Pub Date : 2025-04-01DOI: 10.1101/2023.02.03.526065
Yao Lulu Xing, Dena Panovska, Jong-Whi Park, Stefan Grossauer, Katharina Koeck, Brandon Bui, Emon Nasajpour, Jeffrey J Nirschl, Zhi-Ping Feng, Pierre Cheung, Pardes Habib, Ruolun Wei, Jie Wang, Wes Thomason, Joanne Xiu, Alexander Beck, Katharina Weber, Patrick N Harter, Michael Lim, Kelly Mahaney, Laura M Prolo, Gerald A Grant, Xuhuai Ji, Kyle M Walsh, Jean M Mulcahy Levy, Dolores Hambardzumyan, Claudia Katharina Petritsch
Resistance to BRAF plus MEK inhibition (BRAFi+MEKi) in BRAFV600E-mutant gliomas drives rebound, progression, and high mortality, yet it remains poorly understood. This study addresses the urgent need to develop treatments for BRAFi+MEKi-resistant glioma in novel mouse models and patient-derived materials. BRAFi+MEKi reveals glioma plasticity by heightening cell state transitions along glial differentiation trajectories, giving rise to astrocyte- and immunomodulatory oligodendrocyte (OL)-like states. PD-L1 upregulation in OL-like cells links cell state transitions to tumor evasion, possibly orchestrated by Galectin-3. BRAFi+MEKi induces interferon response signatures, tumor infiltration, and suppression of T cells. Combining BRAFi+MEKi with immune checkpoint inhibition enhances survival in a T cell-dependent manner, reinvigorates T cells, and outperforms individual or sequential therapies in mice. Elevated PD-L1 expression in BRAF-mutant versus BRAF-wildtype glioblastoma supports the rationale for PD-1 inhibition in patients. These findings underscore the potential of targeting glioma plasticity and highlight combination strategies to overcome therapy resistance in BRAFV600E-mutant HGG.
{"title":"BRAF/MEK Inhibition Induces Cell State Transitions Boosting Immune Checkpoint Sensitivity in BRAFV600E -mutant Glioma.","authors":"Yao Lulu Xing, Dena Panovska, Jong-Whi Park, Stefan Grossauer, Katharina Koeck, Brandon Bui, Emon Nasajpour, Jeffrey J Nirschl, Zhi-Ping Feng, Pierre Cheung, Pardes Habib, Ruolun Wei, Jie Wang, Wes Thomason, Joanne Xiu, Alexander Beck, Katharina Weber, Patrick N Harter, Michael Lim, Kelly Mahaney, Laura M Prolo, Gerald A Grant, Xuhuai Ji, Kyle M Walsh, Jean M Mulcahy Levy, Dolores Hambardzumyan, Claudia Katharina Petritsch","doi":"10.1101/2023.02.03.526065","DOIUrl":"10.1101/2023.02.03.526065","url":null,"abstract":"<p><p>Resistance to BRAF plus MEK inhibition (BRAFi+MEKi) in BRAFV600E-mutant gliomas drives rebound, progression, and high mortality, yet it remains poorly understood. This study addresses the urgent need to develop treatments for BRAFi+MEKi-resistant glioma in novel mouse models and patient-derived materials. BRAFi+MEKi reveals glioma plasticity by heightening cell state transitions along glial differentiation trajectories, giving rise to astrocyte- and immunomodulatory oligodendrocyte (OL)-like states. PD-L1 upregulation in OL-like cells links cell state transitions to tumor evasion, possibly orchestrated by Galectin-3. BRAFi+MEKi induces interferon response signatures, tumor infiltration, and suppression of T cells. Combining BRAFi+MEKi with immune checkpoint inhibition enhances survival in a T cell-dependent manner, reinvigorates T cells, and outperforms individual or sequential therapies in mice. Elevated PD-L1 expression in BRAF-mutant versus BRAF-wildtype glioblastoma supports the rationale for PD-1 inhibition in patients. These findings underscore the potential of targeting glioma plasticity and highlight combination strategies to overcome therapy resistance in BRAFV600E-mutant HGG.</p>","PeriodicalId":10344,"journal":{"name":"Chinese Physics Letters","volume":"34 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11482820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82591681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"物理与天体物理","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01DOI: 10.1088/0256-307x/41/9/090501
Zhong-Zhou Lan
