ADVANCED FUNCTIONAL MATERIALS
·
2019
·Vol. 29
·期 12
·1806916
·
IF 15.621
Xiaowei Liu,Yanlin Feng,Guangchao Xu,Yang Chen,Ya Luo,Jinen Song,Yu Bao,Jiqiao Yang,Chune Yu,Yanna Li,Haoyu Ye,Bowen Ke,Bo Chen,Jianping Hu,Jie Xu,Huan Meng,Haiyuan Zhang,Hubing Shi
The combination of BRAF/MEK-targeted therapy with immune checkpoint blockade is regarded as a promising regimen for patients with metastatic melanoma due to their complementary advantages. However, MEK-inhibitor-induced T-cell toxicity impedes effective cooperation. In this experiment, a pH-responsive on-demand controlled release mesoporous silica nanoparticles (MSNPs) system is designed. Fluorescein-isothiocyanate-loaded MSNP can be specifically delivered into tumor cells rather than T-cells. MEK-inhibitor-loaded MSNP avoids proliferative and functional inhibitions of T-cells, while preserving growth suppression of tumor cells in vitro. In an in vivo model, MSNP encapsulation reverses the MEK-inhibitor-induced suppression of activated CD8 + T-cells, and enhances the secretion of INF-γ and IL-2. The combination of BRAF inhibitor plus MSNP-loaded MEK inhibitor and anti-PD-1 antibody synergistically inhibits tumor growth via promoting robust immune-related antitumor response. This work provides a novel and generalized framework for combining T-cell-impaired targeted therapy and immune checkpoint blockade by using a nanoparticle-based delivery system.
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Frontiers in Pharmacology
·
2022
·
IF 5.988
Yuhang Ge,Fei Zhen,Ziqi Liu,Zhaowei Feng,Gui Wang,Chu Zhang,Xingqi Wang,Ying Sun,Xiaohui Zheng,Yajun Bai,Ruiqin Yao
Preterm white matter injury (PWMI) is the most common form of brain damage in premature infants caused by hypoxia-ischemia (HI), inflammation, or excitotoxicity. It is characterized by oligodendrocyte precursor cell (OPC) differentiation disorder and dysmyelination. Our previous study confirmed that alpha-asarone (α-asaronol), a major compound isolated from the Chinese medicinal herb Acorus gramineus by our lab, could alleviate neuronal overexcitation and improve the cognitive function of aged rats. In the present study, we investigated the effect and mechanism of α-asaronol on myelination in a rat model of PWMI induced by HI. Notably, α-asaronol promoted OPC differentiation and myelination in the corpus callosum of PWMI rats. Meanwhile, the concentration of glutamate was significantly decreased, and the levels of PPARγ and glutamate transporter 1 (GLT-1) were increased by α-asaronol treatment. In vitro, it was also confirmed that α-asaronol increased GLT-1 expression and recruitment of the PPARγ coactivator PCG-1a in astrocytes under oxygen and glucose deprivation (OGD) conditions. The PPARγ inhibitor GW9662 significantly reversed the effect of α-asaronol on GLT-1 expression and PCG-1a recruitment. Interestingly, the conditioned medium from α-asaronol-treated astrocytes decreased the number of OPCs and increased the number of mature oligodendrocytes. These results suggest that α-asaronol can promote OPC differentiation and relieve dysmyelination by regulating glutamate levels via astrocyte PPARγ-GLT-1 signaling. Although whether α -asaronol binds to PPARγ directly or indirectly is not investigated here, this study still indicates that α -asaronol may be a promising small molecular drug for the treatment of myelin-related diseases.
