INTRODUCTION OF THE HIGH THROUGHPUT SCREENING SYSTEM

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.

Design and Research of High-throughput Automation System for Food Testing Laboratory

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.

Design and Development of a High-Throughput System for Learning and Memory Research on Zebrafish

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.

HIGH THROUGHPUT DRILLING OF TITANIUM ALLOYS

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.

High Throughput Sequencing of circRNAs in Tomato Leaves Responding to Multiple Stresses of Drought and Heat

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.

Discovery of natural products capable of inducing porcine host defense peptide gene expression using cell-based high throughput screening

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.

High throughput screening of single atomic catalysts with optimized local structures for the electrochemical oxygen reduction by machine learning

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.

A High-affinity Activator of G551D-CFTR Chloride Channel Identified By High Throughput Screening

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.

Self-encoding Functional Resin Applying for Combinatorial Chemistry and High Throughput Screening

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.

A Class of High-affinity Bicyclooctane G551D-CFTR Activators Identified by High Throughput Screening

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.

Carrier and magnetism engineering for monolayer SnS_(2) by high throughput first-principles calculations

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.

3D spiral channels combined with flexible micro-sieve for high-throughput rare tumor cell enrichment and assay from clinical pleural effusion samples

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.

Controllable and high-throughput preparation of microdroplet using an ultra-high speed rotating packed bed

Microdroplets and their dispersion,with a large specific surface area and a short diffusion distance,have been applied in various unit operations and reaction processes.However,it is still a challenge to control the size and size distribution of microdroplets,especially for high-throughput generation.In this work,a novel ultra-high speed rotating packed bed(UHS-RPB)was invented,in which rotating foam packing with a speed of 4000-12000 r·min^(-1) provides microfluidic channels to disperse liquid into microdroplets with high throughput.Then generated microdroplets can be directly dispersed into a continuous falling film for obtaining a mixture of microdroplet dispersion.In this UHS-RPB,the effects of rotational speed,liquid initial velocity,liquid viscosity,liquid surface tension and packing pore size on the average size(d_(32))and size distribution of microdroplets were systematically investigated.Results showed that the UHS-RPB could produce microdroplets with a d_(32) of 25-63μm at a liquid flow rate of 1025 L·h^(-1),and the size distribution of the microdroplets accords well with Rosin-Rammler distribution model.In addi-tion,a correlation was established for the prediction of d_(32),and the predicted d_(32) was in good agreement with the experimental data with a deviation within±15%.These results demonstrated that UHS-RPB could be a promising candidate for controllable preparation of uniform microdroplets.

Design of Raptor-Like LDPC Codes and High Throughput Decoder Towards 100 Gbit/s Throughput

This paper proposes a raptor-like low-density parity-check(RL-LDPC)code design together with the corresponding decoder hardware architecture aiming at next-generation mobile communication.A new kind of protograph different from the 5G new radio(NR)LDPC basic matrix is presented,and a code construction algorithm is proposed to improve the error-correcting performance.A multi-core layered decoder architecture that supports up to 100 Gbit/s throughput is designed based on the special protograph structure.

High-Throughput Growth of Hexagonal Boron Nitride Film Using Porous-Structure Isolation Layer

Chemical vapor deposition is considered as the most hopeful method for the synthesis of large-area high-quality hexagonal boron nitride on the substrate of catalytic metal. However, the size the hexagonal boron nitride films are limited to the size of growth chamber, which indicates a lower production efficiency. In this paper, the utilization efficiency of growth chamber is highly improved by alternately stacking multiple pieces of Cu foils and carbon fiber surface felt with porous structure. Uniform and continuous hexagonal boron nitride films are prepared on Cu foils through chemical vapor deposition utilizing ammonia borane as the precursor. This work develops a simple and practicable method for high-throughput preparation of hexagonal boron nitride films, which could contribute to the industrial application of hexagonal boron nitride. .

