WATER RESEARCH
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2025
·
IF 12.4
Ziyi Zhao,Yanan Mi,Shili Wang,Xuedong Du,Qingrui Zhang
We firstly present a novel strategy for enhancing fluoride removal from contaminated water using defect-engineered UiO-66 (Zr-MOFs), emphasizing the crucial role of pKa in modulator selection. By utilizing modulators with varying pKa values-specifically benzimidazole (BI), benzoic acid (BA), and acetic acid (AA)-we synthesized defect-rich Act-UiO-66-M(X). The higher pKa of BI facilitated greater defect formation, resulting in significantly improved adsorption capacity and faster diffusion rates. Act-UiO-66-BI(8), modulated with BI, showed a higher intensity peak at g = 2.003 in ESR analysis, indicating more oxygen vacancies. Its fluoride adsorption capacity reached 93.59 mg F/g, nearly six times higher than commercial ZrO 2 , with rapid kinetics—evidenced by a kinetic rate constant (k int ) of 2.64 mg/g·min 0.5 and equilibrium achieved within 10 minutes. The kinetic performance was enhanced by 270% compared to raw Act-UiO-66. Furthermore, Act-UiO-66-BI(8) demonstrated high selectivity and stability in high-salinity environments, with a K d coefficient consistently exceeding 17,900 mL/g. The study highlights that selecting modulators based on pKa enhances defect formation, improving active site exposure and pore diffusion, as confirmed by DFT calculations and XPS analysis. The ability of Act-UiO-66-BI(8) to treat up to 1160 kg of wastewater per kg of adsorbent highlights its potential for large-scale water purification, showcasing a promising approach for developing high-performance MOF materials.
研究领域:
环境科学
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材料科学
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DOI
PubMed
高影响因子
CELLULAR AND MOLECULAR LIFE SCIENCES
·
2025
·Vol. 82
·期 1
·1-16
·
IF 6.2
Zhao Xueqin,Li Yuanhao,Yang Liu,Chen Xi,Zhang Jialong,Chen Tong,Wang Haoqi,Li Fei,Cheng Chen,Wu Jingjing,Cong Jingjing,Yin Wenwei,Li Jing,Wang Xuefu
Acetaminophen (APAP) overdose induces acute liver injury and represents the most frequent cause of drug-induced liver injury worldwide. Macrophage-mediated inflammation plays detrimental roles during the early stage of liver injury. However, the potential targets regulating inflammation to improve drug-induced liver injury remains undefined. In this study, we reported that G protein-coupled receptor 35 (GPR35) improves drug-induced liver injury by blocking macrophage-mediated inflammation via the Gαs-cyclic AMP-protein kinase A (Gαs-cAMP-PKA) pathway. The ablation of GPR35 exacerbates APAP-induced liver injury, characterized by higher levels of alanine aminotransferase and aspartate aminotransferase in sera, larger damaged areas, and increased levels of pro-inflammatory cytokines. More hepatic macrophages appeared in the inflamed liver of mice with GPR35 deficiency. In contrast, the agonists of GPR35 alleviated APAP-induced liver injury. The depletion of macrophages abolished GPR35-mediated protection. Mechanistically, GPR35 ablation facilitated the activation of pro-inflammatory AKT, MAPK, and NF-κB signaling pathways at the downstream of Toll-like receptors in macrophages. GPR35 agonists activated Gαs-cAMP-PKA signaling to inhibit the activation of these pro-inflammatory signaling pathways and then suppress the inflammatory response in macrophages. Thus, our findings demonstrate that GPR35 prevents drug-induced liver injury by blocking macrophage-mediated inflammation via the Gαs-cAMP-PKA pathway, indicating that GPR35 is a potential target for the development of novel medicines that control drug-induced liver injury.
