Each year, during the dry season that precedes the summer wind and rainfall Indo-China Peninsula (ICP), significant biomass burning occurs and reaches its peak from March to April. This biomass burning generates large...Each year, during the dry season that precedes the summer wind and rainfall Indo-China Peninsula (ICP), significant biomass burning occurs and reaches its peak from March to April. This biomass burning generates large amounts of aerosols that impact East Asia and surrounding areas through the Asian monsoon. This study aims to investigate the potential connection between biomass burning over the ICP and precipitation in South China during May, along with the physical processes involved. The analysis is based on GLDAS soil moisture reanalysis data and CPC (NOAA) precipitation data covering the period from 1980 to 2021. The research findings indicate a negative (positive) correlation between biomass burning in the ICP region during spring and precipitation in the same region (South China) during May. The circulation patterns corresponding to years with biomass-burning emission anomalies are further investigated, and the impact of biomass-burning emissions in spring on soil moisture and temperature is examined. The results suggest that biomass-burning emissions can significantly affect atmospheric circulation and precipitation, ultimately leading to anomalous precipitation in South China.展开更多
Two simple and rapid analytical methods (DSC and <sup>1</sup>H-NMR), are proposed for determination of meclofenoxate in meclofenoxate hydrochloride for injection. DSC thermogram is recorded without any sam...Two simple and rapid analytical methods (DSC and <sup>1</sup>H-NMR), are proposed for determination of meclofenoxate in meclofenoxate hydrochloride for injection. DSC thermogram is recorded without any sample pretreatment. The response linearity is ensured by linear determination factors R<sup>2</sup>, which is 0.9982. The recoveries of meclofenoxate hydrochloride in sterile powder for injection are from 98.3% to 102.3% (n = 3). The quantitative <sup>1</sup>H-NMR is quick and simple to use. The quantitation of meclofenoxate is reproducible and the relative standard deviation is 1.0%. The accuracy of two methods is validated by comparison with the results obtained by HPLC. The results show that the two methods are capable of quantifying the content of meclofenoxate in meclofenoxate hydrochloride for injection.展开更多
Atmospheric effects have significant influence on the performance of a free-space optical continuous variable quantum key distribution(CVQKD)system.In this paper,we investigate how the transmittance,excess noise and i...Atmospheric effects have significant influence on the performance of a free-space optical continuous variable quantum key distribution(CVQKD)system.In this paper,we investigate how the transmittance,excess noise and interruption probability caused by atmospheric effects affect the secret-key rate(SKR)of the CVQKD.Three signal wavelengths,two weather conditions,two detection schemes,and two types of attacks are considered in our investigation.An expression aims at calculating the interruption probability is proposed based on the Kolmogorov spectrum model.The results show that a signal using long working wavelength can propagate much further than that of using short wavelength.Moreover,as the wavelength increases,the influence of interruption probability on the SKR becomes more significant,especially within a certain transmission distance.Therefore,interruption probability must be considered for CVQKD by using long-signal wavelengths.Furthermore,different detection schemes used by the receiver will result in different transmission distances when subjected to individual attacks and collective attacks,respectively.展开更多
A new device is designed to promote the mixing of high-pressure water jets and powders in typical industrial applications.The water and powder mixing devices traditionally used on offshore platforms are detrimentally ...A new device is designed to promote the mixing of high-pressure water jets and powders in typical industrial applications.The water and powder mixing devices traditionally used on offshore platforms are detrimentally affected by the geometrical configuration of the water nozzle and the powder spraying pipe,which are parallel,resulting in small intersecting volumes of liquid and powder.By allowing the related jets to intersect,in the present work the optimal horizontal distance,vertical distance and intersection angle are determined through a parametric investigation.It is also shown that such values change if the number of water layers is increased from one to two.In such a case,the water and powder intersection volume can be greatly increased because the trajectory of the dry powder particles becomes more chaotic.展开更多
