Precise chemical cue presentation alongside advanced brainwide imaging techniques is important to the study of chemosensory processing in animals.Nevertheless,the dynamic nature of chemical-carrying media,such as wate...Precise chemical cue presentation alongside advanced brainwide imaging techniques is important to the study of chemosensory processing in animals.Nevertheless,the dynamic nature of chemical-carrying media,such as water or air,poses a significant challenge for delivering highly-controlled chemical flow to an animal subject.Moreover,contact-based cue manipulation and delivery easily shift the position of the animal subject,which is often undesirable for high-quality brain imaging.Additionally,more advanced interfacing tools that align with the diverse range of body part sizes of an animal,ranging from micrometer-scale neurons to meter-long limbs,are much needed.This is particularly crucial when dealing with dimensions that are beyond the reach of conventional experimental tools.展开更多
A self-consistent and precise method to determine the time-dependent radiative albedo,i.e.,the ratio of the reemission flux to the incident flux,for an indirect-drive inertial confinement fusion Hohlraum wall material...A self-consistent and precise method to determine the time-dependent radiative albedo,i.e.,the ratio of the reemission flux to the incident flux,for an indirect-drive inertial confinement fusion Hohlraum wall material is proposed.A specially designed symmetrical triple-cavity gold Hohlraum is used to create approximately constant and near-equilibrium uniform radiation with a peak temperature of 160 eV.The incident flux at the secondary cavity waist is obtained from flux balance analysis and from the shock velocity of a standard sample.The results agree well owing to the symmetrical radiation in the secondary cavity.A self-consistent and precise time-dependent radiative albedo is deduced from the reliable reemission flux and the incident flux,and the result from the shock velocity is found to have a smaller uncertainty than that from the multi-angle flux balance analysis,and also to agree well with the result of a simulation using the HYADES opacity.展开更多
To the editor:Transcranial magnetic stimulation(TMS)is a non-invasive brain modulation technique.One important usage of TMS is the transient interruption of cognitive brain function(also named virtual lesion)for inves...To the editor:Transcranial magnetic stimulation(TMS)is a non-invasive brain modulation technique.One important usage of TMS is the transient interruption of cognitive brain function(also named virtual lesion)for investigating precisely where and when a specific cortical region contributes to a specific cognitive function.1 A more important usage of TMS is the treatment of brain disorders by repetitive TMS(rTMS).展开更多
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
BACKGROUND Cerebral infarction,previously referred to as cerebral infarction or ischemic stroke,refers to the localized brain tissue experiencing ischemic necrosis or softening due to disorders in brain blood supply,i...BACKGROUND Cerebral infarction,previously referred to as cerebral infarction or ischemic stroke,refers to the localized brain tissue experiencing ischemic necrosis or softening due to disorders in brain blood supply,ischemia,and hypoxia.The precision rehabilitation nursing model for chronic disease management is a continuous,fixed,orderly,and efficient nursing model aimed at standardizing the clinical nursing process,reducing the wastage of medical resources,and improving the quality of medical services.AIM To analyze the value of a precise rehabilitation nursing model for chronic disease management in patients with cerebral infarction.METHODS Patients(n=124)admitted to our hospital with cerebral infarction between November 2019 and November 2021 were enrolled as the study subjects.The random number table method was used to divide them into a conventional nursing intervention group(n=61)and a model nursing intervention group(n=63).Changes in the nursing index for the two groups were compared after conventional nursing intervention and precise rehabilitation intervention nursing for chronic disease management.RESULTS Compared with the conventional intervention group,the model intervention group had a shorter time to clinical symptom relief(P<0.05),lower Hamilton Anxiety Scale and Hamilton Depression Scale scores,a lower incidence of total complications(P<0.05),a higher disease knowledge mastery rate,higher safety and quality,and a higher overall nursing satisfaction rate(P<0.05).CONCLUSION The precision rehabilitation nursing model for chronic disease management improves the clinical symptoms of patients with cerebral infarction,reducing the incidence of total complications and improving the clinical outcome of patients,and is worthy of application in clinical practice.展开更多
The study explores how educational digitalization enables the precise development of ideological and political education in colleges and universities.Digital transformation enables colleges and universities to accurat...The study explores how educational digitalization enables the precise development of ideological and political education in colleges and universities.Digital transformation enables colleges and universities to accurately define educational objectives,content strategies,effect evaluation,and process management,and realize the precision and intelligence of ideological and political education.The application of big data technology enhances the data-oriented thinking of teachers and students,promotes the accurate application of data,and improves the efficiency of ideological and political education.The research also prospected a new vision of the digital construction of ideological and political courses and clarified the theoretical and practical path of the implementation and evaluation mode of ideological and political courses under digital empowerment.Education digitalization enables precise ideological and political education,which is a key way to promote the innovative development of ideological and political education in colleges and universities and will strongly support the improvement of the overall quality of higher education and the training of excellent talents.展开更多
