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Regulation of TWlK-related potassium channel- 1 （Trek1） restitutes intestinal epithelial barrier function

Cellular & Molecular Immunology 2016年第1期13卷 110-118页

作者： Huang Huang Jiang-Qi Liu Yong Yu Li-Hua Mo Rong-Ti Ge Huan-Ping Zhang Zhi-Gang Liu Peng-Yuan Zheng Ping-Chang Yang Department of Gastroenterology the Second Hospital Zhengzhou University Zhengzhou China ent Institute Shenzhen Key Laboratory of Allergy & Immunology Shenzhen University Shenzhen China ent Hospital Longgang Central Hospital Shenzhen China Brain Body Institute McMaster University Hamilton ON Canada

The disruption of epithelial barrier integrity is an important factor in the pathogenesis of various immune disorders. However, the restitution of the compromised barrier functions is difficult. This study investigates the regulation of TWIK-related potassium channel-1 （Trek1） in the restitution of intestinal epithelial barrier functions. The human colon epithelial cell line T84 was cultured in monolayers and used to observe epithelial barrier functions in vitro. An intestinal allergy mouse model was created. Cytokine levels were determined by enzyme-linked immunosorbent assay and western blotting. The results showed that Trek1 deficiency induced T84 monolayer barrier disruption. Allergic responses markedly suppressed the expression of Trek1 in the intestinal epithelia via activating the mitogen-activated protein kinase pathways and increasing the expression of histone deacetylase-1. The inhibition of histone deacetylase-1 by sodium butyrate or the administration of a butyrate-producing probiotic （Clostridium butyricum） restored the intestinal epithelial barrier functions and markedly enhanced the effect of antigen-specific immunotherapy. The data suggest that Trek1 is required for the maintenance of intestinal epithelial barrier integrity. Allergic responses induce an insufficiency of Trek1 expression in the intestinal epithelia. Trek1 expression facilitates the restoration of intestinal epithelial barrier functions in an allergic environment.

关键词： allergy epithelial barrier, intestine probiotics Trek1

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茶多酚EGCG通过下调STAT3抑制结直肠癌细胞的增殖和迁移

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Gastroenterology Report 2021年第1期9卷 59-70,I0002页

作者： Ke-Wang Luo Jun Xia Bao-Hui Cheng Han-Chao Gao Li-Wu Fu Xin-Le Luo key laboratory People’s Hospital of LonghuaShenzhenGuangdongP.R.China key laboratory of Medical Programming Technology Shenzhen Second People’s HospitalThe First Affiliated Hospital of Shenzhen UniversityShenzhenGuangdongP.R.China Shenzhen Key Laboratory of ENT Longgang ENT Hospital and Institute of ENTShenzhenGuangdongP.R.China Department of Nephrology Shenzhen Longhua District Central HospitalAffiliated Central Hospital of Shenzhen Longhua DistrictGuangdong Medical UniversityShenzhenGuangdongP.R.China State key laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineGuangdong Esophageal Cancer InstituteSun Yat-sen University Cancer CenterGuangzhouGuangdongP.R.China

背景:绿茶是全球最受欢迎的饮品之一,表没食子儿茶素-3-没食子酸酯(EGCG)是绿茶中最具生物活性的茶多酚。本研究旨在探索EGCG对结直肠癌SW480、SW620和LS411N细胞增殖和迁移的作用,并阐明相关机制。方法:采用MTT法、划痕实验和细胞迁移... 详细信息

