Construction and Application of a Regional Kilometer-Scale Carbon Source and Sink Assimilation Inversion System(CCMVS-R)

CO_(2)is one of the most important greenhouse gases(GHGs)in the earth’s atmosphere.Since the industrial era,anthropogenic activities have emitted excessive quantities of GHGs into the atmosphere,resulting in climate warming since the 1950s and leading to an increased frequency of extreme weather and climate events.In 2020,China committed to striving for carbon neutrality by 2060.This commitment and China’s consequent actions will result in significant changes in global and regional anthropogenic carbon emissions and therefore require timely,comprehensive,and objective monitoring and verification support(MVS)systems.The MVS approach relies on the top-down assimilation and inversion of atmospheric CO_(2)concentrations,as recommended by the Intergovernmental Panel on Climate Change(IPCC)Inventory Guidelines in 2019.However,the regional high-resolution assimilation and inversion method is still in its initial stage of development.Here,we have constructed an inverse system for carbon sources and sinks at the kilometer level by coupling proper orthogonal decomposition(POD)with four-dimensional variational(4DVar)data assimilation based on the weather research and forecasting-greenhouse gas(WRF-GHG)model.Our China Carbon Monito ring and Verification Support at the Regional level(CCMVS-R)system can continuously assimilate information on atmospheric CO_(2)and other related information and realize the inversion of regional and local anthropogenic carbon emissions and natural terrestrial ecosystem carbon exchange.Atmospheric CO_(2)data were collected from six ground-based monito ring sites in Shanxi Province,China to verify the inversion effect of regio nal anthropogenic carbon emissions by setting ideal and real experiments using a two-layer nesting method(at 27 and 9 km).The uncertainty of the simulated atmospheric CO_(2)decreased significantly,with a root-mean-square error of CO_(2)concentration values between the ideal value and the simulated after assimilation was close to 0.The total anthropogenic carbon emissions in Shanxi Province in 2019 from the assimilated inversions were approximately 28.6%(17%-38%)higher than the mean of five emission inventories using the bottomup method,showing that the top-down CCMVS-R system can obtain more comprehensive information on anthropogenic carbon emissions.

A New Method for Deriving High-Vertical-Resolution Wind Vector Data from the L-Band Radar Sounding System in China

High-vertical-resolution radiosonde wind data are highly valuable for describing the dynamics of the meso-and microscale atmosphere. However, the current algorithm used in China's L-band radar sounding system for calculating highvertical-resolution wind vectors excessively smooths the data, resulting in significant underestimation of the calculated kinetic energy of gravity waves compared to similar products from other countries, which greatly limits the effective utilization of the data. To address this issue, this study proposes a novel method to calculate high-vertical-resolution wind vectors that utilizes the elevation angle, azimuth angle, and slant range from L-band radar. In order to obtain wind data with a stable quality, a two-step automatic quality control procedure, including the RMSE-F(root-mean-square error F) test and elemental consistency test are first applied to the slant range data, to eliminate continuous erroneous data caused by unstable signals or radar malfunctions. Then, a wind calculation scheme based on a sliding second-order polynomial fitting is utilized to derive the high-vertical-resolution radiosonde wind vectors. The evaluation results demonstrate that the wind data obtained through the proposed method show a high level of consistency with the high-resolution wind data observed using the Vaisala Global Positioning System and the data observed by the new Beidou Navigation Sounding System. The calculation of the kinetic energy of gravity waves in the recalculated wind data also reaches a level comparable to the Vaisala observations.

A Single-Cell Landscape of Human Liver Transplantation Reveals a Pathogenic Immune Niche Associated with Early Allograft Dysfunction

Liver transplantation(LT)is the standard therapy for individuals afflicted with end-stage liver disease.Despite notable advancements in LT technology,the incidence of early allograft dysfunction(EAD)remains a critical concern,exacerbating the current organ shortage and detrimentally affecting the prognosis of recipients.Unfortunately,the perplexing hepatic heterogeneity has impeded characterization of the cellular traits and molecular events that contribute to EAD.Herein,we constructed a pioneering single-cell transcriptomic landscape of human transplanted livers derived from non-EAD and EAD patients,with 12 liver samples collected from 7 donors during the cold perfusion and portal reperfusion stages.Comparison of the 75231 cells of non-EAD and EAD patients revealed an EAD-associated immune niche comprising mucosal-associated invariant T cells,granzyme B^(+)(GZMB^(+))granzyme K^(+)(GZMK^(+))natural killer cells,and S100 calcium binding protein A12^(+)(S100A12^(+))neutrophils.Moreover,we verified this immune niche and its association with EAD occurrence in two independent cohorts.Our findings elucidate the cellular characteristics of transplanted livers and the EAD-associated pathogenic immune niche at the single-cell level,thus,offering valuable insights into EAD onset.

