CELL RESEARCH
·
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.
研究领域:
免疫学
·
细胞生物学
·
生物力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
APPLIED SURFACE SCIENCE
·
2022
·
IF 7.392
Zhiyuan Yu,Xin Gu,Yu Gao,Xiaoli Guan,Shuaizhao Jin,Hongjiang Li,Hui Zhang,Xiang Liu
La 0.67 K 0.33- x Sr x MnO 3 thin films were grown on LaAlO 3 ( 010 ) substrates via sol–gel and spin coating methods. The replacement of K ions with Sr ions affected the e g electron bandwidth and concentration of Mn 3+ /Mn 4+ pairs as well as effectively modulated the magnetic/orbital order and lattice structure. Consequently, the ferromagnetic metal to paramagnetic insulation transition was affected, which further optimized the resistivity, temperature coefficient of resistivity ( TCR ), peak TCR temperature ( T K ), and peak resistivity temperature ( T P ). At temperatures below 230 K, temperature-independent scattering and electron-electron scattering were practically not observed in the films. Overall, electrical properties of films improved with an increase in the Sr doping content. The superior La 0.67 K 0.27 Sr 0.06 MnO 3 film exhibited a maximum TCR of 11.88% K −1 (298.3 K), which is approximately 31% higher than that of bulk ceramic with the same composition . The as-developed films exhibit significant potential for application in uncooled infrared bolometers .
研究领域:
材料科学
·
物理学
✓ 已验证
产品关联
DOI
高影响因子
MOLECULAR CELL
·
2019
·
IF 14.548
Peng Wu,Tongtong Zhang,Baoyu Liu,Panyu Fei,Lei Cui,Rui Qin,Huaying Zhu,Danmei Yao,Ryan J. Martinez,Wei Hu,Chenyi An,Yong Zhang,Junwei Liu,Jiawei Shi,Juan Fan,Weiwei Yin,Jie Sun,Chun Zhou,Xun Zeng,Chenqi Xu,Jianan Wang,Brian D. Evavold,Cheng Zhu,Wei Chen,Jizhong Lou
Summary TCRs recognize cognate pMHCs to initiate T cell signaling and adaptive immunity. Mechanical force strengthens TCR-pMHC interactions to elicit agonist-specific catch bonds to trigger TCR signaling, but the underlying dynamic structural mechanism is unclear. We combined steered molecular dynamics (SMD) simulation, single-molecule biophysical approaches, and functional assays to collectively demonstrate that mechanical force induces conformational changes in pMHCs to enhance pre-existing contacts and activates new interactions at the TCR-pMHC binding interface to resist bond dissociation under force, resulting in TCR-pMHC catch bonds and T cell activation. Intriguingly, cancer-associated somatic mutations in HLA-A2 that may restrict these conformational changes suppressed TCR-pMHC catch bonds. Structural analysis also indicated that HLA polymorphism might alter the equilibrium of these conformational changes. Our findings not only reveal critical roles of force-induced conformational changes in pMHCs for activating TCR-pMHC catch bonds but also have implications for T cell-based immunotherapy.
研究领域:
免疫学
·
生物物理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Fapeng Sun,Wei Liu
2D ionic-electronic coupled materials, offering mobile ions as an additional degree of freedom, open new avenues for device functionality beyond traditional electronic systems. However, harnessing ionic-electronic interactions to achieve broadband photodetection remains unexplored. Here, a van der Waals ionic-electronic semiconductor is reported that exhibits an ultrahigh and anisotropic temperature coefficient of resistance (TCR) of −7.29% °C −1 , which is attributed to its high ionic activation energy. Leveraging both photoelectric and bolometric effects, AIPSe enables dual-mode photodetection across the visible to near-infrared range. Through device engineering with asymmetric Schottky contacts and ionic migration modulation, photodiodes with an ultrahigh rectification ratio of ≈108 and bias-tunable dual-mode operation: photovoltaic detection with a responsivity of 0.385 A W −1 at 532 nm, and bolometric sensing with 0.486 A W −1 at 1550 nm is achieved. These devices demonstrate spectral self-recognition, secure dual-band optical communication, and multi-wavelength imaging capabilities. The work establishes ionic-electronic correlated transport in 2D materials as a new paradigm for beyond-bandgap optoelectronic technologies.
