Nature Communications
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2026
·
IF 18.1
Ye Shiju,Zhao Yanbo,Tu Hanxiao,Han Xue,Liu Tong,Gong Yingchao,Lu Jiangting,Jin Tingting,Luo Wu,Qu Xuefeng,Lai Dongwu,Fu Guosheng,Liang Guang
Hypertensive heart failure highlights an urgent need for effective therapeutic strategies. Protein kinases regulate multiple pathways in cardiac pathophysiology and may provide promising therapeutic targets. Here, we identified a Cyclin-dependent kinase, CDK9, promoting inflammation and cardiac remodeling in terminally differentiated cardiomyocytes. Firstly, kinase enrichment analysis and experimental evidence revealed CDK9 phosphorylation at Thr-186 in both human and mouse hypertrophic heart tissues. CDK9 loss of function via T186A mutation in cardiomyocytes attenuated Ang II-induced heart remodeling and NF-κB-mediated inflammation, whereas CDK9 overactivation by T186E mutation induces. This regulatory function of CDK9 in cardiac remodeling is cell cycle-independent. Further studies demonstrate that the kinase domain of CDK9 directly binds to NF-κB P65 protein, which leads to the CDK9/P65 complex nuclear translocation, P65 phosphorylation, and transcription of inflammatory and hypertrophic genes in cardiomyocytes. This process requires CDK9 Thr-186 phosphorylation and Cyclin T1 presence, but is independent on IKKβ and CDK9-RNAPII pathways. Pharmacological inhibition of CDK9 phosphorylation significantly attenuated Ang II-induced cardiac inflammation, remodeling, and dysfunction in mice. Collectively, Ang II-activated CDK9 directly binds to and phosphorylates P65 to drive cardiac inflammation and remodeling. This study identifies CDK9 as a potential target in heart failure therapeutics.
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EUROPEAN POLYMER JOURNAL
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2025
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IF 6.3
Lifan Li,Yanhao Chen,Jiapeng Ye,Deming Zhou,Lingxiao Jing,Zaixing Zhang,Kun Luan,Junjuan Huang,Xin Tang,Tonghua Zhang
With growing environmental awareness and a focus on sustainable development, the recycling and utilization of natural fibers and renewable resources have become critical issues in recent years. Windmill palm fibers (WPFs) are composed of cellulose microfibrils within a matrix of hemicellulose and lignin, which can harbor bacteria and pose a health risk to the wearer in humid environments. They are also highly flammable resulting in safety hazards during industrial production and use. In this study, we used a click chemistry strategy to conduct a surface modification on WPFs. The treated fibers are fire redundant and antibacterial. The treatment includes two steps: first step is delignification and hemicellulose removal followed by silanes treatment; second step is the click chemical reaction with 6-(((1H-1,2,4-triazol-3-yl)amino)(4-(allyloxy)phenyl)methyl)dibenzo[c,e][ 1 , 2 ]oxaphosphinine 6-oxide (TAPM-DOPO). The burn tests have proved that TAPM-DOPO plays an important role in condensed phase in flame retardancy of WPFs. The sustained burn time was reduced by 71 s. Furthermore, it exhibited excellent bactericidal activity against both E. coli and S. aureus , the inhibition rate reached 99.9% after chlorination. The technology in this study demonstrates a feasible production of the flame retardant and antibacterial WPFs suitable to large-volume manufacturing of textile product.
研究领域:
材料科学
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纺织工程
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生物技术
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EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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2022
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IF 7.088
Li-An Shen,Xinyan Peng,Ya Bao,Chenglong Liu,Hao Zhang,Jianqi Li,Di Zhu,Qingwei Zhang
The β -catenin/B-cell lymphoma 9 (BCL9) protein-protein interaction (PPI) is a potential target for the suppression of hyperactive Wnt/ β -catenin signaling that is vigorously involved in cancer initiation and development. Herein, we first described quercetin and its derivatives had potential inhibitory effects on β -catenin/BCL9 PPI. The most potent compound, quercetin-3′- O -(4-methylpiperazine-1-yl) propyl ( C1 ), directly binded with β -catenin and disrupted the β -catenin/BCL9 interaction in both the protein level and the cellular context. C1 also effectively inhibited colorectal cancer in vitro and showed better selectivity in inhibiting hyperactive Wnt/ β -catenin signaling cells like CT26 and HCT116. And we further confirmed that C1 could inhibit CT26 tumor growth in vivo and regulate the tumor immune microenvironment. This study provides a good chemical probe to explore β-catenin-related biology and a drug-like quercetin derivative as novel β -catenin/BCL9 PPI inhibitors for further drug development.
