CELL RESEARCH
·
2024
·
IF 28.1
Feng Ran,Liu Feng,Li Ruofei,Zhou Zhifen,Lin Zhuoheng,Lin Song,Deng Shengcheng,Li Yingying,Nong Baoting,Xia Ying,Li Zhiyi,Zhong Xiaoqin,Yang Shuhan,Wan Gang,Ma Wenbin,Wu Su,Songyang Zhou
Rheb is a small G protein that functions as the direct activator of the mechanistic target of rapamycin complex 1 (mTORC1) to coordinate signaling cascades in response to nutrients and growth factors. Despite extensive studies, the guanine nucleotide exchange factor (GEF) that directly activates Rheb remains unclear, at least in part due to the dynamic and transient nature of protein–protein interactions (PPIs) that are the hallmarks of signal transduction. Here, we report the development of a rapid and robust proximity labeling system named Pyrococcus horikoshii biotin protein ligase ( Ph BPL)-assisted biotin identification (PhastID) and detail the insulin-stimulated changes in Rheb-proximity protein networks that were identified using PhastID. In particular, we found that the lysosomal V-ATPase subunit ATP6AP1 could dynamically interact with Rheb. ATP6AP1 could directly bind to Rheb through its last 12 amino acids and utilizes a tri-aspartate motif in its highly conserved C-tail to enhance Rheb GTP loading. In fact, targeting the ATP6AP1 C-tail could block Rheb activation and inhibit cancer cell proliferation and migration. Our findings highlight the versatility of PhastID in mapping transient PPIs in live cells, reveal ATP6AP1’s role as an unconventional GEF for Rheb, and underscore the importance of ATP6AP1 in integrating mTORC1 activation signals through Rheb, filling in the missing link in Rheb/mTORC1 activation.
研究领域:
分子生物学
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细胞信号传导
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癌症生物学
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蛋白质组学
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DOI
高影响因子
Probiotics and Antimicrobial Proteins
·
2022
·Vol. 15
·期 2
·400-410
·
IF 5.265
Huang Yu-Ping,Shi Jie-Yan,Luo Si-Chen,Xu Shao-Yan,Zhang Jia-Dong,Molnár István,Yang Qiong-Qiong,Zhang Bo-Bo
Bacterial vaginosis (BV) is a common vaginal disease associated with abnormal changes in the vaginal microbiome. Our previous study found that Lactobacillus rhamnosus has a good therapeutic effect on bacterial vaginosis by inhibiting the most prominent bacterium associated with BV, Gardnerella vaginalis . In this study, we show that acetic acid and lactic acid are the main substances in the cell-free supernatant (CFS) of L. rhamnosus that inhibit the growth of G. vaginalis. Further study on the mechanism showed that acetic acid and lactic acid alter the morphology of the G. vaginalis cells, eventually causing the cells to shrink or burst, resulting in exudation of their intracellular contents. In addition, these two organic acids also dissipate the membrane potential of bacterial cells, affecting their synthesis of ATP. A reduced activity of the Na + /K + -ATPase leads to abnormal ATP metabolism, and ultimately inhibits the growth and reproduction of G. vaginalis . Our study provides valuable information for the widespread application of L. rhamnosus in the treatment of bacterial vaginosis.
研究领域:
微生物学
·
传染病
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女性健康
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DOI
PubMed
高影响因子
RSC Advances
·
2017
·Vol. 7
·期 41
·25746-25752
·
IF 3.108
Li Xu,Qin Xu,Xiaoyu Guo,Ye Ying,Yiping Wu,Ying Wen,Haifeng Yang
Alumina is widely recognized as chemically inert, and resistant to oxidation and high temperature. In this study, Au/Al2O3 nanocomposites (NCs) were prepared by a facile method and were used as a surface enhanced Raman scattering (SERS) substrate for detection of adenosine triphosphate (ATP). This Au/Al2O3-based SERS substrate demonstrated good sensitivity with the lowest detectable concentration of 5 × 10−9 M for ATP and a good linear relationship ranging from 5 × 10−5 to 5 × 10−9 M. The strategy of improvement of SERS detection sensitivity for ATP was based on the consideration of ATP captured by such SERS substrate via chelation of aluminum and phosphates, which was validated by X-ray photoelectron spectroscopy. In addition, alumina as a supporting material could be expected to prolong the stability of such a SERS substrate.
