ARCHIVES OF TOXICOLOGY
·
2025
·
IF 6.9
Hu Liehai,Ren Ke,Li Yichang,Xia Yunhui,Chen Guijuan,Wang Xiaojian,Luo Chunyu,Sun Yun,Li Dongmei
Developmental exposure to environmental pollutants is increasingly recognized as a significant risk factor for autism spectrum disorder (ASD), yet the specific mechanisms by which individual toxicants contribute to this neurodevelopmental disorder remain largely unknown. Methyl ester sulfonate (MES), a widely used anionic surfactant with widespread environmental detection, lacks comprehensive evaluation for developmental neurotoxicity. Here, we exposed pregnant mice to environmentally relevant MES doses (0.06–6 mg/L) from gestational day 8.5 (GD8.5) to postnatal day 21.5 (PND21.5) and assessed their offspring for neurodevelopmental changes. Results showed dose-dependent ASD-like behavioral deficits, including impaired social interactions, heightened anxiety-like behaviors, and increased repetitive/stereotypic patterns. These behavioral anomalies were accompanied by neuropathological alterations, including blood–brain barrier disruption, neuronal loss, and reduced dendritic spine density, indicative of impaired synaptogenesis. Integrative transcriptomic analysis of hippocampal tissue revealed significant dysregulation of key pathways involved in neurodevelopment, prominently featuring the Notch/Hes signaling pathway. Molecular docking simulations suggested that MES could directly interact with Notch receptors, potentially disrupting ligand–receptor interactions. Further in vitro experimental validation demonstrated that MES exposure suppressed neural stem cell differentiation. Collectively, these findings provided evidence that early-life MES exposure acts as a neurodevelopmental toxicant by disrupting Notch/Hes signaling, thereby impairing neuronal differentiation and synaptogenesis, which underlined the observed ASD-like behavioral deficits in mice. This study offers novel mechanistic insights into how environmental factors contribute to ASD pathogenesis and highlights the need for toxicological assessment of widely distributed surfactants.
研究领域:
神经毒理学
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发育神经科学
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环境毒理学
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分子生物学
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行为神经科学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2023
·
IF 7.9
Baohong Li,Zichao Chen,Zhenyong Zhang,Hui Liu,Dongli Han,Haolin Yang,Zhen Zhang
Background: Breast cancer bone metastasis is closely associated with the bone microenvironment. Zuogui Pill (ZGP), a clinically approved formulation in China, effectively regulates the bone microenvironment for the prevention and treatment of osteoporosis. Purpose: Few reports have utilized the ZGP for bone metastasis models. This study investigated the intervention and bone-protective properties of ZGP against breast cancer bone metastasis, explored the potential mechanism, and screened for its active compositions by molecules fishing. Methods: To investigate the intervention efficacy of ZGP and its protein-level mechanism of action, the mouse bone metastasis model and in vitro cell co-culture model were constructed. Affinity ultrafiltration, molecular docking, cellular thermal shift assay and physical scale detection were used to investigate the affinity components of the RANKL protein in ZGP. Results: The administration of ZGP combined with zoledronic acid inhibited the development of tumors and secondary lung metastasis in mice. This translated to a prolonged survival period and enhanced quality of life. ZGP could disrupt the malignant cycle by modulating the Piezo1-Notch-1-GPX4 signaling pathway in the "bone-cancer" communication in the cell co-culture model. Furthermore, 25 chemical components of ZGP were identified, with 10 active compounds exhibiting significant affinity for the RANKL protein. Conclusion: The findings of this work highlighted ZGP's potential for intervening in the progression of breast cancer bone metastasis. Thus, this investigation served as an experimental foundation for expanding the application scope of ZGP and for advancing drug development efforts in bone metastasis treatment.
