SEPARATION AND PURIFICATION TECHNOLOGY
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2024
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IF 8.1
Qunying Sun,Qianxiang Xiao,Qixu Chen,Wen He,Feng He,Hongqing Wang
Efficient and stable photocatalytic materials are urgently needed for the photo-reduction of uranium in wastewater treatment without the addition of external sacrificial agents under air conditions. Herein, we designed and synthesized 1 T@2H MoS 2 QDs (MSQ) modified oxygen-rich defective ZnO photocatalysts 1 T@2H MoS 2 QDs/OV-ZnO (MSQVZO) and systematically investigated its photocatalytic U(VI) activity in various matrices, which exhibited 97 % removal efficiency of uranium after 40 min of visible light irradiation under aerobic conditions, and the order of photocatalytic activity was MSQVZO > OV-ZnO > ZnO. XRD, ESR, XPS, and UV–vis were used for the characterization of the materials. In addition, it was argued using DFT analysis that the introduction of oxygen defects drove the OV-ZnO to interact with the intermediates of the oxygen evolution reaction (OER) reaction more readily than the ZnO, thus improving the activity of the OV-ZnO-based catalysts. More importantly, a new mechanism for photo-reduction of U(VI) was established. It provides an effective strategy for the photo-reduction of U(VI) without a sacrificial agent.
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JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
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2024
·Vol. 43
·期 1
·1-22
·
IF 11.4
Tu Xiaoxuan,Chen Longxian,Zheng Yi,Mu Chenglin,Zhang Zhiwei,Wang Feiyu,Ren Yiqing,Duan Yingxin,Zhang Hangyu,Tong Zhou,Liu Lulu,Sun Xunqi,Zhao Peng,Wang Lie,Feng Xinhua,Fang Weijia,Liu Xia
Background The paucity of reliable biomarkers for predicting immunotherapy efficacy in patients with advanced hepatocellular carcinoma (HCC) has emerged as a burgeoning concern with the expanding use of immunotherapy. This study endeavors to delve into the potential peripheral biomarkers capable of prognosticating efficacy in HCC patients who are poised to receive anti-PD-1 monotherapy within the phase III clinical trial, KEYNOTE394. Additionally, we sought to elucidate the underlying molecular mechanisms for resistance to immune checkpoint blockade (ICB) and propose innovative combination immunotherapy strategies for future clinical application.Methods Patient blood samples were collected for single-cell RNA sequencing to evaluate the immune cell signature before receiving ICB therapy. Subsequently, in vitro assays and in vivo murine model experiments were conducted to validate the mechanism that S100A9+CD14+ monocytes play a role in ICB resistance.Results Our study demonstrates a notable enrichment of S100A9+CD14+ monocytes in the peripheral blood of patients exhibiting suboptimal responses to anti-PD-1 therapy. Moreover, we identified the Mono_S100A9 signature as a predictive biomarker, indicative of reduced efficacy in immunotherapy and decreased survival benefits across various tumor types. Mechanistically, S100A9 activates PD-L1 transcription by directly binding to the CD274 (PD-L1) gene promoter, thereby suppressing T-cell proliferation and cytotoxicity via the PD-1/PD-L1 axis, consequently diminishing the therapeutic effectiveness of subsequent anti-PD-1 treatments. Furthermore, our in vivo studies revealed that inhibiting S100A9 can synergistically enhance the efficacy of anti-PD-1 drugs in the eradication of hepatocellular carcinoma.Conclusion sOur study underscores the significance of S100A9+CD14+ monocytes in predicting inadequate response to ICB treatment and provides insights into the monocyte cell-intrinsic mechanisms of resistance to ICB therapy. We also propose a combined therapeutic approach to enhance ICB efficacy by targeting S100A9.
