MOLECULES
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2023
·Vol. 28
·期 13
·5176
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IF 4.6
Dongrong Cheng,Xiaofeng Wei,Yanting Zhang,Qian Zhang,Jianwei Xu,Jiaxin Yang,Junjie Yu,Antony Stalin,Huan Liu,Jintao Wang,Dian Zhong,Lanying Pan,Wei Zhao,Yuan Chen
Erythromycin is one of the few compounds that remarkably increase ether-a-go-go-related gene (hERG) inhibition from room temperature (RT) to physiological temperature (PT). Understanding how erythromycin inhibits the hERG could help us to decide which compounds are needed for further studies. The whole-cell patch clamp technique was used to investigate the effects of erythromycin on hERG channels at different temperatures. While erythromycin caused a concentration-dependent inhibition of cardiac hERG channels, it also shifted the steady-state activation and steady-state inactivation of the channel to the left and significantly accelerated the onset of inactivation at both temperatures, although temperature itself caused a profound change in the dynamics of hERG channels. Our data also suggest that the binding pattern to S6 of the channels changes at PT. In contrast, cisapride, a well-known hERG blocker whose inhibition is not affected by temperature, does not change its critical binding sites after the temperature is raised to PT. Our data suggest that erythromycin is unique and that the shift in hERG inhibition may not apply to other compounds.Keywords:erythromycin;temperature;hERG;steady-state activation;steady-state inactivation
研究领域:
药理学
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心脏病学
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生物物理学
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DOI
PubMed
高影响因子
CHEMOSPHERE
·
2018
·
IF 4.427
Dezhen Wang,Wentao Zhu,Sen Yan,Zhiyuan Meng,Jin Yan,Miaomiao Teng,Ming Jia,Ruisheng Li,Zhiqiang Zhou
In this study, we used a 1 H NMR based metabolomics strategy combined with gene expression analysis to determine the combined effects of gestational exposure of mice to BPA (10 μg/kg body weight by subcutaneous injection) and arsenic (10 ppb sodium arsenite in drinking water). Results showed that exposure to either BPA or, arsenic or their combination induced age-dependent metabolic disruptions in male mice offspring , and the combined exposure could exacerbate the metabolic changes induced by either BPA or arsenic alone. Moreover, this combined exposure influenced both glucose tolerance and insulin tolerance in mice, along with changing the expression of genes involved in lipid and glucose homeostasis . Specifically, the combined exposure to BPA and arsenic promoted the uptake of glucose and fatty acid from serum to liver, and genes involved in glycogenesis, glucogenesis, and fatty acid oxidation were activated in the liver in the combined exposure group. Taken together, these experimental results highlight the importance of considering the combined toxicity of environmental pollutants at levels relevant to human exposure, especially during the early life stages of mammals.
研究领域:
毒理学
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代谢组学
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环境健康科学
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产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
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2023
·Vol. 35
·期 15
·2211802
·
IF 29.4
Chen Yu Li,Dejin Jiao,Xing Peng Hao,Wei Hong,Qiang Zheng,Zi Liang Wu
Joints, as a flexing element to connect different parts, are widespread in natural systems. Various joints exist in the body and play crucial roles to execute gestures and gaits. These scenarios have inspired the design of mechanical joints with passive, hard materials, which usually need an external power supply to drive the transformations. The incorporation of soft and active joints provides a modular strategy to devise soft actuators and robots. However, transformations of responsive joints under external stimuli are usually in uni-mode with a pre-determined direction. Here, hydrogel joints capable of folding and twisting transformation in bi-mode are reported, which enable the composite hydrogel to form multiple configurations under constant conditions. These joints have an in-plane gradient structure and comprise stiff, passive gel as the frame and soft, active gel as the actuating unit. Under external stimuli, the response mismatch between different gels leads to out-of-plane folding or twisting deformation with the feature of bistability. These joints can be modularly integrated with other gels to afford complex deformations and multistable configurations. This approach favors selective control of hydrogel's architectures and versatile design of hydrogel devices, as demonstrated by proof-of-concept examples. It shall also merit the development of metamaterials, soft actuators, and robots, etc.