研究领域:
肿瘤学
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药理学
·
分子生物学
·
细胞生物学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Soft Matter
·
2015
·Vol. 11
·期 42
·8253-8261
·
IF 4.029
Hussain Haider,Can Hui Yang,Wen Jiang Zheng,Jian Hai Yang,Mei Xiang Wang,Sen Yang,Miklós Zrínyi,Yoshihito Osada,Zhigang Suo,Qiqing Zhang,Jinxiong Zhou,Yong Mei Chen
Most existing magnetic hydrogels are weak and brittle. The development of strong and tough magnetic hydrogels would extend their applications into uncultivated areas, such as in actuators for soft machines and guided catheters for magnetic navigation systems, which is still a big challenge. Here a facile and versatile approach to fabricating highly stretchable, exceptionally tough and notch-insensitive magnetic hydrogels, Fe3O4@Fe-alginate/polyacrylamide (PAAm), is developed, by dispersing alginate-coated Fe3O4 nanoparticles into the interpenetrating polymer networks of alginate and PAAm, with hybrid physical and chemical crosslinks. A cantilever bending beam actuator as well as a proof-of-concept magnetically guided hydrogel catheter is demonstrated. The method proposed in this work can be integrated into other strong and tough magnetic hydrogels for the development of novel hydrogel nanocomposites with both desirable functionality and superior mechanical properties.
研究领域:
生物材料学
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高分子科学
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组织工程
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软体机器人
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介入医学
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功能水凝胶
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纳米复合材料
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DOI
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 36
·30570-30576
·
IF 3.289
Qiang Su,Yajun Wang,Shuang Guan,Huixuan Zhang,Guang Hui Gao,Xinyuan Zhu
Highly stretchable and notch-insensitive hydrogels were rapidly prepared using redox initiators. The hydrogels had a large number of non-covalent crosslinking points, which come from hydrophobic side chains and metal ion coordination without any chemical crosslinking agents. The non-covalent crosslinking points in the hydrogels were stochastic and dynamic, compared to the covalent crosslinking points. When the notched sample was stretched, the hydrophobic segments would contribute to elongation of the hydrogels via molecular stretching. When the hydrogels had a notch, new crosslinking points could be formed via metal ion coordination, even if some previous metal ion–ligand bonds were destroyed. As a result, the sample notch was blunted, widened and merged into the edge gradually under tensile stress. The hydrogels could be elongated up to 12 times their original length and show notch-insensitive properties. Moreover, the metal ion coordination interaction between the amide groups and Fe3+ was proved using Fourier transform infrared spectroscopy (FTIR). The rheological properties and internal morphology of the hydrogels were also measured with different dosages of hydrophobic segments and metal ions. Thus, it was envisioned that the non-covalent bonds would make it possible to create hydrogels with more unexpected properties.
研究领域:
材料科学
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生物医学工程
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产品关联
DOI
高影响因子
Journal of Materials Chemistry A
·
2020
·Vol. 8
·期 39
·20346-20353
·
IF 11.301
Xiwei Guo,Changgeng Zhang,Lei Shi,Qi Zhang,He Zhu
Advanced stretchable and wearable electronic devices have a great potential in the fields of motion detection, health monitoring, and artificial intelligence, substantially increasing the demand for elastic materials. This study reports a novel stretchable, recyclable, notch-insensitive, and conductive material based on amidoximated polyacrylonitrile gel (APANG), which is an elastic substrate, for use in flexible electronics. APANG is prepared by straightforward nucleophilic addition, followed by solidification. APANG exhibits excellent stretchability with a strain of ∼800% and a high fracture energy of 12.92 ± 2.23 kJ m−2 because of a large number of hydrogen bonds among amidoxime groups on polymer chains and among the amidoxime groups and N,N-dimethylformamide molecules. Moreover, due to the reversibility of physical entanglement and dynamic hydrogen bond of polymer chains, the gel can be recycled, thereby avoiding the reprocessing issue of many conventional chemically crosslinked polymer gels. In addition, the existence of free chloride ions in the gel provides good conductivity to the materials. Finally, APANG exhibits good responsivity, recoverability, and reliability as strain sensors, demonstrating its great potential in stretchable and wearable electronic devices.
