The July 2020 Science Journal had to look at the highlights of the study. 

!--webeditor: """""31 July 2020 /prNewswire/ -- --- July 2020 is coming to an end, and what are the highlights of the July Science Journal? The editor has organized this and shared it with you.
1.Science: Heavyweight! Molecular companion-mediated autophagy regulates the pluripotentity of embryonic stem cells and is expected to develop new regenerative therapies doi: 10.1126/science.abb4467; Doi:10.1126/science.abd1431 In a new study, researchers at the Perelman School of Medicine at the University of Pennsylvania in the United States found that the autophage process in embryonic stem cells called CMA (chaperone-mediated autophagy, molecular companion-mediated autophagy), may serve as a new therapeutic target for repairing or regenerating damaged cells and organs.
the results of the study, published in the July 24, 2020 issue of the Journal of Science, are entitled "Chaperone-mediated autophagy regulations the pluripotency of the stem-dome cells".
picture from CC0 Public Domain.
this new preclinical study for the first time shows how embryonic stem cells keep CMAs low to promote this self-renewal, and we have revealed two new ways that can manipulate embryonic stem cells to self-renew and differentiate to turn off this inhibition to enhance CMA activity and differentiate them into specialized cells. "This is an intriguing discovery in stem cell biology for people who want to develop tissue or organ regeneration therapies," said Dr. Xiaolu Yang, a
paper author and professor of cancer biology at the University of Pennsylvania's Perelman School of Medicine.
we reveal two new ways that could manipulate embryonic stem cells to self-renew and differentiate: the CMA and a metabolite called alpha-ketoglutarate, regulated by the CMA.
reasonable intervention or guidance of these functions may be a powerful way to improve the efficiency of regenerative medicine methods.
"2.Science: Significant Progress! It is revealed that tumor initiation cells promote tumor progression through the il-33/TGF-beta niche signal cycle: 10.1126/science.aay1813 a small number of tumor cells with long-term tumor-causing capacity, the tumor initiating cell, TIC, which plays a key role in the development and therapeutic resistance of the cancer.
however, the development of effective TIC targeted therapy is limited due to the lack of identification of TIC vulnerability.
just as normal stem cells are regulated by external cues from a specific microenvironment (i.e. stem cell niche), TIC's stem cell-like state and its offspring's malignant phenotype are controlled by various factors from tic-related tumor microenvironments (so-called TIC niches).
therefore, a mechanism to understand the interaction between TIC and TIC niches can accelerate the development of persistent cancer treatment drugs.
mouse model squamous cell carcinoma (SCC), researchers at Oregon Health and Science University in the United States have previously found that conversion growth factor beta (TGF-beta) induces the emergence of a portion of drug-resistant TICs, resulting in leaching, differentiated offspring.
they observed that these TGF-beta reactive tumor cells were spatially associated with local TGF-beta expression in adjacent substrates.
therefore, the mechanism that causes the "TGF-beta-rich" tumor microenvironment may be the basis for tic-TIC niche interactions and could be used as a new target for destabilizing TIC.
Given that normal stem cells coordinate their niches by sending short-range signals, the researchers hypothesized that TIC might send specific signal molecules to neighboring substrates to induce TIC-supported niches. In a new study,
, by focusing on cytokine milieu and immune cells near TGF-beta reactive TIC, the researchers determined how TIC sepulks produce a spatially unique niche microenvironment, which is necessary for SCC's leaching progression and resistance.
related findings were published on July 17, 2020 in the journal Science, with the title "Tumor-based-starting cells cells an IL-33-TGF-beta-niche signaling loop to promote cancer cancerion".
looking for potential side-secreting regulators in the nearby tumor microenvironment, they found that leukocyte interleukin-33 (IL-33) was the highest rise in TGF-beta reactive TICs.
Given that IL-33 is normally stored in the nucleus of cells, they found that it is released into extracellular space in nRF2-mediated antioxidant reactions, which is a sign of TGF-beta reactive TIC.
this IC-33 from TIC is necessary for SCC's leaching progression and resistance.
mechanism, IL-33 induces a partial accumulation of tumor-related macrophages of the IL-33 receptor ST2 and the high affinity IgE receptor (Fc-RI alpha) at a place close to TIC (i.e. within a radius of 50 m).
these previously unappreciated Fc-RI alpha-macrophages differentiate and alternating from bone marrow-derived cells, creating a niche microenvironment rich in TGF-beta through the IL-33-ST2-NF-B pathway, thus inducing the Secretion of TGF-beta signals to TIC, and further increasing the expression of IL-33.
blocking this pathway or removing Fc-RI alpha-macrophages can reduce the number of TGF-beta reactive TICs, reduce the rate of progression of invasive tumors and chemotherapy resistance.
treatment of resistant TIC is considered to be the main culprit of cancer treatment failure.
by studying mouse models, the researchers revealed the cellular and molecular basis of TIC niches, in which TIC niches promote malignant progression and drug resistance in SCC.
they found an IL-33-TGF-beta niche signal cycle between TIC and FC-RI alpha-macrophage, which provides new insights into the mechanism sepulsied interaction of self-reinforcing TIC-TIC niches.
this interaction may be a potential target for destabilizing TIC to improve cancer treatment.
