214 results about "Mother cells" patented technology

The invention discloses a double-target chimeric antigen receptor for co-expression of CD47 and IL-15, a CAR-T cell and application of the CAR-T cell, and belongs to the technical field of genetic engineering, the double-target chimeric antigen receptor comprises a single-chain antibody scFv-EGFRv III, a single-chain antibody scFv-VEGF, CD47 and IL-15; the nucleotide artificial sequence of the single-chain antibody scFv-EGFRv III is as shown in SEQ ID NO. 6; the nucleotide artificial sequence of the single-chain antibody scFv-VEGF is as shown in SEQ ID NO. 9. According to the application disclosed by the invention, by performing sequence optimization on targets EGFRvIII and VEGF, the anti-tumor effect of CAR-T cells in glioblastoma can be improved, and by integrating immune checkpoint molecules CD47 and interleukin-15, the immunosuppression function of a CD47-SIRP alpha signal channel can be locally exerted.

The invention belongs to the technical field of biological medicine, and particularly relates to an engineered cell microvesicle and a delivery system based on the engineered cell microvesicle, the system realizes efficient preparation of 1-5 [mu] m cell microvesicles, and the cell microvesicles have a large space volume and can be used for preparing the cell microvesicles. The carrier can be used for loading and delivery of target protein, polypeptide and recombinase which are specifically expressed in mother cells. The system transfects mother cells through lentivirus transfection or plasmid transfection to further produce cell microvesicles, and the microvesicles can load more goods and inherit membrane proteins of the mother cells, and can also effectively load intracellular proteins to realize effective delivery. By virtue of good structural stability, high immunogenicity and excellent biocompatibility, the cell microvesicle reduces systematic toxic and side effects of a traditional carrier, is expected to become an effective drug delivery system, and has great application potential in the field of gene therapy.

The present invention addresses the problem of providing: a method for preparing hepatic lineage cells in a large amount and with high purity; and a method for preparing liver system cells which can achieve high graft survival rate in a living body.　The present invention provides: a hepatoblast proliferation promoter and a culture medium, each of which contains a ROCK inhibitor, a TGFβ signaling pathway inhibitor, a Wnt signaling pathway activator, and a growth factor; and a proliferation / culture method using the hepatoblast proliferation promoter or the culture medium.

Disclosed herein are genetically engineered yeast cells capable of producing xylitol. The engineered yeast cell may comprise an exogenous polynucleotide sequence encoding a sugar phosphatase enzyme comprising a sequence at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% identical to at least one of SEQ ID NOs: 8 and 20.

A method of analysing a sample of a plurality of fish oocytes (100) is disclosed The method comprises, for each oocyte in the sample: capturing a first set of images of the oocyte from a plurality of rotational angels when rotated about a first axis of rotation; capturing a second set of images of the oocyte from a plurality of rotational angels when rotated about a second axis of rotation, which second axis of rotation is orthogonal to the first axis of rotation; identifying at least one characteristic (104) of lipid droplet coalescence in the captured first and second sets of images; and based on the identified at least one characteristic of lipid droplet coalescence, classifying the oocyte as belonging to one of a plurality of predefined categories, and based on the distribution of the sampled oocytes in the plurality of categories, attributing a quality parameter to the sample of oocytes, the quality parameter being any one of: a predicted fertilisation rate of the sampled oocytes; a predicted eyed-embryo success rate of the sampled oocytes; and a predicted hatching success rate of the sampled oocytes. A computer-implemented method of attributing a quality measure to a sample of fish oocytes is also disclosed, as is a related computer program and a related oocyte analysis apparatus. A computer-implemented method for training a neural network for use in a system for analysing a sample of fish oocytes is also disclosed.

The invention relates to a method for electrically activating oocytes based on nanosecond pulses. Single oocytes are sequentially and uniformly arranged between two parallel electrodes of an electrode dish, the electrode dish is characterized in that the distance between the electrodes is 1 mm, the electrodes are placed in a culture dish, and the two ends of the two electrodes are sealed; a culture solution is firstly put between the electrodes which are arranged in parallel, mineral oil is covered to prevent the culture solution from being evaporated, after preheating treatment, oocytes are sequentially and uniformly put between the two electrodes which are arranged in parallel one by one, and then nanosecond pulse electric activation treatment is applied. The electrodes which are arranged in parallel are adopted, the oocytes are sequentially and uniformly placed between the electrodes in a single mode, the situation that the electric pulse effect is reduced due to adhesion and stacking of all the cells is avoided, the oocytes receive uniform and equivalent electric pulse sequences, the action effect and stability of electric pulses on the cells are obviously improved, and the operation efficiency of the oocytes is improved. And the reliability and reproducibility of a test conclusion are improved.