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ADVANCED MATERIALS
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2024
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IF 27.4
Ruonan Wang,Huixin Li,Shasha He,Yuanji Feng,Cong Liu,Kai Hao,Danhua Zhou,Xiaoyuan Chen,Huayu Tian
Lymph nodes are crucial immune foci as the primary target for cancer immunotherapy. However, the anti-tumor functions of tumor-draining lymph nodes (TDLNs) are critically suppressed by tumors. Here, a novel spatiotemporal nano-regulator is presented, designed to modulate the dendritic cells (DCs) in TDLNs, establishing a supportive niche for immune surveillance. The DC-mediated nano-regulator (DNR) is established by the self-assembly of an imidazoquinoline (IMDQ) prodrug, inhibitory immune checkpoint (ICP) siRNA, and mannan (a TLR4 agonist). This unique design leverages the spatiotemporal activation of TLR4 and TLR7/8, thereby optimizing DC maturation and cytokine production. This further promotes efficient T cell priming. Simultaneously, the ICP-targeting siRNA mitigates the tolerogenic effects induced by tumor-derived factors and TLR activation, preventing T cell exhaustion. In essence, DNR facilitates potent remodeling of TDLNs and the tumor microenvironment, activating the anti-tumor immunity cascade. When combined with vaccines, DNR greatly promotes tumor regression and the establishment of long-term immunological memory.
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Cellular & Molecular Immunology
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2025
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IF 19.8
Bai Ying,Ren Hui,Leng Shuo,Yuan Mengqin,Jiang YiXin,Zhang Shenyang,Wang Yu,Ju Minzi,Wang Zhi,Xi Wen,Xu Lian,Zheng Bingjing,Li Daxing,Huo Xinchen,Zhu Tianhao,Zhang Beicheng,Shen Ling,Zhang Yuan,Jiang Wei,Zhang John H.,Han Bing,Yao Honghong
Splenic sympathetic activity critically modulates peripheral immunity after ischemic stroke, thus intervention in spleen sympathetic activity represents a promising therapeutic strategy for stroke. However, the mechanisms underlying spleen-brain-immune axis communication remain poorly understood. Here, we utilized a surgical denervation protocol to perform splenic sympathetic denervation (SDN), which significantly attenuated brain injury following stroke. Through single-cell RNA sequencing, we identified a novel GZMK + CD8 + CD27 + CCR7 + T-cell subset in patients with acute ischemic stroke (AIS), which we designated stroke-associated T (Tsa) cells. The expansion of Tsa cells was positively correlated with the severity of clinical symptoms and was driven by the splenic sympathetic nervous system. Stroke-induced sympathetic activation triggers the release of splenic norepinephrine (NE), which preferentially signals through ADRB2 on Tsa cells to promote their mobilization. Additionally, ischemic injury induces endothelial cell-specific expression of CCL19, which chemoattracts Tsa cells into the brain parenchyma via their cognate CCR7 receptor, exacerbating neuroinflammatory injury and neurological deficits in a transient middle cerebral artery occlusion (tMCAO) mouse model. We developed a CCR7-targeting peptide to disrupt this chemotactic axis and reduce T-cell infiltration, thereby mitigating brain injury. Our findings highlight SDN as a promising therapeutic strategy to attenuate ischemia‒reperfusion injury and suggest its potential as an adjunctive therapy for reperfusion treatment in AIS patients.
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Journal of Pharmaceutical Analysis
·
2025
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IF 8.9
Na Liu,Yuzhen Tu,Hanyu Wang,Xiaoqiang Zheng,Fanpu Ji,Mingsha Geng,Xin Wei,Jingman Xin,Wangxiao He,Qian Zhao,Tianya Liu
The Wnt/β-catenin signaling pathway is renowned for its contribution to the immunosuppressive microenvironment in non-small cell lung cancer (NSCLC). Consequently, inhibiting this pathway has emerged as a promising strategy to enhance immune activation and reinstate T cell responses in cancer treatment. In this study, we initially investigate the metabolic characteristics of Wnt-hyperactivated NSCLC using mass spectroscopic detection in a mouse in-situ model and unveil its significant feature of acid accumulation at tumor sites. Building upon this discovery, we design an acid-sensitive peptide-carnosic acid (CA) supramolecular droplet, Pep1@CA, which leverages the acidic microenvironment characteristic of NSCLC for controlled release. By doing so, we aim to enhance targeting efficiency while minimizing off-target effects. As anticipated, Pep1@CA demonstrates potent tumor-specific inhibition of the Wnt signaling pathway and effectively reactivates T cell immunity in Wnt-hyperactivated NSCLC. Importantly, comprehensive in vivo evaluations reveal significant antitumor efficacy alongside excellent biosafety profiles. Collectively, this study provides a therapeutic strategy with promising clinical translational potential for targeting the Wnt signaling pathway and offers theoretical support for its application in immunotherapy. This innovative approach underscores that targeting pathways beyond traditional immunotherapy can also activate tumor immunity, thereby expanding the potential of cancer immunotherapy.
