Oxidative Medicine and Cellular Longevity
·
2022
·
IF 7.31
Bingjie Xue,Bo Ma,Yaoyao Yao,Aimei Zhao,Ying Gao,Jianxun Liu
Cerebral microinfarcts (CMIs) are characterized by sporadic obstruction of small vessels leading to neurons death. They are associated with increased risk of cognitive impairments and may have different risk factors compared with macroinfarcts. CMIs have a high incidence and result in heavy social burden; thus, it is essential to provide reasonable treatment in clinical practice. However, there are relatively few researches on the mechanism and treatment of CMIs, and the literature is composed almost exclusively of community—or hospital based on autopsy or imageological studies focusing on elderly patients. The Bu Yang Huan Wu (BYHW) decoction, a traditional Chinese herbal formula, has long been used to treat stroke and stroke-related diseases, including cognitive impairments. We applied microsphere-induced CMI model in rats to investigate the behavioral and molecular consequences of CMIs and to determine how they were ameliorated by BYHW decoction treatment. We then used the Morris water maze, quantitative proteomics, immunohistochemistry, and other molecular assays and found that activation of the PKA/CREB pathway by BYHW decoction treatment may reverse mitochondrial dysfunction, inhibit apoptosis of hippocampal neurons, and ameliorate CMI-induced cognitive impairments in rats. Collectively, these findings confirmed the therapeutic potential of the BYHW decoction in treating cognitive impairments induced by CMIs and demonstrated a viable mechanism for its action.
研究领域:
神经科学
·
药理学
·
中医药学
·
分子生物学
·
行为科学
✓ 已验证
DOI
PubMed
高影响因子
SENSORS
·
2026
·Vol. 26
·期 10
·3175
·
IF 4
Baohong Sun,Ying Liu,Xinxin Tian,Yu Fang,Jinpei Mei,Yang Chen,Tao Ma
HighlightsWhat are the main findings?A single-material three-channel colorimetric array sensor based on Fe4P2W18polyoxometalate nanozyme achieves 100% discrimination accuracy for glutathione, cysteine, and homocysteine within 5 min.By exploiting pH-dependent stepped catalytic responses (pH 3.5, 4.0, 4.5), the sensor amplifies pKa-driven differences in biothiol molecular charge and structure, enabling a detection limit as low as 0.1 μM and quantification over 1–50 μM.What are the implications of the main findings?This strategy eliminates the need for multi-material sensor arrays while providing mechanistic clarity, offering a simple, rapid, and reliable tool for biothiol analysis in complex biological samples.The sensor successfully distinguishes different cell types (HUVEC, HeLa, A549) and discriminates serum samples from cardiovascular disease patients, demonstrating strong potential for early disease diagnosis.Glutathione (GSH), cysteine (Cys), and homocysteine (Hcy) are essential biothiols involved in redox homeostasis and cell signaling. Yet, their structural similarity poses a significant challenge for accurate discrimination in complex biological samples. Herein, we report a polyoxometalate nanozyme (Fe4P2W18) with an atomically precise structure synthesized via a mild one-step method. Benefiting from its negatively charged surface and multi-electron reduction centers, the nanozyme effectively enriches biothiols under acidic conditions and exhibits excellent peroxidase-like activity. By leveraging its stepped catalytic response across pH 3.5, 4.0, and 4.5, which amplifies the pKa-driven differences in the overall molecular charge and electrostatic properties of biothiols, we constructed a single-material three-channel colorimetric array sensor that generates cross-reactive fingerprints. This sensor achieves 100% discrimination accuracy for GSH, Cys, and Hcy within 5 min, with a detection limit of 0.1 μM. It enables quantitative detection of thiol concentrations between 1 and 50 μM and accurately identifies binary and ternary thiol mixtures. Furthermore, the sensor successfully distinguishes cell types (HUVEC, HeLa, A549) and discriminates serum samples from cardiovascular disease patients. This strategy eliminates the complexity of multi-material arrays while leveraging the well-defined structure of Fe4P2W18to provide mechanistic clarity, offering a simple, rapid, and reliable tool for biothiol analysis and early disease diagnosis.
