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PHYTOMEDICINE · 2023 · IF 7.9

Hederagenin improves Alzheimer's disease through PPARα/TFEB-mediated autophagy

Zhi-shen Xie,Jian-ping Zhao,Li-min Wu,Shuang Chu,Zheng-hao Cui,Yi-ran Sun,Hui Wang,Hui-fen Ma,Dong-rui Ma,Pan Wang,Xiao-wei Zhang,Zhen-qiang Zhang

Background Autophagic flux is coordinated by a network of master regulatory genes, which centered on transcription factor EB (TFEB). The disorders of autophagic flux are closely associated with Alzheimer's disease (AD), and thus restoring autophagic flux to degrade pathogenic proteins has become a hot therapeutic strategy. Hederagenin (HD), a triterpene compound, isolated from a variety food such as Matoa (Pometia pinnata) Fruit, Medicago sativa, Medicago polymorpha L. Previous studies have shown that HD has the neuroprotective effect. However, the effect of HD on AD and underlying mechanisms are unclear. Purpose To determine the effect of HD on AD and whether it promotes autophagy to reduce AD symptoms. Study Design BV2 cells , C. elegans and APP/PS1 transgenic mice were used to explore the alleviative effect of HD on AD and the molecular mechanism in vivo and in vitro . Methods The APP/PS1 transgenic mice at 10 months were randomized into 5 groups ( n  = 10 in each group) and orally administrated with either vehicle (0.5% CMC Na), WY14643 (10 mg/kg/d), low-dose of HD (25 mg/kg/d), high-dose of HD (50 mg/kg/d) or MK-886 (10 mg/kg/d) + HD (50 mg/kg/d) for consecutive 2 months. The behavioral experiments including morris water maze test, object recognition test and Y maze test were performed. The effects of HD on Aβ deposition and alleviates Aβ pathology in transgenic C. elegans were operated using paralysis assay and fluorescence staining assay. The roles of HD in promoting PPARα/TFEB-dependent autophagy were investigated using the BV2 cells via western blot analysis, real-time quantitative PCR (RT-qPCR), molecular docking, molecular dynamic (MD) simulation, electron microscope assay and immunofluorescence. Results In this study, we found that HD upregulated mRNA and protein level of TFEB and increased the distribution of TFEB in the nucleus, and the expressions of its target genes. HD also promoted the expressions of LC3BII/LC3BI, LAMP2, etc. , and promoted autophagy and the degradation of Aβ. HD reduced Aβ deposition in the head area of C. elegans and Aβ-induced paralysis. HD improved cognitive impairment and pathological changes in APP/PS1 mice by promoting autophagy and activating TFEB. And our results also showed that HD could strongly target PPARα. More importantly, these effects were reversed by treatment of MK-886, a selective PPARα antagonist. Conclusion Our present findings demonstrated that HD attenuated the pathology of AD through inducing autophagy and the underlying mechanism associated with PPARα/TFEB pathway.

CAS / MDL: 50892-23-4
研究领域: 神经科学 · 药理学 · 分子生物学 · 细胞生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ACS Omega · 2024 · IF 3.7

Synergistic Effect of Amino-Modified Co-MOF and APP on Improvement of the Fire Safety of the Rigid Polyurethane Foam

Zijin Chen,Shujie Yuan,Xiaoxue Xu

The combustion of rigid polyurethane foam (RPUF) generates significant amounts of toxic and high-temperature smoke, which restricts its application. Here, an amino-modified Co-MOF (NH2–Co-MOF) was synthesized and it was used in conjunction with ammonium polyphosphate (APP) to decrease the flammability of RPUF. We obtained the expected results: the fire safety of RPUF was greatly enhanced by the addition of NH2–Co-MOF and APP. Compared to neat RPUF, the peak heat release rate (pHRR) and total heat release (THR) values of N–C/A/RPUF decreased by 22.5 and 37.4%, respectively. Based on the analysis of combustion products of the gaseous and condensed phases, it can be seen that the synergistic use of NH2–Co-MOF with APP enhances the barrier effect, dilutes combustible gases, and quenches the combustion chain reaction.

