JOURNAL OF PHYSICAL CHEMISTRY B
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2025
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IF 2.9
Wenqi Zhao,Meihuan Yao,Huidan Liu,Tingru Du,Zhijun Guo,Binbin Zhang,Yujie Wang,Guangyue Bai
Tailoring of the arylboronic acid structures is essential for developing specific monosaccharide (MS) recognition receptors, in which the designed boronic acid derivative should have an appropriate pKa, a stereostructure matched with the target MS, and an easily detectable method. Herein, we report a novel bis(m-benzylammonium) boronic acid with an ethyl spacer (BTEAB) as the receptor molecule to MS. Owing to its unique lyotropic acidity and intrinsic fluorescence characteristics in aqueous solution, BTEAB provides a new strategy for the design of MS sensors. The cation−π interaction promotes the self-assembly behavior of BTEAB and the lyotropic acidity and fluorescence quenching induced by aggregation. The aggregation behavior of BTEAB was confirmed by Rayleigh light scattering, fluorescence, and 1H NMR, and its lyotropic acidity is quantified by the decrease in its acid dissociation constant pKa. It was found that the esterification of BTEAB with three model MSs (fructose, glucose, and galactose) does not destroy the aggregates, indicating that the lyotropic acidity is an applicable characteristic for regulating the pH value of MS recognition. The affinity of BTEAB with MS and the structures of BTEAB-MS ester were studied mainly by isothermal titration calorimetry (ITC), fluorescence and NMR. The interaction mechanism of BTEAB with different MS was proposed. This work provides new insights into MS recognition under about physiological pH adjusted by diarylboronic acid aggregation.
研究领域:
分析化学
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生物传感器
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分子识别
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超分子化学
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药物化学
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化学生物学
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PubMed
高影响因子
Scientific Reports
·
2025
·Vol. 15
·期 1
·1-19
·
IF 3.9
Liu Yunxiao,Wang Shuanghu,Younas Ayesha,Lv Jiaojian,Al Mamun Abdullah,Shao Chuxiao
Nonalcoholic Fatty Liver Disease (NAFLD) is characterized by excessive lipid accumulation in hepatocytes and is closely associated with metabolic disturbances such as obesity, dyslipidemia, and insulin resistance. Despite its increasing prevalence and potential progression to severe liver conditions, there is currently no approved pharmaceutical intervention for NAFLD. Traditional Chinese Medicine (TCM) formulations, such as Xiaoyao San (XYS), have shown therapeutic efficacy in treating NAFLD, but the underlying mechanisms remain unclear. This study employed a multi-omics approach to elucidate the therapeutic mechanisms of XYS in NAFLD. A rat model of NAFLD was established using a high-fat diet (HFD). The chemical constituents of XYS were analyzed using UPLC-MS/MS. Transcriptomics and proteomics analyses were performed to identify potential biological targets and signaling pathways involved in the therapeutic effects of XYS. The results were validated using ELISA and Western blotting. UPLC-MS/MS identified 225 prototype chemical components of XYS in the blood. XYS significantly reduced body weight, liver index, and Lee’s index in NAFLD model rats. It ameliorated HFD-induced hepatic steatosis, down-regulated serum levels of ALT, AST, GGT, TG, TC, LDL-C, FBG, IL-1β, IL-6, TNF-α, and ROS, and up-regulated HDL-C levels. Transcriptomics and proteomics analyses revealed that XYS modulated key signaling pathways, including cAMP, TGF-β, NF-κB, and necroptosis. Specifically, XYS down-regulated the expressions of NF-κB, p-NF-κB, FOXO1, TGF-β1, RIP3, and p-MLKL, while up-regulating cAMP, PKA, p-PKA, and PPARα. XYS improves NAFLD by regulating the cAMP/PKA-mediated PPARα, FOXO1, and NF-κB signaling pathways. This study provides a comprehensive understanding of the molecular mechanisms underlying the therapeutic effects of XYS in NAFLD and supports its potential as a novel therapeutic intervention for this condition.