✓ 已验证
DOI
PubMed
高影响因子
NUTRITIONAL NEUROSCIENCE
·
2026
·
IF 3.1
Dawei Xu,Luge Chen,Xiaohu Chen,Weiming Jiang,Lijuan Sun
Background and Objectives Insomnia is a major public health issue that impairs daily functions and quality of life. Sleep-onset difficulty, a common complaint among patients, is accompanied by reduced central serotonin (5-HT) function. β-myrcene from lavender has sedative–hypnotic effects via serotonergic pathways, but most previous studies used intraperitoneal injection, which causes stress and limits clinical translation. Here, we asked whether non-invasive inhalation of β-myrcene produced similar effects in a mouse model of insomnia with low 5-HT function, and explored the underlying mechanisms.Methods β-myrcene was given to PCPA-induced insomnia mice by inhalation (with intraperitoneal injection as a pharmacodynamic control). In the inhalation group, sleep and behavior were evaluated using the amobarbital sodium sleep test and spontaneous locomotor activity test. ELISA, RT-qPCR, Western blot, and 16S rRNA sequencing were applied to study mechanisms.Results Inhaled β-myrcene shortened sleep latency and prolonged sleep duration. It also reduced oxidative stress and modulated GABA, 5-HT, and glutamate levels. These changes were accompanied by upregulation of mRNAs such as GABAARγ2 and 5-HT1A, as well as proteins including GAD65/67 and PKA, suggesting involvement of 5-HT1A/PKA signaling. Additionally, inhalation of β-myrcene was correlated with alterations in gut microbiota composition in PCPA-induced insomnia mice.Conclusions Our findings indicate that inhaled β-myrcene is associated with sedative–hypnotic effects and alterations in gut microbiota composition in PCPA-induced insomnia mice, potentially involving modulation of 5-HT1A/PKA signaling.
✓ 已验证
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2022
·
IF 5.195
Yinsi Lin,Jianhui Su,Mingqiang Wang,Yanzhen Li,Zhongxiang Zhao,Zhanghua Sun
Ethnopharmacological relevance Hypericum sampsonii Hance (Yuanbaocao), a traditional herbal medicine with various pharmacological properties, is traditionally used to treat diarrhea and enteritis in China for hundreds of years. Investigations have uncovered its anti-inflammatory effects and corresponding bioactive constituents in H. sampsonii , however, the mechanisms of action for the treatment of enteritis are still unclear. Aims of the study This study aims to investigate the therapeutic effects and molecular mechanisms of H. sampsonii in a dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice model. Materials and methods The major ingredients of the ethyl acetate extract (HS) in H. sampsonii were analyzed by UPLC-QTOF-MS. The inflammatory state of UC mice was caused by 3% DSS once daily for seven days. During DSS treatment, the mice in the positive drug group and the other three groups were orally administered 5-ASA (positive control) or HS daily. After treatment with HS or 5-ASA for a week, colonic pathological observation and the molecular biological index were performed for therapeutic evaluation, including visual inspection in the length and weight of colons and spleens, pathological morphology by hematoxylin and eosin (HE) staining, determination of oxidative markers, inflammatory cytokines and tumor necrosis factor-alpha (TNF-α) levels in colonic tissues as well as spleen index. Gene expression levels of inflammatory cytokines, antioxidant enzymes and PDE4 were detected using kits and PCR, while the expression of colonic tight junction proteins and relative signals of PKA/CREB signaling pathway were analyzed by Western blot . Results The main components in HS were found to be polycyclic polyprenylated acylphloroglucinols (PPAPs). HS distinctly alleviated DSS-stimulated UC-like lesions symptoms as evidenced by a significant recovery from body weight, colon lengths, and histological injuries of colons. HS reduced the accumulation of pro-inflammatory cytokines and improved the mRNA level of IL-10. Simultaneously, the colonic mRNA expression levels of IL-1β, IL-17, iNOS and COX-2 were all significantly suppressed by HS in a dose-dependent manner. Furthermore, HS restored the protein expression of tight junction-associated protein (ZO-1 and occluding). Besides, HS significantly inhibited the protein level of PDE4 and decreased the expressions of PKA and phosphorylated CREB. Conclusion This is the first work about main composition and anti-UC effect of Hypericum sampsonii Hance. For the first time, this study reveals HS is not toxic in a single dose and exert significantly protective effect in DSS-colitis mice. The underlying mechanisms may involve the improvement to inflammatory status, the protection for intestinal barrier function, the inhibition of PDE4, and the activation of PKA/CREB signaling pathway. This study provided an experimental basis for the traditional application of H. sampsonii Hance in the treatment of diarrhea and dysentery .
