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Super-resolution imaging for in situ monitoring sub-cellular micro-dynamics of small molecule drug

Acta Pharmaceutica Sinica B 2024年第4期14卷 1864-1877页

作者： Huimin Chen Guiqian Fang youxiao Ren Weiwei Zou Kang Ying Zhiwei Yang Qixin Chen School of Pharmaceutical Sciences&Institute of Materia Medica Medical Science and Technology Innovation CenterShandong First Medical University&Shandong Academy of Medical SciencesJinan 250062China MOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed Matter School of PhysicsXi'an Jiaotong UniversityXi'an 710049China Reproductive Medicine Center Department of Obstetrics and Gynecologythe First Affiliated Hospital of Anhui Medical UniversityHefei 230022China

Small molecule drugs play a pivotal role in the arsenal of anticancer pharmacological agents. Nonetheless, their small size poses a challenge when directly visualizing their localization, distribution, mechanism of action (MOA), and target engagement at the subcellular level in real time. We propose a strategy for developing triple-functioning drug beacons that seamlessly integrate therapeutically relevant bioactivity, precise subcellular localization, and direct visualization capabilities within a single molecular entity. As a proof of concept, we have meticulously designed and constructed a boronic acid fluorescence drug beacon using coumarin–hemicyanine (CHB). Our CHB design includes three pivotal features: a boronic acid moiety that binds both adenosine triphosphate (ATP) and adenosine diphosphate (ADP), thus depleting their levels and disrupting the energy supply within mitochondria;a positively charged component that targets the drug beacon to mitochondria;and a sizeable conjugated luminophore that emits fluorescence, facilitating the application of structured illumination microscopy (SIM). Our study indicates the exceptional responsiveness of our proof-of-concept drug beacon to ADP and ATP, its efficacy in inhibiting tumor growth, and its ability to facilitate the tracking of ADP and ATP distribution around the mitochondrial cristae. Furthermore, our investigation reveals that the micro-dynamics of CHB induce mitochondrial dysfunction by causing damage to the mitochondrial cristae and mitochondrial DNA. Altogether, our findings highlight the potential of SIM in conjunction with visual drug design as a potent tool for monitoring the in situ MOA of small molecule anticancer compounds. This approach represents a crucial advancement in addressing a current challenge within the field of small molecule drug discovery and validation.

关键词： Mitochondrial Drug beacon Sub-cellular Small molecule Energy supply Anti-tumor

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Spatial Heterogeneity of Marine Environment Changes:A Case Study in Laizhou Bay and Its Adjacent Waters,China

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Journal of Ocean University of China 2021年第1期20卷 111-123页

作者： wang youxiao YU Ge HU Guobin LIU Dahai College of Environmental Science and Engineering Ocean University of ChinaQingdao 266100China Key Laboratory of Marine Environment and Ecology Ministry of EducationQingdao 266100China State Key Laboratory of Resources and Environmental Information System Institute of Geographic Sciences and Natural Resources ResearchChinese Academy of SciencesBeijing 100101China College of Marine Life Sciences Ocean University of ChinaQingdao 266003China First Institute of Oceanography Ministry of Natural ResourcesQingdao 266061China

Temporal and spatial heterogeneity identifications of marine environment and its changes have great significances in marine spatial planning and offshore pollution control.In this study,considering the integration of marine ecological environment and sea-land interaction,we built a spatialized evaluation model named Marine Environment Change Spatial Assessment(MECSA)to quantify the marine environment status and changes.In MECSA,we applied the geospatial model and the pressure-state-response(PSR)model for processing and integrating evaluation indicators.A case study in the Laizhou Bay showed that the marine environment quality was generally in a declining state from 2009 to 2015.In 2015,the Marine Environment Index(MEI)had decreased by 0.1 compared with 2009,although the two years all reached a‘Good'level.The spatial MEI layers of the two years showed a same distribution:the southwestern part was in poorer status,with a fan ring shape gradually getting better to the northeast.The Marine Organisms Response Index(MORI)contributed the most to the MEI.Therefore,future marine environmental assessment and spatial planning should focus on the identification the marine environment with its changes from the perspective of spatial heterogeneity and systemicity.Based on single indicators and comprehensive evaluation results,we can propose spatially targeted policies and recommendations scientifically.

