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ADVANCED FUNCTIONAL MATERIALS · 2024 · IF 18.5

Sacrificial NH4HCO3 Inhibits Fluoropolymer/Garnet Interfacial Reactions Toward 1mS cm−1 and 5V-Level Composite Solid Electrolyte

Yaping Wang,Pengcheng Yuan,Xiong Xiong Liu,Shengfa Feng,Mufan Cao,Jianxiang Ding,Jiacheng Liu,Song-Zhu Kure-Chu,Takehiko Hihara,Long Pan,ZhengMing Sun

Composite solid electrolytes (CSEs) integrate the fast ion conductivity of inorganic electrolytes and the excellent interfacial compatibility of polymer electrolytes. Typically, fluoropolymers and garnets are promising individuals to formulate cutting-edge CSEs owing to their unique properties. However, the alkaline garnets can induce the dehydrofluorination of fluoropolymers, deteriorating their CSEs performance. Here, for the first time, NH 4 HCO 3 is proposed as a sacrificial inhibitor to effectively prevent the garnet-induced dehydrofluorination, using Li 6.4 La 3 Zr 1.4 Ta 0.6 O 12 (LLZTO) and poly(vinylidene fluoride- co -hexafluoropropylene) (PVH) as symbolic garnets and fluoropolymers, respectively. Various findings demonstrate that NH 4 HCO 3 can buffer the alkalinity of LLZTO, thereby inhibiting the dehydrofluorination of PVH. In addition, NH 4 HCO 3 can completely decompose to volatiles upon drying without compromising the properties of LLZTO and PVH. Additionally, a polymer-in-salt strategy is further introduced by adding high-concentration LiTFSI salt to the above system, resulting in the PVH/LiTFSI/LLZTO (PLL) CSEs. Benefiting from the synergetic coupling of the sacrificial inhibitor and polymer-in-salt strategies, the PLL exhibits an exceptionally high ionic conductivity of 1.2 mS cm −1 at 25 °C and stable voltage of 5.09 V, outperforming other reported CSEs. Consequently, the PLL delivers impressive high-rate cyclability in solid-state lithium-metal batteries with an outstanding capacity retention of 95.4% after 240 cycles at 1 C (25 °C).

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ENERGY & FUELS · 2024 · IF 5.2

Potential of a 1-Amino-2-Propanol/Sulfolane Biphasic Solution for CO2 Capture: Performance and Mechanism Study

Guangjie Chen,Guangying Chen,Miao Fa,Yuxian Yang,Yu Wang,Fei Li,Li Sze Lai,Swee Pin Yeap

In order to reduce the regeneration energy consumption of CO2 capture in the postcombustion capture process and explore the regulatory characteristics of phase separation, a series of 1-amino-2-propanol (MIPA)/sulfolane biphasic solutions were proposed to capture CO2. The effects of the molar ratio on the phase separation behavior, CO2 equilibrium absorption, and desorption performances of MIPA/solfolane biphasic absorbents as well as three ternary solutions with the extra addition of ethanolamine (MEA) were investigated comprehensively in experiments. The results showed that the 4M/5M MIPA/sulfolane biphasic solution exhibited excellent performance with higher CO2 loadings in the phase separation point for a CO2-rich liquid (0.4530 mol/mol), better desorption efficiency (85.53%), and relatively low regeneration energy consumption (32% lower than 30 wt % MEA). Besides, MEA has a positive effect on promoting the phase separation of the MIPA/sulfolane solution and reducing the desorption energy consumption. Furthermore, 1H and 13C nuclear magnetic resonance (NMR) spectroscopy was used to explore the reaction and phase separation mechanisms. The results indicated that generated carbamate salts can increase the ionic strength of the aqueous solution, leading to the accumulation of reacted MIPA or MEA in the water phase and the exclusion of sulfolane from water to form a new liquid phase. The results of this work can provide theoretical support for the future industrial application of MIPA/sulfolane biphasic absorbents and offer some guidance for the mechanism exploration of other biphasic solvent systems.