研究领域:
纳米技术
·
分析化学
·
材料科学
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DOI
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Ning Ding,Bo Zhang,Imran Mahmood Khan,Mingwei Qin,Shuo Qi,Xiaoze Dong,Zhouping Wang,Junsong Yang
The prevalence of pathogenic bacterial infections with high morbidity and mortality poses a widespread challenge to the healthcare system. Therefore, it is imperative to develop nanoformulations capable of adaptively releasing antimicrobial factors and demonstrating multimodal synergistic antimicrobial activity. Herein, an NIR-activated multifunctional synergistic antimicrobial nanospray MXene/ZIF-90@ICG was prepared by incorporating ZIF-90@ICG nanoparticles onto MXene-NH2 nanosheets. MXene/ZIF-90@ICG can on-demand release the antimicrobial factors MXenes, ICG, and Zn2+ in response to variations in pH and ATP levels within the bacterial infection microenvironment. Under NIR radiation, the combination of MXenes, Zn2+, and ICG generated a significant amount of ROS and elevated heat, thereby enhancing the antimicrobial efficacy of PDT and PTT. Meanwhile, NIR excitation could accelerate the further release of ICG and Zn2+, realizing the multimodal synergistic antibacterial effect of PDT/PTT/Zn2+. Notably, introducing MXenes improved the dispersion of the synthesized antimicrobial nanoparticles in aqueous solution, rendering MXene/ZIF-90@ICG a candidate for application as a nanospray. Importantly, MXene/ZIF-90@ICG demonstrated antimicrobial activity and accelerated wound healing in the constructed in vivo subcutaneous Staphylococcus aureus infection model with NIR activation, maintaining a favorable biosafety level. Therefore, MXene/ZIF-90@ICG holds promise as an innovative nanospray for adaptive multimodal synergistic and efficient antibacterial applications with NIR activation.
研究领域:
纳米医学
·
生物材料
·
感染生物学
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2021
·Vol. 19
·期 1
·1-19
·
IF 10.435
Guo Weihong,Chen Zhian,Feng Xiaoli,Shen Guodong,Huang Huilin,Liang Yanrui,Zhao Bingxia,Li Guoxin,Hu Yanfeng
Background Paclitaxel (PTX) has been suggested to be a promising front-line drug for gastric cancer (GC), while P-glycoprotein (P-gp) could lead to drug resistance by pumping PTX out of GC cells. Consequently, it might be a hopeful way to combat drug resistance by inhibiting the out-pumping function of P-gp.Results In this study, we developed a drug delivery system incorporating PTX onto polyethylene glycol (PEG)-modified and oxidized sodium alginate (OSA)-functionalized graphene oxide (GO) nanosheets (NSs), called PTX@GO-PEG-OSA. Owing to pH/thermal-sensitive drug release properties, PTX@GO-PEG-OSA could induced more obvious antitumor effects on GC, compared to free PTX. With near infrared (NIR)-irradiation, PTX@GO-PEG-OSA could generate excessive reactive oxygen species (ROS), attack mitochondrial respiratory chain complex enzyme, reduce adenosine-triphosphate (ATP) supplement for P-gp, and effectively inhibit P-gp’s efflux pump function. Since that, PTX@GO-PEG-OSA achieved better therapeutic effect on PTX-resistant GC without evident toxicity.Conclusion sIn conclusion, PTX@GO-PEG-OSA could serve as a desirable strategy to reverse PTX’s resistance, combined with chemo/photothermal/photodynamic therapy.Graphic Abstract
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DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2021
·
IF 4.098