Spinor Bose–Einstein condensates (BECs) are formed when atoms in the multi-component BECs possess single hyperfine spin states but retain internal spin degrees of freedom. This study concentrates on a (1+1)-dimensional three-couple Gross–Pitaevskii system to depict the macroscopic spinor BEC waves within the mean-field approximation. Regarding the distribution of the atoms corresponding to the three vertical spin projections, a known binary Darboux transformation is utilized to derive the N matter-wave soliton solutions and triple-pole matter-wave soliton solutions on the zero background, where N is a positive integer. For those multiple matter-wave solitons, the asymptotic analysis is performed to obtain the algebraic expressions of the soliton components in the N matter-wave solitons and triple-pole matter-wave solitons. The asymptotic results indicate that the matter-wave solitons in the spinor BECs possess the property of maintaining their energy content and coherence during the propagation and interactions. Particularly, in the N matter-wave solitons, each soliton component contributes to the phase shifts of the other soliton components; and in the triple-pole matter-wave solitons, stable attractive forces exist between the different matter-wave soliton components. Those multiple matter-wave solitons are graphically illustrated through three-dimensional plots, density plot and contour plot, which are consistent with the asymptotic analysis results. The present analysis may provide the explanations for the complex natural mechanisms of the matter waves in the spinor BECs, and may have potential applications in designs of atom lasers, atom interferometry and coherent atom transport.
当多分量玻色-爱因斯坦凝聚体(BEC)中的原子具有单超频自旋态但保留内部自旋自由度时,就会形成自旋玻色-爱因斯坦凝聚体(BEC)。本研究以(1+1)维三偶格罗斯-皮塔耶夫斯基系统为研究对象,在均场近似中描述了宏观自旋玻色-爱因斯坦凝聚态波。关于对应于三个垂直自旋投影的原子分布,利用已知的二元达尔布克斯变换推导出了零背景上的 N 个物质波孤子解和三极物质波孤子解(其中 N 为正整数)。对于这些多重物质波孤子,通过渐近分析得到了 N 个物质波孤子和三极物质波孤子中孤子分量的代数表达式。渐近分析结果表明,自旋BEC中的物质波孤子具有在传播和相互作用过程中保持能量含量和相干性的特性。特别是在N个物质波孤子中,每个孤子分量都对其他孤子分量的相移有贡献;在三极物质波孤子中,不同物质波孤子分量之间存在稳定的吸引力。这些多重物质波孤子通过三维图、密度图和等值线图进行了图解,与渐近分析结果一致。本分析可解释自旋BEC中物质波的复杂自然机制,并有可能应用于原子激光器、原子干涉仪和相干原子传输的设计中。
{"title":"Multiple Soliton Asymptotics in a Spin-1 Bose–Einstein Condensate","authors":"Zhong-Zhou Lan","doi":"10.1088/0256-307x/41/9/090501","DOIUrl":"https://doi.org/10.1088/0256-307x/41/9/090501","url":null,"abstract":"Spinor Bose–Einstein condensates (BECs) are formed when atoms in the multi-component BECs possess single hyperfine spin states but retain internal spin degrees of freedom. This study concentrates on a (1+1)-dimensional three-couple Gross–Pitaevskii system to depict the macroscopic spinor BEC waves within the mean-field approximation. Regarding the distribution of the atoms corresponding to the three vertical spin projections, a known binary Darboux transformation is utilized to derive the <italic toggle=\"yes\">N</italic> matter-wave soliton solutions and triple-pole matter-wave soliton solutions on the zero background, where <italic toggle=\"yes\">N</italic> is a positive integer. For those multiple matter-wave solitons, the asymptotic analysis is performed to obtain the algebraic expressions of the soliton components in the <italic toggle=\"yes\">N</italic> matter-wave solitons and triple-pole matter-wave solitons. The asymptotic results indicate that the matter-wave solitons in the spinor BECs possess the property of maintaining their energy content and coherence during the propagation and interactions. Particularly, in the <italic toggle=\"yes\">N</italic> matter-wave solitons, each soliton component contributes to the phase shifts of the other soliton components; and in the triple-pole matter-wave solitons, stable attractive forces exist between the different matter-wave soliton components. Those multiple matter-wave solitons are graphically illustrated through three-dimensional plots, density plot and contour plot, which are consistent with the asymptotic analysis results. The present analysis may provide the explanations for the complex natural mechanisms of the matter waves in the spinor BECs, and may have potential applications in designs of atom lasers, atom interferometry and coherent atom transport.","PeriodicalId":10344,"journal":{"name":"Chinese Physics Letters","volume":"1 