CELL RESEARCH
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2025
·
IF 25.9
Qin Rui,Zhang Yong,Shi Jiawei,Wu Peng,An Chenyi,Li Zhenhai,Liu Nuo,Wan Ziyan,Hua Ting,Li Xiaolong,Lou Jizhong,Yin Weiwei,Chen Wei
Naturally evolved T-cell receptors (TCRs) exhibit remarkably high specificity in discriminating non-self antigens from self-antigens under dynamic biomechanical modulation. In contrast, engineered high-affinity TCRs often lose this specificity, leading to cross-reactivity with self-antigens and off-target toxicity. The underlying mechanism for this difference remains unclear. Our study reveals that natural TCRs exploit mechanical force to form optimal catch bonds with their cognate antigens. This process relies on a mechanically flexible TCR–pMHC binding interface, which enables force-enhanced CD8 coreceptor binding to MHC-α 1 α 2 domains through sequential conformational changes induced by force in both the MHC and CD8. Conversely, engineered high-affinity TCRs create rigid, tightly bound interfaces with cognate pMHCs of their parental TCRs. This rigidity prevents the force-induced conformational changes necessary for optimal catch-bond formation. Paradoxically, these high-affinity TCRs can form moderate catch bonds with non-stimulatory pMHCs of their parental TCRs, leading to off-target cross-reactivity and reduced specificity. We have also developed comprehensive force-dependent TCR–pMHC kinetics-function maps capable of distinguishing functional and non-functional TCR–pMHC pairs and identifying toxic, cross-reactive TCRs. These findings elucidate the mechano-chemical basis of the specificity of natural TCRs and highlight the critical role of CD8 in targeting cognate antigens. This work provides valuable insights for engineering TCRs with enhanced specificity and potency against non-self antigens, particularly for applications in cancer immunotherapy and infectious disease treatment, while minimizing the risk of self-antigen cross-reactivity.
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JOURNAL OF NANOBIOTECHNOLOGY
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2024
·Vol. 22
·期 1
·1-16
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IF 10.6
Guo Yiming,Wu Jicheng,Chen Lefan,Liu Lujie,Bi Tianxiang,Pan Yuanwei,Meng Qian-Fang,Wang Chaoliang,Rao Lang,Li Qi
Androgen deprivation therapy (ADT) is a crucial and effective strategy for prostate cancer, while systemic administration may cause profound side effects on normal tissues. More importantly, the ADT can easily lead to resistance by involving the activation of NF-κB signaling pathway and high infiltration of M2 macrophages in tumor microenvironment (TME). Herein, we developed a biomimetic nanotherapeutic platform by deriving cell membrane nanovesicles from cancer cells and probiotics to yield the hybrid cellular nanovesicles (hNVs), loading flutamide (Flu) into the resulting hNVs, and finally modifying the hNVs@Flu with Epigallocatechin-3-gallate (EGCG). In this nanotherapeutic platform, the hNVs significantly improved the accumulation of hNVs@Flu-EGCG in tumor sites and reprogramed immunosuppressive M2 macrophages into antitumorigenic M1 macrophages, the Flu acted on androgen receptors and inhibited tumor proliferation, and the EGCG promoted apoptosis of prostate cancer cells by inhibiting the NF-κB pathway, thus synergistically stimulating the antitumor immunity and reducing the side effects and resistance of ADT. In a prostate cancer mouse model, the hNVs@Flu-EGCG significantly extended the lifespan of mice with tumors and led to an 81.78% reduction in tumor growth compared with the untreated group. Overall, the hNVs@Flu-EGCG are safe, modifiable, and effective, thus offering a promising platform for effective therapeutics of prostate cancer. Graphical Abstract
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Nature Sustainability
·
2024
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IF 25.7
Liu Tao,Dong Tiantian,Wang Mengying,Du Xiaofan,Sun Youlong,Xu Gaojie,Zhang Huanrui,Dong Shanmu,Cui Guanglei
Silicon (Si) anode is widely viewed as a game changer for lithium-ion batteries (LIBs) due to its much higher capacity than the prevalent graphite and availability in sufficient quantity and quality. Most Si anode designs are nanostructured to overcome the large volume variation during cycling, but this comes at the expense of manufacturability, cost advantage and other merits. Here we demonstrate that micro-sized Si (μm-Si) recycled from photovoltaic waste can serve as anode material, exhibiting an average Coulombic efficiency of 99.94% and retaining 83.13% of its initial capacity after 200 cycles through the rational electrolyte design. With a formulated ether electrolyte of 3 M LiPF 6 in 1,3-dioxane (DX)/1,2-diethoxyethane (DEE), NCM811||μm-Si pouch cells survive 80 cycles and deliver an energy density of 340.7 Wh kg −1 even under harsh conditions. Responsible for the impressive electrochemical performance is a unique SEI chemistry where the flexible polymer-dominated outer layer well holds fractured Si particles together and the rigid Li 2 O/LiF-rich inner layer serves to facilitate ionic conduction and suppress side reactions. Our work not only suggests a more sustainable supply source for Si particles but also addresses the major problems facing μm-Si anode materials.