CAS / MDL: 77-58-7
研究领域: 材料科学 · 燃烧学 · 化学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Drug Delivery and Translational Research · 2025 · IF 5.5

Low-intensity pulsed ultrasound enhances delivery of 30 nm Q10 for improving mental and memory disorder in APP/PS1 mice

Luo Qi,Ye Xuanjie,Xu Jinan,Sun Zihui,Wang Panpan,Chen Haishu,Gao Tingting,Deng Qiangfeng,Wang Ziwen,Wang Qin,Chen Xiaoxiao,Zhao Zhuowen,Wu Yiqing,Yang Chuang,Lyv Wanjia,Lyv Xingzhou,Li Ye,Zhao Hang,Jiang Ke,Gu Ziqi,Lin Jing,Sun Yu,Tan Tao,Xu Haiyun,Tong Zhiqian

Patients with Alzheimer's disease (AD) often experience mental and memory disorders with poor outcomes. Coenzyme Q10 can degrade formaldehyde (FA) and improve Alzheimer-related symptoms, but its ability to cross the blood–brain barrier (BBB) is limited. This study investigated whether low-intensity pulsed ultrasound (LIPUS) enhances 30 nm Q10 delivery and improve symptoms in AD model mice. Here, 30 nm Q10 was prepared by encapsulating Q10 in liposomes coupled with PEG, creating PEG-Q10@NPs under 30 nm in diameter. Wild-type mice and APPswe/PS1dE9 mice (a familial AD model) received 30 nm Q10 via intraperitoneal injection, or a combination of 30 nm Q10 and LIPUS (50 or 100 100 mW/cm 2 ). Then the mice’s anxiety-like and depression-like behaviors and biochemical index were evaluated. We found that the combination therapy of LIPUS at 100 mW/cm 2 and 30 nm Q10 was more effective in ameliorating psychosis in AD mice than individual treatments with 30 nm Q10. This effectiveness was linked to higher levels of brain Q10, serotonin (5-HT), and dopamine (DA), along with lower levels of FA and plaques. Especially, excessive FA directly inactivated 5-HT and DA in vitro. The enhanced cellular uptake of Q10 and improved BBB permeability facilitated by LIPUS were confirmed in both cultured cells and wild-type mice. Unexpectedly, LIPUS at the different intensity only partially alleviated anxiety and depression symptoms and memory deficits in AD mice. Hence, this combination therapy of LIPUS and 30 nm Q10 is an innovative strategy for ameliorating mental and cognitive disorders in AD. Graphic

CAS / MDL: 64-17-5
研究领域: 神经科学 · 药理学 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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MICROCHIMICA ACTA · 2021 ·Vol. 188 ·期 3 ·1-12 · IF 5.833

Ratiometric determination of Cr(VI) based on a dual-emission fluorescent nanoprobe using carbon quantum dots and a smartphone app

Yao Chixuan,Liu Qingrun,Zhao Ning,Liu Jing-Min,Fang Guozhen,Wang Shuo

A simple dual-colour fluorescent nanoprobe has been designed composed of blue and yellow emission carbon quantum dots (CQDs). This system is inexpensive and easy to operate and was successfully employed for on-site measurements based on a smartphone app. The designed nanoprobe exhibited increased selectivity for Cr(VI), leading to a double stable response of the two CQDs. The dual-emission nanoprobe showed blue-violet fluorescence upon UV irradiation, and the fluorescent emission peaks were located at 418 nm and 552 nm. The blue light emission of CQDs was quenched with increasing Cr(VI) concentration due to the inner filter effect, whereas the yellow light emission was enhanced due to the aggregation-induced emission effect. The different responses of the dual emissions to Cr(VI) resulted in a fluorescent colour variation, thus enabling facile macroscopic visualization. With a smartphone, the change in the fluorescence colour could be observed more apparently than that of a single fluorescence nanoprobe, and the response increased linearly so that the nanoprobe could be applied to instantaneous measurements. Furthermore, the dual-emission nanoprobe was successfully employed for analysing food and water samples. Accurate concentrations were obtained by constructing a calibration plot using a fluorescence spectrometer and a smartphone app; the recoveries were 81.6% to 107.7%, and the relative standard deviation was below 3.6%. Therefore, this smartphone-integrated dual-emission detection system is promising as a new portable method for the on-site measurement of Cr(VI) ions. Graphical abstract * Y-CQDs: yellow emission carbon quantum dots. B-CQDs: blue emission carbon quantum dots. B/Y-CQDs: a mixture of B-CQDs and Y-CQDs.

