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Impacts of Nutlin-3a and exercise on murine double minute 2-enriched glioma treatment

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Neural Regeneration Research 2025年第4期20卷 1135-1152页

作者： Yisheng Chen Zhongcheng fan Zhiwen luo Xueran Kang Renwen Wan fangqi Li Weiwei Lin Zhihua Han Beijie Qi Jinrong Lin Yaying Sun Jiebin Huang Yuzhen Xu Shiyi Chen Department of Sport Medicine Huashan HospitalFudan UniversityShanghaiChina Department of Orthopedic Surgery Hainan Province Clinical Medical CenterHaikou Affiliated Hospital of Central South University Xiangya School of MedicineHaikouHainan ProvinceChina Department of Basic Medicine Shanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Neurosurgery Second Affiliated Hospital of Zhejiang University School of MedicineZhejiang UniversityHangzhouZhejiang ProvinceChina Department of Orthopedics Shanghai General HospitalSchool of Medicine Shanghai Jiao Tong UniversityShanghaiChina Department of Infectious Diseases Children’s Hospital of Fudan UniversityNational Children’s Medical CenterShanghaiChina Department of Rehabilitation The Second Affiliated Hospital of Shandong First Medical UniversityTaianShandong ProvinceChina

Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural *** role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of *** used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other *** demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by *** underscores the intricate relationship between natural compounds such as nutlin-3 and immune *** comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma *** also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic ***-3a inhibited glioma cell proliferation and activated the p53 *** efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or *** using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway ***,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing *** results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma *** research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.

关键词： exercise and SUMO-related gene signatures(ESLRS) glioblastoma management low-grade glioma natural bioactives neural regeneration physical exercise

Engineering high-performance chemiluminescent probes via enzymatic pocket targeting: high-throughput screening for ultralong afterglow imaging of orthotopic hepatocellular carcinoma

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Science China Chemistry 2025年

作者： Shuai Huang Shuaige Bai Ting luo Bin Feng Min Liu fan Zheng Shuang Huang Yanpeng fang Dan Ding Wenbin Zeng Xiangya School of Pharmaceutical Sciences Central South University College of Life Sciences Nankai University

Hepatocellular carcinoma （HCC） is a highly aggressive liver malignancy and the main form of liver cancer. Early diagnosis and treatment of HCC can effectively reduce mortality. Carboxylesterase （CE）-specific detection and imaging can be used for early diagnosis and image-guided surgical of HCC. However, traditional optical probes suffer from poor selectivity and low imaging signal-to-noise ratio. Here, we have constructed a series of chemiluminescent probes for carboxylesterase detection based on the strategy of enzymatic pocket-oriented steric tailoring techniques. The probes with different unique and excellent properties have been obtained through the structure-based steric hindrance adjustment on the recognition site. Here, CE-2 has been successfully used for high-throughput screening of rapid carboxylesterase inhibitors due to its extremely low detection limit (2.5×10-4U mL-1) and fast recognition ability. CE-3 has been successfully used for image-guided surgery of orthotopic hepatocellular carcinoma due to its ultra-long chemiluminescence imaging （over 12 h） of hepatocellular carcinoma. This study may promote advances in the rapid detection and screening of inhibitory drugs for CE and the field of surgical navigation in HCC.

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Selective enhancement of oblique waves caused by finite amplitude second mode in supersonic boundary layer

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Applied Mathematics and Mechanics(English Edition) 2017年第8期38卷 1109-1126页

作者： Cunbo ZHANG jisheng luo Department of Mechanics Tianjin UniversityTianjin 300072China

Nonlinear interactions of the two-dimensional （2D） second mode with oblique modes are studied numerically in a Mach 6.0 fiat-plate boundary layer, focusing on its selective enhancement effect on amplification of different oblique waves. Evolution of oblique modes with various frequencies and spanwise wavenumbers in the presence of 2D second mode is simulated successively, using a modified parabolized stability equation （PSE） method, which is able to simulate interaction of two modes with different frequen- cies efficiently. Numerical results show that oblique modes in a broad band of frequencies and spanwise wavenumbers can be enhanced by the finite amplitude 2D second mode instability wave. The enhancement effect is accomplished by interaction of the 2D second mode, the oblique mode, and a forced mode with difference frequency. Two types of oblique modes are found to be more amplified, i.e., oblique modes with frequency close to that of the 2D second mode and low-frequency first mode oblique waves. Each of them may correspond to one type of transition routes found in transition experiments. The spanwise wavenumber of the oblique wave preferred by the nonlinear interaction is also determined by numerical simulations.

