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| 1 | A novel inhibitor of N^(6)-methyladenosine demethylase FTO induces m RNA methylation and shows anti-cancer activities显示文摘N^(6)-methyladenosine(m^(6)A)modification is critical for m RNA splicing,nuclear export,stability and translation.Fat mass and obesity-associated protein(FTO),the first identified m^(6)A demethylase,is critical for cancer progression.Herein,we developed small-molecule inhibitors of FTO by virtual screening,structural optimization,and bioassay.As a result,two FTO inhibitors namely 18077 and 18097 were identified,which can selectively inhibit demethylase activity of FTO.Specifically,18097 bound to the active site of FTO and then inhibited cell cycle process and migration of cancer cells.In addition,18097 reprogrammed the epi-transcriptome of breast cancer cells,particularly for genes related to P53 pathway.18097 increased the abundance of m^(6)A modification of suppressor of cytokine signaling1(SOCS1)m RNA,which recruited IGF2 BP1 to increase m RNA stability of SOCS1 and subsequently activated the P53 signaling pathway.Further,18097 suppressed cellular lipogenesis via downregulation of peroxisome proliferator-activated receptor gamma(PPARγ),CCAAT/enhancer-binding protein alpha(C/EBPa),and C/EBPβ.Animal studies confirmed that 18097 can significantly suppress in vivo growth and lung colonization of breast cancer cells.Collectively,we identified that FTO can work as a potential drug target and the small-molecule inhibitor 18097 can serve as a potential agent against breast cancer. | Guoyou Xie Xu-Nian Wu Yuyi Ling Yalan Rui Deyan Wu Jiawang Zhou Jiexin Li Shuibin Lin Qin Peng Zigang Li Hongsheng Wang Hai-Bin Luo | 2022 | Acta Pharmaceutica Sinica B2022，12，2： | 4 |
| 2 | Enhanced piezo-response in copper halide perovskites based PVDF composite films显示文摘In-situ fabricated perovskite nanocrystals in polymeric matrix provide new generation composite materials for plenty of cutting edge technology. In this work, we report the in-situ fabrication of copper halide perovskite(MA_2CuCl_4, MA:CH_3NH_3^+) embedded poly(vinylidene fluoride)(PVDF) composite films. The optimized MA_2CuCl_4/PVDF composite films exhibit greatly enhanced piezo-response in comparasion with pure PVDF films. The enhancements were invesitgated and explained by applying piezo-response force microscopy(PFM) measurements and density functional theory(DFT) caculations. We proposed that the high piezoelectric properties of MA_2CuCl_4/PVDF composite films could be related to the large Cu off-centering displacement, the strong interactions between MA_2CuCl_4 and PVDF as well as large stress concentration around the MA_2CuCl_4 particles in the films. These piezoelectric composite films are expected to be suitable functional materials for flexible and/or wearable piezoelectrics. | Sheng Huang Gang Tang Hailong Huang Xian-gang Wu Puming Zhou Lin Zou Lei Xie Jianming Deng Xueyun Wang Haizheng Zhong Jiawang Hong | 2018 | Science Bulletin2018，63，19： | 4 |
| 3 | One-dimensional micro/nanomotors for biomedicine:delivery,sensing and surgery显示文摘The rapid development of artificial micro/nanomachines brings promising strategies to overcome challenges in biomedicine,including delivery,sensing and surgery.One-dimensional(1D)micro/nanomotors are one of the most attractive micro/nanomachines due to their high specific surface area,powerful impetus and weak rotation diffusion.In this review,different propulsion mechanisms and motion control strategies of 1D micro/nanomotors are summarized,and recent efforts towards their fabrication methods and biomedical applications are discussed.We envision the multidisciplinary research efforts in the field of 1D micro/nanomotors will pave their way to practical applications in bioimaging and biomedicine. | Jiawang Guo Yuan Lin | 2020 | Biomaterials Translational2020，1，1： | 1 |
