Colorectal cancer (CRC) is one of the top three most prevalent and deadly cancers. A cancer stem cell (CSC) sub-population that is characterized by the abilities of tumor initiation, self-renewal, ...metastasis and resistance to chemotherapy can suggest new therapeutic targets. However, no such sub-population has been conclusively identified for CRC, and we lack any marker to identify cells with all of the above characteristics. Here, we report that CD51
CRC cells displayed greater sphere-forming and tumorigenic capacities, increased migratory and invasive potentials, and enhanced chemoresistance compared with CD51
CRC cells. CD51 knockdown reduced the side population, sphere formation, cell motility and inhibited tumor incidence and metastasis in an in vivo tumor model. Furthermore, CD51 could bind transforming growth factor beta (TGF-β) receptors, and that it upregulated TGF-β/Smad signaling. These results indicate that CD51 is a novel functional marker for colorectal CSCs which may provide an therapeutic target for the efficient elimination of colorectal CSCs.
Abstract
In 2021, the Institute of High Energy Physics proposed a design of glass scintillator coupled with SiPM as a new solution for the next generation calorimeter, to explore the application of ...glass scintillators in high energy physics and nuclear radiation detection. The Large Area Glass Scintillator Collaboration Group was established to research and develop a glass scintillator with high density, high light yields and fast decay time. Through continuous optimization, the glasses have excellent scintillation performance with a light yield of 1000 ph/MeV and a density of 6 g/cm
3
. Moreover, the neutron response of the glasses was investigated, and different high-energy particles can be distinguished by signal amplitude. In addition, the radiation resistance of different glasses was tested under proton beam. All the glasses appeared opaque and produced a high radioactive background, because Gd element interacts with proton to produce radionuclides with high activity and long half-life.
Glutamate is the main excitatory neurotransmitter in central nervous system (CNS) and NMDA receptors are one of the major classes of ionotropic glutamate receptors. NMDA receptors have been known to ...play critical roles in normal CNS activities, as well as in many pathological conditions, including both acute and chronic diseases. The discovery of glycine as a coagonist of NMDA receptors has led to intensive research of glycine/NMDA antagonists as potential CNS drugs. The robust efficacy of glycine/NMDA antagonists, such as ACEA-1021 (5), in animal model of brain ischemia, together with good safety profile in animal models and in clinical trials, suggested that this class of NMDA antagonists should have good chance of success in the clinic as neuroprotectants. The clinical trial of ACEA-1021 for stroke was discontinued, mainly due to low solubility and lack of metabolism of the drug that led to the observation of crystals in the urine of some of the patients. However, through SAR studies, compounds such as ACEA-1416 (10) have been identified with improved properties, such as higher in vivo potency and site for potential metabolism. Therefore these compounds should be able to overcome some of the liabilities of ACEA-1021 and potentially could be developed as neuroprotectants. Based on the preclinical and clinical studies of glycine/NMDA antagonists, as well as the clinical experiences with t-PA, initiation of treatment within a short time window after the onset of stroke could be critical for the success of these antagonists in clinical trials. This can be accomplished by implementing the procedure developed for t-PA clinical trials, with modification based on the safety profile of glycine/NMDA antagonists, for future clinical trial to administer the drug as soon as possible after stroke onset. In addition, glycine/NMDA antagonists also have other potential therapeutic applications, such as for the treatment of traumatic brain injury, pain, cocaine overdose and convulsions.
Abstract Precision measurements of properties of the Higgs, W and Z bosons are the key scientific goals at future e + e - Higgs factories. A main challenge for these goals is to fulfill an ...unprecedented jet energy resolution, and the design of the hadronic calorimeter (HCAL) is found to be one of the most important factors. The conceptual design of high-granularity glass scintillator hadronic calorimeter (GSHCAL) has been proposed recently, which can achieve a Boson Mass Resolution (BMR) of around 3.38% with an initial parameter configuration and show great potential to significantly increase the sensitivities to the most physics measurements at future e^+e^- colliders. Nevertheless, more studies on the design optimization of the GSHCAL are necessary to balance the key physics performance (i.e. the BMR) and the cost, as well as the engineering complexity. In this paper, the optimizations for several key parameters of the GSHCAL are discussed and different GSHCAL configurations are compared, which provide an important reference for the GSHCAL design. Besides, the R&D progress of high-performance and large-area glass scintillators is also introduced.
Nucleostemin (NS) is preferentially and exclusively expressed in the stem cells and cancer cells, but not in differentiated adult tissues and cells. NS is likely to take part in controlling the ...proliferation and differentiation switch in stem cells and progenitor cells. Its deregulation in cancer also contributes to the elevated proliferation and undifferentiation of cancer cells. However, the mechanisms by which NS helps to maintain both cancer and stem cells in undifferentiated state remain unclear. In this study, we carried out gene profilings using oligonucleotide DNA microarray after knocking down the expression of NS in Hela cells. Of the 21,329 genes, 200 genes were found differentially expressed in NS silenced Hela cells with > 2 fold ratio (either > 2 or < 0.5). Category analysis indicated these differential genes were mainly related with cancer pathogenesis, cell death, cell growth and proliferation. NS related gene pathway analysis suggested NS was mostly involved in the networks of cell cycle and differentiation controls. p53 may not be the only partner of NS in its regulated pathways. c-Myc may directly or indirectly interact with it to control the proliferation and differentiation switch in cancer cells. Our study provides a general view of the NS-target genes, and indicates the possible pathways in which NS plays its role in proliferation control.
In this paper we present the fabrication and near-room temperature electrical transport properties of structures made from the gold-cluster material Au
55
P(C
6
H
5
)
3
12
Cl
6
. We discuss the use ...of electron-beam lithography to define the structures laterally and compare the direct current-voltage characteristics of non-patterned and patterned structures. In both cases non-linear behavior is observed with features that are consistent with Coulomb blockade dominated transport in disordered arrays of clusters. Radio frequency induced plateaus in the current-voltage characteristics demonstrate coherent tunneling. Finally, we show that other ligand stabilized gold-cluster materials can be used to form ordered gold-cluster arrays.
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