研究领域:
材料科学
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软体机器人
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智能材料
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Shuheng Qin,Hui-yue Zhao,Xing-yu Luo,Fei Wang,Jun Liu,Yin Ding,Yong Hu
The acidity and high GSH level in the tumor microenvironment (TME) greatly limit the antitumor activity of nanozymes. Thus, enhancing nanozymes’ activity is fundamentally challenging in tumor therapy. Although the combination of photothermal therapy (PTT) and nanozymes can enhance the catalytic activity, cancer cells will overexpress heat shock proteins (HSPs) at high temperature, aggravating the heat resistance of tumor cells, which in turn compromises the outcome of chemodynamic therapy. Herein, we propose an iron-doped metal–organic framework nanozyme (IB@Fe-ZIF8@PDFA) that can be activated under the weak acidity and high level of GSH, demonstrating the activities of GSH oxidation (GSH-OXD), peroxidase (POD), and NADH oxidase (NADH-OXD). Under laser irradiation, it displays photothermal-enhanced multienzyme activities to simultaneously eliminate tumors and inhibit tumor metastasis. While consuming endogenous GSH, IB@Fe-ZIF8@PDFA promotes the decomposition of H2O2 into ·OH, enhancing ferroptosis in tumor cells. Surprisingly, IB@Fe-ZIF8@PDFA nanozyme can oxide NADH and subsequently limit the ATP supply, reducing the expression of HSPs and significantly weakening the heat resistance of tumor cells during PTT. Meanwhile, H2O2 is generated during this procedure, which can endogenously replenish the consumed H2O2. Thus, this IB@Fe-ZIF8@PDFA nanozyme constitutes a self-cascading platform to consume GSH and NADH, endogenously replenish the H2O2 and continuously generate ·OH to facilitate ferroptosis by disrupting the redox and metabolic homeostasis in tumor cells, achieving tumor elimination and tumor metastasis inhibition.
研究领域:
生物医学工程
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肿瘤学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
Advanced Science
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2023
·
IF 15.1
Jiazhao Yang,Xudong Zhang,Baoliang Lu,Jiawei Mei,Lei Xu,Xianzuo Zhang,Zheng Su,Wei Xu,Shiyuan Fang,Chen Zhu,Dongdong Xu,Wanbo Zhu
Traumatic heterotopic ossification (THO) represents one of the most prominent contributors to post-traumatic joint dysfunction, which currently lacks an effective and definitive preventative approach. Inflammatory activation due to immune dyshomeostasis during the early stages of trauma is believed to be critical in initiating the THO disease process. This study proposes a dual-homeostatic modulation (DHM) strategy to synergistically prevent THO without compromising normal trauma repair by maintaining immune homeostasis and inducing stem cell homeostasis. A methacrylate-hyaluronic acid-based hydrogel spray device encapsulating a curcumin-loaded zeolitic imidazolate framework-8@ceric oxide (ZIF-8@CeO2, CZC) nanoparticles (CZCH) is designed. Photo-crosslinked CZCH is used to form hydrogel films fleetly in periosteal soft tissues to achieve sustained curcumin and CeO2 nanoparticles release in response to acidity and reactive oxygen species (ROS) in the inflammatory microenvironment. In vitro experiments and RNA-seq results demonstrated that CZCH achieved dual-homeostatic regulation of inflammatory macrophages and stem cells through immune repolarization and enhanced efferocytosis, maintaining immune cell homeostasis and normal differentiation. These findings of the DHM strategy are also validated by establishing THO mice and rat models. In conclusion, the CZCH hydrogel spray developed based on the DHM strategy enables synergistic THO prevention, providing a reference for a standard procedure of clinical operations.
研究领域:
生物医学工程
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组织工程
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骨科
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药学
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生物材料
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2019
·
IF 3.571
Weiwei Wang,Yiou Pan,Li Wang,Hang Zhou,Ge Song,Yongwei Wang,Jianxue Liu,Aike Li
Ferulic acid (FA) is a major polyphenolic compound and has been shown to improve the glucose and lipid homeostasis in high-fat diet-induced obese mice. Here, we found the optimal level of dietary FA to ameliorate obesity and obesity-correlated disorders, and identified the responses of gut microbiota to dietary FA in genetic leptin-deficient obese (ob/ob) mice. The ob/ob mice exhibited persistent higher body weights, feed efficiency, white adipose tissue weights, and hepatic lipid accumulation, compared to those of the wild-type mice. However, 0.5% dietary FA suppressed these symptoms in ob/ob mice. The diversity of gut microbiota and the total abundance of obesity- and anti-obesity-related genera were not influenced after FA intervention in ob/ob mice. These data suggest that sufficient intake of FA (0.5%) could be useful for treating obesity or obesity-related diseases, and this weight-control effect is possibly not correlated with the gut–brain axis.