研究领域:
肿瘤学
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分子生物学
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药物研发
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ANALYST
·
2023
·Vol. 148
·期 15
·3518-3523
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IF 4.2
Hao Gu,Guoxin Dai,Zhongqiu Teng,Lina Geng,Wei Xu
Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a universal method for the quantitative analysis of small molecular drugs in therapeutic drug monitoring (TDM). Alternatively, liquid chromatography-miniature mass spectrometry (LC-Mini MS) is a simple operating technique for quantitative analysis. However, the wide chromatographic peaks and long retention times of TDM samples using the LC-Mini MS system deteriorated the accuracy and efficiency of quantitative analysis. Here, an optimized electrospray ionization (ESI) interface setup with a splitter valve and a capillary needle (I.D. 30 μm and O.D. 150 μm) of the LC-Mini MS system was acquired. The chromatographic peaks were narrower and smoother and the retention time was shorter for TDM compounds. Furthermore, a quantitative analysis method for risperidone and the active metabolite 9-hydroxyrisperidone in plasma was developed based on this optimal LC-Mini MS setup. The results showed that the calibration curves of risperidone and 9-hydroxyrisperidone had good linear ranges of 2–100 ng mL−1 (R2 = 0.9931) and 2–100 ng mL−1 (R2 = 0.9915), respectively. Finally, the matrix effects, recoveries and stability of risperidone and 9-hydroxyrisperidone samples were analyzed. The results satisfied the requirements of quantitative validation in routine TDM procedures.
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JOURNAL OF CONTROLLED RELEASE
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2018
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IF 7.877
Jia Song,Chuchu Lin,Xuan Yang,Yanqi Xie,Ping Hu,Huatian Li,Wenbo Zhu,Haiyan Hu
Mitochondria are ideal anti-tumor target due to mitochondria's central regulation role in cell apoptosis and tumor resistance to apoptosis. There are several challenges for mitochondrial targeting drug delivery, including complex multistep preparations, low drug- loading and systemic toxicity from the carriers. To address these issues, we firstly constructed mitochondria-targeting nanodrugs self-assembled from 9-O-octadecyl substituted berberine derivative (BD) using simple nano-precipitation approach. BD-based nanodrugs were modified by DSPE-PEG2000 (distearylphosphatidylethanolamine- methoxypolyethylene glycol 2000) to increase stability. Negatively charged hyaluronic acid (HA) was further coated to conceal positive charges and achieve tumor targeting. PEG and HA dually modified BD NDs (HA/PEG/BD NDs) were prepared with surface charge of −25.8 mV and high drug loading >70%. The degradation of HA by hyaluronidase (HAase) at tumor tissue allowed the exposure of the positively charged PEG/BD NDs to the cells, which is beneficial for cell uptake and further lysosome escape and mitochondrial targeting. Then, HA/PEG/BD NDs were investigated to induce apoptosis through dissipating mitochondria membrane potential, releasing cytochrome C , increasing the activities of caspase 9/3, activating the pro-apoptotic Bax, suppressing the anti-apoptotic Bcl-2 and upregulating ROS levels. In the A549 xenografted tumor model, HA/PEG/BD NDs exhibited obvious tumor cell mitochondrial targeting and significant anti-tumor efficacy. Overall, comparing to conventional nanoparticles , mitochondrial targeting HA/PEG/BD NDs provide a new strategy for cancer treatment with enhanced drug-loading, relatively simplified preparation processes and reduced carrier toxicities.
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CERAMICS INTERNATIONAL
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2019
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IF 3.45
Chunfang Xing,Yunhui Zhang,Bingjing Tao,Haitao Wu,YuanYuan Zhou
Low-firing La 2 Zr 3 (MoO 4 ) 9 (LZM) ceramics were prepared using the reaction-sintering (RS) route for the first time. The crystal structure, sintering characteristics, microstructure and microwave dielectric properties of LZM samples were explored scientifically. A single phase, with trigonal structure in R-3c space group, was formed at 600–800 °C. Dense sample with high relative density (>92 %) and homogeneous microstructure was obtained at 650 °C. Subsequently, EDS analysis revealed that the composition was corresponding to theoretical stoichiometric ratio of chemical formula. The chemical bonds theory of complex crystals and far-infrared spectra analysis were employed to investigate the structure-property relations of LZM samples in detail. Optimum microwave dielectric properties with a dielectric constant ( ε r ) of 10.17, a quality factor ( Q·f ) of 51,578 GHz and a temperature coefficient of resonant frequency ( τ f ) of -29.55 ppm/°C were achieved in LZM sample prepared by the RS process sintered at 650 °C.