研究领域: 分析化学 · 环境科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY · 2019 ·Vol. 140 ·期 2 ·591-602 · IF 2.471

The thermal degradation property and flame-retardant mechanism of coated knitted cotton fabric with chitosan and APP by LBL assembly

Chen Hua-Qi,Xu Ying-Jun,Jiang Zhi-Ming,Jin Xing,Liu Yun,Zhang Lin,Zhang Chuan-Jie,Yan Chao

In order to improve the flame retardancy of knitted cotton fabrics and investigate the flame-retardant mechanism of the system formed by ammonium polyphosphate (APP) and chitosan (CS), flame-retardant knitted cotton fabrics coated with APP and CS were successfully prepared by layer by layer assembly. APP and CS formed the intumescent flame-retardant system, in which CS acted as the carbon source agent and APP acted as both the acid source and foaming agent. The surface micromorphologies before and after flaming of coated knitted cotton fabrics were exploited by scanning electron microscopy. The flammability, combustion behaviors, thermal degradation properties and flame-retardant mechanism of this system were investigated by vertical burning test, cone calorimetry test and thermogravimetric analysis coupled with Fourier transform infrared analysis in N 2 atmosphere, respectively. Compared with the control sample, the deposition of APP and CS endowed the knitted cotton fabrics with improved flame retardancy, higher residual chars, lower heat release rate and total heat release, while increased the smoke production. Improved flame-retardant behaviors are attributed to the thermally stable residual chars, more release of inflammable gases and potential free radical scavengers (PO·) in the gaseous products, named the combination of the condensed-phase and gaseous-phase flame-retardant mechanism.

CAS / MDL: 919-30-2
研究领域: 材料科学 · 纺织工程
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Cell Reports Physical Science · 2023 · IF 8.9

“Signal-on” electrochemical detection of BACE1 for early detection of Alzheimer’s disease

Zhu Chang,Bicheng Zhu,Jinjin Liu,Hui Dong,Yuanqiang Hao,Yanli Zhou,Jadranka Travas-Sejdic,Maotian Xu

Summary β-Secretase, the β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1), is a key hydrolytic enzyme in the pathway of β-amyloid (Aβ) production in the brain of a patient with Alzheimer’s disease (AD). BACE1 is considered a promising biomarker for the early detection of AD. A ferrocene probe (Fc-Probe) is synthesized, where the aldehyde group on the probe can specifically recognize the N terminus of the APP peptide fragment. The sensor’s design involves gold nanoparticles (AuNPs) on a glassy carbon electrode (GCE) surface, which allows for the binding of the APP peptide fragment. When BACE1 cleaves the acetylated APP peptide, the N terminus is exposed and triggers an electrochemical signal from the Fc-Probe. The developed sensor can detect BACE1 in a range of 0.02 to 50 U/mL, with a detection limit of 8.0 mU/mL. Such a BACE1 sensor provides a simple, sensitive, and low-cost detection methodology, enabling the “signal-on” detection of BACE1 activity.

研究领域: 生物化学 · 神经科学 · 分析化学 · 诊断学
✓ 已验证 DOI 高影响因子
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Bioengineering & Translational Medicine · 2022 ·Vol. 7 ·期 3 ·e10395 · IF 10.684

Targeted brain delivery of RVG29-modified rifampicin-loaded nanoparticles for Alzheimer's disease treatment and diagnosis

Ruiyi Zhou,Lihong Zhu,Zhaohao Zeng,Rixin Luo,Jiawei Zhang,Rui Guo,Lei Zhang,Qunying Zhang,Wei Bi