The invention develops a double-line sequential targeted nano-drug delivery system, epigenetic regulation and traditional chemotherapy are combined, and the system is used for accurately and effectively treating acute myelogenous leukemia. The METTL3 inhibitor and the ROS-responsive daunorubicin prodrug are co-delivered in a single nano-drug, and the nano-preparation can realize continuous and double-path drug release according to the oxidation-reduction state in AML cells. In leukemia stem cells with low ROS level, STM2457 is released preferentially to induce differentiation and improve the ROS level of mitochondria, so that DA-ROS is activated, and the effect of delaying cytotoxicity is achieved. On the contrary, the AML mother cells with high ROS level can immediately trigger DA-ROS activation and release the two drugs at the same time, so that the tumor cells are directly killed. This ROS adaptive delivery strategy ensures spatial and temporal accuracy of drug release in heterogeneous AML cell populations.

In various embodiments, provided herein are host cells, methods, and pharmaceutical compositions comprising gastrodin, wherein the gastrodin is produced by a genetically modified plant or plant cell, fungal cell, yeast cell, insect cell, or bacterial cell. In certain embodiments, the present disclosure provides methods and compositions for the production of gastrodin. In yet other embodiments, the present disclosure provides enhanced cells and methods for producing gastrodin.

The invention provides a mother battery piece, a battery piece, a preparation method of the mother battery piece and a photovoltaic module. The battery piece comprises a first semiconductor substrate; the first doped semiconductor layer is arranged in the central region; the isolation groove is formed in the first isolation area and surrounds the central area; wherein the side surface comprises a first sub-surface, and the first sub-surface is connected with the groove wall of the isolation groove; the tunneling passivation contact structure is at least arranged on the second surface; the first passivation layer at least covers the first doped semiconductor layer, the isolation groove and the first sub-surface; wherein the first sub-surface and the second surface are both provided with a plurality of square tower footing structures, the difference between the side length of the largest square tower footing structure on the first sub-surface and the side length of the largest square tower footing structure on the second surface is a first numerical value, and the first numerical value is smaller than or equal to 15 microns. The battery efficiency can be improved, and the manufacturing cost can be reduced.

Certain substances (e.g., large molecules) that ordinarily cannot traverse the cell membrane of cells can be introduced into cells by applying an alternating electric field to the cell for a period of time, wherein the frequency of the alternating electric field is selected so that application of the alternating electric field increases permeability of the cell membrane. Once the permeability of the cell membrane has been increased, the substance is able to cross the cell membrane. This approach is particularly useful in the context of cancer cells (e.g., glioblastoma).

The present invention provides a GD2-targeting CAR-T cell and its preparation and application. Specifically, the present invention provides a GD2-targeting CAR construct, which comprises the scFv fragment of the humanized GD2 antibody 3F8, the human Fc fragment, the ICOS transmembrane region, the ICOS and 4-1BB intracellular regions (co-stimulatory signals), and CD3ζ. The present invention also provides a CAR-T cell based on the above CAR, its preparation method and application. The CAR-T cell of the present invention can significantly inhibit the proliferation of tumor cells in a subcutaneous model of neuroblastoma, has a significant in vivo anti-tumor effect, and can be used for the targeted treatment of neuroblastoma.

The present invention relates to aptamers that specifically bind to the extra-cellular domain of alpha7 / beta1 integrin dimers, conjugates or particles comprising said aptamers, in muscles cells such as skeletal muscle fibres and satellite cells, or in cells aberrantly expressing said domain e.g. tumour cells such as rhabdomyosarcoma (muscle-derived tumours), or glioblastoma cancer stem cells, as well as conjugates comprising said aptamers, therapeutic or diagnostic compositions comprising said conjugates or said aptamers, and their use as a medicament and in diagnostic methods.