研究领域:
光电子学
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材料科学
·
纳米技术
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半导体物理
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光子学
✓ 已验证
产品关联
DOI
高影响因子
CERAMICS INTERNATIONAL
·
2023
·
IF 5.2
Xiaokun Zhu,Xin Gu,Jiamei Han,Jiabin Jiang,Zimeng Pan,Jiachen Wang,Zihao Chen,Xiang Liu
Facile-prepared films with a high-temperature coefficient of resistivity ( TCR ) are crucial for application in high-sensitivity bolometers. In this study, La 0.7 Ca 0.25 K 0.05 MnO 3 (LCKMO) films were grown on (001)-oriented La 0.3 Sr 0.7 Al 0.65 Ta 0.35 O 3 (LSAT) substrates using the spin-coating method. Various sintering temperatures (900 °C ≤ T s ≤ 1050 °C) were utilized in the film preparation, causing the lattice mismatch between films and substrate degraded. The effect of T s on the strain state of films was investigated through X-ray diffraction (XRD) analysis. The distortion of MnO 6 octahedra and the Mn–O bond were assessed using Raman and FTIR spectra, respectively. The structural perfection and elemental valence of films were adjusted via optimizing T s . Meanwhile, the strain state and defect structure were effectively improved with T s increasing. These results indicate that the LCKMO films with high crystalline quality can be achieved by optimizing the sintering process. The TCR of LCKMO films was modified. When T s at 1000 °C, the LCKMO films exhibit the remarkable TCR of 16.29% K -1 at 269.54 K, indicating the substantial potential of LCKMO films in infrared bolometers.
研究领域:
材料科学
·
电子工程
✓ 已验证
DOI
高影响因子
Materials Today Bio
·
2026
·
IF 11
Mingze Yan,Ting Yin,Zhiwei Yu,Guojun Huang,Cheng Xiang,Yourong Jiang,Han Gong,Ting Li,Lizhen Zhu,Hongjiang He,Lintao Cai,Hong Pan
Macrophage have shown great promise in the clinical treatment for head and neck cancer (HNC). However, macrophage therapies confront significant hurdles due to a deficiency of tumor-specific targets and tumor resistance. Herein, we report the development of a magnetotactic bacterial-reprogrammed T-cell receptor macrophage (TCR-M) that integrates human papillomavirus (HPV) associated HNC specific targeting with innate macrophage infiltration capacity, enabling potent immune cytotoxicity against head and neck squamous cell carcinoma (HNSCC). By internalizing magnetotactic bacteria AMB-1, the TCR-M combination achieves tumor-specific targeting and controllable magnetic responsiveness to elicit durable anti-tumor photoimmune response. Notably, AMB-1 incorporation endows macrophages with magnetic navigation capability and laser-responsive polarization into Bac@TCR-M + L, which acquires M1 phenotypes with sustained anti-tumor photoimmune response. Under magnetic actuation, Bac@TCR-M + L demonstrates significantly enhanced tumor site accumulation compared to untreated TCR-M, accompanied by elevated secretion of TNF-α and IFN-γ and augmented reactive oxygen species (ROS) production. Furthermore, Bac@TCR-M + L re-educates tumor-associated macrophages (TAMs) into anti-tumor M1 phenotypes, achieving collaborative tumor destruction. Our findings establish Bac@TCR-M + L as a paradigm-shifting macrophage therapy that integrates microbial engineering, robotic control, and cell therapy, yielding durable anti-tumor effects in HNC treatment and opening new avenues for overcoming cancer resistance.
✓ 已验证
产品关联
DOI
高影响因子
APPLIED SURFACE SCIENCE
·
2026
·
IF 6.9
Yao Wang,Jiabin Jiang,Zhenyu Wang,Haitao Wang,Zihao Chen,Xiaolu Liang,Yiliang Liu,Yufei Du,Jiankun Sun,Xin Gu,Hongjiang Li,Xiang Liu
The electrical transport properties of the La 0.76 Ba 0.24 MnO 3 (LBMO) films are improved by optimizing the pre-sintering temperatures ( T ps ). As T ps increases from 1048 K to 1148 K, the peak temperature coefficient of resistivity ( TCR ) value initially increases and then decreases, and the temperature corresponding to the peak TCR ( T k ) shifts to higher temperatures. At the optimal T ps ( T ps = 1073 K), LBMO films exhibit TCR reaching their maximum value of 12.74% K −1 at T k = 292.02 K. The enhanced room-temperature TCR stems from improved crystallinity, internal strain, crystal structure distortion, and the content of the Mn 4+ of the films. These improvements further optimize aspects such as the double exchange interaction, scattering effect, and activation energy, effectively enhancing electron mobility. The results show that by precisely controlling the T ps , a higher room-temperature TCR value can be attained. This finding provides a critical reference for optimizing the performance of LBMO films, allowing for more efficient and precise tuning of their electrical transport properties.
