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420 results about "Chromatin" patented technology

Chromatin is a complex of DNA and protein found in eukaryotic cells. Its primary function is packaging very long DNA molecules into a more compact, denser shape, which prevents the strands from becoming tangled and plays important roles in reinforcing the DNA during cell division, preventing DNA damage, and regulating gene expression and DNA replication. During mitosis and meiosis, chromatin facilitates proper segregation of the chromosomes in anaphase; the characteristic shapes of chromosomes visible during this stage are the result of DNA being coiled into highly condensed networks of chromatin.

Compositions and methods for nucleic acid processing using blocking agents

Methods and systems for sample preparation techniques that prevent inhibition of reactions such as due to the presence of longer oligonucleotides are presented herein. The methods and systems provided herein allow amplification (e.g., whole genome amplification) and sequencing of chromatin accessible regions of single cells.
Owner:10X GENOMICS INC

Rice nitrogen response regulation network analysis and breeding target identification system and method based on multi-omics data

PendingCN120656539ABiostatisticsBiological modelsUpstream Transcription FactorRegulatory region
The invention discloses a rice nitrogen response regulation and control network analysis and breeding target identification system and method based on multi-omics data. According to the system, organic combination of regulation and control network construction based on single or multiple varieties of materials, key transcription factor recognition and accurate positioning of regulation and control areas where transcription factors play roles is achieved through an expression-chromatin accessibility correlation research method, and cis-trans effect distinguishing of the regulation and control areas is achieved through a deep learning model. The method comprises the following steps: carrying out nitrogen starvation pretreatment on rice, then carrying out nitrogen resupply, collecting a root sample, and carrying out ATAC-seq and RNA-seq sequencing; an eCAAS method is adopted to construct a regulation and control network, and key transcription factors are identified and accurately positioned; the chromatin accessibility difference of different varieties is predicted through a deep learning model, the cis-action effect and the trans-action effect are distinguished, an upstream transcription factor target is provided for genes dominated by the trans-effect, and haplotype and editable regulatory region targets available for direct breeding are provided for genes dominated by the cis-effect.
Owner:HUAZHONG AGRI UNIV

Method for identifying elncRNAs regulation target gene in single cell based on single cell ATAC-seq

PendingCN119580822ANatural language data processingSequence analysisImmune cell differentiationCell type
The invention relates to the technical field of bioinformatics, in particular to a method for identifying an elncRNAs regulation target gene in a single cell based on single cell ATAC-seq. According to the method provided by the invention, a regulatory network of an elncRNAs-target gene on a single cell whole genome is identified by utilizing chromatin co-accessibility based on scATAC-seq data. Meanwhile, the method is applied to immune cell differentiation, and the elncRNAs-target gene regulation dynamic state of immune cell differentiation is accurately recognized. In addition, the biological functions of the elncRNAs in different cell types are further analyzed. The method provided by the invention can help related researchers in the field of biomedicine to more elaborately and accurately predict the regulation effect and function of the elncRNAs under the single cell resolution.
Owner:宁尚伟 +3

Molecular marker for accurately positioning centromere of Chinese trumpet creeper chromosome

The invention relates to the technical field of biology, in particular to a molecular marker for accurately positioning centromere of chromosome of Chinese trumpet creeper, and the sequence of the molecular marker is as shown in SEQ ID NO.1 and SEQ ID NO.2. The method comprises the following steps: specifically enriching a DNA (Deoxyribose Nucleic Acid) sequence combined with a centromere specific histone CENH3 through a chromatin co-immunoprecipitation technology (ChIP), and sequencing the DNA sequence; sequencing data are analyzed to obtain a centromere sequence of the vicia villosa, and two specific repetitive sequences of the centromere of the vicia villosa are obtained after identification and optimization. Primers are designed according to the sequences, PCR amplification is carried out, amplification product sequences are marked, fluorescence in situ hybridization verification is carried out by analyzing a cytogenetics technology, it is proved that the primers are specifically distributed in a centromere area of vicia villosa, and the centromere specificity of the primers is proved. The marker can be used for genetic identification and accurate positioning of the centromere in genome research, and can also be used for cytological identification of the centromere and karyotype research such as chromosome counting and morphological analysis through centromere signal observation.
Owner:NANTONG UNIV

Single-cell multi-omics cell type annotation method based on distribution and knowledge alignment