研究领域:
材料科学
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柔性电子
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高分子化学
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产品关联
DOI
高影响因子
Human Cell
·
2025
·Vol. 38
·期 3
·1-15
·
IF 3.1
Li Chenhao,Wang Xin,Shi Dongliang,Yang Meng,Yang Wenhua,Chen Liang
Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by high recurrence rates, low survival rates, and a lack of therapeutic targets. Regulatory Factor X5 (RFX5) is a critical transcription factor during tumor progression. However, the role of RFX5 involving breast cancer or TNBC has not been studied. This study obtained 60 tumor samples of TNBC for analysis and ascertained that RFX5 is linked with the severe stage. We constructed RFX5 knockdown and overexpression models involving TNBC cells. RFX5 overexpression enhanced TNBC cell proliferation by detecting cell vitality and replication of DNA and analyzing cell cycle data. RFX5 facilitated cell migration and invasion, which were determined by wound healing and Transwell assays. The anti-apoptotic RFX5 properties were confirmed with Hoechst staining and Annexin V/PI apoptosis assays. The Notch pathway was activated in TNBC, and Jagged canonical Notch ligand 1 (JAG1) could enhance TNBC growth and metastasis. RFX5 upregulation elevated JAG1 mRNA and protein levels. Chromatin immunoprecipitation and luciferase reporter assays indicated that RFX5 promoted the transcriptional activation of JAG1 by binding the promoter (− 1890/+ 15 or − 1359/+ 15 area). JAG1 knockdown reduced RFX5-induced expression of Notch signaling-related factors Notch1, NICD, and Hes1. This paper indicated that RFX5 is a transcription factor for JAG1 and established that RFX5 could activate the Notch pathway via transcriptional activation of JAG1 and promote TNBC progression. Targeting RFX5 could be a promising therapeutic approach against TNBC.
研究领域:
肿瘤学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry C
·
2019
·Vol. 8
·期 6
·2043-2053
·
IF 6.641
Lun Zhang,Dong Wang,Liqiang Xu,Xueqian Zhang,Aimin Zhang,Yu Xu
To date, transparent polymeric elastomers with high mechanical toughness and excellent self-healing ability have shown attractive prospects in various fields. However, it is difficult to balance the trade-off between self-healing and mechanical performance, and it is even harder to get a transparent one. Herein, novel polyurea materials, which were cross-linked by rationally designed multi-strength hydrogen bonding interactions as well as covalent bonds, were developed. Covalent cross-links enabled high strength, while multi-strength hydrogen bonds as dynamic cross-links ensured elasticity, energy dissipation and rapid self-healing at room temperature. The designed polymer exhibited exceptional mechanical properties such as high elongation at break (over 1600%), notch-insensitive stretchability (800%), and high toughness of 12 500 J m−2. Additionally, it was observed that the polymer could achieve up to 100% self-healing efficiency after 6 h without any external stimuli and an average transmittance of 92.8% at a film thickness of only 1.3 mm. After scratching, the film could still regain its transparency. Notably, this robust, transparent, stretchable, and self-healing elastomer can be employed as an optical protective coating against damage and will open a new avenue for next-generation sustainable optical-electrical and display screen devices.
