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Acta Pharmaceutica Sinica B 2015年第1期5卷 34-37页

作者： zilan song Meining Wang Ao Zhang CAS Key Laboratory of Receptor Research Synthetic Organic & Medicinal Chemistry LaboratoryShanghai Institute of Materia Medica (SIMM) Chinese Academy of Sciences

The development of inhibitors for the tyrosine anaplastic lymphoma kinase (ALK) has advanced rapidly, driven by biology and medicinal chemistry. The first generation ALK inhibitor crizotinib was granted US FDA approval with only four years of preclinical and clinical testing. Although this drug offers significant clinical benefit to the ALK-positive patients, resistance has been developed through a variety of mechanisms. In addition to ceritinib, alectinib is another second-generation ALK inhibitor launched in 2014 in Japan. This drug has a unique chemical structure bearing a 5H-benzo[b] carbazol-11(611)-one structural scaffold with an IC50 value of 1.9 nmol/L, and is highly potent against ALK bearing the gatekeeper mutation L1196M with an IC50 of 1.56 nmoL/L. In the clinic, alectinib is highly efficacious in treatment of ALK-positive non-small cell lung cancer (NSCLC), and retains potency to combat crizotinib-resistant ALK mutations L11.96.M, F1174L, R1275Q and C1156Y. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. All rights reserved.

关键词： Tyrosine anaplastic lymphoma kinase Alectinib Crizotinib Non-suaall cell lung cancer Resistance ALK mutations EML4-ALK

Small molecules targeting the innate immune cGAS-STING-TBK1 signaling pathway

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Acta Pharmaceutica Sinica B 2020年第12期10卷 2272-2298页

作者： Chunyong Ding zilan song Ancheng Shen Tingting Chen Ao Zhang Research Laboratory of Medicinal Chemical Biology&Frontiers on Drug Discovery(RLMCBFDD) School of PharmacyShanghai Jiao Tong UniversityShanghai 200240China CAS Key Laboratory of Receptor Research Shanghai Institute of Materia Medica(SIMM)Chinese Academy of SciencesShanghai 201203China University of Chinese Academy of Sciences Beijing 100049China

Multiple cancer immunotherapies including chimeric antigen receptor T cell and immune checkpoint inhibitors(ICIs)have been successfully developed to treat various cancers by motivating the adaptive anti-tumor ***,the checkpoint blockade approach has achieved great clinic success as evidenced by several *** and Drug Administration(FDA)-approved antiprogrammed death receptor 1/ligand 1 or anti-cytotoxic T lymphocyte associated protein 4 ***,the majority of cancers have low clinical response rates to these ICIs due to poor tumor ***,the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes-TANK-binding kinase 1(cGAS-STING-TBK1)axis is now appreciated as the major signaling pathway in innate immune response across different *** signaling of this pathway has been closely linked to multiple diseases,including auto-inflammation,virus infection and *** this perspective,we provide an updated review on the latest progress on the development of small molecule modulators targeting the cGAS-STING-TBK1 signaling pathway and their preclinical and clinical use as a new immune stimulatory ***,highlights on the clinical candidates,limitations and challenges,as well as future directions in this field are also ***,small molecule inhibitors targeting this signaling axis and their potential therapeutic use for various indications are discussed as well.

关键词： mmunotherapy Anti-tumor cGAS STING TBK1 Small molecule modulators

Tectonic modes of mantle convection and their implications for Earth's tectonic evolution based on three-dimensional numerical simulations

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Science China Earth Sciences 2025年第1期68卷 270-296页

作者： song XIANG Jinshui HUANG Bingcheng WU School of Earth and Space Sciences University of Science and Technology of China CAS Center of Excellence in Comparative Planetary Studies

Five tectonic modes of mantle convection are obtained and analyzed with three-dimensional numerical models in a spherical shell domain. The five tectonic convective modes are non-plate mobile-lid, plate-like mobile-lid, episodic plate-like mobile-lid, episodic stagnant-lid, and stagnant-lid convective modes, respectively. The typical characteristics of these five tectonic modes and their numerical classification criteria based on plateness, mobility, and their standard deviations are presented and discussed. The results show that the yield stress of the lithosphere has profound effects on the tectonic convective *** the gradual increase of yield stress, the tectonic mode of mantle convection changes from one to another sequentially through the aforementioned five modes. Additionally, as the Rayleigh number increases, the range of yield stress for the platelike mobile-lid convective mode decreases, and the dimensionless transition stress between different tectonic modes ***, the dimensional transition stress between the non-plate mobile-lid convective mode and plate-like mobile-lid convective mode increases with the increase of Rayleigh number, but decreases between other tectonic modes. Furthermore, we find that the transition stress between different tectonic modes is inversely proportional to the internal heating rate, with the transition stress decreasing as the internal heating rate increases. The fitting analysis of the transition stress between tectonic modes shows that Earth's current plate tectonics correspond to a lithospheric yield stress of 150–250 MPa, which aligns with the strength of serpentinized mantle rock determined by experimental petrography. If the Archean mantle was 300°C warmer than it is today, then the Earth was in an episodic stagnant-lid convective mode. The tectonic evolution of the Earth's surface is closely related to the lithospheric strength and the process of thermal evolution. If the lithospheric strength w

