Background Early embryo development plays a pivotal role in determining pregnancy outcomes,postnatal development,and lifelong health.Therefore,the strategic selection of functional nutrients to enhance embryo developm...Background Early embryo development plays a pivotal role in determining pregnancy outcomes,postnatal development,and lifelong health.Therefore,the strategic selection of functional nutrients to enhance embryo development is of paramount importance.In this study,we established a stable porcine trophectoderm cell line expressing dual fluorescent reporter genes driven by the CDX2 and TEAD4 gene promoter segments using lentiviral transfection.Results Three amino acid metabolites—kynurenic acid,taurine,and tryptamine—met the minimum z-score criteria of 2.0 for both luciferase and Renilla luciferase activities and were initially identified as potential metabolites for embryo development,with their beneficial effects validated by qPCR.Given that the identified metabolites are closely related to methionine,arginine,and tryptophan,we selected these three amino acids,using lysine as a standard,and employed response surface methodology combined with our high-throughput screening cell model to efficiently screen and optimize amino acid combination conducive to early embryo development.The optimized candidate amino acid system included lysine(1.87 mmol/L),methionine(0.82 mmol/L),tryptophan(0.23 mmol/L),and arginine(3 mmol/L),with the ratio of 1:0.43:0.12:1.60.In vitro experiments confirmed that this amino acid system enhances the expression of key genes involved in early embryonic development and improves in vitro embryo adhesion.Transcriptomic analysis of blastocysts suggested that candidate amino acid system enhances early embryo development by regulating early embryonic cell cycle and differentiation,as well as improving nutrient absorption.Furthermore,based on response surface methodology,400 sows were used to verify this amino acid system,substituting arginine with the more cost-effective N-carbamoyl glutamate(NCG),a precursor of arginine.The optimal dietary amino acid requirement was predicted to be 0.71%lysine,0.32%methionine,0.22%tryptophan,and 0.10%NCG for sows during early gestation.The optimized amino acid system ratio of the feed,derived from the peripheral release of essential amino acids,was found to be 1:0.45:0.13,which is largely consistent with the results obtained from the cell model optimization.Subsequently,we furtherly verified that this optimal dietary amino acid system significantly increased total litter size,live litter size and litter weight in sows.Conclusions In summary,we successfully established a dual-fluorescent high-throughput screening cell model for the efficient identification of potential nutrients that would promote embryo development and implantation.This innovative approach overcomes the limitations of traditional amino acid nutrition studies in sows,providing a more effective model for enhancing reproductive outcomes.展开更多
High-throughput calculations/simulations are the prerequisite for the efficient design of high-performance materials.In this paper,a machine learning accelerated distributed task management system(Malac-Distmas)was de...High-throughput calculations/simulations are the prerequisite for the efficient design of high-performance materials.In this paper,a machine learning accelerated distributed task management system(Malac-Distmas)was developed to realize the high-throughput calculations(HTCs)and storage of various data.The machine learning was embedded in Malac-Distmas to densify the output data,reduce the amount of calculation and achieve the acceleration of high-throughput calculations.Based on the Malac-Distmas coupling with CALPHAD software,HTCs of thermodynamics,kinetics,and thermophysical properties,including Gibbs free energy,phase diagram,Scheil-Gulliver solidification simulation,thermodynamic properties,thermophysical properties,diffusion simulation,and precipitation simulation,have been performed for demonstration.Furthermore,it is highly anticipated that the Malac-Distmas can also be coupled with any calculation/simulation software/code,which provides a console model to achieve different types of HTCs for efficient alloy design.展开更多
Highly toxic phosgene,diethyl chlorophosphate(DCP)and volatile acyl chlorides endanger our life and public security.To achieve facile sensing and discrimination of multiple target analytes,herein,we presented a single...Highly toxic phosgene,diethyl chlorophosphate(DCP)and volatile acyl chlorides endanger our life and public security.To achieve facile sensing and discrimination of multiple target analytes,herein,we presented a single fluorescent probe(BDP-CHD)for high-throughput screening of phosgene,DCP and volatile acyl chlorides.The probe underwent a covalent cascade reaction with phosgene to form boron dipyrromethene(BODIPY)with bright green fluorescence.By contrast,DCP,diphosgene and acyl chlorides can covalently assembled with the probe,giving rise to strong blue fluorescence.The probe has demonstrated high-throughput detection capability,high sensitivity,fast response(within 3 s)and parts per trillion(ppt)level detection limit.Furthermore,a portable platform based on BDP-CHD was constructed,which has achieved high-throughput discrimination of 16 analytes through linear discriminant analysis(LDA).Moreover,a smartphone adaptable RGB recognition pattern was established for the quantitative detection of multi-analytes.Therefore,this portable fluorescence sensing platform can serve as a versatile tool for rapid and high-throughput detection of toxic phosgene,DCP and volatile acyl chlorides.The proposed“one for more”strategy simplifies multi-target discrimination procedures and holds great promise for various sensing applications.展开更多
To accomplish on-site separation, preconcentration and cold storage of highly volatile organic compounds(VOCs) from water samples as well as their rapid transportation to laboratory, a high-throughput miniaturized pur...To accomplish on-site separation, preconcentration and cold storage of highly volatile organic compounds(VOCs) from water samples as well as their rapid transportation to laboratory, a high-throughput miniaturized purge-and-trap(μP&T) device integrating semiconductor refrigeration storage was developed in this work. Water samples were poured into the purge vessels and purged with purified air generated by an air pump. The VOCs in water samples were then separated and preconcentrated with sorbent tubes. After their complete separation and preconcentration, the tubes were subsequently preserved in the semiconductor refrigeration unit of the μP&T device. Notably, the high integration, small size, light weight, and low power consumption of the device makes it easy to be hand-carried to the field and transport by drone from remote locations, significantly enhancing the flexibility of field sampling. The performances of the device were evaluated by comparing analytical figures of merit for the detection of four cyclic volatile methylsiloxanes(cVMSs) in water. Compared to conventional collection and preservation methods, our proposed device preserved the VOCs more consistently in the sorbent tubes, with less than 5% loss of all analytes, and maintained stability for at least 20 days at 4℃. As a proof-of-concept,10 municipal wastewater samples were pretreated using this device with recoveries ranging from 82.5% to 99.9% for the target VOCs.展开更多