In this article, we reported that carmofur could be induced by some solvent to produce conformational alteration. Ultraviolet (UV) spectra were used to study the conformation alteration of carmofur. Upon the addition ...In this article, we reported that carmofur could be induced by some solvent to produce conformational alteration. Ultraviolet (UV) spectra were used to study the conformation alteration of carmofur. Upon the addition of acid in the some solvent, UV spectroscopy of carmofur could change gradually. When base was added to this system, UV spectroscopy of carmofur could return to the original state, and the change process was reversible. The variable temperature 1H and 13C-NMR spectrum were used to testify that temperature did not have any effect on the conformation alteration of carmofur in Acetonitrile: Trifluoroacetic-acid (9:1). These two conformers of carmofur were structurally stable in Acetonitrile: Trifluoroacetic-acid (9:1).展开更多
Understanding the underlying mechanisms and links between genome evolution and adaptive innovations stands as a key goal in evolutionary studies.Poplars,among the world’s most widely distributed and cultivated trees,...Understanding the underlying mechanisms and links between genome evolution and adaptive innovations stands as a key goal in evolutionary studies.Poplars,among the world’s most widely distributed and cultivated trees,exhibit extensive phenotypic diversity and environmental adaptability.In this study,we present a genus-level super-pangenome comprising 19 Populus genomes,revealing the likely pivotal role of private genes in facilitating local environmental and climate adaptation.Through the integration of pangenomes with transcriptomes,methylomes,and chromatin accessibility mapping,we unveil that the evolutionary trajectories of pangenes and duplicated genes are closely linked to local genomic landscapes of regulatory and epigenetic architectures,notably CG methylation in gene-body regions.Further comparative genomic analyses have enabled the identification of 142202 structural variants across species that intersect with a significant number of genes and contribute substantially to both phenotypic and adaptive divergence.We have experimentally validated a∼180-bp presence/absence variant affecting the expression of the CUC2 gene,crucial for leaf serration formation.Finally,we developed a user-friendly web-based tool encompassing the multi-omics resources associated with the Populus super-pangenome(http://www.populus-superpangenome.com).Together,the present pioneering super-pangenome resource in forest trees not only aids in the advancement of breeding efforts of this globally important tree genus but also offers valuable insights into potential avenues for comprehending tree biology.展开更多
Recent research certified that DOT1L and its mutations represented by R231Q were potential targets for the treatment of lung cancer.Herein,a series of adenosine-containing derivatives were identified with DOT1LR231Q i...Recent research certified that DOT1L and its mutations represented by R231Q were potential targets for the treatment of lung cancer.Herein,a series of adenosine-containing derivatives were identified with DOT1LR231Q inhibition through antiproliferation assay and Western blot analysis in the H460R231Q cell.The most promising compound 37 significantly reduced DOT1LR231Q mediated H3K79 methylation and effectively inhibited the proliferation,self-renewal,migration,and invasion of lung cancer cell lines at low micromolar concentrations.The cell permeability and cellular target engagement of 37 were verified by both CETSA and DARTS assays.In the H460R231Q OE cell-derived xenograft(CDX)model,37 displayed pronounced tumor growth inhibition after intraperitoneal administration at 20 mg/kg dose for 3 weeks(TGI=54.38%),without obvious toxicities.A pharmacokinetic study revealed that 37 possessed tolerable properties(t_(1/2)=1.93±0.91 h,F=97.2%)after intraperitoneal administration in rats.Mechanism study confirmed that 37 suppressed malignant phenotypes of lung cancer carrying R231Q gain-of-function mutation via the MAPK/ERK signaling pathway.Moreover,analysis of the binding modes between molecules and DOT1LWT/R231Q proteins put forward the“Induced-fit”allosteric model in favor to the discovery of potent DOT1L candidates.展开更多
Nanocatalytic therapy shows great potential for therapeutic interventions.However,therapeutic efficiency is often limited by unsatisfactory enzyme activity and lack of the coordination of immune system.Therefore,engin...Nanocatalytic therapy shows great potential for therapeutic interventions.However,therapeutic efficiency is often limited by unsatisfactory enzyme activity and lack of the coordination of immune system.Therefore,engineering nanozymes activity enhancement while activating immune system will be an effective strategy to achieve efficient tumor therapy.Herein,we synthesize a DSPE-PEG-FA modified manganese dioxide-based dual-atom nanozyme(MDF),on which iridium and platinum atoms are anchored.The obtained MDF can simultaneously mimic four enzyme activities of catalase,oxidase,peroxidase,and glutathione oxidase,set off a reactive oxygen species(ROS)storm,cause tumor cell death.The enzyme activity of MDF can be enhanced by its own photothermal effect.Meanwhile,MDF can consume intracellular glutathione and release Mn^(2+),which can prevent generated ROS from consumption and further activate cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes(cGAS-STING)pathway and promote the secretion of type I interferon,which will help promote dendritic cells maturation,present antigens to T lymphocytes to help kill tumor cells.Ultimately,MDF shows excellent tumor suppressive effects.This work provides a new paradigm for the field of nanozymes and offers a new reference for involvement of cGAS-STING pathway activation in tumor catalytic therapy.展开更多