关键词： Tectonic mode of mantle convection Plate-like mobile-lid convection Episodic plate-like mobile-lid convection Episodic stagnant-lid convection Plate tectonics and tectonic evolution of the Earth

Molecular dynamics simulations of helium transport through inorganic mineral nanopores

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Science China Earth Sciences 2025年第1期68卷 237-252页

作者： Dandan song Ping GUAN Chi ZHANG Jiahao REN School of Earth and Space Sciences Peking University

Helium transport through nanoscale inorganic mineral pores and pore throats is essential for its overall migration. To elucidate helium's transport dynamics within nanopores, we employed equilibrium and non-equilibrium molecular dynamics simulations to investigate helium's static self-diffusion and pressure-driven flow in quartz slit-shaped nanopores. We also introduced water and various gases, including hydrogen, methane, ethane, nitrogen, and carbon dioxide, into the nanopores to assess their influence on helium transport. Our findings indicate minimal helium adsorption on quartz pore surfaces. Under conditions where the pore size is less than 5 nm and the pressure under 10 MPa, environmental factors markedly influence helium diffusion. Large pore sizes, high temperatures, and low gas pressures enhance helium desorption and facilitate faster diffusion. We observed a positive correlation between helium flow velocity and factors such as pore size, pressure gradient, and surface smoothness of the pores. Notably, the presence of pore water and carrier gases in quartz nanopores, which diffuse more slowly than helium, tends to reduce helium surface adsorption and slow its diffusion. Among the carrier gases studied, nitrogen showed similar adsorption capacity, diffusivity, and stability to helium, while carbon dioxide displayed the highest adsorption capacity and the slowest diffusion rate, markedly differing from helium. Based on the simulation results, we concluded that water and carrier gases primarily function as transport mediums in helium migration, moving together with helium. Nitrogen, which shares similar properties with helium, effectively assists in this co-migration process. Conversely, carbon dioxide, due to its high adsorption capacity and slow diffusion, tends to be lost during co-migration. As a result, gas reservoirs with high nitrogen levels and low carbon dioxide levels are more likely to have higher helium concentrations. Additionally, the smaller por

关键词： Helium transport Slit nanopores Molecular dynamics simulations Diffusion Flow carriers

CAF-derived exosome-miR-3124-5p promotes malignant biological processes in NSCLC via the TOLLIP/TLR4-MyD88-NF-κB pathway

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Oncology Research 2025年第1期33卷 133-148页

作者： TAO SUN QINGHUA song HUA LIU Department of Respiratory and Critical Care Medicine Affiliated Hospital of Nantong UniversityMedical School of Nantong UniversityNantong226001China Department of Emergency The People’s Hospital of RugaoNantong226500China Department of Haematology The People’s Hospital of RugaoNantong226500China

Background:Lung cancer is a life-threatening disease that occurs worldwide,but is especially common in *** crucial role of the tumour microenvironment(TME)in non-small cell lung cancer(NSCLC)has attracted recent ***-associated fibroblasts(CAFs)are the main factors that contribute to the TME function,and CAF exosomes are closely linked to ***:The expression levels of miR-3124-5p and Toll-interacting protein(TOLLIP)were analysed by bioinformatics prediction combined with RT-qPCR/Western Blot *** were isolated and identified from clinical NSCLC *** electron microscopy and Western Blot were used to identify exosomes from these *** in proliferation(CCK-8 and clone formation),migration(wound healing),and invasion(transwell)of NSCLC cells were *** Luciferase reporter test was applied to clarify the binding of miR-3124-5p to *** TOLLIP/TLR4/MyD88/NF-κB pathway proteins were determined using Western blot ***:MiR-3124-5p is overexpressed in clinical tissues and cells of ***-3124-5p was dramatically enriched in CAF-derived *** experiments revealed that CAFs delivered miR-3124-5p into NSCLC cells via exosomes,stimulating cancer cell ***-3124-5p acted as a sponge to negatively regulate TOLLIP expression,which activated the TLR4/MyD88/NF-κB axis to promote the occurrence and development of *** salvage tests were performed to determine whether CAF-exosome-derived miR-3124-5p plays a pro-cancer role in NSCLC by affecting the TOLLIP signalling ***:These results provide an interesting direction for the diagnosis and therapy of NSCLC.