✓ 已验证
产品关联
DOI
高影响因子
APPLIED SURFACE SCIENCE
·
2023
·
IF 6.7
Jiamei Han,Xin Gu,Xiaokun Zhu,Yixin Yan,Jiabin Jiang,Zihao Chen,Xiang Liu
In this study, Nd 0.67 Sr 0.33 MnO 3 (NSMO) films are deposited on La 0.3 Sr 0.7 Al 0.65 Ta 0.35 O 3 (LSAT) substrates using sol–gel spin coating method and sintered at different temperatures ( T s = 1250, 1300, 1350, 1400 and 1450 °C). Consolidated analysis of their crystal structure, surface morphology and valence states enables one to conclude that increased T s facilitates grain growth and enhances crystallinity of films. Moreover, enhancing T s from 1250 to 1350 °C leads to a decrease in Mn-O bond length ( d (Mn-O) ) and an increase in Mn-O-Mn bond angle ( θ (Mn-O-Mn) ). In the XPS analysis, the Mn 4+ and O 2– content kept increasing with the rise of T s . When Mn 4+ concentration ≤ 33%, the double exchange (DE) interactions was undoubtedly facilitated, which was beneficial for the electrical properties of the NSMO films. These changes eventually result in large temperature coefficient of resistivity ( TCR ). According to these results, Nd 0.67 Sr 0.33 MnO 3 film, with a maximum TCR value of 21.85% K −1 at T s = 1350 °C, are promising materials for the manufacturing of sensitivity switches and infrared bolometers.
研究领域:
材料科学
·
物理学
✓ 已验证
产品关联
DOI
高影响因子
IMMUNITY
·
2025
·
IF 26.3
Yuwei Zhu,Wenbo Gao,Jianlin Zheng,Ye Bai,Xinyu Tian,Tengjin Huang,Zebin Lu,De Dong,Anqi Zhang,Changyou Guo,Zhiwei Huang
Phosphoantigens (pAgs), produced by infected or cancer cells, trigger the assembly of a membrane receptor complex comprising butyrophilin (BTN) members BTN3A1 and BTN2A1, leading to the activation of γδ T cells. BTN3A2 or BTN3A3 forms heteromers with BTN3A1, exhibiting higher γδ T cell receptor (TCR)-stimulating activity than BTN3A1 homomers. Cryoelectron microscopy (cryo-EM) structure reveals a pAg-induced BTN2A1-BTN3A1 heterotetramer with a 2:2 stoichiometry, stabilized by interactions between the intracellular B30.2 domains and the extracellular immunoglobulin V (IgV) domains. BTN3A2 or BTN3A3 heterodimerizes with BTN3A1, forming a pAg-induced tetrameric complex with BTN2A1. However, BTN3A1 heterodimers are more stable than BTN3A1 homodimers in this interaction. Cryo-EM reveals that BTN2A1-BTN3A1-BTN3A2 binds two γδ TCR ectodomains, with one being sandwiched between the IgV domains of BTN2A1 and BTN3A2, while the other interacts with the free BTN2A1 IgV in the complex, as evidenced by functional data. Together, our findings uncover the mechanism of ligand-induced inside-out stabilization of BTN receptor complexes for dimeric activation of γδ TCR.
研究领域:
免疫学
·
结构生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ALLOYS AND COMPOUNDS
·
2021
·
IF 5.316
Xiaohan Yu,Shuaizhao Jin,Xiaoli Guan,Yixin Yan,Kaikai Wu,Liming Zhao,Xiang Liu
La 1- x A x MnO 3 (A = alkaline-earth or alkali metal) perovskites with large temperature coefficient of resistivity ( TCR ) offer immense opportunity for the application in high-performance infrared bolometer. However, numerous studies have revealed that the manganite films with large TCR values are not easily obtained by various fabrication technologies. Herein, a facile sol-gel spin-coating technique was used to prepare La 1- x Ca x MnO 3 (LCMO, 0.280 ≤ x ≤ 0.375) films. All the samples were highly oriented along the out-of-plane direction of La 0.3 Sr 0.7 Al 0.65 Ta 0.35 O 3 (001) substrates. With the rise in Ca doping amount, the resistivity of the films first decreased, and then, increased. This change can be attributed to the competition between the carrier concentration and lattice distortion. The LCMO films displayed large TCR and low-field magnetoresistance ( MR ) values, which exceeded those of previously reported thin films. The maximum TCR and low-field MR values were observed at x = 0.330, reaching 30.13% K −1 (266.43 K) and 68.6% (270.08 K), respectively. The La 0.67 Ca 0.33 MnO 3 film with large TCR and MR values presents potential for the applications in high-sensitivity infrared bolometers and magnetic sensors.