The invention provides a single-cell multi-omics cell type annotation method based on distribution and knowledge alignment, and belongs to the technical field of single-cell type annotation, the method comprises the following steps: obtaining single-cell transcriptome data and single-cell chromatin accessibility sequencing data, and pre-training and training a multi-omics variation auto-encoder model, the multi-omics variational auto-encoder model is combined with a variational auto-encoder and a knowledge distillation technology, and multi-omics single cell data is integrated and annotated through distribution and knowledge alignment. And performing cell type prediction on the single cell transcriptome data and the single cell chromatin accessibility sequencing data which are input at the same time by using the trained multi-omics variational auto-encoder model. According to the method, the problem of limitation of a method only depending on single omics is solved, the synergistic effect between the omics is enhanced, the accuracy of annotation is improved, and the calculation overhead is reduced through knowledge distillation.
Owner:CHENGDU UNIV OF INFORMATION TECH

Multi-omics analysis method and device, electronic equipment and storage medium

The invention discloses a multi-omics analysis method and device, electronic equipment and a storage medium, and relates to the technical field of biological information, and the method comprises the following steps: obtaining a spatial single cell function map set based on multi-omics data, the multiple omics data at least comprise single cell transcriptome data, spatial transcriptome data, single cell chromatin transposase accessibility sequencing ATAC data and whole genome association research GWAS data, and the spatial single cell function map set comprises a plurality of maps used for indicating spatial distribution of different omics data; and establishing a mapping relationship from the spatial transcriptome data to the single cell transcriptome data, wherein the mapping relationship indicates spatial position information of each cell in the single cell transcriptome data. By utilizing the method, the flexibility during multi-omics analysis is improved, and the data integration capability is improved.
Owner:BOAO BIOLOGICAL CO LTD +2

Cattle muscle development related enhancer Enh483 and application thereof in promoting proliferation and / or differentiation of bovine myoblasts

The invention discloses an enhancer Enh483 related to bovine muscle development and application of the enhancer Enh483 in promoting bovine myoblast proliferation and / or differentiation. According to the method, existing ATAC-Seq data and Chip-seq data in the proliferation stage and differentiation stage of buffalo myoblasts are utilized to visually analyze chromatin open areas through IGV to predict annotation enhancers, candidate enhancers Enh483 related to muscle development are screened out, and the enhancers have enhancer activity detected by a dual-luciferase vector report system; after the activity of Enh483 is inhibited, the proliferation and differentiation of buffalo myoblasts can be inhibited, which indicates that Enh483 can promote the proliferation and / or differentiation of buffalo myoblasts. According to the invention, an important theoretical basis is provided for an action mechanism of transcription regulation elements such as enhancers in muscle development, and data support is provided for buffalo breeding and strain breeding.
Owner:GUANGXI UNIV

Application of HHAT gene and TTLL7 gene in liver cancer diagnosis and treatment

The invention discloses an application of an HHAT gene and a TTLL7 gene in liver cancer diagnosis and treatment, relates to the technical field of biology, discloses new prospects of the HHAT gene and the TTLL7 gene in a human genome for the first time, reveals occurrence and development of liver cancer caused by change of a three-dimensional structure and change of chromatin opening degree, and reveals development and development of liver cancer caused by targeting of the gene. The gene can become a therapeutic target for diagnosing or treating liver cancer.
Owner:ZHENGZHOU UNIV

Single cell Hi-C atlas interpolation method and device

PendingCN119694388ABiostatisticsProteomicsAlgorithmBiocomputer
The invention relates to the technical field of biological computing, in particular to a single-cell Hi-C atlas interpolation method and device, and the method comprises the steps: obtaining single-cell sequencing library data and a reference genome, determining the position of the sequencing data in the genome, and carrying out the statistics of the interaction frequency to obtain a Hi-C contact matrix; performing interpolation on the Hi-C contact matrix of any chromatin of the single cell according to similarity of adjacent nodes to obtain an adjacent node interpolation map of the single chromatin of the single cell; calculating an interpolation map of each chromatin of each cell, performing representation learning by taking the interpolation map as an adjacent matrix, splicing vectors to obtain a cell pre-embedded vector, and performing dimensionality reduction to obtain a whole cell embedded vector matrix; a cellular level similarity matrix is calculated by using a single cell embedded vector matrix and converted into a Markov probability transfer matrix, and the Markov probability transfer matrix is used for correcting an adjacent node interpolation map to obtain a Hi-C interpolation map, so that the interpolation accuracy is improved.
Owner:XI'AN UNIVERSITY OF ARCHITECTURE AND TECHNOLOGY

