The advent of gene editing represents one of the most transformative breakthroughs in life science,making genome manipulation more accessible than ever before.While traditional CRISPR/Cas-based gene editing,which invo...The advent of gene editing represents one of the most transformative breakthroughs in life science,making genome manipulation more accessible than ever before.While traditional CRISPR/Cas-based gene editing,which involves double-strand DNA breaks(DSBs),excels at gene disruption,it is less effective for accurate gene modification.The limitation arises because DSBs are primarily repaired via non-homologous end joining(NHEJ),which tends to introduce indels at the break site.While homology directed repair(HDR)can achieve precise editing when a donor DNA template is provided,the reliance on DSBs often results in unintended genome damage.HDR is restricted to specific cell cycle phases,limiting its application.Currently,gene editing has evolved to unprecedented levels of precision without relying on DSB and HDR.The development of innovative systems,such as base editing,prime editing,and CRISPR-associated transposases(CASTs),now allow for precise editing ranging from single nucleotides to large DNA fragments.Base editors(BEs)enable the direct conversion of one nucleotide to another,and prime editors(PEs)further expand gene editing capabilities by allowing for the insertion,deletion,or alteration of small DNA fragments.The CAST system,a recent innovation,allows for the precise insertion of large DNA fragments at specific genomic locations.In recent years,the optimization of these precise gene editing tools has led to significant improvements in editing efficiency,specificity,and versatility,with advancements such as the creation of base editors for nucleotide transversions,enhanced prime editing systems for more efficient and precise modifications,and refined CAST systems for targeted large DNA insertions,expanding the range of applications for these tools.Concurrently,these advances are complemented by significant improvements in in vivo delivery methods,which have paved the way for therapeutic application of precise gene editing tools.Effective delivery systems are critical for the success of gene therapies,and recent developments in both viral and non-viral vectors have improved the efficiency and safety of gene editing.For instance,adeno-associated viruses(AAVs)are widely used due to their high transfection efficiency and low immunogenicity,though challenges such as limited cargo capacity and potential for immune responses remain.Non-viral delivery systems,including lipid nanoparticles(LNPs),offer an alternative with lower immunogenicity and higher payload capacity,although their transfection efficiency can be lower.The therapeutic potential of these precise gene editing technologies is vast,particularly in treating genetic disorders.Preclinical studies have demonstrated the effectiveness of base editing in correcting genetic mutations responsible for diseases such as cardiomyopathy,liver disease,and hereditary hearing loss.These technologies promise to treat symptoms and potentially cure the underlying genetic causes of these conditions.Meanwhile,challenges remain,such as optimizing the safety and specificity of gene editing tools,improving delivery systems,and overcoming off-target effects,all of which are critical for their successful application in clinical settings.In summary,the continuous evolution of precise gene editing technologies,combined with advancements in delivery systems,is driving the field toward new therapeutic applications that can potentially transform the treatment of genetic disorders by targeting their root causes.展开更多
In this study, the authors developed a new irrigation scheme based on the Noah land surface model, and then coupled it with the Weather Research and Forecasting regional climate model. Two simulations (with and witho...In this study, the authors developed a new irrigation scheme based on the Noah land surface model, and then coupled it with the Weather Research and Forecasting regional climate model. Two simulations (with and without irrigation) were conducted over the Yellow River basin for the period April to October 2000-2010. The results indicated that the WRF model is able to successfully capture the spatial pattern and seasonal changes in observed temperature and precipitation over the Yellow River basin. When irrigation was induced, the mean surface air temperature at 2 m (T2m) decreased by 0.1-0.4 K, and there was a correspond increase (decrease) in latent (sensible) heat flux over the irrigated areas, wherein the increase (decrease) reached more than 10 W m-2 over the largest irrigated areas. The cooling effect was consistent with the changes in evapotranspiration and heat fluxes due to irrigation.The changes in lifting condensation level and planetary boundary layer height led to a greater probability of cloud formation and bore a close association with surface fluxes and soil moisture, which then impacted the spatial distribution of T2rn and precipitation.展开更多