Aleurone forms the outermost layer of the rice endosperm and plays a critical role in apoplastic nutrient uptake during endosperm development.Thickening the aleurone layer has been proposed to significantly increase t...Aleurone forms the outermost layer of the rice endosperm and plays a critical role in apoplastic nutrient uptake during endosperm development.Thickening the aleurone layer has been proposed to significantly increase the nutrient content of rice grains.In this study,we used a CRISPR/Cas9-mediated precise base editing method to target OsROS1,a gene associated with aleurone thickness,in the background of the japonica glutinous rice cultivar Zhennuo 19。展开更多
The quality of printed circuit board(PCB)micro-hole processing directly determines the stability of the inner and outer circuit connections.Micro-hole drilling technology is a typical method for PCB micro-hole process...The quality of printed circuit board(PCB)micro-hole processing directly determines the stability of the inner and outer circuit connections.Micro-hole drilling technology is a typical method for PCB micro-hole processing.The problem of optimal control of its drilling force is one of the main factors affecting the quality of micro-hole machining.To address this problem,the thrust forces and torques in PCB drilling were first modeled and analyzed,and the corresponding prediction models were established.The drilling force analysis was carried out through the micro-hole drilling experiment,the specific cutting energy under different feed rates was calculated,the influence of the size effect was clarified,and the accuracy of the prediction model was verified.The result shows that during the drilling of glass fiber cloth,changes in the material removal mechanism are induced as the feed per revolution is varied.When the feed per revolution is less than the tool edge radius,the glass fiber is not cut by the main cutting edge,but is crushed and broken.When the feed per revolution is greater than the radius of the tool edge,the glass fiber is cut by the main cutting edge.At the same time,the established analytical model can accurately reflect the influence of the size effect on the drilling torque in PCB micro-hole drilling,and the error is within 10%.This method has certain practical application value in controlling PCB micro hole processing quality.展开更多
Precise Point Positioning(PPP) technology has developed into a potent instrument for geodetic positioning, ionospheric modeling, tropospheric atmospheric parameter detection, and seismic monitoring.As atmospheric rean...Precise Point Positioning(PPP) technology has developed into a potent instrument for geodetic positioning, ionospheric modeling, tropospheric atmospheric parameter detection, and seismic monitoring.As atmospheric reanalysis data products’ accuracy and spatiotemporal resolution have improved recently, it has become important to apply these products to obtain high-accuracy tropospheric delay parameters, like zenith tropospheric delay(ZTD) and tropospheric horizontal gradient. These tropospheric delay parameters can be applied to PPP to reduce the convergence time and to increase the accuracy in the vertical direction of the position. The European Centre for Medium-Range Weather Forecasts Reanalysis 5(ERA5) atmospheric reanalysis data is the latest product with a high spatiotemporal resolution released by the European Center for Medium-Range Weather Forecasts(ECMWF). Only a few researches have evaluated the application of ERA5 data to Global Navigation Satellite System(GNSS)PPP. Therefore, this study compared and validated the ZTD products derived from ERA5 data using ZTD values provided by 290 global International GNSS Service(IGS) stations for 2016-2017. The results indicated a stable performance for ZTD, with annual average bias and RMS values of 0.23 cm and 1.09 cm,respectively. Further, GNSS observations for one week in each of the four seasons(spring: DOY 92-98;summer: DOY 199-205;autumn: DOY 275-281;and winter: DOY 22-28) from 34 multi-GNSS experiments(MGEX) stations distributed globally in 2016 were considered to evaluate the performance of ERA5-derived tropospheric delay products in GNSS PPP. The performance of ERA5-enhanced PPP was compared with that of the two standard GNSS PPP schemes(without estimated tropospheric horizontal gradient and with estimated tropospheric horizontal gradient). The results demonstrated that ERA5-enhanced GNSS PPP showed no significant improvement in the convergence times in both the Eastern(E) and Northern(N) directions, while the average convergence time over four weeks in the vertical(U)direction improved by 53.3% and 52.7%, respectively(in the case of pngm station). The average convergence times for each week in the U direction of the northern and southern hemisphere stations indicated a decrease of 16.3%, 12.6%, 9.6%, and 9.1%, and 16.9%, 9.6%, 8.9%, and 14.5%, respectively.Regarding positioning accuracy, ERA5-enhanced PPP showed an improvement of 13.3% and 16.2% over the two standard PPP schemes in the U direction, respectively. No significant improvement in the positioning performance was observed in both the E and N directions. Thus, this study demonstrated the potential application of the ERA5 tropospheric parameters-augmented approach to Beidou navigation and positioning.展开更多
This paper explores the effect of precise rehabilitation strategies under the international classification of functioning,disability and health for children and youth(ICF-CY)on the motor function of children with cere...This paper explores the effect of precise rehabilitation strategies under the international classification of functioning,disability and health for children and youth(ICF-CY)on the motor function of children with cerebral palsy.Under the framework of ICF-CY,the observation team is designed and evaluated from physical functions,activities and participation,environmental factors,and devel-ops individualized rehabilitation strategies that are tailored to individual character-istics.The control group was assessed by traditional methods and treatment plans and measures were formulated and guided.The course of treatment was 12 months.The scores of GMFM-88,Peabody Motor Development Scale-2con-cluding fine motor quotient(PDMS-FM),WeeFIM and the ability of daily living(ADL)scale(Barthel index,BI)score were compared before and after treatment.The research shows that precise rehabilitation strategy mode for children with cer-ebral palsy under the ICF-CY framework can effectively improve the motor func-tion and the ability of daily living(ADL)in children with cerebral palsy.Rehabilitation evaluation and treatment mode of children with cerebral palsy under ICF-CY framework can effectively improve the gross motor function of children with cerebral palsy.Individualized evaluation and analysis and guidance of comprehensive rehabilitation treatment have certain advantages.The overall treatment effect is better than that of traditional rehabilitation evaluation.展开更多