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Journal of Neuroinflammation
·
2023
·Vol. 20
·期 1
·1-21
·
IF 9.3
Li Nan,Wang Chunyan,Zhao Yuying,Wang Yigang,Gao Tianyu,Yu Yonghao,Wang Guolin,Zhang Linlin
Background Patients receiving epidural or intrathecal opioids administration for neuraxial analgesia frequently suffer from an irritating itch. STING (stimulator of interferon genes), an innate immune modulator, is strongly implicated in pain pathogenesis via neuron-immune modulation. Given that pain and itch share some common neurocircuits, we evaluate the therapeutic potential of STING agonists in opioid-induced itch and chronic itch.Methods Opioids (morphine, fentanyl and sufentanil) were intrathecally injected to induce acute itch. Chronic itch was induced by dry skin and contact dermatitis. Opioids analgesic effect, itch-induced scratching behavior, spinal expression of STING, phosphorylation of TBK1 (tank-binding kinase 1), IRF3 (interferon regulatory factor-3) and ERK (extracellular signal-regulated kinase), as well as production of IFN-α and IFN-β were examined. STING agonists (DMXAA and ADU-S100), TBK1 inhibitor, recombinant IFN-α and IFN-β elucidated the mechanism and treatment of itch. Whole-brain functional connectivity was evaluated using resting-state fMRI.Results We report the primary expression of STING protein by the spinal dorsal horn neurons. Intraperitoneal injection of DMXAA dose-dependently reduces morphine-induced scratch bouts, without impairing morphine antinociception. Simultaneously, DMXAA alleviates fentanyl- and sufentanil-induced itching-like behavior, and chronic scratching behavior caused by dry skin and contact dermatitis. Furthermore, DMXAA drastically increases spinal phosphorylation of TBK1 and IRF3 following morphine exposure, dry skin and contact dermatitis. DMXAA-induced anti-pruritus effects and spinal productions of IFN-α and IFN-β are compensated by intrathecal delivery of the TBK1 inhibitor. Also, ADU-S100, recombinant IFN-α and IFN-β exhibits remarkable attenuation in scratching behaviors after morphine injection and dermatitis. Recombinant IFN-α inhibits morphine-induced spinal phosphorylation of ERK. Finally, DMXAA prevents dermatitis-induced the increase of cerebral functional connectivity between regions of interests such as primary somatosensory cortex, piriform cortex, retrosplenial cortex, colliculus and ventral thalamus.Conclusion sSTING activation confers protection against opioid-induced itch and chronic itch through spinal up-regulation of TBK1-IRF3-type I interferon cascades in mice, suggesting that STING agonists are promising candidates in translational development for pruritus relief.
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Journal of Materials Chemistry B
·
2014
·Vol. 2
·期 30
·4901-4910
·
IF 0
Wenjie Li,Jing Shi,Chun Zhang,Min Li,Lu Gan,Huibi Xu,Xiangliang Yang
The overexpression of thioredoxin (Trx) 1 is one of the mechanisms for drug resistance in hepatocellular carcinoma (HCC) treatment. The co-delivery of drugs and a short hairpin RNA (shRNA) against Trx1 to silence its expression might provide a promising approach to improve drug sensitivity to chemotherapeutic agents. In this paper, cationic liposomes containing gemini surfactants, soybean lecithin and DOPE were firstly constructed as gene transfection carriers. The length and symmetrical degree of aliphatic chains of gemini surfactants were found to affect gene transfection efficiency of cationic liposomes. Cationic liposome containing gemini surfactants with symmetrical C16 aliphatic chains (L16-2-16) showed the highest transfection efficiency in HCC Bel7402 cells and also displayed the strongest DNA condensation capacity and the highest cellular uptake. Folic acid (FA) targeting further enhanced the transfection efficiency of L16-2-16 by binding to the folate receptor (FR) in FR-overexpressing Bel7402 cells and lipid raft/caveolae-dependent endocytosis might be involved in FA-L16-2-16-mediated gene delivery. Then the multifunctional co-delivery system for doxorubicin (DOX) and Trx1 shRNA was developed via electrostatic interactions between the FA-L16-2-16 and Trx1 shRNA/DOX complex. Co-delivery of Trx1 shRNA and DOX by FA-L16-2-16 inhibited the cell viability and induced apoptosis of Bel7402 cells more efficiently than co-delivery of control shRNA and DOX. The system for co-delivering DOX and Trx1 shRNA could simultaneously achieve gene transfection and drug release in the same cell and increase the intracellular as well as intranuclear DOX concentrations. These results demonstrated that gemini surfactant-based cationic liposomes were promising carriers for the co-delivery of nucleic acids and chemotherapeutic agents to sensitize HCC chemotherapy.
