) significantly increased the expression levels of WT1, PCNA and GDNF, and inhibited the transcription of HES1 and HEY1 . GAS also efficiently restored the decreased expression levels of DDX4, PCNA and PGP9.5 in co-cultured pSSCs suggesting its potential in ameliorating the damage caused by ZEA to Sertoli cells and pSSCs. In conclusion, the present study demonstrates that ZEA disrupts pSSCs self-renewal by affecting the function of porcine Sertoli cell, and highlights the protective mechanism of GAS through the regulation of the NOTCH signaling pathway. These findings may offer a novel strategy for alleviating ZEA-induced male reproductive dysfunction in animal production.

研究领域: 生殖生物学 · 毒理学 · 细胞生物学 · 分子生物学
✓ 已验证 DOI PubMed 高影响因子
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POLYMER · 2019 · IF 3.771

Mechanically robust, notch-insensitive, fatigue resistant and self-recoverable hydrogels with homogeneous and viscoelastic network constructed by a novel multifunctional cross-linker

Yi Wang,Jinrong Wu,Zhenxing Cao,Changshu Ma,Qingbo Tong,Jiangbo Li,Hanchao Liu,Jing Zheng,Guangsu Huang

Designing a homogeneous network is an efficient way to improve the mechanical properties of hydrogels. However, the homogeneous hydrogels usually have negligible notch-insensitivity due to the lack of effective energy dissipation, limiting their practical applications in many fields. Herein, we provide a straightforward method to prepare a category of tough and notch-insensitive polyacrylamide hydrogels crosslinked by a novel cross-linker with multiple vinyl functional groups (TA). Due to the multifunctionality of TA , a relatively uniform network with the coexistence of physical cross-links is constructed by the steric effect between chain radicals on TA molecules during the polymerization. The uniform network distributes stress evenly while the physical cross-links lead to viscoelastic dissipated energy under external force. As a result, the hydrogels achieve an ultrastretchability of 2400% and a tensile toughness of 4.33 MJ/m 3 . Even with a notch of 10 mm, the hydrogels can still be stretched to a strain of 20, indicating an impressive notch-insensitivity. Meanwhile, the hydrogels exhibit high fatigue resistance and good self-recovery. This research offers a facile strategy for designing high-performance hydrogels and may pave the way for their practical application in emerging fields, such as oil displacement agent and artificial cartilage .

CAS / MDL: 57-13-6
研究领域: 材料科学 · 聚合物化学 · 生物医学工程
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Cell Regeneration · 2021 ·Vol. 10 ·期 1 ·1-18 · IF 0

Single-cell analysis defines the lineage plasticity of stem cells in cervix epithelium

Zhao Zixian,Wang Yujia,Wu Yingchuan,Li Dandan,Zhang Ting,Ma Yu,Teng Xiaoming,Zuo Wei

Information about the dynamic change and post-injury regeneration of cervical epithelium is relatively rare, even though it is tightly related to gynecologic malignancy. Here, using a feeder cell-based culturing system, we stably cloned mouse and human P63 and KRT5 expressing cells from the adult cervix as putative cervical stem/progenitor cells (CVSCs). When subjected to differentiation, the cultured cells gave rise to mature cervical epithelium by differentiating into squamous or glandular cells. The ability of endogenous mouse CVSCs to reconstitute cervical epithelium after injury was also evident from the genetic lineage tracing experiments. Single-cell transcriptomic analysis further classified the CVSCs into three subtypes and delineated their bi-lineage differentiation roadmap by pseudo-time analysis. We also tracked the real-time differentiation routes of two representing single CVSC lines in vitro and found that they recapitulated the predicted roadmap in pseudo-time analysis. Signaling pathways including Wnt, TGF-beta, Notch and EGFR were found to regulate the cervical epithelial hierarchy and implicated the different roles of distinct types of cells in tissue homeostasis and tumorigenesis. Collectively, the above data provide a cloning system to achieve stable in vitro culture of a bi-lineage stem/progenitor cell population in the cervix, which has profound implications for our understanding of the cervix stem/progenitor cell function in homeostasis, regeneration, and disease and could be helpful for developing stem cell-based therapies in future.

