Cell Death & Disease
·
2024
·Vol. 15
·期 7
·1-22
·
IF 8.1
Tan Diaoyi,Miao Daojia,Zhao Chuanyi,Shi Jian,Lv Qingyang,Lu Feiyi,Ruan Hailong,Xiong Zhiyong,Zhang Xiaoping
Aldehyde dehydrogenases superfamily (ALDHs), which are ubiquitously present in various organisms with diverse subcellular localizations, play a crucial role in regulating malignant tumor progression; Nevertheless, their involvement in clear cell renal cell carcinoma (ccRCC) has not been elucidated. In this study, we performed comprehensive bioinformatics analyses on the 19 ALDHs genes, and identified ALDH9A1 as a key contributor in ccRCC. Expression patterns and clinical relevance of ALDH9A1 were determined using bioinformatics analyses, real-time PCR, western blotting, and immunohistochemistry. To explore the underlying mechanism behind the tumor suppressor role of ALDH9A1, RNA sequencing, methylated RNA immunoprecipitation, luciferase reporter assay, mass spectroscopy, immunoprecipitation, mutational studies and immunofluorescence were employed. The impact of ALDH9A1 in ccRCC progression and metabolic programming was assessed through both in vitro and in vivo. Here, this study revealed ALDH9A1 as a tumor suppressor gene in ccRCC. The fat mass and obesity associated protein (FTO) was identified as a demethylase for ALDH9A1 mRNA, resulting in its reduced stability and expression levels in ccRCC. Functional experiments demonstrated that the deficiency of ALDH9A1 in ccRCC promoted tumor proliferation, invasion, migration and lipid accumulation. Mechanistic insights illustrated that the diminished levels of ALDH9A1 resulted in the failure to sequester nucleophosmin 1 (NPM1) within cytoplasm, thereby suppressing the transcription of IQ motif containing the GTPase-activating protein 2 (IQGAP2), subsequently activating the AKT-mTOR signaling, ultimately fostering tumor progression and lipid accumulation. In conclusion, the present study highlights the robust prognostic significance of ALDH9A1 and delivers a comprehensive understanding of ALDH9A1-NPM1-IQGAP2-AKT axis in ccRCC. These findings established a solid research foundation for novel therapeutic strategies for ccRCC patients.
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Nano Research
·
2024
·
IF 9.5
Chen Yue,Zhang Xiaoyu,Jiang Jinzhou,Chen Gaoyu,Zhou Kunhong,Zhang Xinwen,Li Fajing,Yuan Caojin,Bao Jianchun,Xu Xiangxing
All inorganic metal halide perovskite nanocrystals (NCs) have attracted much attention for their outstanding optoelectronic properties, which can be tuned by the composition, surface, size and morphology in nanoscale. Herein, we report the microfluidic synthesis of hollow CsPbBr 3 perovskite NCs through the nanoscale Kirkendall effect. The formation mechanism of the hollow structure (Kirkendall void) controlled by the temperature, flow rate, ratios of precursors and ligands was investigated. Compared with the solid CsPbBr 3 NCs of the same size, the hollow CsPbBr 3 NCs exhibit blue shifts in ultraviolet–visible (UV–vis) absorption and photoluminescence (PL) spectra, and remarkably longer PL average lifetime (~ 98.2 ns). Quantum confinement effect, inner surface induced additional trap states and lattice strain of the hollow CsPbBr 3 NCs were discussed in understanding their unique optoelectronic properties. The hollow CsPbBr 3 NC based photodetector exhibits an outstanding negative photoconductivity (NPC) detectivity of 8.9 × 10 12 Jones. They also show potentials in perovskite NC based photovoltaic and light emitting diodes (LEDs).
