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| 1 | Overexpressed Cyclin D1 and CDK4 proteins are responsible for the resistance to CDK4/6 inhibitor in breast cancer that can be reversed by PI3K/mTOR inhibitors显示文摘CDK4/6 inhibitors are the standard treatment in advanced HR+/HER2-breast cancer patients.Nevertheless,the resistance to CDK4/6 inhibitors is inevitable and the strategies to overcome resistance are of great interest.Here,we show that the palbociclibresistant breast cancer cells expressed significantly higher levels of Cyclin D1 and CDK4 proteins because of upregulated protein synthesis.Silencing Cyclin D1 or CDK4 led to cell cycle arrest while silencing Cyclin E1 or CDK2 restored the sensitivity to palbociclib.Furthermore,PI3K/mTOR pathway was hyper-activated in palbociclib-resistant cells,leading to more phosphorylated 4E-BP1 and higher levels of Cyclin D1 and CDK4 translation.Targeting PI3K/mTOR pathway with a specific PI3Kαinhibitor(BYL719)or an mTOR inhibitor(everolimus)reduced the protein levels of Cyclin D1 and CDK4,and restored the sensitivity to palbociclib.The tumor samples expressed significantly higher levels of Cyclin D1,CDK4,p-AKT and p-4E-BP1 after progression on palbociclib treatment.In conclusion,our findings suggest that overexpressed Cyclin D1 and CDK4 proteins lead to the resistance to CDK4/6 inhibitor and PI3K/mTOR inhibitors are able to restore the sensitivity to CDK4/6 inhibitors,which provides the biomarker and rationale for the combinational use of CDK4/6 inhibitors and PI3K/mTOR inhibitors after CDK4/6 inhibitor resistance in breast cancer. | Zijie Cai Jingru Wang Yudong Li Qianfeng Shi Liang Jin Shunying Li Mengdi Zhu Qi Wang Lok Lam Wong Wang Yang Hongna Lai Chang Gong Yandan Yao Yujie Liu Jun Zhang Herui Yao Qiang Liu | 2023 | Science China(Life Sciences)2023，66，1： | 4 |
| 2 | Anti-Seizure and Neuronal Protective Effects of Irisin in Kainic Acid-Induced Chronic Epilepsy Model with Spontaneous Seizures显示文摘An increased level of reactive oxygen species is a key factor in neuronal apoptosis and epileptic seizures.Irisin reportedly attenuates the apoptosis and injury induced by oxidative stress.Therefore,we evaluated the effects of exogenous irisin in a kainic acid(KA)-induced chronic spontaneous epilepsy rat model.The results indicated that exogenous irisin significantly attenuated the KA-induced neuronal injury,learning and memory defects,and seizures.Irisin treatment also increased the levels of brain-derived neurotrophic factor(BDNF)and uncoupling protein 2(UCP2),which were initially reduced following KA administration.Furthermore,the specific inhibitor of UCP2(genipin)was administered to evaluate the possible protective mechanism of irisin.The reduced apoptosis,neurodegeneration,and spontaneous seizures in rats treated with irisin were significantly reversed by genipin administration.Our findings indicated that neuronal injury in KA-induced chronic epilepsy might be related to reduced levels of BDNF and UCP2.Moreover,our results confirmed the inhibition of neuronal injury and epileptic seizures by exogenous irisin.The protective effects of irisin may be mediated through the BDNF-mediated UCP2 level.Our results thus highlight irisin as a valuable therapeutic strategy against neuronal injury and epileptic seizures. | Jie Yu Yao Cheng Yaru Cui Yujie Zhai Wenshen Zhang Mengdi Zhang Wenyu Xin Jia Liang Xiaohong Pan Qiaoyun Wang Hongliu Sun | 2022 | Neuroscience Bulletin2022，38，11： | 1 |
| 3 | Application of Maximum Entropy Theorem in Channel Estimation显示文摘Scholars have been highly concerned with the blind channel estimation of multi-carrier modulation transmission systems, and the decoding process of block codes is usually closely related to channel parameters.Therefore, the accurate estimation of channel parameters is an important method to ensure communication accuracy. According to the transmission characteristics of multi-carrier modulated transmission channels, this paper uses the maximum likelihood theorem and the maximum entropy theorem to put forward a blind channel estimation method based on the proposed received signals. In order to verify the effect of this method, this research utilizes the BP decoding algorithm, which is used in LDPC coding, to calculate the symbol error rate and analyze the estimated effect of the transmission system. The simulation results show that the proposed method can estimate channel parameters effectively, and that the symbol error rate of LDPC decoding is almost similar to that of non-blind channel estimation. This implies that the proposed channel estimation method can effectively improve both channel utilization and transmission efficiency. | ZHANG Zhengyu LOU Jinming JIN Mengdi YAO Yuan ZHU Jingguo | 2020 | Chinese Journal of Electronics2020，29，2： | 1 |