We propose a method of converting the topological charge(TC)of an incident vortex light wave with spiral-slit screens.The phase in the incident vortex beam is redistributed via the optical path adjustment realized by ...We propose a method of converting the topological charge(TC)of an incident vortex light wave with spiral-slit screens.The phase in the incident vortex beam is redistributed via the optical path adjustment realized by changing the in-plane radial distance of the spiral slit.We numerically calculate the light field with Fresnel diffraction theory,and find the expected TC conversion on the observation plane.Our calculations also show that screens of pinholes distributed in a spiral curve can be used for the implementation instead of spiral slits.The method can also be used to distinguish the TCs of the incident vortices by reading the diffracted intensity patterns.展开更多
With a microscopic imaging system composed of microscopic objective,lens and CCD,we observe the complicated structures in the speckle fields on the surface of a rough screen.It is found that such structures contain ri...With a microscopic imaging system composed of microscopic objective,lens and CCD,we observe the complicated structures in the speckle fields on the surface of a rough screen.It is found that such structures contain ridge stripes,large platform-like grains,and shivy grains,exhibiting multiple scales in size and multiple fractalities.Simulations shows these structures are formed by different parts of the rough surface.The experimental curve of the autocorrelation function of the speckle intensity includes the three parts of the central peak,the transition part and the long tail part.Using the sum of self-affine fractal models with different scales and fractalities,we propose theoretically a triple-scale autocorrelation function to describe the speckle field.Fit of this autocorrelation function to the experimental curve gives the values of such parameters as average speckle sizes and fractalities in different scales of the speckle structures.展开更多
文摘The advent of gene editing represents one of the most transformative breakthroughs in life science,making genome manipulation more accessible than ever before.While traditional CRISPR/Cas-based gene editing,which involves double-strand DNA breaks(DSBs),excels at gene disruption,it is less effective for accurate gene modification.The limitation arises because DSBs are primarily repaired via non-homologous end joining(NHEJ),which tends to introduce indels at the break site.While homology directed repair(HDR)can achieve precise editing when a donor DNA template is provided,the reliance on DSBs often results in unintended genome damage.HDR is restricted to specific cell cycle phases,limiting its application.Currently,gene editing has evolved to unprecedented levels of precision without relying on DSB and HDR.The development of innovative systems,such as base editing,prime editing,and CRISPR-associated transposases(CASTs),now allow for precise editing ranging from single nucleotides to large DNA fragments.Base editors(BEs)enable the direct conversion of one nucleotide to another,and prime editors(PEs)further expand gene editing capabilities by allowing for the insertion,deletion,or alteration of small DNA fragments.The CAST system,a recent innovation,allows for the precise insertion of large DNA fragments at specific genomic locations.In recent years,the optimization of these precise gene editing tools has led to significant improvements in editing efficiency,specificity,and versatility,with advancements such as the creation of base editors for nucleotide transversions,enhanced prime editing systems for more efficient and precise modifications,and refined CAST systems for targeted large DNA insertions,expanding the range of applications for these tools.Concurrently,these advances are complemented by significant improvements in in vivo delivery methods,which have paved the way for therapeutic application of precise gene editing tools.Effective delivery systems are critical for the success of gene therapies,and recent developments in both viral and non-viral vectors have improved the efficiency and safety of gene editing.For instance,adeno-associated viruses(AAVs)are widely used due to their high transfection efficiency and low immunogenicity,though challenges such as limited cargo capacity and potential for immune responses remain.Non-viral delivery systems,including lipid nanoparticles(LNPs),offer an alternative with lower immunogenicity and higher payload capacity,although their transfection efficiency can be lower.The therapeutic potential of these precise gene editing technologies is vast,particularly in treating genetic disorders.Preclinical studies have demonstrated the effectiveness of base editing in correcting genetic mutations responsible for diseases such as cardiomyopathy,liver disease,and hereditary hearing loss.These technologies promise to treat symptoms and potentially cure the underlying genetic causes of these conditions.Meanwhile,challenges remain,such as optimizing the safety and specificity of gene editing tools,improving delivery systems,and overcoming off-target effects,all of which are critical for their successful application in clinical settings.In summary,the continuous evolution of precise gene editing technologies,combined with advancements in delivery systems,is driving the field toward new therapeutic applications that can potentially transform the treatment of genetic disorders by targeting their root causes.