Metal 3D printing holds great promise for future digitalized manufacturing.However,the intricate interplay between laser and metal powders poses a significant challenge for conventional trial-and-error optimization.Me...Metal 3D printing holds great promise for future digitalized manufacturing.However,the intricate interplay between laser and metal powders poses a significant challenge for conventional trial-and-error optimization.Meanwhile,the“optimized”yet fixed parameters largely limit possible extensions to new designs and materials.Herein,we report a high throughput design coupled with machine learning(ML)guidance to eliminate the notorious cracks and porosities in metal 3D printing for improved corrosion resistance and overall performance.The high throughput methodologies are mostly on obtaining the printed samples and their structural and physical properties,while ML is used for data analysis by model building for prediction(optimization),and understanding.For 316L stainless steel,we concurrently printed 54 samples with different parameters and subjected them to parallel tests to generate an extensive dataset for ML analysis.An ensemble learning model outperformed the other five single learners while Bayesian active learning recommended optimal parameters that could reduce porosity from 0.57%to below 0.1%.Accordingly,the ML-recommended samples showed higher tensile strength(609.28 MPa)and elongation(50.67%),superior anti-corrosion(I_(corr)=4.17×10^(-8) A·cm^(-2)),and stable alkaline oxygen evolution for>100 hours(at 500 mA·cm^(-2)).Remarkably,through the correlation analysis of printing parameters and targeted properties,we find that the influence of hardness on corrosion resistance is second only to porosity.We then expedited optimization in AlSi7Mg using the learned knowledge and feed hardness and relative density,thus demonstrating the method’s general extensibility and efficiency.Our strategy can significantly accelerate the optimization of metal 3D printing and facilitate adaptable design to accommodate diverse materials and requirements.展开更多
Amphiphiles,including surfactants,have emerged as indispensable elements in materials science and pharmaceutical science,and their functions are highly relying on the critical micelle concentration(CMC)[1,2].Numerous ...Amphiphiles,including surfactants,have emerged as indispensable elements in materials science and pharmaceutical science,and their functions are highly relying on the critical micelle concentration(CMC)[1,2].Numerous fluorimetry-based probes have been developed to measure CMCs[3](Fig.S1).However,CMC measurements using these probes suffer from a time-consuming and laborious procedure and large uncertainties,primarily due to their poor photo-stabilities and highly fluctuating fluorescence backgrounds.展开更多
In this article, we introduce the system of high throughput screening (HTS). Its role in new drug study and current development is described. The relationship between research achievements of genome study and new type...In this article, we introduce the system of high throughput screening (HTS). Its role in new drug study and current development is described. The relationship between research achievements of genome study and new type screening model of new drugs is emphasized. The personal opinions of current problems about HTS study in China are raised.展开更多
In the process of food testing,human operation is an important variable affecting the experimental results.In order to reasonably avoid the influence of human subjective operation behavior on the accuracy of detection...In the process of food testing,human operation is an important variable affecting the experimental results.In order to reasonably avoid the influence of human subjective operation behavior on the accuracy of detection results,the laboratory information management system was used as the information platform to design a high-throughput laboratory automation pre-treatment system based on the deep integration of mechanical principles,visual analysis,high-speed conduction,intelligent storage and other technical systems.The experimental results showed that the system could shorten the sample circulation cycle,effectively improve the laboratory biosafety,and meet the requirements of high-throughput processing of samples.展开更多
Background: Since 2004, zebrafish have become the state-of-the-art, in vivo model for biomedical research due to their genetic and physiological homology with humans, inexpensive high-quantity breeding, and quick deve...Background: Since 2004, zebrafish have become the state-of-the-art, in vivo model for biomedical research due to their genetic and physiological homology with humans, inexpensive high-quantity breeding, and quick development in a highly-controlled environment suitable for longitudinal studies. New Method: To fully utilize the zebrafish model, a novel, automated, high-throughput system was designed. Shoals of five zebrafish were placed in 16 tanks and automatically fed over two days for a total of 16 training sessions. Color LED lights were used as the stimulus for each shoal coinciding with the release of food for a duration of 20 seconds. This system was tested on two age groups: 6- and 11-month-old. Results: After three training sessions, the median height of the school in the tank during stimulus was significantly higher than that of the naïve fish during the first training session. All subsequent training sessions demonstrated similar behaviour. A decline in memory retention, as defined by a reduction in the median height during light stimulus (i.e. no simultaneous food delivery), was observed 8 days post training. Comparison with existing methods: The high-throughput nature of this system allows for simultaneous training of 16 tanks of fish under identical conditions without human interaction and provides a means to rapidly assess their learning and memory behaviours. Conclusion: Results provide a baseline for understanding the normal cognitive processes of learning and memory retention in zebrafish. This work paves the way for future studies on the impacts of therapeutic agents on these cognitive processes.展开更多
The experiments of high throughput drilling of Ti-6Al-4V at 183 m/min cutting speed and 156 mm^3/s material removal rate using a 4 mm diameter WC-Co spiral point drill are conducted. At this material removal rate, it ...The experiments of high throughput drilling of Ti-6Al-4V at 183 m/min cutting speed and 156 mm^3/s material removal rate using a 4 mm diameter WC-Co spiral point drill are conducted. At this material removal rate, it took only 0.57 s to drill a hole in a 6.35 mm thick Ti plate. Supplying the cutting fluid via through-the-drill holes and the balance of cutting speed and feed have proven to be critical for drill life. An inverse heat transfer model is developed to predict the heat flux and the drill temperature distribution in drilling. A three-dimensional finite element modeling of drilling is con-ducted to predict the thrust force and torque. Experimental result demonstrates that, using proper machining process parameters, tool geometry, and fine-grained WC-Co tool material, the high throughput machining of Ti alloy is technically feasible.展开更多
