Abstract
N6-methyladenosine (m6A) is a common modification on endogenous RNA transcripts in mammalian cells. Technologies to precisely modify the RNA m6A levels at specific transcriptomic loci ...empower interrogation of biological functions of epitranscriptomic modifications. Here, we developed a bidirectional dCasRx epitranscriptome editing platform composed of a nuclear-localized dCasRx conjugated with either a methyltransferase, METTL3, or a demethylase, ALKBH5, to manipulate methylation events at targeted m6A sites. Leveraging this platform, we specifically and efficiently edited m6A modifications at targeted sites, reflected in gene expression and cell proliferation. We employed the dCasRx epitranscriptomic editor system to elucidate the molecular function of m6A-binding proteins YTHDF paralogs (YTHDF1, YTHDF2 and YTHDF3), revealing that YTHDFs promote m6A-mediated mRNA degradation. Collectively, our dCasRx epitranscriptome perturbation platform permits site-specific m6A editing for delineating of functional roles of individual m6A modifications in the mammalian epitranscriptome.
In recent years, there have been an increasing number of studies on trigeminal neuralgia (TN). However, a scientific and comprehensive study of the current situation and trends in the field of TN ...research is lacking. The purpose of this study is to summarize and visualize the development, research hotspots, and future trends in TN based on a bibliometric approach.
Studies on TN published from 2001 to 2021 were obtained from the Web of Science Core Collection (WoSCC). Bibliometrics, CiteSpace, and VOSviewer tools were used for bibliometric analysis and visualization.
In total, 4,112 documents were searched. The number of research articles in the field is generally on an upward trend, with the fastest growth in the number of articles from 2017 to 2020. Shanghai Jiao Tong University, Pittsburgh University, and Mayo Clinic are the three institutions with the most publications. Shiting Li and Zakrzewska JM are the most prolific author and top co-cited authors, respectively.
is the most influential journal. The top 5 keywords in that time frame are TN, microvascular decompression, facial pain, stereotactic radiosurgery, and neuropathic pain.
This is the first comprehensive scientific bibliometric analysis of the global research field on TN over the past 21 years, providing a meaningful reference for further exploration of topical issues and research trends in the field.
Concomitant malignant tumors and pregnancy present many difficult questions to both clinicians and patients. Due to no specific guidelines, each aspect of clinical management requires special ...considerations. This current report presents a rare case of a 38-year-old pregnant woman at gestational age 33 weeks with complaints of weakness of her right limbs for 2 weeks. After successive cesarean section and craniotomy, a diagnosis of lung large cell neuroendocrine carcinoma (LCNEC) metastatic to the brain was eventually made. Next generation sequencing (NGS) showed ALK-EML4 gene fusion. Immediately afterwards she was started on the targeted therapy with the ALK inhibitor alectinib. Ten months later, all known lesions exhibited a rapid regression, and no new brain metastases were found. Consequently, the therapeutic effect was considered as a partial response. Then, we review the previous literature using PubMed on maternal malignant brain tumors diagnosed during pregnancy, or lung LCNEC associated with ALK fusion, or ALK inhibitors treatment among the pregnant women, eventually, and discuss the concerns of dealing with these patients.
Aim
The complement cascade is activated and may play an important pathophysiologic role in brain injury after experimental intracerebral hemorrhage (ICH). However, the exact mechanism of specific ...complement components has not been well studied. This study determined the role of complement C1q/C3-CR3 signaling in brain injury after ICH in mice. The effect of minocycline on C1q/C3-CR3 signaling-induced brain damage was also examined.
Methods
There were three parts to the study. First, the natural time course of C1q and CR3 expression was determined within 7 days after ICH. Second, mice had an ICH with CR3 agonists, LA-1 or vehicle. Behavioral score, neuronal cell death, hematoma volume, and oxidative stress response were assessed at 7 days after ICH. Third, the effect of minocycline on C1q/C3-CR3 signaling and brain damage was examined.