Posterior capsule opacification(PCO)remains the predominant complication following cataract surgery,significantly impairing visual function restoration.In this study,we developed a PCO model that closely mimics the an...Posterior capsule opacification(PCO)remains the predominant complication following cataract surgery,significantly impairing visual function restoration.In this study,we developed a PCO model that closely mimics the anatomical structure of the crystalline lens capsule post-surgery.The model incorporated a threaded structure for accurate positioning and observation,allowing for opening and closing.Utilizing 3D printing technology,a stable external support system was created using resin material consisting of a rigid,hollow base and cover.To replicate the lens capsule structure,a thin hydrogel coating was applied to the resin scaffold.The biocompatibility and impact on cellular functionality of various hydrogel compositions were assessed through an array of staining techniques,including calcein-AM/PI staining,rhodamine staining,BODIPY-C11 staining and EdU staining in conjunction with transwell assays.Additionally,the PCO model was utilized to investigate the effects of eight drugs with anti-inflammatory and anti-proliferative properties,including 5-aminoimidazole-4-carboxamide ribonucleotide(AICAR),THZ1,sorbinil,4-octyl itaconate(4-OI),xanthohumol,zebularine,rapamycin and caffeic acid phenethyl ester,on human lens epithelial cells(HLECs).Confocal microscopy facilitated comprehensive imaging of the PCO model.The results demonstrated that the GelMA 605%þPLMA 2%composite hydrogel exhibited superior biocompatibility and minimal lipid peroxidation levels among the tested hydrogels.Moreover,compared to using hydrogel as the material for 3D printing the entire model,applying surface hydrogel spin coating with parameters of 2000 rpm�2 on the resin-based 3D printed base yielded a more uniform cell distribution and reduced apoptosis.Furthermore,rapamycin,4-OI and AICAR demonstrated potent antiproliferative effects in the drug intervention study.Confocal microscopy imaging revealed a uniform distribution of HLECs along the anatomical structure of the crystalline lens capsule within the PCO model,showcasing robust cell viability and regular morphology.In conclusion,the PCO model provides a valuable experimental platform for studying PCO pathogenesis and exploring potential therapeutic interventions.展开更多
“Reactive oxygen species(ROS)engineering”is one of the most promising anti-tumor treatments developed in recent years.Massive explosion of ROS will cause oxidative stress,thereby inducing tumor cell death.However,RO...“Reactive oxygen species(ROS)engineering”is one of the most promising anti-tumor treatments developed in recent years.Massive explosion of ROS will cause oxidative stress,thereby inducing tumor cell death.However,ROS accumulation in tumor cells is eliminated by endogenous cellular self-regulation strategies.In this work,a kind of endogenous/exogenous dual stimulation nanoagent noted as UMZC is developed.Fenton reaction occurs between NH_(2)-MIL-88B(Fe)contained in UMZC and the overexpression of endogenous H_(2)O_(2)to generate ROS,amplified by endogenous H_(2)S of colon tumor cells.In addition,NH_(2)-MIL-88B(Fe)also functions to deplete glutathione(GSH)for stopping it from consuming ROS.Upconversion nanoparticles at the core of UMZC convert near-infrared into visible light,which excites zinc phthalocyanine to initiate the photochemical reaction that generates more ROS,thus alleviating the lack of tissue penetration depth for visible light.Autophagy agonist chitosan oligosaccharides induce enhancement of cellular autophagy for disrupting cellular metabolic stress and the resistance to oxidative stress of tumor cells,allowing“ROS engineering”to fully exert anti-tumor effects.All of ROS generation,GSH depletion,and induced cellular autophagy caused by nanoagents have promoting effects on the occurrence of ferroptosis.Finally,the nanoagents show the ability to effectively treat colon tumors.展开更多
“我们能人工合成一个细胞吗?Can a cell be artificially synthesized?”——这是2021年《科学》期刊新发布的世界最前沿的125个重大科学问题之一。科学家为了揭示“生命起源”的奥秘以及解决世界关注的重大基础科学问题,设计出人造细...“我们能人工合成一个细胞吗?Can a cell be artificially synthesized?”——这是2021年《科学》期刊新发布的世界最前沿的125个重大科学问题之一。科学家为了揭示“生命起源”的奥秘以及解决世界关注的重大基础科学问题,设计出人造细胞这类仿生材料。它们最明显的特点就是具有与生物细胞类似的结构与功能。因此,深入研究人造细胞,不仅有利于研究真实细胞的结构与功能机制,还有助于建立非生物物质与真实细胞之间的联系,从而搭建非生命系统与生命系统之间的桥梁,为生命起源等相关研究提供实验与理论依据。而磷脂囊泡作为目前应用最为广泛的人造细胞更是有着广阔的应用前景。为了使“磷脂囊泡”这类材料以及相关研究技术得到更广泛的认识,本文基于耳熟能详的四大名著之一——《西游记》,讲述了孙悟空凭借火眼金睛帮助磷脂囊泡战胜癌细胞的故事,介绍了磷脂囊泡的设计和制备、代表功能以及体内治疗案例,以期促进广大读者对该技术的理解,并激发更多该技术潜在的应用可能。展开更多