研究领域: 细胞生物学 · 干细胞研究 · 癌症生物学 · 再生医学
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TOXICOLOGY · 2024 · IF 4.8

Maternal exposure to beta-Cypermethrin disrupts placental development by dysfunction of trophoblast cells from oxidative stress

Xiaoli Tang,Yanqing Geng,Rufei Gao,Zhuxiu Chen,Xinyi Mu,Yan Zhang,Xin Yin,Yidan Ma,Xuemei Chen,Fangfang Li,Junlin He

As a broad-spectrum and efficient insecticide, beta-Cypermethrin (β-CYP) poses a health risk to pregnancy. It matters the mechanisms of maternal exposure to β-CYP for impacting reproductive health. The placenta, a transient organ pivotal for maternal-fetal communication during pregnancy, plays a crucial role in embryonic development. The effect of β-CYP exposure on the placenta and its underlying molecular mechanisms remain obscure. The objective of this study was to investigate the effect of β-CYP exposure on placental development and the function of trophoblast, as well as the underlying mechanisms through CD-1 mouse model (1, 10, 20   mg/kg.bw) and in vitro HTR-8/SVneo cell model (12.5, 25, 50, 100   μM). We found slower weight gain and reduced uterine wet weight in pregnant mice with maternal exposure to β-CYP during pregnancy, as well as adverse pregnancy outcomes such as uterine bleeding and embryo resorption. The abnormal placental development in response to β-CYP was noticed, including imbalanced placental structure and disrupted labyrinthine vascular development. Trophoblasts, pivotal in placental development and vascular remodeling, displayed abnormal differentiation under β-CYP exposure. This aberration was characterized by thickened trophoblast layers in the labyrinthine zone, accompanied by mitochondrial and endoplasmic reticulum swelling within trophoblasts. Futher researches on human chorionic trophoblast cell lines revealed that β-CYP exposure induced apoptosis in HTR-8/SVneo cells. This induction resulted in a notable decrease in migration and invasion abilities, coupled with oxidative stress and the inhibition of the Notch signaling pathway. N-acetylcysteine (an antioxidant) partially restored the impaired Notch signaling pathway in HTR-8/SVneo cells, and mitigated cellular functional damage attributed to β-CYP exposure. Collectively, exposure to β-CYP induced oxidative stress and then led to inhibition of the Notch signaling pathway and dysfunction of trophoblast cells, ultimately resulted in abnormal placenta and pregnancy. These findings indicate Reactive Oxygen Species as potential intervention targets to mitigate β-CYP toxicity. The comprehensive elucidation contributes to our understanding of β-CYP biosafety and offers an experimental basis for preventing and managing its reproductive toxicity.

CAS / MDL: 616-91-1
研究领域: 生殖毒理学 · 药理学 · 细胞生物学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Biomaterials Science · 2019 ·Vol. 7 ·期 4 ·1632-1642 · IF 5.251

Phenylboronic acid-functionalized polyamidoamine-mediated miR-34a delivery for the treatment of gastric cancer

Zheyu Song,Xiao Liang,Yudi Wang,Haobo Han,Jiebing Yang,Xuedong Fang,Quanshun Li

In the present research, a tumor-targeted gene carrier, PPP, was constructed through the modification of phenylboronic acid onto the surface of a polyamidoamine dendrimer, and then miR-34a delivery was employed as a model to evaluate its anti-tumor efficacy. The carrier PPP was identified to possess favorable miR-34a binding and condensation ability and meanwhile protect miR-34a against nuclease degradation. Through confocal laser scanning microscopy and flow cytometry analysis, PPP-mediated cellular uptake of miR-34a was found to proceed through a sialic acid-dependent endocytosis pathway and the nanoparticles could achieve endosome/lysosome escape within 6 h. Further, an anti-proliferative effect could be obtained after PPP/miR-34a transfection through the induction of cell apoptosis. Meanwhile, the inhibition of migration and invasion could be realized through blocking the Notch-1 signaling pathway after PPP/miR-34a treatment. Finally, PPP possessed acceptable safety and inhibited in vivo tumor growth through the in situ apoptosis of tumor sites, which relied on the specific tumor-targeting ability and long circulation time in the blood. In summary, the derivative PPP could be potentially utilized as an efficient carrier for miR-34a delivery to achieve an anti-tumor response in clinical use.