Background:In-feed antibiotics are being phased out in livestock production worldwide.Alternatives to antibiotics are urgently needed to maintain animal health and production performance.Host defense peptides(HDPs)are...Background:In-feed antibiotics are being phased out in livestock production worldwide.Alternatives to antibiotics are urgently needed to maintain animal health and production performance.Host defense peptides(HDPs)are known for their broad-spectrum antimicrobial and immunomodulatory capabilities.Enhancing the synthesis of endogenous HDPs represents a promising antibiotic alternative strategy to disease control and prevention.Methods:To identify natural products with an ability to stimulate the synthesis of endogenous HDPs,we performed a high-throughput screening of 1261 natural products using a newly-established stable luciferase reporter cell line known as IPEC-J2/pBD3-luc.The ability of the hit compounds to induce HDP genes in porcine IPEC-J2 intestinal epithelial cells,3D4/31 macrophages,and jejunal explants were verified using RT-qPCR.Augmentation of the antibacterial activity of porcine 3D4/31 macrophages against a Gram-negative bacterium(enterotoxigenic E.coli)and a Gram-positive bacterium(Staphylococcus aureus)were further confirmed with four selected HDP-inducing compounds.Results:A total of 48 natural products with a minimum Z-score of 2.0 were identified after high-throughput screening,with 21 compounds giving at least 2-fold increase in luciferase activity in a follow-up dose-response experiment.Xanthohumol and deoxyshikonin were further found to be the most potent in inducing pBD3 mRNA expression,showing a minimum 10-fold increase in IPEC-J2,3D4/31 cells,and jejunal explants.Other compounds such as isorhapontigenin and calycosin also enhanced pBD3 mRNA expression by at least 10-fold in both IPEC-J2 cells and jejunal explants,but not 3D4/31 cells.In addition to pBD3,other porcine HDP genes such as pBD2,PG1-5,and pEP2C were induced to different magnitudes by xanthohumol,deoxyshikonin,isorhapontigenin,and calycosin,although clear gene-and cell type-specific patterns of regulation were observed.Desirably,these four compounds had a minimum effect on the expression of several representative inflammatory cytokine genes.Furthermore,when used at HDP-inducing concentrations,these compounds showed no obvious direct antibacterial activity,but significantly augmented the antibacterial activity of 3D4/31 macrophages(P<0.05)against both Gram-negative and Gram-positive bacteria.Conclusions:Our results indicate that these newly-identified natural HDP-inducing compounds have the potential to be developed as novel alternatives to antibiotics for prophylactic and therapeutic treatment of infectious diseases in livestock production.展开更多
Our aim is to study the roles of a new emerging group of non-coding RNAs, circRNAs, in tomato(Solanum lycopersicum L.) plants grown at the combination of drought and heat, two of the most usual stress conditions known...Our aim is to study the roles of a new emerging group of non-coding RNAs, circRNAs, in tomato(Solanum lycopersicum L.) plants grown at the combination of drought and heat, two of the most usual stress conditions known to frequently happen in field. Tomato seedlings from cultivar‘Jinling Meiyu’ were treated without stresses(control), at water shortage, high temperature and subjected the multiple stresses. In total, 467 circRNAs were identified with 87.82% from exon using high throughput sequencing technology. Among the circRNAs, 70 were from chr1 with the range from 23 to 49 from the other chromosomes. In detail, 156 circRNAs were shared in the four libraries, while 21, 17 and 36 circRNAs were only shown in drought, heat and multiple stresses libraries, respectively. Through a differential expression analysis, four, seven and nine circRNAs were differentially regulated in tomato at drought, heat and multiple stresses as compared with control. These circRNAs played roles on photosynthesis, starch and sucrose metabolism, RNA transport, RNA degradation, spliceosome, ribosome, etc. Our study underlined the potential role of circRNAs involved in the abiotic stress response in tomato, which might pave the way for studying biological roles of circRNAs responding to multiple stresses in plants.展开更多
Single atomic catalysts(SACs),especially metal-nitrogen doped carbon(M-NC)catalysts,have been extensively explored for the electrochemical oxygen reduction reaction(ORR),owing to their high activity and atomic utiliza...Single atomic catalysts(SACs),especially metal-nitrogen doped carbon(M-NC)catalysts,have been extensively explored for the electrochemical oxygen reduction reaction(ORR),owing to their high activity and atomic utilization efficiency.However,there is still a lack of systematic screening and optimization of local structures surrounding active centers of SACs for ORR as the local coordination has an essential impact on their electronic structures and catalytic performance.Herein,we systematic study the ORR catalytic performance of M-NC SACs with different central metals and environmental atoms in the first and second coordination sphere by using density functional theory(DFT)calculation and machine learning(ML).The geometric and electronic informed overpotential model(GEIOM)based on random forest algorithm showed the highest accuracy,and its R^(2) and root mean square errors(RMSE)were 0.96 and 0.21,respectively.30 potential high-performance catalysts were screened out by GEIOM,and the RMSE of the predicted result was only 0.12 V.This work not only helps us fast screen high-performance catalysts,but also provides a low-cost way to improve the accuracy of ML models.展开更多
High throughput experimentation is employed to establish a ternary system with the compositional range of 30.8 mol.%-75.7 mol.%SiO_(2),16.6 mol.%-61.7 mol.%Yb_(2)O_(3),and 6.3 mol.%-4.1 moll.%Ho_(2)O_(3) through co-sp...High throughput experimentation is employed to establish a ternary system with the compositional range of 30.8 mol.%-75.7 mol.%SiO_(2),16.6 mol.%-61.7 mol.%Yb_(2)O_(3),and 6.3 mol.%-4.1 moll.%Ho_(2)O_(3) through co-sputtering deposition on one combinatorial material chip.Considering their application in advanced SiC_(f)/SiC CMC,the phase composition and mechanical properties of samples with various RE/Si ratios and Yb/Ho ratios are comprehensively investigated.Chemical stability and thermal expansion compatibility between SiC and RE silicates with different compositions are also validated.Optimized materials for the application of environmental barrier coating and interphase for SiC_(f)/SiC CMC are screened respectively according to the above trends and data.This work is a case study to establish a composition-property library for RE_(2)O_(3)-SiO_(2) compounds.It is inspired more complicated multicomponent RE silicates could be prepared and characterized by high throughput experimentation,accelerating the design and screening of promising optimal candidates.展开更多
