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| 1 | Minimal invasive microscopic tooth preparation in esthetic restoration: a specialist consensus显示文摘By removing a part of the structure,the tooth preparation provides restorative space,bonding surface,and finish line for various restorations on abutment.Preparation technique plays critical role in achieving the optimal result of tooth preparation.With successful application of microscope in endodontics for>30 years,there is a full expectation of microscopic dentistry.However,as relatively little progress has been made in the application of microscopic dentistry in prosthodontics,the following assumptions have been proposed:Is it suitable to choose the tooth preparation technique under the naked eye in the microscopic vision?Is there a more accurate preparation technology intended for the microscope?To obtain long-term stable therapeutic effects,is it much easier to achieve maximum tooth preservation and retinal protection and maintain periodontal tissue and oral function health under microscopic vision?Whether the microscopic prosthodontics is a gimmick or a breakthrough in obtaining an ideal tooth preparation should be resolved in microscopic tooth preparation.This article attempts to illustrate the concept,core elements,and indications of microscopic minimally invasive tooth preparation,physiological basis of dental pulp,periodontium and functions involved in tool preparation,position ergonomics and visual basis for dentists,comparison of tooth preparation by naked eyes and a microscope,and comparison of different designs of microscopic minimally invasive tooth preparation techniques.Furthermore,a clinical protocol for microscopic minimally invasive tooth preparation based on target restorative space guide plate has been put forward and new insights on the quantity and shape of microscopic minimally invasive tooth preparation has been provided. | Haiyang Yu Yuwei Zhao Junying Li Tian Luo Jing Gao Hongchen Liu Weicai Liu Feng Liu Ke Zhao Fei Liu Chufan Ma Juergen MSetz Shanshan Liang Lin Fan Shanshan Gao Zhuoli Zhu Jiefei Shen Jian Wang Zhimin Zhu Xuedong Zhou | 2019 | International Journal of Oral Science2019，11，4： | 25 |
| 2 | Identification and primary genetic analysis of Arabidopsis stomatal mutants in response to multiple stresses显示文摘In response to variable environmental conditions, guard cells located in the leaf epidermis can integrate and cope with a multitude of complicated stimuli, thereby making stomata in an appro- priate state. However, many signaling components in guard cell signaling remain elusive. In our laboratory, a tool for non-invasive remote infrared thermal images was used to screen an ethyl methane sulfonate-mutagenized population for Arabidopsis stomatal response mutants under multiple stresses (ABA, H2O2, CO2, etc.). More than forty 'hot' or 'cold' mutants were isolated (above or below 0.5℃ in con- trast to normal plantlets). Identification and primary genetic analysis of these mutants show that they are monogenic recessive mutations and there exist distinct difference in stomata apertures compared to wild type. These mutants in response to various environmental stresses and hormones were comprehen- sively investigated, which enables us to further un- derstand the cross-talk in different signal transduction pathways. | SONG Yuwei KANG Yanli LIU Hao ZHAO Xiaoliang WANG Pengtao AN Guoyong ZHOU Yun MIAO Chen SONG Chunpeng | 2006 | Chinese Science Bulletin2006，51，21： | 11 |
| 3 | Immunopotentiator Thymosin Alpha-1 Promotes Neurogenesis and Cognition in the Developing Mouse via a Systemic Th1 Bias显示文摘In early life, the immune system plays an essential role in brain development. In our study, the immunopotentiator thymosin alpha-1(Ta1) was peripherally administered to neonatal mice to explore whether the peripheral immunopotentiator affects neurodevelopment and cognition, and to further investigate the relevant mechanism. Compared with the control group, the Ta1 mice displayed better cognitive abilities in early life. The numbers of 5-bromodeoxyuridine(Brd U)+, nestin+,T-box transcription factor 