Jing Xu,Huanhuan Li,Selva Sharma Arumugam,Yawen Rong,Pingyue Wang,Quansheng Chen
Adenosine triphosphate (ATP) is an energy molecule of significant importance, and, the monitoring of ATP in living cells is considerable for the clinical diagnosis of many related diseases, including cancer. Upconversion nanoparticles (UCNPs) have recently been attracting widespread interest in biomedical applications due to their chemical and thermal stability, high sensitivity, good biocompatibility, and excellent tissue penetration. Herein, a Cy3-aptamer-cDNA- UCNPs nanosensor was synthesized, based on the luminescence resonance energy transfer (LRET) between UCNPs and Cy3 for monitoring ATP in living cells. It showed a selective sensing ability for ATP levels by changes of fluorescence intensity of UNCPs at 536 nm. The investigated biosensor showed a precise, efficient detection with sufficient selectivity which was achieved through the optimization of conditions. In the range of 1–1000 μM, the ATP-induced changes of the fluorescence intensity were linearly proportional to the ATP concentrations. Furthermore, the cytotoxicity assay revealed that the UCNPs sensor exhibited favorable biocompatibility, implicating the use of UCNPs in vivo imaging. This study highlights the potential of using a combination of UCNPs and ATP-binding aptamer to design an ATP-activatable probe for fluorescence-mediated imaging in living cells. These results implied that the nanosensor can be applicable for the monitoring of intracellular ATP by fluorescence imaging and the quantitative analysis of biological liquids.
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DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2019
·
IF 9.518
Ting Xue,Yingying Sheng,Jingkun Xu,Yingying Li,Xinyu Lu,Yifu Zhu,Xuemin Duan,Yangping Wen
The environmental stability, water-processibility and life-span of black phosphorene (BP) severely limit the application of its electronic devices in aqueous system containing oxygen. We reported the controllable preparation of in-situ reduction and deposition of silver nanoparticles on the BP surface and its amino-functionalized multi-walled carbon nanotubes (NH 2 -MWCNT) nanocomposite . With the addition of both NH 2 -MWCNT and Ag + , the BP-based nanocomposite was prepared by ultrasonic-assisted liquid-phase exfoliation and was dispersed in carboxymethyl cellulose sodium (CMC) aqueous solution. The morphology, microstructure, and electrochemical properties of the nanohybrid were characterized. NH 2 -MWCNT-BP-AgNPs showed high environmental stability, good water-processibility, satisfactory life-spans, superior electrocatalytic capacity with enzyme-like kinetic characteristics. The nanohybrid was applied as electrochemical sensors for single/simultaneous analysis of uric acid (UA), xanthine (XT) and hypoxanthine (HX). Excellent voltammetric responses for simultaneous determination in linear ranges of 0.1–800 μM with a limit of detection (LOD) of 0.052 μM for UA, 0.5–680 μM with a LOD of 0.021 μM for XT, and 0.7–320 μM with a LOD of 0.025 μM for HX under optimal conditions. Besides, the developed nanozyme sensor was employed for simultaneous voltammetric analysis of UA, XT and HX in real samples with acceptable recoveries. This work will provide theoretical guidance and experimental support for the preparation and application of two-dimensional materials, nanozymes and sensing devices.