High-throughput single-cell multi-omics three-dimensional genome detection method and system

The invention provides a high-throughput single-cell multi-omics three-dimensional genome detection method and system. The detection method comprises the following steps: enzyme digestion reaction of fixed cells; carrying out proximity ligation treatment on the cells subjected to the enzyme digestion reaction; carrying out analysis treatment including reverse transcription on the treated cells, and respectively constructing a DNA library and an RNA library; and sequencing to obtain three-dimensional genomics information in a single cell. A high-throughput single-cell multi-omics three-dimensional genomics detection technology is designed, chromatin in cells is subjected to opening treatment through different methods, chromatin opening sites are enriched, the throughput of generated data is greatly improved, and the detection accuracy is greatly improved while the chromatin openness is detected in a single cell. The capability of detecting interaction between chromatin open sites and the gene expression capability are improved.
Owner:ZHEJIANG UNIV

Method for screening molecular markers based on apparent annotation information to carry out whole genome selective breeding

The invention discloses a method for screening molecular markers based on apparent annotation information to carry out whole genome selective breeding, which comprises the following steps: step A, carrying out phenotype determination and genome sequencing on growth traits of a litopenaeus vannamei breeding population to obtain phenotype data and SNP (Single Nucleotide Polymorphism) typing data; step B, performing GS analysis by using phenotype data and SNP typing data, predicting a genome breeding value of a breeding population through a mainstream breeding model, and screening out an optimal breeding model; and step C, classifying chromatin states through ChromHMM analysis by combining the optimal breeding model with the key histone modified region, and screening out the functional SNPs with the key histone modified region. The SNPs have relatively strong functional relevance, are used for different regional groups, and can provide more accurate molecular markers for growth character genetic analysis of bred animals by using less SNPs under the same prediction accuracy, so that the accuracy of genetic breeding value estimation and the cross-group effect are remarkably improved, and the breeding process is accelerated.
Owner:SANYA INST OF OCEANOGRAPHY OCEAN UNIV OF CHINA +1

Method for analyzing single-cell Hi-C regulatory scale chromatin band

ActiveCN121617480ABiostatisticsProteomicsCellular RegulationChromatosome
The invention relates to a biological information data processing technology, in particular to a method for analyzing a single-cell Hi-C regulation scale chromatin band, which comprises the following steps: preprocessing single-cell Hi-C data to generate pseudo-batch Hi-C data; performing normalization processing on the pseudo batch Hi-C data to extract a Hi-C contact matrix of each chromosome; identifying and detecting false batch strips from the Hi-C contact matrix; projecting the pseudo batch strips to the original single cell Hi-C data to obtain single cell strips; and carrying out quantitative analysis on the single-cell strip in the original single-cell Hi-C data. According to the method, the regulation and control scale chromatin bands with definite endpoints and directivity can be stably identified, and a band set with remarkable statistics is output.
Owner:SUN YAT SEN UNIV

Cells and methods for engineering cells with persistent transgene expression

Aspects of the present disclosure provide engineered induced pluripotent stem cell (iPSC)-derived mesenchymal stromal cells (EiMSCs) that exhibit persistent transgene expression. Persistent transgene expression may be achieved through use of an engineered chromatin opening sequence (ECOS). The engineered EiMSCs of the present disclosure can comprise a therapeutic polypeptide comprising one or more cytokines for the treatment of a metabolic disease, a proliferative disease, an autoimmune disease, a neurological disease, or any combination thereof.
Owner:FACTOR BIOSCIENCE INC

Neural network calculation method and device for gene expression regulation and control analysis

The invention discloses a neural network calculation method and device for gene expression regulation and control analysis, and relates to the technical field of bioinformatics, and the method comprises the steps: obtaining first feature data and second feature data; constructing an input feature comprising a plurality of regulation and control hierarchies; and inputting the input features of the plurality of regulation levels and the second feature data into the target neural network model, and outputting a prediction result of the gene expression state. According to the neural network calculation method provided by the invention, chromatin accessibility and three-dimensional space interaction data are deeply fused through a dynamic routing module, so that the problem of'black box 'which is inaccurate in prediction and difficult to explain in a traditional deep learning model is solved in a mode of explicitly simulating a real biological regulation mechanism; and a key gene regulatory pathway can be accurately identified.
Owner:ACADEMY OF MILITARY MEDICAL SCIENCES