背景:绿茶是全球最受欢迎的饮品之一,表没食子儿茶素-3-没食子酸酯(EGCG)是绿茶中最具生物活性的茶多酚。本研究旨在探索EGCG对结直肠癌SW480、SW620和LS411N细胞增殖和迁移的作用,并阐明相关机制。方法:采用MTT法、划痕实验和细胞迁移实验体外检测EGCG对结肠癌细胞的抗增殖和抗迁移作用,利用Annexin V-FITC/PI双染法和JC-1染色法评估EGCG对结直肠癌细胞凋亡的影响。此外,采用免疫印迹法检测蛋白表达的变化及可能的变化机制,并利用实时定量PCR和双重荧光素酶报告实验检测mRNA的表达和启动子活性。结果:MTT和流式细胞术结果显示,茶多酚EGCG可通过诱导结直肠癌细胞凋亡抑制细胞增殖。划痕实验和细胞迁移实验表明,EGCG可剂量依赖性地抑制SW480细胞迁移。免疫印迹显示,EGCG可通过激活Caspase-3和PARP诱导凋亡。EGCG在3种结直肠癌细胞系中均可显著下调STAT3和磷酸化STAT3(p-STAT3)。EGCG还可导致结直肠癌细胞中Bcl-2、MCL-1、Vimentin表达降低和E-cadherin表达升高。此外,当STAT3被抑制时,EGCG对结直肠癌细胞的增殖和迁移没有明显作用。荧光素酶报告实验进一步表明,EGCG通过抑制STAT3启动子活性下调STAT3的转录。结论:我们的研究阐明了EGCG可通过下调STAT3表达来抑制SW480、SW620和LS411N结直肠癌细胞的增殖和迁移,为EGCG用于结直肠癌的辅助治疗提供了科学依据。

关键词： EGCG colon cancer STAT3 SW480 SW620 LS411N

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Interleukin- 13 interferes with activation-induced t-ce apoptosis by repressing p53 expression

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Cellular & Molecular Immunology 2016年第5期13卷 669-677页

作者： Li Yang Ling-Zhi Xu Zhi-Qiang Liu Gui Yang Xiao-Rui Geng Li-Hua Mo Zhi-Gang Liu Peng-Yuan Zheng Ping-Chang Yang Department of Gastroenterology the Zhengzhou People's Hospital Zhengzhou China Department of Gastroenterology the Fifth Affiliated Hospital of Zhengzhou University Zhengzhou China shenzhen key laboratory of Allergy and Immunology Shenzhen University School of Medicine and State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University Shenzhen China ent Institute of shenzhen University Longgang Central Hospital Shenzhen China

The etiology and the underlying mechanism of CD4＋ T-cell polarization are unclear. This study sought to investigate the mechanism by which interleukin （IL）-13 prevents the activation-induced apoptosis of CD4＋ T cells. Here we report that CD4＋ T cells expressed IL-13 receptor a2 in the intestine of sensitized mice. IL-13 suppressed both the activation-induced apoptosis of CD4＋ T cells and the expression of p53 and FasL. Exposure to recombinant IL-13 inhibited activation-induced cell death （AICD） along with the expression of p53, caspase 3, and tumor necrosis factor-a in CD4＋ T cells. Administration of an anti-lL-13 antibody enhanced the effect of specific immunotherapy on allergic inflammation in the mouse intestine, enforced the expression of p53 in intestinal CD4＋ T cells, and enhanced the frequency of CD4＋ T-cell apoptosis upon challenge with specific antigens. In summary, blocking IL-13 enhances the therapeutic effect of antigen-specific immunotheraov by regulating aDoptosis and thereby enforcing AICD in CD4＋ T cells.

关键词： activation-induced cell death apoptosis interleukin 13 T lymphocytes Th2 polarization

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Inhibiting DNA methylation alleviates cisplatininduced hearing loss by decreasing oxidative stress-induced mitochondria-dependent apoptosis via the LRP1-PI3K/AKT pathway

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Acta Pharmaceutica Sinica B 2022年第3期12卷 1305-1321页

作者： Yingzi He Zhiwei Zheng Chang Liu Wen Li Liping Zhao Guohui Nie Huawei Li ent Institute and Otorhinolaryngology Department of Eye&ent Hospital State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceFudan UniversityShanghai 200031China NHC key laboratory of Hearing Medicine(Fudan University) Shanghai 200031China Department of Otolaryngology and Institute of Translational Medicine Shenzhen Second People’s Hospital/the First Affiliated Hospital of Shenzhen University Health Science CenterShanghai 200032China Institutes of Biomedical Sciences Fudan UniversityShanghai 200032China The Institutes of Brain Science and the Collaborative Innovation Center for Brain Science Fudan UniversityShenzhen 518035China