研究领域:
营养学
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微生物学
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代谢学
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药理学
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2025
·
IF 15.7
Hu Xuewen,Zhou Tiantian,Cui Tiansi,Du Yuanjiao,Song Chunyu,Chang Weiping,Xiong Juan,Qin Jichao,Deng Lin,Ji Wei-Ke
Sigma Non-Opioid Intracellular Receptor 1 (SigmaR1) is a member of the sigma family of receptors that interacts with a variety of psychotomimetic drugs and is involved in a wide range of cellular and physiological functions. Despite its increasing importance in human physiology and disease, the subcellular localization of SigmaR1 and its molecular function remain poorly defined. Using endogenous tagging and cell fractionation, we show that SigmaR1 is a type II integral ER membrane protein that is specifically enriched at ER sheets. A short region at the N-terminus of SigmaR1 promotes its ER-sheet localization. Importantly, our biochemical studies demonstrate that SigmaR1 directly interacts with components of the translocon complex including TRAPα and Nicalin. In addition, we found that a β-barrel at the C-terminal of SigmaR1 binds phosphatidylcholine (PC), and the binding of PC strengthens the association of SigmaR1 with the translocon complex. SigmaR1 knockout systematically impaired cellular protein and lipid homeostasis, resulting in accumulation of lipid droplets in hepatocytes. Collectively, we propose that SigmaR1 is an auxiliary translocon factor that binds lipids to regulate protein and lipid droplet homeostasis, which may underlie the broad and vital roles of SigmaR1 in physiology and disease.
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2023
·
IF 6.8
Yang Xu,Yuting Gui,Dan Zhi,Jie Pi,Xinhua Liu,Jianguo Xiang,Deliang Li,Junhua Li
Cadmium (Cd) is one of the dominant metal pollutants present in the aquatic environment that affects ion homeostasis, oxidative stress (OS) and immune responses of aquatic organisms. Given the physicochemical similarities between Cd 2+ and calcium (Ca 2+ ) ions, their antagonism may facilitate the mitigation of Cd-induced toxicity. To better understand the role of Ca in protecting against Cd-induced toxicity in teleosts, juvenile grass carp were exposed to Cd (measured concentration 3 μg/L) and a gradient of Ca concentrations (measured concentration 1.5 mg/L, 2.5 mg/L, 3.0 mg/L, and 3.5 mg/L in the control (CTL) group, low calcium (LCA) group, medium calcium (MCA) group, and high calcium (HCA) group, respectively) for 30 days. Inductively coupled plasma mass spectrometry (ICP-MS) data analyses showed that simultaneous exposure to Ca impaired the accumulation of Cd in all tested tissues. Besides, Ca addition maintained the plasma ion (Na + , K + , Cl - ) homeostasis, alleviated Cd-induced oxidative stress (OS), and regulated the activities and transcriptional levels of ATPase. Furthermore, transcriptional heatmap analysis demonstrated that several indicator genes for OS and calcium signaling pathway were found to be significantly modulated by Ca addition. This work delineates a protective effect of Ca against Cd-induced toxicity in grass carp, providing new insight into the possible solutions to Cd pollution issues in aquaculture industry.
研究领域:
环境科学
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水产养殖学
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毒理学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2020
·
IF 8.758
Guojian Yang,Baige Yang,Weijia Mu,Yinghao Ge,Yiru Cai,Zhiqiang Yao,Zhaoyu Ma,Yu-Mo Zhang,Sean Xiao-An Zhang
Due to the high energy efficiency and a wide range of potential applications in daily life, bistable electrochromic devices (BECDs) have gained extensive attention in recent years. However, poor bistability and slow response rate are the main barriers, which restrict the development of BECDs. Herein, a transparent multidimensional electrode with indium tin oxide (ITO) nanofibers and gold nanoparticles was fabricated to improve both the bistability and responsiveness of devices. Its criss-crossed ITO nanofibers with high length-to-diameter ratios to reduce the distance of heterogeneous electron transfer and its gold nanoparticles to form a stable Au–S bond to avoid self-erasing of electrochromic materials have been demonstrated and discussed systematically. This device based on the transparent multidimensional working electrode had a shorter response time (1/5) and a longer bistability (12/1) compared with the prototype devices based on common fluorine-doped tin oxide electrodes. Besides, this device had a promising electrochromic performance with a high coloration efficiency of 448.27 cm2/C and a switching stability with no significant attenuation after 1200 cycles.