研究领域:
药理学
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代谢疾病
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系统生物学
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PubMed
高影响因子
PHYTOMEDICINE
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2026
·
IF 11.3
Wen-Biao Zu,Zhao-Jie Wang,Dong-Mei Tang,Qin-Yu Lu,Yan-Yan Zhu,Zhong-Shun Zhou,Mei-Zhen Wei,Xiao-Dong Luo
Background Fungal diseases affect over one billion individuals worldwide and represent a significant public health concern. Oral candidiasis (OC) is a common fungal infection primarily caused by Candida albicans. Eriocapitella rivularis is a traditional medicinal herb for the treatment of oral fungal infections. Purpose This study aimed to identify potent antifungal compounds from E. rivularis and elucidate their underlying mechanisms of action. Methods Bio-guided isolation combined with network pharmacology was used to identify anti- C. albicans compounds from E. rivularis , followed by metabolomics analysis to explore potential regulatory pathways. Antifungal activity and synergistic efficacy were evaluated using broth microdilution, checkerboard, and time-kill assays. Biofilm inhibition was assessed through quantitative and biochemical analyses. Reverse transcription quantitative polymerase chain reaction was performed to elucidate molecular mechanisms. An in vivo murine OC model was employed to verify efficacy. Results Prosapogenin CP4 disrupted the fungal cell wall, targeted ergosterol to induce plasma membrane permeabilization, inactivated mitochondrial function, and inhibited hyphal growth, potentially through interference with ABC transporters, modulation of cAMP export, and induction of metabolic disorders. Prosapogenin CP4 and ursolic acid exhibited a synergistic inhibitory effect against fluconazole-resistant C. albicans (FICI = 0.375) with low resistance. This combination regulated genes in the Ras/cAMP/PKA signalling pathway, significantly inhibited biofilm formation and reduced fungal burden, inflammatory responses, and fungal colonisation in murine oral tissues, with efficacy comparable or superior to that of nystatin. Conclusion The finding presents a synergistic phytomedicine strategy using two triterpenoids from E. rivularis as a promising therapeutic approach for OC, particularly biofilm-associated infections.
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高影响因子
ACS Applied Materials & Interfaces
·
2021
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IF 9.229
Fang Yuan,Yujing Kong,Jia You,Cuiling Zhang,Yuezhong Xian
Precise modulation of pH in living cells plays a vital role in the study of many diseases, such as cancer and rheumatoid arthritis. Here, a series of imine-linked covalent organic frameworks (COFs) were rationally designed and developed for pH sensing in tumor cells and zebrafish. Four monomers were chosen to synthesize COFs (COF1–COF4) with different pKa by a simple orthogonal combination through condensation reaction. The as-obtained COFs exhibited a sensitive pH-dependent fluorescence response compared to their building blocks. Among them, COF2 possessed a high crystallinity, excellent fluorescence, and suitable pKa for biosensing. For bioimaging applications, COF2 was modified with poly-d-lysine (PDL) to improve its biocompatibility and endocytosis efficiency. After that, PDL-modified COF2 (PDL@COF2) was used as a novel fluorescence probe with a superior linear pH response over the range from 5.0 to 8.0 due to its fully reversible protonation and deprotonation. The fluorescent PDL@COF2 was further employed as a good candidate for pH imaging in tumor cells and zebrafish. The as-constructed environment-sensitive fluorescent COFs have greatly expanded the applications of COFs in the biological area.
研究领域:
生物医学工程
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材料科学
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生物传感器
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荧光成像
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高影响因子
ONCOGENE
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2018
·Vol. 37
·期 22
·2953-2966
·
IF 6.854
Cheng Yan,Gao Xing-Hua,Li Xian-Jing,Cao Qiu-Hua,Zhao Dan-Dan,Zhou Jin-Rong,Wu Hong-Xi,Wang Yun,You Lin-Jun,Yang Hong-Bao,He Yun-Long,Li Yong-Ren,Bian Jin-Song,Zhu Qing-Yi,Birnbaumer Lutz,Yang Yong
Depression drives cancer progression and induces poor clinical outcome. However, the mechanisms underlying depression and cancer outcomes are unclear. In this work, we investigated 98 prostate cancer patients and found that patients with high score of psychological depression were correlated with tumor invasion and metastasis. We found focal adhesion kinase (FAK) was increased in cancer patients with metastatic features and high score of depression. FAK knockdown completely blocked depression-promoted tumor invasion in orthotopic transplantation tumors. In Hi-myc mice and a murine model of depression, sympathetic activation was detected in the prostate tissue. Further we showed that FAK activation was dependent on a cAMP-PKA signaling pathway. Our results demonstrated that the activation of a sympathetic-FAK signaling pathway in prostate cancer patients with high degrees of depression facilitates tumor invasion. We suggest that blocking β2AR with propranolol or inhibiting FAK activation with PF562 271 may be novel strategies for depressed patients with invasive prostate cancer.