Methods, kits and systems for determining the status of lung cancer and methods for treating lung cancer based on same

PCT designated stage expiredWO2025081121A1Microbiological testing/measurementDNA methylationCell free
The present disclosure includes, among other things, methods, kits, and systems for determining the status of lung cancer. In various embodiments, the present disclosure relates to the use of one or more histone modifications, chromatin accessibility, binding of one or more transcription factors, and / or DNA methylation that that are characteristic of the status of lung cancer. In some embodiments, differential modifications and / or differential accessibility are detected and quantified at one or more genomic loci of a biological sample, e.g., in cell-free DNA (cfDNA) from a liquid biopsy sample obtained or derived from a subject with lung cancer. In various embodiments a determined status is useful, e.g., in selecting treatment for and / or treating a lung cancer.
Owner:PRECEDE BIOSCIENCES INC +1

Methods, kits and systems for determining the her2 status of cancer and methods for treating cancer based on same

PCT designated stage expiredWO2025081100A1Microbiological testing/measurementDNA methylationCell free
The present disclosure includes, among other things, methods, kits, and systems for determining HER2 status of cancer, e.g., a breast, gastric / gastroesophageal, colorectal, or lung cancer. In various embodiments, the present disclosure relates to the use of one or more histone modifications, chromatin accessibility, binding of one or more transcription factors, and / or DNA methylation that that are characteristic of HER2 status of cancer. In some embodiments, differential modifications and / or differential accessibility are detected and quantified at one or more genomic loci of a biological sample, e.g., in cell-free DNA (cfDNA) from a liquid biopsy sample obtained or derived from a subject with cancer. In various embodiments a determined HER2 status is useful, e.g., in selecting treatment for and / or treating a cancer, e.g., a breast, gastric / gastroesophageal, colorectal, or lung cancer.
Owner:PRECEDE BIOSCIENCES INC +1

Artificial intelligence-based detection of gene conservation and expression preservation at base resolution

PendingUS20250201348A1BiostatisticsBiological modelsReference genesTranscription initiation
The technology disclosed relates to detecting gene conservation and expression preservation. In particular, the technology disclosed relates to detecting gene conservation and epigenetic signals for a reference genetic sequence in comparison to a variant of the reference genetic sequence at base resolution through the generation of a plurality of alternative representations of the sequence in chromatin form which may represent evolutionary conservation, transcription initiation, or epigenetic signals, mapping the plurality of alternative chromatin sequences to a gene expression alterability classifier to generate a gene expression class prediction for the variant, and mapping the alternative chromatin sequence to a pathogenicity predictor to detect pathogenicity of variants.
Owner:ILLUMINA INC

Gene regulation network inference method and device, storage medium and electronic equipment

The embodiment of the invention provides a gene regulation network inference method and device, a storage medium and electronic equipment. The method comprises the following steps: acquiring a first time sequence corresponding to a target cell type; the first time sequence comprises accessible chromatin sequencing data and single cell transcriptome sequencing data at different first time points; constructing a corresponding first gene regulation network according to the accessible chromatin sequencing data at each first time point; pruning the first gene regulatory network based on single cell transcriptome sequencing data to obtain a second gene regulatory network corresponding to each first time point; and deducing a plurality of second gene regulatory networks corresponding to the first time sequence based on a pre-constructed gene regulatory network prediction model to obtain a target gene regulatory network corresponding to the target cell type at a second time point, the second time point at least comprising a future time point and / or a missing time point in the first time sequence. The method can improve the inference accuracy of the gene regulatory network.
Owner:BEIJING HUADA BIO & INFORMATION FUSION TECHNOLOGY RESEARCH CO LTD

Methods, kits and systems for determining the er status of cancer and methods for treating cancer based on same