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MOLECULES
·
2024
·Vol. 29
·期 23
·5730
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IF 4.2
Zefeng Jiang,Tongyang Song,Bowen Huang,Chengqiang Qi,Zifu Peng,Tong Wang,Yuliang Li,Linjing Ye
Platanus officinalis fibers (PFs) taking advantage of high-availability, eco-friendly and low-cost characteristics have attracted significant focus in the field of biomaterial application. Polyethyleneimine grafted with polydopamine on magnetic Platanus officinalis fibers (PEI-PDA@M-PFs) were prepared through a two-step process of mussel inspiration and the Michael addition reaction, which can work as an effective multifunctional biomass adsorbent for anionic dye with outstanding separation capacity and efficiency. The as-prepared PEI-PDA@M-PFs possess desirable hydrophilicity, magnetism and positive charge, along with abundant amino functional groups on the surface, facilitating efficient adsorption and the removal of Eriochrome Black T (EBT) dyes from water. In addition to the formation mechanism, the adsorption properties, including adsorption isotherms, kinetics, and the reusability of the absorbent, were studied intensively. The as-prepared PEI-PDA@M-PFs achieved a theoretical maximum adsorption capacity of 166.11 mg/g under optimal conditions (pH 7.0), with 10 mg of the adsorbent introduced into the EBT solution. The pseudo-second-order kinetic and Langmuir models were well matched with experimental data. Moreover, thermodynamic data ΔH > 0 revealed homogeneous chemical adsorption with a heat-absorption reaction. The adsorbent remained at high stability and recyclability even after five cycles of EBT adsorption processes. These above findings provide new insights into the adsorption processes and the development of biologic material for sustainable applications.
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Arthritis & Rheumatology
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2025
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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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JOURNAL OF CONTROLLED RELEASE
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2024
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IF 10.5
Xinyi Li,Yuyi Qian,Xin Lu,Mingzhen Xu,Simin He,Jianping Zhang,Shaoli Song
Transarterial radioembolization (TARE) is a recommended locoregional strategy for intermediate hepatocellular carcinoma (HCC), whereas, the effect is insufficient to reverse the immunosuppression tumor microenvironment, and the overall benefits for patients remain to be improved. In this study, a multifunctional microsphere (MS) 131 I-ICT/R848-MS is developed to propose an approach combined with TARE, icaritin (ICT) and immune modulator resiquimod (R848). ICT and iodine-131 ( 131 I) radiation can induce immunogenic cell death, which, in combination with R848, will boost dendritic cell (DC) maturation. Decellularized liver model and SPECT/CT imaging revealed high specificity and long retention of microspheres. Radioactive distribution of 131 I in tumor on 7 d following 131 I-MS injection was over 7 times of that in normal liver tissue (4.26 ± 1.21 % ID/g vs 0.57 ± 0.23 % ID/g). 131 I-ICT/R848-MS embolization brought significant immune activation, where the ratio of cytotoxic T lymphocytes to regulatory T cells in tumor sites upregulated from 1.75 ± 0.20 to 24.31 ± 1.79, and DC maturation in lymph nodes increased from 8.90 ± 1.51 % to 34.70 ± 3.12 %. Enhanced anti-tumor efficacy with no relapse was proved in rat orthotopic N1S1 HCC models. These results demonstrated the great potential of this multifunctional embolic agent to treat HCC through transarterial radio-immuno-chemoembolization (TARICE).