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Advanced Fiber Materials
·
2024
·
IF 17.2
Qi Lin,Huang Yong,Liu Zheng,Liu Jiangshan,Wang Jing,Xu Huilun,Yang Hao,Liu Limin,Feng Ganjun,Zhang Shuyu,Li Yubao,Zhang Li
Delayed healing of diabetic wounds poses a major challenge to human health due to severe vascular dysfunction, sustained inflammation, and vulnerability to microbial infection. Herein, we constructed multidimensionally nano-topologized electrospun polycaprolactone (PCL) fibrous membranes with shish-kebab nanoarrays on each fiber through self-induced crystallization, on which the CuO 2 –MgO 2 bimetallic peroxide nanodots (BPNs) were anchored by polydopamine (PDA) as the bridging layer. When activated by the acidic microenvironment (typically infected diabetic wound), BPNs on fibers reacted immediately to release Cu 2+ and Mg 2+ ions together with hydrogen peroxide (H 2 O 2 ) molecules, which were then transferred into ·OH radicals through Fenton-type reactions catalyzed by Cu 2+ for instant bacteria elimination. At the same time, the released Cu 2+ and Mg 2+ ions were retained to improve the angiogenesis and suppress the inflammation infiltration, thus remodeling the wound microenvironment. Meanwhile, the one-dimensional (1D)-constructed nano shish-kebabs and PDA coating on fibers provided additional topological activation for cell adhesion and directed migration along the aligned fiber orientation. Through the meticulous design, the resultant membranes markedly accelerated the infected wound healing in the diabetic rat model. This study pioneers a unique design to develop a nanocomposite fibrous membrane that combines multidimensional topologies with chemodynamic therapy (CDT), for efficiently combating infected diabetic wounds. Graphical abstract
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JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-17
·
IF 12.6
Zhu Huan,Zhang Zhaoyuan,Jiang Rong,Xu Liangfu,Yang Xiangdi,Chen Jie,Wang Zhenning,Xu Xiao,Liu Zhigang
Radiotherapy (RT) effectiveness is limited by low DNA damage in tumor cells, surrounding tissue harm, and tumor radioresistance with active DNA repair. Herein, we have engineered a two-dimensional nanomaterial consisting of MXene nanosheets at its core, coated with gold nanorods and a cisplatin shell, and further modified with polyvinyl alcohol, referred to as APMP. The APMP exploits its distinctive electronic properties and photothermal effects to augment radiosensitivity and impede DNA damage repair mechanisms. In vitro experiments demonstrate that APMP elevates reactive oxygen species (ROS) production to approximately 2.6 times higher than that achieved with radiotherapy alone, thereby significantly enhancing the sensitivity to radiotherapy. Combining APMP with photothermal therapy (PTT) and RT is a promising glioblastoma treatment strategy, achieving tumor destruction via localized hyperthermia and overcoming radioresistance. This approach achieves precise tumor targeting, reducing side effects and enhancing therapeutic response in preclinical models. The novel core-shell design enables potent radiotherapy-specific radiosensitizers that drive immunogenic cell death, enhancing glioblastoma combination immunotherapy. This universal strategy heralds a new era in integrating radiotherapy sensitizers with immunotherapy. Graphical
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Journal of Orthopaedic Surgery and Research
·
2024
·Vol. 19
·期 1
·1-15
·
IF 2.8
Xiao Gongyi,Li Xiangwei,Yang Huiping,Zhang Ruobin,Huang Junlan,Tian Yu,Nie Mao,Sun Xianding
Background The larval zebrafish tail fin can completely regenerate in 3 days post amputation. mTOR , the main regulator of cell growth and metabolism, plays an essential role in regeneration. Lots of studies have documented the role of mTOR in regeneration. However, the mechanisms involved are still not fully elucidated. Materials and results This study aimed to explore the role and mechanism of mTOR in the regeneration of larval zebrafish tail fins. Initially, the spatial and temporal expression of mTOR signaling in the larval fin was examined, revealing its activation following tail fin amputation. Subsequently, a mTOR knockout ( mTOR -KO) zebrafish line was created using CRISPR/Cas9 gene editing technology. The investigation demonstrated that mTOR depletion diminished the proliferative capacity of epithelial and mesenchymal cells during fin regeneration, with no discernible impact on cell apoptosis. Insight from SMART-seq analysis uncovered alterations in the cell cycle, mitochondrial functions and metabolic pathways when mTOR signaling was suppressed during fin regeneration. Furthermore, mTOR was confirmed to enhance mitochondrial functions and Ca 2 + activation following fin amputation. These findings suggest a potential role for mTOR in promoting mitochondrial fission to facilitate tail fin regeneration. Conclusion In summary, our results demonstrated that mTOR played a key role in larval zebrafish tail fin regeneration, via promoting mitochondrial fission and proliferation of blastema cells.
