The Wide Field Survey Telescope(WFST) is a dedicated photometric surveying facility being built jointly by University of Science and Technology of China(USTC) and the Purple Mountain Observatory(PMO). It is equipped w...The Wide Field Survey Telescope(WFST) is a dedicated photometric surveying facility being built jointly by University of Science and Technology of China(USTC) and the Purple Mountain Observatory(PMO). It is equipped with a 2.5-meter diameter primary mirror, an active optics system, and a mosaic CCD camera with 0.73 gigapixels on the primary focal plane for highquality image capture over a 6.5-square-degree field of view. The installation of WFST near the summit of Saishiteng mountain in the Lenghu region is scheduled in summer of 2023, and the operation is planned to start three months later. WFST will scan the northern sky in four optical bands(u, g, r and i) at cadences from hourly/daily in the deep high-cadence survey(DHS) program, to semi-weekly in the wide field survey(WFS) program. During a photometric night, a nominal 30 s exposure in the WFS program will reach a depth of 22.27, 23.32, 22.84, and 22.31(AB magnitudes) in these four bands, respectively, allowing for the detection of a tremendous amount of transients in the low-z universe and a systematic investigation of the variability of Galactic and extragalactic objects. In the DHS program, intranight 90 s exposures as deep as 23(u) and 24 mag(g), in combination with target of opportunity follow-ups, will provide a unique opportunity to explore energetic transients in demand for high sensitivities, including the electromagnetic counterparts of gravitational wave events, supernovae within a few hours of their explosions,tidal disruption events and fast, luminous optical transients even beyond redshift of unity. In addition, the final 6-year co-added images, anticipated to reach g■25.8 mag in WFS or 1.5 mags deeper in DHS, will be of fundamental importance to general Galactic and extragalactic science. The highly uniform legacy surveys of WFST will serve as an indispensable complement to those of the Vera C. Rubin Observatory's Legacy Survey of Space and Time(LSST) that monitors the southern sky.展开更多
The LIGO detection of gravitational waves(GW) from merging black holes in 2015 marked the beginning of a new era in observational astronomy. The detection of an electromagnetic signal from a GW source is the critical ...The LIGO detection of gravitational waves(GW) from merging black holes in 2015 marked the beginning of a new era in observational astronomy. The detection of an electromagnetic signal from a GW source is the critical next step to explore in detail the physics involved. The Antarctic Survey Telescopes(AST3),located at Dome A, Antarctica, is uniquely situated for rapid response time-domain astronomy with its continuous night-time coverage during the austral winter. We report optical observations of the GW source(GW 170817) in the nearby galaxy NGC 4993 using AST3. The data show a rapidly fading transient at around 1 day after the GW trigger, with the i-band magnitude declining from 17:23 ± 0:13 magnitude to 17:72 ± 0:09 magnitude in ~1:8 h. The brightness and time evolution of the optical transient associated with GW 170817 are broadly consistent with the predictions of models involving merging binary neutron stars. We infer from our data that the merging process ejected about ~10^(-2) solar mass of radioactive material at a speed of up to 30% the speed of light.展开更多
Cisplatin is one of the most successful antitumor agents, yet also restricted by its poor cellular uptake and low selectivity. Since 3-(2-nitrophenyl) propionic acid(NPPA) has been reported as a bioreductive prodrug m...Cisplatin is one of the most successful antitumor agents, yet also restricted by its poor cellular uptake and low selectivity. Since 3-(2-nitrophenyl) propionic acid(NPPA) has been reported as a bioreductive prodrug moiety, herein we combined NPPA with cisplatin(compound 1) to improve its lipophilicity and targetability and then to improve the antitumor outcomes. In addition, compound 2 possessing 3-phenyl propionic acid(PPA) was also synthesized as a comparison to test the influence of the NPPA to the cytotoxicity, since PPA was not a bioreductive moiety. Bioevaluations showed that 1 displayed more potent antitumor potency than cisplatin and 2, suggesting Pt(II) complexes possessing NPPA groups may be a good strategy for future platinum drug discovery.展开更多