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Human Cell
·
2025
·Vol. 38
·期 3
·1-14
·
IF 3.1
Zhu Xiao-Yu,Li Pi-Song,Qu Hui,Ai Xing,Zhao Zi-Ting,He Jia-Bei
Radiotherapy resistance, is usually caused by enhanced tumor stemness and poses a significant challenge in treating breast cancer (BRCA). In this study, we investigated the molecular regulatory mechanism of radiotherapy sensitivity in BRCA associated with replication factor C4 (RFC4) and insulin-like growth factor 2 mRNA binding protein 2 mRNA Binding Protein 2 (IGF2BP2). RFC4 expression was increased in BRCA cell lines and tissues, and high RFC4 expression in BRCA patients predicted the occurrence of lymphatic metastasis. RFC4-specific short hairpin RNA sequences or RFC4 coding sequences were subsequently cloned and inserted into plasmid vectors to downregulate or upregulate RFC4 expression. Knockdown of RFC4 attenuated stemness, as evidenced by a reduction in sphere formation and the downregulation of CD44 and SOX2. RFC4 silencing inhibited migration and invasion, promoted apoptosis, and improved sensitivity to radiotherapy (4-Gy X-ray). The results were detected by a wound healing assay, a transwell assay, and flow cytometry. The overexpression of RFC4 had the opposite effect on BRCA cells. Like RFC4 expression, IGF2BP2 expression was also increased in the cancer tissues of breast cancer patients. The results of the dual luciferase assay and RIP assay confirmed the binding of IGF2BP2 to the RFC4 mRNA coding sequence. Knockdown of RFC4 eliminated the effects of IGF2BP2 overexpression on increasing cell viability, invasion, the expression of stemness markers and radioresistance, suggesting that the effect of RFC4 on the stemness of BRCA cells was regulated by IGF2BP2. In conclusion, we reported that RFC4, a key regulator of BRCA progression, promoted radioresistance in BRCA and was positively regulated by IGF2BP2.
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Nature Communications
·
2024
·Vol. 15
·期 1
·1-10
·
IF 14.7
Wang Tianjiao,Xin Yu,Chen Bingfeng,Zhang Bin,Luan Sen,Dong Minghua,Wu Yuxuan,Cheng Xiaomeng,Liu Ye,Liu Huizhen,Han Buxing
Achieving selective hydrodeoxygenation of α, β-unsaturated carbonyl groups to alkenes poses a substantial challenge due to the presence of multiple functional groups. In this study, we develop a ZnNC-X catalyst (X represents the calcination temperature) that incorporates both Lewis acidic-basic sites and Zn-N x sites to address this challenge. Among the catalyst variants, ZnNC-900 catalyst exhibits impressive selectivity for alkenes in the hydrodeoxygenation of α, β-unsaturated carbonyl compounds, achieving up to 94.8% selectivity. Through comprehensive mechanism investigations and catalyst characterization, we identify the Lewis acidic-basic sites as responsible for the selective hydrogenation of C=O bonds, while the Zn-N x sites facilitate the subsequent selective hydrodeoxygenation step. Furthermore, ZnNC-900 catalyst displays broad applicability across a diverse range of unsaturated carbonyl compounds. These findings not only offer valuable insights into the design of effective catalysts for controlling alkene selectivity but also extend the scope of sustainable transformations in synthetic chemistry.