A stably transfected CHO cell line coexpressing G551D-CFTR and iodide-sensitive yellow fluorescent protein mutant EYFP-H148Q-I152L was successfully established and used as assay model to identify small-molecule activa...A stably transfected CHO cell line coexpressing G551D-CFTR and iodide-sensitive yellow fluorescent protein mutant EYFP-H148Q-I152L was successfully established and used as assay model to identify small-molecule activators of G551D-CFTR chloride channel from 100000 diverse combinatorial compounds by high throughput screening on a customized Beckman robotic system. A bicyclooctane compound was identified to activate G551D-CFTR chloride channel with high-affinity(K d=1.8 μmol/L). The activity of the bicyclooctane compound is G551D-CFTR-specific, reversible and non-toxic. The G551D-CFTR activator may be useful as a tool to study the mutant G551D-CFTR chloride channel structure and transport properties and as a candidate drug to cure cystic fibrosis caused by G551D-CFTR mutation.展开更多
A novel solid phase organic synthesis resin was synthesized for combinatorial high-throughput screening,which based on FTIR spectra self-encoding functional resin technology. A new deconvolution strategy termed positi...A novel solid phase organic synthesis resin was synthesized for combinatorial high-throughput screening,which based on FTIR spectra self-encoding functional resin technology. A new deconvolution strategy termed position encoding deconvolution had illustrated and was compared with some popular combinatorial deconvolution strategies in efficiency and information content. The mimic high throughput screening of hexapeptide library successfully proved the applying of the self-encoding functional resin technology and the position encoding deconvolution strategy.展开更多
The glycine-to-aspartic acid missense mutation at the codon 551(G551D) of the cystic fibrosis transmembrane conductance regulator(CFTR) is one of the five most frequent cystic fibrosis(CF) mutations associated with a ...The glycine-to-aspartic acid missense mutation at the codon 551(G551D) of the cystic fibrosis transmembrane conductance regulator(CFTR) is one of the five most frequent cystic fibrosis(CF) mutations associated with a severe CF phenotype. To explore the feasibility of pharmacological correction of disrupted activation of CFTR chloride channel caused by G551D mutation, we developed a halide-sensitive fluorescence miniassay for G551D-CFTR in Fisher rat thyroid(FRT) epithelial cells for the discovery of novel activators of G551D-CFTR. A class of bicyclooctane small molecule compounds that efficiently stimulate G551D-CFTR chloride channel activity was identified by high throughput screening via the FRT cell-based assay. This class of compounds selectively activates G551D-CFTR with a high affinity, whereas little effect of the compounds on wildtype CFTR can be seen. The discovery of a class of bicyclooctane G551D-CFTR activators will permit the analysis of structure-activity relationship of the compounds to identify ideal leads for in vivo therapeutic studies.展开更多
Alphaviruses,which contain a variety of mosquito-borne pathogens,are important pathogens of emerging/reemerging infectious diseases and potential biological weapons.Currently,no specific antiviral drugs are available ...Alphaviruses,which contain a variety of mosquito-borne pathogens,are important pathogens of emerging/reemerging infectious diseases and potential biological weapons.Currently,no specific antiviral drugs are available for the treatment of alphaviruses infection.For most highly pathogenic alphaviruses are classified as risk group-3 agents,the requirement of biosafety level 3(BSL-3)facilities limits the live virus-based antiviral study.To facilitate the antiviral development of alphaviruses,we developed a high throughput screening(HTS)platform based on a recombinant Semliki Forest virus(SFV)which can be manipulated in BSL-2 laboratory.Using the reverse genetics approach,the recombinant SFV and SFV reporter virus expressing eGFP(SFV-eGFP)were successfully rescued.The SFV-eGFP reporter virus exhibited robust eGFP expression and remained relatively stable after four passages in BHK-21 cells.Using a broad-spectrum alphavirus inhibitor ribavirin,we demonstrated that the SFV-eGFP can be used as an effective tool for antiviral study.The SFV-eGFP reporter virus-based HTS assay in a 96-well format was then established and optimized with a robust Z0 score.A section of reference compounds that inhibit highly pathogenic alphaviruses were used to validate that the SFV-eGFP reporter virus-based HTS assay enables rapid screening of potent broad-spectrum inhibitors of alphaviruses.This assay provides a safe and convenient platform for antiviral study of alphaviruses.展开更多
Two-dimensional(2D)semiconducting tin disulfide(SnS_(2))has been widely used for optoelectronic applications.To functionalize SnS_(2) for extending its application,we investigate the stability,electronic and magnetic ...Two-dimensional(2D)semiconducting tin disulfide(SnS_(2))has been widely used for optoelectronic applications.To functionalize SnS_(2) for extending its application,we investigate the stability,electronic and magnetic properties of substitutional doping by high throughput first-principles calculations.There are a lot of elements that can be doped in monolayer SnS_(2).Nonmetal in group A can introduce p-type and n-type carriers,while most metals in group A can only lead to p-type doping.Not only 3d,but also 4d and 5d transition metals in groups VB to VⅢB9 can introduce magnetism in SnS_(2),which is potentially applicable for spintronics.This study provides a comprehensive view of functionalization of SnS_(2) by substitutional doping,which will guide further experimental realization.展开更多
The sieving and enrichment of rare tumor cells from large-volume pleural effusion(PE)samples is a promising technique for cell-based lung tumor diagnosis and drug tests,which features high throughput and recovery,puri...The sieving and enrichment of rare tumor cells from large-volume pleural effusion(PE)samples is a promising technique for cell-based lung tumor diagnosis and drug tests,which features high throughput and recovery,purification,as well as viability rates of rare target cells as the prerequisites for high sensitivity,specificity,and accuracy of tumor cell analysis.In this paper,we propose a three-dimensional(3 D)sieving method for rare tumor cell enrichment,which effectively eliminates the"dead zones"in traditional two-dimensional(2 D)cell filters with a dimension-raising strategy to satisfy the requirements mentioned above.The prototype device was combined with a funnel-shaped holder,a flexible micropore membrane in the middle,and a3 D spiral fluid channel covered on the membrane as a three-layer ice-creaming cone composite structure.Driven by gravity alone,the device performed as follows:(1)20-fold throughput compared with the 2 D commercial planee hich was up to 20 mL/min for a threefold dilution of whole blood sample;(2)high recovery rates of 84.5%±21%,86%±25%,83%±14%for 100,1000,and 10000 cells/mL,respectively,in 30 mL phosphate buffer saline(PBS)sample,and a 100%positive detection rate in the case of≤5 A549 cells in 1 mL PBS;(3)a typical purification rate of 85.5%±9.1%;and(4)a viability rate of>93%.In the demonstration application,this device effectively enriched rare target cells from large volumes(>25 mL)of clinical pleural effusions.The following results indicated that tumor cells were easy-to-discover in the enriched PE samples,and the proliferation capability of purified cells was(>4.6 times)significantly stronger than that of unprocessed cells in the subsequent 6-day culture.The above evaluation indicates that the proposed easily reproducible method for the effective execution of rare cell enrichments and assays is expected to become a practical technique for clinical cell-based tumor diagnosis.展开更多