Results
There were increased numbers of C1q-positive and CR3-positive cells after ICH. Almost all perihematomal C1q-positive and CR3-positive cells were microglia/macrophages. CR3 agonist LA-1 aggravated neurological dysfunction, neuronal cell death, and oxidative stress response on day 7 after ICH, as well as enhancing the expression of the CD163/HO-1 pathway and accelerating hematoma resolution. Minocycline treatment exerted neuroprotective effects on brain injury following ICH, partly due to the inhibition of C1q/C3-CR3 signaling, and that could be reversed by LA-1.
Conclusions
The complement C1q/C3-CR3 signaling is upregulated after ICH. The activation of C1q/C3-CR3 signaling by LA-1 aggravates brain injury following ICH. The neuroprotection of minocycline, at least partly, is involved with the repression of the C1q/C3-CR3 signaling pathway.
The gut microbiota plays a key role in regulating intracerebral hemorrhage (ICH)-induced neuroinflammation. The anti-neuroinflammatory effects of metformin (Met) have been reported in many central ...nervous system (CNS) diseases. However, whether Met regulates neuroinflammation through the gut microbiota in ICH-induced brain injury remains unknown. We found that Met treatment substantially alleviated neurological dysfunction and reduced neuroinflammation by inhibiting pro-inflammatory polarization of microglia/macrophages in mice with ICH. Moreover, Met treatment altered the microbiota composition and improved intestinal barrier function. The expression of lipopolysaccharide-binding protein (LBP), a biomarker of intestinal barrier damage, was also significantly reduced by Met treatment. Neuroinflammation was also potently ameliorated after the transplantation of fecal microbiota from Met-treated ICH mice. The neuroprotective effects of fecal microbiota transplantation (FMT) were similar to those of oral Met treatment. However, suppression of the gut microbiota negated the neuroprotective effects of Met in ICH mice. Therefore, Met is a promising therapeutic agent for neuroinflammation owing to ICH-induced imbalance of the gut microbiota.
Matricellular proteins are nonstructural extracellular matrix components that are expressed at low levels in normal adult tissues and are upregulated during development or under pathological ...conditions. Tenascin C (TNC), a matricellular protein, is a hexameric and multimodular glycoprotein with different molecular forms that is produced by alternative splicing and post-translational modifications. Malignant gliomas are the most common and aggressive primary brain cancer of the central nervous system. Despite continued advances in multimodal therapy, the prognosis of gliomas remains poor. The main reasons for such poor outcomes are the heterogeneity and adaptability caused by the tumor microenvironment and glioma stem cells. It has been shown that TNC is present in the glioma microenvironment and glioma stem cell niches, and that it promotes malignant properties, such as neovascularization, proliferation, invasiveness, and immunomodulation. TNC is abundantly expressed in neural stem cell niches and plays a role in neurogenesis. Notably, there is increasing evidence showing that neural stem cells in the subventricular zone may be the cells of origin of gliomas. Here, we review the evidence regarding the role of TNC in glioma progression, propose a potential association between TNC and gliomagenesis, and summarize its clinical applications. Collectively, TNC is an appealing focus for advancing our understanding of gliomas.
Abstract
How to reduce the amount of wasted cooling in corridors and gaps is a problem in data center air conditioning design. Modeling the data center airflow data and simulating the temperature ...distribution are the prerequisites and key points to solve this problem. This paper uses the optimal idea to establish a mathematical model to simulate the location of the air conditioning vent. Determine the layout of the computer cabinet based on the analysis of the internal and external environment of the computer cabinet. The external environment analysis is mainly the analysis of several directions: According to the CFD simulation and simulation, the wind speed and tuyere arrangement of the air supply port are compared and the optimal wind speed of the air supply port is obtained. For the problem of the ceiling height and the spacing of the upper air outlet, discuss the method of determining the air supply spacing on the air duct so that the upper air supply can cover all the air inlets of the cabinet to achieve the most reasonable air supply flow. For the numerical simulation and optimization of the airflow organization in the equipment room, it is easy to know that the farther away from the air conditioner, the higher the temperature is relative to the air conditioner, and the wind speed far from the air conditioner is relatively large, so the temperature in the distance is higher. Also, because the hot aisle has no ventilation slots, its temperature must be higher than the cold aisle. Therefore, the temperature in the hot aisle is higher than the ground and the air conditioner is far away. According to the airflow dynamic equation and the K-ε turbulence model equation, the Fluent software is used, and combined with the data given in the data center room, the airflow data is simulated. Finally, the best solution for setting the position of the air conditioning air outlet is given.