关键词： marine environment quality spatial heterogeneity PSR Laizhou Bay

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Assessment of tree-ring mercury radial translocation and age effect in Masson pine:Implications for historical atmospheric mercury reconstruction

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Journal of Environmental Sciences 2024年第4期138卷 266-276页

作者： Xu Liu Xun wang Dingyong wang College of Resources and Environment Southwest UniversityChongqing 400715China State Key Laboratory of Environmental Geochemistry Institute of GeochemistryChinese Academy of SciencesGuiyang 550081China

The tree ring has been regarded as an emerging archive to reconstruct historical atmospheric mercury(Hg)trends,but with the large knowledge gaps in the reliability.In this study,we comprehensively evaluated the Hg source,radial translocation and age effect of Masson pine(Pinus massoniana)tree ring at Mt.Jinyun in Chongqing,to assess the suitability of such tree ring as the archive of atmospheric Hg.Results showed that distinct variabilities among Masson pine tree-ring Hg concentration profiles.The Hg concentration significantly increased along with stem height(P<0.05),indicating the Hg in tree rings mainly derived from foliage uptake atmospheric Hg.We found a distinct age effect that the tree ring of young trees had the higher Hg concentration.Besides,we used the advection-diffusion model to demonstrate how Hg concentration shifted by the advection or/and diffusion in tree rings.The modeling results showed that the advection induced radial translocation during the young growth period of tree was a plausible mechanism to result in the tree-ring Hg record largely different from the trend of anthropogenic Hg emissions in Chongqing.We finally suggest that in further Hg dendrochemistry,better discarding the tree-ring Hg profile of the young growth period to reduce impacts of the radial translocation and age effect.

关键词： Masson pine Tree-ring mercury Radial translocation Tree age effect

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Pushing the boundaries: an interview with Dae-Hyun Kim on terahertz devices

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National Science Review 2024年第3期11卷 42-45页

作者： Defu wang the Center for Carbon-based Electronics School of Electronics Peking University

Ⅲ–Ⅴ compound semiconductors, such as InGaAs/InAlAs, exhibit exceptional carrier transport properties, establishing them as fundamental elements in terahertz(THz) applications crucial for the development of 6G netwo...

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Branched alkanes with quaternary carbon atoms in Chinese soils: Potential environmental implications

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Chinese Science Bulletin 2006年第9期51卷 1115-1122页

作者： BAI Yan FANG Xiaomin wang Yongli Fabien Kenig CHEN Xiuling wang youxiao Key Laboratory of Western China's Environmental Systems Ministry of Education of China & College of Resources and Environment Lanzhou University Lanzhou 730000 China Institute of Tibetan Plateau Research Chinese Academy of Sciences Beijing 100085 China State Key Laboratory of Gas Geochemistry Chinese Academy of Sciences Lanzhou 730000 China Department of Earth and Environmental Sciences University of Illi nois at Chicago Chicago IL 60607 USA

Lipids extracted from 26 modern soils collected from different climate zones in China and Mongolia are analyzed using gas chromatography- mass spectrometry. These extracts contain pseudo- homologous families of 5,5-diethylalkanes (5,5- DEAs), 6,6-diethylalkanes, 5-butyl-5-ethylalkanes and 6-butyl-6-ethylalkanes, which are first detected in modern soils. All these pseudohomologous series display exclusively odd or exclusively even carbon numbers, clearly indicating a biosynthetic origin, and their carbon number distributions generally covary. The distributions of 5,5-DEAs exhibit strong regional variations, correlated with the spatial distributions of climate and vegetation. The lower molecular weight 5,5-DEAs, maximizing at C21 or C23, dominate in southeast and southwest China samples, while the higher molecular weight 5,5-DEAs with a mode at C29 dominate in cold, arid northwest China and Mongolia. The results demonstrate that the distribution of 5,5-DEAs can serve as a new independent proxy, indicating variations in soil ecosystems and climates, just like the well-known proxy of n-C15—21/n-C22—33 ratios.