研究领域:
肿瘤学
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精神病学
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分子生物学
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PubMed
高影响因子
AICHE JOURNAL
·
2024
·Vol. 70
·期 4
·e18366
·
IF 3.5
Meng-Meng Du,Bao-Chang Sun,Bei-Bei Wang,Yong Luo,Liang-Liang Zhang,Guang-Wen Chu,Hai-Kui Zou,Jian-Feng Chen
In this work, the kinetics study on the reaction between CO 2 and tertiary amine catalyzed by zinc(II)-1,4,8,11-tetraazacyclotetradecane complexes (CM) and zinc(II)-1,4,7,10-tetraazacyclododecane complexes (CN) was carried out in a stopped-flow device. The effects of the catalyst concentration, type of tertiary amines, and temperature on the reaction rate ( ν ) and catalytic activity ( φ ) were studied. It was found that the catalyst concentration, tertiary amine with higher p K a , and temperature had positive effects on ν . ν in N -methyl diethanolamine solution with 10.0 mol m −3 CM and CN were 16.62 and 26.05 folds than the uncatalyzed ν at 298 K, respectively. φ increased with increasing catalyst concentration, decreasing temperature and tertiary amine's p K a . In addition, the kinetics behavior of tertiary amine-CM/CN-CO 2 systems conformed to the Michaelis–Menten model. The activation energies in catalytic systems were 4%–15% lower than that in the non-catalytic systems.
研究领域:
化学动力学
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催化
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无机化学
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环境化学
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高影响因子
LUMINESCENCE
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2022
·Vol. 37
·期 6
·922-929
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IF 2.613
Tingting Feng,Shuzhu Yan,Zheng Wang,Xiaohui Fan
In this study, we present a facile and low-cost approach for detecting protein kinase A (PKA) by assembling a purpose-designed carboxyfluorescein (FAM)-labelled peptide with carboxylic carbon nanoparticles (CNPs). Fluorescence of the FAM-labelled peptide gradually decreases to a low background signal as a result of the electron transfer from CNPs to FAM-labelled peptide via the peptide, which acts as a bridge. The reaction in the sensor in the presence of adenosine 5′-triphosphate and PKA phosphorylates the substrate peptide and disrupts the electrostatic repulsive force between the CNPs and the peptide, therefore altering the spectroscopic signal of the system. The change in fluorescence signal was directly proportional to the PKA concentration in the range 0–1.8 U/ml with a detection limit of 0.04 U/ml. These results suggest that PKA activity can be effectively measured using the developed PKA biosensor. Moreover, the fluorescence biosensor was successfully used in the investigation of PKA in spiked human embryonic kidney (HEK) 293 cells lysates, indicating its potential applications in protein kinase-related biochemical fundamental research.
研究领域:
生物化学
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分子生物学
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分析化学
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PubMed
高影响因子
THERIOGENOLOGY
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2026
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IF 2.9
Jiahao Zhao,Xiangyu Zhou,Baoyi You,Bowen Cheng,Jiashuo Hu,Yuxuan Lu,Dianrui Xu,Xiwei Zhang,Chunlong Yan,Qingshan Gao,Haixing Liu,Qingguo Jin
Florfenicol (FLO) is widely used to treat bacterial respiratory diseases and hoof rot in cattle at various physiological stages. However, residues of FLO that accumulate in cattle may have adverse effects on animal health. Although FLO has been reported to exhibit embryotoxic and cytotoxic properties, the mechanism underlying its effects on bovine granulosa cells (GCs) remains poorly understood. In this study, we treated GCs with FLO at concentrations of 0, 10, and 100 μg/mL for 48 h to evaluate the effects of FLO on cell viability, mitochondrial function, and steroid hormone synthesis. The results showed that FLO treatment was associated with increased apoptosis, reduced GC proliferation, and impaired mitochondrial function. In addition, FLO treatment was accompanied by decreased ATP levels and increased intracellular reactive oxygen species (ROS). Furthermore, FLO exposure was associated with changes in PROG and E2 production, decreased protein expression of StAR and CYP11A1, and reduced levels of adenylate cyclase (AC), cyclic adenosine monophosphate (cAMP), and protein kinase A (PKA). The antioxidant N-acetyl-L-cysteine (NAC) partially attenuated these changes. In conclusion, our findings suggest that FLO exposure is associated with GC dysfunction and impaired steroidogenesis. These effects may be related to oxidative stress, mitochondrial dysfunction, and alterations in the cAMP/PKA/StAR signaling pathway, although direct causal relationships remain to be further elucidated.