研究领域:
材料科学
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纳米技术
·
电化学
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产品关联
DOI
PubMed
高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2025
·
IF 3.1
Liu Wencheng,Liu Rifu,Yang Yue,Cheng Lixue,Feng Xiaobing,Li Qinglei
This study investigated the potential therapeutic effect of kaempferol on osteoporosis by regulating bone homeostasis through the YAP. The ovariectomy model was constructed. The changes in bone and liver tissue were observed through HE staining. Bone metabolism and inflammatory markers were quantitatively analyzed using RT-qPCR and ELISA. Changes in the YAP/NF-κB signaling pathway were detected through Western blot and immunofluorescence. In vitro, the activity and secretion levels of MC3 T3-E1-differentiated osteoblasts were assessed using CCK- 8 and ELISA. The effects of osteoblast-secreted factors on osteoclast-induced differentiation were analyzed using alizarin red staining, phalloidin staining, ELISA, TRAP staining, and SEM. Finally, the regulatory effects of kaempferol on the expression of bone homeostasis in osteoclasts were examined by immunofluorescence and Western blot. Kaempferol treatment improved trabecular bone structure, increased bone density, and modulated bone metabolism by enhancing OPG expression and suppressing TRAP, NFATC1, and RANKL levels. Kaempferol inhibited the activation of the NF-κB pathway and increased YAP expression, reducing inflammatory factors. In vitro, kaempferol promoted osteoblast differentiation and inhibited osteoclast activity. These effects were most pronounced at higher kaempferol doses and were associated with improved bone remodeling and reduced bone resorption. Kaempferol exhibits significant potential for osteoporosis treatment by regulating bone homeostasis, mitigating inflammation through modulating the YAP.
研究领域:
药理学
·
骨生物学
·
信号通路研究
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产品关联
DOI
PubMed
高影响因子
IMMUNITY
·
2024
·
IF 25.5
Jiping Sun,Youqin Zhang,Qingbing Zhang,Lin Hu,Linfeng Zhao,Hongdong Wang,Yue Yuan,Hongshen Niu,Dongdi Wang,Huasheng Zhang,Jianyue Liu,Xujiao Feng,Xiaohui Su,Ju Qiu,Jing Sun,Heping Xu,Catherine Zhang,Kathleen Wang,Yan Bi,Edgar G. Engleman,Lei Shen
Adipose tissue group 2 innate lymphoid cells (ILC2s) help maintain metabolic homeostasis by sustaining type 2 immunity and promoting adipose beiging. Although impairment of the ILC2 compartment contributes to obesity-associated insulin resistance, the underlying mechanisms have not been elucidated. Here, we found that ILC2s in obese mice and humans exhibited impaired liver kinase B1 (LKB1) activation. Genetic ablation of LKB1 disrupted ILC2 mitochondrial metabolism and suppressed ILC2 responses, resulting in exacerbated insulin resistance. Mechanistically, LKB1 deficiency induced aberrant PD-1 expression through activation of NFAT, which in turn enhanced mitophagy by suppressing Bcl-xL expression. Blockade of PD-1 restored the normal functions of ILC2s and reversed obesity-induced insulin resistance in mice. Collectively, these data present the LKB1-PD-1 axis as a promising therapeutic target for the treatment of metabolic disease.
研究领域:
免疫学
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代谢生物学
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医学
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DOI
PubMed
高影响因子
JOURNAL OF MATERIALS CHEMISTRY
·
2012
·Vol. 22
·期 15
·7502-7506
·
IF 5.968
Hechun Jiang,Pengcheng Dai,Zhenyu Feng,Weiliu Fan,Jinhua Zhan
Cu2ZnSnS4 (CZTS) is acknowledged as an alternative to traditional p-type semiconductors. Traditionally obtained CZTS, however, is mostly kesterite or stannite phase, which features a tetragonal crystal cell. Herein, novel orthorhombic CZTS has been synthesized via an ethylenediamine-assisted hydrothermal method. Ethylenediamine plays an important part in the construction of the orthorhombic phase. Kesterite CZTS was also obtained in an ultrapure water system without ethylenediamine. The structure was confirmed by XRD, XPS and HRTEM. The band gap of the orthorhombic CZTS is about 1.45 eV, which approaches the optimum value for solar photoelectric conversion. What's more, we found that this orthorhombic CZTS is metastable. After annealing at 500 °C, a phase transformation from the orthorhombic structure to the tetragonal kesterite structure was achieved. The photoelectric response was also characterised, which demonstrated its potential for application in photovoltaic devices.
研究领域:
材料科学
·
光伏技术
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）