Cisplatin-related ototoxicity is a critical side effect of chemotherapy and can lead to irreversible hearing loss.This study aimed to assess the potential effect of the DNA methyltransferase(DNMT)inhibitor RG108 on cisplatin-induced ototoxicity.Immunohistochemistry,apoptosis assay,and auditory brainstem response(ABR)were employed to determine the impacts of RG108 on cisplatin-induced injury in murine hair cells(HCs)and spiral ganglion neurons(SGNs).Rhodamine 123 and TMRM were utilized for mitochondrial membrane potential(MMP)assessment.Reactive oxygen species(ROS)amounts were evaluated by Cellrox green and Mitosox-red probes.Mitochondrial respiratory function evaluation was performed by determining oxygen consumption rates(OCRs).The results showed that RG108 can markedly reduce cisplatin induced damage in HCs and SGNs,and alleviate apoptotic rate by protecting mitochondrial function through preventing ROS accumulation.Furthermore,RG108 upregulated BCL-2 and downregulated APAF1,BAX,and BAD in HEI-OC1 cells,and triggered the PI3K/AKT pathway.Decreased expression of low-density lipoprotein receptor-related protein 1(LRP1)and high methylation of the LRP1 promoter were observed after cisplatin treatment.RG108 treatment can increase LRP1expression and decrease LRP1 promoter methylation.In conclusion,RG108 might represent a new potential agent for preventing hearing loss induced by cisplatin via activating the LRP1-PI3K/AKT pathway.

关键词： Cisplatin DNMT Apoptosis Hair cell Spiral ganglion neurons RG108 Mitochondrial dysfunction ROS

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Inhibition of histone methyltransferase PRMT5 attenuates cisplatininduced hearing loss through the PI3K/Akt-mediated mitochondrial apoptotic pathway

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Journal of Pharmaceutical Analysis 2023年第6期13卷 590-602页

作者： Zhiwei Zheng Benyu Nan Chang Liu Dongmei Tang Wen Li Liping Zhao Guohui Nie Yingzi He ent Institute and Department of Otorhinolaryngology Eye&ENT HospitalState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceNHC Key Laboratory of Hearing Medicine(Fudan University)Fudan UniversityShanghai200031China Department of Otorhinolaryngology-Head and Neck Surgery The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical UniversityWenzhou325000ZhejiangChina Department of Otolaryngology-Head and Neck Surgery The Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou510630China Department of Otolaryngology Shenzhen Institute of Translational MedicineShenzhen Second People's HospitalThe First Affiliated Hospital of Shenzhen UniversityShenzhen518035GuangdongChina

This study aimed to evaluate the therapeutic potential of inhibiting protein arginine methyltransferase 5(PRMT5)in cisplatin-induced hearing loss.The effects of PRMT5 inhibition on cisplatin-induced auditory injury were determined using immunohistochemistry,apoptosis assays,and auditory brainstem response.The mechanism of PRMT5 inhibition on hair cell survival was assessed using RNA-seq and Cleavage Under Targets and Tagment-quantitative polymerase chain reaction(CUT&Tag-qPCR)analyses in the HEI-OC1 cell line.Pharmacological inhibition of PRMT5 significantly alleviated cisplatin-induced damage to hair cells and spiral ganglion neurons in the cochlea and decreased apoptosis by protecting mitochondrial function and preventing the accumulation of reactive oxygen species.CUT&Tag-qPCR analysis demonstrated that inhibition of PRMT5 in HEI-OC1 cells reduced the accumulation of H4R3me2s/H3R8me2s marks at the promoter region of the Pik3ca gene,thus activating the expression of Pik3ca.These findings suggest that PRMT5 inhibitors have strong potential as agents against cisplatininduced ototoxicity and can lay the foundation for further research on treatment strategies of hearing loss.