Dissecting the brain with spatially resolved multi-omics

Recent studies have highlighted spatially resolved multi-omics technologies,including spatial genomics,transcriptomics,proteomics,and metabolomics,as powerful tools to decipher the spatial heterogeneity of the brain.Here,we focus on two major approaches in spatial transcriptomics(next-generation sequencing-based technologies and image-based technologies),and mass spectrometry imaging technologies used in spatial proteomics and spatial metabolomics.Furthermore,we discuss their applications in neuroscience,including building the brain atlas,uncovering gene expression patterns of neurons for special behaviors,deciphering the molecular basis of neuronal communication,and providing a more comprehensive explanation of the molecular mechanisms underlying central nervous system disorders.However,further efforts are still needed toward the integrative application of multi-omics technologies,including the real-time spatial multi-omics analysis in living cells,the detailed gene profile in a whole-brain view,and the combination of functional verification.

High-throughput transcriptional profiling of perturbations by Panax ginseng saponins and Panax notoginseng saponins using TCM-seq

Panax ginseng(PG)and Panax notoginseng(PN)are highly valuable Chinese medicines(CM).Although both CMs have similar active constituents,their clinical applications are clearly different.Over the past decade,RNA sequencing(RNA-seq)analysis has been employed to investigate the molecular mechanisms of extracts or monomers.However,owing to the limited number of samples in standard RNA-seq,few studies have systematically compared the effects of PG and PN spanning multiple conditions at the transcriptomic level.Here,we developed an approach that simultaneously profiles transcriptome changes for multiplexed samples using RNA-seq(TCM-seq),a high-throughput,low-cost workflow to molecularly evaluate CM perturbations.A species-mixing experiment was conducted to illustrate the accuracy of sample multiplexing in TCM-seq.Transcriptomes from repeated samples were used to verify the robustness of TCM-seq.We then focused on the primary active components,Panax notoginseng saponins(PNS)and Panax ginseng saponins(PGS)extracted from PN and PG,respectively.We also characterized the transcriptome changes of 10 cell lines,treated with four different doses of PNS and PGS,using TCM-seq to compare the differences in their perturbing effects on genes,functional pathways,gene modules,and molecular networks.The results of transcriptional data analysis showed that the transcriptional patterns of various cell lines were significantly distinct.PGS exhibited a stronger regulatory effect on genes involved in cardiovascular disease,whereas PNS resulted in a greater coagulation effect on vascular endothelial cells.This study proposes a paradigm to comprehensively explore the differences in mechanisms of action between CMs based on transcriptome readouts.

Preparation and evaluation of nattokinaseloaded self-double-emulsifying drug delivery system

In the present study,we prepared nattokinase-loaded self-double-emulsifying drug delivery system(SDEDDS)and investigated its preliminary pharmacodynamics.The type and concentration of oil phase,inner aqueous phase and emulsifier were screened to prepare optimum nattokinase-loaded SDEDDS.Next,the optimum formulations were characterized based on microstructure,volume-weighted mean droplet size,self-emulsifying rate,yield,storage stability,in vitro release and in vivo pharmacodynamics studies.The water/oil/watermultiple emulsions exhibited typicalmultiple structure,with relatively small volumeweighted mean droplet size 6.0±0.7μm and high self-emulsifying ability(self-emulsifying time<2 min).Encapsulation of nattokinase was up to 86.8±8.2%.The cumulative release of nattokinase within 8 h was about 30%,exhibiting a sustained release effect.The pharmacodynamics study indicated that nattokinase-loaded SDEDDS could significantly prolong the whole blood clotting time in mouse and effectively improve the carrageenan-induced tail thrombosis compared with nattokinase solution.Moreover,we showed that SDEDDS could successfully self-emulsify into water/oil/water multiple emulsions upon dilution in dispersion medium with gentle stirring and effectively protect nattokinase activity in gastric environment.Our findings suggested that SDEDDS could be a promising strategy for peptide and protein drugs by oral administration.