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Cell Communication and Signaling
·
2024
·Vol. 22
·期 1
·1-20
·
IF 8.2
Guo Junchen,Wang Shanjie,Wan Xin,Liu Xiaoxuan,Wang Zeng,Liang Chenchen,Zhang Zhenming,Wang Ye,Yan Miao,Wu Pengyan,Fang Shaohong,Yu Bo
Ferroptosis is a regulatory cell death process pivotal in myocardial ischemia–reperfusion (I/R) injury. However, the precise mechanism underlying myocardial ferroptosis remains less known. In this study, we investigated the pathophysiological mechanisms of methylmalonic acid (MMA) associated with ferroptosis activation in cardiomyocytes after I/R. We found an increase level of MMA in patients with acute myocardial injury after reperfusion and AC16 cells under hypoxia/reoxygenation (H/R) condition. MMA treatment was found to be associated with excessive oxidative stress in cardiomyocytes, leading to ferroptosis-related myocardial injury. In mice with I/R injury, MMA treatment aggravated myocardial oxidative stress and ferroptosis, which amplified the myocardial infarct size and cardiac dysfunction. Mechanistically, MMA promoted NOX2/4 expression to increase reactive oxygen species (ROS) production in cardiomyocytes, aggravating myocardial injury. Notably, the increased ROS further activated ferroptosis by inhibiting solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) expression. In addition, MMA decreased the ectopic nuclear distribution of nuclear factor E2-related factor 2 (NRF2) by increasing the interaction between NRF2 and kelch-like ECH-associated protein 1 (KEAP1). This impeded the activation of GPX4/SLC7A11, downstream of NRF2, activating ferroptosis and aggravating myocardial cell injury. Collectively, our study indicates that MMA activates oxidative stress and ROS generation, which induces ferroptosis to exacerbate cardiomyocyte injury in an I/R model. These findings may provide a new perspective for the clinical treatment of I/R injury and warrant further investigation.
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ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2018
·Vol. 410
·期 8
·2211-2219
·
IF 3.307
Qu Fei,Mao Beibei,Xue Fangfang,Xia Lian,You Jinmao,Song Cuihua
In this paper, fluorescent Ag nanoclusters (Ag NCs) templated by hyperbranched polyethyleneimine (PEI) are utilized as a versatile probe through the photoinduced electron transfer (PET) between PEI-Ag NCs and G-quadruplex-hemin complexes. In the presence of hemin and target molecule, the specific conjugation with its aptamer induces the conformational change of the DNA sequence, releasing the G-quadruplex sequence part. Once the G-quadruplex-hemin complexes are introduced, electron transfer from the PEI-Ag NCs to G-quadruplex-hemin complexes occurs, resulting in fluorescence quenching. Through changing the sensing DNA sequence, this novel PET system enables the specific detection of target DNA and adenosine triphosphate (ATP) with the wide linear range of 1–200 nM and 5–500 nM, respectively, and the corresponding limit of detection as low as 0.3 nM for target DNA and 1.5 nM for ATP. In addition, the proposed method is successfully applied to the determination of ATP in human serum samples with satisfactory recoveries, and a logic gate is fabricated using target molecules and hemin as inputs and the fluorescence signal of PEI-Ag NCs as an output.
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MICROCHIMICA ACTA
·
2018
·Vol. 185
·期 2
·1-8
·
IF 5.705
Cheng Xia,Cen Yao,Xu Guanhong,Wei Fangdi,Shi Menglan,Xu Xiaoman,Sohail Muhammad,Hu Qin
The authors describe a fluorometric aptamer based assay for adenosine triphosphate (ATP). It is based on the use of carbon dots (CDs) and graphene oxide (GO). The resultant CD-aptamer is adsorbed on the surface of GO via π-stacking and hydrophobic interaction, and the fluorescence of CD-aptamer is quenched via fluorescence resonance energy transfer (FRET) between CDs and GO. If ATP is present, it will bind to the aptamer and the CD-aptamer will be desorbed from GO. This will suppress FRET and the fluorescence of the CDs is restored. Under the optimal conditions and at typical excitation/emission wavelengths of 358/455 nm, the assay has a 80 pM detection limit and a linear range that extends from 0.10 to 5.0 nM concentrations of ATP. The method was successfully applied to the determination of ATP in yogurt samples. This method can also be conceivably applied to the detection of other analytes for which appropriate aptamers are available.
