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| 1 | EGFR TKIs impair lysosome-dependent degradation of SQSTM1 to compromise the effectiveness in lung cancer显示文摘Tyrosine kinase inhibitors for epidermal growth factor receptor(EGFR TKIs)greatly improved clinical outcomes of patients with non-small cell lung cancer(NSCLC).Unfortunately,primary and acquired resistance limits their clinical benefits.To overcome such resistance,new generations of EGFR TKIs have been developed by targeting newly identified mutations in EGFR.However,much less effort has been put into alternative strategies,such as targeting the intrinsic protective responses to EGFR TKIs.In this study,we found that EGFR TKIs,including gefitinib and AZD9291,impaired lysosome-dependent degradation of SQSTM1,thus compromising their anti-cancer efficiency.By accumulating in the lysosome lumen,gefitinib and AZD9291 attenuated lysosomal acidification and impaired autolysosomal degradation of SQSTM1 owing to their intrinsic alkalinity.As a result,SQSTM1 protein was stabilized in response to gefitinib and AZD9291 treatment and conferred EGFR TKI resistance.Depleting SQSTM1 significantly increased the sensitivity of NSCLC cells to gefitinib and AZD9291 both in vitro and in vivo.Furthermore,a chemically modified gefitinib analog lacking alkalinity displayed stronger inhibitory effects on NSCLC cells.Therefore,targeting accumulated SQSTM1 or chemically modified EGFR TKIs may represent new strategies to increase the effectiveness of EGFR targeted therapy. | Lixian Yang Shilong Ying Shiman Hu Xiangtong Zhao Muchun Li Miaoqin Chen Yiran Zhu Ping Song Liyuan Zhu Tingting Jiang Huimin An Neelum Aziz Yousafzai Wenxia Xu Zhiguo Zhang Xian Wang Lifeng Feng Hongchuan Jin | 2019 | Signal Transduction and Targeted Therapy2019，4，1： | 2 |
| 2 | A rapid response photochromic diarylethene material for rewritable holographic data storage显示文摘A novel diarylethene,namely 4,5-(2,5-dimethyl thiophene) phthalimide,was synthesized and successfully introduced to rewritable holographic data storage.Upon the alternative illumination of UV and visible light(>400 nm),this compound underwent rapid,reversible inter-conversion between colorless open-ring isomer and yellow-green ring-closed form in both solution and polymethyl methacrylate(PMMA) film.Subsequently,we investigated the characteristics of volume homographic recording of the diarylethene-doped PMMA film(1 m thick).The maximum refractive index modulation(0.87‰) of the film during recording could be reached within just 120 s which gave the ability of fast recording.The high quality reconstruction after 50 write/erase cycles demonstrated its excellent fatigue-resistance and high resolution.All those results indicated that this molecule was a reliable fast write/erase holographic storage material. | ZHANG Qi LI JingMing NIU LiHong CHEN ZiHui YANG Lin ZHANG ShiMan CAO LiangCai ZHANG FuShi | 2013 | Chinese Science Bulletin2013，58，1： | 1 |
| 3 | Mapping the distributions of blood-sucking mites and mite-borne agents in China:a modeling study显示文摘Background:Emerging mite-borne pathogens and associated disease burdens in recent decades are raising serious public health concerns,yet their distributions and ecology remain under-investigated.We aim to describe the geographical distributions of blood-sucking mites and mite-borne agents and to assess their ecological niches in China.Methods:We mapped 549 species of blood-sucking mites belonging to 100 genera at the county level and eight mite-associated agents detected from 36 species of blood-sucking mites in China during 1978–2020.Impacts of climatic and environmental factors on the ecology of 21 predominant vector mites and a leading pathogen,Orientia tsutsugamushi,were assessed using boosted regression tree(BRT)models,and model-predicted risks were mapped.We also estimated the model-predicted number,area and population size of afected counties for each of the 21 mite species in China.Results:Laelaps echidninus is the leading mite species that potentially afects 744 million people,followed by La.jettmari(517 million)and Eulaelaps stabularis(452 million).Leptotrombidium scutellare is the mite species harboring the highest variety of mite-borne agents including four Rickettsia species and two viruses,followed by Eu.stabularis(2 agents),L.palpale(2)and La.echidninus(2).The top two agents that parasitize the largest number of mite species are O.tsutsugamushi(28 species)and hantavirus(8).Mammalian richness,annual mean temperature and precipitation of the driest quarter jointly determine the ecology of the mites,forming four clusters of major mite species with distinct geographic distributions.High-risk areas of O.tsutsugamushi are mainly distributed in southern and eastern coastal provinces where 71.5 million people live.Conclusions:Ecological niches of major mite species and mite-borne pathogens are much more extensive than what have been observed,necessitating expansion of current fled surveillance. | Tao Wang Fanfei Meng Tianle Che Jinjin Chen Haiyang Zhang Yang Ji Zhengwei Fan Guoping Zhao Wenhui Zhang Baogui Jiang Qiang Xu Chenlong Lv Taoxing Shi Shiman Ruan Lanzheng Liu Wei Liu Yang Yang Liqun Fang | 2022 | Infectious Diseases of Poverty2022，11，2： | 0 |