基金supported by National Natural Science Foundation of China (32172747 and 32425052)
文摘Background Early embryo development plays a pivotal role in determining pregnancy outcomes,postnatal development,and lifelong health.Therefore,the strategic selection of functional nutrients to enhance embryo development is of paramount importance.In this study,we established a stable porcine trophectoderm cell line expressing dual fluorescent reporter genes driven by the CDX2 and TEAD4 gene promoter segments using lentiviral transfection.Results Three amino acid metabolites—kynurenic acid,taurine,and tryptamine—met the minimum z-score criteria of 2.0 for both luciferase and Renilla luciferase activities and were initially identified as potential metabolites for embryo development,with their beneficial effects validated by qPCR.Given that the identified metabolites are closely related to methionine,arginine,and tryptophan,we selected these three amino acids,using lysine as a standard,and employed response surface methodology combined with our high-throughput screening cell model to efficiently screen and optimize amino acid combination conducive to early embryo development.The optimized candidate amino acid system included lysine(1.87 mmol/L),methionine(0.82 mmol/L),tryptophan(0.23 mmol/L),and arginine(3 mmol/L),with the ratio of 1:0.43:0.12:1.60.In vitro experiments confirmed that this amino acid system enhances the expression of key genes involved in early embryonic development and improves in vitro embryo adhesion.Transcriptomic analysis of blastocysts suggested that candidate amino acid system enhances early embryo development by regulating early embryonic cell cycle and differentiation,as well as improving nutrient absorption.Furthermore,based on response surface methodology,400 sows were used to verify this amino acid system,substituting arginine with the more cost-effective N-carbamoyl glutamate(NCG),a precursor of arginine.The optimal dietary amino acid requirement was predicted to be 0.71%lysine,0.32%methionine,0.22%tryptophan,and 0.10%NCG for sows during early gestation.The optimized amino acid system ratio of the feed,derived from the peripheral release of essential amino acids,was found to be 1:0.45:0.13,which is largely consistent with the results obtained from the cell model optimization.Subsequently,we furtherly verified that this optimal dietary amino acid system significantly increased total litter size,live litter size and litter weight in sows.Conclusions In summary,we successfully established a dual-fluorescent high-throughput screening cell model for the efficient identification of potential nutrients that would promote embryo development and implantation.This innovative approach overcomes the limitations of traditional amino acid nutrition studies in sows,providing a more effective model for enhancing reproductive outcomes.
基金support from the Youth Talent Project of Innovation-driven Plan at Central South University(Grant No.2282019SYLB026)is greatly acknowledgedsupport from the Fundamental Research Funds for the Central Universities of Central South University(Grant No.2019zzts854).
文摘High-throughput calculations/simulations are the prerequisite for the efficient design of high-performance materials.In this paper,a machine learning accelerated distributed task management system(Malac-Distmas)was developed to realize the high-throughput calculations(HTCs)and storage of various data.The machine learning was embedded in Malac-Distmas to densify the output data,reduce the amount of calculation and achieve the acceleration of high-throughput calculations.Based on the Malac-Distmas coupling with CALPHAD software,HTCs of thermodynamics,kinetics,and thermophysical properties,including Gibbs free energy,phase diagram,Scheil-Gulliver solidification simulation,thermodynamic properties,thermophysical properties,diffusion simulation,and precipitation simulation,have been performed for demonstration.Furthermore,it is highly anticipated that the Malac-Distmas can also be coupled with any calculation/simulation software/code,which provides a console model to achieve different types of HTCs for efficient alloy design.
基金the financial support of the National Natural Science Foundation of China(No.22168009)。
文摘Highly toxic phosgene,diethyl chlorophosphate(DCP)and volatile acyl chlorides endanger our life and public security.To achieve facile sensing and discrimination of multiple target analytes,herein,we presented a single fluorescent probe(BDP-CHD)for high-throughput screening of phosgene,DCP and volatile acyl chlorides.The probe underwent a covalent cascade reaction with phosgene to form boron dipyrromethene(BODIPY)with bright green fluorescence.By contrast,DCP,diphosgene and acyl chlorides can covalently assembled with the probe,giving rise to strong blue fluorescence.The probe has demonstrated high-throughput detection capability,high sensitivity,fast response(within 3 s)and parts per trillion(ppt)level detection limit.Furthermore,a portable platform based on BDP-CHD was constructed,which has achieved high-throughput discrimination of 16 analytes through linear discriminant analysis(LDA).Moreover,a smartphone adaptable RGB recognition pattern was established for the quantitative detection of multi-analytes.Therefore,this portable fluorescence sensing platform can serve as a versatile tool for rapid and high-throughput detection of toxic phosgene,DCP and volatile acyl chlorides.The proposed“one for more”strategy simplifies multi-target discrimination procedures and holds great promise for various sensing applications.
基金the National Natural Science Foundation of China (No. 22306146)the PhD Scientific Research Startup Foundation of Xihua University (No. RX2200002003) for their financial support。
文摘To accomplish on-site separation, preconcentration and cold storage of highly volatile organic compounds(VOCs) from water samples as well as their rapid transportation to laboratory, a high-throughput miniaturized purge-and-trap(μP&T) device integrating semiconductor refrigeration storage was developed in this work. Water samples were poured into the purge vessels and purged with purified air generated by an air pump. The VOCs in water samples were then separated and preconcentrated with sorbent tubes. After their complete separation and preconcentration, the tubes were subsequently preserved in the semiconductor refrigeration unit of the μP&T device. Notably, the high integration, small size, light weight, and low power consumption of the device makes it easy to be hand-carried to the field and transport by drone from remote locations, significantly enhancing the flexibility of field sampling. The performances of the device were evaluated by comparing analytical figures of merit for the detection of four cyclic volatile methylsiloxanes(cVMSs) in water. Compared to conventional collection and preservation methods, our proposed device preserved the VOCs more consistently in the sorbent tubes, with less than 5% loss of all analytes, and maintained stability for at least 20 days at 4℃. As a proof-of-concept,10 municipal wastewater samples were pretreated using this device with recoveries ranging from 82.5% to 99.9% for the target VOCs.