Nanomachines and ultrastructures inside cells are the basic units involved in life activities.They perform specific physiological functions through close cooperation with each other.Seeing is believing.Studying the in...Nanomachines and ultrastructures inside cells are the basic units involved in life activities.They perform specific physiological functions through close cooperation with each other.Seeing is believing.Studying the in situ assembly and function of these complicated and precise nanostructures has been a hot topic in life science.Cryo-electron tomography(cryo-ET)is currently the main technique for in situ structural analysis.However,due to the limitation of electron beam penetration,cell and tissue samples should be milled to lamella of~200 nanometers using focused ion beams(FIB)for imaging.However,the random milling technique brings great challenges to the study of specific targets with relatively low abundance in cells.The prepared cryo-lamella sample often fails to retain the target of interest.展开更多
GAO Caixia’s group from the Institute of Genetics and Developmental Biology(IGDB)of the Chinese Academy of Sciences(CAS)has developed a new genome editing technology that achieves efficient and precise targeted inser...GAO Caixia’s group from the Institute of Genetics and Developmental Biology(IGDB)of the Chinese Academy of Sciences(CAS)has developed a new genome editing technology that achieves efficient and precise targeted insertion of large DNA segments in plants.The new technology,called prime editing-mediated recombination of opportune targets(PrimeRoot),combines an optimized dual-ePPE editor protein previously published by the group with a highly efficient tyrosine site-specific recombinase,Cre.It can achieve one-step,precise targeted insertion of large DNA segments in rice and maize with an efficiency up to 6%and has been used to successfully insert DNA segments up to 11.1 kb.展开更多
The potential application of gold nanoparticles(GNPs)in biomedicine has been extensively reported.However,there is still too much puzzle about their real face and potential health risks in comparison with the commerci...The potential application of gold nanoparticles(GNPs)in biomedicine has been extensively reported.However,there is still too much puzzle about their real face and potential health risks in comparison with the commercial drug molecules.The emergence of atomically precise gold nanoclusters(APGNCs)provides the opportunity to address the puzzle due to their ultrasmall size,defined molecular formula,editable surface engineering,available structures and unique physicochemical properties including excellent biocompatibility,strong luminescence,enzyme-like activity and efficient renal clearance,et al.Recently,these advantages of APGNCs also endow them promising performances in healthcare such as bioimaging,drug delivery,antibacterial and cancer therapy.Especially,their clear composition and structures like the commercial drug molecules facilitate the study of their functions and the structure-activity relationship in healthcare,which is essential for the guided design of APGNC nanomedicine.Therefore,this review will focus the advantages and recent progress of APGNCs in health care and envision their prospects for the future.展开更多
Precision therapy has become the preferred choice attributed to the optimal drug concentration in target sites,increased therapeutic efficacy,and reduced adverse effects.Over the past few years,sprayable or injectable...Precision therapy has become the preferred choice attributed to the optimal drug concentration in target sites,increased therapeutic efficacy,and reduced adverse effects.Over the past few years,sprayable or injectable thermosensitive hydrogels have exhibited high therapeutic potential.These can be applied as cell-growing scaffolds or drug-releasing reservoirs by simply mixing in a free-flowing sol phase at room temperature.Inspired by their unique properties,thermosensitive hydrogels have been widely applied as drug delivery and treatment platforms for precision medicine.In this review,the state-of-theart developments in thermosensitive hydrogels for precision therapy are investigated,which covers from the thermo-gelling mechanisms and main components to biomedical applications,including wound healing,anti-tumor activity,osteogenesis,and periodontal,sinonasal and ophthalmic diseases.The most promising applications and trends of thermosensitive hydrogels for precision therapy are also discussed in light of their unique features.展开更多
The spread of tuberculosis(TB),especially multidrug-resistant TB and extensively drug-resistant TB,has strongly motivated the research and development of new anti-TB drugs.New strategies to facilitate drug combination...The spread of tuberculosis(TB),especially multidrug-resistant TB and extensively drug-resistant TB,has strongly motivated the research and development of new anti-TB drugs.New strategies to facilitate drug combinations,including pharmacokinetics-guided dose optimization and toxicology studies of first-and second-line anti-TB drugs have also been introduced and recommended.Liquid chromatography-mass spectrometry(LC-MS)has arguably become the gold standard in the analysis of both endo-and exo-genous compounds.This technique has been applied successfully not only for therapeutic drug monitoring(TDM)but also for pharmacometabolomics analysis.TDM improves the effectiveness of treatment,reduces adverse drug reactions,and the likelihood of drug resistance development in TB patients by determining dosage regimens that produce concentrations within