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DOI
PubMed
高影响因子
Journal of Biomedical Nanotechnology
·
2019
·Vol. 15
·期 2
·319-328
·
IF 0
Hu Xiongwei,Zhang Mengmeng,Xue Qian,Cai Ting
Nanoparticles have great promise in drug delivery, but their functional mechanisms are very complicated. Monitoring the payloads or carriers by conventional labeling strategies may result in an inaccurate perception of the effectiveness of nano drug delivery systems (NDDSs). A GSH/ATP
dual-responsive fluorescence enhancement probe was developed by manipulating the electron transfer pathways of surface-modified quantum dots (QDs). Because the intracellular concentrations of GSH and ATP are one hundred times greater than those in the extracellular environment, the intracellular
drug release process could be observed by the fluorescence signal of this probe after it is loaded into NDDSs as drug simulants. As a proof-of-concept investigation, the intracellular drug release behaviors of classical liposomes were studied by loading this probe, and the observed results
strongly support the known drug delivery mechanism of these systems. Although more studies are needed to investigate the in vivo performance of the probe, this study may encourage further investigations of other intracellular environment-responsive smart probes for deciphering the in vivo
fate of NDDSs.
研究领域:
生物医学工程
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纳米医学
·
药理学
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DOI
PubMed
ChemistrySelect
·
2023
·Vol. 8
·期 5
·e202204363
·
IF 2.1
Tingting Xu,Panpan Xu,Guilin Xu,Mengyao Liu,Yinggui Zhu
Graphical In the study, Ru(bpy) 3 2+ was used as the luminophore, HEPES buffer was served as the co-reactant, and ATP was added to the system to amplify the luminous signal. It was speculated that ATP acts as an co-reaction accelerator to promote the oxidation of HEPES to HEPES + ⋅, more HEPES⋅ can be generated, which then reacts with oxidized Ru(bpy) 3 3+ to emit stronger ECL signals. Moreover, I - consumes ATP, Ru(bpy) 3 2+ , and HEPES, leading to a decrease in ECL signal. Adenosine triphosphate is an important biological molecule that provides energy and substrate for various cellular biochemical processes,it's ubiquitous in our lives. In this work, a novel electrochemiluminescence (ECL) sensor composed of Ru(bpy) 3 2+ , 2-[4-(2-hydroxyethyl)piperazin-1-yl] ethanesulfonic acid (HEPES) and adenosine 5’-triphosphate disodium salt (ATP) was developed for the first time. In this ECL system, Ru(bpy) 3 2+ was used as the luminophore, HEPES buffer was served as the co-reactant, and ATP was added to the system to amplify the luminous signal to investigate the ECL behavior. Through fluorescence spectroscopy, ECL spectroscopy, and cyclic voltammetry (CV), it can be hypothesized that the possible ECL mechanism is that ATP acts as an advanced co-reaction promoter to accelerate the oxidation of HEPES to HEPES + ⋅, more HEPES⋅ can be generated, which then reacts with oxidized Ru(bpy) 3 3+ to emit stronger ECL signals. Subsequently, the influence of the ATP concentrations and the CV scanning speed was investaged. Moreover, it was observed that I − could quench the ECL intensity, the linear relationship range of I − concentration is from 10 −3 to 10 −6 m , the limit of detection is 3.7×10 −8 m (signal/noise=3), therefore, a new, highly sensitive, and selective ECL approach for I − detection was created.
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高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Huan Wang,Xinchen Liu,Xiangyu Yan,Yong Du,Fang Pu,Jinsong Ren,Xiaogang Qu
Anticancer nanomedicines used for ferroptosis therapy generally rely on the direct delivery of Fenton catalysts to drive lipid peroxidation in cancer cells. However, the therapeutic efficacy is limited by the ferroptosis resistance caused by the intracellular anti-ferroptotic signals. Herein, we report the intrinsic ATPase-mimicking activity of a vanadium carbide MXene nanozyme (PVCMs) to pharmacologically modulate the nuclear factor erythroid 2-related factor 2 (Nrf2) program, which is the master anti-ferroptotic mediator in the ironclad defense system in triple-negative breast cancer (TNBC) cells. The PVCMs perform high ATPase-like activity that can effectively and selectively catalyze the dephosphorylation of ATP to generate ADP. Through a cascade mechanism initiated by falling energy status, PVCMs can powerfully hinder the Nrf2 program to selectively drive ferroptosis in TNBC cells in response to PVCMs-induced glutathione depletion. This study provides a paradigm for the use of pharmacologically active nanozymes to moderate specific cellular signals and elicit desirable pharmacological activities for therapeutic applications.