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ChemistrySelect
·
2025
·Vol. 10
·期 21
·e06152
·
IF 2
Shuai Wang,BingXi Song,Ze Su,Yijie Cai,Long Liu,Chang Su,Yanqiang Zhang
Graphical A new ionic liquid plasticizer [NTAZ][NTf 2 ] was synthesized. Compared with the traditional plasticizer DOA, [NTAZ][NTf 2 ] can significantly improve the energy of the propellant formulation. Energetic plasticizer is an important means to improve the energy performance of solid propellants, but there is no suitable energetic plasticizer for HTPB/TDI system. In this work, a nitrate-functionalized ionic liquid plasticizer of 1-Methyl-4-(8-(Nitrooxy)octyl)-1,2,4-triazolium bis((trifluoromethyl)sulfonyl)imide ([NTAZ][NTf 2 ]) was synthesized, and the energy was increased by the combination of nitrate functional group and 1,2,4-triazole cation. The hydrogen bond between the anion and the cation and HTPB achieves a good plasticizing effect. When 6% [NTAZ][NTf 2 ] was added to HTPB/TDI system, the glass transition temperature decreased from −63.41 °C to −64.84 °C, the tensile strength increased from 0.52 MPa to 0.79 MPa, and the storage modulus increased from 64.02 MPa to 110.32 MPa. When 4% DOA is replaced by the same amount of [NTAZ][NTf 2 ] in the HTPB formulation system, the specific impulse is increased from 261.0 s to 271.4 s. This study will guide the design and application of new energetic solid propellant plasticisers, both theoretically and experimentally.
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Arthritis & Rheumatology
·
2025
·
IF 10.9
Jin-Fen Ma,Ting Xu,Hao-Xian Zhu,Xiao-Min Chen,Liang Li,Zhi-Bin Zhao,Liwei Lu,Yang Li,Zhe-Xiong Lian,Cai-Yue Gao
Objective Activated T cells play a pivotal pathogenic role in the progression of Sjögren disease (SjD); however, there are currently no targeted therapies specifically designed to address them. This study aims to identify pathogenic CD8 + T cells in SjD and develop targeted therapeutic strategies. Methods Il12b-/-Il2ra-/- mice, a murine model for overlapping primary biliary cholangitis and SjD, were employed in this study. Pathogenic CD8 + T cells were identified through single-cell RNA sequencing and flow cytometry analyses of samples from both patients with SjD and relevant murine models. Shared T cell receptor analysis was conducted to trace the potential precursors of pathogenic CD8 + T cells. The efficacy of PD-1-targeted chimeric antigen receptor (CAR)–T cell therapy was evaluated through the assessment of salivary gland secretory function, immunologic profiles, and histopathological changes in the murine model. Results We identified PD-1 as a comprehensive marker of clonally expanded and activated pathogenic CD8 + T cells in the salivary glands and peripheral tissues. Flow cytometry further confirmed the activation phenotype and cytotoxicity of PD-1 + CD8 + T cells in the salivary glands of patients with SjD. Notably, the number of PD-1 + CD8 + T cells in the labial glands positively correlated with disease activity in patients with SjD. These findings highlight the therapeutic potential of depleting PD-1 + CD8 + T cells in SjD. Furthermore, PD-1-targeted CAR-T cell therapy significantly alleviated SjD symptoms in a murine model. Conclusion We identified the pathogenic role of PD-1 + CD8 + T cells in both patients with SjD and a murine model and demonstrated the efficacy of PD-1-targeted CAR-T cell therapy in SjD model mice. Our findings suggest a promising avenue for developing clinical therapeutic strategies for patients with SjD.
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FUEL
·
2025
·
IF 7.5
Kaiwei Wang,Hao Ruan,Fumin Wang,Yi Zhai,Mingshuai Sun,Yan Chen,Jiaxing Zhang,Yihao Wang,Xuyang Zou,Xubin Zhang
The construction of abundant TiO 6 active sites within the zeolite framework is essential for further enhancing the catalytic performance of TS-1 zeolite. Here, we employ a strategy involving treatment with a mixture of amines and ammonium salts to generate abundant TiO 6 species within zeolites synthesized with the assistance of N,N-dimethylformamide (DMF). It was observed that during the post-treatment process, the presence of amines and ammonium salts plays a key role for the formation of highly active TiO 6 species. The incorporation of DMF can significantly enhance the TiO 6 content in the post-treated zeolite, increasing it to 61.5 % compared with 28.5 % in the zeolite synthesized without DMF. The effect of the DMF/SiO 2 ratio in the synthesized gel on the morphology and catalytic performance was also examined. It is noteworthy that the incorporation of DMF influences the microenvironment of the Ti active sites following post-treatment. 1 H MAS NMR analysis reveals that the characteristic peaks corresponding to Ti-OH and isolated Si-OH groups in the DMF-synthesized catalyst are significantly intensified after treatment with amines and ammonium salts. When H 2 O 2 is employed as an oxidant, the optimal catalytic performance achieves a cyclohexene conversion of 51.1 % and a cyclohexene oxide yield of 39.4 %, with a high TOF value of 92.77 h −1 . Notably, the catalyst exhibits a significantly conversion rate of 79.4 % and a yield of 72.7 % using O 2 as the oxidant.