Per-and polyfluorinated alkyl substances(PFASs) are commonly used in industrial processes and daily life products.Because they are persistent, they accumulate in the environment, wildlife and humans.Although many stud...Per-and polyfluorinated alkyl substances(PFASs) are commonly used in industrial processes and daily life products.Because they are persistent, they accumulate in the environment, wildlife and humans.Although many studies have focused on two of the most representative PFASs, PFOS and PFOA, the potential toxicity of short-chain PFASs has not yet been given sufficient attention.We used a battery of assays to evaluate the toxicity of several four-carbon and six-carbon perfluorinated sulfonates and carboxyl acids(PFBS,PFHxS, PFBA and PFHxA), with a human mesenchymal stem cell(hMSC) system.Our results demonstrate significant cyto-and potential developmental toxicity for all the compounds analyzed, with shared but also distinct mechanisms of toxicity.Moreover, the effects of PFBS and PFHxS were stronger than those of PFBA and PFHxA, but occurred at higher doses compared to PFOS or PFOA.展开更多
Root crown phenotyping measures the top portion of crop root systems and can be used for marker-assisted breeding,genetic mapping,and understanding how roots influence soil resource acquisition.Several imaging protoco...Root crown phenotyping measures the top portion of crop root systems and can be used for marker-assisted breeding,genetic mapping,and understanding how roots influence soil resource acquisition.Several imaging protocols and image analysis programs exist,but they are not optimized for high-throughput,repeatable,and robust root crown phenotyping.The RhizoVision Crown platform integrates an imaging unit,image capture software,and image analysis software that are optimized for reliable extraction of measurements from large numbers of root crowns.The hardware platform utilizes a backlight and a monochrome machine vision camera to capture root crown silhouettes.The RhizoVision Imager and RhizoVision Analyzer are free,open-source software that streamline image capture and image analysis with intuitive graphical user interfaces.The RhizoVision Analyzer was physically validated using copper wire,and features were extensively validated using 10,464 groundtruth simulated images of dicot and monocot root systems.This platform was then used to phenotype soybean and wheat root crowns.A total of 2,799 soybean(Glycine max)root crowns of 187 lines and 1,753 wheat(Triticum aestivum)root crowns of 186 lines were phenotyped.Principal component analysis indicated similar correlations among features in both species.The maximum heritability was 0.74 in soybean and 0.22 in wheat,indicating that differences in species and populations need to be considered.The integrated RhizoVision Crown platform facilitates high-throughput phenotyping of crop root crowns and sets a standard by which open plant phenotyping platforms can be benchmarked.展开更多
Catalytic asymmetric aza-Michael represents one of the most convenient and atom-economical approaches for the rapid construction of biologically active chiralβ-amino acid frameworks.However,the direct enantioselectiv...Catalytic asymmetric aza-Michael represents one of the most convenient and atom-economical approaches for the rapid construction of biologically active chiralβ-amino acid frameworks.However,the direct enantioselective addition of nitrogen-based nucleophiles to intrinsically low reactivity ofα,β-unsaturated carboxylic acid,ester,and amide,as well as simpleα,β-unsaturated nitrile,remains a long-standing challenge.展开更多
In this paper,we consider a networked game with coupled constraints and focus on variational Nash equilibrium seeking.For distributed algorithm design,we eliminate the coupled constraints by employing local Lagrangian...In this paper,we consider a networked game with coupled constraints and focus on variational Nash equilibrium seeking.For distributed algorithm design,we eliminate the coupled constraints by employing local Lagrangian functions and construct exact penalty terms to attain multipliers'optimal consensus,which yields a set of equilibrium conditions without any coupled constraint and consensus constraint.Moreover,these conditions are only based on strategy and multiplier variables,without auxiliary variables.Then,we present a distributed order-reduced dynamics that updates the strategy and multiplier variables with guaranteed convergence.Compared with many other distributed algorithms,our algorithm contains no auxiliary variable,and therefore,it can save computation and communication.展开更多
文摘Each year, during the dry season that precedes the summer wind and rainfall Indo-China Peninsula (ICP), significant biomass burning occurs and reaches its peak from March to April. This biomass burning generates large amounts of aerosols that impact East Asia and surrounding areas through the Asian monsoon. This study aims to investigate the potential connection between biomass burning over the ICP and precipitation in South China during May, along with the physical processes involved. The analysis is based on GLDAS soil moisture reanalysis data and CPC (NOAA) precipitation data covering the period from 1980 to 2021. The research findings indicate a negative (positive) correlation between biomass burning in the ICP region during spring and precipitation in the same region (South China) during May. The circulation patterns corresponding to years with biomass-burning emission anomalies are further investigated, and the impact of biomass-burning emissions in spring on soil moisture and temperature is examined. The results suggest that biomass-burning emissions can significantly affect atmospheric circulation and precipitation, ultimately leading to anomalous precipitation in South China.