An ultra-robust fingerprinting method for quality assessment of traditional Chinese medicine using multiple reaction monitoring mass spectrometry

Chromatographic fingerprinting has been perceived as an essential tool for assessing quality and chemical equivalence of traditional Chinese medicine.However,this pattern-oriented approach still has some weak points in terms of chemical coverage and robustness.In this work,we proposed a multiple reaction monitoring(MRM)-based fingerprinting method in which approximately 100 constituents were simultaneously detected for quality assessment.The derivative MRM approach was employed to rapidly design MRM transitions independent of chemical standards,based on which the large-scale fingerprinting method was efficiently established.This approach was exemplified on QiShenYiQi Pill(QSYQ),a traditional Chinese medicine-derived drug product,and its robustness was systematically evaluated by four indices:clustering analysis by principal component analysis,similarity analysis by the congruence coefficient,the number of separated peaks,and the peak area proportion of separated peaks.Compared with conventional ultraviolet-based fingerprints,the MRM fingerprints provided not only better discriminatory capacity for the tested normal/abnormal QSYQ samples,but also higher robustness under different chromatographic conditions(i.e.,flow rate,apparent pH,column temperature,and column).The result also showed for such large-scale fingerprints including a large number of peaks,the angle cosine measure after min-max normalization was more suitable for setting a decision criterion than the unnormalized algorithm.This proof-of-concept application gives evidence that combining MRM technique with proper similarity analysis metrices can provide a highly sensitive,robust and comprehensive analytical approach for quality assessment of traditional Chinese medicine.

A quality control method for high-resolution radiosonde temperature and wind data

This study proposes a method to derive the climatological limit thresholds that can be used in an operational/historical quality control procedure for Chinese high vertical resolution(5–10 m)radiosonde temperature and wind speed data.The whole atmosphere is divided into 64 vertical bins,and the profiles are constructed by the percentiles of the values in each vertical bin.Based on the percentile profiles(PPs),some objective criteria are developed to obtain the thresholds.Tibetan Plateau field data are used to validate the effectiveness of the method in the application of experimental data.The results show that the derived thresholds for 120 operational stations and 3 experimental stations are effective in detecting the gross errors,and those PPs can clearly and instantly illustrate the characteristics of a radiosonde variable and reveal the distribution of errors.

Synergistic combination of arbuscular mycorrhizal fungi and plant growth-promoting rhizobacteria modulates morpho-physiological characteristics and soil structure in Nitraria tangutorum bobr.Under saline soil conditions

Nitraria tangutorum Bobr.,a typical xero-halophyte,can be used for vegetation restoration and reconstruction in arid and semiarid regions affected by salinity.However,global climate change and unreasonable human activity have exacerbated salinization in arid and semi-arid regions,which in turn has led to the growth inhibition of halophytes,including N.tangutorum.Arbuscular mycorrhizal fungi(AMF)and plant growth-promoting rhizobacteria(PGPR)have the potential to improve the salt tolerance of plants and their adaptation to saline soil environments.In this study,the effects of single and combined inoculations of AMF(Glomus mosseae)and PGPR(Bacillus amyloliquefaciens FZB42)on N.tangutorum were evaluated in severe saline soil conditions.The results indicate that AMF and PGPR alone may not adapt well to the real soil environment,and cannot ensure the effect of either growth promotion or salt-tolerance induction on N.tangutorum seedlings.However,the combination of AMF and PGPR significantly promoted mycorrhizal colonization,increased biomass accumulation,improved morphological development,enhanced photosynthetic performance,stomatal adjustment ability,and the exchange of water and gas.Co-inoculation also significantly counteracted the adverse effect of salinity on the soil structure of N.tangutorum seedlings.It is concluded that the effectiveness of microbial inoculation on the salt tolerance of N.tangutorum seedlings depends on the functional compatibility between plants and microorganisms as well as the specific combinations of AMF and PGPR.