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Brain Sciences
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2022
·Vol. 12
·期 5
·571
·
IF 3.333
Chao Song,Chao Gao,Zhenxin Wang
(1) Background: Chemotherapy-induced cognitive impairment (CICI) is often observed in cancer patients and impairs their life quality. Grape-seed-orientated procyanidin has been shown to have anti-inflammatory and neuroprotective effects, yet its effects in preventing CICI have not been investigated. (2) Method: Adult male mice received 2.3 mg/kg cisplatin or saline injections for three cycles consisting of five daily injections followed by 5 days of rest. Procyanidin or saline was administered 1 h prior to cisplatin treatment. Cognitive testing, gelatin zymography, and blood–brain-barrier (BBB) penetration tests were performed after treatment cessation. RAW264.7 cells were treated by stimulated supernatant of SHSY5Y cells. In addition, high-mobility group protein B1 (HMGB1) expression and MMP-9 activity were tested. (3) Results: Repeated cisplatin treatment increased BBB penetration, MMP-9 activity, impaired performance in contextual fear conditioning, and novel object recognition tasks. The knockout of MMP-9 rescues cognitive impairment and cisplatin-induced upregulation of HMGB1 in SHSY5Y cells. HMGB1/TLR4/IP3K/AKT signaling contributes to the increased MMP-9 activity in RAW264.7 cells. Procyanidin treatment attenuates MMP-9 activity, BBB damage, and CICI. (4) Conclusions: The results indicated that MMP-9 activation and BBB disruption is involved in CICI. Procyanidin may effectively alleviate the harmful effects of cisplatin.Keywords:cisplatin;chemotherapy;MMP-9;RAW264.7 cells;procyanidin;blood–brain barrier (BBB);chemotherapy-induced cognitive impairment (CICI)
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APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
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2022
·Vol. 194
·期 7
·3044-3065
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IF 3.094
Qiu Ren,Dai Jianmin,Meng Lingqiang,Gao Hongmin,Wu Mengdie,Qi Feifan,Feng Jing,Pan Hongzhi
Porous carbon sphere materials have a large variety of applications in several fields due to the large surface area, adaptable porosity, and good conductivity they possess. Obtaining a steady carbon sphere using the green synthesis method remains a significant challenge. In this experiment, covalent organic frameworks (COFs) were used as a precursor and Fe 3 O 4 NPs were integrated into the precursor in order to synthesize a porous carbon sphere material using the one-step pyrolysis method. COFs have an ordered porous structure, perpetual porosity, large surface area, and low density and display good environmental tolerance. These properties make them an excellent precursor for synthesizing porous carbon sphere, which maintains good morphology at high temperatures, and it is not involved in the removal of dangerous reagent and small size restrictions during the synthesis process. In addition to the formation of a porous carbon sphere, transition metal carbon material that contains N element can be an active catalyst. The composites exhibit better activity when Fe is doped into carbon materials containing N element than that of other doped transition metals including Mn and Co. In this situation, the integration of Fe 3 O 4 NPs and N element in the COF precursor exposed the active sites of the composites and the two substances synergistically improved the electrocatalytic properties, and the composites were named Fe 3 O 4 @NPCS. The constructed Fe 3 O 4 @NPCS/GCE immunosensor was applied as a means of detecting CA19-9 antigen and presented a wide linear range from 0.00001 to 10 U/mL with a low detection limit of 2.429 μU/mL (S/N = 3). In addition, the prepared immunosensor was utilized for detecting CA19-9 antigen in the real human serum, and the recovery rates were in the range from 95.24% to 106.38%. Therefore, a porous carbon sphere prepared by COFs as a precursor can be applied for the detection of CA19-9 antigen in real samples, which could be an excellent strategy for CA19-9 antigen detection and could potentially promote the development of COF materials in various electrochemical fields.
