Early invasive growth along specific anatomical structures, especially the white matter tract, is regarded as one of the main causes of poor therapeutic outcome of people with gliomas. We show that ...some glioma stem cells (GSCs) are preferentially located along white matter tracts, which exhibit a demyelinated phenotype, at the invasive frontier of glioma tissues. These GSCs are CD133
Notch1
, whereas the nerve fibers express the Notch ligand Jagged1. The Notch-induced transcription factor Sox9 promotes the transcription of SOX2 and the methylation level of the NOTCH1 promoter is attenuated by the upregulation of SOX2 to reinforce NOTCH1 expression in GSCs. This positive-feedback loop in a cohort of glioma subjects is correlated with a poor prognosis. Inhibition of Notch signaling attenuates the white-matter-tract tropism of GSCs. These findings provide evidence indicating that the NOTCH1-SOX2 positive-feedback loop controls GSC invasion along white matter tracts.
A central neural circuit for itch sensation Mu, Di; Deng, Juan; Liu, Ke-Fei ...
Science (American Association for the Advancement of Science),
08/2017, Letnik:
357, Številka:
6352
Journal Article
Recenzirano
Although itch sensation is an important protective mechanism for animals, chronic itch remains a challenging clinical problem. Itch processing has been studied extensively at the spinal level. ...However, how itch information is transmitted to the brain and what central circuits underlie the itch-induced scratching behavior remain largely unknown. We found that the spinoparabrachial pathway was activated during itch processing and that optogenetic suppression of this pathway impaired itch-induced scratching behaviors. Itch-mediating spinal neurons, which express the gastrin-releasing peptide receptor, are disynaptically connected to the parabrachial nucleus via glutamatergic spinal projection neurons. Blockade of synaptic output of glutamatergic neurons in the parabrachial nucleus suppressed pruritogen-induced scratching behavior. Thus, our studies reveal a central neural circuit that is critical for itch signal processing.
The contribution of long noncoding RNAs (lncRNAs) to pancreatic cancer progression and the regulatory mechanisms of their expression are attractive areas. In the present study, the overexpression of ...lncRNA-BX111887 (BX111) in pancreatic cancer tissues was detected by microarray and further validated in a cohort of pancreatic cancer tissues. We further demonstrated that knockdown or overexpression of BX111 dramatically repressed or enhanced proliferation and invasion of pancreatic cancer cells. Mechanically, BX111 activated transcription of ZEB1, a key regulator for epithelia-mesenchymal transition (EMT), via recruiting transcriptional factor Y-box protein (YB1) to its promoter region. Moreover, we revealed that BX111 transcription was induced by hypoxia-inducible factor (HIF-1α) in response to hypoxia. In addition, BX111 contributed to the hypoxia-induced EMT of pancreatic cells by regulating expression of ZEB1 and its downstream proteins E-cadherin and MMP2. Coincidence with in vitro results, BX111 depletion effectively inhibited growth and metastasis of xenograft tumor in vivo. The clinical samples of pancreatic cancer further confirmed a positive association between BX111 and ZEB1. Moreover, high BX111 expression was correlated with late TNM stage, lymphatic invasion and distant metastasis, as well as short overall survival time in patients. Taken together, our findings implicate a hypoxia-induced lncRNA contributes to metastasis and progression of pancreatic cancer, and suggest BX111 might be applied as a potential biomarker and therapeutic target for pancreatic cancer.
Metabolism reprogramming has been linked with the initiation, metastasis, and recurrence of cancer. The aldehyde dehydrogenase (ALDH) family is the most important enzyme system for aldehyde ...metabolism. The human ALDH family is composed of 19 members. ALDH1A3 participates in various physiological processes in human cells by oxidizing all‐trans‐retinal to retinoic acid. ALDH1A3 expression is regulated by many factors, and it is associated with the development, progression, and prognosis of cancers. In addition, ALDH1A3 influences a diverse range of biological characteristics within cancer stem cells and can act as a marker for these cells. Thus, growing evidence indicates that ALDH1A3 has the potential to be used as a target for cancer diagnosis and therapy.
Efficient production of ammonia using environmentally friendly techniques under ambient conditions is crucial to renewable energy storage and industrial applications, and catalysts with new reaction ...pathways are highly desirable. In this work, black phosphorus (BP) is used as a metal‐free 2D catalyst for the photoelectrochemical (PEC) nitrogen reduction reaction (NRR). The electrode is fabricated by layer‐by‐layer assembly of BP nanosheets on an indium tin oxide substrate. The PEC NRR activity in the N2 saturated aqueous electrolyte without a sacrificial agent is excellent, as exemplified by an ammonia yield rate of 102.4 µg h−1 mgcat.−1 and Faradaic efficiency of 23.3% at −0.4 V, which are the best among nonmetal catalysts for synthesis of ammonia by photocatalysis and electrocatalysis. Furthermore, the BP electrode shows excellent stability after 6 consecutive cycles. The excellent PEC catalytic properties are attributed to the light excitation enhanced electrocatalytic process and that the external bias promoted photocatalytic process improves ammonia production synergistically. The results not only demonstrate the great potential of BP in PEC catalysis, but also identify a promising technique to produce ammonia under ambient conditions using solar energy and electric energy.
Black phosphorus (BP) is developed as a metal‐free 2D catalyst for the photoelectrochemical synthesis of ammonia at ambient conditions. The ammonia yield rate and Faradaic efficiency in acid electrolyte is determined as 102.4 µg h−1 mgcat.−1 and 23.3%, respectively. The excellent catalytic properties of BP are attributed to the synergistic effects of photoexcitation enhanced electrocatalysis and external bias promoted photocatalysis.