研究领域:
纳米医学
·
癌症生物学
·
药理学
·
生物化学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Mei Xue,Zhiwen Ma,Yali Pan,Sihui Mao,Yingqiang Sun,Yupeng Yuan
Using photoluminescent (PL) graphitic carbon nitride (g-C 3 N 4 ) to convert ultraviolet (UV) light into chloroplast absorbed blue or near infrared (NR) is an attractive methodology to facilitate sunlight energy storage and carbon sequestration by microalgae. However, most researches focus on inhibiting water bloom by g-C 3 N 4 , applying PL g-C 3 N 4 to promote growth of microalgae is rarely reported. Accordingly, PL g-C 3 N 4 is synthesized by a microwave heating method and co–cultured with Chlorella vulgaris ( C. vulgaris ) with concentration of 0, 50, and 250 mg/L, named as C. vulgaris -0, C. vulgaris -50, and C. vulgaris -250, respectively, to study effect of PL g-C 3 N 4 on growth of C. vulgaris . Results indicate that there is no significant effect of microwave synthesized g-C 3 N 4 on morphology of microalgae cells, while cell viability and growth rate of C. vulgaris -50 is obviously enhanced. Further analysis indicates that, on the one hand, PL fluorescence at 615 nm enlarges light absorption of microalgae; on the other hand, photogenerated electrons by g-C 3 N 4 accelerate electron transfer in photosystem, subsequently enhancing formation of NADPH and ATP, which is favorable to growth of microalgae. Metabolism analysis illustrates that glucose, fructose, and galactose, involved in glycolysis and photosynthesis, are all up-regulated in C. vulgaris -50 group. This work reveals low concentration of PL g-C 3 N 4 facilitates protein synthesis and energy metabolism through enhancing light absorption and electron transfers, providing a biochemical strategy to enhance carbon sequestration.
研究领域:
环境科学
·
微生物学
·
生物技术
·
生物化学
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DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Yuangui Tang,Chenyun Dai,Huihui Yang,Xian Yang,Ziyu Chen,Jinxiu Dou,Liuxu Zhang,Tao Bai,Junfang Zheng
Non-histone proteins localized in membrane, cytosol and nucleus are lactylated to promote tumor progression. However, whether mitochondrial proteins undergo lactylation and contribute to tumor progression remains unexplored. Here, we identified multiple lactylated mitochondrial proteins in human renal cell carcinoma (RCC) cells using lactylome profiling. Among these, malate dehydrogenase 2 (MDH2)–the only lactylated protein in the tricarboxylic acid (TCA) cycle–emerged as a key target, with K239 as its lactylation site. MDH2 K239la levels are regulated by KAT8 and SIRT3. Under low-glucose, high-lactate conditions mimicking the tumor microenvironment, MDH2 K239la elevated the NADH/NAD + ratio to drive ATP production and boosted NADPH generation to reduce ROS. This enables cells to alleviate oxidative stress, sustain mitochondrial function, and promote RCC malignancy in vitro and in vivo . Mechanistically, MDH2 K239la enhances MDH2 enzymatic activity and strengthens its interaction with the citrate transporter SLC25A1. This facilitates citrate efflux, fueling IDH1-dependent NADPH production when lactate serves as an energy source. Collectively, we unveil a lactylation-dependent mechanism that reprograms mitochondrial metabolism to confer oxidative stress resistance and drive RCC progression. Targeting mitochondrial proteins lactylation, exemplified by MDH2 K239la , represents a promising therapeutic strategy for RCC.
研究领域:
癌症生物学
·
生物化学
·
细胞生物学
·
分子生物学
·
代谢工程
·
肿瘤学
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PubMed
高影响因子
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