研究领域:
材料科学
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聚合物化学
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自修复材料
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光学涂层
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柔性电子学
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DOI
高影响因子
Biochemistry and Cell Biology
·
2017
·Vol. 95
·期 4
·
IF 1.895
Junhong Guan,Xiangtai Wei,Shengtao Qu,Tao Lv,Qiang Fu,Ye Yuan
Stroke is a common cerebrovascular disease in aging populations, and constitutes the second highest principle cause of mortality and the principle cause of permanent disability, and ischemic stroke is the primary form. Osthole is a coumarin derivative extracted from the fruits of Cnidium monnieri (L.) Cusson. In this study, we established a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) in vivo and found that MCAO/R caused cerebral infarction, hippocampus neuronal injury and apoptosis, and also activated the Notch 1 signaling pathway. However, treatment with osthole further enhanced the activity of Notch 1 signaling and reduced the cerebral infarction as well as the hippocampus neuronal injury and apoptosis induced by MCAO/R in a dose-dependent manner. The same results were observed in a primary neuronal oxygen glucose deficiency/reperfusion (OGD/R) model in vitro, and the effect of osthole could be blocked by an inhibitor of Notch 1 signaling, N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine tert-butyl ester (DAPT). Therefore, we demonstrated that osthole injection prevented rat ischemia–reperfusion injury via activating the Notch 1 signaling pathway in vivo and in vitro in a dose-dependent manner, which may be significant for clinical treatment of ischemic stroke.
研究领域:
神经科学
·
药理学
·
分子生物学
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DOI
PubMed
高影响因子
Cell Reports Medicine
·
2026
·
IF 14
Lizhou Lin,Xiao Li,Wenyun Guo,Jirong Xie,Xiaolong Li,Xin Guan,Chongke Zhao,HaoHao Yin,Huixiong Xu
Solid tumors impose coupled stromal and immunologic barriers that limit T cell infiltration and function. Here, we engineer Salmonella VNP 20009 to express gas vesicles (GVs), creating an intratumoral cavitation source that converts low-intensity focused ultrasound (LIFUS) into localized mechanical forces. LIFUS-activated GVs remodel the tumor microenvironment by reducing cancer-associated fibroblast (CAF) abundance, decompressing the matrix, and selectively disrupting CAF-CD8 + T cell communication via a mechanosensitive Notch1-Jagged1 axis. Single-cell RNA sequencing reveals a redistribution of CD8 + T cell states, characterized by enrichment of cytotoxic effector populations and attenuation of NOTCH signaling in memory-associated cells. These biomechanical changes enhance intratumoral CD8 + T cell infiltration and restore effector cytokine production. Leveraging this mechanism, we develop a mechano-priming approach for adoptive T cell therapies. Pre-conditioning with LIFUS-driven GVs improves CD8 + T cell cytotoxicity, strengthens tumor cell adhesion, reduces exhaustion signatures, and achieves durable tumor control and extended survival in orthotopic and metastatic models.
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2026
·Vol. 27
·期 5
·2111
·
IF 5.6
Mengting Xu,Yunmiao Ma,Mengxin Liu,Yueqiu Chen,Zongyi Duan,Zhenya Shen,Yanchao Han
Congenital valve defects account for a substantial proportion of cardiovascular malformations, yet the molecular mechanisms orchestrating cardiac valve development remain incompletely elucidated. While Bone morphogenetic protein (BMP) signaling is essential for valvulogenesis, the specific contributions of individual BMP ligands, particularly the teleost-specificbmp16, have not been characterized. Using the CRISPR/Cas9 system, we generated abmp16null knockout and delineated critical roles of this ligand in valvular morphogenesis.bmp16knockout embryos display a significant reduction in Sox9-positive valvular cells and exhibit severely dysplastic arterial valves, characterized by increased interleaflet distance, thickened leaflets, and shortened leaflet lengths. These morphological abnormalities correlate with impaired valve function, culminating in progressive blood regurgitation, ventricular dilation, and pericardial edema. Mechanistically, loss ofbmp16or pharmacological inhibition of BMP signaling significantly downregulatesnotch1bexpression in developing valves, while pharmacological activation of Notch signaling rescues the regurgitation phenotype inbmp16mutants. Collectively, our findings establishbmp16as a novel regulator of valve development and uncover a functional BMP-Notch signaling axis required for vertebrate valvulogenesis, providing new insights into the molecular mechanisms that govern cardiac valve formation and pathogenesis.