The present invention relates to a medium composition for in vitro fertilization and / or in vitro culture comprising a compound represented by chemical formula 1 or a pharmaceutically acceptable salt thereof, and a method using same. The compound or composition suppresses reactive oxygen species and lipid peroxidation in ovarian granulosa cells to preventing cytotoxicity and mitochondrial dysfunction caused by apoptosis and ferroptosis, leading to an improvement in the quality of aged oocytes, and to increase the developmental rate and blastocyst formation rate of pre-implantation embryos, thereby improving the efficiency of in vitro fertilization. In addition, treatment with the medium composition during the vitrification process of in vitro–fertilized embryos improves re-expansion and survival rates, thereby reducing structural and metabolic damage. Accordingly, the present invention can be advantageously applied to an assisted reproductive technology for treating infertility and subfertility, and in vitro fertilization and / or in vitro culture for improving the propagation efficiency of livestock.

Methods and compositions for generating B lineage cells, such as plasmablasts, plasma cells, and protein producing or protein secreting B cells are disclosed. The methods can involve stage-specific differentiation from stem cells or stem cell-derived hematopoietic progenitor cells through one or more intermediates to B lineage cells, such as plasmablasts, plasma cells, and protein producing or protein secreting B cells.

Disclosed herein are genetically engineered yeast cells capable of producing xylitol and characterized by a deletion or disruption in a native gene encoding an erythrose reductase at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% identical to at least one of SEQ ID NO:295. The genetically engineered yeast cell may additionally be engineered to overexpress a native RPE enzyme, express an exogenous XPDH enzyme, express an exogenous XKS enzyme, express an exogenous XDH enzyme, overexpress a native X5PP enzyme, and / or express an exogenous X5PP enzyme.

The present invention relates to a yeast cell, in particular a recombinant yeast cell, the cell lacking enzymatic activity needed for the NADH-dependent glycerol synthesis or the cell having a reduced enzymatic activity with respect to the NADH-dependent glycerol synthesis compared to its corresponding wild-type yeast cell, the cell comprising one or more heterologous nucleic acid sequences encoding an NAD+-dependent acetylating acetaldehyde dehydrogenase (EC 1.2.1.10) activity. The invention further relates to the use of a cell according to the invention in the preparation of ethanol.

Disclosed are methods and compositions for generating B lineage cells, such as plasmablasts, plasma cells, and protein-producing or protein-secreting B cells. The methods may relate to stage-specific differentiation from stem cells or stem-cell derived hematopoietic progenitors through one or more intermediates to B lineage cells, such as plasmablasts, plasma cells, and protein-producing or protein-secreting B cells.

This invention discloses an engineered CAR-T cell targeting HIF-1α and its application in tumor immunotherapy. The CAR-T cell expresses a chimeric antigen receptor regulated by the hypoxia-responsive element HRE promoter, with its extracellular domain specifically binding to HIF-1α and its intracellular domain employing the 4-1BB+CD3ζ signaling module. Simultaneously, through immune checkpoint knockout and cytokine / chemokine modification, it achieves hypoxia-dependent activation, anti-exhaustion, high infiltration, and strong killing effects. The CAR-T cells of this invention significantly improve the adaptability to the solid tumor microenvironment and therapeutic efficacy, reduce off-target toxicity, and can be used to prepare drugs for treating malignant tumors such as lung cancer, liver cancer, pancreatic cancer, colorectal cancer, and glioblastoma, possessing significant clinical translational value.

The application belongs to the technical field of biology and particularly relates to a functional recombinant Cas9 protein targeted to an ovocyte of Procambarus clarkii and application thereof. The protein is NLs-VgSP-Cas9-NLs. The application directly delivers the recombinant Cas9 protein, thereby reducing the risk of integration of exogenous genes. By specifically targeting the ovocyte, off-target effects on somatic cells can be avoided, the efficiency of editing of germ cells is improved, and early development or genetic manipulation can be conveniently studied. The ovocyte of Procambarus clarkii is large, the recombinant Cas9 protein is efficiently delivered by receptor-mediated endocytosis on the surface of the ovocyte, and the problem that microinjection of zygotes cannot be implemented is solved.