the therapeutic target window.Based on TDM,the dose would be optimized individually to achieve favorable outcomes.Pharmacometabolomics is essential in generating and validating hypotheses regarding the metabolism of anti-TB drugs,aiding in the discovery of potential biomarkers for TB diagnostics,treatment monitoring,and outcome evaluation.This article highlighted the current progresses in TDM of anti-TB drugs based on LC-MS bioassay in the last two decades.Besides,we discussed the advantages and disadvantages of this technique in practical use.The pressing need for non-invasive sampling approaches and stability studies of anti-TB drugs was highlighted.Lastly,we provided perspectives on the prospects of combining LC-MS-based TDM and pharmacometabolomics with other advanced strategies(pharmacometrics,drug and vaccine developments,machine learning/artificial intelligence,among others)to encapsulate in an all-inclusive approach to improve treatment outcomes of TB patients.展开更多
Additive Runge-Kutta methods designed for preserving highly accurate solutions in mixed-precision computation were previously proposed and analyzed.These specially designed methods use reduced precision for the implic...Additive Runge-Kutta methods designed for preserving highly accurate solutions in mixed-precision computation were previously proposed and analyzed.These specially designed methods use reduced precision for the implicit computations and full precision for the explicit computations.In this work,we analyze the stability properties of these methods and their sensitivity to the low-precision rounding errors,and demonstrate their performance in terms of accuracy and efficiency.We develop codes in FORTRAN and Julia to solve nonlinear systems of ODEs and PDEs using the mixed-precision additive Runge-Kutta(MP-ARK)methods.The convergence,accuracy,and runtime of these methods are explored.We show that for a given level of accuracy,suitably chosen MP-ARK methods may provide significant reductions in runtime.展开更多
Background:Limited research has been conducted on the influence of autophagy-associated long non-coding RNAs(ARLncRNAs)on the prognosis of hepatocellular carcinoma(HCC).Methods:We analyzed 371 HCC samples from TCGA,id...Background:Limited research has been conducted on the influence of autophagy-associated long non-coding RNAs(ARLncRNAs)on the prognosis of hepatocellular carcinoma(HCC).Methods:We analyzed 371 HCC samples from TCGA,identifying expression networks of ARLncRNAs using autophagy-related genes.Screening for prognostically relevant ARLncRNAs involved univariate Cox regression,Lasso regression,and multivariate Cox regression.A Nomogram was further employed to assess the reliability of Riskscore,calculated from the signatures of screened ARLncRNAs,in predicting outcomes.Additionally,we compared drug sensitivities in patient groups with differing risk levels and investigated potential biological pathways through enrichment analysis,using consensus clustering to identify subgroups related to ARLncRNAs.Results:The screening process identified 27 ARLncRNAs,with 13 being associated with HCC prognosis.Consequently,a set of signatures comprising 8 ARLncRNAs was successfully constructed as independent prognostic factors for HCC.Patients in the high-risk group showed very poor prognoses in most clinical categories.The Riskscore was closely related to immune cell scores,such as macrophages,and the DEGs between different groups were implicated in metabolism,cell cycle,and mitotic processes.Notably,high-risk group patients demonstrated a significantly lower IC50 for Paclitaxel,suggesting that Paclitaxel could be an ideal treatment for those at elevated risk for HCC.We further identified C2 as the Paclitaxel subtype,where patients exhibited higher Riskscores,reduced survival rates,and more severe clinical progression.Conclusion:The 8 signatures based on ARLncRNAs present novel targets for prognostic prediction in HCC.The drug candidate Paclitaxel may effectively treat HCC by impacting ARLncRNAs expression.With the identification of ARLncRNAsrelated isoforms,these results provide valuable insights for clinical exploration of autophagy mechanisms in HCC pathogenesis and offer potential avenues for precision medicine.展开更多
The electrical resistivity method is a geophysical tool used to characterize the subsoil and can provide an important information for precision agriculture. The lack of knowledge about agronomic properties of the soil...The electrical resistivity method is a geophysical tool used to characterize the subsoil and can provide an important information for precision agriculture. The lack of knowledge about agronomic properties of the soil tends to affect the agricultural coffee production system. Therefore, research related to geoelectrical properties of soil such as resistivity for characterization the region of the study for coffee cultivation purposes can improve and optimize the production. This resistivity method allows to investigate the subsurface through different techniques: 1D vertical electrical sounding and electrical imaging. The acquisition of data using these techniques permitted the creation of 2D resistivity cross section from the study area. The geoelectrical data was acquired by using a resistivity meter equipment and was processed in different softwares. The results of the geoelectrical characterization from 1D resistivity model and 2D resistivity electrical sections show that in the study area of Kabiri, there are 8 varieties of geoelectrical layers with different resistivity or conductivity. Near survey in the study area, the lowest resistivity is around 0.322 Ω·m, while the highest is about 92.1 Ω·m. These values illustrated where is possible to plant coffee for suggestion of specific fertilization plan for some area to improve the cultivation.展开更多
基金funded by a Croucher Innovation Award(CIA20CU01)from the Croucher Foundationthe General Research Fund(14100122)+4 种基金the Collaborative Research Fund(C6027-19GF&C7074-21GF)the Area of Excellence Scheme(AoE/M-604/16)of the Research Grants Councilthe University Grants Committee of Hong Kong,Chinathe Excellent Young Scientists Fund(Hong Kong and Macao,China)(82122001)from the National Natural Science Foundation of Chinathe Lo’s Family Charity Fund Limited(all to HK).
