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IL-13/IL-13RA2 signaling promotes colorectal cancer stem cell tumorigenesis by inducing ubiquitinated degradation of p53

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Genes & Diseases 2024年第1期11卷 495-508页

作者： Baoyu He Jing Liang Qianqian Qin Yuqin Zhang Shuo Shi Jinghe Cao Zhixin Zhang Qingli Bie Rou Zhao Li Wei Baogui Zhang Bin Zhang Department of Laboratory Medicine Affiliated Hospital of Jining Medical UniversityJining Medical UniversityJiningShandong 272000China Postdoctoral Mobile Station of Shandong university of Traditional Chinese Medicine JinanShandong 250355China Department of Reproductive Medicine Affiliated Hospital of Jining Medical UniversityJining Medical UniversityJiningShandong 272000China Department of Gastrointestinal Surgery Affiliated Hospital of Jining Medical UniversityJining Medical UniversityJiningShandong 272000China Institute of Forensic Medicine and Laboratory Medicine Jining Medical UniversityJiningShandong 272067China

Cancer stem cells(CSCs)are considered tumor-initiating cells and the main drivers of disease progression.Targeting these rare cancer cells,however,remains challenging with respect to therapeutic benefit.Here,we report the up-regulation of IL-13RA2 expression in colorectal cancer(CRC)tissues and spheroid cells.The expression of IL-13RA2 was positively correlated with canonical stemness markers in CRC.We further demonstrated that the level of IL-13 was up-regulated in the serum of CRC patients.Biologically,recombinant IL-13(rIL13)stimulation promoted the sphere formation,proliferation,and migration of CRC cells in vitro and enhanced tumorigenesis in vivo.This phenotype could be reversed by knocking down IL-13RA2.Mechanistically,IL-13 activated autophagy by inducing LC3I/LC3II transformation in CRC-CSCs,which was crucial for the biological functions of IL-13.We further demonstrated that IL-13RA2 acted as a modular link of the E3 ligase UBE3C and the substrate p53 protein,enhancing the interaction of UBE3C and p53,thereby inducing the K48-linked ubiquitination of p53.In conclusion,the IL-13/IL-13RA2 signaling cascade promotes CRC-CSC self-renewal and tumorigenesis by inducing p53 ubiquitination,adding an important layer to the connection between IL-13 and p53,which can be translated into novel targeted therapies.

关键词： Autophagy Colorectal cancer stem cells IL-13/IL-13RA2 signaling p53

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Noise-Tolerant ZNN-Based Data-Driven Iterative Learning Control for Discrete Nonaffine Nonlinear MIMO Repetitive Systems

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IEEE/CAA Journal of Automatica Sinica 2024年第2期11卷 344-361页

作者： Yunfeng Hu Chong Zhang Bo Wang Jing Zhao Xun Gong Jinwu Gao Hong Chen State Key Laboratory of Automotive Simulation and Control Jilin UniversityJilin UniversityChangchun 130025China College of Communication Engineering Jilin UniversityJilin UniversityChangchun 130025China Department of Electromechanical Engineering University of MacaoMacao 999078China School of Artificial Intelligence Jilin UniversityChangchun 130012China IEEE College of Electronics and Information Engineering Tongji UniversityShanghai 200092China

Aiming at the tracking problem of a class of discrete nonaffine nonlinear multi-input multi-output(MIMO) repetitive systems subjected to separable and nonseparable disturbances, a novel data-driven iterative learning control(ILC) scheme based on the zeroing neural networks(ZNNs) is proposed. First, the equivalent dynamic linearization data model is obtained by means of dynamic linearization technology, which exists theoretically in the iteration domain. Then, the iterative extended state observer(IESO) is developed to estimate the disturbance and the coupling between systems, and the decoupled dynamic linearization model is obtained for the purpose of controller synthesis. To solve the zero-seeking tracking problem with inherent tolerance of noise,an ILC based on noise-tolerant modified ZNN is proposed. The strict assumptions imposed on the initialization conditions of each iteration in the existing ILC methods can be absolutely removed with our method. In addition, theoretical analysis indicates that the modified ZNN can converge to the exact solution of the zero-seeking tracking problem. Finally, a generalized example and an application-oriented example are presented to verify the effectiveness and superiority of the proposed process.

