Highlights of science journals in January 2020

January 31, 2020 / BIOON / -- January 2020 is coming to an end What are the highlights of Science Journal in January? Xiaobian has sorted this out and shared it with you 1 Science: a major breakthrough! To reveal the mechanism of brain edema after stroke doi: 10.1126/science.aax7171 brain edema (cerebellar edema) is a swelling in the brain, which is a serious and potentially fatal complication of stroke In a new study of mice, researchers from medical center of University of Rochester and University of Copenhagen in Denmark found for the first time that the glymphatic system, which is usually related to waste removal, was abnormal during a stroke, resulting in cerebrospinal fluid flooding the brain, causing brain edema and brain cell drowning Relevant research results were published online in the journal Science on January 30, 2020, and the title of the paper is "cererospinal fluid influx drives acute ischemic tissue swelling" The picture is from cc0 public domain Dr Maiken Nedergaard, co-author of the paper and co director of the center for translational neurology at the University of Rochester Medical Center, said: "these findings suggest that the lymphoid system of the brain plays a key role in the acute tissue swelling of the brain after a stroke Understanding this dynamic change driven by electrical activity storms in the brain points the way to developing potential therapeutic strategies that may improve stroke outcomes " 2 Science: a major breakthrough! In a new study, researchers from the Chinese Academy of Sciences, Tongji University, Tsinghua University, Nanjing Medical University and the University of Chicago found a previously unknown way to make our gene expression a reality They found that RNA itself regulates the way DNA is transcribed, rather than the one-way flow of genetic instructions from DNA to RNA to proteins This discovery is of great significance to our understanding of human diseases and drug design The related research results were published online in the journal Science on January 16, 2020 The title of the paper is "N6 metadata of chromosome associated regulatory RNA regulations chromatin state and transcription" The corresponding authors are Dr Dali Han of Beijing Institute of genomics, Chinese Academy of Sciences, Dr Yawei Gao of School of life science and technology, Tongji University and Dr Chuan he of University of Chicago The researchers found that messenger RNA molecules, previously thought to transmit only instructions from DNA to proteins, actually exert their own influence on the proteins This is done by a reversible chemical reaction called methylation The key breakthrough in this study is to confirm that this methylation is reversible This is not a one-way deal It can be erased and reversed They also found that a group of RNAs called chromosomal associated regulatory RNAs (carrna) use the same RNA methylation process, but they do not encode proteins or directly participate in protein expression But they control how DNA itself is stored and transcribed 3 Science: great progress! RNA vaccine makes claudin car-t cells more effective against solid tumor doi: 10.1126/science.aay5967 Adoptive T cell therapy using T cells expressing car after gene transformation has achieved clinical success in B-cell malignant tumors However, in patients with solid tumors, car-t cell therapy has encountered challenges and is not so effective A key obstacle is the limited number of cell surface targets that allow high cancer specific expression and low risk of off-tumor / on-target toxicity of tumor eradication Recently, scientists have reported the cancer-related expression of CLDN6 CLDN6 is a quadruple membrane protein involved in tight junction In a new study, to assess whether CLDN6 can be used as a target for car-t cell therapy, researchers from biopharmaceutical New Technologies Corporation (bintech) in Germany analyzed its expression in a complete set of human and mouse tissues The results showed that the level of CLDN6 transcripts was higher in human fetal stomach, lung and kidney tissues, but could not be detected in normal adult tissue samples In addition, as before, CLDN6 transcript levels are generally higher in a variety of human cancers, such as testicular, ovarian, cervical, and lung adenocarcinoma In mice, CLDN6 is widely expressed in fetal organs, but it is down regulated before delivery, which results in its lack of expression in most organs of adult mice This shows that CLDN6 is a kind of carcinoembryonic cell surface antigen in a strict sense, and has an ideal expression profile suitable for car-t cell targeting The related research results were recently published in the Journal of science The title of the paper is "an RNA vaccine drives expansion and efficiency of claudin car T cells against solid tumors" When cldn6-car-t cells were co cultured with CLDN6 positive human tumor cell lines, they observed the up regulation of IFN γ secretion and T cell activation markers, but this did not happen when co cultured with CLDN6 negative tumor cells Cldn6-car-t cells can also effectively clear the globules of CLDN6 positive PA-1 ovarian cancer The results showed that cldn6-car-t cells could be eliminated completely by knocking out CLDN6 with CRISPR / cas9, which confirmed the high efficacy and target specificity of cldn6-car-t cells In recent years, these researchers