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Catalysts
·
2022
·Vol. 12
·期 7
·688
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IF 4.501
Guolei Xiao,Weibin Chen,Yaming Cai,Shifan Zhang,Di Wang,Dandan Cai
Layered double hydroxide (LDH) has emerged as a promising electrocatalyst; however, the synthetic method usually requires high temperature and high pressure, and sulfate-intercalated LDH is rarely reported. Herein, the sulfate-intercalated CoFe LDH nanosheets were successfully fabricated at ambient temperature via a facile strategy, using two-dimensional ZIF-9(III) as a template and FeSO4as both etchant and iron source. When the as-prepared sulfate-intercalated CoFe LDH acts as an electrocatalyst, it presents superior electrocatalytic performance for the oxygen evolution reaction (OER), requiring low overpotential (η@10 mA cm−2= 218 mV) with a small Tafel slope of 59.9 mV dec−1in 1.0 M KOH, which compares favorably with commercial RuO2and most reported transition-metal electrocatalysts. The high catalytic activity of CoFe LDH might be ascribed to the large interlayer space distance originating from special SO42−ions and the strong synergistic effects between Fe and Co. This work provides a novel and feasible approach to designing highly efficient electrocatalysts based on advanced LDH materials for OER.Keywords:facile synthesis;sulfate-intercalated CoFe LDH;two-dimensional ZIF-9(III);electrocatalysts;oxygen evolution reaction
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ANALYST
·
2021
·Vol. 146
·期 22
·6893-6901
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IF 4.616
Hui Chen,Longqiang Xing,Huiru Guo,Caixia Luo,Xuedian Zhang
A graphene oxide (GO)-based nanocarrier that imparts tumor-selective delivery of dual-drug with enhanced therapeutic index, is introduced. GO is conjugated with Au@Ag and Fe3O4 nanoparticles, which facilitates it with SERS tracking and magnetic targeting abilities, followed by the covalent binding of the anti-HER2 antibody, thus allowing it to both actively and passively target SKBR3 cells, human breast cancer cells expressed with HER2. Intracellular drug delivery behaviors are probed using SERS spectroscopy in a spatiotemporal manner, which demonstrates that nanocarriers are internalized into the lysosomes and release the drug in response to the acidic microenvironment. The nanocarriers loaded with dual-drug possess increased cancer cytotoxicity in comparison to those loaded with a single drug. Attractively, the enhanced cytotoxicity against cancer cells is achieved with relatively low concentrations of the drug, which is demonstrated to be involved in the drug adsorption status. These results may give us the new prospects to design GO-based delivery systems with rational drug dosages, thus achieving optimal therapeutic response of the multi-drug with increased tumor selectivity and reduced side effects.
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Oncology Letters
·
2021
·Vol. 21
·期 3
·1-1
·
IF 2.967
Huizhe Zheng,Bin Yan,Qi Wu,Jingli Zhang
Chemotherapy drug 5‑fluorouracil (5‑FU) is the first‑line treatment for colorectal cancer (CRC); however, 5‑FU resistance decreases CRC therapeutic efficiency. A previous study revealed that microRNA (miR)‑9‑5p serves an antitumor effect in CRC. However, the effect of miR‑9‑5p in CRC chemoresistance remains unknown. In the present study, two CRC cell lines, including HT‑29 and HCT‑116 cells, were used to investigate the impact of miR‑9‑5p in overcoming 5‑FU resistance. The results revealed that treatment with 5‑FU decreased CRC cell viability and upregulated miR‑9‑5p expression in both CRC cells. Knockdown of miR‑9‑5p decreased HCT‑116 cell sensitivity to 5‑FU and inhibited apoptosis. By contrast, miR‑9‑5p overexpression enhanced the sensitivity of HT‑29 cells to 5‑FU and induced apoptosis. Additionally, it was confirmed that miR‑9‑5p directly targeted high mobility group A2 (HMGA2). HMGA2 overexpression reversed miR‑9‑5p‑induced HT‑29 apoptosis. The present study indicated that miR‑9‑5p enhanced the sensitivity of CRC cells to 5‑FU via downregulating HMGA2 expression.
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JOURNAL OF MATERIALS SCIENCE-MATERIALS IN ELECTRONICS
·
2020
·Vol. 31
·期 15
·12620-12627
·
IF 2.22
Ma Xiaomeng,Li Congyi,Fan Zijia,Wu Haitao,Zhang Yuping,Zhang Zhiliang
Low temperature-sintered ceramics Nd 2 Zr 3 (MoO 4 ) 9 were successfully prepared via reaction-sintering method. The sintering behavior, microwave dielectric properties, crystal structure, and microstructure were analyzed systematically. XRD and Rietveld refinement results revealed that all samples formed a pure trigonal structure phase with the space group of R-3c. Density determination showed that ceramics possessed the highest relative density when sintered at 800 °C for 6 h. SEM image further confirmed that ceramics possessed dense and homogeneous microstructure at the optimum sintering temperature 800 °C. Far infrared spectra analysis showed the structural phonon oscillation at infrared region played an important role in polarization. Nd 2 Zr 3 (MoO 4 ) 9 ceramics obtained the optimum microwave dielectric properties of ε r = 10.01, Q × f = 55,923 GHz, τ f = − 13.81 ppm/ °C when sintered at 800 °C for 6 h.
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危险品化学品经营许可证（带存储）