eLife
·
2018
·
IF 7.616
Dao-Lai Zhang,Yu-Jing Sun,Ming-Liang Ma,Yi-jing Wang,Hui Lin,Rui-Rui Li,Zong-Lai Liang,Yuan Gao,Zhao Yang,Dong-Fang He,Amy Lin,Hui Mo,Yu-Jing Lu,Meng-Jing Li,Wei Kong,Ka Young Chung,Fan Yi,Jian-Yuan Li,Ying-Ying Qin,Jingxin Li,Alex R B Thomsen,Alem W Kahsai,Zi-Jiang Chen,Zhi-Gang Xu,Mingyao Liu,Dali Li,Xiao Yu,Jin-Peng Sun
Luminal fluid reabsorption plays a fundamental role in male fertility. We demonstrated that the ubiquitous GPCR signaling proteins Gq and β-arrestin-1 are essential for fluid reabsorption because they mediate coupling between an orphan receptor ADGRG2 (GPR64) and the ion channel CFTR. A reduction in protein level or deficiency of ADGRG2, Gq or β-arrestin-1 in a mouse model led to an imbalance in pH homeostasis in the efferent ductules due to decreased constitutive CFTR currents. Efferent ductule dysfunction was rescued by the specific activation of another GPCR, AGTR2. Further mechanistic analysis revealed that β-arrestin-1 acts as a scaffold for ADGRG2/CFTR complex formation in apical membranes, whereas specific residues of ADGRG2 confer coupling specificity for different G protein subtypes, this specificity is critical for male fertility. Therefore, manipulation of the signaling components of the ADGRG2-Gq/β-arrestin-1/CFTR complex by small molecules may be an effective therapeutic strategy for male infertility.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
·
IF 6.2
Yongjia Cheng,Yao Chen,Jianjun Liu,Dongyang Li,Juan Zhang,Chaojie Li,Wen Yang,Zhiwei Lei
Plants release a variety of defensive volatiles in response to biotic stress. The present study examined interactions between Colletotrichum fructicola and the defense volatiles induced by this fungal species in the tea cultivar “Qiancha No. 1”. Analysis of the volatiles emitted from C. fructicola-infected leaves of “Qiancha No. 1” revealed that four volatiles showed a relative content increase of more than 2%. Fungicidal activity assays demonstrated that decanal exhibited the strongest antifungal activity among the four volatiles. Further physiological experiments demonstrated that the antifungal mechanism of decanal was associated with disruption of the cell wall and the membrane. Transcriptome analysis revealed that the genes encoding Chitinase 1, chitin synthase 1, and endochitinase42 were identified as potential targets that may be involved in cell wall degradation by decanal. Additionally, genes encoding cytochrome P450-DIT2 and multidrug resistance protein fer6 were identified as potential targets that may be associated with membrane damage. This study is the first to demonstrate that decanal acts as a direct defense volatile in the interaction between C. fructicola and “Qiancha No. 1,” highlighting its potential as an effective antifungal agent.
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JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2025
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IF 9.7
Shengkai Sun,Yuan Li,Yusen Chen,Dehong Chen,Yu Yang,Meng Liu,Shaoxiang Li,Binjie Li,Xuan Sun,Sadritdin Turabdjanov,Sardor Donaev,Lei Wang,Bin Li
Volatile organic compounds (VOCs) in the atmosphere pose a critical global challenge due to their detrimental health effects. The ultraviolet (UV)/Fenton-like system has shown promise for VOC degradation. However, maintaining long-term catalytic efficiency by minimizing intermediate byproduct accumulation remains key challenges. In this study, a novel core–shell catalyst is developed which composed of anatase-phase titanium dioxide (TiO 2 ) nanoparticles deposited on titanium silicalite-1 (TS-1) via a Stöber method in an ethanol/ammonia mixture. The TS-1@TiO 2 structure promotes efficient spatial separation of photogenerated electrons and holes under UV irradiation, enhancing the activation of H 2 O 2 to yield highly reactive free radicals ( OH, OOH and O 2 − ) for effective xylene degradation. In a UV/H 2 O 2 bubble reactor, the TS-1@TiO 2 catalyst demonstrates stable xylene degradation efficiency (75 % over 200 min), surpassing the performance of standalone TS-1 (53.2 %) and TiO 2 (62.1 %). This design addresses critical challenges in sustained radical generation and intermediate suppression, offering a robust strategy to improve the longevity and efficiency of UV/H 2 O 2 systems for environmental remediation.