DNA methyl transferase(DNMT) and histone deacetylase(HDAC) are well recognized epigenetic targets for discovery of antitumor agents.In this study,we designed and synthesized a series of nucleoside base hydroxamic acid...DNA methyl transferase(DNMT) and histone deacetylase(HDAC) are well recognized epigenetic targets for discovery of antitumor agents.In this study,we designed and synthesized a series of nucleoside base hydroxamic acid derivatives as DNMT and HDAC dual inhibitors.MTT assays and enzymatic inhibitory activity tests indicated that compound 204 exhibited potent DNMT1 and HDAC1/6 inhibitory potency simultaneously in enzymatic levels and at cellular levels,inducing hypomethylation of p16 and hyperacetylation of histones H_(3) K9 and H4 K8.Besides,204 remarkably inhibited proliferation against cancer cells U937 by prompting G0/G1 cell cycle arrest.Molecular docking models explained the functional mechanism of 204 inhibiting DNMT1 and HDAC.Preliminary studies on metabolic profiles revealed that 204 showed desirable stability in liver microsomes.Our study suggested that 204 inhibiting DNMT and HDAC concurrently can be a potential lead compound for epigenetic cancer therapy.展开更多
Multiple histone deacetylase inhibitors (HDACi) and DNA methyltransferase inhibitors (DNMTi) have been developed for cancer therapy. However, the research on their mechanisms of action is not sophisticated enough. In ...Multiple histone deacetylase inhibitors (HDACi) and DNA methyltransferase inhibitors (DNMTi) have been developed for cancer therapy. However, the research on their mechanisms of action is not sophisticated enough. In this study, we reported a dual HDAC and DNMT inhibitor 208 and found it induced G1 cell cycle arrest and apoptosis in U937 cells. Proteome and bioinformatic analyses revealed that the combined inhibition of DNMT1 and HDAC by 208 affected the expression of a series of proteins involved in many biological processes. We observed that several proteins associated with G1 cell cycle arrest and apoptosis were down regulated after 208 treatment, including p85α, MEK, and CDK4, suggesting that 208 induces cell cycle arrest and apoptosis through the p85α/MEK-mediated pathway in U937 cells. Moreover, biological function analysis showed that the combined epigenetic inhibition influenced various processes, including the synthesis and processing of RNA, translation, protein transport, and DNA repair. These findings provide novel insight into the potential mechanisms of multifunctional epigenetic inhibitors, which supports their further improvement and development.展开更多
In this study,we designed and synthesized a series of phthalazinone acridine derivatives as dual PARP and Topo inhibitors.MTT assays indicated that most of the compounds significantly inhibited multiple cancer cells p...In this study,we designed and synthesized a series of phthalazinone acridine derivatives as dual PARP and Topo inhibitors.MTT assays indicated that most of the compounds significantly inhibited multiple cancer cells proliferation.In addition,all the compounds displayed Topo Ⅱ inhibition activity at 10 mol/L,and also possessed good PARP-1 inhibitory activities.Subsequent mechanistic studies showed that compound 9 a induced remarkable apoptosis and caused prominent S cell cycle arrest in HCT116 cells.Our study suggested that 9 a inhibiting Topo and PARP concurrently can be a potential lead compound for cancer therapy.展开更多
基金supported by the Cyrus Chun Ying Tang Foundationsthe Major Science and Technology Project of Qinghai Province(Grant No.2019ZJ-A10)+4 种基金the 111 Project for“Observational and Theoretical Research on Dark Matter and Dark Energy”(Grant No.B23042)the National Natural Science Foundation of China(Grant Nos.11833007,12073078,12173088,12192221,12192224,12233008,12273036,and 12273113)the Frontier Scientific Research Program of Deep Space Exploration Laboratory(Grant No.2022-QYKYJH-HXYF-012)the support from the USTC Research Funds of the Double First-Class Initiative(Grant No.YD2030002009)Project for Young Scientists in Basic Research of the Chinese Academy of Sciences(Grant No.YSBR-061),respectively。