研究领域:
药理学
·
免疫学
·
分子生物学
·
胃肠病学
·
传统中药
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2022
·Vol. 23
·期 18
·10208
·
IF 6.208
Chen Gong,Daiying Xu,Daiyuan Sun,Xue Zhang
For optimal proteolytic function, the proteasome core (CP or 20S) must associate with activators. The cAMP-PKA pathway is reported to affect the activity of the proteasome in humans. However, the relationship between the proteasome and PKA is not well characterized. Our results showed that the major catalytic subunit Cpk1 was degraded without the protection of Pkr. Eleven (out of 67)pkrsuppressors had FgBlm10 C-terminal truncation, one suppressor had an amino acid change mutation in thePRE6 ortholog (FGRRES_07282), and one in thePRE5 ortholog (FGRRES_05222). These mutations rescued the defects in growth and conidial morphology, Cpk1 stability, and PKA activities in thepkrmutant. The interaction of FgBlm10 with FgPre5 and FgPre6 were detected by co-immunoprecipitation, and the essential elements for their interaction were characterized, including the FgBlm10 C-terminus, amino acid D82 of FgPre6 and K62 of FgPre5. Additional FgBlm10-interacting proteins were identified in the wild type andpkrmutant, suggesting that PKA regulates the preference of FgBlm10-mediated proteasome assembly. In addition, PKA indirectly affected the phosphorylation of FgBlm10, and its localization in the nucleus. The truncation of the FgBlm10 C terminus also enhanced nuclear import and bleomycin resistance, suggesting its role in proteasome assembly at DNA damage sites. Collectively, our data demonstrated that regulation between PKA and proteasome degradation is critical for the vegetative growth ofF. graminearum.Keywords:FgBlm10;26S proteasome;PKA;degradation;Fusarium graminearum
研究领域:
分子生物学
·
微生物学
·
植物病理学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Wen Zhang,An Bu,Qingyuan Ji,Luofu Min,Song Zhao,Yuxin Wang,Jing Chen
We report a class of pKa-directed, precise incorporation of phosphonate ligands into a zirconium-based metal–organic framework (Zr-MOF), MOF-808, via ligand exchange. By replacing of formate ligands with methylphosphonic acid (MPA), ethanephosphonic acid (EPA), and vinylphosphonic acid (VPA), whose pKa values are slightly higher than that of the benzenetricarboxylic acid (BTC) linker in MOF-808, daughter MOFs can be synthesized without controlling the stoichiometric amounts of added MPA. The methylphosphonate MOFs (808-MPAs) demonstrate high porosities, with only small changes in the pore diameter and specific surface area when compared with the parent MOF-808. PXRD patterns and structure refinements indicate the expansion of the lattice for all MOFs after decorating with methylphosphonate ligands. The XPS spectra reveal a charge redistribution of the Zr6 node after ligand exchange. FTIR and 31P MAS NMR spectra, combined with DFT calculation, suggest that the methylphosphonate ligand is connected to the Zr6 node as CH3P(O)(OZr)(OH) species with an accessible acidic P–OH group. Besides, 808-MPAs demonstrate excellent chemical stability in concentrated HCl, concentrated HNO3, hot water, and 0.2 mol/L trifluoroacetic acid solutions. Impressively, 808-MPAs show ultrafast adsorption performance for uranyl ions using the ion-exchange property of P–OH sites in their cavity environment, with an equilibrium time of 10 min, much quicker than the previous adsorbents. The present study demonstrates a series of important proof-of-concept examples of the pKa-directed Zr-MOFs with tunable phosphonate-terminated ligands, which can extend to other phosphonate-functionalized Zr-based framework platforms in the near future.