!--/ewebeditor:!--webeditor:pagetitle"--3.Science: Early incomplete B-cell tolerance in human fetuses facilitates the accumulation of multi-reactive B cells doi: 10.1126/science.ay9733 wide range of immunoglobulin gene rearrangement seisquids that enable humans to identify a wide range of potential pathogens.
this antibody bank (antibody repertoire, also translated as antibody spectrum) is subject to additional restrictions during early life to prevent the production of autologous reactive B cells, after all, tolerance does not seem to be complete.
, neonatal serum is rich in autoantibodies, which also suggests that B-cell tolerance during pregnancy has not yet been fully established.
B cells are the main pillars of our adaptive immune system.
they develop in the bone marrow and then circulate in the blood.
B cells are responsible for producing antibodies against invasive pathogens (so-called antigens).
each B cell is highly specific to an antigen.
antibodies are larger protein molecules called immunoglobulins that are secreted into the bloodstream.
they are also produced in the form of membrane binding and are present on the surface of B cells and are therefore called B-cell receptors (BCR). in a new study
, researchers at Yale University and Rochester University in the United States assessed the responsiveness of more than 450 antibodies cloned from B cells in the liver, bone marrow and spleen of human fetuses.
the results of the study, published in the July 17, 2020 issue of The Journal of Science, are entitled "Autoreactivity in na?ve human fetal B cells is es sed with commensal bacteria recognition".
images from Science, 2020, doi:10.1126/science.aay9733.
they found that incomplete B-cell tolerance in early human fetuses facilitates the accumulation of multi-reactive B cells, which can bind to apoptosis and symbiotic bacteria from healthy adults without any somatic cell hypermutations.
these reactive B cells are produced before they come into contact with bacteria, which may promote later beneficial symbiotic-host interactions and/or enhance the host's defenses in the first week of life.
, thelimited pre-immune antibody pool of fetal immunoassays therefore contains potentially beneficial autoactive congenital B-cell specificity, which may help to remove apoptosis cells during development and promote the formation of the gut microbiome after birth.
4.Science: Uncovering how metastatic cancer progresses in an unfavourable cobweb subcavity environment? doi: 10.1126/science.aaz2193; doi:10.1126/science.abb7041 Recently, scientists from institutions such as Memorial Sloan Kettering Cancer Center have revealed how metastatic cancer can have a subsometry under the adverse cobwebs (subarachrach) in a study published in the international journal Science. In the article, researchers describe how RNA sequencing was used to study patients with the metormembrane metastases, a type of cancer involving the spinal and meninges.
study, the researchers focused on a particular type of cancer in the central nervous system called the roulith membrane metastasis (LS), which they wanted to explain why a particular type of cancer not only appears in the subcavity of the cobweb, which is separated from the central nervous system, which is filled with cerebrospinal fluid, in this hostile environment.
researchers first collected samples of cerebrospinal fluid from the bodies of five patients with gentle meninges metastasis and then sequenced them on single-cellRNA, and found that cancer cells may have a high affinity iron collection system that helps cancer cells use iron ions found in cerebrospinal fluid, which the researchers say is found in the cerebrospinal fluid. There are almost no iron ions, which make it a valuable "commodity" that is important for DNA synthesis and cell metabolism, and using this iron ion collection system can help cancer cells perform better than macrophages, thus allowing them to gain the upper hand, and ultimately this iron ion capture not only promotes cancer cell survival, but also helps the cancer progress. later
researchers will continue to delve into the development of new targeted therapies based on the findings of this paper to treat metastatic cancers.
5.Science full-text compilation! Our scientists have structurally revealed a powerful therapeutic antibody and SARS-CoV-2 and SARS-CoV mechanism doi: 10.1126/science.abc5881 According to the World Health Organization (WHO), as of June 8, 2020, the 2019 coronavirus epidemic (COVID-19) pandemic has caused more than 7 million infections in more than 200 countries/regions and caused death.
the pathogen that caused the pandemic is an emerging coronavirus: SARS-CoV-2, which is associated with the closely related SARS-CoV, which belongs to the Coronavirus family of beta coronavirus.
the stinging glycoprotein (S) located in the SARS-CoV-2 and SARS-CoV envelopes has approximately 80% amino acid sequence consistency, and both viruses use human angiotensin conversion enzyme 2 (hACE2) to enter the host cell.
cell entry is achieved through viral-receptor binding mediated by The S protein homologous tripolymer, followed by viral-host membrane fusion, where this binding is carried out through the receptor binding domain (RBD) of the S protein.
destroys this key role of S proteins in infection establishment as the main goal of neutralizing antibodies, as well as therapeutic interventions and vaccine design.
H014 is a therapeuticly valuable B-line coronavirus cross-neutralizing antibodies, pictured from Science, 2020, doi:10.1126/science.abc5881.
THE RBD of SARS-CoV and SARS-CoV-2 has about 75% amino acid sequence consistency, so it is possible to find cross neutralizing antibodies targeting RBD. In a new study,
, researchers from the Chinese Academy of Sciences, the University of Chinese Academy of Military Medicine, the Chinese Academy of Medicine and Drug Administration, the Chinese Academy of Medical Sciences, the Beijing Concord Medical College, Beijing Shenzhou Cell Biotechnology Company and Beijing Yiju Shenzhou Technology Co., Ltd. used phage display technology to build an antibody bank that was produced from peripheral lymphocytes derived from mice immunized with recombinant SARS-CoVD.
use SARS-CoV-2 RBD as a target for screening the phage antibody pool to find potential targets.
will show antibodies that are tightly bound to SARS-CoV-2 RBD for further optimization as chimeric antibodies and test their neutrality using a pseudoviral system based on the blister oral inflammatory virus (VSV).