2(Tbr2)+, Brd U+/doublecortin(DCX)+, Brd U+/ionized calcium-binding adaptor molecule 1(Iba1)+, and Brd U+/neuronal nuclei(Neu N)+ cells in the hippocampus were increased in the Ta1 group,accompanied by increased interleukin-4(IL-4), interferon-gamma, brain-derived neurotrophic factor, nerve growth factor, and insulin-like growth factor-1 as well as decreased IL-6 and tumor necrosis factor-a. Furthermore, the Ta1-group showed a Th1-polarized immune response, and the neurotrophic factors were positively associated with the Th1/Th2 ratio. More importantly, administration of Ta1 blocked lipopolysaccharide-induced impairment of hippocampal neurogenesis in early life. These findings suggest that peripheral Ta1 contributes to neurogenesis and cognition probably through a systemic Th1 bias, as well as neuroprotection against LPS infection by Ta1. | Ge Wang Fen He Yunlong Xu Yuwei Zhang Xiao Wang Chunhua Zhou Yihong Huang Juntao Zou | 2017 | Neuroscience Bulletin2017，33，6： | 8 |
| 4 | MIKC^(C)-type MADS-box genes in Rosa chinensis: the remarkable expansion of ABCDE model genes and their roles in floral organogenesis显示文摘MIKC^(C)-type MADS-box(MIKC^(C))genes encode transcription factors that have crucial roles in controlling floral organogenesis and flowering time in plants.Although this gene family has been well characterized in many plant species,its evolutionary and comprehensive functional analysis in rose is lacking.In this study,58 non-redundant MIKC^(C)uni-transcripts were extensively identified from rose transcriptomes.Phylogenetic analysis placed these genes into 12 clades with their Arabidopsis and strawberry counterparts,and revealed that ABCDE model(including AP1/FUL,AP3/PI,AG,and SEP clades),and SOC1 and AGL6 clade genes have remarkably expanded in Rosa chinensis,whereas genes from the FLC and AGL17 clades were undetectable.Sequence alignments suggest that the AP3/PI clade may contribute to more specific functions in rose due to a high variation of amino acid residues within its MADS-box domains.A comparative analysis of gene expression in specific floral organ differentiation stages and floral organs between R.chinensis cv.Old Blush and the closely related mutant genotype R.chinensis cv.Viridiflora(floral organs mutated into leaf-like structures)further revealed the roles of ABCDE model genes during floral organogenesis in rose.Analysis of co-expression networks provided an overview of the regulatory mechanisms of rose MIKC^(C)genes and shed light on both the prominent roles of AP3/PI clade genes in floral organogenesis and the roles of RcAGL19,RcAGL24,and RcSOC1 in regulating floral transition in rose.Our analyses provide an overall insight of MIKC^(C)genes in rose and their potential roles in floral organogenesis. | Jinyi Liu Xiaodong Fu Yuwei Dong Jun Lu Min Ren Ningning Zhou Changquan Wang | 2018 | Horticulture Research2018，5，1： | 7 |
| 5 | Aerosol size distributions during haze episodes in winter in Jinan, China显示文摘 | Yuwei Sun Xuehua Zhou Wenxing Wang | 2016 | Particuology2016，14，5： | 7 |
| 6 | Effects of preventive acupuncture or moxibustion at the Guanyuan acupoint on expression of interleukin-2 and its receptors in hypothalamus, serum, and uterus of menopausal rats显示文摘BACKGROUND: Previous studies have indicated preventive acupuncture and moxibustion at the Guanyuan point have positive effects on the immune system of menopausal rats. OBJECTIVE: To observe the effects of preventive acupuncture or moxibustion at the Guanyuan point on interleukin-2 (IL-2) and its receptor (IL-2R mRNA) levels in hypothalamus, serum, and uterus of menopausal rats. DESIGN: Randomized control animal experiment. SETTING: School of Acupuncture and Moxibustion, Beijing University of Chinese Medicine. MATERIALS: This study was performed at the Laboratory of Beijing University of Chinese Medicine from November 2004 to July 2005. The vaginal smear method was used to determine the estrus cycle of 9.5-month-old Sprague Dawley (SD) female rats. Three continuous estrus cycles were measured, and 160 rats with estrus cycle disorder, weighing (300 ± 20) g, were included in this study. The rats were randomly