MOLECULES
·
2025
·Vol. 30
·期 16
·3400
·
IF 4.6
Lina Hu,Mengjiao Li,Zheng Liu,Hui Yan,Xuekun Wang,Shiben Wang
To discover novel, potent anticonvulsant compounds, a series of compounds containing triazole structural fragments were synthesized and evaluated for their anticonvulsant activity. Compounds6f(maximal electroshock (MES), 50% effective dose (ED50) = 13.1 mg/kg; subcutaneous pentylenetetrazole (scPTZ), ED50= 19.7 mg/kg) and6l(MES, ED50= 9.1 mg/kg;scPTZ, ED50= 19.0 mg/kg) showed the best activity in MES andscPTZ tests. The results of an affinity test showed that the potent compounds had better binding to the GABAAreceptors. The results of an inhibitory neurotransmitter GABA content test in brain tissue indicated that compounds6fand6lexerted anticonvulsant activity which may be associated with the increase of GABA content in the rat brain. Elevated plus maze (EPM) assay results showed that compounds6fand6lpossessed anxiolytic effects, and their effects correlated with the binding sites of benzodiazepines (BZs) in the GABAAreceptors. Molecular docking was performed to investigate the interactions of the studied compound6lwith the GABAAreceptors on the molecular level.
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Catalysts
·
2025
·Vol. 15
·期 7
·694
·
IF 4
Ziyan Mi,Huayun Long,Yuhua Jia,Yue Ma,Cuilan Miao,Yan Xie,Xiaomei Zhu,Jiahui Huang
The development of non-noble metal catalysts for gas-phase propylene epoxidation with H2/O2remains challenging due to their inadequate activity and stability. Herein, we report a Cs+-modified Ni/TS-1 catalyst (9%Ni-Cs/TS-1), which exhibits unprecedented catalytic performance, giving a state-of-the-art PO formation rate of 382.9 gPO·kgcat−1·h−1with 87.8% selectivity at 200 °C. The catalyst stability was sustainable for 150 h, far surpassing reported Ni-based catalysts. Ni/TS-1 exhibited low catalytic activity. However, the Cs modification significantly enhanced the performance of Ni/TS-1. Furthermore, the intrinsic reason for the enhanced performance was elucidated by multiple techniques such as XPS, N2physisorption, TEM,29Si NMR, NH3-TPD-MS, UV–vis, and so on. The findings indicated that the incorporation of Cs+markedly boosted the reduction of Ni, enhanced Ni0formation, strengthened Ni-Ti interactions, reduced acid sites to inhibit PO isomerization, improved the dispersion of Ni nanoparticles, reduced particle size, and improved the hydrophobicity of Ni/TS-1 to facilitate propylene adsorption/PO desorption. The 9%Ni-Cs/TS-1 catalyst demonstrated exceptional performance characterized by a low cost, high activity, and long-term stability, offering a viable alternative to Au-based systems.