| 4 | Highly Prevalent SARS-CoV-2 Antigenemia in COVID-19 Patients显示文摘Background:Many issues,such as severity assessment and antibody responses,remain to be answered eagerly for evaluation and understanding of COVID-19.Immune lesion is one of key pathogenesis of the disease.It would be helpful to understand the disease if an investigation on antigenemia and association was conducted in the patients with SARS-CoV-2 infection.Methods:A total of 156 patients admitted to the First People’s Hospital of Hefei or Anhui Provincial Hospital on January to February 2020 were involved in this study.SARS-CoV-2 nucleocapsid(NP)antigen,specific IgM/IgG antibodies,and RNA were detected in sequential sera from three COVID-19 patients,and additional 153 COVID-19 patients by means of NP-antigen capture enzyme-linked immunosorbent assay,colloidal gold quick diagnosis,and real-time RT-PCR,respectively.The clinical types of COVID-19 patients were classified into asymptomatic,mild,moderate,severe,and critical,following on the Chinese guideline of COVID-19 diagnosis and treatment.The demographic and clinical data of patients were obtained for comparable analysis.Results:NP antigen was detected in 5 of 20 sequential sera collected from three COVID-19 patients with typically clinical symptoms,and 60.13%(92/153)expanded samples collected within 17days after illness onset.No SARS-CoV-2 RNA segment was detected in these sera.The NP positive proportion reached a peak(84.85%,28/33)on 6 to 8days after illness onset.Both NP concentration and positive proportion were increased with the increase of clinical severity of COVID-19.Compared to NP negativepatients,NP positive patients had older age[years,medians(interquartileranges(IQR)),49(6)vs.31(11)],lowerpositive proportion of NP specific IgM[27.17%(25/92)vs.59.02%(36/61)],and IgG[21.74%(20/92)vs.59.02%(36/61)]antibodies,and longer duration[days,medians(IQR),24(10)vs.21(13)]from illness to recovery.Conclusions:SARS-CoV-2 NP antigenemia occurred in COVID-19,and presented highly prevalent at early stage of the disease.The antigenemia was related to clinical severity of the disease,and may beresponsible for the delay of detectable SARS-Cov-2IgM. | Wenyan Zhang Wei Liu Jiawang Lin Jing Jin Kefu Zhao Liwei Zhu Xiuzhen Wang Lijie Wang Renshu Tang Yindi Zhu Wei Zhou Enqing You Lei Zhang Xuxiang Liu Jinju Wu Lili Chen Wenjing Wang Qiang Zhang Rongbao Gao | 2022 | Infectious Diseases & Immunity2022，2，3： | 0 |
| 5 | Seasonal Characteristics of Forecasting Uncertainties in Surface PM_(2.5)Concentration Associated with Forecast Lead Time over the Beijing-Tianjin-Hebei Region显示文摘Forecasting uncertainties among meteorological fields have long been recognized as the main limitation on the accuracy and predictability of air quality forecasts.However,the particular impact of meteorological forecasting uncertainties on air quality forecasts specific to different seasons is still not well known.In this study,a series of forecasts with different forecast lead times for January,April,July,and October of 2018 are conducted over the Beijing-Tianjin-Hebei(BTH)region and the impacts of meteorological forecasting uncertainties on surface PM_(2.5)concentration forecasts with each lead time are investigated.With increased lead time,the forecasted PM_(2.5)concentrations significantly change and demonstrate obvious seasonal variations.In general,the forecasting uncertainties in monthly mean surface PM_(2.5)concentrations in the BTH region due to lead time are the largest(80%)in spring,followed by autumn(~50%),summer(~40%),and winter(20%).In winter,the forecasting uncertainties in total surface PM_(2.5)mass due to lead time are mainly due to the uncertainties in PBL heights and hence the PBL mixing of anthropogenic primary particles.In spring,the forecasting uncertainties are mainly from the impacts of lead time on lower-tropospheric northwesterly winds,thereby further enhancing the condensation production of anthropogenic secondary particles by the long-range transport of natural dust.In summer,the forecasting uncertainties result mainly from the decrease in dry and wet deposition rates,which are associated with the reduction of near-surface wind speed and precipitation rate.In autumn,the forecasting uncertainties arise mainly from the change in the transport of remote natural dust and anthropogenic particles,which is associated with changes in the large-scale circulation. | Qiuyan DU Chun ZHAO Jiawang FENG Zining YANG Jiamin XU Jun GU Mingshuai ZHANG Mingyue XU Shengfu LIN | 2024 | Advances in Atmospheric Sciences2024，41，5： | 0 |