The present invention relates to a yeast cell, in particular a recombinant yeast cell, the cell lacking enzymatic activity needed for the NADH-dependent glycerol synthesis or the cell having a reduced enzymatic activity with respect to the NADH-dependent glycerol synthesis compared to its corresponding wild-type yeast cell, the cell comprising one or more heterologous nucleic acid sequences encoding an NAD+-dependent acetylating acetaldehyde dehydrogenase (EC 1.2.1.10) activity. The invention further relates to the use of a cell according to the invention in the preparation of ethanol.

Microfluidic systems are configured to process liquid samples that include cumulus-oocyte complexes (COCs), such as raw follicular fluid, in an automated and continuous manner to produce oocytes separate or “denuded” from surrounding cumulus cells. The systems include a substrate and a channel that can have two or more sub-channels. Each channel includes an inlet, an outlet, and one or more stages arranged in series. Each of the stages includes one or more expansion units and one or more constriction units. At least one stage includes constriction units having jagged internal surfaces, e.g., teeth, that help remove the cumulus cells from the COCs.

The present invention relates to an sgRNA sequence for targeted knockout of the IGFL3 gene and its application in enhancing the radiosensitivity of glioblastoma, belonging to the field of biotechnology. The sgRNA sequence is IGFL3-sgRNA-1 or IGFL3-sgRNA-3, and a CRISPR / Cas9 vector for targeted knockout of the IGFL3 gene is constructed using this sgRNA. The above vector was transfected into human glioblastoma cell line U251, and it was identified that the IGFL3 gene could be efficiently knocked out in this cell, and 2 U251 cell lines with knocked-out IGFL3 gene were screened. By targeted knockout of the IGFL3 gene, the radiosensitivity of human glioblastoma cell line U251 can be effectively enhanced. The present invention lays a foundation for studying the role of the IGFL3 gene in the radiosensitivity of glioblastoma, and also provides a powerful tool for developing this gene as a potential molecular target for enhancing the radiosensitivity of glioblastoma.

The present invention belongs to the field of molecular biology and genetics, and in particular relates to a method for editing a bovine gene based on Pro-iCHI. The present invention provides a method for editing a bovine gene based on Pro-iCHI. Protamine is transiently expressed in gene-edited b-haSCs, which are then injected to mature oocytes to obtain reconstructed embryos. Protamine can eliminate abnormal DNA methylation resulting from oocyte intracytoplasmic haSCs injection and enable the nucli to compress into sperm-like structures, and the obtained bovine Pro-iCHI embryos can successfully develop into blastocysts, with a blastocyst rate comparable to that of the embryos obtained by in vitro fertilization. Moreover, in the present invention, a protamine-encoding gene is inserted into a Saccharomyces cerevisiae protein expression vector for transient expression, which ensures that abnormal DNA methylation is erased, without integration into the genome resulting in the insertion of exogenous genes.

The invention belongs to the technical field of biology, and particularly relates to cherax quadricarinatus oocyte targeted functional recombinant Cas9 protein and application thereof. Specifically, the protein is NLs-VgSP-Cas9-NLs (Nuclear Leukemia Sequence-Vector Through direct delivery of the recombinant Cas9 protein, the risk of exogenous gene integration is reduced. Through specific targeting of oocytes, off-target effect on somatic cells can be avoided, germ cell editing efficiency is improved, and research of early development or genetic manipulation is facilitated. The cherax quadricarinatus oocytes are large, the recombinant Cas9 protein is efficiently delivered through endocytosis mediated by oocyte surface receptors, and the problem that microinjection of fertilized eggs cannot be implemented is solved.

The MYC and NMYC transcription factors (TFs) play a key role in cell proliferation and are overexpressed in most cancer cells. However, in normal cells their overexpression triggers safeguard mechanisms promoting cell death and cellular senescence, which are bypassed in cancer cells. Here, the inventors reveal that in normal cells MYC binds to the Inositol 1,4,5-Trisphosphate Receptor type 1 (ITPR1) gene and upregulates its expression, triggering an ER-mitochondria calcium (Ca2+) transfer, which is involved in MYC-induced cell death and senescence. Supporting a tumor suppressive role of MYC / ITPR1 axis, ITPR1 expression is generally decreased in cancer and reactivation of this pathway induces cancer cell death. Nevertheless, some cancer cells, generally expressing high levels of MYCN and / or MYC, also express high level of ITPR1, which correlates with high expression of BCL2, encoding an inhibitor of ITPR1. Strikingly, in high-risk MYCN-amplified neuroblastoma, ITPR1 expression is controlled by NMYC and its level correlates with worse patient survival. In these cells, blocking the interaction between BCL2 and ITPR1, via an BCL2-BH4 domain inhibitor induces mitochondrial Ca2+ accumulation and cell death, and decreases tumor size. Thus, the present invention relates to a method for treating MYChigh cancer, and in particular NMYC--amplified neuroblastoma in a subject by administering an BCL2-BH4 domain inhibitor.