关键词：烷烃 BAQCs 脂类土壤环境影响

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Enrichment of anammox biomass during mainstream wastewater treatment driven by achievement of partial denitrification through the addition of bio-carriers

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Journal of Environmental Sciences 2024年第3期137卷 181-194页

作者： Yuqing Ma Bo wang Xiaodi Li Shuo wang Wen wang Yongzhen Peng National Engineering Laboratory for Advanced Municipal Wastewater Treatment and Reuse Technology Engineering Research Center of BeijingBeijing University of TechnologyBeijing 100124China

Anammox is widely considered as the most cost-effective and sustainable process for nitrogen removal.However,how to achieve the enrichment of anammox biomass remains a challenge for its large-scale application,especially in mainstream wastewater treatment.In this study,the feasibility of enrichment of anammox biomass was explored through the realization of partial denitrification and the addition of bio-carriers.By using ordinary activated sludge,a sequencing batch reactor(SBR)followed by an up-fow anaerobic sludge bed(UASB)was operated at 25±2℃ for 214 days.The long-term operation was divided into five phases,in which SBR and UASB were started-up in Phases I and II,respectively.By eliminating oxygen and adjusting the infow ratios in Phases III-V,advanced nitrogen removal was achieved with the effuent total nitrogen being 4.7 mg/L and the nitrogen removal efficiency being 90.5%in Phase V.Both in-situ and ex-situ activity tests demonstrated the occurrence of partial denitrification and anammox.Moreover,16S rRNA high-throughput sequencing analysis revealed that Candidatus Brocadia was enriched from below the detection limit to in biofilms(0.4%in SBR,2.2%in UASB)and the foc sludge(0.2%in SBR,1.3%in UASB),while Thauera was mainly detected in the foc sludge(8.1%in SBR,8.8%in UASB),which might play a key role in partial denitrification.Overall,this study provides a novel strategy to enrich anammox biomass driven by rapid achievement of partial denitrification through the addition of bio-carriers,which will improve large-scale application of anammox processes in mainstream wastewater treatment.

关键词： Enrichment Anammox biomass Bio-carriers Partial denitrification Mainstream wastewater

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Performance and mechanism of La-Fe metal-organic framework as a highly efficient adsorbent for fluoride removal from mine water

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Journal of Environmental Sciences 2024年第5期139卷 245-257页

作者： Chaomin Jia Jianbing wang Huijiao wang Sichao Zhu Xiaohui Zhang Yuxiang wang School of Chemical&Environmental Engineering China University of Mining&Technology-BeijingBeijing 100083China Beijing Polytechnic Beijing 100176China Chinese Society for Urban Studies Beijing 100835China

Water fluoride pollution has caused non-negligible harm to the environment and humans,and thus it is crucial to find a suitable treatment technology.In this study,La-Fe@PTA adsorbent was synthesized for the defluoridation of mine water.The results showed that the optimum conditions for defluoridation by La-Fe@PTA were p H close to 7.0,the initial F-concentration of 10 mg/L,the dosage of 0.5 g/L and the adsorption time of 240 min.Compared with SO_4^(2-),Cl^(-),NO_(3)^(-),Ca^(2+)and Mg^(2+),CO_(3)^(2-)and HCO_(3)^(-)presented severer inhibition on fluoride uptake by La-Fe@PTA.The adsorption process fits well with the pseudo-second-order kinetic model and Freundlich model,and the maximum adsorption capacity of Langmuir model was 95 mg/g.Fixed-bed adsorption results indicated that fluoride in practical fluorinated mine water could be effectively removed from 3.6 mg/L to less than 1.5 mg/L within130 bed volume(BV)by using 1.5 g La-Fe@PTA.Furthermore,the adsorbent still had good adsorption capacity after regeneration,which confirms the great application potential of La-Fe@PTA as a fluoride ion adsorbent.The mechanism analysis showed that La-Fe@PTA adsorption of fluorine ions is a physicochemical reaction driven by electrostatic attraction and ion exchange.