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CLINICAL AND EXPERIMENTAL HYPERTENSION
·
2025
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IF 3.5
Hao Wang,Ke Zhou,Xiaoling Chen,Yao Tong,Qiuyan Jiang,Qiang She,Jun Xiao
Myocardial infarction (MI) is a leading cause of morbidity and mortality globally, primarily due to oxidative stress-induced cardiomyocyte apoptosis and adverse cardiac remodeling. OL-FS13, a neuroprotective peptide derived from Odorrana livida, has previously shown anti-apoptotic effects in cerebral ischemia models. However, its role in myocardial protection remains unclear. In this study, we investigated the cardioprotective effects of OL-FS13 in both in vitro and in vivo models of MI. Hydrogen peroxide (H₂O₂) was used to induce oxidative stress in primary neonatal rat cardiomyocytes, while permanent ligation of the left anterior descending (LAD) coronary artery was employed to establish a murine MI model. OL-FS13 treatment significantly attenuated cardiomyocyte apoptosis, reduced ROS accumulation, improved left ventricular function, and decreased infarct size. Mechanistically, OL-FS13 activated the Nrf2/HO-1 signaling pathway, restoring antioxidant protein levels and suppressing oxidative stress-induced apoptosis. Pharmacological inhibition of Nrf2 with ML385 abrogated the antioxidant and anti-apoptotic effects of OL-FS13 both in vitro and in vivo, confirming the central role of this pathway. These findings demonstrate that OL-FS13 exerts potent cardioprotective effects via Nrf2/HO-1 pathway activation and ROS suppression, suggesting its potential as a novel therapeutic agent for the treatment of myocardial infarction.
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BIOMATERIALS
·
2024
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IF 12.8
Jiajia Luo,Yaqi Shang,Ning Zhao,Xiaoying Lv,Zheng Wang,Xin Li,Xuan Meng,Yanjun Zhao
ABSTRACT Ferroptosis has been recognized as a promising therapeutic strategy for cancer due to its unique mechanism of action. However, the upregulation of stearoyl-CoA desaturase 1 (SCD1) in ovarian cancer leads to resistance to ferroptotic therapy. Zinc ion (Zn 2+ ) serves as the cofactor of SCD1. It was hypothesized that selective deprivation of Zn 2+ from SCD1 could sensitize ferroptotic ovarian cancer therapy. Here, we report a hypoxia-responsive polymer micelle for enhanced ferroptosis of ovarian cancer cells. An SCD1 inhibitor, PluriSIn 1 (Plu), and a ferroptosis inducer, Auranofin (Aur), were co-encapsulated in nitroimidazole-bearing micelles. Under the hypoxic tumor microenvironment, the conversion of nitroimidazole to aminoimidazole triggered the cargo release and induced the depletion of antioxidant molecules (e.g., glutathione, thioredoxin, and NADPH). Meanwhile, because of the strong coordination between aminoimidazole and Zn 2+ compared to that of histidine and Zn 2+ , such conversion can deprive the metal cofactor of SCD1, hence sensitizing the action of Plu and Aur. The proof-of-concept was demonstrated in cell and animal models with minimal systemic toxicity. The current work integrates ferroptosis induction with SCD1 inhibition in a hypoxia-responsive vehicle, offering a promising strategy for addressing the ferroptosis resistance and opening novel avenues for managing difficult-to-treat ovarian cancer.