研究领域:
材料科学
·
环境科学
·
化学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENERGY & FUELS
·
2017
·
IF 3.091
Moxia Li,Helei Liu,Xiao Luo,Paitoon Tontiwachwuthikul,Zhiwu Liang
In this work, three promising tertiary amines—1-(2-hydroxyethyl)piperidine (1-(2-HE)PP), 3-(diethylamino)-1,2-propanediol (DEA-1,2-PD), and N-(2-hydroxyethyl)pyrolidine (1-(2-HE)PRLD)—were experimentally studied and the results presented in terms of pKa, the protonation calibration curves, and ion speciation plots. The pKa of these amines were determined in the temperature range of 294–320 K. The protonation calibration curves for the three amines were also developed based on 13C NMR detection. In addition, ion (amine, amineH+, HCO3–, and CO32–) speciation plots for the three tertiary amines were developed at the temperature of 298 K, at the amine concentration of 1.0 M, over the CO2 loading ranges of 0–0.897 mol CO2/mol amine for 1-(2-HE)PP, 0–0.915 mol CO2/mol amine for DEA-1,2-PD, and 0–0.927 mol CO2/mol amine for 1-(2-HE)PRLD by using the pH method, the 13C NMR method, and the pH + 13C NMR method. By comparing the ion (amine, amineH+, HCO3–, and CO32–) concentrations of the three tertiary amines obtained from these three methods, it can be concluded that each of these three methods could be used to develop the ion speciation plots of amine–CO2–H2O systems, but there are some significant differences between them.
研究领域:
化学工程
·
环境科学
✓ 已验证
DOI
高影响因子
Frontiers in Immunology
·
2025
·
IF 5.9
Jikai He,Jiaqi Jia,Wenhao Qu,Shuyu Zhang,Keyu Fan,Runze Lin,Wei Zhao,Yan Niu,Yanqiang Huang,Lizhou Jia
Objective To analyze differences in gut microbiota composition, metabolites, and metabolic pathways between healthy individuals and colorectal cancer (CRC) patients, and to investigate the inhibitory effects of N-methylserotonin (NMS) produced by Bacteroides ovatus (B.o) from orange fiber on CRC progression and its underlying mechanisms. Methods (1) Fecal samples from CRC patients (n=26) and healthy controls (n=20) were collected for metagenomic sequencing and untargeted metabolomics analysis; (2) The ability of B.o to produce NMS from orange fiber was validated in vitro ; (3) A CRC mouse model was established using azoxymethane (AOM)/dextran sulfate sodium (DSS) induction, followed by evaluation of body weight, rectal bleeding, colorectal length, tumor number, and intestinal barrier function; (4) Network pharmacology, molecular docking, and western blot analysis were combined to verify the mechanism of action; (5) 16S rRNA sequencing was performed to analyze gut microbiota changes. Results (1) CRC patients showed significantly increased metabolic pathways including glycolysis, methane metabolism, beneficial amino acid degradation, and linoleic acid degradation, along with significantly decreased B.o abundance and NMS levels, which were positively correlated; (2) NMS significantly inhibited CRC cell proliferation, migration, and invasion, while promoting apoptosis; (3) Combined treatment with B.o and orange fiber or NMS alone reduced tumorigenesis and improved intestinal barrier function; (4) Mechanistic studies revealed that these effects could be mediated through downregulation of 5-hydroxytryptamine receptor 1D (HTR1D) expression and inhibition of the cAMP/PKA/IκBα/NF-κB pathway; (5) The treatments optimized gut microbiota structure and metabolite composition. Conclusion B.o and its metabolite NMS possibly inhibit CRC progression by modulating the HTR1D-mediated cAMP/PKA/NF-κB signaling pathway, while improving gut microbiota structure, providing a novel therapeutic target for CRC prevention and treatment.