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JOURNAL OF MOLECULAR HISTOLOGY
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2025
·Vol. 56
·期 3
·1-14
·
IF 2.2
Wen Jingli,Geng Lei,Wang Ruohan,Zhang Xiaolei,Sui Yanmin,Liu Xiaofang,Han Xin
Breast cancer is a common malignancy in women, and it has an absence of effective therapies. Carboxylesterase 1 (CES1), a member of the carboxylesterase family, has anti-tumor properties in several types of cancer. However, the function of CES1 in breast cancer remains unclear. Peroxisome proliferator-activated receptor gamma (PPARG) is a downstream regulator of CES1 and exhibits anti-breast cancer properties. Both CES1 and PPARG were downregulated in breast cancer tissues. Low CES1 and PPARG expression were linked to poorer breast cancer survival. We constructed CES1 knockdown and overexpression models of breast cancer cells by CES1 overexpressing plasmids and plasmids containing short hairpin RNA. High expression of CES1 inhibited breast cancer cell proliferation, evidenced by diminished cell viability, decreased DNA replication, and G1 phase arrest. CES1 overexpression decreased the protein levels of CDK2, CDK6 and cyclin B1 in breast cancer cells. CES1 inhibited the Bcl-2/Bax axis and increased Cleaved caspase-3 levels. Transwell assays showed that CES1 inhibited cell migration and invasion. CES1 increased E-cadherin protein expression and decreased Vimentin protein expression. CES1 knockdown facilitated the proliferation, migration, and invasion of breast cancer cells. CES1 was found to regulate PPARG expression in breast cancer cells positively. We transfected PPARG-interfering plasmids into breast cancer cells with CES1 overexpression. Inhibition of PPARG abrogated the anti-growth and anti-metastasis functions of CES1 in breast cancer cells. This study elucidates that CES1 inhibits the malignant progression of breast cancer by up-regulating the expression of PPARG. Graphical
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2025
·Vol. 26
·期 6
·2727
·
IF 4.9
Kang Li,Xiaomei Ge,Wei Liu,Lei Huang,Xinye Lv,Yuhui Tang,Zhehao He,Yingxue Yang,Miaofen Chen,Jianguo Zeng,Pi Cheng
B-cell lymphoma-2 (Bcl-2) family proteins are fundamental regulators of intrinsic cell apoptosis, and overexpression of apoptotic proteins (Bcl-2 and Mcl-1) is a characteristic of many haematological malignancies. Thus, it is necessary to discover novel inhibitors to treat leukemia. In the current study, we synthesized a series of quercetagetin derivatives (compounds2a–2t,3a–3jand4a–4g) and evaluated their anticancer activities on four leukemia cells (U937, K562, K562R and KG-1). Among those synthesized derivatives, compounds2aexhibited the best antiproliferative activity (IC50= 0.276, 0.159, 0.312 and 0.271 µM to U937, K562, K562R and KG-1, respectively). In addition,2ainduced apoptosis in K562 and markedly arrested the cell cycle G2/M phase of K562. The Western blot assay showed that2ais a potential inhibitor that can effectively suppress the expression of Bcl-2 and Mcl-1. The molecular docking study predicted that2ahad firm interactions with the active pockets of Bcl-2 and Mcl-1. Finally, in silico pharmacokinetic evaluation of2aindicated its potential as an anti-leukemia drug lead in the future.
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BIOLOGY OF REPRODUCTION
·
2025
·
IF 3
Zhang Yingying,Zhang Eryun,Li Ling,Ren Yongwei,Zhang Jinqiu,Zheng Qiutong,Sun Minya,Zhao Shaojie,Cui Yugui,Gu Ying,Xu Zhice
The risk of multiple placental thrombosis is significantly elevated in preeclampsia, and the vascular endothelium plays a vital role in coagulation processes through the secretion of Integrin alpha 2b, von Willebrand factor, and tissue factor. However, the underlying pathological mechanisms remain unclear. In this study, placental blood vessels were collected from both preeclampsia and normal pregnancies. Protein levels of Integrin alpha 2b were found to be up-regulated in preeclampsia samples compared to controls, indicating enhanced coagulation function in preeclampsia placental tissue. Additionally, higher cholesterol levels of plasma and lower AlkB homolog 1 expression in placental blood vessels of preeclampsia were found, overall DNA N6-methyldeoxyadenosine levels were up-regulated. Interestingly, the DNA N6-methyldeoxyadenosine level at the Integrin alpha 2b promoter was decreased. Cholesterol overload experiments in human umbilical vein endothelial cells demonstrated that cholesterol regulates the protein expression of AlkB homolog 1 and Integrin alpha 2b in a concentration-dependent manner. Furthermore, Integrin alpha 2b protein expression was increased following AlkB homolog 1 knockout, but no changes were observed when cholesterol was incubated with AlkB homolog 1 knockout cells. These findings provide critical insights into the roles of cholesterol levels, AlkB homolog 1, and Integrin alpha 2b in coagulation function within placental blood vessels. This information may contribute to further investigations of potential therapeutic targets and early prevention strategies for placental thrombosis in preeclampsia.