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Foods
·
2022
·Vol. 11
·期 19
·2978
·
IF 5.561
Wenyan Lin,Yaping Liu,Jianbing Di,Gang Ren,Wei Wang,Weichun He,Yu Wang
Root mustard is plentiful in vitamins and minerals but shrivels and molds easily. In this study, freshly harvested root mustard was fumigated with various concentrations of 1-Methycyclopropene(1-MCP) (1 µL L−1, 1.5 µL L−1, and 2.0 µL L−1) for 24 h and stored at ambient temperature (17 ± 1 °C) for 35 d. Our data showed that 1-MCP fumigation had a striking preservation effect on maintaining weight loss, fruit firmness, lignin, Vc content, and moisture content, inhibiting respiratory intensity and ethylene release rate, as well as decreasing cell permeability and malondialdehyde (MDA) accumulation and maintaining cell membrane integrity of root mustard. In addition, lipoxygenase (LOX), pyruvate dehydrogenase (PDH), and polyphenol oxidase (PPO) activities were significantly reduced throughout the storage period. In contrast, the activities of succinate dehydrogenase (SDH), superoxide dismutase (SOD), ascorbate peroxidase (APX), phenylalanine deaminase (PAL), and peroxidase (POD) remained at high levels. Results showed that 1-MCP treatments were effective in maintaining the quality of root mustard, and the preservation effect of 1.0 μL·L−11-MCP was better than other concentrations of 1-MCP. This study could serve as a theoretical reference for root mustard preservation.Keywords:1-MCP;root mustard;physiology;storage quality
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Frontiers in Pharmacology
·
2021
·
IF 5.811
Yang Xiaohua,Zhang Min,Lu Zhihong,Zhi Linping,Xue Huan,Liu Tao,Liu Mengmeng,Cui Lijuan,Liu Zhihong,He Peifeng,Liu Yunfeng,Zhang Yi
Glucagon-like peptide-1 receptor (GLP-1R) agonist-based therapeutics for type 2 diabetes mellitus have attracted worldwide attention. However, there are challenges in the development of small molecule GLP-1R agonists owing to the complexity of ligand recognition and signal induction mechanisms. Here, we attained S6 using virtual screening and fluorescent imaging plate reader (FLIPR)-based calcium assays. The purpose of this study was to identify and characterize S6, a novel small molecule GLP-1R agonist. Data from cellular thermal shift assay (CETSA) and Bio-Layer Interferometry (BLI) indicated that S6 could bind potently with GLP-1R. Radioimmunoassay data showed that S6 potentiated insulin secretion in a glucose-dependent manner and the insulinotropic effect was mediated by GLP-1R. Calcium imaging techniques suggested that S6 elevated the intracellular calcium concentration [(Ca2+)i] by activating GLP-1R. In patch-clamp experiments, we demonstrated that S6 inhibited voltage-dependent K+ (Kv) channels in a GLP-1R-dependent fashion. Besides, S6 significantly prolonged action potential duration but had no effect on voltage-dependent Ca2+ channels. In summary, these findings indicate that S6 stimulates glucose-dependent insulin secretion mainly by acting on GLP-1R, inhibiting Kv channels, increasing (Ca2+)i. This study will provide direction for the screening and development of novel small-molecule agents targeting GLP-1R in the future.
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PLANT PHYSIOLOGY AND BIOCHEMISTRY
·
2025
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IF 5.7
Feixiong Zheng,Zhangting Xu,Xiaoji Deng,Yiming Sun,Jaime A. Teixeira da Silva,Xiaoxia Shen,Zhenming Yu
Salt stress severely constrains plant growth and productivity, so understanding the underlying mechanisms of salt stress is crucial for the genetic improvement of plants. Aquaporins (AQPs), which facilitate the transport of water or nutrients, exert an indispensable role in plants' response to salt stress. The AQP family in Dendrobium officinale , a commercially important medicinal and edible orchid, has not been identified or functionally characterized, while an understanding of this plant's tolerance to salinity remains unexplored. In this study, a genome-wide identification of AQP genes in D. officinale was performed using a salt-induced transcriptome. The 28 AQP members were mined and classified into four subfamilies (NIPs, PIPs, SIPs, and TIPs), and their physicochemical and bioinformatic properties were analyzed. Overexpression of DoTIP1-1 in D. officinale significantly enhanced salt tolerance via the accumulation of proline and water-soluble polysaccharides that improved water retention. Furthermore, salt tolerance was fortified by the improved activity of antioxidant enzymes (peroxidase and superoxide dismutase), allowing reactive oxygen species to be scavenged, and augmenting photosynthetic efficiency due to the upregulated expression of stress-responsive genes. This study provides the first comprehensive analysis of the AQP family in D. officinale and demonstrates that DoTIP1-1 is a key genetic determinant for enhancing salt tolerance, offering significant potential for the genetic improvement of this plant to resist abiotic stress.