Schematic of a novel fluorometric ATP assay based on the fluorescence resonance energy transfer (FRET) between aptamer modified carbon dots (CD-aptamer) and graphene oxide (GO). CD-aptamer was used as the energy donor and molecular recognition probe, and GO acted as energy acceptor. This assay exhibits high sensitivity and selectivity with a detection limit as low as 80 pM.
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JOURNAL OF CHEMICAL SCIENCES
·
2018
·Vol. 130
·期 1
·1-11
·
IF 1.254
Lin Hongyan,Lin Jiafeng,Zhao Jing,Tian Yuan,Wang Xiang,Liu Guocheng
Abstract Three new cadmium(II) coordination compounds \([\hbox {Cd}_{2} (\hbox {L})_{2} (\hbox {btec}) (\hbox {H}_{2} \hbox {O})_{2}] \cdot \hbox {3H}_{2} \hbox {O}\) ( 1 ), [Cd(HL)(btb)] ( 2 ) and \([\hbox {Cd}(\hbox {L})(\hbox {pda})] \cdot \hbox {2H}_{2} \hbox {O}\) ( 3 ) were prepared by hydrothermal reactions of cadmium(II) chloride with ligands L ( \(\hbox {L} = \hbox {N}\) , \(\hbox {N}^{\prime }\) -bis(3-pyridyl)octandiamide) in the presence of different aromatic polycarboxylates ( \(\hbox {H}_{4} \hbox {btec} = \hbox {1,2,4,5-benzenetetracarboxylic acid}\) , \(\hbox {H}_{3} \hbox {btb} = \hbox {1,3,5-tri(4-carboxylphenyl)benzene}\) , \(\hbox {H}_{2} \hbox {pda} = \hbox {1,4-phenylenediacetic acid}\) ). The structures of compounds 1 – 3 have been determined by X-ray single crystal diffraction analyses and further characterized by infrared spectroscopy (IR), powder X-ray diffraction (PXRD) and thermogravimetric (TG) analyses. Compound 1 displays a 3D metal-organic framework with (4,4,4)-connected \(\{6^{2}.8^{4}\} \{6^{3}.8^{3}\} \{6^{4}.8^{2}\}\) topology constructed from 2D \([\hbox {Cd}_{2} (\hbox {btec})]_{\mathrm{n}}\) layers and \(\mu _{2}\) -bridging L ligands. Compound 2 is a 3D (3,3)-connected \(\{10^{3}\}\) topological network based on the 3D \([\hbox {Cd(btb)}]_{\mathrm{n}}^{\mathrm{n}-}\) framework and the protonated monodentate HL ligand. Compound 3 shows a 2D layer with (3,5)-connected \((4^{2} \cdot 6^{7} \cdot 8)(4^{2} \cdot 6)\) topological structure, which are further linked by hydrogen bonding interactions to form a 3D supramolecular network. The influences of three aromatic polycarboxylates on the structures of title compounds are investigated. Further, the fluorescent properties of three cadmium(II) compounds and their fluorescent sensing properties towards small solvent molecules and metal cations have been studied.
Graphical Abstract
Three new Cd(II) coordination compounds based on the flexible bis(pyridyl)-bis(amide) ligand and three different polycarboxylates have been hydrothermally synthesized. The polycarboxylates with diverse carboxyl groups and various structures play an important role in constructing three Cd(II) compounds. The thermal stabilities, fluorescent and fluorescence sensing properties of the three Cd(II) compounds towards small solvent molecules and metal cations have been reported.