研究领域:
材料科学
·
物理学
✓ 已验证
产品关联
DOI
高影响因子
Translational Cancer Research
·
2020
·
IF 0.986
Qi-Hua Yuan,Guodong Liu,Qiuhui Hu,Jingwen Wang,Kaiming Leng
Background Globally, gastric carcinoma (GC) is one of the most commonly encountered malignancies and is the second highest contributor to cancer mortality. Lapatinib is a potent, orally-bioavailable small-molecule inhibitor of both epidermal growth factor receptor and human epidermal growth factor receptor-2 tyrosine kinases, and is administered to treat GC. However, a large proportion of patients either develop resistance to or do not respond to lapatinib, often because the treatment activates alternative signaling pathways. It is, therefore, vital to identify the key pathways which mediate resistance to lapatinib treatment. Methods The lapatinib sensitivity-related genes were extracted from the CellMiner database (version 2.2) using “NCI-60 Analysis Tools”. The differentially expressed genes (DEGs) in gastric cancer were derived from The Cancer Genome Atlas (TCGA) database, the protein-protein interaction (PPI) network was derived from the Human Protein Reference Database (HPRD), and the Database for Annotation, Visualization and Integrated Discovery (DAVID) facilitated the functional analysis. The cell function was tested by CCK-8 cell viability assay, colony formation assay, acridine orange/ethidium bromide (AO/EB) staining, and Transwell assay. Results The functional linkage networks of lapatinib sensitivity were constructed. Two modules were identified, and pathway analysis indicated that these modules were involved in several pathways, including the neuroactive ligand-receptor interaction network and the Rap1 signaling pathway. Finally, the breast cancer anti-estrogen resistance 1 ( BCAR1 ) gene was selected for further study with lapatinib-resistant SUN216 cells (SUN216/LR). We found the expression of BCAR1 was upregulated in SUN216/LR cells compared to SUN216 cells. The IC50 of lapatinib in SUN216/LR cells was reduced upon BCAR1 knockdown, as measured by a CCK-8 assay. A clonogenic assay showed fewer SUN216/LR colonies with BCAR1 knockdown and lapatinib treatment. Conclusions In brief, we efficiently identified those crucial modules highly related to lapatinib sensitivity in GC by using a topological network method. BCAR1 was identified as a potentially critical gene that plays a role in lapatinib sensitivity, and experiments confirmed that BCAR1 might contribute to lapatinib resistance in GC. These results provide further insight into the molecular basis of lapatinib sensitivity and may offer novel strategies for the future treatment of GC.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Translational Cancer Research
·
2019
·
IF 1.07
Guangyuan Sun,Fei Guo,Xueliang Wu,Lei Han,Jun Xue
Background LncRNA cancer susceptibility candidate 9 (CASC9) is up-regulated in various cancers. In this study, we explored the role of CASC9 in colon cancer (CC). Methods The level of CASC9 in CC tissues, adjacent normal tissues, intestinal epithelial cells (HIEC) and CC cell lines was evaluated by qRT-PCR. HCT116 and SW480 CC cells were transfected with siCASC9. The cell growth and cell proliferation makers (Ki-67 and PCNA) were detected by CCK-8, colony formation and western blotting, respectively. The cell apoptosis and cell cycle were determined by flow cytometry. MicroRNA sponged by CASC9 was predicted by starBase and verified by dual-luciferase reporter assay. Further analyses were performed to investigate the role of CASC9 sponging the microRNA in CC cells by transfection or co-transfection of siCASC9 and miR-145-5p inhibitor. Results LncRNA CASC9 was high-expressed in CC cells and tissues, especially in CC at advanced TNM stages. In HCT116 and SW480 cells, knockdown of CASC9 suppressed cell proliferation, promoted cell apoptosis and arrested cell cycle at G0/G1 phase. Furthermore, CASC9 was observed to sponge and regulate the expression of miR-145-5p, which was down-regulated in CC tissues. Moreover, increased cell proliferation and decreased cell apoptosis and arrested cell cycle caused by miR-145-5p inhibitor were abrogated by the knockdown of CASC9. Conclusions LncRNA CASC9 is an oncogene in CC cells through sponging miR-145-5p. The findings in the current study provide a new understanding on CASC9 in CC.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）