基金sponsored by the National Key Research and Development Program of China(No.2023YFB4604800,2021YFA1202300)the Natural and Science Foundation of China(Grant Nos.52201041,52275331,52205358)+1 种基金the Key Research and Development Program of Hubei Province(Nos.2024BCB091,2022CFA031)the Hong Kong Scholars Program(No.XJ2022014)。
文摘Metal 3D printing holds great promise for future digitalized manufacturing.However,the intricate interplay between laser and metal powders poses a significant challenge for conventional trial-and-error optimization.Meanwhile,the“optimized”yet fixed parameters largely limit possible extensions to new designs and materials.Herein,we report a high throughput design coupled with machine learning(ML)guidance to eliminate the notorious cracks and porosities in metal 3D printing for improved corrosion resistance and overall performance.The high throughput methodologies are mostly on obtaining the printed samples and their structural and physical properties,while ML is used for data analysis by model building for prediction(optimization),and understanding.For 316L stainless steel,we concurrently printed 54 samples with different parameters and subjected them to parallel tests to generate an extensive dataset for ML analysis.An ensemble learning model outperformed the other five single learners while Bayesian active learning recommended optimal parameters that could reduce porosity from 0.57%to below 0.1%.Accordingly,the ML-recommended samples showed higher tensile strength(609.28 MPa)and elongation(50.67%),superior anti-corrosion(I_(corr)=4.17×10^(-8) A·cm^(-2)),and stable alkaline oxygen evolution for>100 hours(at 500 mA·cm^(-2)).Remarkably,through the correlation analysis of printing parameters and targeted properties,we find that the influence of hardness on corrosion resistance is second only to porosity.We then expedited optimization in AlSi7Mg using the learned knowledge and feed hardness and relative density,thus demonstrating the method’s general extensibility and efficiency.Our strategy can significantly accelerate the optimization of metal 3D printing and facilitate adaptable design to accommodate diverse materials and requirements.
基金supported by Shanghai Municipal Commission of Science and Technology,China(Grant No.:19XD1400300)the National Natural Science Foundation of China(Grant Nos.:821040821,82273867,and 82030107).
文摘Amphiphiles,including surfactants,have emerged as indispensable elements in materials science and pharmaceutical science,and their functions are highly relying on the critical micelle concentration(CMC)[1,2].Numerous fluorimetry-based probes have been developed to measure CMCs[3](Fig.S1).However,CMC measurements using these probes suffer from a time-consuming and laborious procedure and large uncertainties,primarily due to their poor photo-stabilities and highly fluctuating fluorescence backgrounds.
文摘In this article, we introduce the system of high throughput screening (HTS). Its role in new drug study and current development is described. The relationship between research achievements of genome study and new type screening model of new drugs is emphasized. The personal opinions of current problems about HTS study in China are raised.
文摘In the process of food testing,human operation is an important variable affecting the experimental results.In order to reasonably avoid the influence of human subjective operation behavior on the accuracy of detection results,the laboratory information management system was used as the information platform to design a high-throughput laboratory automation pre-treatment system based on the deep integration of mechanical principles,visual analysis,high-speed conduction,intelligent storage and other technical systems.The experimental results showed that the system could shorten the sample circulation cycle,effectively improve the laboratory biosafety,and meet the requirements of high-throughput processing of samples.
文摘Background: Since 2004, zebrafish have become the state-of-the-art, in vivo model for biomedical research due to their genetic and physiological homology with humans, inexpensive high-quantity breeding, and quick development in a highly-controlled environment suitable for longitudinal studies. New Method: To fully utilize the zebrafish model, a novel, automated, high-throughput system was designed. Shoals of five zebrafish were placed in 16 tanks and automatically fed over two days for a total of 16 training sessions. Color LED lights were used as the stimulus for each shoal coinciding with the release of food for a duration of 20 seconds. This system was tested on two age groups: 6- and 11-month-old. Results: After three training sessions, the median height of the school in the tank during stimulus was significantly higher than that of the naïve fish during the first training session. All subsequent training sessions demonstrated similar behaviour. A decline in memory retention, as defined by a reduction in the median height during light stimulus (i.e. no simultaneous food delivery), was observed 8 days post training. Comparison with existing methods: The high-throughput nature of this system allows for simultaneous training of 16 tanks of fish under identical conditions without human interaction and provides a means to rapidly assess their learning and memory behaviours. Conclusion: Results provide a baseline for understanding the normal cognitive processes of learning and memory retention in zebrafish. This work paves the way for future studies on the impacts of therapeutic agents on these cognitive processes.
基金Selected from Proceedings of the 7th International Conference on Frontiers of Design and Manufacturing (ICFDM’2006).
文摘The experiments of high throughput drilling of Ti-6Al-4V at 183 m/min cutting speed and 156 mm^3/s material removal rate using a 4 mm diameter WC-Co spiral point drill are conducted. At this material removal rate, it took only 0.57 s to drill a hole in a 6.35 mm thick Ti plate. Supplying the cutting fluid via through-the-drill holes and the balance of cutting speed and feed have proven to be critical for drill life. An inverse heat transfer model is developed to predict the heat flux and the drill temperature distribution in drilling. A three-dimensional finite element modeling of drilling is con-ducted to predict the thrust force and torque. Experimental result demonstrates that, using proper machining process parameters, tool geometry, and fine-grained WC-Co tool material, the high throughput machining of Ti alloy is technically feasible.