文摘Two simple and rapid analytical methods (DSC and <sup>1</sup>H-NMR), are proposed for determination of meclofenoxate in meclofenoxate hydrochloride for injection. DSC thermogram is recorded without any sample pretreatment. The response linearity is ensured by linear determination factors R<sup>2</sup>, which is 0.9982. The recoveries of meclofenoxate hydrochloride in sterile powder for injection are from 98.3% to 102.3% (n = 3). The quantitative <sup>1</sup>H-NMR is quick and simple to use. The quantitation of meclofenoxate is reproducible and the relative standard deviation is 1.0%. The accuracy of two methods is validated by comparison with the results obtained by HPLC. The results show that the two methods are capable of quantifying the content of meclofenoxate in meclofenoxate hydrochloride for injection.
基金Project supported by the National Natural Science Foundation of China(Grant No.62071180)Fundamental Research Funds for the Central Universities,China(Grant No.2020MS099)。
文摘Atmospheric effects have significant influence on the performance of a free-space optical continuous variable quantum key distribution(CVQKD)system.In this paper,we investigate how the transmittance,excess noise and interruption probability caused by atmospheric effects affect the secret-key rate(SKR)of the CVQKD.Three signal wavelengths,two weather conditions,two detection schemes,and two types of attacks are considered in our investigation.An expression aims at calculating the interruption probability is proposed based on the Kolmogorov spectrum model.The results show that a signal using long working wavelength can propagate much further than that of using short wavelength.Moreover,as the wavelength increases,the influence of interruption probability on the SKR becomes more significant,especially within a certain transmission distance.Therefore,interruption probability must be considered for CVQKD by using long-signal wavelengths.Furthermore,different detection schemes used by the receiver will result in different transmission distances when subjected to individual attacks and collective attacks,respectively.
基金This work comes from the National Science and Technology Major Special Offshore Platform Polymer Rapid Dissolution Technology Research Project[Grant No.2016ZX05060].
文摘A new device is designed to promote the mixing of high-pressure water jets and powders in typical industrial applications.The water and powder mixing devices traditionally used on offshore platforms are detrimentally affected by the geometrical configuration of the water nozzle and the powder spraying pipe,which are parallel,resulting in small intersecting volumes of liquid and powder.By allowing the related jets to intersect,in the present work the optimal horizontal distance,vertical distance and intersection angle are determined through a parametric investigation.It is also shown that such values change if the number of water layers is increased from one to two.In such a case,the water and powder intersection volume can be greatly increased because the trajectory of the dry powder particles becomes more chaotic.
文摘In this article, we reported that carmofur could be induced by some solvent to produce conformational alteration. Ultraviolet (UV) spectra were used to study the conformation alteration of carmofur. Upon the addition of acid in the some solvent, UV spectroscopy of carmofur could change gradually. When base was added to this system, UV spectroscopy of carmofur could return to the original state, and the change process was reversible. The variable temperature 1H and 13C-NMR spectrum were used to testify that temperature did not have any effect on the conformation alteration of carmofur in Acetonitrile: Trifluoroacetic-acid (9:1). These two conformers of carmofur were structurally stable in Acetonitrile: Trifluoroacetic-acid (9:1).
基金supported by the National Key Research and Development Program of China(2022YFD2201200 to J.W.and 2021YFD2200202 to T.Y.and J.L.)National Natural Science Foundation of China(32371695 and 31971567 to J.W.)Fundamental Research Funds for the Central Universities(2023SCUNL105 and SCU2022D003 to J.W.).