关键词： Non-small cell lung cancer(NSCLC) Cancer-associated fibroblasts(CAFs) Exosomes miR-3124-5p Toll-interacting protein(TOLLIP)

Constraints on holographic QCD phase transitions from PTA observations

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 71-78页

作者： song He Li Li Sai Wang Shao-Jiang Wang Center for Theoretical Physics and College of Physics Jilin University School of Physical Science and Technology Ningbo University Max Planck Institute for Gravitational Physics (Albert Einstein Institute) CAS Key Laboratory of Theoretical Physics Institute of Theoretical Physics Chinese Academy of Sciences School of Fundamental Physics and Mathematical Sciences Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of Sciences (UCAS) School of Physical Sciences University of Chinese Academy of Sciences (UCAS) Theoretical Physics Division Institute of High Energy Physics Chinese Academy of Sciences

The underlying physics of QCD phase transition in the early Universe remains largely unknown due to its strong-coupling nature during the quark-gluon plasma/hadron gas transition, yet a holographic model has been proposed to quantitatively fit the lattice QCD data while with its duration of the first-order phase transition(FoPT) left undetermined. At specific baryon chemical potential, the first-order QCD phase transition agrees with the observational constraint of baryon asymmetry. It, therefore, provides a scenario for phase transition gravitational waves(GWs) within the standard model of particle physics. If these background GWs could contribute dominantly to the recently claimed common-spectrum red noise from pulsar timing array(PTA) observations, the duration of this FoPT can be well constrained, and the associated primordial black holes are still allowed by current observations.

关键词： pulsar timing array QCD phase transition gravitational waves primordial black holes

Neuronal regulated cell death in aging-related neurodegenerative diseases:key pathways and therapeutic potentials

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Neural Regeneration Research 2025年第8期20卷 2245-2263页

作者： Run song Shiyi Yin Jiannan Wu Junqiang Yan Department of Neurology The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina Neuromolecular Biology Laboratory The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina

Regulated cell death(such as apoptosis,necroptosis,pyroptosis,autophagy,cuproptosis,ferroptosis,disulfidptosis)involves complex signaling pathways and molecular effectors,and has been proven to be an important regulatory mechanism for regulating neuronal aging and ***,excessive activation of regulated cell death may lead to the progression of aging-related *** review summarizes recent advances in the understanding of seven forms of regulated cell death in age-related ***,the newly identified ferroptosis and cuproptosis have been implicated in the risk of cognitive impairment and neurodegenerative *** forms of cell death exacerbate disease progression by promoting inflammation,oxidative stress,and pathological protein *** review also provides an overview of key signaling pathways and crosstalk mechanisms among these regulated cell death forms,with a focus on ferroptosis,cuproptosis,and *** instance,FDX1 directly induces cuproptosis by regulating copper ion valency and dihydrolipoamide S-acetyltransferase aggregation,while copper mediates glutathione peroxidase 4 degradation,enhancing ferroptosis ***,inhibiting the Xc-transport system to prevent ferroptosis can increase disulfide formation and shift the NADP^(+)/NADPH ratio,transitioning ferroptosis to *** insights help to uncover the potential connections among these novel regulated cell death forms and differentiate them from traditional regulated cell death *** conclusion,identifying key targets and their crosstalk points among various regulated cell death pathways may aid in developing specific biomarkers to reverse the aging clock and treat age-related neurodegenerative conditions.

关键词： apoptosis autophagy cuproptosis disulfidptosis ferroptosis necroptosis neurodegenerative disease neurological aging diseases PANoptosis pyroptosis

Passive activity enhances residual control ability in patients with complete spinal cord injury

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Neural Regeneration Research 2025年第8期20卷 2337-2347页

作者： Yanqing Xiao Mingming Gao Zejia He Jia Zheng Hongming Bai Jia-Sheng Rao Guiyun song Wei song Xiaoguang Li Beijing Key Laboratory for Biomaterials and Neural Regeneration Beijing Advanced Innovation Center for Biomedical EngineeringSchool of Biological Science and Medical EngineeringBeihang UniversityBeijingChina Department of Rehabilitation Evaluation China Rehabilitation Research CenterBeijingChina Cardiac Center Beijing Children’s HospitalCapital Medical UniversityBeijingChina The State Key Laboratory of Virtual Reality Technology and Systems Beihang UniversityBeijingChina Department of Rehabilitation Engineering China Rehabilitation Science InstituteBeijingChina

Patients with complete spinal cord injury retain the potential for volitional muscle activity in muscles located below the spinal injury ***,because of prolonged inactivity,initial attempts to activate these muscles may not effectively engage any of the remaining neurons in the descending pathway.A previous study unexpectedly found that a brief clinical round of passive activity significantly increased volitional muscle activation,as measured by surface *** this study,we further explored the effect of passive activity on surface electromyographic signals during volitional control tasks among individuals with complete spinal cord *** patients with chronic complete thoracic spinal cord injury were *** electromyography data from eight major leg muscles were acquired and compared before and after the passive activity *** results indicated that the passive activity led to an increased number of activated volitional muscles and an increased frequency of *** the cumulative root mean square of surface electromyography amplitude for volitional control of movement showed a slight increase after passive activity,the difference was not statistically *** findings suggest that brief passive activity may enhance the ability to initiate volitional muscle activity during surface electromyography tasks and underscore the potential of passive activity for improving residual motor control among patients with motor complete spinal cord injury.