研究领域:
药理学
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肝脏病学
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免疫学
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DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY
·
2023
·
IF 10.9
Jianmao Zheng,Jiyuan Zuo,Cairong Xiao,Qining Guo,Xiaobin Fu,Chengyun Ning,Peng Yu
The induction of dental pulp stem cells (DPSCs) into odontogenic differentiation is a cutting-edge method of dental pulp regeneration treatment. However, it remains a challenge to develop biomaterials and therapies that can induce odontogenic differentiation. Here, we propose a wireless electrical stimulation strategy to induce DPSCs odontogenic differentiation via K 0.5 Na 0.5 NbO 3 piezoelectric nanoparticles (KNN) and polarized KNN (PKNN), which can be endocytosed by DPSCs. In vitro, several odontogenic differentiation indexes were also increased in DPSCs treated with KNN and PKNN, and the increase was more obvious in the PKNN group. Intracellular wireless electrical field promoted mitochondrial calcium concentration via mitochondrial calcium unidirectional transporter (MCU), increased the production of adenosine triphosphate (ATP), and induced odontogenic differentiation through the activation of the cAMP-PKA signaling pathway. In vivo, dental pulp-like tissue was induced by electrical stimulation wirelessly with KNN and PKNN, which was more clinically friendly compared with the wired device, and the induction was more obvious in the PKNN group consistent with in vitro experiments. In conclusion, this work demonstrates the potential of PKNN as an effective stimulus that can induce odontogenic differentiation of DPSCs and be applied to dental pulp regeneration treatment.
研究领域:
牙科学
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生物材料
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干细胞生物学
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纳米技术
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再生医学
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DOI
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2018
·
IF 5.667
Ting Yin,Sheng Zhang,Mengxuan Li,Carl Redshaw,Xin-Long Ni
Supramolecular p K a shifts, have attracted much attention in catalytic and biomimetic studies because of their excellent property to modify the acidity or basicity of the substrate in aqueous media by host-guest inclusion. Here, Fluorescence indicator displacement based on cucurbit[8]uril encapsulation of the dye acridine leads to the recognition of the peptide drug octreotide in aqueous solution via distinctive pH signals was expolited. This is thought to be a result of competitive host-guest interactions involving a supramolecular p K a shift.
研究领域:
生物化学
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药物化学
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分析化学
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DOI
高影响因子
PROCESS BIOCHEMISTRY
·
2021
·
IF 3.757
Yonghua Hu,Yuan Zhou,Xiaohua Hu,Qiaoling Chen,Yan Shi,Jiangxing Zhuang,Qin Wang
Cefotaxime sodium (CTX) was found to inhibit the activity of mushroom tyrosinase. The present study was conducted to investigate its inhibition of melanogenesis in B16F10 cells. CTX was found to inhibit melanin synthesis in B16F10 cells at a concentrations less than 200 μmol/L with no cytotoxicity. CTX reduced tyrosinase activity in a dose-dependent manner. CTX inhibited melanin formation from the results of the Masson-Fontana melanin staining and transmission electron microscope CTX influenced melanin production by influencing the expression of the proteins MITF, TRP-1, TRP-2 and TYR. Furthermore, CTX could down-regulate the intracellular cAMP/PKA/CREB contents, affecting the expression of MITF, and further down-regulate the expression of TRP-1, TRP-2 and TYR to inhibit melanin. Furthermore, CTX has been shown to inhibit body pigmentation in zebrafish. These results may provide a theoretical foundation for the new application of CTX in the field of medicine.
研究领域:
药理学
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细胞生物学
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分子生物学
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DOI
高影响因子
JOURNAL OF PERIODONTAL RESEARCH
·
2025
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IF 3.4
Jiaying Song,Xingyi Li,Kailibinuer Abuduwaili,Yue Sun,Jiangbo Li,Danying Chen,Zhuofan Chen,Zhipeng Li,Baoxin Huang
Aim Periodontitis is a chronic inflammatory disease initiated by dysbiosis of the local microbial community. As a non-specific phosphodiesterase inhibitor, dipyridamole features anti-oxidant and anti-inflammatory properties. This study aimed to investigate the effects of dipyridamole in an experimental rat model of periodontitis. Methods Thirty rats were divided randomly into three groups ( n = 10): non-ligature group (NL), ligature-induced periodontitis group (L), and ligature-induced periodontitis with dipyridamole administered group (L + D). All rats were euthanized on Day 14. Alveolar bone resorption was analyzed by microcomputed tomography. The mRNA levels of Il1b , Il6 , tumor necrosis factor alpha ( Tnfa ), and inducible nitric oxide synthase ( iNos ) in gingival tissue were assessed by real-time quantitative polymerase