文摘Precise chemical cue presentation alongside advanced brainwide imaging techniques is important to the study of chemosensory processing in animals.Nevertheless,the dynamic nature of chemical-carrying media,such as water or air,poses a significant challenge for delivering highly-controlled chemical flow to an animal subject.Moreover,contact-based cue manipulation and delivery easily shift the position of the animal subject,which is often undesirable for high-quality brain imaging.Additionally,more advanced interfacing tools that align with the diverse range of body part sizes of an animal,ranging from micrometer-scale neurons to meter-long limbs,are much needed.This is particularly crucial when dealing with dimensions that are beyond the reach of conventional experimental tools.
基金This work was supported by the National Natural Science Foundation of China(Grant No.12004351).
文摘A self-consistent and precise method to determine the time-dependent radiative albedo,i.e.,the ratio of the reemission flux to the incident flux,for an indirect-drive inertial confinement fusion Hohlraum wall material is proposed.A specially designed symmetrical triple-cavity gold Hohlraum is used to create approximately constant and near-equilibrium uniform radiation with a peak temperature of 160 eV.The incident flux at the secondary cavity waist is obtained from flux balance analysis and from the shock velocity of a standard sample.The results agree well owing to the symmetrical radiation in the secondary cavity.A self-consistent and precise time-dependent radiative albedo is deduced from the reliable reemission flux and the incident flux,and the result from the shock velocity is found to have a smaller uncertainty than that from the multi-angle flux balance analysis,and also to agree well with the result of a simulation using the HYADES opacity.
基金Ministry Key Project(JW0890006)Key Realm R&D Program of Guangdong Province(2019B030335001)+1 种基金Department of Science and Technology of Sichuan Province(2022NSFSC0808)Key Medical Discipline of Hangzhou,The Cultivation Project of the Province-leveled Preponderant Characteristic Discipline of Hangzhou Normal University(18JYXK046,20JYXK004).
文摘To the editor:Transcranial magnetic stimulation(TMS)is a non-invasive brain modulation technique.One important usage of TMS is the transient interruption of cognitive brain function(also named virtual lesion)for investigating precisely where and when a specific cortical region contributes to a specific cognitive function.1 A more important usage of TMS is the treatment of brain disorders by repetitive TMS(rTMS).
基金supported by a grant from The National Natural Science Foundation of China(82270355)。
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.
文摘BACKGROUND Cerebral infarction,previously referred to as cerebral infarction or ischemic stroke,refers to the localized brain tissue experiencing ischemic necrosis or softening due to disorders in brain blood supply,ischemia,and hypoxia.The precision rehabilitation nursing model for chronic disease management is a continuous,fixed,orderly,and efficient nursing model aimed at standardizing the clinical nursing process,reducing the wastage of medical resources,and improving the quality of medical services.AIM To analyze the value of a precise rehabilitation nursing model for chronic disease management in patients with cerebral infarction.METHODS Patients(n=124)admitted to our hospital with cerebral infarction between November 2019 and November 2021 were enrolled as the study subjects.The random number table method was used to divide them into a conventional nursing intervention group(n=61)and a model nursing intervention group(n=63).Changes in the nursing index for the two groups were compared after conventional nursing intervention and precise rehabilitation intervention nursing for chronic disease management.RESULTS Compared with the conventional intervention group,the model intervention group had a shorter time to clinical symptom relief(P<0.05),lower Hamilton Anxiety Scale and Hamilton Depression Scale scores,a lower incidence of total complications(P<0.05),a higher disease knowledge mastery rate,higher safety and quality,and a higher overall nursing satisfaction rate(P<0.05).CONCLUSION The precision rehabilitation nursing model for chronic disease management improves the clinical symptoms of patients with cerebral infarction,reducing the incidence of total complications and improving the clinical outcome of patients,and is worthy of application in clinical practice.
基金2022 University-Level General Project“Empowering Precise Ideological and Political Education in Higher Education with Educational Digitalization”(Project number:jsesd202209)。
文摘The study explores how educational digitalization enables the precise development of ideological and political education in colleges and universities.Digital transformation enables colleges and universities to accurately define educational objectives,content strategies,effect evaluation,and process management,and realize the precision and intelligence of ideological and political education.The application of big data technology enhances the data-oriented thinking of teachers and students,promotes the accurate application of data,and improves the efficiency of ideological and political education.The research also prospected a new vision of the digital construction of ideological and political courses and clarified the theoretical and practical path of the implementation and evaluation mode of ideological and political courses under digital empowerment.Education digitalization enables precise ideological and political education,which is a key way to promote the innovative development of ideological and political education in colleges and universities and will strongly support the improvement of the overall quality of higher education and the training of excellent talents.