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JOURNAL OF MATERIALS SCIENCE-MATERIALS IN ELECTRONICS
·
2025
·Vol. 36
·期 7
·420
·
IF 2.8
Chen Yuan-Bin,Tang Ling
A solid-state reaction method was successfully employed to synthesize [(Zn 0.8 Mg 0.2 ) 1-x Ni x ] 2 SiO 4 microwave dielectric ceramics by partially substituting [Zn 0.8 Mg 0.2 ] 2+ with Ni 2+ ions. XRD analysis indicated that the proportion of the primary Zn 2 SiO 4 phase decreases with increasing Ni 2+ content, while the secondary MgNi(SiO 4 ) phase becomes predominant. This phase transition contributes to a reduction in dielectric loss. The sintering behavior, phase composition, microstructure, and microwave dielectric properties of the ceramics were systematically investigated. The incorporation of Ni 2+ ions lowered the optimal sintering temperature from 1325 to 1400 °C. SEM analysis revealed that an optimal Ni 2+ substitution level enhanced the grain density within the [(Zn 0.8 Mg 0.2 ) 1-x Ni x ] 2 SiO 4 ceramic matrix. The relationship between Q × f and the average grain size as well as grain uniformity was analyzed. The trend of τ f is primarily governed by the total V izn-o and E zn-o . Additionally, the relationship between lattice vibrations, Raman shifts, and dielectric properties was investigated using Raman spectroscopy. Certainly, the [(Zn 0.8 Mg 0.2 ) 0.8 Ni 0.2 ] 2 SiO 4 ceramic, sintered at 1325 °C, exhibits an exemplary set of microwave dielectric properties: an εr value of 6.8, a Q × f value of 27,185 GHz, and a τ f value of − 37 ppm/ °C.
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MARINE POLLUTION BULLETIN
·
2025
·
IF 4.9
Jia Shi,Dan Xu,Qiao Ma
p -Chloro- m -xylenol (PCMX), a widely used antimicrobial agent, poses potential ecological risks due to its ubiquitous distribution and documented toxicity to aquatic vertebrates. Although microbial degradation represents a key natural attenuation pathway, the molecular mechanisms governing PCMX biodegradation remain elusive. Here, we report the isolation of three novel Rhodococcus strains from marine sediments capable of mineralizing PCMX. Among these, strain R. ruber SJ-1 completely metabolized 30 mg/L PCMX within 72 h and maintained significant degradation capacity under high-salinity stress. Integrated genomic and transcriptomic analyses revealed that PCMX exposure triggered extensive transcriptional reprogramming in strain SJ-1, with 1063 genes upregulated and 533 downregulated. PCMX inhibited core cellular functions, including key genes related to cell stress resistance, energy production, central carbon metabolism, fatty acid metabolism, and protein biosynthesis. Concurrently, aromatic catabolism pathways were markedly induced. A highly upregulated gene cluster ( sj4821 - sj4838 ) was identified as pivotal for PCMX metabolism, encompassing a flavin-dependent monooxygenase (NphA1-sj, sj4831 ; 2145.26-fold) and catechol 2,3-dioxygenase (C23O, sj4838 , 2052.43-fold) genes. Quantitative PCR assays further validated the upregulation patterns. Based on bioinformatics and high-resolution mass spectrometry analyses, we proposed that strain SJ-1 converted PCMX to 4-chloro-3,5-dimethylcatechol via ortho -hydroxylation, followed by meta -cleavage of the aromatic ring. This study presents the first documented evidence of PCMX degradation by a marine Rhodococcus isolate. Our findings reveal the molecular mechanisms driving PCMX detoxification and cellular adaptation, establishing a foundation for bioremediation in saline ecosystems.