文摘The Wide Field Survey Telescope(WFST) is a dedicated photometric surveying facility being built jointly by University of Science and Technology of China(USTC) and the Purple Mountain Observatory(PMO). It is equipped with a 2.5-meter diameter primary mirror, an active optics system, and a mosaic CCD camera with 0.73 gigapixels on the primary focal plane for highquality image capture over a 6.5-square-degree field of view. The installation of WFST near the summit of Saishiteng mountain in the Lenghu region is scheduled in summer of 2023, and the operation is planned to start three months later. WFST will scan the northern sky in four optical bands(u, g, r and i) at cadences from hourly/daily in the deep high-cadence survey(DHS) program, to semi-weekly in the wide field survey(WFS) program. During a photometric night, a nominal 30 s exposure in the WFS program will reach a depth of 22.27, 23.32, 22.84, and 22.31(AB magnitudes) in these four bands, respectively, allowing for the detection of a tremendous amount of transients in the low-z universe and a systematic investigation of the variability of Galactic and extragalactic objects. In the DHS program, intranight 90 s exposures as deep as 23(u) and 24 mag(g), in combination with target of opportunity follow-ups, will provide a unique opportunity to explore energetic transients in demand for high sensitivities, including the electromagnetic counterparts of gravitational wave events, supernovae within a few hours of their explosions,tidal disruption events and fast, luminous optical transients even beyond redshift of unity. In addition, the final 6-year co-added images, anticipated to reach g■25.8 mag in WFS or 1.5 mags deeper in DHS, will be of fundamental importance to general Galactic and extragalactic science. The highly uniform legacy surveys of WFST will serve as an indispensable complement to those of the Vera C. Rubin Observatory's Legacy Survey of Space and Time(LSST) that monitors the southern sky.
基金supported by the National Basic Research Program(973 Program)of China(2013CB834900)the Chinese Polar Environment Comprehensive Investigation&Assessment Program(CHINARE2016-02-03)+21 种基金the National Natural Science Foundation of China(11573014,11673068,11325313,11633002,11433009,11725314)the Key Research Program of Frontier Sciences(QYZDY-SSW-SLH010,QYZDB-SSW-SYS005)the Strategic Priority Research Program"multi-waveband gravitational wave Universe”(XDB23040000)the Youth Innovation Promotion Association(2011231)of Chinese Academy of Sciencesfunds from Tsinghua UniversityNanjing UniversityBeijing Normal UniversityUniversity of New South WalesTexas A&M Universitythe Australian Antarctic Divisionthe National Collaborative Research Infrastructure Strategy(NCRIS)of Australiafunding from the Chinese Academy of Sciences through the Center for Astronomical Mega-Science and National Astronomical Observatory of China(NAOC)made possible through the use of the AAVSO Photometric All-Sky Survey(APASS)funded by the Robert Martin Ayers Sciences Fundfunded by the Australian Research Council(ARC)Centre of Excellence for Gravitational Wave Discovery(OzGrav),CE170100004the ARC Centre of Excellence for All-sky Astrophysics(CAASTRO),CE110001020the Centre of Excellence for All-sky Astrophysics in 3-Dimensions(ASTRO-3D),CE170100013provided by the Australian Astronomical Observatory(AAO)the ARC Future Fellowship grant,FT130101219supported by the National Basic Research Program(Project 973)of China(2014CB845800)the National Natural Science Foundation of China(11633001 and 11373014)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB23000000)
文摘The LIGO detection of gravitational waves(GW) from merging black holes in 2015 marked the beginning of a new era in observational astronomy. The detection of an electromagnetic signal from a GW source is the critical next step to explore in detail the physics involved. The Antarctic Survey Telescopes(AST3),located at Dome A, Antarctica, is uniquely situated for rapid response time-domain astronomy with its continuous night-time coverage during the austral winter. We report optical observations of the GW source(GW 170817) in the nearby galaxy NGC 4993 using AST3. The data show a rapidly fading transient at around 1 day after the GW trigger, with the i-band magnitude declining from 17:23 ± 0:13 magnitude to 17:72 ± 0:09 magnitude in ~1:8 h. The brightness and time evolution of the optical transient associated with GW 170817 are broadly consistent with the predictions of models involving merging binary neutron stars. We infer from our data that the merging process ejected about ~10^(-2) solar mass of radioactive material at a speed of up to 30% the speed of light.
