Since cancer stem cells (CSCs) were first identified in leukemia in 1994, they have been considered promising therapeutic targets for cancer therapy. These cells have self-renewal capacity and differentiation potential and contribute to multiple tumor malignancies, such as recurrence, metastasis, heterogeneity, multidrug resistance, and radiation resistance. The biological activities of CSCs are regulated by several pluripotent transcription factors, such as OCT4, Sox2, Nanog, KLF4, and MYC. In addition, many intracellular signaling pathways, such as Wnt, NF-κB (nuclear factor-κB), Notch, Hedgehog, JAK-STAT (Janus kinase/signal transducers and activators of transcription), PI3K/AKT/mTOR (phosphoinositide 3-kinase/AKT/mammalian target of rapamycin), TGF (transforming growth factor)/SMAD, and PPAR (peroxisome proliferator-activated receptor), as well as extracellular factors, such as vascular niches, hypoxia, tumor-associated macrophages, cancer-associated fibroblasts, cancer-associated mesenchymal stem cells, extracellular matrix, and exosomes, have been shown to be very important regulators of CSCs. Molecules, vaccines, antibodies, and CAR-T (chimeric antigen receptor T cell) cells have been developed to specifically target CSCs, and some of these factors are already undergoing clinical trials. This review summarizes the characterization and identification of CSCs, depicts major factors and pathways that regulate CSC development, and discusses potential targeted therapy for CSCs.Signal Transduction and Targeted Therapy (2020) 5:8; https://doi.
Recent analysis by manufacturers and network operators has shown that current wireless networks are not very energy efficient, particularly the base stations by which terminals access services from the network. In response to this observation the Mobile Virtual Centre of Excellence (VCE) Green Radio project was established in 2009 to establish how significant energy savings may be obtained in future wireless systems. This article discusses the technical background to the project and discusses models of current energy consumption in base station devices. It also describes some of the most promising research directions in reducing the energy consumption of future base stations.
Objective To provide a comprehensive and systematic analysis of demographic characteristics, clinical symptoms, laboratory findings and imaging features of coronavirus disease 2019 (COVID‐19) in pediatric patients. Methods A meta‐analysis was carried out to identify studies on COVID‐19 from December 25, 2019 to April 30, 2020. Results A total of 48 studies with 5829 pediatric patients were included. Children at all ages were at risk for COVID‐19. The main illness classification ranged as: 20% (95% CI: 14 to 26%, I 2 =91.4%) asymptomatic, 33% (95% CI: 23 to 43%, I 2 =95.6%) mild and 51% (95% CI: 42 to 61%, I 2 =93.4%) moderate. The typical clinical manifestations were fever 51% (95% CI: 45 to 57%, I 2 =78.9%) and cough 41% (95% CI: 35 to 47%, I 2 =81.0%). The common laboratory findings were normal white blood cell 69% (95% CI: 64 to 75%, I 2 =58.5%), lymphopenia 16% (95% CI: 11 to 21%, I 2 =76.9%) and elevated creatine‐kinase MB (CK‐MB) 37% (95% CI: 25 to 48%, I 2 =59.0%). The frequent imaging features were normal images 41% (95% CI: 30 to 52%, I 2 =93.4%) and ground‐glass opacity 36% (95% CI: 25 to 47%, I 2 =92.9%). Among children under 1‐year old, critical cases account for 14% (95% CI: 13 to 34%, I 2 =37.3%) that should be of concern. In addition, vomiting occurred in 33% (95% CI: 18 to 67%, I 2 =0.0%) cases that may also need attention. Conclusions Pediatric patients with COVID‐19 may experience milder illness with atypical clinical manifestations and rare lymphopenia. High incidence of critical illness and vomiting symptoms reward attention in children under 1‐year old. This article is protected by copyright. All rights reserved.
A high performance, binder-free flexible silicon electrode with high Si content up to 92% is developed for lithium ion batteries with a novel cellulose-based topological microscroll structure.
BackgroundAlthough accumulating data have suggested the development of cancer in systemic lupus erythematosus (SLE) patients, these results remain inconsistent. To examine such a putative association, this analysis reports the association between SLE and the risks of 24 cancer types.MethodsOnline databases PubMed, EMBASE, and Web of Science were searched comprehensively for eligible studies, published up to 15 May 2018. Pooled standardized incidence rates (SIRs) with 95% confidence intervals (CIs) were utilized to reveal their associations.ResultsA total of 24 eligible studies were ultimately enrolled. Our results indicated that SLE was associated with increased risk of overall cancers, cancer risk in both genders, non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, leukemia, multiple myeloma, cervix, vagina/vulva, renal, bladder, esophagus, gastric, hepatobiliary, lung, oropharynx, larynx, non-melanoma skin, and thyroid cancers. Additionally, SLE could reduce the risk of prostate cancer and cutaneous melanoma; however, it was not significantly associated with breast, uterus, ovarian, pancreatic, colorectal, or brain cancers.ConclusionsOur results shed light SLE being correlated with increased risk for 16 involved cancers and decreased risk for prostate cancer and cutaneous melanoma. This comprehensive meta-analysis provides epidemiological evidence supporting the associations between SLE and cancer risk. This evidence could be utilized to drive public policies and to help guide personalized medicine to better manage SLE and reduce associated cancer morbidity and mortality.Electronic supplementary materialThe online version of this article (10.1186/s13075-018-1760-3) contains supplementary material, which is available to authorized users.