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY
·
2017
·Vol. 86
·期 12
·2744-2751
·
IF 0.553
Ying S.,Wang Jia,Xu C.,Kang Y.,Zhang X.,Shi L.,Fan L.,Wang Z.,Zhou J.,Wu X.,Wu J.,Li W.,Liang G.
Fibroblast growth factor receptor 1 (FGFR1) is considered a therapeutic target for multiple cancers, including gastric cancer. FGFR1 inhibitors, being ATP competitors, can prevent the kinase domain and the downstream signaling cascade from phosphorylation and thus have the potential to treat cancers associated with aberrant FGFR1 activation. However, untargeted inhibition may cause numerous side effects. Thus, a non-ATP competitive FGFR1 inhibitor should be urgently identified and explored. In this study, we designed and synthesized 17 derivatives of nordihydroguaiaretic acid (NDGA), a known ATP-independent FGFR3 inhibitor. In the kinase activity assay, 3,5-bis(2-fluorobenzylidene)piperidin-4-one ( 1B ) showed the highest kinase inhibitory activity among all derivatives and was thus identified as a non-ATP-competitive FGFR1 inhibitor. In the biological effect evaluation, 1B restrained the FGFR−FRS2−ERK signaling pathway in a dose-dependent manner and inhibited the growth of two gastric cancer cell lines. Overall, 1B can be considered as a potential candidate for treating gastric cancer and as an outstanding lead compound for the discovery of novel non-ATPcompetitive FGFR1 inhibitors.
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BIOSENSORS & BIOELECTRONICS
·
2021
·
IF 10.618
Qian Han,Cun Wang,Pingkun Liu,Gui Zhang,Li Song,Yingzi Fu
The excellent characteristics of porphyrins have inspired widespread interest in electrochemiluminescence (ECL). However, the limited ECL intensity and poor stability of porphyrins in aqueous solution are still severely restricted further biological application . Here, we subtly synthesized a functionalized europium and 5,10,15,20-tetrakis (4-carboxyphenyl) porphyrin (TCPP) coordination polymer (Eu-PCP) by a one-step solvothermal method . In sharp contrast to the pristine TCPP, Eu-PCP showed a higher and more stable ECL red-light emission (673 nm) at low potential (−1.1 V, vs Ag/AgCl), which was 7.7-fold higher ECL intensity and 4.6-fold efficiency. In view of the crucial role of mucin 1 (MUC1) in tumor overexpression , it was selected as the target molecule. Combined with exonuclease III (Exo III)-assisted recycling amplification strategy, a ternary ECL biosensor was constructed for the MUC1 detection based on Eu-PCP as a satisfied ECL emitter, gold nanoparticles capped CeO 2 (CeO 2 @Au) as the coreactant accelerator and peroxydisulfate as coreactant. Meanwhile, gold nanoparticles capped MnO 2 (MnO 2 @Au) was used as the quenching probe to achieve a highly sensitive detection of MUC1. The proposed biosensor exhibited a wide linear range from 1 fg mL −1 to 10 ng mL −1 with a low limit of detection (0.32 fg mL −1 ). By changing the corresponding target recognition DNA , this strategy could be expanded to detect other biomarkers.