CAS / MDL: 301-04-2 51805-45-9
研究领域: 癌症研究 · 分子生物学 · 基因治疗
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Bioactive Materials · 2022 · IF 16.874

Injectable bone marrow microniches by co-culture of HSPCs with MSCs in 3D microscaffolds promote hematopoietic reconstitution from acute lethal radiation

Haiwei Liang,Yanxiao Ao,Wenjing Li,Kaini Liang,Baixue Tang,Junyang Li,Jianwei Wang,Xiaoyu Zhu,Yanan Du

Hematopoietic syndrome of acute radiation syndrome (h-ARS) is an acute illness resulted from the damage of bone marrow (BM) microenvironment after exposure to radiation. Currently, the clinical management of h-ARS is limited to medication-assisted treatment, while there is still no specific therapy for the hematopoietic injury from high-dose radiation exposure. Our study aimed to assemble biomimetic three-dimensional (3D) BM microniches by co-culture of hematopoietic stem and progenitor cells (HSPCs) and mesenchymal stem cells (MSCs) in porous, injectable and viscoelastic microscaffolds in vitro . The biodegradable BM microniches were then transplanted in vivo into the BM cavity for the treatment of h-ARS. We demonstrated that the maintenance of HSPCs was prolonged by co-culture with MSCs in the porous 3D microscaffolds with 84 μm in pore diameter and 11.2 kPa in Young's modulus compared with 2D co-culture system. Besides, the minimal effective dose and therapeutic effects of the BM microniches were investigated on a murine model of h-ARS, which showed that the intramedullary cavity-injected BM microniches could adequately promote hematopoietic reconstitution and mitigate death from acute lethal radiation with a dose as low as 1000 HSPCs. Furthermore, the mRNA expression of Notch1 and its downstream target gene Hes1 of HSPCs were increased when co-cultured with MSCs, while the Jagged1 expression of the co-cultured MSCs was upregulated, indicating the significance of Notch signaling pathway in maintenance of HSPCs. Collectively, our findings provide evidence that biomimetic and injectable 3D BM microniches could maintain HSPCs, promote hematopoiesis regeneration and alleviate post-radiation injury, which provides a promising approach to renovate conventional HSPCs transplantation for clinical treatment of blood and immune disorders.

研究领域: 干细胞研究 · 再生医学 · 辐射生物学 · 组织工程
✓ 已验证 DOI PubMed 高影响因子
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Cell Metabolism · 2024 · IF 27.7

Nicotinamide metabolism face-off between macrophages and fibroblasts manipulates the microenvironment in gastric cancer

Yu Jiang,Yawen Wang,Guofeng Chen,Fei Sun,Qijing Wu,Qiong Huang,Dongqiang Zeng,Wenjun Qiu,Jiao Wang,Zhiqi Yao,Bishan Liang,Shaowei Li,Jianhua Wu,Na Huang,Yuanyuan Wang,Jingsong Chen,Xiaohui Zhai,Li Huang,Beibei Xu,Masami Yamamoto,Tetsuya Tsukamoto,Sachiyo Nomura,Wangjun Liao,Min Shi

Immune checkpoint blockade has led to breakthroughs in the treatment of advanced gastric cancer. However, the prominent heterogeneity in gastric cancer, notably the heterogeneity of the tumor microenvironment, highlights the idea that the antitumor response is a reflection of multifactorial interactions. Through transcriptomic analysis and dynamic plasma sample analysis, we identified a metabolic “face-off” mechanism within the tumor microenvironment, as shown by the dual prognostic significance of nicotinamide metabolism. Specifically, macrophages and fibroblasts expressing the rate-limiting enzymes nicotinamide phosphoribosyltransferase and nicotinamide N-methyltransferase, respectively, regulate the nicotinamide/1-methylnicotinamide ratio and CD8+ T cell function. Mechanistically, nicotinamide N-methyltransferase is transcriptionally activated by the NOTCH pathway transcription factor RBP-J and is further inhibited by macrophage-derived extracellular vesicles containing nicotinamide phosphoribosyltransferase via the SIRT1/NICD axis. Manipulating nicotinamide metabolism through autologous injection of extracellular vesicles restored CD8+ T cell cytotoxicity and the anti-PD-1 response in gastric cancer.

研究领域: 肿瘤学 · 免疫学 · 代谢学 · 癌症生物学
✓ 已验证 DOI PubMed 高影响因子
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY · 2019 · IF 4.527

Natural harmine negatively regulates the developmental signaling network of Drosophila melanogaster (Drosophilidae: Diptera) in vivo