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WATER AIR AND SOIL POLLUTION
·
2024
·Vol. 235
·期 8
·1-16
·
IF 3.8
Deng Wenchao,Wang Guanghui,Wang Bing,Deng Nansheng
The contamination of soil with cadmium (Cd) poses a significant risk to both food safety and human health. It is crucial to urgently identify an effective technology for remediating Cd-contaminated soil. In the present study, a novel sulfur modified biochar supported ferrous sulfide (FeS@SBC) composite was fabricated by calcination and hydrothermal method. Indoor culture, column leaching, and pot experiments were employed to examine the immobilization effect of FeS@SBC on Cd in contaminated soil. The outcomes illustrated a significant immobilization effect on the Cd-contaminated soil with the application of FeS@SBC. After incubating the soil with the stabilizer for 28 d, the Cd that was previously highly mobile underwent a transformation into an immobilized state. In the experiment on leaching using simulated acid rain, the treatment with FeS@SBC showed a noteworthy decrease in the cumulative loss and leaching efficiency of Cd when compared to the control experiment. It achieved reductions of 70.9% and 71.6%, respectively. The adsorption and immobilization mechanisms resulted from co-precipitation, ion exchange and surface complexation. In the outdoor pot experiment, after 28 d of growth, the water spinach in contaminated soil treated with FeS@SBC has a better growth compared to the control group, with a biomass increase of 134.95%. Additionally, the values of BCF and TF of Cd decreased by 62.25% and 40.39%, respectively, and the available concentration of Cd in the soil decreased by 23.87%. The FeS@SBC composite shows promise as an effective stabilizer for remediating Cd-contaminated soil.
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Nature Communications
·
2024
·Vol. 15
·期 1
·1-10
·
IF 14.7
Cui Fangyan,Li Jingzhen,Lai Chen,Li Changzhan,Sun Chunhao,Du Kai,Wang Jinshu,Li Hongyi,Huang Aoming,Peng Shengjie,Hu Yuxiang
Conventionally, rocking-chair batteries capacity primarily depends on cation shuttling. However, intrinsically high-charge-density metal-ions, such as Al 3+ , inevitably cause strong Coulombic ion-lattice interactions, resulting in low practical energy density and inferior long-term stability towards rechargeable aluminium batteries (RABs). Herein, we introduce tunable quantum confinement effects and tailor a family of anion/cation co-(de)intercalation superlattice cathodes, achieving high-voltage anion charge compensation, with extra-capacity, in RABs. The optimized superlattice cathode with adjustable van der Waals not only enables facile traditional cation (de)intercalation, but also activates O 2– compensation with an extra anion reaction. Furthermore, the constructed cathode delivers high energy-density (466 Wh kg –1 at 107 W kg −1 ) and one of the best cycle stability (225 mAh g –1 over 3000 cycles at 2.0 A g –1 ) in RABs. Overall, the anion-involving redox mechanism overcomes the bottlenecks of conventional electrodes, thereby heralding a promising advance in energy-storage-systems.