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142206936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"物理与天体物理","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We present a novel approach for generating stable three-dimensional (3D) spatiotemporal solitons (SSs) within a rotating Bose–Einstein condensate, incorporating spin–orbit coupling (SOC), a weakly anharmonic potential and cold Rydberg atoms. This intricate system facilitates the emergence of quasi-stable 3D SSs with topological charges |m| ≤ 3 in two spinor components, potentially exhibiting diverse spatial configurations. Our findings reveal that the Rydberg long-range interaction, spin–orbit coupling, and rotational angular frequency exert significant influence on the domains of existence and stability of these solitons. Notably, the Rydberg interaction contributes to a reduction in the norm of topological solitons, while the SOC plays a key role in stabilizing the SSs with finite topological charges. This research of SSs exhibits potential applications in precision measurement, quantum information processing, and other advanced technologies.
{"title":"Rydberg-Induced Topological Solitons in Three-Dimensional Rotation Spin–Orbit-Coupled Bose–Einstein Condensates","authors":"Yang Wang, Jinlong Cui, Hongkai Zhang, Yuan Zhao, Siliu Xu, Qin Zhou","doi":"10.1088/0256-307x/41/9/090302","DOIUrl":"https://doi.org/10.1088/0256-307x/41/9/090302","url":null,"abstract":"We present a novel approach for generating stable three-dimensional (3D) spatiotemporal solitons (SSs) within a rotating Bose–Einstein condensate, incorporating spin–orbit coupling (SOC), a weakly anharmonic potential and cold Rydberg atoms. This intricate system facilitates the emergence of quasi-stable 3D SSs with topological charges |<italic toggle=\"yes\">m</italic>| ≤ 3 in two spinor components, potentially exhibiting diverse spatial configurations. Our findings reveal that the Rydberg long-range interaction, spin–orbit coupling, and rotational angular frequency exert significant influence on the domains of existence and stability of these solitons. Notably, the Rydberg interaction contributes to a reduction in the norm of topological solitons, while the SOC plays a key role in stabilizing the SSs with finite topological charges. This research of SSs exhibits potential applications in precision measurement, quantum information processing, and other advanced technologies.","PeriodicalId":10344,"journal":{"name":"Chinese Physics Letters","volume":"57 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142206935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"物理与天体物理","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The synthetic Floquet lattice, generated by multiple strong drives with mutually incommensurate frequencies, provides a powerful platform for quantum simulation of topological phenomena. In this study, we propose a 4-band tight-binding model of the Chern insulator with a Chern number C = ±2 by coupling two layers of the half Bernevig–Hughes–Zhang lattice and subsequently mapping it onto the Floquet lattice to simulate its topological properties. To determine the Chern number of our Floquet-version model, we extend the energy pumping method proposed by Martin et al. [2017 Phys. Rev. X7 041008] and the topological oscillation method introduced by Boyers et al. [2020 Phys. Rev. Lett.125 160505], followed by numerical simulations for both methodologies. The simulation results demonstrate the successful extraction of the Chern number using either of these methods, providing an excellent prediction of the phase diagram that closely aligns with the theoretical one derived from the original bilayer half Bernevig–Hughes–Zhang model. Finally, we briefly discuss a potential experimental implementation for our model. Our work demonstrates significant potential for simulating complex topological matter using quantum computing platforms, thereby paving the way for constructing a more universal simulator for non-interacting topological quantum states and advancing our understanding of these intriguing phenomena.