Evaluation of Uncertainty in Determination of Reducing Sugar Content in Sugarcane

[ Objective] This study aimed to establish an effective method for evaluating uncertainty in determination of reducing sugar content in sugarcane with Lane-Ernon method. [ Method] Based on analysis of the main sources of uncertainty in determination of reducing sugar content in sugarcane and mathematical model construction, combined uncertainty and expanded uncertainty were determined to establish the method for evaluation of uncertainty in determination. [ Result] Among uncertainties in determination of reducing sugar content in sugarcane with Lane-Ernon method, the greatest uncertainty was introduced by duplicate determination. According to results of statistical analysis, the expanded uncertainty in determination of reducing sugar content was 0.012%. [ Conclusion] This study provided theo- retical reference for evaluation of uncertainty in determination of reducing sugar content in sugarcane.

STABILITY OF GLOBAL MAXWELLIAN FOR NON-LINEAR VLASOV-POISSON-FOKKER-PLANCK EQUATIONS

In this article, we establish the exponential time decay of smooth solutions around a global Maxwellian to the non-linear Vlasov–Poisson–Fokker–Planck equations in the whole space by uniform-in-time energy estimates. The non-linear coupling of macroscopic part and Fokker–Planck operator in the model brings new difficulties for the energy estimates, which is resolved by adding tailored weighted-in-v energy estimates suitable for the Fokker–Planck operator.

Mapping the dynamic degree of aeolian desertification in the Shiyang River Basin from 1975 to 2010

The Shiyang River Basin is an area of China that is severly affected by aeolian desertification.Thus,we established an aeolian desertified land classification system for visual interpretation,which classified the Aeolian Desertified Land(ADL)into Slight(SL),Moderate(M),Severe(S)and Extremely Severe(ES)according to the severity.Imagery of Landsat series(acquired in 1975,1990,2000 and 2010)were employed to monitor the status,trend and spatial pattern of aeolian desertification,especially to map the overall spatial pattern of ADL dynamics by proposing a new Dynamic Index(DI)in the Shiyang River Basin from 1975 to 2010.The results show a generally decreasing trend from 1975 to 2010.However,the ES ADL kept increasing throughout the whole study period.Moreover,the area of ADLs with different severity increased with increasing severity,this S and ES ADLs dominated characteristics of aeolian desertification was contrary to those sandy lands in eastern China where was dominated by SL and M ADLs.Among the three sub-periods of 1975−1990,1990−2000 and 2000−2010,the first two were the restoration stage,while the last one was the expansion stage of aeolian desertification.Moreover,all these new ADLs occurred in Minqin County during 2000−2010,indicating a detrimental increase of aeolian desertification in Minqin,and the concentration of ADLs toward the lower reaches of the Shiyang River Basin.The DI works well to identify areas with desertification changes no matter the sub-periods.Moreover,DI results disclosed a stable status of aeolian desertification,and the DI decreased with increasing ADL severity.These results indicate that it will be difficult to control the expansion of aeolian desertification in Minqin County over an extended period of time.Thus,we suggest effective and long-lasting aeolian desertification control programs in the Shiyang River Basin,especially in Minqin,and SL and MADLs should have priority in facilitating a quick reversal of aeolian desertification.

The Hydrodynamic Limit of Nonlinear Fokker-Planck Equation

The non-linear Fokker-Planck equation arises in describing the evolution of stochastic system, which is a variant of the Boltzmann equation modeling the evolution of the random system with Brownian motion, where the collision term is replaced by a drift-diffusion operator. This model conserves mass, momentum and energy;the dissipation is much weaker than that in a simplified model we considered before which conserved only mass, thus more difficult to analyze. The macro-micro decomposition of the solution around the local Maxwellian introduced by T.-P. Liu, T. Yang and S.-H. Yu for Boltzmann equation is used, to reformulate the model into a fluid-type system incorporate viscosity and heat diffusion terms, coupled with an equation of the microscopic part. The viscosity and heat diffusion terms can give dissipative mechanism for the analysis of the model.

Non-Maxwellian Kinetic Modelling of City Size Distribution

To extend the kinetic formulation of city size distribution introduced in [1], the non-Maxwellian kinetic modeling is introduced in the present study, in which a variable collision kernel is used in the underlying kinetic equation of Boltzmann type. By resorting to the well-known grazing asymptotic, a kinetic Fokker-Planck counterpart is obtained. The equilibrium of the Fokker-Planck equation belongs to the class of generalized Gamma distributions. Numerical test shows good fit of the generalized Gamma distribution with the city size distribution of China.