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ARCHIVES OF MICROBIOLOGY
·
2024
·Vol. 206
·期 8
·1-26
·
IF 2.3
Li Can,Wang Jun,Li Hao,Wang Yemei,Wu Hui,Wei Wenfan,Wu Daqiang,Shao Jing,Wang Tianming,Wang Changzhong
Candida auris , a rapidly spreading multi-drug‐resistant fungus, is causing lethal infections under certain conditions globally. Baicalin (BE), an active ingredient extracted from the dried root of Scutellaria baicalensis Georgi, exhibits antifungal activity. However, studies have shown the distinctive advantages of Traditional Chinese medicine in combating fungal infections, while the effect of BE, an active ingredient extracted from the dried roots of Scutellaria baicalensis Georgi, on C. auris, remains unknown. Therefore, this study aims to evaluate the potential of BE as an antifungal agent against the emerging multidrug‐resistant C. auris . Various assays and models, including microbroth dilution, time growth curve analysis, spot assays, adhesion tests, flocculation test, cell surface hydrophobicity assay, hydrolase activity assays, XTT assay, violet crystal assay, scanning electron microscope (SEM), confocal laser scanning microscope (CLSM), flow cytometry, Live/dead fluorescent staining, reactive oxygen species (ROS), cell wall assay, aggregation assay, porcine skin model, Galleria mellonella larvae ( G. mellonella larvae) infection model, and reverse transcription–quantitative polymerase chain reaction (RT-PCR) were utilized to investigate how baicalein suppresses C. auris through possible multifaceted mechanisms. The findings indicate that BE strongly inhibited C. auris growth, adhesion, and biofilm formation. It also effectively reduced drug resistance and aggregation by disrupting the cell membrane and cell wall while reducing colonization and invasion of the host. Transcriptome analysis showed significant modulation in gene expression related to different virulence factors post‐BE treatment. In conclusion, BE exhibits significant effectiveness against C. auris , suggesting its potential as a viable treatment option due to its multifaceted suppression mechanisms. Graphical abstract Schematic representation of this study. Baicalein (BE) can effectively hinder the growth and colonization of C. auris by disrupting the expression of multiple virulence factors. This results in a strong antifungal effect, providing protection to the host from infection.
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Nature Communications
·
2025
·Vol. 16
·期 1
·1-15
·
IF 15.7
Tian Jia-Hong,Huang Siyuan,Wang Ze-Han,Li Juan-Juan,Song Xianhui,Jiang Ze-Tao,Shi Bing-Sen,Zhao Ying-Ying,Zhang Hui-Yan,Wang Ke-Rang,Hu Xin-Yue,Zhang Xinge,Guo Dong-Sheng
Pathogenic intracellular bacteria pose a significant threat to global public health due to the barriers presented by host cells hindering the timely detection of hidden bacteria and the effective delivery of therapeutic agents. To address these challenges, we propose a tandem diagnosis-guided treatment paradigm. A supramolecular sensor array is developed for simple, rapid, accurate, and high-throughput identification of intracellular bacteria. This diagnostic approach executes the significant guiding missions of screening a customized host-guest drug delivery system by disclosing the rationale behind the discrimination. We design eight azocalix[4]arenes with differential active targeting, cellular internalization, and hypoxia responsiveness to penetrate cells and interact with bacteria. Loaded with fluorescent indicators, these azocalix[4]arenes form a sensor array capable of discriminating eight intracellular bacterial species without cell lysis or separation. By fingerprinting specimens collected from bacteria-infected mice, the facilitated accurate diagnosis offers valuable guidance for selecting appropriate antibiotics. Moreover, mannose-modified azocalix[4]arene (ManAC4A) is screened as a drug carrier efficiently taken up by macrophages. Doxycycline loaded with ManAC4A exhibits improved efficacy against methicillin-resistant Staphylococcus aureus -infected peritonitis. This study introduces an emerging paradigm to intracellular bacterial diagnosis and treatment, offering broad potential in combating bacterial infectious diseases.