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Scientific Reports
·
2018
·Vol. 8
·期 1
·1-9
·
IF 4.122
Yuan Dandan,Ding Lairong,Sun Zhaomei,Li Xuemei
Here, we report a novel magnetic resonance imaging (MRI)/fluorescence bimodal amplification platform for the detection of glutathione (GSH) on the basis of redoxable manganese dioxide (MnO 2 ) nanosheets, which can be readily applied as a DNA nanocarrier, fluorescence quencher, and intracellular GSH-activated MRI contrast agent. The binding of aptamers that absorbed on the MnO 2 nanosheets to their target can facilitating the endocytosis of target-nanoprobes. Once endocytosed, the MnO 2 nanosheets can react with cellular GSH, resulting in the disintegration of nanosheets to generate plenty of Mn 2+ ions for MRI and releases the primers which were adsorbed on the MnO 2 nanosheets. Then the rolling circle amplification (RCA) reaction was initiated to amplify the fluorescence signal. In addition, after treatment with GSH, the MnO 2 nanosheets were reduced and then most of the fluorescence was recovered. Therefore, this MnO 2 nanoprobe exhibits excellent selectivity, suggesting a potential detection platform for analyzing the glutathione level in cells.
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FIBERS AND POLYMERS
·
2017
·Vol. 18
·期 11
·2204-2211
·
IF 1.113
Xu QingBo,Gu JiaYuan,Zhao Yang,Ke XiaTing,Liu XiangDong
L-cysteine (Cys) and silver nanoparticles (Ag NPs) were successfully linked onto the cotton fabric surfaces. The Cys molecules were covalently linked to the cotton fibers via esterification with the cellulose hydroxyl groups, and the Ag NPs tightly adhered to the fiber surface via coordination bonds with the Cys thiol groups. As a result, the Ag NPs coating on the cotton fabric showed an excellent antibacterial function with an outstanding laundering durability. The bacterial reduction rates (BR) efficiency reached 100 % for Escherichia coli ( E. coli ) and Staphylococcus aureus ( S. aureus ). After 50 consecutive laundering cycles, the bacterial reduction rates (BR) against E. coli and S. aureus were maintained over 97 %. It has potential applications in a wide variety of fields such as sportswear, socks, and medical textile.
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JOURNAL OF NANOBIOTECHNOLOGY
·
2017
·Vol. 15
·期 1
·1-17
·
IF 4.946
Zhou Yi,Wen Huaying,Gu Liang,Fu Jijun,Guo Jiayi,Du Lingran,Zhou Xiaoqin,Yu Xiyong,Huang Yugang,Wang He
Background Chemotherapeutic drugs used for cancer therapy frequently encounter multiple-drug resistance (MDR). Nanoscale carriers that can target tumors to accumulate and release drugs intracellularly have the greatest potential for overcoming MDR. Glucose transporter-1 (GLUT-1) and glutathione (GSH) overexpression in cancer cells was exploited to assemble aminoglucose (AG)-conjugated, redox-responsive nanomicelles from a single disulfide bond-bridged block polymer of polyethylene glycol and polylactic acid (AG-PEG-SS-PLA). However, whether this dual functional vector can overcome MDR in lung cancer is unknown. Results In this experiment, AG-PEG-SS-PLA was synthetized successfully, and paclitaxel (PTX)-loaded AG-PEG-SS-PLA (AG-PEG-SS-PLA/PTX) nanomicelles exhibited excellent physical properties. These nanomicelles show enhanced tumor targeting as well as drug accumulation and retention in MDR cancer cells. Caveolin-dependent endocytosis is mainly responsible for nanomicelle internalization. After internalization, the disulfide bond of AG-PEG-SS-PLA is cleaved in the presence of high intracellular glutathione levels, causing the hydrophobic core to become a polar aqueous solution, which subsequently results in nanomicelle disassembly and the rapid release of encapsulated PTX. Reduced drug resistance was observed in cancer cells in vitro. The caspase-9 and caspase-3 cascade was activated by the AG-PEG-SS-PLA/PTX nanomicelles through upregulation of the pro-apoptotic proteins Bax and Bid and suppression of the anti-apoptotic protein Bcl-2, thereby increasing apoptosis. Furthermore, significantly enhanced tumor growth inhibition was observed in nude mice bearing A549/ADR xenograft tumors after the administration of AG-PEG-SS-PLA/PTX nanomicelles via tail injection. Conclusions These promising results indicate that AG-PEG-SS-PLA/PTX nanomicelles could provide the foundation for a paradigm shift in MDR cancer therapy.
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