基金supported by the National Key Research and Development Program of China[grant number 2016YFA0600403]the National Natural Science Foundation of China[grant numbers 41305062,41530532]the China Special Fund for Meteorological Research in the Public Interest[grant number GYHY201506001-1]
文摘In this study, the authors developed a new irrigation scheme based on the Noah land surface model, and then coupled it with the Weather Research and Forecasting regional climate model. Two simulations (with and without irrigation) were conducted over the Yellow River basin for the period April to October 2000-2010. The results indicated that the WRF model is able to successfully capture the spatial pattern and seasonal changes in observed temperature and precipitation over the Yellow River basin. When irrigation was induced, the mean surface air temperature at 2 m (T2m) decreased by 0.1-0.4 K, and there was a correspond increase (decrease) in latent (sensible) heat flux over the irrigated areas, wherein the increase (decrease) reached more than 10 W m-2 over the largest irrigated areas. The cooling effect was consistent with the changes in evapotranspiration and heat fluxes due to irrigation.The changes in lifting condensation level and planetary boundary layer height led to a greater probability of cloud formation and bore a close association with surface fluxes and soil moisture, which then impacted the spatial distribution of T2rn and precipitation.
基金Supported by the National Natural Science Foundation of China under Grant No 10974122.
文摘We propose a method of converting the topological charge(TC)of an incident vortex light wave with spiral-slit screens.The phase in the incident vortex beam is redistributed via the optical path adjustment realized by changing the in-plane radial distance of the spiral slit.We numerically calculate the light field with Fresnel diffraction theory,and find the expected TC conversion on the observation plane.Our calculations also show that screens of pinholes distributed in a spiral curve can be used for the implementation instead of spiral slits.The method can also be used to distinguish the TCs of the incident vortices by reading the diffracted intensity patterns.
基金the National Natural Science Foundation of China under Grant Nos 10974122 and 10874105.
文摘With a microscopic imaging system composed of microscopic objective,lens and CCD,we observe the complicated structures in the speckle fields on the surface of a rough screen.It is found that such structures contain ridge stripes,large platform-like grains,and shivy grains,exhibiting multiple scales in size and multiple fractalities.Simulations shows these structures are formed by different parts of the rough surface.The experimental curve of the autocorrelation function of the speckle intensity includes the three parts of the central peak,the transition part and the long tail part.Using the sum of self-affine fractal models with different scales and fractalities,we propose theoretically a triple-scale autocorrelation function to describe the speckle field.Fit of this autocorrelation function to the experimental curve gives the values of such parameters as average speckle sizes and fractalities in different scales of the speckle structures.
文摘产卵场保护区建立是养护渔业资源和渔业可持续发展的重要方式,为验证大陈洋产卵场保护区建立的效果,以大陈洋产卵场保护区为研究区域,基于层次分析法(analytic hierarchy process),以2018年春(4月)、秋(11月)两季渔业资源和环境调查数据为依据,从产卵场保护区的环境和生态(一级指标)角度考虑,建立以污染物、水质、群落结构、资源密度等7个二级指标和26个三级指标的评价体系,通过综合健康评价指数(comprehensive health indicator,I_(c,h)),表征大陈洋产卵场保护区健康状况,并利用2021年春(4月)、秋(11月)两季渔业资源调查数据与保护区建立初期渔业资源情况进行对比。结果显示:2018年大陈洋产卵场保护区春季和秋季I_(c,h)分别为0.514和0.511,均处于亚健康状态。虽然保护区内环境状况优良,但保护区内生物多样性低,资源密度和资源补充群体数量不足,这表明大陈洋产卵场保护区渔业资源情况不容乐观。经过一段时间的恢复,保护区内渔业资源情况略有所好转,说明保护区的设立有一定的效果。综合健康评价体系在一定程度上客观地反映了大陈洋产卵场保护区健康状况,研究结果可为保护区建立效果评价提供基础数据,也对大陈洋地区的渔业可持续发展具有重要意义。