Alzheimer's disease (AD) is an aging-related neurodegenerative disease. The main pathological features of AD are β-amyloid protein (Aβ) deposition and tau protein hyperphosphorylation. Currently, there are no effective drugs for the etiological treatment of AD. Rifampicin (RIF) is a semi-synthetic broad-spectrum antibiotic with anti-β-amyloid deposition, anti-inflammatory, anti-apoptosis, and neuroprotective effects, but its application in AD treatment has been limited for its strong hydrophobicity, high toxicity, short half-life, low bioavailability, and blood–brain barrier hindrance. We designed a novel brain-targeted and MRI-characteristic nanomedicine via loading rabies virus protein 29 (RVG29), rifampicin, and Gd on poly ( l -lactide) nanoparticles (RIF@PLA-PEG-Gd/Mal-RVG29). The cytotoxicity assay demonstrated that RIF@PLA-PEG-Gd/Mal-RVG29 had favorable biocompatibility and security. Fluorescence imaging in vivo showed that PLA-PEG-Gd/Mal-RVG29 could deliver rifampicin into the brain by enhancing cellular uptake and brain targeting performance, leading to improvement of the bioavailability of rifampicin. In in vivo study, RIF@PLA-PEG-Gd/Mal-RVG29 improved the spatial learning and memory capability of APP/PS1 mice in the Morris water maze, as compared to rifampicin. Immunofluorescence, TEM, immunoblotting, and H&E staining revealed that RIF@PLA-PEG-Gd/Mal-RVG29 reduced Aβ deposition in hippocampal and cortex of APP/PS1 mice, improved the damage of synaptic ultrastructure, increased the expression level of PSD95 and SYP, as well as reduced the necrosis of neurons. These findings suggest that RIF@PLA-PEG-Gd/Mal-RVG29 may be an effective strategy for the treatment of AD.

CAS / MDL: 67-43-6
研究领域: 神经科学 · 药学 · 纳米技术 · 药物递送系统
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Redox Biology · 2023 · IF 11.4

Lead aggravates Alzheimer's disease pathology via mitochondrial copper accumulation regulated by COX17

Dingbang Huang,Lixuan Chen,Qiuyi Ji,Yang Xiang,Qin Zhou,Kaiju Chen,Xiaoshun Zhang,Fei Zou,Xingmei Zhang,Zaihua Zhao,Tao Wang,Gang Zheng,Xiaojing Meng

Alzheimer's disease (AD) is a common neurodegenerative disease that is associated with multiple environmental risk factors, including heavy metals. Lead (Pb) is a heavy metal contaminant, which is closely related to the incidence of AD. However, the research on the role of microglia in Pb-induced AD-like pathology is limited. To determine the mechanism by which Pb exposure aggravates AD progression and the role of microglial activation, we exposed APP/PS1 mice and Aβ 1-42 -treated BV-2 cells to Pb. Our results suggested that chronic Pb exposure exacerbated learning and memory impairments in APP/PS1 mice. Pb exposure increased the activation of microglia in the hippocampus of APP/PS1 mice, which was associated with increased deposition of Aβ 1-42 , and induced hippocampal neuron damage. Pb exposure upregulated copper transporter 1 (CTR1) and downregulated copper P-type ATPase transporter (ATP7A) in the hippocampus of APP/PS1 mice and Aβ 1-42 -treated BV-2 cells. Moreover, Pb enhanced mitochondrial translocation of the mitochondrial copper transporter COX17, leading to an increase in mitochondrial copper concentration and mitochondrial damage. This could be reversed by copper-chelating agents or by inhibiting the mitochondrial translocation of COX17. The increased mitochondrial copper concentration caused by increased mitochondrial translocation of COX17 after Pb exposure may be related to the enhanced mitochondrial import pathway of AIF/CHCHD4. These results indicate that Pb induces the activation of microglia by increasing the concentration of copper in the mitochondria of microglia, and microglia release inflammatory factors to promote neuroinflammation, thus aggravating the pathology of AD. The present study provides new ideas for the prevention of Pb-induced AD.