PCT designated stage expiredWO2025081094A2Microbiological testing/measurementDNA methylationCell free
The present disclosure includes, among other things, methods, kits, and systems for determining ER status of cancer, e.g., a breast cancer. In various embodiments, the present disclosure relates to the use of one or more histone modifications, chromatin accessibility, binding of one or more transcription factors, and / or DNA methylation that that are characteristic of ER status of cancer. In some embodiments, differential modifications and / or differential accessibility are detected and quantified at one or more genomic loci of a biological sample, e.g., in cell-free DNA (cfDNA) from a liquid biopsy sample obtained or derived from a subject with cancer. In various embodiments a determined ER status is useful, e.g., in selecting treatment for and / or treating a cancer, e.g., a breast cancer.
Owner:PRECEDE BIOSCIENCES INC +1

Compositions and methods for modulating chromatin state

Aspects of the present disclosure are directed to at least methods and compositions for diagnosis and / or treatment of diseases associated with aberrant levels of m5C RNA, including but not limited chromatin associate RNA (caRNA). The disease may comprise cancer and / or pre-cancerous cells. The disease may be associated with mutations in a TET2 pathway, including but not limited to mutations in TET2, IDH1, IDH2, and / or ASXL1 encoding genes. Treatment of a disease may comprises administration of one or more inhibitors of MBD6, TET2, and / or NSUN2. Also provided herein are methods of treatment of a disease in an individual comprising administering one or more inhibitors of MBD6, TET2, and / or NSUN2 to the individual determined to have aberrant m5C RNA modifications.
Owner:UNIVERSITY OF CHICAGO

Gene editing methods for modulating expression of id-3, an inhibitor of DNA-binding transcription factors, thereby affecting t-cell function

PCT designated stage expiredWO2025030118A1HydrolasesGenetically modified cellsAntigen receptorsHuman cell
The present disclosure provides gene editing methods for modulating the expression of an inhibitor of DNA-binding E-protein transcription factors, namely Id3, and thereby affecting T cell function. First, it provides experimental evidence that Id3 is critical to the persistence and function of tissue-infiltrating GVHD T cells in a mouse model. Id3 reduces chromatin accessibility (ChrAcc) of transcription factors (TFs) that drive T cell PD-1 transcription, differentiation and dysfunction. Id3 loss increases PD-1 expression and impairs tissue-infiltrating Th1 cells. Second, it provides proof-of-concept that targeting ID3 in human T cells using a CRIPSR / Cas9 knockout (KO) prevents xeno-GVHD but preserves the anti-leukemic activity of chimeric antigen receptor (CAR)-T cells. Third, it provides experimental evidence that ectopic expression of Id3 in engineered human CAR-T cells enhances the ability of these cells to eliminate tumors.
Owner:HACKENSACK MERIDIAN HEALTH INC

Gene editing methods for modulating expression of id-3, an inhibitor of DNA-binding transcription factors, thereby affecting t-cell function

The present disclosure provides gene editing methods for modulating the expression of an inhibitor of DNA-binding E-protein transcription factors, namely Id3, and thereby affecting T cell function. First, it provides experimental evidence that Id3 is critical to the persistence and function of tissue-infiltrating GVHD T cells in a mouse model. Id3 reduces chromatin accessibility (ChrAcc) of transcription factors (TFs) that drive T cell PD-1 transcription, differentiation and dysfunction. Id3 loss increases PD-1 expression and impairs tissue-infiltrating Th1 cells. Second, it provides proof-of-concept that targeting ID3 in human T cells using a CRIPSR / Cas9 knockout (KO) prevents xeno-GVHD but preserves the anti-leukemic activity of chimeric antigen receptor (CAR)-T cells. Third, it provides experimental evidence that ectopic expression of Id3 in engineered human CAR-T cells enhances the ability of these cells to eliminate tumors.
Owner:HACKENSACK MERIDIAN HEALTH INC

Prediction of chromatin state

PCT designated stageWO2025158025A1BiostatisticsProteomicsCytosineAssay
Methods of predicting a chromatin state metric associated with a genomic region in a sample are provided. The methods comprise: receiving sequence data comprising genetic data and epigenetic data indicative of the presence of one or more epigenetic bases including methylated cytosine and hydroxymethylated cytosine at one or more genomic positions, the one or more epigenetic bases, the genetic data and epigenetic data obtained from a single assay; and predicting for each base or set of bases of the genomic region and using the sequence data associated with the genomic region, a value of the chromatin state metric, wherein the predicting is performed using a machine learning model.
Owner:BIOMODAL LTD