文摘Understanding the underlying mechanisms and links between genome evolution and adaptive innovations stands as a key goal in evolutionary studies.Poplars,among the world’s most widely distributed and cultivated trees,exhibit extensive phenotypic diversity and environmental adaptability.In this study,we present a genus-level super-pangenome comprising 19 Populus genomes,revealing the likely pivotal role of private genes in facilitating local environmental and climate adaptation.Through the integration of pangenomes with transcriptomes,methylomes,and chromatin accessibility mapping,we unveil that the evolutionary trajectories of pangenes and duplicated genes are closely linked to local genomic landscapes of regulatory and epigenetic architectures,notably CG methylation in gene-body regions.Further comparative genomic analyses have enabled the identification of 142202 structural variants across species that intersect with a significant number of genes and contribute substantially to both phenotypic and adaptive divergence.We have experimentally validated a∼180-bp presence/absence variant affecting the expression of the CUC2 gene,crucial for leaf serration formation.Finally,we developed a user-friendly web-based tool encompassing the multi-omics resources associated with the Populus super-pangenome(http://www.populus-superpangenome.com).Together,the present pioneering super-pangenome resource in forest trees not only aids in the advancement of breeding efforts of this globally important tree genus but also offers valuable insights into potential avenues for comprehending tree biology.
基金supported by the National Natural Science Foundation of China(No.82173685 and No.82073320)Chinese Pharma-ceutical Association-Yi ling Biomedical Innovation Fund(No.CPAYLJ202001,China)+3 种基金Liao Ning Revitalization Talents Program(No.XLYC2002115,China)Key R&D Plan of Liaoning Province in 2020(No.2020020215-JH2/103,China)Development Project of Ministry of Education Innovation Team(No.IRT1073,China)Natural Science Foundation of Shenyang(22-315-6-11,China).
文摘Recent research certified that DOT1L and its mutations represented by R231Q were potential targets for the treatment of lung cancer.Herein,a series of adenosine-containing derivatives were identified with DOT1LR231Q inhibition through antiproliferation assay and Western blot analysis in the H460R231Q cell.The most promising compound 37 significantly reduced DOT1LR231Q mediated H3K79 methylation and effectively inhibited the proliferation,self-renewal,migration,and invasion of lung cancer cell lines at low micromolar concentrations.The cell permeability and cellular target engagement of 37 were verified by both CETSA and DARTS assays.In the H460R231Q OE cell-derived xenograft(CDX)model,37 displayed pronounced tumor growth inhibition after intraperitoneal administration at 20 mg/kg dose for 3 weeks(TGI=54.38%),without obvious toxicities.A pharmacokinetic study revealed that 37 possessed tolerable properties(t_(1/2)=1.93±0.91 h,F=97.2%)after intraperitoneal administration in rats.Mechanism study confirmed that 37 suppressed malignant phenotypes of lung cancer carrying R231Q gain-of-function mutation via the MAPK/ERK signaling pathway.Moreover,analysis of the binding modes between molecules and DOT1LWT/R231Q proteins put forward the“Induced-fit”allosteric model in favor to the discovery of potent DOT1L candidates.
基金supported by the National Natural Science Foundation of China(52371254,22020102003)the Jilin Province Youth Science and Technology Talent Support Project(QT202229)+1 种基金the Program of Science and Technology Development Plan of Jilin Province of China(YDZJ202302CXJD065)the Natural Science Foundation of Chongqing of China(cstc2021jcyj-msxmX0936)。
文摘Nanocatalytic therapy shows great potential for therapeutic interventions.However,therapeutic efficiency is often limited by unsatisfactory enzyme activity and lack of the coordination of immune system.Therefore,engineering nanozymes activity enhancement while activating immune system will be an effective strategy to achieve efficient tumor therapy.Herein,we synthesize a DSPE-PEG-FA modified manganese dioxide-based dual-atom nanozyme(MDF),on which iridium and platinum atoms are anchored.The obtained MDF can simultaneously mimic four enzyme activities of catalase,oxidase,peroxidase,and glutathione oxidase,set off a reactive oxygen species(ROS)storm,cause tumor cell death.The enzyme activity of MDF can be enhanced by its own photothermal effect.Meanwhile,MDF can consume intracellular glutathione and release Mn^(2+),which can prevent generated ROS from consumption and further activate cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes(cGAS-STING)pathway and promote the secretion of type I interferon,which will help promote dendritic cells maturation,present antigens to T lymphocytes to help kill tumor cells.Ultimately,MDF shows excellent tumor suppressive effects.This work provides a new paradigm for the field of nanozymes and offers a new reference for involvement of cGAS-STING pathway activation in tumor catalytic therapy.