基金supported by the Ministry of Agriculture and Rural Affairs of China,the Jiangsu Provincial Key Research and Development Program(Grant No.BE2022383)Key Laboratory of Jiangsu Province for Agrobiology,China(Grant No.JKLA2021-ZD01)the Exploratory Project of the Jiangsu Academy of Agricultural Sciences,China(Grant No.ZX(21)1201).
文摘Aleurone forms the outermost layer of the rice endosperm and plays a critical role in apoplastic nutrient uptake during endosperm development.Thickening the aleurone layer has been proposed to significantly increase the nutrient content of rice grains.In this study,we used a CRISPR/Cas9-mediated precise base editing method to target OsROS1,a gene associated with aleurone thickness,in the background of the japonica glutinous rice cultivar Zhennuo 19。
基金National Natural Science Foundation of China(No.51805079)Fundamental Research Funds for the Central Universities,China(No.2232021D-15)Shanghai Science and Technology Program(No.20DZ2251400)。
文摘The quality of printed circuit board(PCB)micro-hole processing directly determines the stability of the inner and outer circuit connections.Micro-hole drilling technology is a typical method for PCB micro-hole processing.The problem of optimal control of its drilling force is one of the main factors affecting the quality of micro-hole machining.To address this problem,the thrust forces and torques in PCB drilling were first modeled and analyzed,and the corresponding prediction models were established.The drilling force analysis was carried out through the micro-hole drilling experiment,the specific cutting energy under different feed rates was calculated,the influence of the size effect was clarified,and the accuracy of the prediction model was verified.The result shows that during the drilling of glass fiber cloth,changes in the material removal mechanism are induced as the feed per revolution is varied.When the feed per revolution is less than the tool edge radius,the glass fiber is not cut by the main cutting edge,but is crushed and broken.When the feed per revolution is greater than the radius of the tool edge,the glass fiber is cut by the main cutting edge.At the same time,the established analytical model can accurately reflect the influence of the size effect on the drilling torque in PCB micro-hole drilling,and the error is within 10%.This method has certain practical application value in controlling PCB micro hole processing quality.
基金funded by the National Natural Foundation of China (Grant No.4170402741864002)+2 种基金the Guangxi Natural Science Foundation of China (2020GXNSFBA297145)the “Ba Gui Scholars” program of the provincial government of Guangxithe Innovation Project of Guangxi Graduate Education (Grant No. YCSW20211209)
文摘Precise Point Positioning(PPP) technology has developed into a potent instrument for geodetic positioning, ionospheric modeling, tropospheric atmospheric parameter detection, and seismic monitoring.As atmospheric reanalysis data products’ accuracy and spatiotemporal resolution have improved recently, it has become important to apply these products to obtain high-accuracy tropospheric delay parameters, like zenith tropospheric delay(ZTD) and tropospheric horizontal gradient. These tropospheric delay parameters can be applied to PPP to reduce the convergence time and to increase the accuracy in the vertical direction of the position. The European Centre for Medium-Range Weather Forecasts Reanalysis 5(ERA5) atmospheric reanalysis data is the latest product with a high spatiotemporal resolution released by the European Center for Medium-Range Weather Forecasts(ECMWF). Only a few researches have evaluated the application of ERA5 data to Global Navigation Satellite System(GNSS)PPP. Therefore, this study compared and validated the ZTD products derived from ERA5 data using ZTD values provided by 290 global International GNSS Service(IGS) stations for 2016-2017. The results indicated a stable performance for ZTD, with annual average bias and RMS values of 0.23 cm and 1.09 cm,respectively. Further, GNSS observations for one week in each of the four seasons(spring: DOY 92-98;summer: DOY 199-205;autumn: DOY 275-281;and winter: DOY 22-28) from 34 multi-GNSS experiments(MGEX) stations distributed globally in 2016 were considered to evaluate the performance of ERA5-derived tropospheric delay products in GNSS PPP. The performance of ERA5-enhanced PPP was compared with that of the two standard GNSS PPP schemes(without estimated tropospheric horizontal gradient and with estimated tropospheric horizontal gradient). The results demonstrated that ERA5-enhanced GNSS PPP showed no significant improvement in the convergence times in both the Eastern(E) and Northern(N) directions, while the average convergence time over four weeks in the vertical(U)direction improved by 53.3% and 52.7%, respectively(in the case of pngm station). The average convergence times for each week in the U direction of the northern and southern hemisphere stations indicated a decrease of 16.3%, 12.6%, 9.6%, and 9.1%, and 16.9%, 9.6%, 8.9%, and 14.5%, respectively.Regarding positioning accuracy, ERA5-enhanced PPP showed an improvement of 13.3% and 16.2% over the two standard PPP schemes in the U direction, respectively. No significant improvement in the positioning performance was observed in both the E and N directions. Thus, this study demonstrated the potential application of the ERA5 tropospheric parameters-augmented approach to Beidou navigation and positioning.
基金This work is supported by General Project of Nanjing Municipal Health Commission(No.YKK19108).
