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| 1 | Real-time whole-brain imaging of hemodynamics and oxygenation at micro-vessel resolution with ultrafast wide-field photoacoustic microscopy显示文摘High-speed high-resolution imaging of the whole-brain hemodynamics is critically important to facilitating neurovascular research.High imaging speed and image quality are crucial to visualizing real-time hemodynamics in complex brain vascular networks,and tracking fast pathophysiological activities at the microvessel level,which will enable advances in current queries in neurovascular and brain metabolism research,including stroke,dementia,and acute brain injury.Further,real-time imaging of oxygen saturation of hemoglobin(sO_(2))can capture fast-paced oxygen delivery dynamics,which is needed to solve pertinent questions in these fields and beyond.Here,we present a novel ultrafast functional photoacoustic microscopy(UFF-PAM)to image the whole-brain hemodynamics and oxygenation.UFF-PAM takes advantage of several key engineering innovations,including stimulated Raman scattering(SRS)based dual-wavelength laser excitation,water-immersible 12-facet-polygon scanner,high-sensitivity ultrasound transducer,and deep-learning-based image upsampling.A volumetric imaging rate of 2 Hz has been achieved over a field of view(FOV)of 11×7.5×1.5 mm^(3) with a high spatial resolution of~10 μm.Using the UFF-PAM system,we have demonstrated proof-of-concept studies on the mouse brains in response to systemic hypoxia,sodium nitroprusside,and stroke.We observed the mouse brain's fast morphological and functional changes over the entire cortex,including vasoconstriction,vasodilation,and deoxygenation.More interestingly,for the first time,with the whole-brain FOV and micro-vessel resolution,we captured the vasoconstriction and hypoxia simultaneously in the spreading depolarization(SD)wave.We expect the new imaging technology will provide a great potential for fundamental brain research under various pathological and physiological conditions. | Xiaoyi Zhu Qiang Huangl Anthony Dispirito Tri Vu Qiangzhou Rong Xiaorui Peng Huaxin Sheng Xiling Shen Qifa Zhou Laiming Jiang Ulrike Hoffmann Junjie Yao | 2022 | Light(Science & Applications)2022，11，6： | 2 |
| 2 | An integrative drug repositioning framework discovered a potential therapeutic agent targeting COVID-19显示文摘The global spread of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)requires an urgent need to find effective therapeutics for the treatment of coronavirus disease 2019(COVID-19).In this study,we developed an integrative drug repositioning framework,which fully takes advantage of machine learning and statistical analysis approaches to systematically integrate and mine large-scale knowledge graph,literature and transcriptome data to discover the potential drug candidates against SARS-CoV-2.Our in silico screening followed by wet-lab validation indicated that a poly-ADP-ribose polymerase 1(PARP1)inhibitor,CVL218,currently in Phase I clinical trial,may be repurposed to treat COVID-19.Our in vitro assays revealed that CVL218 can exhibit effective inhibitory activity against SARS-CoV-2 replication without obvious cytopathic effect.In addition,we showed that CVL218 can interact with the nucleocapsid(N)protein of SARS-CoV-2 and is able to suppress the LPS-induced production of several inflammatory cytokines that are highly relevant to the prevention of immunopathology induced by SARS-CoV-2 infection. | Yiyue Ge Tingzhong Tian Suling Huang Fangping Wan Jingxin Li Shuya Li Xiaoting Wang Hui Yang Lixiang Hong Nian Wu Enming Yuan Yunan Luo Lili Cheng Chengliang Hu Yipin Lei Hantao Shu Xiaolong Feng Ziyuan Jiang Yunfu Wu Ying Chi Xiling Guo Lunbiao Cui Liang Xiao Zeng Li Chunhao Yang Zehong Miao Ligong Chen Haitao Li Hainian Zeng Dan Zhao Fengcai Zhu Xiaokun Shen Jianyang Zeng | 2021 | Signal Transduction and Targeted Therapy2021，6，5： | 0 |
| 3 | ALDOB介导的果糖代谢促进肠癌肝转移的代谢重编程显示文摘文章简介各类恶性肿瘤中结直肠癌新生发病率(10.2%)位居第三,致死率(9.2%)位居第二。肠癌转移后5年存活率小于10%,是造成肠癌患者死亡的主要原因,也是肠癌治疗的困难所在。肝脏是肠癌主要的转移器官,大约70%转移向肝脏。那么肠癌细胞转移到肝脏以后. | 卜鹏程 Kai-Yuan Chen Kun Xiang Christelle Johnson Scott B.Crown Nikolai Rakhilin Yiwei Ai Lihua Wang Rui Xi Inna Astapova Yan Han Jiahe Li Bradley B.Barth Min Lu Ziyang Gao Robert Mines Liwen Zhang Mark Herman David Hsu Guo-Fang Zhang Xiling Shen | 2019 | 科学新闻2019，0，2： | 0 |
| 4 | Integrated chromatin and transcriptomic profiling of patient-derived colon cancer organoids identifies personalized drug targets to overcome oxaliplatin resistance显示文摘Colorectal cancer is a leading cause of cancer deaths.Most colorectal cancer patients eventually develop chemoresistance to the current standard-of-care therapies.Here,we used patient-derived colorectal cancer organoids to demonstrate that resistant tumor cells undergo significant chromatin changes in response to oxaliplatin treatment.Integrated transcriptomic and chromatin accessibility analyses using ATAC-Seq and RNA-Seq identified a group of genes associated with significantly increased chromatin accessibility and upregulated gene expression.CRISPR/Cas9 silencing of fibroblast growth factor receptor 1(FGFR1)and oxytocin receptor(OXTR)helped overcome oxaliplatin resistance.Similarly,treatment with oxaliplatin in combination with an FGFR1 inhibitor(PD166866)or an antagonist of OXTR(L-368,899)suppressed chemoresistant organoids.However,oxaliplatin treatment did not activate either FGFR1 or OXTR expression in another resistant organoid,suggesting that chromatin accessibility changes are patient-specific.The use of patient-derived cancer organoids in combination with transcriptomic and chromatin profiling may lead to precision treatments to overcome chemoresistance in colorectal cancer. | Kuei-Ling Tung Kai-Yuan Chen Marcos Negrete Tianyi Chen Alexias Safi Abed Alhalim Aljamal Lingyun Song Gregory E.Crawford Shengli Ding David S.Hsu Xiling Shen | 2021 | Genes & Diseases2021，8，2： | 0 |
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