Gaofeng Cui,Haiqi Yuan,Zhiyan Jiang,Jing Zhang,Zhipeng Sun,Guohua Zhong

The widely distributed β-carboline alkaloids exhibit promising psychopharmacological and biochemical effects. Harmine, a natural β-carboline, can inhibit insect growth and development with unclear mechanisms. In this study, harmine (at 0-200 mg/L) showed a dose-dependent inhibitory effect on the pupal weight, length, height, pupation rate and eclosion rate of fruit flies Drosophila melanogaster , which was similar to the inhibition induced by the well-known botanical insect growth regulator azadirachtin . Moreover, the expression levels of major regulators from the developmental signaling network were down-regulated during the pupal stage except Numb , Fringe , Yorkie and Pten . The Notch, Wnt, Hedgehog and TGF-β pathways mainly played vital roles in coping with harmine exposure in pupae stage, while the Hippo, Hedgehog and TGF-β elements were involved in the sex differences. Notch , Hippo , Hedgehog , Dpp and Armadillo were proved to be suppressed in the developmental inhibition with fly mutants, while Numb and Punt were increased by harmine. In conclusion, harmine significantly inhibited the development of Drosophila by negatively affecting their developmental signaling network during different stages. Our results establish a preliminary understanding of the developmental signaling network subjected to botanical component-induced growth inhibition and lay the groundwork for further application.

CAS / MDL: 442-51-3
研究领域: 昆虫学 · 分子生物学 · 发育生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Cell Death & Disease · 2022 ·Vol. 13 ·期 8 ·1-11 · IF 9.685

A dopamine-methacrylated hyaluronic acid hydrogel as an effective carrier for stem cells in skin regeneration therapy

Gong Meihua,Yan Fei,Yu Li,Li Furong

Adipose-derived stem cells (ADSCs) show potential in skin regeneration research. A previous study reported the failure of full-thickness skin self-repair in an injury area exceeding 4 cm in diameter. Stem cell therapies have shown promise in accelerating skin regeneration; however, the low survival rate of transplanted cells due to the lack of protection during and after transplantation leads to low efficacy. Hence, effective biomaterials for the delivery and retention of ADSCs are urgently needed for skin regeneration purposes. Here, we covalently crosslinked hyaluronic acid with methacrylic anhydride and then covalently crosslinked the product with dopamine to engineer dopamine-methacrylated hyaluronic acid (DA-MeHA). Our experiments suggested that the DA-MeHA hydrogel firmly adhered to the skin wound defect and promoted cell proliferation in vitro and skin defect regeneration in vivo. Mechanistic analyses revealed that the beneficial effect of the DA-MeHA hydrogel combined with ADSCs on skin defect repair may be closely related to the Notch signaling pathway. The ADSCs from the DA-MeHA hydrogel secrete high levels of growth factors and are thus highly efficacious for promoting skin wound healing. This DA-MeHA hydrogel may be used as an effective potential carrier for stem cells as it enhances the efficacy of ADSCs in skin regeneration.

CAS / MDL: 85073-19-4
研究领域: 生物材料 · 组织工程 · 干细胞疗法 · 伤口愈合
✓ 已验证 产品关联 DOI PubMed 高影响因子
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MOLECULAR & CELLULAR PROTEOMICS · 2026 · IF 6.3

Multidimensional Proteomics Reveals the Pro-apoptotic Mechanism of Platycodin D: Targeting RFC4 to Regulate the Notch Signaling Axis in Non-Small Cell Lung Cancer

Hongyu Zhang,Baojin Zhou,Jingwen Liu,Yan Ren

Background and aim Platycodin D (PD), a major bioactive saponin isolated from the traditional Chinese medicine (TCM) Platycodon grandiflorus , has shown promising therapeutic potential against non-small cell lung cancer (NSCLC). However, the functional mechanisms of PD in NSCLC progression remains unclear. This study aimed to explore the pharmacological mechanism of PD against NSCLC. Materials and methods Thermal proteome profiling (TPP) approach, molecular docking, cellular thermal shift assay (CETSA) and peptide-centric local stability assay (PELSA) were employed to identify the potential binding target of PD. Subsequent Western Blot and immunoprecipitation-Western Blot (IP-WB) experiments were conducted to investigate the downstream signaling pathways of the target. Furthermore, proteomic and ubiquitinomic profiling of PD-treated cells were performed to investigate its functions on global. Results Replication factor C subunit 4 (RFC4) was identified as a potential binding target of PD by TPP and their binding sites were further exposed by PELSA. PD-RFC4 complex promotes the degradation of Notch1 and Notch3 by reducing nuclear entry of their domains. Compared with control treatment, the differentially expressed proteins induced by PD were found to be primarily involved in ferroptosis, ubiquitination, platinum drug resistance and ribosome-related processes. The ubiquitin proteome analysis revealed that proteins associated with the Notch pathway underwent ubiquitin modifications. Conclusions PD binds to RFC4 and inhibits its activity, leading to downregulation of the Notch signaling pathway, ultimately triggering cancer cell apoptosis. PD is a natural product with potential therapeutic value for NSCLC.

✓ 已验证 DOI PubMed 高影响因子
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