chain reaction (qRT-PCR). Inflammation level, osteoclasts, and macrophages infiltration were analyzed histologically. RAW264.7 macrophages were stimulated with Porphyromonas gingivalis lipopolysaccharide ( P.g. LPS) to induce M1 polarization. Different concentration of dipyridamole (0/2/10 μM) was added simultaneously. To explore the role of PKA/PKG pathways, RAW 264.7 macrophages were pretreated with 10 μM H-89 (PKA inhibitor) or 1 μM KT-5823 (PKG inhibitor), respectively. Expression of pro-inflammatory cytokines and M1 markers were detected by qRT-PCR, ELISA, and flow cytometry. Results Dipyridamole administration reduced alveolar bone loss, protein levels of inflammatory cytokines, and osteoclastogenesis in rats with experimental periodontitis. It also showed a tendency to decrease mRNA levels of Il1b , Il6 , and Tnfa but without significant differences in gingival tissues. Moreover, the infiltration of macrophage and M1 macrophage polarization in gingival tissue of periodontitis rats were inhibited by dipyridamole administration. In addition, dipyridamole could downregulate the gene expression of Il1b and Tnfa , as well as the protein level of TNF-α, CD86, and iNOS in RAW264.7 treated with P.g. LPS. When PKA/PKG pathways were blocked, the suppression of TNF-α, CD86, and iNOS was reversed significantly. Conclusion Dipyridamole alleviated experimental periodontitis in rat models by regulating M1 polarization via activation of PKA/PKG pathways and emerges as a hopeful remedy for periodontitis. Graphical As non-specific phosphodiesterase inhibitor, dipyridamole reduced alveolar bone loss, expression level of inflammatory cytokines, and osteoclast genesis in ligature-induced periodontitis of rats by regulating M1 macrophage polarization via activation of PKA/PKG pathways, emerging as a hopeful treatment for periodontal disease.
研究领域:
牙医学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
mBio
·
2025
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IF 4.7
Kaili Duan,Shaozhe Qin,Fangling Cui,Liangyuan Zhao,Yongqing Huang,Jin-Rong Xu,Guanghui Wang
Deoxynivalenol (DON), a mycotoxin primarily produced by Fusarium species, is commonly found in cereal grains and poses risks to human and animal health, as well as global grain trade. This study demonstrates that methyl jasmonate (MeJA), a natural plant hormone, inhibits the growth and conidiation of Fusarium graminearum. Importantly, MeJA significantly reduces DON production by suppressing TRI gene expression and toxisome formation. To explore the molecular mechanism, we identified MeJA-tolerant mutants, including a transcription factor MRT1 and cAMP-PKA pathway-related genes (FgGPA1 and FgSNT1). MeJA treatment reduced PKA activity and intracellular cAMP levels in F. graminearum, suggesting it targets the cAMP-PKA pathway. Notably, the MeJA-resistant mutant FgGPA1R178H enhanced fungal growth, DON production, and cAMP levels in the presence of MeJA. Exogenous cAMP alleviated MeJA’s inhibitory effects on DON production, further supporting this pathway’s involvement. Interestingly, MeJA had no effect on all three MAP kinase pathways (Mgv1, Gpmk1, and FgHog1). Truncated and phospho-mimicking mutations in Mrt1 or FgSnt1 conferred MeJA resistance, suggesting they may act downstream of the cAMP-PKA pathway. In conclusion, MeJA presents a promising approach to control F. graminearum growth and DON production.
研究领域:
植物病理学
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分子生物学
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真菌学
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DOI
PubMed
高影响因子
PHARMACEUTICAL RESEARCH
·
2022
·Vol. 39
·期 9
·2263-2276
·
IF 4.58
He Xiaoshuang,Wei Yuanfeng,Wang Shiru,Zhang Jianjun,Gao Yuan,Qian Shuai,Pang Zunting,Heng Weili
Honokiol (HK), a BCS class II drug with a wide range of pharmacological activities, has poor solubility and low oral bioavailability, severely limiting its clinical application. In the current study, incorporating a water-soluble meglumine (MEG) into the crystal lattice of HK molecule was performed to improve its physicochemical properties. The binary mixture of HK and MEG was obtained by anti-solvent method and characterized by TGA, DSC, FTIR, and PXRD. The SCXRD analysis showed that two HK − molecules and two MEG + molecules were coupled in each unit cell via the ionic interaction along with intermolecular hydrogen bonds, suggesting the formation of a salt, which was further confirmed by the XPS measurements. However, the ∆pK a value between HK and MEG was found to be less than 1, which did not follow the oft-quoted ∆pK a rule for salt formation. After salification with MEG, the solubility and dissolution rate of HK exhibited 3.50 and 25.33 times improvement than crystalline HK, respectively. Simultaneously, the powder flowability, tabletability and stability of HK-MEG salt was also significantly enhanced, and the salt was not more hygroscopic, and that salt formation did not compromise processability in that regard. Further, in vivo pharmacokinetic study showed that C max and AUC 0-t of HK-MEG salt were enhanced by 2.92-fold and 2.01-fold compared to those of HK, respectively, indicating a considerable improvement in HK oral bioavailability.