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PLoS Neglected Tropical Diseases · 2025 ·Vol. 19 ·期 1 ·e0012769 · IF 3.4

Nb-FAR-1: A key developmental protein affects lipid droplet accumulation and cuticle formation in Nippostrongylus brasiliensis

Wenmin Qi,Fei Shen,Chuyue Wang,Juan Wen,Xi Pan,Zhongying Zhao,Lihua Xiao,Yaoyu Feng,Dongjuan Yuan

Fatty acid and retinol binding proteins (FARs) are lipid-binding protein that may be associated with modulating nematode pathogenicity to their hosts. However, the functional mechanism of FARs remains elusive. We attempt to study the function of a certain FAR that may be important in the development of Nippostrongylus brasiliensis . Nb -FAR-1 was highly expressed throughout developmental stages by RNA-seq data and qPCR analyses, and Nb -FAR-1 was a secretory protein and abundant in the excretory-secretory products. Nb -FAR-1 could bind fatty acids and retinol. Fatty acid pattern of parasitic adults was more similar to rat intestine than to free-living L3s, indicating that N . brasiliensis may be dependent on the host to obtain fatty acids. Lentivirus-mediated RNAi was performed on L3s, resulting in a reduction in the expression of Nb - far-1 gene. Furthermore, these RNAi effects could be maintained in several generations. The offspring L3s in Nb - far-1 RNAi group had a reduction in lipid droplets within the subcuticle and the swelling of the perioral epidermis, accompanied with down-regulated expression of enzymes in amino acid and glycerolipid metabolism and glycometabolism for growth by RNA-seq data. Adults in Nb - far-1 RNAi group had the crumpled epidermis loosely attached to the basal membrane of body surface and the breakage of mouth epidermis, accompanied with a decrease in adult egg-shedding and an appearance of abnormal eggs. In vitro culture of eggs showed decreased efficiency of egg hatchability and larval development in the Nb - far-1 RNAi group. Transcriptomic analysis showed that interference with Nb - far-1 expression induced downregulated expression of major sperm protein and serpin for reproduction, and collagen for epidermis formation in adults, most of which were relatively high expression in adults but low expression in L3s in the WT group. Thus, Nb -FAR-1 may affect the reproduction, growth, and development of N . brasiliensis by regulating the level of lipids. Fatty acid and retinol-binding protein 1 (FAR-1) is lipid-binding protein that may be associated with modulation of host immune responses and provide insights into nematode pathogenicity to their hosts. However, the role of FAR-1 protein on parasitic nematodes remains unclear. Nippostrongylus brasiliensis was employed to identify the characteristics of Nb - far-1 gene, its expression patterns, ligand binding properties and the functions associated with it. The secretory Nb -FAR-1 protein was found to be highly expressed in N . brasiliensis ESPs and demonstrated affinity for fatty acids and retinol. Interference with Nb - far-1 gene expression resulted in a reduction in the formation of lipid droplets in L3s, a decrease in a rate of adult egg-shedding, egg hatchability, and larval development. Therefore, we proposed that N . brasiliensis Nb -FAR-1 protein may serve as a causative agent in nematode growth, development, and reproduction by regulating the level of lipids.

CAS / MDL: 107-92-6
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Molecular Medicine Reports · 2024 ·Vol. 29 ·期 5 ·1-14 · IF 3.4

Resveratrol ameliorates ulcerative colitis by upregulating Nrf2/HO‑1 pathway activity: Integrating animal experiments and network pharmacology