研究领域: 神经科学 · 毒理学 · 神经退行性疾病
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF ETHNOPHARMACOLOGY · 2019 · IF 3.414

Notopterygium incisum extract (NRE) rescues cognitive deficits in APP/PS1 Alzhneimer's disease mice by attenuating amyloid-beta, tau, and neuroinflammation pathology

Xiao-wen Jiang,Wen-wu Liu,Yu-ting Wu,Qiong Wu,Hong-yuan Lu,Zi-hua Xu,Hui-yuan Gao,Qing-chun Zhao

Ethnopharmacological relevance Alzheimer's disease (AD) is a frequently occurring disease of the elderly, and “deficiency” is the root of AD. Most famous experts of traditional Chinese medicine believe that the disease is based on deficiency, and the deficiency of kidney essence is the basis. Notopterygium incisum  (Qiang huo) is beneficial to bladder, liver, and kidneys. It is used to treat liver and kidney deficiency, language difficulties, and mental coma. Qiang huo yu feng tang has been used to treat liver and kidney deficiency, unclear language and mental paralysis in many traditional Chinese medicine books and records. In modern times, it has been used to treat AD and exhibited favourable efficacy. Aim of the study This study attempts to investigate the effects of furocoumarins from Notopterygium incisum (NRE) on the Aβ cascade, tau pathology and inflammatory pathology of AD. Materials and methods In this study, we reported a detailed protocol for stabilizing HEK APPswe293T cells with lentivirus for the first time. This cell line can secrete high concentration of Aβ. In addition, we treated N2a cells with AKT/PKC specific inhibitors (wortmannin/GF-109203X) and established a tau pathological cell model (AKT/PKC N2a) by activating GSK3β and triggering hyperphosphorylation of tau. The Aβ levels and the expression of phosphorylated tau were detected by ELISA and Western blot . The cognitive ability of NRE on APP/PS1 mice was detected using a Morris water maze (MWM) assay and Aβ contents were also evaluated. Results In HEK APPswe293T cells, NRE (10, 20, 40 μg/mL) significantly inhibited the secretion and production of Aβ in dose dependent manner. In addition, NRE also suppressed the expression of phosphorylated tau in wortmannin/GF-109203X treated N2a cells. Furthermore, NRE ameliorated the cognitive impairment of APP/PS1 mice, and the contents of Aβ, IL-1β and TNF-α were significantly depressed in hippocampus and cortex. Conclusion In conclusion, our results demonstrated that NRE has a potential anti-AD effect via the inhibition of the Aβ cascade, tau pathology and neuroinflammation in vitro and in vivo.

研究领域: 药理学 · 神经科学 · 传统中医 · 分子生物学
✓ 已验证 DOI PubMed 高影响因子
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ACS Applied Polymer Materials · 2026 · IF 5.2

Flame-Retardant and Electromagnetic Interference Shielding Hierarchical Composites by Interfacial Integration of TPU/APP@ZrCu-MOF/SCF and Functionalized Polyester Fabric

Yongqian Shi,Jinke Wu,Libi Fu,Haoxin Niu,Can Liao,Fuqiang Yang,Longcheng Tang,Wei Zhang,Ting Qiu

Developing flexible textiles with effective electromagnetic interference (EMI) shielding is highly attractive for wearable devices and electronic protection applications. However, achieving both excellent flame retardancy and EMI shielding performance in flexible textile systems remains a great challenge due to the inherent flammability of textiles and the poor durability of modified coatings. In this work, thermoplastic polyurethane (TPU) incorporating a metal–organic framework-encapsulated ammonium polyphosphate (APP@ZrCu-MOF) and short carbon fibers serves as the outer layers. The polyester (PET) fabric modified by the alternating deposition of MXene and reduced graphene oxide is used as the intermediate layer. These components are assembled into a flexible multilayer composite by employing an air-assisted hot-pressing technique. Among the prepared composites, TMS4P3 exhibits markedly improved fire safety, which has a high limiting oxygen index of 29.5%. Compared with the unmodified PET/TPU composite, the peak heat release rate, total heat release, peak smoke production rate, and total smoke release of TMS4P3 decrease by 44.9, 41.4, 60.0, and 42.7%, respectively. In addition, TMS4P3 exhibits average EMI shielding effectiveness values of 30.4 and 31.9 dB in the X and Ku bands, respectively. This study provides a promising approach for broadening the applications of PET fabrics and TPU and offers an effective strategy for the fabrication of multifunctional flexible composites.