divided into four groups: preventive acupuncture group (n =48), preventive moxibustion group (n =48), model groups (n =48), and 10-month-old group (n =16). Sixteen 3.5-month-old healthy SD female rats, weighing (240 ± 20) g, were also assigned to the young group. All rats were clean grade and were purchased from the Laboratory Animal Center, Beijing University of Chinese Medicine. The experiment was in accordance with animal ethics standards. METHODS: Acupuncture was applied to the preventive acupuncture group at 10 months of age. The needle was inserted upward and perpendicularly two fen to a point that was two fen below the Guanyuan point. The rats freely moved around during needle retention (20 minutes). Acupuncture was administered twice a week and continued for eight weeks. A moxa cone (small) moxibustion was applied to the preventive moxibustion group at 10 months of age. The rats were caught gently and kept at the same position as the preventive acupuncture group. The moxa cone was ignited and held to the Guanyuan point directly. Only one moxa cone was used each time. After moxibustion, the local skin turned slightly red. Moxibustion was used twice a week and continued for eight weeks. Nothing except gently catching and lying was administered to the model group and the young group. MAIN OUTCOME MEASURES: Radioimmunoassay, in situ hybridization, and similar methods were employed to detect IL-2 in serum and the uterus, as well as IL-2R mRNA expression in the hypothalamus and uterus arcuate nuclei, of the preventive acupuncture group, preventive moxibustion group, model groups (at 12, 14, and 16 months), 10 month old group (at 10 months), and the young group (at 4 months). RESULTS: All 176 rats were included in the final analysis. ① IL-2R mRNA: IL-2R mRNA expression decreased significantly in the uterus of 12-, 14-, and 16-month-old model groups and in the hypothalamus of 14- and 16-month-old model groups (P < 0.05-0.01). Compared to the same month-aged model groups, the expression of IL-2R mRNA increased significantly in the hypothalamus and uterus of 16-month-old preventive acupuncture or moxibustion groups (P < 0.05-0.01).② IL-2: IL-2 in serum of 12- and 14-month-old model groups and in the uterus of 12-, 14-, and 16-month-old model groups decreased significantly compared to the young group (P < 0.05-0.01). IL-2 serum levels increased significantly in the 16-month-old group with preventive moxibustion; in addition, IL-2 expression levels increased significantly in the uterus of the 12-month-old group with preventive moxibustion, as well as the 12- and 16-month-old groups with preventive acupuncture (P < 0.05-0.01). CONCLUSION: As a rat ages and becomes menopausal, IL-2R mRNA expression in the hypothalamus anduterus, as well as IL-2 levels in the serum and uterus, decrease. However, preventive acupuncture and preventive moxibustion can repress the decrease to some extent. This effect is even greater in the late stages of menopause (16-month-old rats). | Xiaohong Li Yuwei He Jieping Xie Lufen Zhang Dengfang Zhou Jinghui Zhai Rui Zhan Jun Zhou Limin Qu Yangchun Tian | 2008 | Neural Regeneration Research2008，3，1： | 5 |
| 7 | A grid-based clustering algorithm for wild bird distribution显示文摘 | Yuwei WANG Yuanchun ZHOU Ying LIU Ze LUO Danhuai GUO Jing SHAO Fei TAN Liang WU Jianhui LI Baoping YAN | 2013 | Frontiers of Computer Science2013，7，4： | 4 |
| 8 | Effect of stimulating the acupoints Feishu (BL 13) and Dazhui (GV14) on transdermal uptake of sinapine thiocyanate in asthma gel显示文摘OBJECTIVE: To investigate the effect of stimulating the acupoints Feishu(BL 13) and Dazhui(GV 14) on the transdermal uptake of sinapine thiocyanate contained in a gel used for the management of asthma.METHODS: Thirty Sprague-Dawley rats were randomly divided into three equal groups using a random number table: the Feishu(BL 13) acupoint group, the Dazhui(GV 14) acupoint group, and the nonacupoint group or control group. Using micro-dialysis technology, preprocessed skin probes were implanted into the rats at Feishu(BL 13), Dazhui(GV 14), and a nonacupoint site. Asthma gel was then placed on the