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CHEMISTRY-A EUROPEAN JOURNAL
·
2025
·
IF 3.7
Zhicheng Tang,Tianwei Wang,Hua Lin,Shoulong Hao,Shufen Zhang,Rongwen Lu
Amination of 1-amino-4-bromoanthraquinone-2-sulfonic acid (BAA), crucial for anthraquinone-type dyes production, relies on Cu+ catalysis. However, Cu+ disproportionation causes catalyst deactivation, requiring large amounts of Cu catalysts (e.g., CuSO4 or CuCl) and reductants (e.g., FeSO4), introducing heavy metals and increasing water consumption to remove byproducts and metals, raising both environmental and economic costs. To address these challenges, we introduce a groundbreaking strategy for the in-situ generation of Cu+ using symmetrical Cu electrodes under alternating current (AC) electrolysis. This method achieves 100% conversion of BAA in the amination with 3,5-diamino-2,4,6-trimethylbenzene sulfonic acid (M Acid) with 95% yield, while also providing a solution to the issue of Cu+ disproportionation without the need for any additional copper catalysts or reductants, demonstrating a broad substrate scope and significantly reducing water usage in post-treatment. Characterization techniques, including X-ray photoelectron spectroscopy, X-ray diffraction, and electrochemical impedance spectroscopy, reveal that the passive Cu2O film formed on the symmetrical Cu electrodes under AC electrolysis continuously generates Cu+, which is crucial for the reaction. This approach is scalable, environmentally friendly, and holds great potential for industrial applications, offering substantial economic benefits while reducing environmental impact.
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TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2025
·
IF 3.4
Xuemin Xian,Xin Zhao,Xingchen Zhou,Hanfang Liu,Changxi Li,Xinquan Wu,Yuhang Chen,Keyue Ye,Hongwei Yang,Mingxi Li,Jianyun Yan,Xiuli Zhang
Vascular calcification (VC) is a common complication of chronic kidney disease (CKD), with oxidative stress identified as a key contributor to VC progression. Honokiol (HKL), a biphenolic compound derived from plants, has been found to be effective in treating various models of cardiovascular disease through the mitigation of oxidative stress. However, its effects on VC remain unexplored. To elucidate the effects of HKL on VC, a CKD rat model, a vitamin D 3 -overload-induced mouse model of vascular calcification, and a high-phosphate-induced human vascular smooth muscle cell (VSMC) calcification model were established. Calcification levels were assessed using Alizarin Red staining, calcium quantification, and Western blotting of osteogenic markers. Oxidative stress was assessed by measuring reactive oxygen species. Furthermore, transcriptome sequencing was employed to identify molecules and pathways affected by HKL. HKL was found to significantly reduce calcification in both in vivo and in vitro models. It also mitigated oxidative stress induced by high phosphate in human VSMCs. Mechanistically, HKL upregulated heme oxygenase-1 (HMOX-1), thereby inhibiting oxidative stress and reducing calcification. Pharmacological inhibition of HMOX-1 counteracted the protective effect of HKL on vascular calcification. In summary, the findings suggest that HKL ameliorates VC by upregulating HMOX-1 and decreasing oxidative stress.
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Molecular Biomedicine
·
2025
·Vol. 6
·期 1
·1-18
·
IF 10.1
Yao Yu,Liu Yu-ying,Li Jian-feng,Chen Yun-shuo,Shi Lei,Shen Yang,Yang Li-li,Yang Qing
Acute myeloid leukemia (AML), the most common leukemia in adults, exhibits immune escape characteristics like solid tumors. The expression of indoleamine 2,3-dioxygenase 1 (IDO1), a well-recognized immune checkpoint, has been detected in AML blast cells and is associated with poor clinical outcome. Although an imbalance of B cell subpopulations exists in AML patients’ bone marrow microenvironment, the role of B cells and their interaction with IDO1 in AML have yet to be elucidated. Herein, with bioinformatic analysis, we found the close correlations between IDO1 expression and survival and B cell subpopulation proportions in AML patients. Further, our investigation into IDO1 expression and activity, B cell subpopulation proportions and immunosuppressive interleukin-10 (IL-10) level in AML cells and clinical samples revealed significant findings. Using a co-culture system of healthy human PBMCs and AML cell lines, we demonstrated that high IDO1 expression in AML cells could alter the proportions of total B, regulatory B and memory B cells, and increased the level of IL-10. Finally, with the IDO1 inhibitor RY103 designed by our laboratory, we found that IDO1 inhibition had good anti-leukemic effect and restored the abnormal proportions of B cell subpopulations in AML mice. Our study is the first to reveal the modulation of IDO1 on B cell subpopulations in AML, making a significant breakthrough in understanding the immune escape mechanisms of AML. Application of IDO1 inhibitor, such as RY103, targeting the imbalance of B cell subpopulations can lead to innovative treatments for AML.