Neural stimulation with high spatial and temporal precision is desirable both for studying the realtime dynamics of neural networks and for prospective clinical treatment of neurological diseases. Optical stimulation of genetically targeted neurons expressing the light sensitive channel protein Channelrhodopsin (ChR2) has recently been reported as a means for millisecond temporal control of neuronal spiking activities with cell-type selectivity. This offers the prospect of enabling local delivery of optical stimulation and the simultaneous monitoring of the neural activity by electrophysiological means, both in the vicinity of and distant to the stimulation site. We report here a novel dual-modality hybrid device, which consists of a tapered coaxial optical waveguide ('optrode') integrated into a 100 element intra-cortical multi-electrode recording array. We first demonstrate the dual optical delivery and electrical recording capability of the single optrode in in vitro preparations of mouse retina, photo-stimulating the native retinal photoreceptors while recording light-responsive activities from ganglion cells. The dual-modality array device was then used in ChR2 transfected mouse brain slices. Specifically, epileptiform events were reliably optically triggered by the optrode and their spatiotemporal patterns were simultaneously recorded by the multi-electrode array.
Textile displays are poised to revolutionize current electronic devices, and reshape the future of electronics and related fields such as biomedicine and soft robotics. However, they remain unavailable due to the difficulty of directly constructing electroluminescent devices onto the textile-like substrate to really display desired programmable patterns. Here, a novel textile display is developed from continuous electroluminescent fibers made by a one-step extrusion process. The resulting displaying textile is flexible, stretchable, three-dimensionally twistable, conformable to arbitrarily curved skins, and breathable, and can dynamically display a series of desired patterns, making it useful for bioinspired electronics, soft robotics, and electroluminescent skins, among other applications. It is demonstrated that these displaying textiles can also communicate with a computer and mouse brain for smart display and camouflage applications. This work may open up a new direction for the integration of wearable electroluminescent devices with the human body, providing new and promising communication platforms.
Using a well characterized model of cell-cell actin-based adherens junction (AJ) disruption by suppressing the intratesticular testosterone level in adult rats with testosterone-estradiol implants, we have confirmed earlier findings that Sertoli-germ cell AJ dynamics are regulated by the activation of kinases via putative signaling pathways but with some unexpected findings as follows. First, the loss of germ cells from the seminiferous epithelium during androgen suppression was associated with a surge in myotubularin-related protein 2 (MTMR2, a lipid phosphatase, in which adult MTMR2-/- mice were recently shown to be azoospermic because of the loss of cell adhesion function between germ and Sertoli cells); kinases: phosphatidylinositol 3-kinase, c-Src, and C-terminal Src kinase; adaptors: alpha-actinin, vinculin, afadin, and p130 Crk-associated protein; and AJ-integral membrane proteins at the ectoplasmic specialization (ES, a testis-specific cell-cell actin-based AJ type) site: N-cadherin, beta-catenin, integrin beta1, and nectin 3. Second, MTMR2, instead of structurally interacting with phosphatidylinositol 3-kinase, a protein and lipid kinase, was shown to associate only with c-Src, a nonreceptor protein tyrosine kinase, as demonstrated by both coimmunoprecipitation and fluorescent microscopy at the site of apical ES, but none of the kinases, adaptors, and AJ-integral proteins that were examined. Collectively, these results suggest that the MTMR2/c-Src is an important phosphatase/kinase protein pair in AJ dynamics in the testis. Because c-Src is known to associate with the cadherin/catenin protein complex at the ES in the testis, we next sought to investigate any changes in the protein-protein interactions of this protein complex during androgen suppression-induced germ cell loss. Indeed, there was a loss of N-cadherin and beta-catenin association, accompanied by a surge in Tyr phosphorylation of beta-catenin, during germ cell loss from the epithelium. Third, and perhaps the most important of all, during natural recovery of the epithelium after removal of testosterone-estradiol implants when spermatids were reattaching to Sertoli cells, an increase in N-cadherin and beta-catenin association was detected with a concomitant loss in the increased Tyr phosphorylation in beta-catenin. In summary, these results illustrate that the cadherin/catenin is a crucial cell adhesion complex that regulates AJ dynamics in the testis, and its functionality is likely modulated by the MTMR2/c-Src protein complex.
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