关键词： supersonic boundary layer boundary layer instability nonlinear mode interaction

Global instability of Stokes layer for whole wave numbers

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Applied Mathematics and Mechanics(English Edition) 2016年第8期37卷 999-1012页

作者： Wei KONG jisheng luo Department of Mechanics Tianjin University

The study on the global instability of a Stokes layer, which is a typical unsteady flow, is usually a paradigm for understanding the instability and transition of unsteady flows. Previous studies suggest that the neutral curve of the global instability obtained by the Floquet theory is only mapped out in a limited range of wave numbers （0.2 ≤ a ≤ 0.5）. In this paper, the global instability is investigated with numerical simulations for all wave numbers. It is revealed that the peak of the disturbances displays irregularity rather than the periodic evolution while the wave number is beyond the above range. A ＂neutral point＂ is redefined, and a neutral curve of the global instability is presented for the whole wave numbers with this new definition. This work provides a deeper understanding of the global instability of unsteady flows.

关键词： Stokes layer instantaneous instability Floquet theory neutral curve

Applications of EPSE method for predicting crossflow instability in swept-wing boundary layers

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Applied Mathematics and Mechanics(English Edition) 2017年第7期38卷 981-996页

作者： Xuezhi LU jisheng luo Department of Mechanics Tianjin University Tianjin 300072 China

The nth-order expansion of the parabolized stability equation （EPSEn） is obtained from the Taylor expansion of the linear parabolized stability equation （LPSE） in the streamwise direction. The EPSE together with the homogeneous boundary conditions forms a local eigenvalue problem, in which the streamwise variations of the mean flow and the disturbance shape function are considered. The first-order EPSE （EPSE1） and the second-order EPSE （EPSE2） are used to study the crossflow instability in the swept NLF（2）-0415 wing boundary layer. The non-parallelism degree of the boundary layer is strong. Compared with the growth rates predicted by the linear stability theory （LST）, the results given by the EPSE1 and EPSE2 agree well with those given by the LPSE. In particular, the results given by the EPSE2 are almost the same as those given by the LPSE. The prediction of the EPSE1 is more accurate than the prediction of the LST, and is more efficient than the predictions of the EPSE2 and LPSE. Therefore, the EPSE1 is an efficient ey prediction tool for the crossflow instability in swept-wing boundary-layer flows.

关键词： swept-wing boundary layer crossflow instability nomparallelism expansionof parabolized stability equation (EPSE) eN prediction tool

Nonlinear interaction mechanisms of disturbances in supersonic flat-plate boundary layers

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Science China(Physics,Mechanics & Astronomy) 2014年第11期57卷 2141-2151页

作者： YU Min luo jisheng Department of Mechanics Tianjin University

Due to the complexity of compressible flows,nonlinear hydrodynamic stability theories in supersonic boundary layers are not *** order to reveal the nonlinear interaction mechanisms of the rapidly amplified 3-D disturbances in supersonic boundary layers at high Mach numbers,the nonlinear evolutions of different disturbances in flat-plate boundary layers at Mach number 4.5,6 and 8 are analyzed by numerical *** can be concluded that the 3-D disturbances are amplified rapidly when the amplitude of the 2-D disturbance reaches a certain *** most rapidly amplified 3-D disturbances are Klebanoff type(K-type)disturbances which have the same frequency as the 2-D *** these K-type 3-D disturbances,the disturbances located at the junction of upper branch and lower branch of the neutral curve are amplified *** analyzing the relationship between the amplification rate and the spanwise wavenumber of the 3-D disturbances at different evolution stages,the mechanism of the spanwise wavenumber selectivity of K-type 3-D disturbances in the presence of a finite amplitude 2-D disturbance is explained.