| 6 | N6-methyladenosine facilitates mitochondrial fusion of colorectal cancer cells via induction of GSH synthesis and stabilization of OPA1 mRNA显示文摘Mitochondria undergo fission and fusion that are critical for cell survival and cancer development,while the regulatory factors for mitochondrial dynamics remain elusive.Herein we found that RNA m^(6)A accelerated mitochondria fusion of colorectal cancer(CRC)cells.Metabolomics analysis and function studies indicated that m^(6)A triggered the generation of glutathione(GSH)via the upregulation of RRM2B-a p53-inducible ribonucleotide reductase subunit with anti-reactive oxygen species potential.This in turn resulted in the mitochondria fusion of CRC cells.Mechanistically,m^(6)A methylation of A1240 at 3'UTR of RRM2B increased its mRNA stability via binding with IGF2BP2.Similarly,m^(6)A methylation of A2212 at the coding sequence(CDS)of OPA1-an essential GTPase protein for mitochondrial inner membrane fusion-also increased mRNA stability and triggered mitochondria fusion.Targeting m^(6)A through the methyltransferase inhibitor STM2457 or the dm^(6)ACRISPR system significantly suppressed mitochondria fusion.In vivo and clinical data confirmed the positive roles of the m^(6)A/mitochondrial dynamics in tumor growth and CRC progression.Collectively,m^(6)A promoted mitochondria fusion via induction of GSH synthesis and OPA1 expression,which facilitated cancer cell growth and CRC development. | Jiawang Zhou Haisheng Zhang Ke Zhong Lijun Tao Yu Lin Guoyou Xie Yonghuang Tan You Wu Yunqing Lu Zhuojia Chen Jiexin Li Xin Deng Qin Peng Zigang Li Hongsheng Wang | 2024 | National Science Review2024，11，3： | 0 |
| 7 | Design and comparative analysis of self-propelling drill bit applied to deep-sea stratum drilling robot显示文摘Robotic subsea stratum drilling robot is a method for new subsea stratigraphic geological investigation and resource exploration.Resistance at the front end is the main source of resistance to the robot’s motion in the strata.Since there is no continuous and strong downward drilling force as in conventional drilling rigs,robot movement relies heavily on the drill bit to reduce the drilling resistance.In this study we propose a self-propelling drill bit that can discharge soil debris to provide propulsive force and reduce the resistance.The key parameter of the drill bit design,the spiral blade lead angle,was determined by theoretical analysis of the drill bit’s soil discharging effect.To verify the structural advantages of the self-propelling drill bit in reducing resistance,a comparative analysis with a conventional conical drill bit was conducted.The drilling process of both bits was simulated using finite element simulation at various rotation speeds,the penetration force and torque data of both drill bits were obtained,and tests prepared accordingly in subsea soil were conducted.The simulations and tests verified that the penetration force of the self-propelling drill bit was lower than that of the conventional conical drill bit.The self-propelling drill bit can reduce the resistance effectively,and may play an important role in the stratum movement of drilling robots. | Peihao ZHANG Xingshuang LIN Hao WANG Jiawang CHEN Zhenwei TIAN Zixin WENG Ziqiang REN Peng ZHOU | 2023 | Journal of Zhejiang University-Science A(Applied Physics & Engineering)2023，24，10： | 0 |
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