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2025
·Vol. 26
·期 9
·4095
·
IF 4.9
Ekaterina A. Litus,Marina P. Shevelyova,Alisa A. Vologzhannikova,Evgenia I. Deryusheva,Alina V. Chaplygina,Victoria A. Rastrygina,Andrey V. Machulin,Valeria D. Alikova,Aliya A. Nazipova,Maria E. Permyakova,Victor V. Dotsenko,Sergei E. Permyakov,Ekaterina L. Nemashkalova
Clinical data as well as animal and cell studies indicate that certain antidiabetic drugs, including glucagon-like peptide 1 receptor agonists (GLP-1RAs), exert therapeutic effects in Alzheimer’s disease (AD) by modulating amyloid-β peptide (Aβ) metabolism. Meanwhile, the direct interactions between GLP-1RAs and Aβ and their functional consequences remain unexplored. In this study, the interactions between monomeric Aβ40/Aβ42 of GLP-1(7-37) and its several analogs (semaglutide (Sema), liraglutide (Lira), exenatide (Exen)) were studied using biolayer interferometry and surface plasmon resonance spectroscopy. The quaternary structure of GLP-1RAs was investigated using dynamic light scattering. The effects of GLP-1RAs on Aβ fibrillation were assessed using the thioflavin T assay and electron microscopy. The impact of GLP-1RAs on Aβ cytotoxicity was evaluated via the MTT assay. Monomeric Aβ40 and Aβ42 directly bind to GLP-1(7-37), Sema, Lira, and Exen, with the highest affinity for Lira (the lowest estimates of equilibrium dissociation constants were 42–60 nM). GLP-1RAs are prone to oligomerization, which may affect their binding to Aβ. GLP-1(7-37) and Exen inhibit Aβ40 fibrillation, whereas Sema promotes it. GLP-1 analogs decrease Aβ cytotoxicity toward SH-SY5Y cells, while GLP-1(7-37) enhances Aβ40 cytotoxicity without affecting the cytotoxic effect of Aβ42. Overall, GLP-1RAs interact with Aβ and differentially modulate its fibrillation and cytotoxicity, suggesting the need for further studies of our observed effects in vivo.
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CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Aonan Qiao,Yu Liu,Fei Li,Haixia Pan,Yanan Guo,Yang Liu,Xianliang Yi,Hao Zhou
Manganese-oxidizing bacteria (MnOB) mediate the oxidation of Mn(II) in both natural and engineered environments. Although numerous MnOB have been isolated, the regulatory mechanisms governing their Mn(II)-oxidizing activity in response to nitrogen sources remain poorly understood. This study investigates how nitrogen sources affect the Mn(II)-oxidizing capability of Pseudomonas sp. AN-1. Mn(II) oxidation was completely inhibited in NH 4 + -supplemented cultures, with no detectable BioMnOx production throughout a 10-day incubation period. In contrast, complete oxidation of 100 μM Mn(II) occurred within 27 h when either NO 3 − or NO 2 − as the nitrogen source. Intriguingly, Mn(II) oxidation exhibited a histidine concentration-dependent pattern: no oxidation was observed at 0.5–1.0 mM histidine, whereas complete oxidation occurred at 2.5 mM. Transcriptomics and proteomics revealed NO 3 − -fed cultures exhibited significantly higher expression of manganese oxidation genes, including mnxG and mcoA , compared to histidine-supplemented cultures. Further analysis identified the MnxS/MnxR as essential for initiating the transcription of mnxG and mcoA . Bioinformatic analysis revealed this regulatory system is widely distributed in the genus Pseudomonas and frequently co-occurs with mnxG and mcoA . This study provides insight into nitrogen-source dependent regulation of bacterial Mn(II) oxidation, uncovering concentration-dependent effects and identifying the MnxS/MnxR system as a key regulatory node that integrates nitrogen sensing with Mn(II) oxidation.