| 4 | Targeting nuclear acid-mediated immunity in cancer immune checkpoint inhibitor therapies显示文摘Cancer immunotherapy especially immune checkpoint inhibition has achieved unprecedented successes in cancer treatment.However,there are many patients who failed to benefit from these therapies,highlighting the need for new combinations to increase the clinical efficacy of immune checkpoint inhibitors.In this review,we summarized the latest discoveries on the combination of nucleic acid-sensing immunity and immune checkpoint inhibitors in cancer immunotherapy.Given the critical role of nuclear acid-mediated immunity in maintaining the activation of T cell function,it seems that harnessing the nuclear acidmediated immunity opens up new strategies to enhance the effect of immune checkpoint inhibitors for tumor control. | Miaoqin Chen Shiman Hu Yiling Li Ting Ting Jiang Hongchuan Jin Lifeng Feng | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 0 |
| 5 | Integrated proteogenomic characterization across major histological types of pituitary neuroendocrine tumors显示文摘Pituitary neuroendocrine tumor(PitNET)is one of the most common intracranial tumors.Due to its extensive tumor heterogeneity and the lack of high-quality tissues for biomarker discovery,the causative molecular mechanisms are far from being fully defined.Therefore,more studies are needed to improve the current clinicopathological classification system,and advanced treatment strategies such as targeted therapy and immunotherapy are yet to be explored.Here,we performed the largest integrative genomics,transcriptomics,proteomics,and phosphoproteomics analysis reported to date for a cohort of 200 PitNET patients.Genomics data indicate that GNAS copy number gain can serve as a reliable diagnostic marker for hyperproliferation of the PIT1 lineage.Proteomics-based classification of PitNETs identified 7 clusters,among which,tumors overexpressing epithelial-mesenchymal transition(EMT)markers clustered into a more invasive subgroup.Further analysis identified potential therapeutic targets,including CDK6,TWIST1,EGFR,and VEGFR2,for different clusters.Immune subtyping to explore the potential for application of immunotherapy in PitNET identified an association between alterations in the JAK1-STAT1-PDL1 axis and immune exhaustion,and between changes in the JAK3-STAT6-FOS/JUN axis and immune infiltration.These identified molecular markers and alternations in various clusters/subtypes were further confirmed in an independent cohort of 750 PitNET patients.This proteogenomic analysis across traditional histological boundaries improves our current understanding of PitNET pathophysiology and suggests novel therapeutic targets and strategies. | Fan Zhang Qilin Zhang Jiajun Zhu Boyuan Yao Chi Ma Nidan Qiao Shiman He Zhao Ye Yunzhi Wang Rui Han Jinwen Feng Yongfei Wang Zhaoyu Qin Zengyi Ma Kai Li Yichao Zhang Sha Tian Zhengyuan Chen Subei Tan Yue Wu Peng Ran Ye Wang Chen Ding Yao Zhao | 2022 | Cell Research2022，32，12： | 0 |
| 6 | Role of main RNA modifications in cancer:N^(6)-methyladenosine,5-methylcytosine,and pseudouridine显示文摘Cancer is one of the major diseases threatening human life and health worldwide.Epigenetic modification refers to heritable changes in the genetic material without any changes in the nucleic acid sequence and results in heritable phenotypic changes.Epigenetic modifications regulate many biological processes,such as growth,aging,and various diseases,including cancer.With the advancement of next-generation sequencing technology,the role of RNA modifications in cancer progression has become increasingly prominent and is a hot spot in scientific research.This review studied several common RNA modifications. | Chen Xue Qingfei Chu Qiuxian Zheng Shiman Jiang Zhengyi Bao Yuanshuai Su Juan Lu Lanjuan Li | 2022 | Signal Transduction and Targeted Therapy2022，7，5： | 0 |
| 7 | Microscopic Characteristics and Routine Detection of Hedyotis hedyotidea(DC.)Merr.显示文摘[Objectives]To study the microscopic characteristics and routine detection of Hedyotis hedyotidea(DC.)Merr.[Methods]The microscopic characteristics of the root,stem cross section and the whole plant powder of H.hedyotidea were studied by the methods of slide-shaft section,biological staining and microscopic imaging;the routine detection items such as moisture,ash,acid-insoluble ash and extract were detected and analyzed in accordance with the requirements of Chinese Pharmacopoeia.[Results]The microscopic characteristics of the root,the stem and the whole plant powder of H.hedyotidea were obtained.The moisture content of 10 batches of H.hedyotidea samples was in the range of 4.25%-7.90%,the water-soluble extract is in the range of 15.08%-22.52%,the total ash was in the scope of 8.27%-10.45%,and the acid-insoluble ash was in 0.13%-0.95%.The proposed water content of H.hedyotidea should not exceed 10.00%,the water-soluble extract should not be less than 12.00%,the total ash content should not exceed 13.00%,and the acid-insoluble ash content should not exceed 1.20%.[Conclusions]The results of this experiment can provide a reference for the quality control and quality standard of H.hedyotidea. | Guoshen WANG Shiman CHEN Shenggao YIN Canfei ZHANG Yanxia CEN Hailin LU | 2023 | Medicinal Plant2023，14，5： | 0 |
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