基金supported by the National Natural Science Foundation of China(31972576)the Beijing Natural Science Foundation(6202004)+2 种基金the Special Program on Science and Technology Innovation Capacity Building of BAAFS(KJCX20180414 and KJCX201914)the USDA National Institute of Food and Agriculture(2018-68003-27462 and 2018-33610-28252)the Oklahoma Center for the Advancement of Science and Technology(AR19-27)。
文摘Background:In-feed antibiotics are being phased out in livestock production worldwide.Alternatives to antibiotics are urgently needed to maintain animal health and production performance.Host defense peptides(HDPs)are known for their broad-spectrum antimicrobial and immunomodulatory capabilities.Enhancing the synthesis of endogenous HDPs represents a promising antibiotic alternative strategy to disease control and prevention.Methods:To identify natural products with an ability to stimulate the synthesis of endogenous HDPs,we performed a high-throughput screening of 1261 natural products using a newly-established stable luciferase reporter cell line known as IPEC-J2/pBD3-luc.The ability of the hit compounds to induce HDP genes in porcine IPEC-J2 intestinal epithelial cells,3D4/31 macrophages,and jejunal explants were verified using RT-qPCR.Augmentation of the antibacterial activity of porcine 3D4/31 macrophages against a Gram-negative bacterium(enterotoxigenic E.coli)and a Gram-positive bacterium(Staphylococcus aureus)were further confirmed with four selected HDP-inducing compounds.Results:A total of 48 natural products with a minimum Z-score of 2.0 were identified after high-throughput screening,with 21 compounds giving at least 2-fold increase in luciferase activity in a follow-up dose-response experiment.Xanthohumol and deoxyshikonin were further found to be the most potent in inducing pBD3 mRNA expression,showing a minimum 10-fold increase in IPEC-J2,3D4/31 cells,and jejunal explants.Other compounds such as isorhapontigenin and calycosin also enhanced pBD3 mRNA expression by at least 10-fold in both IPEC-J2 cells and jejunal explants,but not 3D4/31 cells.In addition to pBD3,other porcine HDP genes such as pBD2,PG1-5,and pEP2C were induced to different magnitudes by xanthohumol,deoxyshikonin,isorhapontigenin,and calycosin,although clear gene-and cell type-specific patterns of regulation were observed.Desirably,these four compounds had a minimum effect on the expression of several representative inflammatory cytokine genes.Furthermore,when used at HDP-inducing concentrations,these compounds showed no obvious direct antibacterial activity,but significantly augmented the antibacterial activity of 3D4/31 macrophages(P<0.05)against both Gram-negative and Gram-positive bacteria.Conclusions:Our results indicate that these newly-identified natural HDP-inducing compounds have the potential to be developed as novel alternatives to antibiotics for prophylactic and therapeutic treatment of infectious diseases in livestock production.
基金funding from National Natural Science Foundation of China (Grant No. 31601745)Natural Science Foundation of Jiangsu Province (Grant No. BK20160579)Aarhus University Research Foundation (Grant No. 30379)
文摘Our aim is to study the roles of a new emerging group of non-coding RNAs, circRNAs, in tomato(Solanum lycopersicum L.) plants grown at the combination of drought and heat, two of the most usual stress conditions known to frequently happen in field. Tomato seedlings from cultivar‘Jinling Meiyu’ were treated without stresses(control), at water shortage, high temperature and subjected the multiple stresses. In total, 467 circRNAs were identified with 87.82% from exon using high throughput sequencing technology. Among the circRNAs, 70 were from chr1 with the range from 23 to 49 from the other chromosomes. In detail, 156 circRNAs were shared in the four libraries, while 21, 17 and 36 circRNAs were only shown in drought, heat and multiple stresses libraries, respectively. Through a differential expression analysis, four, seven and nine circRNAs were differentially regulated in tomato at drought, heat and multiple stresses as compared with control. These circRNAs played roles on photosynthesis, starch and sucrose metabolism, RNA transport, RNA degradation, spliceosome, ribosome, etc. Our study underlined the potential role of circRNAs involved in the abiotic stress response in tomato, which might pave the way for studying biological roles of circRNAs responding to multiple stresses in plants.
基金financially supported by the National Key Research and Development Program of China (2018YFA0702002)the Beijing Natural Science Foundation (Z210016)the National Natural Science Foundation of China (21935001)。
文摘Single atomic catalysts(SACs),especially metal-nitrogen doped carbon(M-NC)catalysts,have been extensively explored for the electrochemical oxygen reduction reaction(ORR),owing to their high activity and atomic utilization efficiency.However,there is still a lack of systematic screening and optimization of local structures surrounding active centers of SACs for ORR as the local coordination has an essential impact on their electronic structures and catalytic performance.Herein,we systematic study the ORR catalytic performance of M-NC SACs with different central metals and environmental atoms in the first and second coordination sphere by using density functional theory(DFT)calculation and machine learning(ML).The geometric and electronic informed overpotential model(GEIOM)based on random forest algorithm showed the highest accuracy,and its R^(2) and root mean square errors(RMSE)were 0.96 and 0.21,respectively.30 potential high-performance catalysts were screened out by GEIOM,and the RMSE of the predicted result was only 0.12 V.This work not only helps us fast screen high-performance catalysts,but also provides a low-cost way to improve the accuracy of ML models.
基金supported by the National Natural Science Foun-dation of China under Grant Nos.U21A2063,52002376National Key R&D Program of China under Grant No.2021YFB3702300+1 种基金Key Research Program of the Chinese Academy of Sciences under Grant No.ZDRW-CN-2021-2-2LiaoNing Revitalization Talents Pro-gram under Grant No.XLYC2002018,Natural Science Foundation of Liaoning Province under Grant No.2020-MS-006.
文摘High throughput experimentation is employed to establish a ternary system with the compositional range of 30.8 mol.%-75.7 mol.%SiO_(2),16.6 mol.%-61.7 mol.%Yb_(2)O_(3),and 6.3 mol.%-4.1 moll.%Ho_(2)O_(3) through co-sputtering deposition on one combinatorial material chip.Considering their application in advanced SiC_(f)/SiC CMC,the phase composition and mechanical properties of samples with various RE/Si ratios and Yb/Ho ratios are comprehensively investigated.Chemical stability and thermal expansion compatibility between SiC and RE silicates with different compositions are also validated.Optimized materials for the application of environmental barrier coating and interphase for SiC_(f)/SiC CMC are screened respectively according to the above trends and data.This work is a case study to establish a composition-property library for RE_(2)O_(3)-SiO_(2) compounds.It is inspired more complicated multicomponent RE silicates could be prepared and characterized by high throughput experimentation,accelerating the design and screening of promising optimal candidates.
基金the Start- up Fund for Returned Overseas Scholars from Northeast Normal U niversity,National ScienceFund for Distinguished Young Scholars (No. 30 32 5 0 11) ,Distinguished Young Scholars Fund of Jilin Province(No.2 0 0 30 112 ) ,Excellent Young Teachers
文摘A stably transfected CHO cell line coexpressing G551D-CFTR and iodide-sensitive yellow fluorescent protein mutant EYFP-H148Q-I152L was successfully established and used as assay model to identify small-molecule activators of G551D-CFTR chloride channel from 100000 diverse combinatorial compounds by high throughput screening on a customized Beckman robotic system. A bicyclooctane compound was identified to activate G551D-CFTR chloride channel with high-affinity(K d=1.8 μmol/L). The activity of the bicyclooctane compound is G551D-CFTR-specific, reversible and non-toxic. The G551D-CFTR activator may be useful as a tool to study the mutant G551D-CFTR chloride channel structure and transport properties and as a candidate drug to cure cystic fibrosis caused by G551D-CFTR mutation.