研究领域:
肿瘤学
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放射肿瘤学
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免疫疗法
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医学影像
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药理学
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Journal of Materials Chemistry B
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2017
·Vol. 5
·期 48
·9532-9545
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IF 4.543
Meng Lv,Sha Li,Haijie Zhao,Kewei Wang,Qianqian Chen,Zhong Guo,Zonghua Liu,Wei Xue
In order to enhance the cellular immune response of vaccines, numerous vaccine delivery systems have been developed, especially cationic nanoparticle carriers. Cationic polymer dots (PDs) have been widely used for biomedical imaging and drug delivery due to their excellent photoluminescence, small size and abundant positive charge. In this study, polyethyleneimine (600 Da) (PEI600)-modified redox-responsive hyperbranched poly(amido amine) (PAA-PEI600) and partially carbonized PAA-PEI600 PDs were designed and prepared as vaccine carriers to deliver the model antigen protein ovalbumin (OVA). Then, OVA-specific immune responses induced by PAA-PEI600/OVA and PDs/OVA nanoparticles were evaluated in vivo. The results suggest that the PAA-PEI600/OVA and PDs/OVA nanoparticles enhanced OVA-specific immune responses when compared to OVA alone. Further, PDs/OVA nanoparticles induced more potent OVA-specific cellular immune responses, including higher levels of the OVA-specific IgG2a/IgG1 antibody ratio, splenocyte proliferation, IL-12 and IFN-γ cytokines, maturation of dendritic cells, effector memory CD4+ T cells and CD8+ T cells as well as cytotoxic T lymphocytes (CTLs) than PAA-PEI600/OVA nanoparticles did. Moreover, subcutaneously injected PDs/OVA nanoparticles significantly inhibited tumor growth of the mice bearing E.G7-OVA tumor and extended mice survival. All the results show that immunization with PDs/OVA nanoparticles elicited more effective OVA-specific cellular immune responses. PDs could serve as promising vaccine delivery systems for cancer immunotherapy.
研究领域:
生物医学工程
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免疫学
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癌症研究
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药学
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JOURNAL OF MOLECULAR LIQUIDS
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2021
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IF 6.165
Zilong Cui,Liang Yao,Jingling Ye,Zhi Wang,Yonghong Hu
In the research, the solubility of curcumin was studied by static equilibrium method combined with HPLC. The solubility data of curcumin was measured in twelve pure solvents (dimethyl sulfoxide, tetrahydrofuran, acetone, ethyl acetate, isopropanol, acetonitrile, 1-butanol, ethanol, methanol, xylenes, n-hexane and n-heptane) and three binary solvent mixtures (acetone + tetrahydrofuran, acetonitrile + tetrahydrofuran and n-hexane + tetrahydrofuran) at different temperature (T = 278.15–323.15 K) under atmospheric pressure. The solubility values demonstrate that the solubility increased with the increase of temperature in all solvents. The modified Apelblat model and the Buchowski-Ksiazczak λh model were used to fitted the solubility data in pure solvents, the combined nearly ideal binary solvent/ Redlich-Kister (CNIBS/R-K) model and the Jouyban-Acree model were employed to adopt the solubility data in binary solvent mixtures. The RAD max of the modified Apelblat model and the λh model are 2.621% and 5.831%, the RMSD max are 6.9 × 10 -4 and 1.62 × 10 -3 , respectively. The RAD max of the CNIBS/R-K model and the Jouyban-Acree model are 2.249% and 4.901%, the RMSD max are 9.33 × 10 -3 and 3.67 × 10 -3 . Meanwhile, the KAT-LSER model was used to explore the effect of the solvation of curcumin. The fitting results of all equations prove the accuracy of the experimental data, these solubility data are very important for optimizing the extraction process and recrystallization of curcumin.