skin at Feishu(BL 13), Dazhui(GV14) acupoints, and the nonacupoint for all groups.Dialysate was collected every 30 min for 12 h. The normalized concentration of sinapine thiocyanate in the skin was determined by high-performance liquid chromatography.RESULTS: The rat in vivo transdermal experiment demonstrated that the quantity-time equation showed a good linear correlation with zero-order kinetics(r > 0.99). The transdermal behavior was in accordance with the first-order rate open model in which the transdermal penetration rates and the accumulative amounts of sinapine thiocyanate in the skin at the acupoint sites were greater than those through the skin of the nonacupoint site. The systemic maximum concentration and the area under the curve of sinapine thiocyanate in the acupoint groups were significantly greater than in the nonacupoint group. A lag time was observed in both acupoint groups, but not in the nonacupoint group.CONCLUSION: Stimulating the acupoints promotes the percutaneous absorption of sinapine thiocyanate and also controls its release, reducing concentration fluctuations in the blood. | Fan Wentao Huang Yuwei Wang Lisheng Liao Weiguo Li Zhou Wu Yinai Liao Fengyun Yu Jianye Liu Qiang | 2017 | Journal of Traditional Chinese Medicine2017，37，4： | 3 |
| 9 | Water permeability in MXene membranes: Process matters显示文摘Recent studies have shown impressive transport behaviors of water and ions within lamellar MXene membranes,which endows great promise in developing advanced separation application based high performance MXene membranes.However,most of the researches focused on modification of MXene nanoflakes and optimizing interlayer distance,leaving the impact of membrane fabrication process marginal.In this work,we studied the water flux of membranes made by vacuum filtration using delaminated MXene nanoflakes as the building-blocks.Our results show that the water permeability is extremely sensitive to the process,especially at the drying process,loading and deposit rate of nanoflakes(the feeding concentration).We find that the voids from less ordered stack rather than in-plane defects and interlayer galleries contribute to the large water permeability.The voids can be effectively avoided via deposition of MXene nanoflakes at a slow rate.Manipulating the stack of MXene nanoflakes during vacuum filtration and drying are critical for development of MXene membranes with desired performance for water permeation. | Hang Zhou Yuwei Wang Fuqiang Wang Hao Deng Yongchen Song Changping Li Zheng Ling | 2020 | Chinese Chemical Letters2020，31，6： | 3 |
| 10 | Modulating the optical and electrical properties of MAPbBr_(3) single crystals via voltage regulation engineering and application in memristors显示文摘Defect density is one of the most significant characteristics of perovskite single crystals(PSCs)that determines their optical and electrical properties,but few strategies are available to tune this property.Here,we demonstrate that voltage regulation is an efficient method to tune defect density,as well as the optical and electrical properties of PSCs.A three-step carrier transport model of MAPbBr_(3) PSCs is proposed to explore the defect regulation mechanism and carrier transport dynamics via an applied bias.Dynamic and steady-state photoluminescence measurements subsequently show that the surface defect density,average carrier lifetime,and photoluminescence intensity can be efficiently tuned by the applied bias.In particular,when the regulation voltage is 20 V(electrical poling intensity is 0.167 Vμm^(−1)),the surface defect density of MAPbBr_(3) PSCs is reduced by 24.27%,the carrier lifetime is prolonged by 32.04%,and the PL intensity is increased by 112.96%.Furthermore,a voltage-regulated MAPbBr_(3) PSC memristor device shows an adjustable multiresistance,weak ion migration effect and greatly enhanced device stability.Voltage regulation is a promising engineering technique for developing advanced perovskite optoelectronic devices. | Jun Xing Chen Zhao Yuting Zou Wenchi Kong Zhi Yu Yuwei Shan Qingfeng Dong Ding Zhou Weili Yu Chunlei Guo | 2020 | Light(Science & Applications)2020，9，1： | 3 |