关键词： complete spinal cord injury cycle training epidural electrical stimulation motor training passive activity physiological state spinal cord circuit surface electromyography volitional control task

Domain generalization with semi-supervised learning for people-centric activity recognition

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Science China(Information Sciences) 2025年第1期68卷 171-188页

作者： Jing LIU Wei ZHU Di LI Xing HU Liang song Academy for Engineering & Technology Fudan University Shanghai East-bund Research Institute on Networking Systems of AI School of Optoelectronic Information and Computer Engineering University of Shanghai for Science & Technology

People-centric activity recognition is one of the most critical technologies in a wide range of real-world applications,including intelligent transportation systems, healthcare services, and brain-computer interfaces. Large-scale data collection and annotation make the application of machine learning algorithms prohibitively expensive when adapting to new tasks. One way of circumventing this limitation is to train the model in a semi-supervised learning manner that utilizes a percentage of unlabeled data to reduce the labeling burden in prediction tasks. Despite their appeal, these models often assume that labeled and unlabeled data come from similar distributions, which leads to the domain shift problem caused by the presence of distribution gaps. To address these limitations, we propose herein a novel method for people-centric activity recognition,called domain generalization with semi-supervised learning(DGSSL), that effectively enhances the representation learning and domain alignment capabilities of a model. We first design a new autoregressive discriminator for adversarial training between unlabeled and labeled source domains, extracting domain-specific features to reduce the distribution gaps. Second, we introduce two reconstruction tasks to capture the task-specific features to avoid losing information related to representation learning while maintaining task-specific consistency. Finally, benefiting from the collaborative optimization of these two tasks, the model can accurately predict both the domain and category labels of the source domains for the classification task. We conduct extensive experiments on three real-world sensing datasets. The experimental results show that DGSSL surpasses the three state-of-the-art methods with better performance and generalization.

关键词： activity recognition deep learning domain generalization semi-supervised learning adversarial training

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A robust statistical prediction model for late-summer heavy precipitation days in North China

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Science China Earth Sciences 2025年第1期68卷 158-171页

作者： Shunli JIANG Tingting HAN Xin ZHOU Huijun WANG Zhicong YIN Xiaolei song Collaborative Innovation Center on Forecast and Evaluation of Meteorological Disasters/Key Laboratory of Meteorological Disaster Ministry of Education Nanjing University for Information Science and Technology Nansen-Zhu International Research Centre Institute of Atmospheric Physics Chinese Academy of Sciences Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai)

Recently, heavy precipitation(HP) events have occurred frequently in North China(NC), causing devastating economic losses and human fatalities. However, the short-term climate prediction of HP is quite limited. Combining year-to-year increment(DY) method and sliding correlations, we developed a robust seasonal prediction model for late-summer HP days(HPDs) in NC during 1982–2022, utilizing three independent predictors—February sea surface temperature(SST) in the Indian Ocean(SST＿IO), February snow depth over North Asia(SDE＿NA), and May melted snow depth in NC(MSDE＿NC). The SST＿IO anomalies affect NC's precipitation through the Pacific-Japan pattern. The SDE＿NA anomalies are associated with East Asian anomalous anticyclone by southeastern propagation of Rossby wave at Eurasia. The MSDE＿NC anomalies are followed by vertical motion and moisture anomalies in situ and thereby cause precipitation anomalies. This prediction model can well simulate the variations of the HPDs, with a correlation coefficient(CC) of 0.81(0.65) between the observed and predicted HPDs＿DY(HPDs＿anomaly). The percentage with the same sign for 15 extreme HPDs＿anomaly years(PSSE) is 100%.Moreover, in the cross-validation test during 1982–2022, the PSSE for HPDs＿anomaly is as high as 100%, along with a low rootmean-square error of 1.14. For independent hindcasts during 2013–2022, the CC between the observed and predicted HPDs＿DY(HPDs＿anomaly) is 0.93(0.83), together with high Nash-Sutcliffe efficiency(0.82) and agreement index(0.89). Specifically, the predictions are broadly consistent with the observations for 2015, 2016, 2017, 2021, and 2022, reflecting excellent performance of this prediction model of HPDs in NC.

关键词： Heavy precipitation at North China Year-to-year increment approach Robust seasonal prediction Sea surface temperature Snow depth

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