Xinya Yu,Xiaoxi Li,Yunchun Xu,Yuwei Li,Ye Zhou,Junhua Zhang,Le Guo

Ulcerative colitis (UC) is a chronic idiopathic inflammatory condition affecting the rectum and colon. Inflammation and compromisation of the intestinal mucosal barrier are key in UC pathogenesis. Resveratrol (Res) is a naturally occurring polyphenol that exhibits anti‑inflammatory and antioxidant properties. Nuclear factor erythroid‑2‑related factor 2/heme oxygenase 1 (Nrf2/HO‑1) pathway regulates occurrence and development of numerous types of diseases through anti‑inflammatory and antioxidant activity. However, it is not clear whether Nrf2/HO‑1 pathway is involved in the treatment of Res in UC. Therefore, the present study aimed to investigate whether Res modulates the Nrf2/HO‑1 signaling pathway to attenuate UC in mice. Dextran sulfate sodium (DSS) was used to induce experimental UC in male C57BL/6J mice. Disease activity index (DAI) and hematoxylin eosin (H&E) staning was used to assessed the magnitude of colonic lesions in UC mice. ELISA) was utilized to quantify inflammatory cytokines (IL‑6, IL‑1β, TNF‑α and IL‑10) in serum and colon tissues. Immunohistochemistry and Western blot were used to evaluate the expression levels of tight junction (TJ) proteins [zonula occludens (ZO)‑1 and Occludin] in colon tissues. Pharmacokinetic (PK) parameters of Res were derived from TCMSP database. Networkpharmacology was employed to identify the biological function and pharmacological mechanism of Res in the process of relieving UC, and the key target was screened. The binding ability of Res and key target was verified by molecular docking. Finally, the effectiveness of key target was substantiated by Western blot. Res decreased DAI, ameliorated histopathological changes such as crypt loss, disappeatance of the mucosal epithelium, and inflammatory infiltration in mice. Additionally, Res decreased expression of pro‑inflammatory cytokines IL‑6, IL‑1β and TNF‑α and increased anti‑inflammatory factor IL‑10 expression. Res also restored the decreased protein expression of ZO‑1 and occludin after DSS treatment, increasing the integrity of the intestinal mucosal barrier. The PK properties of Res suggested that Res possesses the therapeutic potential for oral administration. Network pharmacology revealed that Res alleviated UC through anti‑inflammatory and antioxidant pathways, and confirmed that Nrf2 has a high binding affinity with Res and is a key target of Res against UC. Western blotting demonstrated that Res treatment increased the protein levels of Nrf2 and HO‑1. In conclusion, Res treatment activated the Nrf2/HO‑1 pathway to decrease clinical symptoms, inflammatory responses, and intestinal mucosal barrier damage in experimental UC mice.

CAS / MDL: 10102-40-6
✓ 已验证 产品关联 DOI PubMed 高影响因子
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PHYTOMEDICINE · 2024 · IF 6.7

Sarmentol H derived from Sedum sarmentosum Bunge directly targets FXR to mitigate cholestasis by recruiting SRC-1

Zhenxiu Liu,Lin Chen,Mingyun Chen,Lang Linghu,Zhihua Liao,Min Chen,Guowei Wang

Background Farnesoid X receptor (FXR) is a vital receptor for bile acids and plays an important role in the treatment of cholestatic liver disease. In addition to traditional bile acid-based steroidal agonists, synthetic alkaloids are the most commonly reported non-steroidal FXR agonists. Sarmentol H is a nor-sesquiterpenoid obtained from Sedum sarmentosum Bunge, and in vitro screening experiments have shown that it might be related to the regulation of the FXR pathway in a previous study. Purpose To investigate the therapeutic effects of sarmentol H on cholestasis and to determine whether sarmentol H directly targets FXR to mitigate cholestasis. Furthermore, this study aimed to explore the key amino acid residues involved in the binding of sarmentol H to FXR through site-directed mutagenesis. Methods An intrahepatic cholestasis mouse model was established to investigate the therapeutic effects of sarmentol H on cholestasis. In vitro experiments, including Co-Ip and FXR-EcRE-Luc assays, were performed to assess whether sarmentol H activates FXR by recruiting the receptor coactivator SRC1. CETSA, SIP, DARTS, and ITC were used to determine the binding of sarmentol H to FXR protein. The key amino acid residues for sarmentol H binding to FXR were analyzed by molecular docking and site-directed mutagenesis. Finally, we conducted in vivo experiments on wild-type and Fxr −/− mice to further validate the anticholestatic target of sarmentol H. Results Sarmentol H had significant ameliorative effects on the pathological conditions of cholestatic mice induced with ANIT. In vitro experiments suggested that it is capable of activating FXR and regulating downstream signaling pathways by recruiting SRC1. The target validation experiments showed that sarmentol H had the ability to bind to FXR as a ligand (K D  = 2.55 μmol/L) and enhance the stability of its spatial structure. Moreover, site-directed mutagenesis revealed that THR292 and TYR365 were key binding sites for sarmentol H and FXR. Furthermore, knockout of the Fxr gene resulted in a significantly higher degree of ANIT-induced cholestatic liver injury than that in wild-type cholestatic mice, and the amelioration of cholestasis or regulatory effects on FXR downstream genes by sarmentol H also disappeared in Fxr −/− cholestatic mice. Conclusion Sarmentol H is an FXR agonist. This is the first study to show that it exerts a significant therapeutic effect on cholestatic mice, and can directly bind to FXR and activate it by recruiting the coactivator SRC1.