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Pharmaceutics · 2025 ·Vol. 17 ·期 2 ·177 · IF 5.5

Advanced Nanopharmaceutical Intervention for the Reduction of Inflammatory Responses and the Enhancement of Behavioral Outcomes in APP/PS1 Transgenic Mouse Models

Jun Li,Dongqing Huang,Wanchen Liao,Yulin Wang,Yibiao Liu,Ping Luan

Background: The excessive accumulation of Aβ plays a critical role in the development of Alzheimer’s disease. However, the therapeutic potential of drugs like curcumin is often limited by low biocompatibility and BBB permeability. In this study, we developed a nanomaterial, BP-PEG-Tar@Cur, which was designed to enhance the biocompatibility of (curcumin) Cur, target Aβ, and augment BBB permeability through near-infrared (NIR) photothermal effects.Methods: Soluble Aβ, ThT fluorescence, and Aβ depolymerization fluorescence experiments were conducted to evaluate the ability of BP-PEG-Tar@Cur to inhibit Aβ aggregation and dissociate Aβ fibrils. Cell uptake assays were performed to confirm the targeting ability of BP-PEG-Tar@Cur towards Aβ. In vitro mitochondrial ROS clearance and in vivo detection of inflammatory factors were used to assess the anti-inflammatory and antioxidant properties of the nanodrug. Water maze behavioral experiments were conducted to evaluate the effect of BP-PEG-Tar@Cur on spatial memory, learning ability, and behavioral disorders in AD mice.Results: The nanodrug effectively inhibited Aβ aggregation and dissociated Aβ fibrils in vitro. BP-PEG-Tar@Cur demonstrated efficiency in curbing ROS overproduction in mitochondria and dampening the activation of microglia and astrocytes triggered by Aβ aggregation. Water maze behavioral experiments revealed that BP-PEG-Tar@Cur enhanced spatial memory, learning ability, and alleviated behavioral disorders in AD mice.Conclusions: Collectively, these findings demonstrate that BP-PEG-Tar@Cur has the potential to be an effective targeted drug for inhibiting Aβ aggregation and improving cognitive impairment in AD mice.

研究领域: 神经科学 · 药理学 · 纳米医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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POLYMERS FOR ADVANCED TECHNOLOGIES · 2025 ·Vol. 36 ·期 3 ·e70151 · IF 3.4

Polydopamine by APP Template With SiC and Silane Hybrid Coating One-Step Co-Deposited UHMWPE Fibers and Corona Reinforced Epoxy Composites

Kaijun Yu,Fanmin Kong,Guodong Jiang

Due to low surface energy, high chemical inertness, and poor interfacial properties of ultra-high molecular weight polyethylene (UHMWPE) fibers, it was difficult to achieve good adhesion with the matrix interface. Surface coating modification based on polydopamine (PDA) was widely applied to build high-performance and specifically functional surface modifications. In order to improve the interfacial adhesion between UHMWPE fibers and epoxy resin, this study used a one-step process with ammonium polyphosphate (APP) as a template to deposit a hybrid coating of PDA and N -(2-aminoethyl)-3-aminopropyltrimethoxysilane (KH792)/3-aminopropyltriethoxysilane (KH550)/nano silicon carbide (SiC) on the surface of UHMWPE fibers. Additionally, corona treatment was applied to increase oxygen-containing functional groups on fibers while also improving the processing technology of composites. Due to the polymerization of PDA, the deposition of SiC, and the hydrolysis-condensation of silanes, the nanohybrid coating can provide rich connection points and nanoparticles for hybrid fabrics without affecting the inherent strength of fibers. Corona improved surface roughness, and hybrid coatings enhanced the interfacial adhesion between the resin matrix and fibers. The UHMWPE fiber/epoxy composite material after improved composite technology exhibited excellent mechanical properties. Compared with untreated composite laminates, interfacial shear strength (IFSS) was increased by 88.81%, flexural strength was enhanced by 87.89%, impact strength was improved by 64.39%, and tensile strength was raised by 26.58%. The study showed that the nanohybrid coating co-deposited with PDA and corona enhanced the interfacial bond between epoxy resin and UHMWPE fibers, increased relative friction at the fracture interface, and improved load transfer between UHMWPE fibers and matrix.

CAS / MDL: 7631-86-9 77-86-1
研究领域: 材料科学 · 表面化学 · 复合材料工程
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