The utilization of chitosan/Bletilla striata hydrogels to elevate anti-adhesion,anti-inflammatory and pro-angiogenesis properties of polypropylene mesh in abdominal wall repair

Polypropylene(PP)mesh is commonly used in abdominal wall repair due to its ability to reduce the risk of organ damage,infections and other complications.However,the PP mesh often leads to adhesion formation and does not promote functional tissue repair.In this study,we synthesized one kind of aldehyde Bletilla striata polysaccharide(BSPA)modified chitosan(CS)hydrogel based on Schiff base reaction.The hydrogel exhibited a porous network structure,a highly hydrophilic surface and good biocompatibility.We wrapped the PP mesh inside the hydrogel and evaluated the performance of the resulting composites in a bilateral 1×1.5cm abdominal wall defect model in rats.The results of gross observation,histological staining and immunohistochemical staining demonstrated the positive impact of the CS hydrogel on anti-adhesion and wound healing effects.Notably,the addition of BSPA to the CS hydrogel further improved the performance of the composites in vivo,promoting wound healing by enhancing collagen deposition and capillary rearrangement.This study suggested that the BSPA-modified CS hydrogel significantly promoted the anti-adhesion,anti-inflammatory and pro-angiogenesis properties of PP meshes during the healing process.Overall,this work offers a novel approach to the design of abdominal wall repair patches.

洋中脊俯冲的动力学过程

洋中脊和俯冲带是两个端元的地质构造单元,分别代表离散型和汇聚型的板块边界.但是,二者并不是相互独立的,而是存在强烈的相互作用,如洋中脊以不同形式参与俯冲.我们总结了洋中脊参与俯冲的几种主要形式,即构造环境转变后的洋中脊反转俯冲,汇聚作用下洋中脊与其他构造单元在俯冲启动上的竞争关系,以及洋中脊随俯冲板块输入俯冲带;并概述了与之相关的地球动力学数值模拟,这些研究对理解洋中脊参与俯冲的动力学过程给出了新的认识.(1)在构造汇聚作用下,洋中脊可以反转俯冲;洋中脊的热结构和弱流变强度为俯冲启动提供了重要条件.消亡洋中脊随着温度扩散、强度增加,俯冲难度增大.(2)洋中脊反转俯冲的自然实例相对较少,可能的原因是,与其他洋内及陆缘构造单元(如大洋拆离断层、裂谷型陆缘等)存在竞争关系.模拟揭示了洋中脊与洋内及陆缘构造单元的俯冲竞争关系,并定量阐述了重要物理参数的控制作用.(3)没有形成俯冲带的洋中脊,一个重要归宿是随俯冲板块一并输入到俯冲带.其中,近平行输入和垂直输入是两种端元模式,二者都会影响俯冲过程.洋中脊近平行输入到俯冲带的过程可以用二维模型近似模拟,模拟结果揭示了洋中脊的输入会导致俯冲板块在海沟附近和在板内断离两种形式.洋中脊垂直输入俯冲带可能会导致俯冲板块撕裂并形成板块窗,其动力学过程需要用三维模型系统检验.除了上述介绍的几种洋中脊俯冲过程,更多的洋中脊俯冲模式(如洋中脊倾斜输入俯冲带,洋中脊与转换断层竞争下的俯冲启动)仍需进一步探讨.

CRA-40/Atmosphere—The First-Generation Chinese Atmospheric Reanalysis(1979–2018):System Description and Performance Evaluation

Atmospheric reanalysis reproduces the past atmospheric conditions through assimilation of historical meteorological observations with fixed version of a numerical weather prediction(NWP)model and data assimilation(DA)system.It is widely used in weather,climate,and even business-related research and applications.This paper reports the development of CMA’s first-generation global atmospheric reanalysis(RA)covering 1979–2018(CRA-40;CRA refers to CMA-RA).CRA-40 is produced by using the Global Spectral Model(GSM)/Gridpoint Statistical Interpolation(GSI)at a 6-h time interval and a TL574 spectral(34-km)resolution with the model top at 0.27 hPa.A large number of reprocessed satellite data and widely collected conventional observations were assimilated during the reanalyzing process,including the reprocessed atmospheric motion vector(AMV)products from FY-2C/D/E/G satellites,dense conventional observations(at about 120 radiosonde and 2400 synoptic stations)over China,as well as MWHS-2 and GNSS-RO observations from FY-3C.The reanalysis fitting to observations is improved over time,especially for surface pressure with root-mean-square error reduced from 1.05 hPa in 1979 to 0.8 hPa,and for upper air temperature from 1.65 K in 1979 to 1.35 K,in 2018.The patterns of global analysis increments for temperature,specific humidity,and zonal wind are consistent with the changes in the observing system.Near surface temperature from the model’s 6-h forecast reflects the global warming trend reasonably.The CRA-40 precipitation pattern matches well with those of GPCP and other reanalyses.CRA-40 also successfully captures the QBO and its vertical and temporal development,hemispherical atmospheric circulation change,and moisture transport by the East Asian summer monsoon.CRA is now operationally running in near real time as a climate data assimilation system in CMA.