关键词： Adaptive control control system synthesis data-driven iterative learning control neurocontroller nonlinear discrete time systems

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Fucosyltransferase 8 regulates adult neurogenesis and cognition of mice by modulating the Itga6-PI3K/Akt signaling pathway

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Science China(Life Sciences) 2024年第7期67卷 1427-1440页

作者： Hongfeng Guo Qihang Sun Xiaoli Huang Xiaohao Wang Feng Zhang Wenzheng Qu Jinling Liu Xuejun Cheng Qiang Zhu Wen Yi Qiang Shu Xuekun Li The Children’s Hospital National Clinical Research Center for Child HealthSchool of MedicineZhejiang UniversityHangzhou 310052China The Institute of Translational Medicine School of MedicineZhejiang UniversityHangzhou 310029China College of Life Sciences Zhejiang UniversityHangzhou 310058China Binjiang Institute of Zhejiang university Hangzhou 310053China Zhejiang university Cancer Center Zhejiang UniversityHangzhou 310029China

Fucosyltransferase 8(Fut8)and core fucosylation play critical roles in regulating various biological processes,including immune response,signal transduction,proteasomal degradation,and energy metabolism.However,the function and underlying mechanism of Fut8 and core fucosylation in regulating adult neurogenesis remains unknown.We have shown that Fut8 and core fucosylation display dynamic features during the differentiation of adult neural stem/progenitor cells(aNSPCs)and postnatal brain development.Fut8 depletion reduces the proliferation of a NSPCs and inhibits neuronal differentiation of aNSPCs in vitro and in vivo,respectively.Additionally,Fut8 deficiency impairs learning and memory in mice.Mechanistically,Fut8 directly interacts with integrinα6(Itga6),an upstream regulator of the PI3kAkt signaling pathway,and catalyzes core fucosylation of Itga6.Deletion of Fut8 enhances the ubiquitination of Itga6 by promoting the binding of ubiquitin ligase Trim21 to Itga6.Low levels of Itga6 inhibit the activity of the PI3K/Akt signaling pathway.Moreover,the Akt agonist SC79 can rescue neurogenic and behavioral deficits caused by Fut8 deficiency.In summary,our study uncovers an essential function of Fut8 and core fucosylation in regulating adult neurogenesis and sheds light on the underlying mechanisms.

关键词： Fut8 adult neural stem/progenitor cells neurogenesis Itga6 PI3K/Akt

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Females adopt sexual catalepsy to facilitate mating

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Current Zoology 2024年第2期70卷 174-181页

作者： Jihe Liu Keke Liu Yu Tang Weihua Wang Xiang Xu Jianhui Liang Yonghong Xiao Mark A.Elgar College of Life Sciences Jinggangshan UniversityJi'anJiangxi 343009China Pharmaceutical Center Tsinghua UniversityBeijing 100084China College of Life Sciences Hunan Normal UniversityChangshaHunan 410081China School of Pharmaceutical Sciences Peking UniversityBeijing 100083China School of BioSciences University of MelbourneMelbourneVictoria 3010Australia School of Life Sciences and Technology Tongii UniversityShanghai 200092China

Theory predicts that males and females of dioecious species typically engage in an evolutionary sexual conflict over the frequency and choice of mating partner.Female sexual cannibalism,a particularly dramatic illustration of this conflict,is widespread in certain animal taxa including spiders.Nevertheless,females of some funnel weaving spiders that are generally aggressive to conspecifics enter a cataleptic state after male courtship,ensuring the males can mate without risk of attack.In this study,we demonstrated that the physical posture and duration,metabo-lites,and central neurotransmitters of females of Aterigena aculeata in sexual catalepsy closely resemble females in thanatosis but are distinct from those in anesthesia,indicating that the courted females feign death to eliminate the risk of potentially aggressive responses and thereby allow preferred males to mate.Unlike the taxonomically widespread thanatosis,which generally represents a deceptive visual signal that acts against the interest of the receivers,sexual catalepsy of females in the funnel weaving spiders may deliver a sexual-receptive signal to the courting males and thereby benefit both the signal senders and receivers.Therefore,sexual catalepsy in A.aculeata may not reflect a conflict butrather a confluence of interest betweenthe sexes.