| 4 | A single-cell transcriptome atlas of the aging human and macaque retina显示文摘The human retina is a complex neural tissue that detects light and sends visual information to the brain.However,the molecular and cellular processes that underlie aging primate retina remain unclear.Here,we provide a comprehensive transcriptomic atlas based on 119520 single cells of the foveal and peripheral retina of humans and macaques covering different ages.The molecular features of retinal cells differed between the two species,suggesting distinct regional and species specializations of the human and macaque retinae.In addition,human retinal aging occurred in a region-and cell-type-specific manner.Aging of human retina exhibited a foveal to peripheral gradient.MYO9A-rods and a horizontal cell subtype were greatly reduced in aging retina,indicating their vulnerability to aging.Moreover,we generated a dataset showing the cell-type-and region-specific gene expression associated with 55 types of human retinal disease,which provides a foundation to understanding of the molecular and cellular mechanisms underlying human retinal diseases.Such datasets are valuable to understanding of the molecular characteristics of primate retina,as well as molecular regulation of aging progression and related diseases. | Wenyang Yi Yufeng Lu Suijuan Zhong Mei Zhang Le Sun Hao Dong Mengdi Wang Min Wei Haohuan Xie Hongqiang Qu Rongmei Peng Jing Hong Ziqin Yao Yunyun Tong Wei Wang Qiang Ma Zeyuan Liu Yuqian Ma Shouzhen Li Chonghai Yin Jianwei Liu Chao Ma Xiaoqun Wang Qian Wu Tian Xue | 2021 | National Science Review2021，8，4： | 1 |
| 5 | Seismic activities before and after the impoundment of the Xiangjiaba and Xiluodu reservoirs in the lower Jinsha River显示文摘The lower Jinsha River basin is located at the junction of Sichuan and Yunnan provinces in Southwest China,a region with intense tectonic movements and frequent moderate to strong seismic activities.Cascade hydropower stations have been constructed along the lower Jinsha River since 2012.However,research on the effect of the impoundment of large-scale cascade reservoirs in a river basin on local seismic activities is currently lacking.Accurately identifying earthquake locations is essential for studying reservoir-induced earthquakes.Analyzing the spatiotemporal migration process of seismic activities based on complete and precise earthquake relocation is fundamental for determining the fluid diffusion coefficient,constructing fault models for reservoir areas,identifying earthquake types,exploring earthquake mechanisms,and evaluating seismic hazards.The seismicity pattern in the Xiangjiaba and Xiluodu reservoir areas,where seismic activities had been weak for a long time,has changed with the successive impoundment of the two reservoirs,showing microseismic events and seismic clusters.We investigated the spatiotemporal characteristics of seismic activities in the Xiangjiaba and Xiluodu reservoir areas using the waveform cross-correlation-based double-difference relocation technique and the b-value analysis method.We discovered that seismic events after the impoundment of these two reservoirs exhibited different characteristics in different regions.The seismic activities at the Xiluodu dam quickly responded to the rising water level,with the seismic intensity decaying rapidly afterward.These events were concentrated in the limestone strata along both sides of the Jinsha River,with a shallow focal depth,generally within 5 km,and a high b-value of approximately 1.2.Such features are close to those of karst-type earthquakes.Microseismic activities frequent occur on the eastern bank of the Yongshan reservoir section downstream of the Xiluodu dam,with two parallel NW-trending earthquake strips visible after precise earthquake relocation.The M_(S)5.2 earthquake near Wuji town on August 17,2014,had prominent foreshocks and aftershocks distributed in a clear NW-trending 20-km-long strip,perpendicular to the riverbank.These seismic events had a low b-value of approximately 0.7.The orientation of the node plane revealed by the strike-slip focal mechanism of the mainshock is consistent with that of the strip formed by the foreshock-mainshock-aftershock sequence,indicating the existence of a NW-striking concealed fault.Seismic activities near the Yanjin-Mabian fault upstream of the Xiangjiaba reservoir area since 2013 were concentrated in a NW-trending strip,with several near EW-trending seismic clusters on its western side,and with the largest event having a magnitude of M_(L)3.7.So far,the impoundment of the Xiangjiaba and Xiluodu reservoirs has not triggered seismic activities on the large Jinyang-Ebian and Yanjin-Mabian faults nearby. | Ce Zhao Cuiping Zhao Hongfu Lei Mengdi Yao | 2022 | Earthquake Science2022，35，5： | 0 |