研究领域:
肿瘤学
·
微生物组研究
·
分子生物学
·
代谢组学
·
胃肠病学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Carbohydrate Polymer Technologies and Applications
·
2026
·
IF 7.6
Yongqi Cao,Ziyi Zhang,Wei Wang,Wenbo Yi,Annan Ji,Tongjun Liu,Liping Tan
Lignocellulosic biorefinery is severely limited by the inherent recalcitrance of lignin–carbohydrate complexes. Although polyol-based deep eutectic solvents (DESs) serve as green pretreatment media that suppress lignin recondensation by inhibiting benzyl carbocation generation, their practical enzymatic saccharification performance remains inferior to other DES categories. To overcome this critical drawback, the present work rationally constructed ternary polyol DESs mediated by acids with different pKa, and systematically evaluated their capacity to deconstruct peanut straw for enhanced sugar recovery. Under the ternary choline chloride–1,3-propanediol–oxalic acid DES treatment, a remarkable glucose yield of 92.53% was achieved after 72 h of enzymatic hydrolysis. Density functional theory (DFT) calculations further revealed the underlying molecular mechanisms: the multi-site hydrogen-bonding network formed by the ternary DES competitively breaks the inherent hydrogen bonds within lignin, effectively cleaving interunit lignin–carbohydrate linkages. Compared with binary DESs, the optimized ternary system achieves superior delignification and saccharification efficiencies simultaneously. This study not only provides an eco-efficient pretreatment route for agricultural waste, but also advances molecular-level understanding of DES–lignin intermolecular interactions. The gradient pKa acid co-modulation strategy proposed here can serve as a general framework for custom-designing task-specific DESs for diverse lignocellulose biorefinery applications.
✓ 已验证
DOI
高影响因子
BIOORGANIC CHEMISTRY
·
2026
·
IF 5.1
Sheng-Li Wu,Xiao-Feng He,Pianchou Gongpan,Xiao-Yan Huang,Chang-An Geng
DCA stimulated GLP-1 secretion in STC-1 and NCI-H716 cells. • DCA decreased fasting blood glucose levels by promoting GLP-1 secretion in db/db mice. • DCA ameliorated glucose intolerance and insulin resistance and lowered serum TC levels. • DCA promoted GLP-1 secretion through specific activation on TGR5/PKA/MEK/ERK pathway. Type 2 diabetes mellitus (T2DM) is a heterogeneous metabolic disorder characterized by insulin resistance and progressive β cell dysfunction. Deoxycalyxin A (DCA), a unique diarylheptanoid-chalcone hybrid isolated from Alpinia katsumadai , was identified as a novel stimulator of GLP 1 secretion in both STC-1 (EC 50 : 10.7 μM) and NCI-H716 (EC 50 : 13.4 μM) cells. Oral administration of DCA (40 and 80 mg/kg) in db/db mice significantly reduced fasting blood glucose, ameliorated glucose intolerance and insulin resistance by enhancing endogenous GLP-1 secretion, and lowered the total serum cholesterol levels. Mechanistic study demonstrated that DCA identify the TGR5 receptor, which induces a significant increase in intracellular cyclic AMP (cAMP) levels, which activates PKA with subsequent sequential phosphorylation of MEK1/2 and ERK activation, ultimately enhancing GLP-1 secretion. Our findings identify DCA as a novel TGR5 agonist to stimulate GLP-1 secretion via the TGR5/PKA/MEK/ERK pathway, which has the potential to be developed as a promising antidiabetic lead with a distinct mechanism of action. DCA, a unique diarylheptanoid-chalcone from Alpinia katsumadai , is a novel TGR5 agonist to stimulate GLP-1 secretion via PKA/MEK/ERK pathway, which has the potential to be developed as a promising antidiabetic candidate. Download: Download high-res image (123KB) Download: Download full-size image
✓ 已验证
DOI
高影响因子
JOURNAL OF POLYMER RESEARCH
·
2026
·Vol. 33
·期 6
·232
·
IF 3.5