关键词： Protein arginine methyltransferase 5 (PRMT5) LLY-283 Cisplatin Hearing loss Hair cell Spiral ganglion neuron

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Bioinspired structural color particles with multi-layer graphene oxide encapsulated nanoparticle components

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Bioactive Materials 2020年第4期5卷 917-923页

作者： Yuxiao Liu Yuetong Wang Yu Wang Yilai Shu Hui Tan Yuanjin Zhao Department of Neurosurgery Health Science CenterThe First Affiliated Hospital of Shenzhen UniversityShenzhen518035China ent Institute and Otorhinolaryngology Department of the Affiliated Eye and ent Hospital State Key Laboratory of Medical NeurobiologyInstitute of Biomedical SciencesFudan UniversityShanghai200031China Department of Clinical laboratory The Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing210008China State key laboratory of Bioelectronics School of Biological Science and Medical EngineeringSoutheast UniversityNanjing210096China

Because of the unique features of spherical symmetry,angle-independency,good monodispersity,controllable components and morphologies,structural color particles(SCPs)have found great significances in various fields such as sensing,monitoring,biological assays,etc.Here,inspired by the melanosome-derived bright structural colors and the self-adhesivity of mussels,we present a kind of bioinspired SCPs assembled from polydopamine(PDA)-adhered multi-layer graphene oxide(GO)encapsulated silica nanoparticles(SNs).It is demonstrated that compared with traditional SCPs,the designed particles possess brighter and more vibrant structural colors,and no complicated modification is required during the functionalization process due to the abundant inherent functional groups of GO.The resultant SCPs are verified to be capable for direct hybridization chain reaction and multiplexed nucleic acid assays.These properties indicate the promising prospects of our designed SCPs.

关键词： Bioinspired Structural color Graphene oxide Colloidal crystal Microfluidics

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OGSRN:Optical-guided super-resolution network for SAR image

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Chinese Journal of Aeronautics 2022年第5期35卷 204-219页

作者： Yanshan LI Li ZHOU Fan XU Shifu CHEN ATR National key laboratory of Defense Technology Shenzhen UniversityShenzhen 518060China Guangdong key laboratory of Intelligent Information Processing Shenzhen UniversityShenzhen 518060China

Although Convolutional Neural Networks(CNNs)have significantly improved the development of image Super-Resolution(SR)technology in recent years,the existing SR methods for SAR image with large scale factors have rarely been studied due to technical difficulty.A more efficient method is to obtain comprehensive information to guide the SAR image reconstruction.Indeed,the co-registered High-Resolution(HR)optical image has been successfully applied to enhance the quality of SAR image due to its discriminative characteristics.Inspired by this,we propose a novel Optical-Guided Super-Resolution Network(OGSRN)for SAR image with large scale factors.Specifically,our proposed OGSRN consists of two sub-nets:a SAR image SuperResolution U-Net(SRUN)and a SAR-to-Optical Residual Translation Network(SORTN).The whole process during training includes two stages.In stage-1,the SR SAR images are reconstructed by the SRUN.And an Enhanced Residual Attention Module(ERAM),which is comprised of the Channel Attention(CA)and Spatial Attention(SA)mechanisms,is constructed to boost the representation ability of the network.In stage-2,the output of the stage-1 and its corresponding HR SAR images are translated to optical images by the SORTN,respectively.And then the differences between SR images and HR images are computed in the optical space to obtain feedback information that can reduce the space of possible SR solution.After that,we can use the optimized SRUN to directly produce HR SAR image from Low-Resolution(LR)SAR image in the testing phase.The experimental results show that under the guidance of optical image,our OGSRN can achieve excellent performance in both quantitative assessment metrics and visual quality.

关键词： SAR image Super-resolution Optical image Attention mechanisms Convolutional Nerual Networks(CNNs)

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Additively Manufactured Flexible Electronics with Ultrabroad Range and High Sensitivity for Multiple Physiological Signals'Detection

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Research 2022年第4期2022卷 707-717页

作者： Huanhuan Feng Yaming Liu Liang Feng Limeng Zhan Shuaishuai Meng Hongjun Ji Jiaheng Zhang Mingyu Li Peng He Weiwei Zhao Jun Wei Sauvage laboratory for Smart Materials Shenzhen Key Laboratory of Flexible Printed Electronics TechnologyHarbin Institute of Technology(Shenzhen)China State key laboratory of Advanced Welding and Joining(shenzhen) Harbin Institute of Technology(Shenzhen)China State key laboratory of Advanced Welding and Joining Harbin Institute of TechnologyChina