| 11 | Modulation of Beta Oscillations for Implicit Motor Timing in Primate Sensorimotor Cortex during Movement Preparation显示文摘Motor timing is an important part of sensorimotor control. Previous studies have shown that beta oscillations embody the process of temporal perception in explicit timing tasks. In contrast, studies focusing on beta oscillations in implicit timing tasks are lacking. In this study, we set up an implicit motor timing task and found a modulation pattern of beta oscillations with temporal perception during movement preparation. We trained two macaques in a repetitive visually-guided reach-to-grasp task with different holding intervals. Spikes and local field potentials were recorded from microelectrode arrays in the primary motor cortex, primary somatosensory cortex, and posterior parietal cortex. We analyzed the association between beta oscillations and temporal interval in fixedduration experiments(500 ms as the Short Group and1500 ms as the Long Group) and random-duration experiments(500 ms to 1500 ms). The results showed that the peak beta frequencies in both experiments ranged from15 Hz to 25 Hz. The beta power was higher during the hold period than the movement(reach and grasp) period.Further, in the fixed-duration experiments, the mean poweras well as the maximum rate of change of beta power in the first 300 ms were higher in the Short Group than in the Long Group when aligned with the Center Hit event. In contrast, in the random-duration experiments, the corresponding values showed no statistical differences among groups. The peak latency of beta power was shorter in the Short Group than in the Long Group in the fixed-duration experiments, while no consistent modulation pattern was found in the random-duration experiments. These results indicate that beta oscillations can modulate with temporal interval in their power mode. The synchronization period of beta power could reflect the cognitive set maintaining working memory of the temporal structure and attention. | Hongji Sun Xuan Ma Liya Tang Jiuqi Han Yuwei Zhao Xuejiao Xu Lubin Wang Peng Zhang Luyao Chen Jin Zhou Changyong Wang | 2019 | Neuroscience Bulletin2019，35，5： | 2 |
| 12 | A practical method utilizing multi-spectral LiDAR to aid points cloud matching in SLAM显示文摘Light Detection and Ranging(LiDAR)sensors are popular in Simultaneous Localization and Mapping(SLAM)owing to their capability of obtaining ranging information actively.Researchers have attempted to use the intensity information that accompanies each range measurement to enhance LiDAR SLAM positioning accuracy.However,before employing LiDAR intensities in SLAM,a calibration operation is usually carried out so that the intensity is independent of the incident angle and range.The range is determined from the laser beam transmitting time.Therefore,the key to using LiDAR intensities in SLAM is to obtain the incident angle between the laser beam and target surface.In a complex environment,it is difficult to obtain the incident angle robustly.This procedure also complicates the data processing in SLAM and as a result,further application of the LiDAR intensity in SLAM is hampered.Motivated by this problem,in the present study,we propose a Hyperspectral LiDAR(HSL)-based-intensity calibration-free method to aid point cloud matching in SLAM.HSL employed in this study can obtain an eight-channel range accompanied by corresponding intensity measurements.Owing to the design of the laser,the eight-channel range and intensity were collected with the same incident angle and range.According to the laser beam radiation model,the ratio values between two randomly selected channels’intensities at an identical target are independent of the range information and incident angle.To test the proposed method,the HSL was employed to scan a wall with different coloured papers pasted on it(white,red,yellow,pink,and green)at four distinct positions along a corridor(with an interval of 60 cm in between two consecutive positions).Then,a ratio value vector was constructed for each scan.The ratio value vectors between consecutive laser scans were employed