研究领域:
化学工程
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药物化学
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EUROPEAN JOURNAL OF PHARMACOLOGY
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2026
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IF 5.7
Min Cai,Ruijuan Qi,Muqing Wang,Congyu Wu,Qian Chen,Yilin Guo,Yu Liu,Xin Huang,Yuan Gao,Yun Qi
DET decreases the transcription and translation of IL-2 in ConA-activated T cells. • DET inhibits ConA-activated NF-κB pathway, but fails to suppress MAPK signaling. • DET dampens ConA-induced nuclear translocation of NFAT. • DET directly suppresses calcineurin (CaN) activity not by reducing cytoplasmic Ca 2+ . • DET lowers serum IL-2 level of anti-CD3 antibody-treated mice. Deoxyelephantopin (DET) is a sesquiterpene lactone isolated from Elephantopus scaber , a traditional medicinal plant valued for its heat-clearing and detoxifying properties. As one of the major bioactive components, DET exhibits a variety of pharmacological activities, such as antitumor, antimicrobial, and anti-inflammatory effects. Nevertheless, its effect on T cell activation remains underexplored. Our study indicated that DET suppressed the proliferation and interleukin-2 (IL-2) production in T cells activated by various stimuli for T cell receptor (TCR)/CD3 signaling (i.e., concanavalin A (ConA), anti-CD3 antibody, and allogeneic major histocompatibility complex (MHC)). Mechanistically, DET lowered IL-2 mRNA level without affecting its stability in ConA-activated Jurkat T cells. Among three nuclear transcriptional pathways (mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB), nuclear factor of activated T cells (NFAT)) triggered by ConA, DET did not suppress MAPK signaling, but significantly inhibited NF-κB activation by hindering inhibitor of kappa-B alpha (IκBα) phosphorylation and degradation, thereby preventing p65 nuclear translocation. Concurrently, DET could dampen the activation of NFAT signaling through inhibiting the activity of calcineurin (CaN) to impede NFAT nuclear translocation independent of decreasing cytoplasmic Ca 2+ (Ca 2+ [c] ). Unlike classical CaN inhibitors (CNIs), DET inhibits CaN activity without involving immunophilins. In vivo , DET could also reduce serum IL-2 level in acute T-cell activation mouse model induced by intravenous injection of anti-CD3 antibody. In conclusion, our findings reveal DET's dual mechanisms (NF-κB and NFAT inhibition) responsible for repressing IL-2 expression in the activated T cells, which may provide a promising candidate for the development of a novel IL-2 suppressive agent. Download: Download high-res image (270KB) Download: Download full-size image
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JOURNAL OF NANOBIOTECHNOLOGY
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2026
·Vol. 24
·期 1
·382
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IF 15
Jiang Zhou,Li Yuning
Lung cancer (LC) remains a leading cause of cancer-related mortality worldwide, and the limited efficacy of immunotherapy due to treatment resistance underscores the urgent need for new therapeutic strategies. In the present study, CD93-targeted poly(lactic-co-glycolic acid) (PLGA) nanoparticles encapsulating resveratrol (CD93-NPs@RSV) were developed to remodel the metabolic fitness of CD8 + tumor-infiltrating lymphocytes. The nanoparticles were precisely engineered and characterized using dynamic light scattering, transmission electron microscopy, and in vivo imaging, which confirmed their stability and tumor-targeting capability. Mechanistic studies revealed that CD93-NPs@RSV suppressed CD93 expression, facilitated apoptosis-inducing factor (AIF) mitochondrial translocation, and activated oxidative phosphorylation (OXPHOS), thereby enhancing T cell function in the tumor microenvironment. Transcriptomic and proteomic analyses further confirmed regulation of the CD93-AKT-PAK5-AIF signaling axis. In a Lewis LC model, CD93-NPs@RSV significantly inhibited tumor progression and displayed strong synergy with anti-PD-1 therapy, resulting in improved survival outcomes. Collectively, our study demonstrates that CD93-NPs@RSV provide a powerful nanotechnology-driven approach to reverse immunotherapy resistance by reprogramming T cell metabolism. These findings establish a promising paradigm for precision cancer immunotherapy and underscore the translational potential of targeted nanomedicine in overcoming therapeutic bottlenecks in LC. Graphical abstract The alternative text for this image may have been generated using AI.
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