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产品关联
DOI
PubMed
高影响因子
ChemPlusChem
·
2020
·Vol. 85
·期 9
·2158-2165
·
IF 2.753
Jianbo Yang,Yongxu Du,Xuelin Li,Congde Qiao,Haihui Jiang,Jiyong Zheng,Cunguo Lin,Libin Liu
Graphical Quick and strong : Self-healing hydrogels were synthesized by random copolymerization of the three monomers. The reversible ionic bond formed between the monomers effectively enhanced the degree of cross-linking of the polymer network, thus furnishing the hydrogels with excellent mechanical and self-healing properties, which can be produced in a short time. The strain energy dissipation of reversible ionic bonds enhanced the fatigue resistance of the hydrogels and made them notch-insensitive. Introducing self-healing properties into hydrogels can prolong their application lifetime. However, achieving mechanical strength without sacrificing self-healing properties is still a major challenge. We prepared a series of zwitterionic polymer hydrogels by random copolymerization of zwitterionic ionic monomer (SBMA), cationic monomer (DAC) and hydrophilic monomer (HEMA). The ionic bonds and hydrogen bonds formed in the hydrogels can efficiently dissipate energy and rebuild the network. The resulting hydrogels show high mechanical strength (289–396 KPa of fracture stress, 433–864 % of fracture stress) and have great fatigue resistance. The hydrogel with a 1 : 1 molar ratio of SBMA:DAC possesses the best self-healing properties (self-healing efficiency up to 96.5 % at room temperature for 10 h). The self-healing process is completely spontaneous and does not require external factors to assist. In addition, the hydrogel also possesses notch insensitivity with a fracture energy of 12000 J m −2 . After combining the conductivity of RGO aerogel, the hydrogel/RGO composites show good strain sensitivity with high reliability and self-healing ability, which has certain significance in broadening the application of these zwitterionic hydrogels.
研究领域:
材料科学
·
生物医学工程
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DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2024
·
IF 7.6
Yu-Jia Lin,Hong-Mei Li,Yan-Rong Gao,Ping-Fan Wu,Bin Cheng,Chen-Long Yu,Yu-Xin Sheng,Hai-Ming Xu
The aim of this study is to investigate the adverse effects of benzophenones (BPs) on the intestinal tract of mice and the potential mechanism. F1-generation ICR mice were exposed to BPs (benzophenone-1, benzophenone-2, and benzophenone-3) by breastfeeding from birth until weaning, and by drinking water after weaning until maturity. The offspring mice were executed on postnatal day 56, then their distal colons were sampled. AB-PAS staining, HE staining, immunofluorescence, Transmission Electron Microscope, immunohistochemistry, Western Blot and RT-qPCR were used to study the effects of BPs exposure on the colonic tissues of offspring mice. The results showed that colonic microvilli appeared significantly deficient in the high-dose group, and the expression of tight junction markers Zo-1 and Occludin was significantly down-regulated and the number of goblet cells and secretions were reduced in all dose groups, and the expression of secretory cell markers MUC2 and KI67 were decreased, as well as the expression of intestinal stem cell markers Lgr5 and Bmi1 , suggesting that BPs exposure caused disruption of intestinal barrier and imbalance in the composition of the intestinal stem cell pool. Besides, the expression of cellular inflammatory factors such as macrophage marker F4/80 and tumor necrosis factor TNF-α was elevated in the colonic tissues of all dose groups, and the inflammatory infiltration was observed, which means the exposure of BPs caused inflammatory effects in the intestinal tract of F1-generation mice. In addition, the contents of Notch/Wnt signaling pathway-related genes, such as Dll-4 , Notch1 , Hes1 , Ctnnb1 and Sfrp2 were significantly decreased in each high-dose group ( P < 0.05), suggesting that BPs may inhibit the regulation of Notch/Wnt signaling pathway. In conclusion, exposure to BPs was able to imbalance colonic homeostasis, disrupt the intestinal barrier, and trigger inflammation in the offspring mice, which might be realized through interfering with the Notch/Wnt signaling pathway.
研究领域:
毒理学
·
分子生物学
·
环境科学
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产品关联
DOI
PubMed
高影响因子
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