研究领域:
药学
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药物制剂
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药物递送
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DOI
PubMed
高影响因子
Journal of Ginseng Research
·
2022
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IF 5.735
Ye-ying Jiang,Rong-yun Wei,Kai Tang,Zhen Wang,Ning-hua Tan
Background Mechanisms of synaptic plasticity in retinal ganglion cells (RGCs) are complex and the current knowledge cannot explain. Growth and regeneration of dendrites together with synaptic formation are the most important parameters for evaluating the cellular protective effects of various molecules. The effect of ginsenoside Rg1 (Rg1) on the growth of retinal ganglion cell processes has been poorly understood. Therefore, we investigated the effect of ginsenoside Rg1 on the neurite growth of RGCs. Methods Expression of proteins and mRNA were detected by Western blot and qPCR. cAMP levels were determined by ELISA. In vivo effects of Rg1 on RGCs were evaluated by hematoxylin and eosin, and immunohistochemistry staining. Results This study found that Rg1 promoted the growth and synaptic plasticity of RGCs neurite by activating the cAMP/PKA/CREB pathways. Meanwhile, Rg1 upregulated the expression of GAP43, Rac1 and PAX6, which are closely related to the growth of neurons. Meantime, H89, an antagonist of PKA, could block this effect of Rg1. In addition, we preliminarily explored the effect of Rg1 on enhancing the glycolysis of RGCs, which could be one of the mechanisms for its neuroprotective effects. Conclusion Rg1 promoted neurite growth of RGCs through cAMP/PKA/CREB pathways. This study may lay a foundation for its clinical use of optic nerve diseases in the future.
研究领域:
神经科学
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药理学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
SCHIZOPHRENIA BULLETIN
·
2025
·
IF 4.8
Fan Rui,Pu Jianlin,Zhang Jin,Yu Minglan,Wang Tingting,Geng Xiaoqi,Dong Wei,Ma Rong,Wang Binglong,Wu Jianfei,Liu Kezhi,Hashimoto Kenji,Xiang Bo
BackgroundSocial withdrawal is a core symptom of schizophrenia (SCZ), yet its underlying molecular mechanisms remain unclear. Gα13 (GNA13), a G protein alpha subunit, has been implicated in SCZ susceptibility. This study investigated the role of Gα13 in social behavior by overexpressing it in the medial prefrontal cortex (mPFC) pyramidal neurons of mice.Study DesignIn this study, we first constructed CRE recombinase overexpressing Gα13 gene mice using CRISPR/Cas9 technology, tested the social behaviors by three-box socialization test, detected the changes of neuronal activities during social activities in mice by calcium signal fiber-optic recordings, observed the changes of dendritic spines by Golgi staining, applied RNA sequencing (RNA-Seq) to find the relevant targets, and observed whether it could reverse the abnormalities by pharmacological experiments social behavior. The electrophysiological characteristics of Gα13 overexpression were investigated using the whole-cell membrane clamp technique, followed by assessment of the severity of SCZ patients and social withdrawal using the PANSS scale and measurement of human plasma Gα13 protein levels using the ELISA technique, and the clinical correlation between the two was assessed.Study ResultsGα13 overexpression (Gα13-OE) mice exhibited significant social deficits in the three-chamber test, showing reduced sociability but normal social novelty recognition. Fiber photometry recordings revealed decreased neuronal activity during social interactions, and Golgi staining showed reduced dendritic spine density in mPFC pyramidal neurons. RNA-Seq identified downregulation of Adcyap1, affecting the cAMP/PKA signaling pathway and NMDA receptor (NMDAR) function. Pharmacological activation of Adcyap1 with PACAP-38 or NMDAR with D-cycloserine rescued the social deficits and restored synaptic function. Conversely, knockdown of Gα13 in an MK-801-induced SCZ mouse model ameliorated social behavior abnormalities. Clinically, patients with SCZ exhibited elevated plasma levels of Gα13, which positively correlated with the severity of social withdrawal symptoms measured by the PANSS G16 item.ConclusionsThese findings suggest that overexpression of Gα13 in the mPFC impairs social behavior by disrupting neuronal function and synaptic plasticity via the Adcyap1/cAMP/PKA/NMDAR pathway. Targeting Gα13 may offer a novel therapeutic strategy for addressing social deficits in SCZ.