关键词： female catalepsy funnel weaving spiders mate choice mating strategy sexual behavior.

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Influence of aging, mitochondrial dysfunction, and inflammation on Parkinson's disease

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Neural Regeneration Research 2024年第6期19卷 1197-1198页

作者： Davide Cossu Nobutaka Hatiori Department of Neurology Juntendo University Department of Biomedical Sciences Sassari University

Aging is associated with chronic form of inflammation called inflammaging,which results from immune system changes.Inflammaging plays a crucial role in the pathogenesis of various neurodegenerative diseases(Dabravolsk...

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Segment-wise learning control for trajectory tracking of robot manipulators under iteration-dependent periods

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Science China(Information Sciences) 2024年第3期67卷 155-166页

作者： Fan ZHANG Deyuan MENG Kaiquan CAI The Seventh Research Division Beihang University School of Automation Science and Electrical Engineering Beihang University School of Electronics and Information Engineering Beihang University

This paper is concerned with the amplitude boundedness problem of adaptive iterative learning control(AILC) for robot manipulators operating with iteration-dependent periods. By introducing virtual memory slots for storing historical data, a practical AILC method is proposed to achieve the segmentwise learning. This method requires less memory storage for historical information of previous iterations,especially in comparison with that of the conventional AILC methods using point-wise learning strategies.It is shown that not only the energy boundedness but also the amplitude boundedness of estimates and inputs of practical AILC can be guaranteed. Moreover, the practical AILC method can achieve the perfect tracking objective regardless of iteration-dependent periods when the robot manipulators have a persistent full learning property. In addition, a solution to the visual manipulator platform is provided and deployed based on Coppeliasim and Matlab, which helps to show the amplitude boundedness of learning results and the perfect tracking performances of the proposed practical AILC method for robot manipulators.

关键词： amplitude boundedness iteration-dependent period iterative learning control robot manipulator segment-wise virtual memory slot

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Neuronal trafficking as a key to functional recovery in immune-mediated neuropathies

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Neural Regeneration Research 2024年第11期19卷 2331-2332页

作者： Felix Kohle Michael Schroeter Department of Neurology University of Cologne and University Hospital CologneCologneGermany

Immune-mediated neuropathies are rare diseases of the peripheral nervous system(PNS),substantially affecting patients’functionality and quality of life.They are amenable to immunomodulatory treatments,which in many cases stabilize disease progression,but long-term deficits persist in many patients.Such long-term deficits are particularly observed in monophasic autoimmune neuropathies like Guillain-Barrésyndrome and also in chronic variants,e.g.,chronic inflammatory demyelinating neuropathy(Fadia et al.,2019).

关键词： diseases autoimmune

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Advances in functional MRI research in bipolar disorder:from the perspective of mood states

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General Psychiatry 2024年第1期37卷 33-43页

作者： Yankun Wu Yun-Ai Su Linlin Zhu Jitao Li Tianmei Si Department of Clinical Psychopharmacology Peking University Sixth HospitalPeking University Institute of Mental HealthNHC Key Laboratory of Mental Health(Peking University)National Clinical Research Center for Mental Disorders(Peking University Sixth Hospital)BeijingChina Peking university Sixth Hospital Peking University Institute of Mental HealthNHC Key Laboratoryof Mental Health(Peking University)National Clinical Research Centerfor Mental Disorders(Peking University Sixth Hospital)BeijingChina

Bipolar disorder is characterised by recurrent and alternating episodes of mania/hypomania and depression.Current breakthroughs in functional MRI techniques have uncovered the functional neuroanatomy of bipolar disorder.However,the pathophysiology underlying mood instability,mood switching and the development of extreme mood states is less well understood.This reviewpresents a comprehensive overviewof current evidence from functional MRI studies from the perspective of mood states.We first summarise the disrupted brain activation patterns and functional connectivity that have been reported in bipolar disorder,irrespective of the mood state.We next focus on research that solely included patients in a single mood state for a better understanding of the pathophysiology of bipolar disorder and research comparing patients with different mood states to dissect mood state-related effects.Finally,we briefly summarise current theoretical models and conclude this review by proposing potential avenues for future research.A comprehensive understanding of the pathophysiology with consideration of mood states could not only deepen our understanding of how acute mood episodes develop at a neurophysiological level but could also facilitate the identification of biological targets for personalised treatment and the development of new interventions for bipolar disorder.