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Journal of Ginseng Research
·
2022
·
IF 5.735
Hong-Yan Guo,Yue Xing,Yu-Qiao Sun,Can Liu,Qian Xu,Fan-Fan Shang,Run-Hui Zhang,Xue-Jun Jin,Fener Chen,Jung Joon Lee,Dongzhou Kang,Qing-Kun Shen,Zhe-Shan Quan
Background Ginseng possesses antitumor effects, and ginsenosides are considered to be one of its main active chemical components. Ginsenosides can further be hydrolyzed to generate secondary saponins, and 20( R )-panaxotriol is an important sapogenin of ginsenosides. We aimed to synthesize a new ginsengenin derivative from 20( R )-panaxotriol and investigate its antitumor activity in vivo and in vitro . Methods Here, 20( R )-panaxotriol was selected as a precursor and was modified into its derivatives. The new products were characterized by 1 H-NMR, 13 C-NMR and HR-MS and evaluated by molecular docking, MTT, luciferase reporter assay, western blotting, immunofluorescent staining, colony formation assay, EdU labeling and immunofluorescence, apoptosis assay, cells migration assay, transwell assay and in vivo antitumor activity assay. Results The derivative with the best antitumor activity was identified as 6,12-dihydroxy-4,4,8,10,14-pentamethyl-17-(2,6,6-trimethyltetrahydro-2 H -pyran-2-yl)hexadecahydro-1 H -cyclopenta[a]phenanthren-3-yl( tert -butoxycarbonyl)glycinate ( A11 ). The focus of this research was on the antitumor activity of the derivatives. The efficacy of the derivative A11 (IC 50 < 0.3 μM) was more than 100 times higher than that of 20( R )- panaxotriol (IC 50 > 30 μM). In addition, A11 inhibited the protein expression and nuclear accumulation of the hypoxia-inducible factor HIF-1α in HeLa cells under hypoxic conditions in a dose-dependent manner. Moreover, A11 dose-dependently inhibited the proliferation, migration, and invasion of HeLa cells, while promoting their apoptosis. Notably, the inhibition by A11 was more significant than that by 20( R )-panaxotriol ( p < 0.01) in vivo . Conclusion To our knowledge, this is the first study to report the production of derivative A11 from 20( R )-panaxotriol and its superior antitumor activity compared to its precursor. Moreover, derivative A11 can be used to further study and develop novel antitumor drugs.
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Advanced Healthcare Materials
·
2020
·Vol. 9
·期 11
·1901783
·
IF 7.367
Ting Hong,Yazhong Wei,Xiaomei Xue,Yongyong Li,Haiqing Dong,Xiaoyu Guo,Xueyin Shi,Bin He
Great progress has been made in miRNA nanodelivery for the treatment of myocardial infarction (MI). However, miRNA nanodelivery within the infarct is impeded by microvascular obstruction as a local circulatory disorder caused by microthrombus formation in microvessels. Knowing that low molecular weight heparin (LMWH) can effectively prevent microthrombus formation in microcirculation, it is hypothesized whether surface modification of the nanocarrier with LMWH can overcome microvascular obstruction in the infarct area for better miRNA delivery. Herein, a novel nanocomlex consisting of dendrigraft poly- l -lysine (DGL)-loaded miR-1 inhibitor as the core to decrease apoptosis of cardiomyocytes and LMWH as the shell to overcome microvascular obstruction of the infarct area is developed. The results show that this anti-coagulative nanocomlex is able to reduce microthrombus formation in microvessels and inhibit blood-coagulation factor Xa, thereby overcoming microvascular obstruction in the infarct area. In addition, it further enhances the uptake of miR-1 inhibitor within the infarct and decreases myocardiocyte apoptosis, thus improving the cardiac function and attenuating the myocardial fibrosis. In conclusion, modification of DGL-loaded miR-1 inhibitor with LMWH helps overcome microvascular obstruction in delivering the drug to the infarct area, thus providing a promising therapeutic strategy for achieving a better therapeutic outcome of MI.
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