基金supported by research grants from the National Natural Science Foundation of China(82122017,82271069 and 81900839)Shanghai Science and Technology Commission(22xtcx00103)Clinical Science and Technology Innovation Project of Shanghai Shenkang Hospital Development Center(SHDC12019X08,SHDC12020111 and SHDC2020CR4078).
文摘Posterior capsule opacification(PCO)remains the predominant complication following cataract surgery,significantly impairing visual function restoration.In this study,we developed a PCO model that closely mimics the anatomical structure of the crystalline lens capsule post-surgery.The model incorporated a threaded structure for accurate positioning and observation,allowing for opening and closing.Utilizing 3D printing technology,a stable external support system was created using resin material consisting of a rigid,hollow base and cover.To replicate the lens capsule structure,a thin hydrogel coating was applied to the resin scaffold.The biocompatibility and impact on cellular functionality of various hydrogel compositions were assessed through an array of staining techniques,including calcein-AM/PI staining,rhodamine staining,BODIPY-C11 staining and EdU staining in conjunction with transwell assays.Additionally,the PCO model was utilized to investigate the effects of eight drugs with anti-inflammatory and anti-proliferative properties,including 5-aminoimidazole-4-carboxamide ribonucleotide(AICAR),THZ1,sorbinil,4-octyl itaconate(4-OI),xanthohumol,zebularine,rapamycin and caffeic acid phenethyl ester,on human lens epithelial cells(HLECs).Confocal microscopy facilitated comprehensive imaging of the PCO model.The results demonstrated that the GelMA 605%þPLMA 2%composite hydrogel exhibited superior biocompatibility and minimal lipid peroxidation levels among the tested hydrogels.Moreover,compared to using hydrogel as the material for 3D printing the entire model,applying surface hydrogel spin coating with parameters of 2000 rpm�2 on the resin-based 3D printed base yielded a more uniform cell distribution and reduced apoptosis.Furthermore,rapamycin,4-OI and AICAR demonstrated potent antiproliferative effects in the drug intervention study.Confocal microscopy imaging revealed a uniform distribution of HLECs along the anatomical structure of the crystalline lens capsule within the PCO model,showcasing robust cell viability and regular morphology.In conclusion,the PCO model provides a valuable experimental platform for studying PCO pathogenesis and exploring potential therapeutic interventions.
基金supported by the financial aid from the National Natural Science Foundation of China(Nos.52371254 and 22020102003)the Program of Science and Technology Development Plan of Jilin Province of China(Nos.20220508076RC and YDZJ202302CXJD065).
文摘“Reactive oxygen species(ROS)engineering”is one of the most promising anti-tumor treatments developed in recent years.Massive explosion of ROS will cause oxidative stress,thereby inducing tumor cell death.However,ROS accumulation in tumor cells is eliminated by endogenous cellular self-regulation strategies.In this work,a kind of endogenous/exogenous dual stimulation nanoagent noted as UMZC is developed.Fenton reaction occurs between NH_(2)-MIL-88B(Fe)contained in UMZC and the overexpression of endogenous H_(2)O_(2)to generate ROS,amplified by endogenous H_(2)S of colon tumor cells.In addition,NH_(2)-MIL-88B(Fe)also functions to deplete glutathione(GSH)for stopping it from consuming ROS.Upconversion nanoparticles at the core of UMZC convert near-infrared into visible light,which excites zinc phthalocyanine to initiate the photochemical reaction that generates more ROS,thus alleviating the lack of tissue penetration depth for visible light.Autophagy agonist chitosan oligosaccharides induce enhancement of cellular autophagy for disrupting cellular metabolic stress and the resistance to oxidative stress of tumor cells,allowing“ROS engineering”to fully exert anti-tumor effects.All of ROS generation,GSH depletion,and induced cellular autophagy caused by nanoagents have promoting effects on the occurrence of ferroptosis.Finally,the nanoagents show the ability to effectively treat colon tumors.
文摘“我们能人工合成一个细胞吗?Can a cell be artificially synthesized?”——这是2021年《科学》期刊新发布的世界最前沿的125个重大科学问题之一。科学家为了揭示“生命起源”的奥秘以及解决世界关注的重大基础科学问题,设计出人造细胞这类仿生材料。它们最明显的特点就是具有与生物细胞类似的结构与功能。因此,深入研究人造细胞,不仅有利于研究真实细胞的结构与功能机制,还有助于建立非生物物质与真实细胞之间的联系,从而搭建非生命系统与生命系统之间的桥梁,为生命起源等相关研究提供实验与理论依据。而磷脂囊泡作为目前应用最为广泛的人造细胞更是有着广阔的应用前景。为了使“磷脂囊泡”这类材料以及相关研究技术得到更广泛的认识,本文基于耳熟能详的四大名著之一——《西游记》,讲述了孙悟空凭借火眼金睛帮助磷脂囊泡战胜癌细胞的故事,介绍了磷脂囊泡的设计和制备、代表功能以及体内治疗案例,以期促进广大读者对该技术的理解,并激发更多该技术潜在的应用可能。
基金supported by the National Natural Science Foundation of China (Nos.21876197, 21577166, 21707160)the Chinese Academy of Sciences (Nos.XDB14040301, 29[2015]30, QYZDJ-SSW-DQC017)the K.C.Wong Education Foundation.