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JOURNAL OF NANOBIOTECHNOLOGY
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2026
·
IF 15
Ma Tianyu,Li Qiang,Chen Xingwu,Dong Jixiang,Jiang Yuqing,Li Shanshan
Bioactive peptides are promising candidates for hair regeneration, but their topical application is often limited by poor skin delivery and the need for frequent dosing. To overcome these challenges, we designed a palmitoylated peptide, Pal-MPAPO, and incorporated it into a hyaluronic acid-based hydrogel microneedle (MN) system for localized transdermal delivery. The fabricated MNs showed adequate mechanical strength for skin insertion and provided a time-dependent, prolonged release of Pal-MPAPO. In human dermal papilla cells (DPCs), Pal-MPAPO activated the Wnt/β-catenin pathway and increased intracellular cyclic adenosine monophosphate (cAMP) levels in a predominantly VPAC1-dependent manner. Additional VPAC2 validation did not reveal a significant contribution to cAMP signaling under the tested conditions. Functional interactions between Pal-MPAPO and VPAC1 were supported by molecular docking, molecular dynamics simulations, receptor knockdown, and fluorescence imaging. In a C57BL/6 mouse model, Pal-MPAPO-loaded MNs significantly promoted hair regrowth, achieving efficacy comparable to minoxidil but at a reduced application frequency. These findings identify Pal-MPAPO as a potential peptide candidate for hair regeneration and suggest that hydrogel MN-assisted delivery provides a localized peptide administration strategy. Graphical The alternative text for this image may have been generated using AI.
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高影响因子
BIORESOURCE TECHNOLOGY
·
2026
·
IF 9
Jing Cao,Linxiong Luo,Haiyan Yang,Zhengjun Shi,Chun Shi,Taohong Li,Jing Yang
A deep eutectic solvent (DES) composed of triethylbenzylammonium chloride and oxalic acid (TEBAC/OA) was employed to pretreat D. giganteus (DG). To enhance the pretreatment efficiency, acids with varying pKa values—including p-toluenesulfonic acid (PTSA), salicylic acid (SA), formic acid (FA), glycolic acid (GA), acetic acid (AA), and propionic acid (PA)—were incorporated into the binary TEBAC-based DES. It was found that the pKa of the third acid component exhibited a negative correlation with the removal of lignin and xylan, as well as with the subsequent enzymatic saccharification yield. Notably, the SA-assisted DES pretreatment resulted in 98.74% xylan removal and 92.24% delignification. Moreover, the enzymatic hydrolysis efficiency improved from 53.21% for the binary DES-pretreated DG to 70.69% for the TEBAC/OA-SA-pretreated DG. Computational modeling revealed a reduction in both the number of hydrogen bonds and the interaction forces among cellulose-hemicellulose-lignin within the TEBAC/OA-SA system, which facilitated effective fractionation of bamboo. The TEBAC/OA-SA pretreated DG exhibited marked morphological and structural alterations, characterized by the lowest crystallinity-to-cellulose ratio and hydrophobicity, along with the highest cellulose accessibility. Furthermore, DES lignin (DL) and surface lignin (SL) displayed lower molecular weights and reduced hydrophobicity compared to residual lignin (RL), and their inhibitory effect on enzymatic saccharification was considerably weaker. By adjusting the pKa of the DES system, this study successfully achieved efficient fractionation of bamboo and enhanced enzymatic saccharification, thereby offering valuable insights for the design of tailored DES-based pretreatment strategies.