文摘This paper explores the effect of precise rehabilitation strategies under the international classification of functioning,disability and health for children and youth(ICF-CY)on the motor function of children with cerebral palsy.Under the framework of ICF-CY,the observation team is designed and evaluated from physical functions,activities and participation,environmental factors,and devel-ops individualized rehabilitation strategies that are tailored to individual character-istics.The control group was assessed by traditional methods and treatment plans and measures were formulated and guided.The course of treatment was 12 months.The scores of GMFM-88,Peabody Motor Development Scale-2con-cluding fine motor quotient(PDMS-FM),WeeFIM and the ability of daily living(ADL)scale(Barthel index,BI)score were compared before and after treatment.The research shows that precise rehabilitation strategy mode for children with cer-ebral palsy under the ICF-CY framework can effectively improve the motor func-tion and the ability of daily living(ADL)in children with cerebral palsy.Rehabilitation evaluation and treatment mode of children with cerebral palsy under ICF-CY framework can effectively improve the gross motor function of children with cerebral palsy.Individualized evaluation and analysis and guidance of comprehensive rehabilitation treatment have certain advantages.The overall treatment effect is better than that of traditional rehabilitation evaluation.
文摘Nanomachines and ultrastructures inside cells are the basic units involved in life activities.They perform specific physiological functions through close cooperation with each other.Seeing is believing.Studying the in situ assembly and function of these complicated and precise nanostructures has been a hot topic in life science.Cryo-electron tomography(cryo-ET)is currently the main technique for in situ structural analysis.However,due to the limitation of electron beam penetration,cell and tissue samples should be milled to lamella of~200 nanometers using focused ion beams(FIB)for imaging.However,the random milling technique brings great challenges to the study of specific targets with relatively low abundance in cells.The prepared cryo-lamella sample often fails to retain the target of interest.
文摘GAO Caixia’s group from the Institute of Genetics and Developmental Biology(IGDB)of the Chinese Academy of Sciences(CAS)has developed a new genome editing technology that achieves efficient and precise targeted insertion of large DNA segments in plants.The new technology,called prime editing-mediated recombination of opportune targets(PrimeRoot),combines an optimized dual-ePPE editor protein previously published by the group with a highly efficient tyrosine site-specific recombinase,Cre.It can achieve one-step,precise targeted insertion of large DNA segments in rice and maize with an efficiency up to 6%and has been used to successfully insert DNA segments up to 11.1 kb.
基金supported by the National Natural Science Foundation of China(21971246,22371108,22075122)Taishan Scholar Foundation of Shandong Province(tsqn202211242)the Chunhui Program of the Ministry of Education of China(HZKY20220463).
文摘The potential application of gold nanoparticles(GNPs)in biomedicine has been extensively reported.However,there is still too much puzzle about their real face and potential health risks in comparison with the commercial drug molecules.The emergence of atomically precise gold nanoclusters(APGNCs)provides the opportunity to address the puzzle due to their ultrasmall size,defined molecular formula,editable surface engineering,available structures and unique physicochemical properties including excellent biocompatibility,strong luminescence,enzyme-like activity and efficient renal clearance,et al.Recently,these advantages of APGNCs also endow them promising performances in healthcare such as bioimaging,drug delivery,antibacterial and cancer therapy.Especially,their clear composition and structures like the commercial drug molecules facilitate the study of their functions and the structure-activity relationship in healthcare,which is essential for the guided design of APGNC nanomedicine.Therefore,this review will focus the advantages and recent progress of APGNCs in health care and envision their prospects for the future.
基金financially supported by the National Natural Science Foundation of China(Grants 52172276)fund from Anhui Provincial Institute of Translational Medicine(2021zhyx-B15)。
文摘Precision therapy has become the preferred choice attributed to the optimal drug concentration in target sites,increased therapeutic efficacy,and reduced adverse effects.Over the past few years,sprayable or injectable thermosensitive hydrogels have exhibited high therapeutic potential.These can be applied as cell-growing scaffolds or drug-releasing reservoirs by simply mixing in a free-flowing sol phase at room temperature.Inspired by their unique properties,thermosensitive hydrogels have been widely applied as drug delivery and treatment platforms for precision medicine.In this review,the state-of-theart developments in thermosensitive hydrogels for precision therapy are investigated,which covers from the thermo-gelling mechanisms and main components to biomedical applications,including wound healing,anti-tumor activity,osteogenesis,and periodontal,sinonasal and ophthalmic diseases.The most promising applications and trends of thermosensitive hydrogels for precision therapy are also discussed in light of their unique features.
基金sponsored by the National Research Foundation of Korea(NRF)Grant funded by the Korean government(MSIT)(Grant No.:2018R1A5A2021242).