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Journal of Inorganic and Organometallic Polymers and Materials
·
2024
·
IF 3.9
Zhao Qiong,Duan Jianying
Membranous glomerulonephritis (MN) is clinically marked by significant proteinuria or nephrotic syndrome, and pathologically by a uniform thickening of the glomerular capillary basement membrane due to diffuse subepithelial immune complex deposition without notable cell proliferation. In this study, we synthesized a novel therapeutic agent, compound 1, designed for synergistic use with Eculizumab (Ecu) in MN treatment. To optimize the delivery and therapeutic effect of this combination, we developed an advanced composite drug carrier, mPEG-pHPMA@CP1@1@Ecu, incorporating methoxy polyethylene glycol (mPEG) and poly(2-hydroxypropyl methacrylamide) (pHPMA) with a metal-organic framework known as CP1. Structural and compositional integrity of this carrier was rigorously characterized. Our studies demonstrated that mPEG-pHPMA@CP1@1@Ecu could significantly mitigate hypoxia-induced renal tubular epithelial cell damage, highlighting the synergistic potential of compound 1 and Ecu. This new carrier system shows promising therapeutic potential for MN management.
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Nature Communications
·
2025
·Vol. 16
·期 1
·1-11
·
IF 15.7
Wang Zhigui,Lu Guolong,Wei Tianran,Meng Ge,Cai Haoxiang,Feng Yanhong,Chu Ke,Luo Jun,Hu Guangzhi,Wang Dingsheng,Liu Xijun
Aqueous redox flow batteries (RFBs) incorporating polysulfide/iodide chemistries have received considerable attention due to their safety, high scalability, and cost-effectiveness. However, the sluggish redox kinetics restricted their output energy efficiency and power density. Here we designed a defective MoS 2 nanosheets supported Co single-atom catalyst that accelerated the transformation of S 2− /S x 2− and I − /I 3 − redox couples, hence endow the derived polysulfide–iodide RFB with an initial energy efficiency (EE) of 87.9% and an overpotential of 113 mV with an average EE 80.4% at 20 mA cm −2 and 50% state-of-charge for 50 cycles, and a maximal power density of 95.7 mW cm −2 for an extended cycling life exceeding 850 cycles at 10 mA cm −2 and 10% state-of-charge. In situ experimental and theoretical analyses elucidate that Co single atoms induce the generation of abundant sulfur vacancies in MoS 2 via a phase transition process, which synergistically contributed to the enhanced adsorption of reactants and key reaction intermediates and improved charge transfer, resulting in the enhanced RFB performance.
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JOURNAL OF MATERIALS SCIENCE
·
2025
·
IF 3.9
Wang Yifan,Dong Wenjian,Yan Xuefeng,Li Xia,Yu Liangmin
Tin-free self-polishing antifouling coatings are prevalent today. However, its high Cu 2 O content endangers the marine environment. Leveraging the fluorescent properties of coating to prevent fouling is an environmentally friendly antifouling coating development. In this paper, four unreported fluorescent structural carbazole amide derivatives (FSCAD) were synthesized by Friedel–Crafts alkylation reaction. Their fluorescence, antibacterial, and algal inhibition properties were examined. The fluorescent properties test results showed that the four FSCAD exhibited high fluorescence properties. The results of antibacterial test and anti-algae growth test showed that the maximum bacterial inhibition rate can reach 90%, and the growth inhibition rate of three kinds of microalgae can reach more than 75%. It was added to the antifouling coating system as an antifouling agent instead of the traditional antifouling agent Cu 2 O. The abrasion rate, contact angle, surface morphology, and roughness of the coatings were determined by dynamic simulation experiments, and the antifouling properties of the coatings were evaluated by the anti-algae sedimentation test and marine environment antifouling experiments. The results of dynamic simulation experiments showed that adding FSCAD does not affect the wettability and surface state of the coating. Anti-algae sedimentation test exhibited that marine antifouling coatings with FSCAD showed excellent inhibition on the sedimentation of microalgae. The anti-fouling performance of the coating was tested in the marine environment antifouling experiments. The results showed that the coating exhibited excellent anti-fouling performance, with minimal biofouling was attached to the surface of the coating. Especially, the antifouling performance with compound A was better than that of chlorothalonil. Graphical abstract
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危险品化学品经营许可证（带存储）