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PHYTOTHERAPY RESEARCH
·
2025
·
IF 6.3
Xian Zheng,Yuanyue Jiang,Wenbo Wang,Kekang Sun,Libin Zhou,Yanru Zhang,Jie Cui,Haiyan Yu,Wenbin Dong,Baofei Yan
Ulcerative colitis (UC) is a chronic inflammatory disease of the colon, characterized by recurrent flare-ups and limited effectiveness of available drug therapies. Asiatic acid (AA), a triterpenoid compound extracted from Centella asiatica , has shown promising pharmacological activities and therapeutic potential in several inflammation-related diseases. However, AA's efficacy in treating UC and its precise mechanisms of action remain to be fully explored. This study aimed to provide a comprehensive assessment of AA's therapeutic effects on UC and to investigate its underlying mechanisms, with a focus on gut microbiota interactions. In our study, a dextran sulfate sodium-induced UC mouse model was used to evaluate AA's therapeutic potential and explore its impact on gut microbiota composition and function. We further used an antibiotic cocktail and fecal microbiota transplantation assays to substantiate the role of gut microbiota in AA's mechanisms of action. A metabolomic analysis was also conducted to identify key metabolic pathways and gut microbiota-derived metabolites involved in AA's effects. Our findings demonstrated that AA significantly alleviates symptoms of UC, including reducing weight loss, slowing disease progression, mitigating colonic inflammation, and restoring immune balance. Mechanistically, the beneficial effects of AA were strongly linked to alterations in the gut microbiota and its metabolites, particularly γ-glutamyltyrosine. This metabolite was found to regulate the cyclic adenosine monophosphate/protein kinase A/nuclear factor kappa-B signaling pathway, which plays a crucial role in inflammatory responses. Overall, these findings strongly suggest that AA holds promise as a therapeutic agent for UC by modulating the gut microbiota and influencing critical inflammatory pathways.
研究领域:
药理学
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胃肠病学
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微生物组研究
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炎症性疾病
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代谢组学
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DOI
PubMed
高影响因子
MOLECULAR PLANT PATHOLOGY
·
2024
·Vol. 25
·期 9
·e70003
·
IF 4.8
Kai Yin,Zhijian Hu,Meiting Yuan,Weidong Chen,Xinping Bi,Guobing Cui,Zhibin Liang,Yi Zhen Deng
Sugarcane smut fungus Sporisorium scitamineum produces polyamines putrescine (PUT), spermidine (SPD), and spermine (SPM) to regulate sexual mating/filamentous growth critical for pathogenicity. Besides de novo biosynthesis, intracellular levels of polyamines could also be modulated by oxidation. In this study, we identified two annotated polyamine oxidation enzymes (SsPAO and SsCuAO1) in S. scitamineum . Compared to the wild type ( MAT-1 ), the ss1pao Δ and ss1cuao1 Δ mutants were defective in sporidia growth, sexual mating/filamentation, and pathogenicity. The addition of a low concentration of cAMP (0.1 mM) could partially or fully restore filamentation of ss1pao Δ × ss2pao Δ or ss1cuao1 Δ × ss2cuao1 Δ. cAMP biosynthesis and hydrolysis genes were differentially expressed in the ss1pao Δ × ss2pao Δ or ss1cuao1 Δ × ss2cuao1 Δ cultures, further supporting that SsPAO- or SsCuAO1-based polyamine homeostasis regulates S. scitamineum filamentation by affecting the cAMP/PKA signalling pathway. During early infection, PUT promotes, while SPD inhibits, the accumulation of reactive oxygen species (ROS) in sugarcane, therefore modulating redox homeostasis at the smut fungus–sugarcane interface. Autophagy induction was found to be enhanced in the ss1pao Δ mutant and reduced in the ss1cuao1 Δ mutant. Exogenous addition of cAMP, PUT, SPD, or SPM at low concentration promoted autophagy activity under a non-inductive condition (rich medium), suggesting a cross-talk between polyamines and cAMP signalling in regulating autophagy in S. scitamineum . Overall, our work proves that SsPAO- and SsCuAO1-mediated intracellular polyamines affect intracellular redox balance and thus play a role in growth, sexual mating/filamentation, and pathogenicity of S. scitamineum .
研究领域:
真菌学
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植物病理学
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分子生物学
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PubMed
高影响因子
危险品化学品经营许可证（带存储）