to match the point cloud.A classic Iterative Closest Point(ICP)algorithm was employed to estimate the HSL motion using the range information from the matched point clouds.According to the test results,we found that pink and green papers were distinctive at 650,690,and 720 nm.A ratio value vector was constructed using 650-nm spectral information against the reference channel.Furthermore,compared with the classic ICP using range information only,the proposed method that matched ratio value vectors presented an improved performance in heading angle estimation.For the best case in the field test,the proposed method enhanced the heading angle estimation by 72%,and showed an average 25.5%improvement in a featureless spatial testing environment.The results of the primary test indicated that the proposed method has the potential to aid point cloud matching in typical SLAM of real scenarios. | Changhui Jiang Yuwei Chen Wenxin Tian Ziyi Feng Wei Li Chunchen Zhou Hui Shao Eetu Puttonen Juha Hyyppä | 2020 | Satellite Navigation2020，1，1： | 2 |
| 13 | Single cell analysis reveals inhibition of angiogenesis attenuates the progression of heterotopic ossification in Mkx^(−/−)mice显示文摘Tendon heterotopic ossification(HO)is characterized by bone formation inside tendon tissue,which severely debilitates people in their daily life.Current therapies fail to promote functional tissue repair largely due to our limited understanding of HO pathogenesis.Here,we investigate the pathological mechanism and propose a potential treatment method for HO.Immunofluorescence assays showed that the Mohawk(MKX)expression level was decreased in human tendon HO tissue,coinciding with spontaneous HO and the upregulated expression of osteochondrogenic and angiogenic genes in the tendons of Mkx^(−/−)mice.Single-cell RNA sequencing analyses of wild-type and Mkx^(−/−)tendons identified three cell types and revealed the excessive activation of osteochondrogenic genes during the tenogenesis of Mkx^(−/−)tendon cells.Single-cell analysis revealed that the gene expression program of angiogenesis,which is strongly associated with bone formation,was activated in all cell types during HO.Moreover,inhibition of angiogenesis by the small-molecule inhibitor BIBF1120 attenuated bone formation and angiogenesis in the Achilles tendons of both Mkx mutant mice and a rat traumatic model of HO.These findings provide new insights into the cellular mechanisms of tendon HO and highlight the inhibition of angiogenesis with BIBF1120 as a potential treatment strategy for HO. | Junxin Lin Yuwei Yang Wenyan Zhou Chao Dai Xiao Chen Yuanhao Xie Shan Han Huanhuan Liu Yejun Hu Chenqi Tang Varitsara Bunpetch Dandan Zhang Yishan Chen Xiaohui Zou Di Chen Wanlu Liu Hongwei Ouyang | 2022 | Bone Research2022，10，4： | 1 |
| 14 | Application of photochemical reactions of Se in natural waters by hydride generation atomic fluorescence spectrometry显示文摘 | CHEN Yuwei ZHOU Mingda TONG Jian | 2005 | Analytica Chimica Acta2005，，545： | 1 |
| 15 | A Photoelectric-Stimulated MoS_(2) Transistor for Neuromorphic Engineering显示文摘The von Neumann bottleneck has spawned the rapid expansion of neuromorphic engineering and brain-like networks.Synapses serve as bridges for information transmission and connection in the biological nervous system.The direct implementation of neural networks may depend on novel materials and devices that mimic natural neuronal and synaptic behavior.By exploiting the interfacial effects between MoS_(2) and AlOx,we demonstrate that an h-BN-encapsulated MoS_(2) artificial synapse transistor can mimic the basic synaptic behaviors,including EPSC,PPF,LTP,and LTD.Efficient optoelectronic spikes enable simulation of synaptic gain,frequency,and weight plasticity.The Pavlov classical conditioning experiment was successfully simulated by electrical tuning,showing associated learning behavior.In addition,h-BN encapsulation effectively improves the environmental time stability of our devices.Our h-BN-encapsulated MoS_(2) artificial synapse provides a new paradigm for hardware implementation of neuromorphic engineering. | Shuiyuan Wang Xiang Hou Lan Liu Jingyu Li Yuwei Shan Shiwei Wu David Wei Zhang Peng Zhou | 2019 | Research2019，，1： | 1 |