CAS / MDL: 128-13-2 551-06-4
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FUEL · 2024 · IF 6.7

Promoting propane dehydrogenation over Zn/hollow porous silicalite-1 catalysts via modulating the electronic structures of Pt

Fuwen Yang,Jie Zhang,Jinwei Chen,Gang Wang,Tong Yu,Junyu Zhao,Qian Li,Zongbo Shi,Runsheng Zhuo,Ruilin Wang

Propane dehydrogenation (PDH) provides a promising way to meet the requirement of propylene supply, but the commonly-used Pt-based catalysts still suffer from unsatisfactory stability and deactivation. Herein, an interfacial regulation strategy is developed to construct the Cu, Pt, and Zn species modified hollow porous silicalite-1 (CuPt/Zn-HPS-1). Owing to the regulation role of Pt, the electron-deficient [ZnOH] + Lewis acid sites accelerated the C-H activation, which was beneficial to achieve the excellent PDH performance. More importantly, the additionally introduced Cu 2+ further modulated the geometric structure and electronic density of Pt, thus effectively improving the anti-sintering ability and alleviating the coke deposition. Benefiting from the interfacial regulation and Lewis active [ZnOH] + sites, the optimal CuPt/Zn-HPS-1 catalyst exhibited an excellent catalytic PDH performance with the initial propane conversion of 30.4 % and propylene selectivity of 99.0 %. The CuPt/Zn-HPS-1 also demonstrated robust recycling stability in reaction-regeneration cycling test with the smaller deactivation rate constant. This work affords a strategy for improving PDH performance in practical industrial application.

CAS / MDL: 94442-22-5
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EUROPEAN JOURNAL OF PHARMACOLOGY · 2024 · IF 4.2

Protecting against ferroptosis in hyperuricemic nephropathy: The potential of ferrostatin-1 and its inhibitory effect on URAT1

Yongmei Li,Fengxin Zheng,Shiqi Zhong,Kunlu Zhao,Hui Liao,Jiacheng Liang,Qiang Zheng,Huicong Wu,Shifan Zhang,Ying Cao,Ting Wu,Jianxin Pang