| 6 | Hybridization chain reaction-based DNA nanomaterials for biosensing,bioimaging and therapeutics显示文摘DNA nanomaterials hold great promise in biomedical fields due to its excellent sequence programmability,molecular recognition ability and biocompatibility.Hybridization chain reaction(HCR)is a simple and efficient isothermal enzyme-free amplification strategy of DNA,generating nicked double helices with repeated units.Through the design of HCR hairpins,multiple nanomaterials with desired functions are assembled by DNA,exhibiting great potential in biomedical applications.Herein,the recent progress of HCR-based DNA nanomaterials for biosensing,bioimaging and therapeutics are summarized.Representative works are exemplified to demonstrate how HCR-based DNA nanomaterials are designed and constructed.The challenges and prospects of the development of HCR-based DNA nanomaterials are discussed.We envision that rationally designing HCR-based DNA nanomaterials will facilitate the development of biomedical applications. | Zhaoyue Lv Mengxue Huang Peiran Li Mengdi Xu Chi Yao Dayong Yang | 2024 | Chinese Chemical Letters2024，35，2： | 0 |
| 7 | Cellbow:a robust customizable cell segmentation program显示文摘Backgrounds Time-lapse live cell imaging of a growing cell population is routine in many biological investigations.A major challenge in imaging analysis is accurate segmentation,a process to define the boundaries of cells based on raw image data.Current segmentation methods relying on single boundary features have problems in robustness when dealing with inhomogeneous foci which invariably happens in cell population imaging.Methods:Combined with a multi-layer training set strategy,we developed a neural-network-based algorithm—Cellbow.Results'Cellbow can achieve accurate and robust segmentation of cells in broad and general settings.It can also facilitate long-term tracking of cell growth and division.To facilitate the application of Cellbow,we provide a website on which one can online test the software,as well as an I mage J plugin for the user to visualize the performance before software installation.Conclusions Cellbow is customizable and generalizable.It is broadly applicable to segmenting fluorescent images of diverse cell types with no further training needed.For bright-field images,only a small set of sample images of the specific cell type from the user may be needed for training. | Huixia Ren Mengdi Zhao Bo Liu Ruixiao Yao Qi liu Zhipeng Ren Zirui Wu Zongmao Gao Xiaojing Yang Chao Tang | 2020 | Quantitative Biology2020，8，3： | 0 |
| 8 | Construction and Optimization of Liquefied Natural Gas Regasification Cold Energy Comprehensive Utilization System on Floating Storage Regasification Unit显示文摘In this paper, the efficient utilization of liquefied natural gas(LNG) vaporization cold energy in offshore liquefied natural gas floating storage regasification unit(FSRU) is studied. On the basis of considering different boil-off gas(BOG) practical treatment processes, a cascade comprehensive utilization scheme of cold energy of LNG based on the longitudinal three-stage organic Rankine cycle power generation and the low-grade cold energy used to frozen seawater desalination was proposed. Through the comparative analysis of the effects of the pure working fluid and eight mixed working fluids on the performance of the new system, the combination scheme of system mixed working fluid with the highest exergy efficiency of the system was determined. Then, the genetic algorithm was used to optimize the parameters of the new system. After optimization, the net output power of the LNG cold energy comprehensive utilization system proposed in this paper was 5186 kW, and the exergy efficiency is 30.6%. Considering the power generation and freshwater revenue, the annual economic benefit of the system operating is 18.71 million CNY. | YAO Shouguang WANG Mengdi YAN Likun ZHANG Qiang YE Yong | 2022 | Journal of Thermal Science2022，31，6： | 0 |
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