| 16 | Optimal programmable unambiguous discriminator between two unknown latitudinal states显示文摘Two unknown states can be unambiguously distinguished by a universal programmable discriminator, which has been widely discussed in previous works and the optimal solution has also been obtained. In this paper, we investigate the programmable unambiguous discriminator between two unknown 'latitudinal' states, which lie in a subspace of the total state space. By equivalence of unknown pure states to known average mixed states, the optimal solution for this problem is systematically derived, and the analytical success probabilities for the optimal unambiguous discrimination are obtained. It is beyond one's expectation that the optimal setting for the programmable unambiguous discrimination between two unknown 'latitudinal' states is the same as that for the universal ones. The results in this work can be used for the realization of the programmable discriminator in laboratory. | XiaoBing Sunian YuWei Li Tao Zhou | 2016 | Science China(Physics,Mechanics & Astronomy)2016，59，10： | 1 |
| 17 | Synthesis and luminescence properties of SrBPO 5 :Eu 2+ , Mn 2+ phosphor for light-emitting diodes显示文摘 | Yuwei Lan Linghong Yi Liya Zhou Zhangfa Tong Fuzhong Gong Rongfang Wang | 2010 | Physica B: Physics of Condensed Matter2010，，16： | 1 |
| 18 | Metabolic profiling based on LC/MS to evaluate unintended effects of transgenic rice with cry1Ac and sck genes显示文摘 | Yuwei Chang Chunxia Zhao Zhen Zhu Zeming Wu Jia Zhou Yanni Zhao Xin Lu Guowang Xu | 2012 | Plant Molecular Biology (-)2012，，4： | 1 |
| 19 | Dye sensitized solar cells using freestanding TiO 2 nanotube arrays on FTO substrate as photoanode显示文摘 | Qi Pang Limin Leng Lijuan Zhao Liya Zhou Chunjie Liang Yuwei Lan | 2010 | Materials Chemistry and Physics2010，，3： | 1 |
| 20 | EGFR signaling promotes nuclear translocation of plasma membrane protein TSPAN8 to enhance tumor progression via STAT3-mediated transcription显示文摘TSPAN family of protei ns are gen erally con sidered to assemble as multimeric complexes on the plasma membra ne.Our previous work uncovered that TSPAN8 can translocate into the nucleus as a membrane-free form,a process that requires TSPAN8 palmitoylation and association with cholesterol to promote its extraction from the plasma membrane and subsequent binding with 14-3-30 and importin-p.However,what upstream signal(S)regulate(s)the nuclear translocation of TSPAN8,the potential function of TSPAN8 in the n ucleus,and the un derlying molecular mechanisms all remai n unclear.Here,we dem on strate that,epidermal growth factor receptor(EGFR)signaling induces TSPAN8 nuclear translocation by activating the kinase AKTZ which in turn directly phosphorylates TSPAN8 at Ser129,an event essential for its binding with 14-3-30 and importin B1.In the nucleus,phosphorylated TSPAN8 interacts with STAT3 to enhance its chromatin occupancy and therefore regulates transcription of downstream cancer-promoting genes,such as MYC,BCL2,MMP9,etc.The EGFR-AKT-TSPAN8-STAT3 axis was found to be hyperactivated in multiple human cancers,and associated with aggressive phe no type and dismal prog nosis.We further developed a humanized mono clonal antibody hT8Ab4 that specifically recognizes the large extracellular loop of TSPAN8(TSPAN8-LEL),thus being able to block the extract!on of TSPAN8 from the plasma membrane and consequently its nuclear localization.Importantly,both in vitro and in vivo studies demonstrated an antitumor effect of hT8Ab4.Collectively,we discovered an unconventional function of TSPAN8 and dissected the underlying molecular mechanisms,which not only showcase a new layer of biological complexity of traditional membrane proteins,but also shed light on TSPAN8 as a novel therapeutic target for refractory cancers. | Xiaoqing Lu Liwei An Guangjian Fan Lijuan Zang Weiyi Huang Junjian Li Jun Liu Weiyu Ge Yuwei Huang Jingxuan Xu Shaoqian Du Tianhao Zhou Huijing Yin Li Yu Shi Jiao Hongxia Wang | 2022 | Cell Research2022，32，4： | 1 |
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