文摘Per-and polyfluorinated alkyl substances(PFASs) are commonly used in industrial processes and daily life products.Because they are persistent, they accumulate in the environment, wildlife and humans.Although many studies have focused on two of the most representative PFASs, PFOS and PFOA, the potential toxicity of short-chain PFASs has not yet been given sufficient attention.We used a battery of assays to evaluate the toxicity of several four-carbon and six-carbon perfluorinated sulfonates and carboxyl acids(PFBS,PFHxS, PFBA and PFHxA), with a human mesenchymal stem cell(hMSC) system.Our results demonstrate significant cyto-and potential developmental toxicity for all the compounds analyzed, with shared but also distinct mechanisms of toxicity.Moreover, the effects of PFBS and PFHxS were stronger than those of PFBA and PFHxA, but occurred at higher doses compared to PFOS or PFOA.
基金The work was funded by the Noble Research Institute,LLCthe USDA NIFA EAGER program(2017-67007-26953)+1 种基金the Department of Energy ARPA-E ROOTS program(DE-AR0000822)the United Soybean Board(1420-532-5613).
文摘Root crown phenotyping measures the top portion of crop root systems and can be used for marker-assisted breeding,genetic mapping,and understanding how roots influence soil resource acquisition.Several imaging protocols and image analysis programs exist,but they are not optimized for high-throughput,repeatable,and robust root crown phenotyping.The RhizoVision Crown platform integrates an imaging unit,image capture software,and image analysis software that are optimized for reliable extraction of measurements from large numbers of root crowns.The hardware platform utilizes a backlight and a monochrome machine vision camera to capture root crown silhouettes.The RhizoVision Imager and RhizoVision Analyzer are free,open-source software that streamline image capture and image analysis with intuitive graphical user interfaces.The RhizoVision Analyzer was physically validated using copper wire,and features were extensively validated using 10,464 groundtruth simulated images of dicot and monocot root systems.This platform was then used to phenotype soybean and wheat root crowns.A total of 2,799 soybean(Glycine max)root crowns of 187 lines and 1,753 wheat(Triticum aestivum)root crowns of 186 lines were phenotyped.Principal component analysis indicated similar correlations among features in both species.The maximum heritability was 0.74 in soybean and 0.22 in wheat,indicating that differences in species and populations need to be considered.The integrated RhizoVision Crown platform facilitates high-throughput phenotyping of crop root crowns and sets a standard by which open plant phenotyping platforms can be benchmarked.
基金the National Natural Science Foundation of China(grant nos.21672033,21801039,and 21831002)the Jilin Educational Committee(grant no.JJKH20190269KJ)the Fundamental Research Funds for the Central Universities,and the Ten Thousand Talents Program for generous financial support.
文摘Catalytic asymmetric aza-Michael represents one of the most convenient and atom-economical approaches for the rapid construction of biologically active chiralβ-amino acid frameworks.However,the direct enantioselective addition of nitrogen-based nucleophiles to intrinsically low reactivity ofα,β-unsaturated carboxylic acid,ester,and amide,as well as simpleα,β-unsaturated nitrile,remains a long-standing challenge.
基金supported in part by the National Key Research and Development Program of China under grant 2022YFA1004700in part by the Natural Science Foundation of China under grant 72171171in part by Shanghai Municipal Science and Technology Major Project under grant 2021SHZDZX0100.
文摘In this paper,we consider a networked game with coupled constraints and focus on variational Nash equilibrium seeking.For distributed algorithm design,we eliminate the coupled constraints by employing local Lagrangian functions and construct exact penalty terms to attain multipliers'optimal consensus,which yields a set of equilibrium conditions without any coupled constraint and consensus constraint.Moreover,these conditions are only based on strategy and multiplier variables,without auxiliary variables.Then,we present a distributed order-reduced dynamics that updates the strategy and multiplier variables with guaranteed convergence.Compared with many other distributed algorithms,our algorithm contains no auxiliary variable,and therefore,it can save computation and communication.