Hyperuricemic nephropathy (HN) is characterized by renal fibrosis and tubular necrosis caused by elevated uric acid levels. Ferroptosis, an iron-dependent type of cell death, has been implicated in the pathogenesis of kidney diseases. The objective of this study was to explore the role of ferroptosis in HN and the impact of a ferroptosis inhibitor, ferrostatin-1 (Fer-1). The study combined adenine and potassium oxonate administration to establish a HN model in mice and treated HK-2 cells with uric acid to simulate HN conditions. The effects of Fer-1 on the renal function, fibrosis, and ferroptosis-associated molecules were investigated in HN mice and HK-2 cells treated with uric acid. The HN mice presented with renal dysfunction characterized by elevated tissue iron levels and diminished antioxidant capacity. There was a significant decrease in the mRNA and protein expression levels of SLC7A11, GPX4, FTL-1 and FTH-1 in HN mice. Conversely, treatment with Fer-1 reduced serum uric acid, serum creatinine, and blood urea nitrogen, while increasing uric acid levels in urine. Fer-1 administration also ameliorated renal tubule dilatation and reduced renal collagen deposition. Additionally, Fer-1 also upregulated the expression levels of SLC7A11, GPX4, FTL-1, and FTH-1, decreased malondialdehyde and iron levels, and enhanced glutathione in vivo and in vitro . Furthermore, we first found that Fer-1 exhibited a dose-dependent inhibition of URAT1, with the IC 50 value of 7.37 ± 0.66 μM. Collectively, the current study demonstrated that Fer-1 effectively mitigated HN by suppressing ferroptosis, highlighting the potential of targeting ferroptosis as a therapeutic strategy for HN.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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BMC Complementary Medicine and Therapies · 2022 ·Vol. 22 ·期 1 ·1-13 · IF 2.838

Pharmacokinetics and pharmacodynamics of bioactive compounds in Penyanqing preparation in THP-1 inflammatory cells induced by Lipopolysaccharide

Gong Linna,Miao Zhishuo,Zhang Li,Shi Birui,Xiao Zuoqi,Qiu Panzi,Liu Menghua,Zou Wei

Background Penyanqing (PYQ), a traditional Chinese medicine (TCM), has a good clinical efficacy for the treatment of pelvic inflammatory disease (PID). Previously, researches on its anti-inflammatory effect and mechanism in vitro, in silico, and in vivo have been reported by our team. However, the interrelationship between the anti-inflammatory activity and the active compounds in PYQ are not clear. Here, the pharmacokinetics-pharmacodynamics (PK-PD) study was carried out for more proper clinical use.Methods The plasma concentrations of salvianolic acid B (SAB), protocatechualdehyde (PRO), paeoniflorin (PE), astilbin (AST), ferulic acid (FE), and chlorogenic acid (CH) in SD rats after PYQ administration were determined by a selective and rapid HPLC–MS/MS method. In addition, the PK-PD on cell model was used to explore the relationship between the plasma concentration and inflammatory biomarkers (TNF-α, IL-1β).Results The results of this study showed that the six components could reach the peak blood concentration within 0.29 h, indicating the rapid absorption of it. The eliminations of AST, CH, FE, PE, and PRO were relatively fast due to their mean residence times (MRTs) within 3 h, while the elimination of SAB was slower (MRT 5.67 ± 0.66 h). Combined with a THP-1 cell model, there was a significant correlation between inflammatory factors and component plasma concentrations with correlation coefficients in the range of -0.9—-0.746. Correspondingly, the drug-containing plasma obtained at 0.25 h point exhibited the best inhibition effect on production of IL-1β and TNF-α in LPS-induced THP-1 cells.Conclusion The six main components in PYQ could be quickly absorbed, and there was a potential good correlation between their pharmacokinetics and the pharmacodynamics of PYQ.

✓ 已验证 DOI PubMed 高影响因子
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FOOD CHEMISTRY · 2021 · IF 7.514

Overexpression and biochemical characterization of a truncated endo-α (1 → 3)-fucoidanase from alteromonas sp. SN-1009

Chenlu Zhu,Zebin Liu,Lishi Ren,Siming Jiao,Xuebing Zhang,Qiukuan Wang,Zhimin Li,Yuguang Du,Jian-Jun Li