Ran Zhipeng,Wu Yeping,Chen Mao,Zhang Yinyu,Xiao Peishuang,Chen Keping,Zhao Xiuli
Based on the study of thiol-epoxy click chemistry under bulk polymerization conditions, this study addresses the challenge of uncontrollably fast curing kinetics in traditional systems by establishing a pKa-based mechanism-reactivity relationship and proposing a proton-mediated on-demand curing strategy. Through systematic investigation using catalysts with varying acid dissociation constants (pKa), we clarify that the reaction proceeds via a base-catalyzed mechanism when the catalyst’s pKa significantly exceeds that of the thiol, whereas a nucleophilic addition-initiated mechanism dominates when the catalyst’s pKa is lower. Building on this mechanistic insight, the introduction of a proton donor (mercaptopropionic acid, MPA) enables precise regulation of the reaction kinetics. By constructing a “proton donor–catalyst–thiol” triad with a sequential pKa gradient (pKa of proton donor < pKa of catalyst < pKa of thiol), a prolonged and stable dormant period is achieved, after which rapid, autocatalytic polymerization proceeds. This approach successfully decouples pot life from curing speed, transforming the epoxy-thiol system from “immediately reactive” to “curable on-demand.” Furthermore, the effects of epoxy electrophilicity and thiol pKa on the kinetics are elucidated. This study not only resolves long-standing mechanistic controversies but also provides a universal, predictable, and easily implementable chemical framework for designing advanced thermosetting materials with tailored processability and performance.
✓ 已验证
DOI
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Yimurang Hamiti,Kai Liu,Xin Yang,Sulong Wang,Xiriaili Kadier,Aihemaitijiang Yusufu
Large bone defects present significant clinical challenges, with distraction osteogenesis (DO) requiring prolonged treatment periods and yielding suboptimal outcomes. Calcitonin gene-related peptide (CGRP) demonstrates potent bone-forming activity but suffers from rapid degradation and a short half-life, limiting its therapeutic applications. This study engineered sustained-release CGRP microspheres using poly(D,L-lactide-co-glycolide)/nano-hydroxyapatite/graphene oxide (PLGA/nHA/GO) composite matrices via W/O/W double emulsion-solvent evaporation method to address these limitations. The fabricated microspheres exhibited uniform spherical morphology (51.15 ± 0.40 μm), high encapsulation efficiency (86.14 ± 2.5 %), and sustained CGRP release over 42 days. In vitro studies compared four groups: control (untreated), blank microspheres, free CGRP solution, and CGRP-loaded microspheres. CGRP microspheres significantly enhanced rat bone marrow mesenchymal stem cell proliferation, migration capacity, and osteogenic differentiation compared to all other treatment groups. Mechanistic investigations confirmed activation of the cAMP/PKA/CREB signaling pathway with upregulation of osteogenic transcription factors (Runx2, Osterix) and bone matrix proteins (osteopontin, osteocalcin). In a rat femoral distraction osteogenesis model, CGRP microspheres demonstrated superior bone regeneration compared to control, blank microspheres, and free CGRP groups: substantially increased bone mineral density, significantly improved biomechanical properties, and accelerated bone formation. Histological analysis confirmed enhanced bone maturation and integration This engineered sustained-release system represents a promising therapeutic platform for enhancing bone regeneration through targeted molecular pathway activation, offering significant potential for clinical translation in orthopedic applications.
研究领域:
生物医学工程
·
骨科
·
组织工程
·
药物递送系统
·
分子生物学
✓ 已验证
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）