由频率互不相称的多个强驱动力产生的合成 Floquet 晶格为拓扑现象的量子模拟提供了一个强大的平台。在本研究中,我们通过耦合半贝内维格-赫希斯-张晶格的两层,提出了一个切尔诺数为 C = ±2 的切尔绝缘体的 4 带紧束缚模型,并随后将其映射到 Floquet 晶格上,以模拟其拓扑特性。为了确定我们的 Floquet 版本模型的切尔数,我们扩展了 Martin 等人提出的能量泵方法[2017 Phys. Rev. X 7 041008]和 Boyers 等人提出的拓扑振荡方法[2020 Phys.模拟结果表明,无论采用上述哪种方法,都能成功地提取出切尔诺数,并提供了极好的相图预测,与最初的双层半贝内维格-赫希斯-张模型得出的理论相图非常吻合。最后,我们简要讨论了我们模型的潜在实验实现方法。我们的工作展示了利用量子计算平台模拟复杂拓扑物质的巨大潜力,从而为构建更通用的非相互作用拓扑量子态模拟器铺平了道路,并推进了我们对这些有趣现象的理解。
{"title":"Simulating a Chern Insulator with C = ±2 on Synthetic Floquet Lattice","authors":"Ling-Xiao Lei, Wei-Chen Wang, Guang-Yao Huang, Shun Hu, Xi Cao, Xin-Fang Zhang, Ming-Tang Deng, Ping-Xing Chen","doi":"10.1088/0256-307x/41/9/090301","DOIUrl":"https://doi.org/10.1088/0256-307x/41/9/090301","url":null,"abstract":"The synthetic Floquet lattice, generated by multiple strong drives with mutually incommensurate frequencies, provides a powerful platform for quantum simulation of topological phenomena. In this study, we propose a 4-band tight-binding model of the Chern insulator with a Chern number <italic toggle=\"yes\">C</italic> = ±2 by coupling two layers of the half Bernevig–Hughes–Zhang lattice and subsequently mapping it onto the Floquet lattice to simulate its topological properties. To determine the Chern number of our Floquet-version model, we extend the energy pumping method proposed by Martin <italic toggle=\"yes\">et al.</italic> [2017 <italic toggle=\"yes\">Phys. Rev. X</italic> <bold>7</bold> 041008] and the topological oscillation method introduced by Boyers <italic toggle=\"yes\">et al.</italic> [2020 <italic toggle=\"yes\">Phys. Rev. Lett.</italic> <bold>125</bold> 160505], followed by numerical simulations for both methodologies. The simulation results demonstrate the successful extraction of the Chern number using either of these methods, providing an excellent prediction of the phase diagram that closely aligns with the theoretical one derived from the original bilayer half Bernevig–Hughes–Zhang model. Finally, we briefly discuss a potential experimental implementation for our model. Our work demonstrates significant potential for simulating complex topological matter using quantum computing platforms, thereby paving the way for constructing a more universal simulator for non-interacting topological quantum states and advancing our understanding of these intriguing phenomena.","PeriodicalId":10344,"journal":{"name":"Chinese Physics Letters","volume":"255 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142206934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"物理与天体物理","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01DOI: 10.1088/0256-307x/41/9/091201
Jin-Zi Wu, Jin-Yi Pang, Jia-Jun Wu
<italic toggle="yes">P<sub>c</sub></italic>(4457) has been discovered over five years, but the parity of this particle remains undetermined. We propose a new interpretation for <italic toggle="yes">P<sub>c</sub></italic>(4457), which is the state generated from the coupled-channel <inline-formula>