基金Shenzhen Sci & Tech Bureau (Nos. JCYJ20160301153959476 and JCYJ20160324163734374)
文摘Cisplatin is one of the most successful antitumor agents, yet also restricted by its poor cellular uptake and low selectivity. Since 3-(2-nitrophenyl) propionic acid(NPPA) has been reported as a bioreductive prodrug moiety, herein we combined NPPA with cisplatin(compound 1) to improve its lipophilicity and targetability and then to improve the antitumor outcomes. In addition, compound 2 possessing 3-phenyl propionic acid(PPA) was also synthesized as a comparison to test the influence of the NPPA to the cytotoxicity, since PPA was not a bioreductive moiety. Bioevaluations showed that 1 displayed more potent antitumor potency than cisplatin and 2, suggesting Pt(II) complexes possessing NPPA groups may be a good strategy for future platinum drug discovery.
基金financial supports from China Postdoctoral Science Foundation (No.2018M631825)Shenzhen Development and Reform Committee (No.2019156)+2 种基金Shenzhen Science,Technology and Innovation Commission (No.JCYJ20180306174248782)Department of Science and Technology of Guangdong Province (No.2017B030314083)Shenzhen Bay Laboratory Open Funding (No.SZBL2019062801009)。
文摘DNA methyl transferase(DNMT) and histone deacetylase(HDAC) are well recognized epigenetic targets for discovery of antitumor agents.In this study,we designed and synthesized a series of nucleoside base hydroxamic acid derivatives as DNMT and HDAC dual inhibitors.MTT assays and enzymatic inhibitory activity tests indicated that compound 204 exhibited potent DNMT1 and HDAC1/6 inhibitory potency simultaneously in enzymatic levels and at cellular levels,inducing hypomethylation of p16 and hyperacetylation of histones H_(3) K9 and H4 K8.Besides,204 remarkably inhibited proliferation against cancer cells U937 by prompting G0/G1 cell cycle arrest.Molecular docking models explained the functional mechanism of 204 inhibiting DNMT1 and HDAC.Preliminary studies on metabolic profiles revealed that 204 showed desirable stability in liver microsomes.Our study suggested that 204 inhibiting DNMT and HDAC concurrently can be a potential lead compound for epigenetic cancer therapy.
基金financial supports from Shenzhen Development and Reform Committee(No. 20151961)China Postdoctoral Science Foundation(No. 2018M631825)Department of Science and Technology of Guangdong Province (No. 2017B030314083)
文摘Multiple histone deacetylase inhibitors (HDACi) and DNA methyltransferase inhibitors (DNMTi) have been developed for cancer therapy. However, the research on their mechanisms of action is not sophisticated enough. In this study, we reported a dual HDAC and DNMT inhibitor 208 and found it induced G1 cell cycle arrest and apoptosis in U937 cells. Proteome and bioinformatic analyses revealed that the combined inhibition of DNMT1 and HDAC by 208 affected the expression of a series of proteins involved in many biological processes. We observed that several proteins associated with G1 cell cycle arrest and apoptosis were down regulated after 208 treatment, including p85α, MEK, and CDK4, suggesting that 208 induces cell cycle arrest and apoptosis through the p85α/MEK-mediated pathway in U937 cells. Moreover, biological function analysis showed that the combined epigenetic inhibition influenced various processes, including the synthesis and processing of RNA, translation, protein transport, and DNA repair. These findings provide novel insight into the potential mechanisms of multifunctional epigenetic inhibitors, which supports their further improvement and development.
基金financial supports from the Shenzhen Development and Reform Committee(Nos.20151961 and 2019156)Department of Science and Technology of Guangdong Province(No.2017B030314083)。
文摘In this study,we designed and synthesized a series of phthalazinone acridine derivatives as dual PARP and Topo inhibitors.MTT assays indicated that most of the compounds significantly inhibited multiple cancer cells proliferation.In addition,all the compounds displayed Topo Ⅱ inhibition activity at 10 mol/L,and also possessed good PARP-1 inhibitory activities.Subsequent mechanistic studies showed that compound 9 a induced remarkable apoptosis and caused prominent S cell cycle arrest in HCT116 cells.Our study suggested that 9 a inhibiting Topo and PARP concurrently can be a potential lead compound for cancer therapy.