关键词： Adsorption La-Fe@PTA Fluoride ion Mine water Mechanism

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Analysis of Hot Topics Regarding Global Smart Elderly Care Research—1997-2021

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China CDC weekly 2024年第9期6卷 157-161页

作者： Hongman wang Hong Chen Yuqi wang School of Health Humanities Peking UniversityBeijingChina Center for Global Public Health Chinese Center for Disease Control and PreventionBeijingChina

Summary What is already known about this topic?With the assistance of the internet,big data,cloud computing,and other technologies,the concept of smart elderly care has emerged.What is added by this report?This study presents information on the countries or regions that have conducted research on smart elderly care,as well as identifies global hotspots and development trends in this field.

关键词： Smart internet smart

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Continuous-wave operation of 1550 nm low-threshold triple-lattice photonic-crystal surface-emitting lasers

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Light(Science & Applications) 2024年第3期13卷 446-453页

作者： Ziye wang Xia Liu Pinyao wang Huanyu Lu Bo Meng Wei Zhang Lijie wang Yanjing wang Cunzhu Tong State Key Laboratory of Luminescence and Applications Changchun Institute of OpticsFine Mechanics and PhysicsChinese Academy of SciencesChangchun 130033China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijing 100049China Central Research Institute Planning Dept 2012 LabsHuawei Technologies Company Ltd.Shenzhen 518129China

Benefitting from narrow beam divergence,photonic crystal surface-emitting lasers are expected to play an essential role in the ever-growing fields of optical communication and light detection and ranging.Lasers operating with 1.55μm wavelengths have attracted particular attention due to their minimum fiber loss and high eye-safe threshold.However,high interband absorption significantly decreases their performance at this 1.55μm wavelength.Therefore,stronger optical feedback is needed to reduce their threshold and thus improve the output power.Toward this goal,photonic-crystal resonators with deep holes and high dielectric contrast are often used.Nevertheless,the relevant techniques for high-contrast photonic crystals inevitably complicate fabrication and reduce the final yield.In this paper,we demonstrate the first continuous-wave operation of 1.55μm photonic-crystal surface-emitting lasers by using a‘triple-lattice photonic-crystal resonator’,which superimposes three lattice point groups to increase the strength of in-plane optical feedback.Using this geometry,the in-plane 180°coupling can be enhanced threefold compared to the normal single-lattice structure.Detailed theoretical and experimental investigations demonstrate the much lower threshold current density of this structure compared to‘single-lattice’and‘double-lattice’photonic-crystal resonators,verifying our design principles.Our findings provide a new strategy for photonic crystal laser miniaturization,which is crucial for realizing their use in future high-speed applications.

关键词： resonator crystal lattice

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Determining an optimal control strategy for anthropogenic VOC emissions in China based on source emissions and reactivity

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Journal of Environmental Sciences 2024年第2期136卷 248-260页

作者： Ruipeng wang Xiaoqi wang Shuiyuan Cheng Jiaxian Zhu Xinyu Zhang Long Cheng Kai wang Key Laboratory of Beijing on Regional Air Pollution Control Faculty of Environment and LifeBeijing University of TechnologyBeijing 100124China

An evidence-based control strategy for emission reduction of VOC sources can effectively solve the regional PM2.5and O3compound pollution in China.We estimated the anthropogenic VOC emission inventory in China in 2018 and established a source profile database containing 129 sources based on localized detection and the latest research results.Then,the distribution of the ozone formation potential(OFP)and secondary organic aerosol formation potential(SOAFP)for emission sources was analyzed.Moreover,priority control routes for VOC emission sources were proposed for different periods.Anthropogenic VOC emissions in China reached 27,211.8 Gg in 2018,and small passenger cars,industrial protective coatings,biomass burning,heavy trucks,printing,asphalt paving,oil storage and transportation,coking,and oil refining were the main contributors.Industrial protective coatings,small passenger cars,and biomass burning all contributed significantly to OFP and SOAFP.Priority in emission reduction control should be given to industrial protective coatings,small passenger cars,heavy trucks,coking,printing,asphalt paving,chemical fibers,and basic organic chemical sources over the medium and long term in China.In addition,the priority control route for VOC emission sources should be adjusted according to the variations in VOC emission characteristics and regional differences,so as to obtain the maximum environmental benefits.

关键词： Volatile organic compounds Anthropogenic emission inventory Reactivity Emission projection Priority control route

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