stimulated tumor related T cells in cancer patients' natural cell bank by intravenous injection of liposomal antigen encoding RNA (RNA LPX) The nanoparticles deliver antigens to APCs in the spleen, lymph nodes and bone marrow, and initiate a toll like receptor (TLR) - dependent type I IFN driven immune activation program to promote antigen-specific T cell activation and strong proliferation In order to verify whether the improved method can play a role as car-t cell amplifying RNA vaccine (carvac), these researchers carried out a series of experiments First, they tested whether CLDN6 was shown on the surface of dendritic cells to stimulate cldn6-car-t cells in vitro They detected the dose-dependent expression of CLDN6 on the surface of dendritic cells treated with different doses of rna-lpx encoding CLDN6 The resulting expression of CLDN6 on the surface of dendritic cells induces the activation, cytokine secretion and proliferation of cldn6-car-t cells co cultured with dendritic cells in a dose-dependent manner After intravenous injection of cldn6-lpx to BALB / c mice, CLDN6 expression was detected on the surface of spleen dendritic cells and macrophages, but not on the surface of lymphocytes, which confirmed that CLDN6 was only delivered to antigen-presenting cells (such as dendritic cells and megaphagocytes) in vivo NK cells, B cells and T cells were strongly activated in spleen and lymph nodes of mice injected cldn6-lpx Since the most prominent serious adverse event of car-t cell therapy is cytokine release syndrome (CRS), these researchers explored the possibility of increased systemic cytokine release when cldn6-car-t cells are used in combination with carvac strategy They analyzed the levels of IFN γ, IL6 and NF α in the serum of cldn6-car-t cells transplanted mice after cldn6-lpx inoculation In addition to the slight transient increase of IFN γ in the early stage, no significant increase of proinflammatory cytokines was observed In addition, the spleen of mice inoculated with cldn6-lpx single time or repeatedly did not show any obvious pathological changes in structure; at different time points after receiving cldn6-lpx repeated inoculation, their spleen cells were composed of CD11c + dendritic cells and CD11c + dendritic cells In F4 / 80 + macrophage population, there was a slight temporary decline, but there was no quantitative change in T cell, B cell and NK cell population These findings suggest that carvac can be used to improve the antitumor effect of car-t cells This provides a new strategy for the use of car-t cells in the treatment of solid tumors that are difficult to treat However, these results are achieved in preclinical models, and whether they are the same in human body remains to be verified by further research 4 Science: it is the first time to build a three-dimensional organ like DOI of human forebrain: 10.1126/science.aay1645 In a new study, researchers from Stanford University in the United States have built a human forebrain like organ for the first time The relevant research results were published in the Science Journal on January 24, 2020, and the title of the paper is "single cell transcription diversity is a hallmark of development potential" In this paper, they describe the cultivation and application of this kind of organ Picture from science, 2020, DOI: 10.1126/science.aay1645 In most of the history of biological science, people have to use experimental animals to study the functional living brain - for ethical reasons, it is impossible to study the human brain in this way But in recent years, scientists have found a way to grow cells into clusters as substitutes for human organs, thus providing a better choice They are called organoids, and they are made from pluripotent stem cells that can differentiate into any type of human cell People use drugs and growth factors to guide them to grow into the types of organs they want to study In other studies, the brain or other nerve tissue has been cultivated - in this new study, the researchers have made further progress: inducing stem cells to grow into forebrain organs, and they live longer, which allows them to learn more about brain development As a spherical structure, human forebrain organs can self assemble into different parts of forebrain The forebrain includes the organs of the upper thalamus, thalamus, subthalamus and the hypothalamus These real organs play a key role in cognition, sensory processing and motor function As part of the study, the researchers also found a way to significantly prolong the life span of human forebrain organs (up to 300 days), enough to see them develop into more complex structures They hope that such a long period of growth will allow the study of brain diseases to develop and may find ways to prevent them 5 Science: new technology helps to find the most dangerous cancer cells doi: 10.1126/science.aax0249 in a new study, researchers from Stanford University, China West Lake University and Leiden University Medical Center in the Netherlands found that finding a number can help them develop the most dangerous cancer cells They also found that the number of genes cells use to make RNA is a reliable indicator of cell development, a finding that may make targeting oncogenes easier The relevant research results were published in the Science Journal on January 24, 2020, and the title of the paper was "Single-cell transcriptional divers"