Prevention strategies of postoperative adhesion in soft tissues by applying biomaterials:Based on the mechanisms of occurrence and development of adhesions

Postoperative adhesion(POA)widely occurs in soft tissues and usually leads to chronic pain,dysfunction of adjacent organs and some acute complications,seriously reducing patients’quality of life and even being life-threatening.Except for adhesiolysis,there are few effective methods to release existing adhesion.However,it requires a second operation and inpatient care and usually triggers recurrent adhesion in a great incidence.Hence,preventing POA formation has been regarded as the most effective clinical strategy.Biomaterials have attracted great attention in preventing POA because they can act as both barriers and drug carriers.Nevertheless,even though much reported research has been demonstrated their efficacy on POA inhibition to a certain extent,thoroughly preventing POA formation is still challenging.Meanwhile,most biomaterials for POA prevention were designed based on limited experiences,not a solid theoretical basis,showing blindness.Hence,we aimed to provide guidance for designing anti-adhesion materials applied in different soft tissues based on the mechanisms of POA occurrence and development.We first classified the postoperative adhesions into four categories according to the different components of diverse adhesion tissues,and named them as“membranous adhesion”,“vascular adhesion”,“adhesive adhesion”and“scarred adhesion”,respectively.Then,the process of the occurrence and development of POA were analyzed,and the main influencing factors in different stages were clarified.Further,we proposed seven strategies for POA prevention by using biomaterials according to these influencing factors.Meanwhile,the relevant practices were summarized according to the corresponding strategies and the future perspectives were analyzed.

Towards reliable assessment of hydrogen oxidation electrocatalysts for anion-exchange membrane fuel cells

Recent advancement of proton exchange membrane fuel cells has led to commercial sales of fuel-cell cars but market barrier exists because this technology heavily relies on platinum catalyst.Given the permission of adopting platinum-group-metal-free catalysts,anion-exchange membrane fuel cell has received notable attention.However,the sluggish kinetics of anodic hydrogen oxidation reaction(HOR)largely limit the cell efficiency.Although many high-performance HOR catalysts have been reported,there are analytical uncertainties in the literature concerning the assessment of the catalyst activity.Here we determine the origin of false HOR currents in the recorded polarization curves and propose a rigorous approach to eliminate them.We unveil experimentally the uncertainties of obtaining exchange current densities(j0)using Tafel plot from Bulter–Volmer equation and recommend employing the micro-polarization region method.For bulky catalysts that cannot establish a well-defined diffusion layer,we suggest applying external stirring bar to offer certain level of enforced convection and using j0 to compare the activity.

Laser capture microdissection for biomedical research: towards high-throughput, multi-omics, and single-cell resolution

Spatial omics technologies have become powerful methods to provide valuable insights into cells and tissues within a complex context,significantly enhancing our understanding of the intricate and multifaceted biological system.With an increasing focus on spatial heterogeneity,there is a growing need for unbiased,spatially resolved omics technologies.Laser capture microdissection(LCM)is a cutting-edge method for acquiring spatial information that can quickly collect regions of interest(ROIs)from heterogeneous tissues,with resolutions ranging from single cells to cell populations.Thus,LCM has been widely used for studying the cellular and molecular mechanisms of diseases.This review focuses on the differences among four types of commonly used LCM technologies and their applications in omics and disease research.Key attributes of application cases are also highlighted,such as throughput and spatial resolution.In addition,we comprehensively discuss the existing challenges and the great potential of LCM in biomedical research,disease diagnosis,and targeted therapy from the perspective of high-throughput,multi-omics,and single-cell resolution.