Minerals such as calcium carbonates and calcium phosphates are often used as drug protein carriers, which are urgently required for drug protein‐based therapy, due to their high biocompatibility. ...However, their performance is constrained by some obstacles, such as the low loading capacity and short circulation half‐life. Inspired by the in vivo growth of biominerals via the soluble protein‐stabilized amorphous precursors, herein drug proteins are directly used to stabilize amorphous carbonated calcium phosphate (ACCP) in a controlled mineralization environment. The bioactivity of the drugs in the ACCP carrier is preserved due to the mild synthesis condition. The intrinsically high absorption capability of the ACCP nanoparticles (NPs) leads to an ultra‐high protein loading capacity. In addition, the amorphous nature of the carrier ensures the homogeneous distribution of the protein molecules in the carrier, by which the drugs exhibit long‐term release in vitro. The effectiveness of this strategy by the high osteogenic ability of insulin‐like growth factor‐1 loaded ACCP NPs is demonstrated. Therefore, this biomimetic strategy provides a promising nanoplatform for drug protein‐based applications.
Inspired by the role of soluble proteins in biomineralization, drug proteins are used to stabilize amorphous carbonated calcium phosphate (ACCP) nanoparticles (NPs) under controlled conditions. The ACCP NPs exhibit a high protein loading amount and long‐acting release time. As a demonstration, ACCP loaded with insulin‐like growth factor‐1 shows excellent osteogenesis ability due to the well‐retained bioactivity of the protein.
A wideband linearly polarized transmitarray antenna operating in 7-16 GHz is presented in this paper. First, a wideband element with three metallic layers is proposed, which is composed of a split ...circular ring connected by a narrow strip in the middle layer, and two polarizers in the upper and bottom layers. This element features a low transmission loss and approximately linear phase curves in a wide frequency band over one octave. Then, an optimization method is introduced to design the transmitarray that follows the bandwidth definition of 1 dB gain drop. The first key point of this method is determining the transmitarray element distribution with the weighted reference phases. The second is realizing wideband performances by controlling the calculated directivities and radiation patterns of the modified wideband transmitarray model at all operating frequencies. In the experiment, a <inline-formula> <tex-math notation="LaTeX">25\times 25 </tex-math></inline-formula>-element horn-fed transmitarray with a <inline-formula> <tex-math notation="LaTeX">240 \times 240 </tex-math></inline-formula> mm 2 aperture area is designed and fabricated. The simulated results show that its bandwidths of 0.5, 1.5, and 3 dB gain drop are 41%, 56%, and 71%, respectively. Moreover, a peak aperture efficiency of 40.7% is achieved. Measured results agree reasonably well with the simulated ones. These results validate the proposed wideband element and the optimization method.
Group 2 innate lymphoid cells (ILC2s) are emerging as key players in the pathogenesis of allergic airway inflammation. The mechanisms regulating ILC2, however, are not fully understood. Here, we ...found that ICAM-1 is required for the development and function of ILC2. ICAM-1-deficient (
) mice displayed significantly lower levels of ILC2s in the bone marrow and peripheral tissues than wild-type controls. CLP transfer and in vitro culture assays revealed that the regulation of ILC2 by ICAM-1 is cell intrinsic. Furthermore, ILC2s from
mice were functionally impaired, as indicated by the diminished production of type-2 cytokines in response to IL-33 challenge. The reduction in lung ILC2s caused a clear remission of airway inflammation in
mice after administration of papain or
We further demonstrate that ILC2 defects caused by ICAM-1 deficiency are due to ERK signaling-dependent down-regulation of GATA3 protein. Collectively, these observations identify ICAM-1 as a novel regulator of ILC2.
The human genome contains thousands of noncoding RNAs (ncRNAs), which are thought to lack open reading frames (ORFs) and cannot be translated. Some ncRNAs reportedly have important functions, ...including epigenetic regulation, chromatin remolding, protein modification, and RNA degradation, but the functions of most ncRNAs remain elusive. Through the application and development of ribosome profiling and sequencing technologies, an increasing number of studies have discovered the translation of ncRNAs. Although ncRNAs were initially defined as noncoding RNAs, a number of ncRNAs actually contain ORFs that are translated into peptides. Here, we summarize the available methods, tools, and databases for identifying and validating ncRNA-encoded peptides/proteins, and the recent findings regarding ncRNA-encoded small peptides/proteins in cancer are compiled and synthesized. Importantly, the role of ncRNA-encoding peptides/proteins has application prospects in cancer research, but some potential challenges remain unresolved. The aim of this review is to provide a theoretical basis that might promote the discovery of more peptides/proteins encoded by ncRNAs and aid the further development of novel diagnostic and prognostic cancer markers and therapeutic targets.
•Some ncRNAs are translated into stable peptides or proteins, expanding the landscape of the proteome.•Some tools, methods and databases are designed for identifying and validating ncRNA-encoded peptides related with cancer.•The translation of lncRNAs provides a novel molecular mechanism to participate in complex regulatory networks of cells.•CircRNA-encoded peptides in cancer may become drug targets and biomarkers for diagnosing or predicting the prognosis.
The direct asymmetric α‐hydroxylation of β‐dicarbonyl compounds has been developed using cinchona‐derived phase‐transfer catalysts in batch and semi‐flow processes. Using visible light as the driving ...force and air as oxidant, the corresponding products were obtained in excellent yields (up to 96%) and good enantioselectivities (up to 90% ee). The catalyst acts as a chiral center and a catalytic center and forms a chiral enolate complex with the substrate to act as a photosensitive center in the reaction. The use of semi‐flow photochemical processes allowed a reduction in reaction time (24 h to 0.89 h) and good yields (up to 93%) and enantioselectivities (up to 88% ee) were obtained.
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