关键词： disturbance supersonic junction branch introducing selectivity compressible hydrodynamic explained infinity

Extension of e^N method to general three-dimensional boundary layers

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Applied Mathematics and Mechanics(English Edition) 2017年第7期38卷 1007-1018页

作者： Lei ZHAO Gaotong YU jisheng luo Department of Mechanics Tianjin University The 41st Institute of No.6 Academy China Aerospace Science & Industry Corporation

In order to extend the eN method to general three-dimensional boundary layers, the conservation law of the imaginary parts for the wave parameters with a fixed wave vector is deduced. The compatibility relationship （CR） and the general theory of ray tracing （RT）, which have been extensively used in conservative systems, are applied to a general three-dimensional boundary layer belonging to non-conservative systems. Two kinds of eN methods, i.e., the eN-CR method and the eN-RT method, are established. Both the two kinds of methods can wavenumber and the amplitude of the be used to predict the evolutions of the spanwise disturbances in general three-dimensional boundary layers. The reliability of the proposed methods is verified and validated by performing a direct numerical simulation （DNS） in a hypersonic general three-dimensional boundary layer over an aircraft model. The results are also compared with those obtained by other eN methods, indicating that the proposed methods have great potential applications in improving the transition prediction accuracy in general three-dimensional boundary layers.

关键词： eN method ray tracing theory transition prediction three-dimensionalboundary layer

Response of a hypersonic blunt cone boundary layer to slow acoustic waves with assessment of various routes of receptivity

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Applied Mathematics and Mechanics(English Edition) 2018年第11期39卷 1643-1660页

作者： Bingbing WAN jisheng luo Caihong SU Laboratory for High-Speed Aerodynamics School of Mechanical Engineering Tianjin University

The hypersonic boundary-layer receptivity to slow acoustic waves is investigated for the Mach 6 flow over a 5-degree half-angle blunt cone with the nose radius of 5.08 mm. The plane acoustic wave interacts with the bow shock, and generates all types of disturbances behind the shock, which may take various routes to generate the boundarylayer unstable mode. In this paper, two routes of receptivity are investigated in *** is through the disturbance in the entropy layer. The other is through the slow acoustic wave transmitted downstream the bow shock, which can excite the boundary-layer mode due to the synchronization mechanism. The results show that, for a low frequency slow acoustic wave, the latter route plays a leading role. The entropy-layer instability wave is able to excite the first mode near the neutral point, but its receptivity efficiency is much lower.

关键词： receptivity entropy layer blunt cone hypersonic boundary layer

Improvement for expansion of parabolized stability equation method in boundary layer stability analysis

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Applied Mathematics and Mechanics(English Edition) 2018年第12期39卷 1737-1754页

作者： Yufeng HAN Jianxin LIU jisheng luo Department of Mechanics Tianjin UniversityTianjin 300072China Tianjin Key Laboratory of Modern Engineering Mechanics Tianjin 300072China

An improved expansion of the parabolized stability equation(iEPSE) method is proposed for the accurate linear instability prediction in boundary layers. It is a local eigenvalue problem, and the streamwise wavenumber α and its streamwise gradient dα/dx are unknown variables. This eigenvalue problem is solved for the eigenvalue dα/dx with an initial α, and the correction of α is performed with the conservation relation used in the PSE. The i EPSE is validated in several compressible and incompressible boundary layers. The computational results show that the prediction accuracy of the i EPSE is significantly higher than that of the ESPE, and it is in excellent agreement with the PSE which is regarded as the baseline for comparison. In addition, the unphysical multiple eigenmode problem in the EPSE is solved by using the i EPSE. As a local non-parallel stability analysis tool, the i EPSE has great potential application in the eNtransition prediction in general three-dimensional boundary layers.

关键词： parabolized stability equation(PSE) instability non-parallelism boundary layer