文摘The spread of tuberculosis(TB),especially multidrug-resistant TB and extensively drug-resistant TB,has strongly motivated the research and development of new anti-TB drugs.New strategies to facilitate drug combinations,including pharmacokinetics-guided dose optimization and toxicology studies of first-and second-line anti-TB drugs have also been introduced and recommended.Liquid chromatography-mass spectrometry(LC-MS)has arguably become the gold standard in the analysis of both endo-and exo-genous compounds.This technique has been applied successfully not only for therapeutic drug monitoring(TDM)but also for pharmacometabolomics analysis.TDM improves the effectiveness of treatment,reduces adverse drug reactions,and the likelihood of drug resistance development in TB patients by determining dosage regimens that produce concentrations within the therapeutic target window.Based on TDM,the dose would be optimized individually to achieve favorable outcomes.Pharmacometabolomics is essential in generating and validating hypotheses regarding the metabolism of anti-TB drugs,aiding in the discovery of potential biomarkers for TB diagnostics,treatment monitoring,and outcome evaluation.This article highlighted the current progresses in TDM of anti-TB drugs based on LC-MS bioassay in the last two decades.Besides,we discussed the advantages and disadvantages of this technique in practical use.The pressing need for non-invasive sampling approaches and stability studies of anti-TB drugs was highlighted.Lastly,we provided perspectives on the prospects of combining LC-MS-based TDM and pharmacometabolomics with other advanced strategies(pharmacometrics,drug and vaccine developments,machine learning/artificial intelligence,among others)to encapsulate in an all-inclusive approach to improve treatment outcomes of TB patients.
基金supported by ONR UMass Dartmouth Marine and UnderSea Technology(MUST)grant N00014-20-1-2849 under the project S31320000049160by DOE grant DE-SC0023164 sub-award RC114586-UMD+2 种基金by AFOSR grants FA9550-18-1-0383 and FA9550-23-1-0037supported by Michigan State University,by AFOSR grants FA9550-19-1-0281 and FA9550-18-1-0383by DOE grant DE-SC0023164.
文摘Additive Runge-Kutta methods designed for preserving highly accurate solutions in mixed-precision computation were previously proposed and analyzed.These specially designed methods use reduced precision for the implicit computations and full precision for the explicit computations.In this work,we analyze the stability properties of these methods and their sensitivity to the low-precision rounding errors,and demonstrate their performance in terms of accuracy and efficiency.We develop codes in FORTRAN and Julia to solve nonlinear systems of ODEs and PDEs using the mixed-precision additive Runge-Kutta(MP-ARK)methods.The convergence,accuracy,and runtime of these methods are explored.We show that for a given level of accuracy,suitably chosen MP-ARK methods may provide significant reductions in runtime.
文摘Background:Limited research has been conducted on the influence of autophagy-associated long non-coding RNAs(ARLncRNAs)on the prognosis of hepatocellular carcinoma(HCC).Methods:We analyzed 371 HCC samples from TCGA,identifying expression networks of ARLncRNAs using autophagy-related genes.Screening for prognostically relevant ARLncRNAs involved univariate Cox regression,Lasso regression,and multivariate Cox regression.A Nomogram was further employed to assess the reliability of Riskscore,calculated from the signatures of screened ARLncRNAs,in predicting outcomes.Additionally,we compared drug sensitivities in patient groups with differing risk levels and investigated potential biological pathways through enrichment analysis,using consensus clustering to identify subgroups related to ARLncRNAs.Results:The screening process identified 27 ARLncRNAs,with 13 being associated with HCC prognosis.Consequently,a set of signatures comprising 8 ARLncRNAs was successfully constructed as independent prognostic factors for HCC.Patients in the high-risk group showed very poor prognoses in most clinical categories.The Riskscore was closely related to immune cell scores,such as macrophages,and the DEGs between different groups were implicated in metabolism,cell cycle,and mitotic processes.Notably,high-risk group patients demonstrated a significantly lower IC50 for Paclitaxel,suggesting that Paclitaxel could be an ideal treatment for those at elevated risk for HCC.We further identified C2 as the Paclitaxel subtype,where patients exhibited higher Riskscores,reduced survival rates,and more severe clinical progression.Conclusion:The 8 signatures based on ARLncRNAs present novel targets for prognostic prediction in HCC.The drug candidate Paclitaxel may effectively treat HCC by impacting ARLncRNAs expression.With the identification of ARLncRNAsrelated isoforms,these results provide valuable insights for clinical exploration of autophagy mechanisms in HCC pathogenesis and offer potential avenues for precision medicine.
文摘The electrical resistivity method is a geophysical tool used to characterize the subsoil and can provide an important information for precision agriculture. The lack of knowledge about agronomic properties of the soil tends to affect the agricultural coffee production system. Therefore, research related to geoelectrical properties of soil such as resistivity for characterization the region of the study for coffee cultivation purposes can improve and optimize the production. This resistivity method allows to investigate the subsurface through different techniques: 1D vertical electrical sounding and electrical imaging. The acquisition of data using these techniques permitted the creation of 2D resistivity cross section from the study area. The geoelectrical data was acquired by using a resistivity meter equipment and was processed in different softwares. The results of the geoelectrical characterization from 1D resistivity model and 2D resistivity electrical sections show that in the study area of Kabiri, there are 8 varieties of geoelectrical layers with different resistivity or conductivity. Near survey in the study area, the lowest resistivity is around 0.322 Ω·m, while the highest is about 92.1 Ω·m. These values illustrated where is possible to plant coffee for suggestion of specific fertilization plan for some area to improve the cultivation.