关键词： anatomy bipolar functional

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Ultra-high-Q free-space coupling to microtoroid resonators

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Light(Science & Applications) 2024年第4期13卷 682-695页

作者： Sartanee Suebka Euan McLeod Judith Su Wyant College of Optical Sciences University of ArizonaTucsonAZUSA Department of Biomedical Engineering University of ArizonaTucsonAZUSA

Whispering gallery mode(WGM)microtoroid resonators are one of the most sensitive biochemical sensors in existence,capable of detecting single molecules.The main barrier for translating these devices out of the laboratory is that light is evanescently coupled into these devices though a tapered optical fiber.This hinders translation of these devices as the taper is fragile,suffers from mechanical vibration,and requires precise positioning.Here,we eliminate the need for an optical fiber by coupling light into and out from a toroid via free-space coupling and monitoring the scattered resonant light.A single long working distance objective lens combined with a digital micromirror device(DMD)was used for light injection,scattered light collection,and imaging.We obtain Q-factors as high as 1:6´108 with this approach.Electromagnetically induced transparency(EIT)-like and Fano resonances were observed in a single cavity due to indirect coupling in free space.This enables improved sensing sensitivity.The large effective coupling area(~10μm in diameter for numerical aperture=0.14)removes the need for precise positioning.Sensing performance was verified by combining the system with the frequency locked whispering evanescent resonator(FLOWER)approach to perform temperature sensing experiments.A thermal nonlinear optical effect was examined by tracking the resonance through FLOWER while adjusting the input power.We believe that this work will be a foundation for expanding the implementation of WGM microtoroid resonators to real-world applications.

关键词： coupling scattered precise

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Cardiac regeneration: Pre-existing cardiomyocyte as the hub of novel signaling pathway

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Genes & Diseases 2024年第2期11卷 747-759页

作者： Tao Wang Xinzhe Chen Kai Wang Jie Ju Xue Yu Wanpeng Yu Cuiyun Liu Yin Wang Institute for Translational Medicine The Affiliated Hospital of Qingdao UniversityCollege of MedicineQingdao UniversityQingdaoShandong 266023China College of Medicine Qingdao UniversityQingdaoShandong 266023China

In the mammalian heart,cardiomyocytes are forced to withdraw from the cell cycle shortly after birth,limiting the ability of the heart to regenerate and repair.The development of multimodal regulation of cardiac proliferation has verified that pre-existing cardiomyocyte proliferation is an essential driver of cardiac renewal.With the continuous development of genetic lineage tracking technology,it has been revealed that cell cycle activity produces polyploid cardiomyocytes during the embryonic,juvenile,and adult stages of cardiogenesis,but newly formed mononucleated diploid cardiomyocytes also elevated sporadically during myocardial infarction.It implied that adult cardiomyocytes have a weak regenerative capacity under the condition of ischemia injury,which offers hope for the clinical treatment of myocardial infarction.However,the regeneration frequency and source of cardiomyocytes are still low,and the mechanism of regulating cardiomyocyte proliferation remains further explained.It is noteworthy to explore what force triggers endogenous cardiomyocyte proliferation and heart regeneration.Here,we focused on summarizing the recent research progress of emerging endogenous key modulators and crosstalk with other signaling pathways and furnished valuable insights into the internal mechanism of heart regeneration.In addition,myocardial transcription factors,non-coding RNAs,cyclins,and cell cycle-dependent kinases are involved in the multimodal regulation of pre-existing cardiomyocyte proliferation.Ultimately,awakening the myocardial proliferation endogenous modulator and regeneration pathways may be the final battlefield for the regenerative therapy of cardiovascular diseases.

关键词： Cardiac regeneration Cell cycle re-enter Myocardial infarction Pre-existing cardiomyocyte proliferation Regenerative therapy of cardiovascular diseases

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