This invention belongs to the medical field and establishes a clinically relevant mouse glioblastoma treatment model, obtaining "cured" mice. When these "cured" mice were re-challenged with tumors, the tumors spontaneously regressed, and the animals achieved long-term survival. This indicates that the "cured" mice acquired immunity to the tumor, and these mice are named "cured-immune" mice. Intracranial inoculation of tumor cells into the "cured-immune" mice specifically induced a microglia subset exhibiting high expression of the purinergic receptor P2ry12 gene. High ) and immune-boosting functional characteristics, P2ry12 infusion Hi Small glial subsets significantly prolonged the survival time of glioma-bearing mice. Compared with the control group, P2ry12 in "cured-immune" (LTS) mice was significantly reduced. High Ccl12 low Differentially expressed genes in microglial cell subsets are enriched in signaling pathways that promote immune function, hence P2ry12 High Ccl12 low Microglial cell subsets have therapeutic effects on gliomas.

A simpler and lower-cost method and associated hardware are described for recovering biopharmaceutical products from cell factories in higher yields by a liquid nitrogen-based pre-treatment of cell factories followed by gentler disintegration of cellular factories by tunable, pressurizing and de-pressurizing cycle with gaseous nitrogen. The cell factories are heterologous expression systems and could be based on plant cells, mammalian cells, algal cells, yeast cells or even bacterial cells. The pre-treatment step with liquid nitrogen softens the tougher cell wall structures thus enabling cells to be disrupted relatively easily during the gaseous nitrogen-based pressurizing / depressurizing cycle. This invention can enhance the yield of biopharmaceutical products from expression systems and reduce the overall cycle-time and further down-stream processing and polishing cost of biopharmaceutical products.

The invention provides a double-target chimeric antigen receptor, a CAR-T cell and application of the double-target chimeric antigen receptor and the CAR-T cell, and belongs to the technical field of hybrid peptides. The double-target chimeric antigen receptor comprises EGFRvIII scFv and GRP78 scFv; the nucleotide sequence of the EGFRvIII scFv is as shown in SEQ ID NO. 2; and the nucleotide sequence of the GRP78 scFv is as shown in SEQ ID NO. 4. According to the invention, by targeting two antigen targets of EGFRvIII and GRP78, the targeting specificity is enhanced, and the ability of CAR-T cells to kill glioblastoma is enhanced. Compared with a single-target CAR-T cell (EGFRvIII-CAR-T cell or GRP78-CAR-T cell), the T cell modified by the double-target chimeric antigen receptor provided by the invention has better cell factor secretion capability and better killing effect on tumor cells.

The present application relates to the technical field of biological medicine, and more particularly to a culture solution, a kit and an application for in-vitro maturation of aged oocytes. Through in-vitro experiments, the present application adds exogenous stromal cell-derived factor 1, establishes a culture system for in-vitro maturation of aged oocytes, and reveals the molecular mechanism of stromal cell-derived factor 1 playing a role through autophagy, thereby providing a new solution for improving the fertility of aged women and improving the success rate of assisted reproductive technology, and having important clinical application value.

The application provides application of MTA1 which is highly expressed in glioma stem cells (GSC) in treatment of glioblastoma (GBM). The application firstly proposes that GSC in GBM highly expresses MTA1 protein molecules, the highly expressed MTA1 is positively correlated with poor prognosis of GBM patients, and also promotes the stemness, cell proliferation and spheroid formation ability of GSC. Targeting the highly expressed MTA1 in GSC can inhibit the malignant progression of GBM. The application provides a new target and inhibitor for targeted treatment of GBM.