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FUEL
·
2016
·
IF 3.611
Qi Du,Yiping Guo,Huanan Duan,Hua Li,Yujie Chen,Hezhou Liu
Hierarchical TS-1 (HTS-1) zeolite has been successfully synthesized through a novel three-step crystallization method by using a cheap and eco-friendly polymer PVA as the mesopore template. The HTS-1 particles possess an interesting stacking structure and are constructed of smaller crystals with an average diameter of 30 nm. The mesopores of HTS-1 are formed by the stacking of the smaller TS-1 nanocrystals . The catalytic results show that the HTS-1 exhibits much higher catalytic activity than conventional TS-1 in the oxidative desulfurization of dibenzothiophene (DBT) and 4,6-dimethyldibenzothiophene (4,6-DMDBT) due to the presence of intracrystal mesopores. In addition, the three-step crystallization method plays a key role in the preparation of HTS-1, which effectively solves the problem that PVA is unstable and unsuitable to be used as mesopore template under high crystallization temperature .
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Journal of Energy Storage
·
2024
·
IF 8.9
Hao Chen,Si-Miao Huang,Dong-Ting Zhang,Min-Peng Li,Chen-Yang Li,Yu-Ping Qiu,Xiao-Rui Wang,Tian-Peng Xu,Mao-Cheng Liu
The self-stacking of MXenes-Ti 3 CN limits the accessibility of nanochannels , reduces the ion diffusion kinetics, and hinders its application in alkali metal ion storage field. This study proposes a point-to-point mortise and tenon joining strategy to fabricate a composite structure of 1,4-phenylenediacetic acid-Ti 3 CN (1,4-PDEA-Ti 3 CN) by grafting rigid and flexible 1,4-phenylenediacetic acid (1,4-PDEA) into the amino-functionalized Ti 3 CN interlayers. The rigid and flexible 1,4-PDEA contributes to a pillar effect in the layered structure of Ti 3 CN, which is benefit to prevent the self-stacking and maintain a stable 2D layered structure. As a result, the interlayer spacing of Ti 3 CN is expanded from 1.20 to 1.46 nm and the Na + diffusion coefficient is improved from 1.16 × 10 −6 to 1.99 × 10 −6 cm 2 s −1 after point-to-point 1,4-PDEA grafting. The 1,4-PDEA-Ti 3 CN achieves a reversible discharge specific capacity of 202.3 mAh g −1 at a current density of 0.1 A g −1 after 770 cycles. Even at a high current density of 5 A g −1 , the 1,4-PDEA-Ti 3 CN still possesses a reversible discharge specific capacity of 137 mAh g −1 and it still maintains the high specific capacity of 256.1 mAh g −1 when the current density comes back to 0.1 A g −1 . This point-to-point mortise and tenon joining strategy provides a novel approach for designing other 2D energy storage materials with long cycle stability and high-rate capability.
研究领域:
材料科学
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电化学储能
·
纳米材料
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能源化学
·
二维材料
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2026
·
IF 4.8
Zhima Yangcuo,Xiaodan Zheng,Yajuan Zhang,Xin Yang,Xinyi Zheng,Hang Zhu,Wenhui Chen,Qihong Cai
Under alkaline conditions with sodium hydroxide (NaOH), both 1-naphthol (1-NAP) and 2-naphthol (2-NAP) transitioned from their molecular forms to ionic forms, resulting in redshifts of their fluorescence spectra. Thus, not only the interference of 2-NAP raman peak was eliminated, but the fluorescence intensity of two naphthols was also enhanced, thereby improving the selectivity and sensitivity of their analysis. Due to their structural similarity, the conventional fluorescence spectra of 1-NAP and 2-NAP overlapped and interfered with each other, precluding their simultaneous measurement without prior separation. In this study, the wavelength difference (Δλ) = 140 nm was selected for synchronous fluorescence spectrometry (SFS) scanning to simplify the spectra. However, the interference of 2-NAP on 1-NAP remained significant. So, the second-order derivative technique combined with SFS was adopted. The method that eliminated the severe interference between 1-NAP and 2-NAP and wastewater background by utilizing spectral parameters. Finally, a new second-order derivative SFS for simultaneous determination of 1-NAP and 2-NAP was first established. The detection limits were 0.0850 ng·mL −1 for 1-NAP and 0.1066 ng·mL −1 for 2-NAP, with linear ranges of 0.5–80 ng·mL −1 and 0.5–50 ng·mL −1 , respectively. Recoveries of two naphthols in wastewater were 87.53%–93.50% (1-NAP) and 89.85%–104.00% (2-NAP). The new SFS established in this research has been successfully applied to the analysis and detection of 1-NAP and 2-NAP residues in wastewater, achieving satisfactory results. It is expected to become a new routine detection method for 1-NAP and 2-NAP.
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