Setdb1 inhibitor for use in the treatment of uveal melanoma

Metastatic uveal melanomas are highly resistant to all existing treatments. To identify actionable vulnerabilities, the inventors conducted a CRISPR-Cas9 knockout screen using a library composed of chromatin remodelers. They revealed that the histone H3 methyltransferase SETDB1 plays a critical role in metastatic uveal melanoma cell proliferation and survival. Functionally, SETDB1 knockdown triggers decreased expression of genes related to replication and cell cycle and promotes growth arrest associated with increased markers for DNA damage and senescence entry. Using pre-clinical model, they further demonstrated that anti-SETDB1 therapy tumor growth in vivo. The inventors identify SETDB1 as a new relevant therapeutic target for the treatment of metastatic uveal melanomas. The present invention relates to a method for treating uveal melanoma in a subject in need thereof comprising a step of administering said subject with a therapeutically effective amount of SETDB1 inhibitor.
Owner:INST NAT DE LA SANTE & DE LA RECHERCHE MEDICALE (INSERM) +1

Rongchang pig T2T genome assembly method

PendingCN121227691ADNA preparationContigGenomic annotation
The invention discloses a Rongchang pig T2T genome assembly method. The method comprises the following steps: 1) collecting and sequencing a sample; 2) genome investigation and assembly; 3) genome annotation; wherein in the sequencing step, three sequencing technical means, namely, a three-generation gene sequencing technology PacBio, Nanopore PromethION 48 short reading and chromatin conception capture (HiC), are adopted, and the Rongchang pig genome is subjected to sequencing and sequence splicing together. The Contig N50 value of the genome is nearly three times that of Sscrofa11.1, and the improvement is mainly embodied in a complex genome region (centromere and telomere regions), so that the genome becomes the most complete genome available at present.
Owner:CHONGQING ACAD OF ANIMAL SCI

Method for detecting accessibility of space chromatin and application thereof

The invention discloses a method for detecting accessibility of space chromatin and application of the method. The method comprises the following steps: (1) slicing a tissue sample to be detected on a chip with spatial information; (2) fixing, permeabilizing and dyeing a tissue sample to be detected; (3) preparing fragmented genome DNA (deoxyribonucleic acid); (4) performing DNA hybridization based on a transfer mode; (5) carrying out connection and terminal repair reaction on the fragmented genome DNA by using DNA polymerase and DNA ligase; (6) denaturation and melting; and (7) sequencing. According to the method, the transcriptional activity state of chromatin can be reflected through chromatin accessibility sequencing analysis, staining imaging and chromatin accessibility information can be obtained on the same tissue slice at the same time without complex micro-fluidic equipment, experimental operation is easy, repeatability is high, and the analysis result is more remarkable.
Owner:BMKMANU TECH CO LTD

Artificial intelligence-based epigenetics at base resolution

The technology disclosed relates to reliably identifying variants that cause extreme levels of gene expression. Extreme levels of gene expression include under expression and over expression. Then, these variants are used to train artificial intelligence based models for a variety of prediction tasks. One example of the prediction tasks is to produce per-base resolution for chromatin sequences. Another example of the chromatin task is to produce gene expression changes caused by the reliably identified variants.
Owner:ILLUMINA INC

Method and kit for RNA-chromatin interaction capture and analysis

The invention discloses a method and a kit for RNA-chromatin interaction capture and analysis. According to the present invention, with the adoption of the Mode-specific in situ RNA-chromatin interaction capture technology (MiRCIC) technology, the dual targeting of the specific RNA and the interaction mode during the RNA-chromatin interaction detection process can be achieved, and the dual targeting of the specific RNA and the interaction mode can be further achieved; the F (ab ') 2 fragment is coupled with an oligonucleotide fragment modified by biotin and NH2 to generate the F (ab') 2 fragment-oligonucleotide conjugate, and the F (ab ') 2 fragment-oligonucleotide conjugate is applied to detection, enrichment and analysis of RNA-chromatin interaction. And economic, rapid and high-sensitivity capture, enrichment and analysis on specific interaction mode-mediated and specific RNA-participated RNA-chromatin interaction in a cell in situ can be realized.
Owner:THE THIRD AFFILIATED HOSPITAL OF PLA NAVAL MEDICAL UNIVERSITY