In present study, photoionization and dissociation of acetic acid dimers have been studied with the synchrotron vacuum ultraviolet photoionization mass spectrometry and theoretical calculations. ...Besides the intense signal corresponding to protonated cluster ions (CH(3)COOH)(n)·H(+), the feature related to the fragment ions (CH(3)COOH)H(+)·COO (105 amu) via β-carbon-carbon bond cleavage is observed. By scanning photoionization efficiency spectra, appearance energies of the fragments (CH(3)COOH)·H(+) and (CH(3)COOH)H(+)·COO are obtained. With the aid of theoretical calculations, seven fragmentation channels of acetic acid dimer cations were discussed, where five cation isomers of acetic acid dimer are involved. While four of them are found to generate the protonated species, only one of them can dissociate into a C-C bond cleavage product (CH(3)COOH)H(+)·COO. After surmounting the methyl hydrogen-transfer barrier 10.84 ± 0.05 eV, the opening of dissociative channel to produce ions (CH(3)COOH)(+) becomes the most competitive path. When photon energy increases to 12.4 eV, we also found dimer cations can be fragmented and generate new cations (CH(3)COOH)·CH(3)CO(+). Kinetics, thermodynamics, and entropy factors for these competitive dissociation pathways are discussed. The present report provides a clear picture of the photoionization and dissociation processes of the acetic acid dimer in the range of the photon energy 9-15 eV.
A novel threshold photoelectron-photoion coincidence (TPEPICO) imaging spectrometer at the U14-A beamline of the Hefei National Synchrotron Radiation Laboratory is presented. A set of open electron ...and ion lenses are utilized to map velocity imaging of photoelectrons and photoions simultaneously, in which a repelling electric field using an extra lens is applied to magnify images of photoelectrons instead of traditional accelerating electric field in order to suppress the contribution of energetic electrons in the threshold photoelectron spectroscopy (TPES) and the mass-selected TPEPICO spectroscopy. The typical energy resolution of TPES is measured to be 9 meV (full width at half maximum), as shown on the (2)P(1/2) ionization of argon. The measured mass resolving power for the present TPEPICO imaging spectrometer is above 900 of M/DeltaM. Subsequently as a benchmark, oxygen molecule is photoionized by monochromatic synchrotron radiation at 20.298 eV and dissociates to an oxygen atomic ion and a neutral oxygen atom, and the translation energy distribution of oxygen atomic ion is measured by the time-sliced imaging based on mass-selected TPEPICO experiment. The kinetic energy resolution of the present ion velocity imaging is better than 3% of DeltaE/E.
The mesenchymal (MES) phenotype of glioblastoma (GBM) is the most aggressive and therapy-resistant subtype of GBM. The MES phenotype transition during tumor progression results from both ...tumor-intrinsic genetic alterations and tumor-extrinsic microenvironmental factors. In this study, we sought to identify genes that can modulate the MES phenotype via both mechanisms. By integrating weighted gene co-expression network analysis (WGCNA) and the differential expression analysis of hypoxia-immunosuppression-related genes, we identified the plasminogen activator, urokinase receptor (PLAUR) as the hub gene. Functional enrichment analysis and GSVA analysis demonstrated that PLAUR was associated with the MES phenotype of glioma and the hypoxia-immunosuppression-related microenvironmental components. Single-cell sequencing analysis revealed that PLAUR mediated the ligand-receptor interaction between tumor-associated macrophages (TAMs) and glioma cells. Functional experiments in vitro with cell lines or primary glioma cells and xenograft models using BALB/c nude mice confirmed the role of PLAUR in promoting the MES phenotype of GBM. Our findings indicate that PLAUR regulates both glioma cells and tumor cell-extrinsic factors that favor the MES phenotype and suggest that PLAUR might be a potential target for GBM therapy.
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