High performance receiving and processing technology in satellite beam hopping communication

Beam-hopping technology has become one of the major research hotspots for satellite communication in order to enhance their communication capacity and flexibility.However,beam hopping causes the traditional continuous time-division multiplexing signal in the forward downlink to become a burst signal,satellite terminal receivers need to solve multiple key issues such as burst signal rapid synchronization and high-per-formance reception.Firstly,this paper analyzes the key issues of burst communication for traffic signals in beam hopping sys-tems,and then compares and studies typical carrier synchro-nization algorithms for burst signals.Secondly,combining the requirements of beam-hopping communication systems for effi-cient burst and low signal-to-noise ratio reception of downlink signals in forward links,a decoding assisted bidirectional vari-able parameter iterative carrier synchronization technique is pro-posed,which introduces the idea of iterative processing into car-rier synchronization.Aiming at the technical characteristics of communication signal carrier synchronization,a new technical approach of bidirectional variable parameter iteration is adopted,breaking through the traditional understanding that loop struc-tures cannot adapt to low signal-to-noise ratio burst demodula-tion.Finally,combining the DVB-S2X standard physical layer frame format used in high throughput satellite communication systems,the research and performance simulation are con-ducted.The results show that the new technology proposed in this paper can significantly shorten the carrier synchronization time of burst signals,achieve fast synchronization of low signal-to-noise ratio burst signals,and have the unique advantage of flexible and adjustable parameters.

A machine learning accelerated distributed task management system(Malac-Distmas)and its application in high-throughput CALPHAD computation aiming at efficient alloy design

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.

Dynamic microphysiological system chip platform for high-throughput,customizable,and multi-dimensional drug screening

Spheroids and organoids have attracted significant attention as innovative models for disease modeling and drug screening.By employing diverse types of spheroids or organoids,it is feasible to establish microphysiological systems that enhance the precision of disease modeling and offer more dependable and comprehensive drug screening.High-throughput microphysiological systems that support optional,parallel testing of multiple drugs have promising applications in personalized medical treatment and drug research.However,establishing such a system is highly challenging and requires a multidisciplinary approach.This study introduces a dynamic Microphysiological System Chip Platform(MSCP)with multiple functional microstructures that encompass the mentioned advantages.We developed a high-throughput lung cancer spheroids model and an intestine-liverheart-lung cancer microphysiological system for conducting parallel testing on four anti-lung cancer drugs,demonstrating the feasibility of the MSCP.This microphysiological system combines microscale and macroscale biomimetics to enable a comprehensive assessment of drug efficacy and side effects.Moreover,the microphysiological system enables evaluation of the real pharmacological effect of drug molecules reaching the target lesion after absorption by normal organs through fluid-based physiological communication.The MSCP could serves as a valuable platform for microphysiological system research,making significant contributions to disease modeling,drug development,and personalized medical treatment.

Hepatitis C Virus Experimental Model Systems and Antiviral drug Research

An estimated 130 million people worldwide are chronically infected with hepatitis C virus (HCV) making it a leading cause of liver disease worldwide. Because the currently available therapy of pegylated interferon-alpha and ribavirin is only effective in a subset of patients, the development of new HCV antivirals is a healthcare imperative. This review discusses the experimental models available for HCV antiviral drug research, recent advances in HCV antiviral drug development, as well as active research being pursued to facilitate development of new HCV-specific therapeutics.

Drug discovery from traditional Chinese herbal medicine using high content imaging technology

Traditional Chinese medicine(TCM) has been widely used in China and other Asia countries for thousands of years to treat or prevent human diseases. Chinese herbal medicine, one of the most important components of TCM, has unique diversities in chemical components, and thus results in a wide range of biological activities. However, pharmaceutical industry is facing a major challenge to develop a large population of novel natural products and drugs, and considerable efforts have not resulted in highvolume of novel drug discovery and productivity. At present, increasing attention has been paid to Chinese herb medicine modernization in combination with the cutting-age technologies of drug discovery, especially the high throughput selection. High content imaging is an image-based high throughput screening method by using automated microscopy and image analysis software to capture and analyze phenotypes at a large scale to investigate multiple biological features simultaneously in the biological complex. Here, we described the pipeline of the state-of-the-art high content imaging technology, summarized the applications of the high content imaging technology in drug discovery from traditional Chinese herbal medicine, and finally discussed the current challenges and future perspectives for development of high throughput image-based screening technology in novel drug research and discovery.