研究领域:
神经生物学
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精神病学
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分子神经科学
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信号转导
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行为神经科学
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转化医学
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突触生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Gao Rongyin,Zhang Ximei,Zou Kun,Meng Duo,Lv Jinpeng
Cutaneous pigmentation was recently shown to be an event regulated by clock proteins. Cryptochrome (CRY) is a key protein composing the feedback loop of circadian clock, however, the function of CRY in melanocytes remains unclear. Here, we found that KL001, a synthetic small molecule modulator of CRY1, inhibited melanin synthesis, as well as reduced melanocyte dendrite elongation and melanosome transport. In addition, the dominant role of CRY1 in KL001-induced anti-melanogenesis was revealed by small interfering RNA transfection. Cellular tyrosinase activity and expression level of melanogenic proteins, including tyrosinase, TRP-1, TRP-2, and transport proteins like Rab27a, Cdc42 and Myosin Va induced by α-MSH were remarkably reversed after KL001 treatment. Mechanistically, CRY1 activation inhibited melanogenesis through CREB-dependent downregulation of MITF and CREB phosphorylation was mediated by classical cAMP/PKA pathway. In addition, the other CRY1 activator, KL044 also suppressed cAMP/PKA/CREB pathway and inhibited melanogenesis. Finally, anti-melanogenic efficacy of KL001 was confirmed by determination of melanin contents in UVB-tanning model of brown guinea pigs, which indicated that targeting CRY1 activity, via topical application of small molecule activator, can be utilized therapeutically to manage human pigmentary disorders.
研究领域:
细胞生物学
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分子生物学
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药理学
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皮肤科
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产品关联
DOI
PubMed
高影响因子
CURRENT NEUROVASCULAR RESEARCH
·
2025
·Vol. 22
·期 1
·70-85
·
IF 1.7
Ziteng Yang,Yuanqi Zuo,Guangyun Wang,Ning Wang
Introduction: The endothelial barrier is composed of brain microvascular endothelial cells (BMECs) and tight junction (TJ) proteins. Musk is a valuable ingredient in Traditional Chinese Medicine (TCM). It is used in the treatment of stroke because of its ability to induce resuscitation. The core component of musk is muscone. Previous studies have evidenced that muscone may be involved in the treatment of ischemic stroke (IS), but the underlying mechanism is still unclear. The main objective of this study was to explore the protective effect of muscone on OGD/R-induced endothelial barrier disruption and determine its underlying mechanism. Methods: OGD/R-induced damage to BMECs was assessed using the MTT and LDH assays. The apoptosis level in BMECs was determined using western blot and Hoechst staining. Western blot, immunofluorescence, and phalloidin staining were used to assess the expressions of TJ proteins and pathway proteins expression. A monolayer cell barrier was constructed using BMECs in vitro, and the permeability of the barrier was assessed by TEER as well as the transmissivity of sodium fluorescein. Molecular docking, DARTS, and CETSA were used to verify the regulatory effect of muscone on the pathway. Results: Muscone reduced OGD/R-induced apoptosis of BMEC cells, inhibited the degradation of TJ proteins, promoted the coherent expression of ZO-1 on the membrane, and restored TEER. Mechanistic studies showed that H-89 reversed the promoting effects of muscone on pathway proteins and promoted the disassembly of the actin cytoskeleton, which, in turn, promotes BMEC apoptosis and TJ protein degradation, ultimately disrupting the endothelial barrier. Discussion: The inhibition of BMEC apoptosis and improvement of endothelial barrier damage by muscone may be an important mechanism for treating ischemic stroke. Conclusion: We demonstrated that muscone could reduce OGD/R-induced hyperpermeability of the brain endothelial barrier by activating the PKA/RHOA/MLC pathway.
研究领域:
神经科学
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药理学
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中医中药
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）