Flexible electronics can be seamlessly attached to human skin and used for various purposes, such as pulse monitoring, pressure measurement, tensile sensing, and motion detection. Despite their broad applications, most flexible electronics do not possess both high sensitivity and wide detection range simultaneously;their sensitivity drops rapidly when they are subjected to even just medium pressure. In this study, ultrabroad-range, high-sensitivity flexible electronics are fabricated through additive manufacturing to address this issue. The key to possess high sensitivity and a wide detection range simultaneously is to fabricate flexible electronics with large depth-width ratio circuit channels using the additive manufacturing inner-rinsing template method. These electronics exhibit an unprecedented high sensitivity of 320 kPa^(−1) over the whole detection range, which ranges from 0.3 to 30,000 Pa (five orders of magnitude). Their minimum detectable weight is 0.02 g (the weight of a fly), which is comparable with human skin. They can stretch to over 500% strain without breaking and show no tensile fatigue after 1000 repetitions of stretching to 100% strain. A highly sensitive and flexible electronic epidermal pulse monitor is fabricated to detect multiple physiological signals, such as pulse signal, breathing rhythm, and real-time beat-to-beat cuffless blood pressure. All of these signals can be obtained simultaneously for detailed health detection and monitoring. The fabrication method does not involve complex expensive equipment or complicated operational processes, so it is especially suitable for the fabrication of large-area, complex flexible electronics. We believe this approach will pave the way for the application of flexible electronics in biomedical detection and health monitoring.

关键词： fatigue additive stretching

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Track-Oriented Marginal Poisson Multi-Bernoulli Mixture Filter for Extended Target Tracking

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Chinese Journal of Electronics 2023年第5期32卷 1106-1119页

作者： DU Haocui XIE Weixin LIU Zongxiang LI Liangqun ATR key laboratory Shenzhen University Guangdong key laboratory of Intelligent Information Processing Shenzhen University

In this paper, we derive and propose a track-oriented marginal Poisson multi-Bernoulli mixture(TO-MPMBM) filter to address the problem that the standard random finite set filters cannot build continuous trajectories for multiple extended targets. First, the Poisson point process model and the multi-Bernoulli mixture(MBM) model are used to establish the set of birth trajectories and the set of existing trajectories, respectively.Second, the proposed filter recursively propagates the marginal association distributions and the Poisson multiBernoulli mixture(PMBM) density over the set of alive trajectories. Finally, after pruning and merging process,the trajectories with existence probability greater than the given threshold are extracted as the estimated target trajectories. A comparison of the proposed filter with the existing trajectory filters in two classical scenarios confirms the validity and reliability of the TO-MPMBM filter.

关键词： Extended target tracking Random finite set Poisson multi-Bernoulli mixture Poisson point process Marginal distribution Target trajectory

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A Low Complexity Distributed Multitarget Detection and Tracking Algorithm

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Chinese Journal of Electronics 2023年第3期32卷 429-437页

作者： FAN Jiande XIE Weixin LIU Zongxiang ATR key laboratory Shenzhen University Guangdong key laboratory of Intelligent Information Processing Shenzhen University

In this paper, we propose a low complexity distributed approach to address the multitarget detection/tracking problem in the presence of noisy and missing data. The proposed approach consists of two components: a distributed flooding scheme for measurements exchanging among sensors and a sampling-based clustering approach for target detection/tracking from the aggregated measurements. The main advantage of the proposed approach over the prevailing Markov-Bayes-based distributed filters is that it does not require any priori information and all the information required is the measurement set from multiple sensors. A comparison of the proposed approach with the available distributed clustering approaches and the cutting edge distributed multiBernoulli filters that are modeled with appropriate parameters confirms the effectiveness and the reliability of the proposed approach.

关键词： Sensor fusion Distributed multitarget tracking Constrained clustering Flooding Average consensus

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