Endo -fucoidanases are important in structural analysis of fucoidans and preparation of fuco-oligosaccharides. However their enzymological properties and analysis of degradation products are scarcely investigated. Truncated endo - α (1 → 3)-fucoidanase Fda1 (tFda1B from Alteromonas sp. was overexpressed and characterized, showing highest activity at pH 7.0, 35 °C, and 1.0 M NaCl. Its K m and k cat were 3.88 ± 0.81 mg/mL and 0.82 ± 0.17 min −1 . Fe 3+ and Mn 2+ enhanced activity by 100% and 19.5% respectively. Co 2+ and Cu 2+ completely inactivated tFda1B, whereas Ni 2+ , Mg 2+ , Zn 2+ , Pb 2+ , Ca 2+ , Ba 2+ and Li + decreased activity by 58.8%, 56.0%, 50.6%, 47.7%, 28.9%, 15.6% and 37.5%, respectively. Catalytic residues were identified through structure and sequence alignment, and confirmed by mutagenesis. Degradation products of Kjellmaniella crassifolia fucoidan by tFda1B were characterized by LC-ESI-MS/MS, confirming tFda1B belongs to endo -(1 → 3)-fucoidanases, and backbone of K. crassifolia fucoidan is 1 → 3 fucoside linkage. This endo - α (1 → 3)-fucoidanase would be useful for elucidating fucoidan structures, and be used as a food enzyme.

✓ 已验证 DOI PubMed 高影响因子
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Acta Pharmaceutica Sinica B · 2019 · IF 5.808

Evodiamine-inspired dual inhibitors of histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) with potent antitumor activity

Yahui Huang,Shuqiang Chen,Shanchao Wu,Guoqiang Dong,Chunquan Sheng

A great challenge in multi-targeting drug discovery is to identify drug-like lead compounds with therapeutic advantages over single target inhibitors and drug combinations. Inspired by our previous efforts in designing antitumor evodiamine derivatives, herein selective histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) dual inhibitors were successfully identified, which showed potent in vitro and in vivo antitumor potency. Particularly, compound 30a was orally active and possessed excellent in vivo antitumor activity in the HCT116 xenograft model (TGI = 75.2%, 150 mg/kg, p.o .) without significant toxicity, which was more potent than HDAC inhibitor vorinostat, TOP inhibitor evodiamine and their combination. Taken together, this study highlights the therapeutic advantages of evodiamine-based HDAC1/TOP2 dual inhibitors and provides valuable leads for the development of novel multi-targeting antitumor agents.

✓ 已验证 DOI PubMed 高影响因子
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BIOCONJUGATE CHEMISTRY · 2015 · IF 4.513

Nanoparticle siRNA against BMI-1 with a Polyethylenimine–Laminarin Conjugate for Gene Therapy in Human Breast Cancer

Xueling Ren,Lei Liu,Yuxue Zhou,Yan Zhu,Hong Zhang,Zhenzhong Zhang,Huixiang Li

The B-cell-specific Moloney leukemia virus inset site 1 gene (BMI-1) has attracted considerable attention in recent years because of its key role in breast cancer development and metastasis. The downregulation of BMI-1 expression via small interfering RNA (siRNA) effectively inhibits tumor growth. However, the successful application of this therapy is limited by the unavailability of an appropriate vector for siRNA transfer. Therefore, this study aimed to construct a novel laminarin-based nonviral gene transfer vector to carry a constructed BMI-1-targeting siRNA and to investigate the in vitro and in vivo antitumor effects of this siRNA on breast cancer cells. To enhance the siRNA-carrying capacity, we introduced polyethylenimine (PEI) to laminarin’s surface via N,N′-carbonyldiimidazole, which produced the cationic PEI-modified laminarin conjugate nLP. Subsequent in vitro experiments indicated that nLP not only formed a nanoparticle with a diameter of 200 nm through electrostatic interactions with siRNA but also showed high efficiency (95.0%) in the delivery siRNA to MCF-7 cells. The nanoparticle targeting BMI-1 (nLP/siBMI-2) reduced BMI-1 expression in breast MCF-7 cells by 90.9% reduction. An in vivo tumor suppression experiment demonstrated that the nLP/siBMI-2 nanoparticle had relatively low toxicity and good gene-therapeutic efficacy, with a tumor inhibition rate of 46.6%.

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