文摘A novel solid phase organic synthesis resin was synthesized for combinatorial high-throughput screening,which based on FTIR spectra self-encoding functional resin technology. A new deconvolution strategy termed position encoding deconvolution had illustrated and was compared with some popular combinatorial deconvolution strategies in efficiency and information content. The mimic high throughput screening of hexapeptide library successfully proved the applying of the self-encoding functional resin technology and the position encoding deconvolution strategy.
基金the Start- up Fund for Returned Overseas Scholars from Northeast Normal U niversity,National ScienceFund for Distinguished Young Scholars(No.30 32 5 0 11) ,Distinguished Young Scholars Fund of Jilin Province(No.2 0 0 30 112 ) ,Excellent Young Teachers Pr
文摘The glycine-to-aspartic acid missense mutation at the codon 551(G551D) of the cystic fibrosis transmembrane conductance regulator(CFTR) is one of the five most frequent cystic fibrosis(CF) mutations associated with a severe CF phenotype. To explore the feasibility of pharmacological correction of disrupted activation of CFTR chloride channel caused by G551D mutation, we developed a halide-sensitive fluorescence miniassay for G551D-CFTR in Fisher rat thyroid(FRT) epithelial cells for the discovery of novel activators of G551D-CFTR. A class of bicyclooctane small molecule compounds that efficiently stimulate G551D-CFTR chloride channel activity was identified by high throughput screening via the FRT cell-based assay. This class of compounds selectively activates G551D-CFTR with a high affinity, whereas little effect of the compounds on wildtype CFTR can be seen. The discovery of a class of bicyclooctane G551D-CFTR activators will permit the analysis of structure-activity relationship of the compounds to identify ideal leads for in vivo therapeutic studies.
基金supported by the Creative Research Group Program of Natural Science Foundation of Hubei Province (2022CFA021)National Natural Science Foundation of China (81702005).
文摘Alphaviruses,which contain a variety of mosquito-borne pathogens,are important pathogens of emerging/reemerging infectious diseases and potential biological weapons.Currently,no specific antiviral drugs are available for the treatment of alphaviruses infection.For most highly pathogenic alphaviruses are classified as risk group-3 agents,the requirement of biosafety level 3(BSL-3)facilities limits the live virus-based antiviral study.To facilitate the antiviral development of alphaviruses,we developed a high throughput screening(HTS)platform based on a recombinant Semliki Forest virus(SFV)which can be manipulated in BSL-2 laboratory.Using the reverse genetics approach,the recombinant SFV and SFV reporter virus expressing eGFP(SFV-eGFP)were successfully rescued.The SFV-eGFP reporter virus exhibited robust eGFP expression and remained relatively stable after four passages in BHK-21 cells.Using a broad-spectrum alphavirus inhibitor ribavirin,we demonstrated that the SFV-eGFP can be used as an effective tool for antiviral study.The SFV-eGFP reporter virus-based HTS assay in a 96-well format was then established and optimized with a robust Z0 score.A section of reference compounds that inhibit highly pathogenic alphaviruses were used to validate that the SFV-eGFP reporter virus-based HTS assay enables rapid screening of potent broad-spectrum inhibitors of alphaviruses.This assay provides a safe and convenient platform for antiviral study of alphaviruses.
基金Project supported by the National Natural Science Foundation of China(Grant No.91833302).
文摘Two-dimensional(2D)semiconducting tin disulfide(SnS_(2))has been widely used for optoelectronic applications.To functionalize SnS_(2) for extending its application,we investigate the stability,electronic and magnetic properties of substitutional doping by high throughput first-principles calculations.There are a lot of elements that can be doped in monolayer SnS_(2).Nonmetal in group A can introduce p-type and n-type carriers,while most metals in group A can only lead to p-type doping.Not only 3d,but also 4d and 5d transition metals in groups VB to VⅢB9 can introduce magnetism in SnS_(2),which is potentially applicable for spintronics.This study provides a comprehensive view of functionalization of SnS_(2) by substitutional doping,which will guide further experimental realization.
基金supported by the National Key Research and Development Program of China(No.2018YFC2001100)the National Natural Science Foundation of China(Nos.61774167 and 61801477)+2 种基金the Instrument Development Program of the Chinese Academy of Sciences,Beijing Municipal Natural Science Foundation(Nos.4192062 and 4182072)Beijing Municipal Administration of Hospitals Incubating Program(No.PX2017050)Youth Innovation Promotion Association of Chinese Academy of Sciences。
文摘The sieving and enrichment of rare tumor cells from large-volume pleural effusion(PE)samples is a promising technique for cell-based lung tumor diagnosis and drug tests,which features high throughput and recovery,purification,as well as viability rates of rare target cells as the prerequisites for high sensitivity,specificity,and accuracy of tumor cell analysis.In this paper,we propose a three-dimensional(3 D)sieving method for rare tumor cell enrichment,which effectively eliminates the"dead zones"in traditional two-dimensional(2 D)cell filters with a dimension-raising strategy to satisfy the requirements mentioned above.The prototype device was combined with a funnel-shaped holder,a flexible micropore membrane in the middle,and a3 D spiral fluid channel covered on the membrane as a three-layer ice-creaming cone composite structure.Driven by gravity alone,the device performed as follows:(1)20-fold throughput compared with the 2 D commercial planee hich was up to 20 mL/min for a threefold dilution of whole blood sample;(2)high recovery rates of 84.5%±21%,86%±25%,83%±14%for 100,1000,and 10000 cells/mL,respectively,in 30 mL phosphate buffer saline(PBS)sample,and a 100%positive detection rate in the case of≤5 A549 cells in 1 mL PBS;(3)a typical purification rate of 85.5%±9.1%;and(4)a viability rate of>93%.In the demonstration application,this device effectively enriched rare target cells from large volumes(>25 mL)of clinical pleural effusions.The following results indicated that tumor cells were easy-to-discover in the enriched PE samples,and the proliferation capability of purified cells was(>4.6 times)significantly stronger than that of unprocessed cells in the subsequent 6-day culture.The above evaluation indicates that the proposed easily reproducible method for the effective execution of rare cell enrichments and assays is expected to become a practical technique for clinical cell-based tumor diagnosis.