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CELLULAR AND MOLECULAR LIFE SCIENCES
·
2023
·Vol. 80
·期 3
·1-16
·
IF 8
Li Xiaoxue,Zhang Yumeng,Chang Jianghao,Zhang Chenglin,Li Lin,Dai Yifan,Yang Haiyuan,Wang Ying
Previous studies have shown that mfat-1 transgenic mice have protective effects against some central nervous system (CNS) disorders, owing to the high docosahexaenoic acid (DHA) content enriched in their brains. However, whether this protective effect is connected to the blood – brain barrier (BBB) remains unclear. This study aims to investigate the mechanisms of the protective effect against hypoxic-ischemic brain damage (HIBD) of mfat-1 transgenic mice. mfat-1 mice not only demonstrated a significant amelioration of neurological dysfunction and neuronal damage but also partly maintained the physiological permeability of the BBB after HIBD. We initially showed this was associated with elevated major facilitator superfamily domain-containing 2a (Mfsd2a) expression on the BBB, resulting from more lysophosphatidylcholine (LPC)-DHA entering the brain. Wild-type (WT) mice showed a similar Mfsd2a expression trend after long-term feeding with an LPC-DHA-rich diet. Knockdown of Mfsd2a by siRNA intra-cerebroventricular (ICV) injection neutralized the protective effect against HIBD-induced BBB disruption in mfat-1 mice, further validating the protective function of Mfsd2a on BBB. HIBD-induced BBB high permeability was attenuated by Mfsd2a, primarily through a transcellular pathway to decrease caveolae-like vesicle-mediated transcytosis. Taken together, these findings not only reveal that mfat-1 transgenic mice have higher expression of Mfsd2a on the BBB, which partly sustains BBB permeability via vesicular transcytosis to alleviate the severity of HIBD, but also suggest that dietary intake of LPC-DHA may upregulate Mfsd2a expression as a novel therapeutic strategy for BBB dysfunction and survival in HIBD patients.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2021
·
IF 6.953
Wenchao Zhang,Weiyi Wang,Xin Liu,Ying Chen,Kang Ouyang,Zuzhang Wei,Huan Liu,Weijian Huang
Porcine astrovirus (PAstV) is prevalent in pigs worldwide and could cause clinical symptoms such as diarrhea and encephalitis. The capsid protein (Cap) of PAstV plays a determinant role for virus immunological characteristics. In this study, the major antigenic regions of PAstV1 Cap were expressed through prokaryotic expression systems and immunized to BALB/c mice. Finally, two anti-Cap monoclonal antibodies (named mAb F4-4 and D3F10) were screened by indirect immune-fluorescence assay (IFA). A series of truncated GST-fused or artificially synthesized peptides were used to detect their reactivity with the mAbs and PAstV positive serum. Two novel B cell epitopes ( 120- GNNTFG -125 , 485- RISDPTWFSA -494 ) were identified by using these two mAbs. Moreover, sequence alignment result showed that epitope 120- GNNTFG -125 was highly conserved in type 1 PAstV capsid protein. Cross-reactivity analysis further confirmed the genotype-specificity of mAb F4-4. The results of this study demonstrated to be the first description of monoclonal antibody preparation and B-cell epitope mapping on PAstV capsid protein, which may provide new information on the biological significance of PAstV capsid protein and lay a foundation for the development of PAstV immunological tests and genotype diagnostic methods.
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