In the context of globalization, upper-middle-class parents choose international schools as an educational strategy to prepare their children to become cosmopolitans through the accumulation of ...linguistic and cosmopolitan cultural capital that can be transferred and bring advantages in the future. This article examines how legislative changes influence the international school market in China, affect parents’ choices while raising an ‘international’ child. In order to gain a competitive edge, this research hypothesized that parents might alter their school selection strategy and begin to accumulate ‘start-up’ capital for their children before compulsory schooling.
T-cell receptor (TCR) is crucial in T cell-mediated virus clearance. To date, TCR bias has been observed in various diseases. However, studies on the TCR repertoire of COVID-19 patients are lacking. ...Here, we used single-cell V(D)J sequencing to conduct comparative analyses of TCR repertoire between 12 COVID-19 patients and 6 healthy controls, as well as other virus-infected samples. We observed distinct T cell clonal expansion in COVID-19. Further analysis of VJ gene combination revealed 6 VJ pairs significantly increased, while 139 pairs significantly decreased in COVID-19 patients. When considering the VJ combination of α and β chains at the same time, the combination with the highest frequency on COVID-19 was TRAV12-2-J27-TRBV7-9-J2-3. Besides, preferential usage of V and J gene segments was also observed in samples infected by different viruses. Our study provides novel insights on TCR in COVID-19, which contribute to our understanding of the immune response induced by SARS-CoV-2.
•We performed single-cell V(D) J sequencing for 12 COVID-19 patients.•Comparative analyses of TCR repertoire between COVID-19 patients and controls, as well as other virus-infected samples.•TCR clonal diversity is significantly reduced in COVID-19 patients.•Preferential usage of T cell receptor is significantly different in several viral infections.
Abstract
Azulene-based conjugated systems are of great interests due to their unusual structures and photophysical properties. Incorporation of a transition metal into azulene skeleton presents an ...intriguing opportunity to combine the
d
π
-
p
π
and
p
π
-
p
π
conjugated properties. No such metallaazulene skeleton however has been reported to date. Here, we describe our development of an efficient 5 + 2 annulation reaction to rapid construction of a unique metal-containing 5-5-7 scaffold, termed metalla-dual-azulene (MDA), which includes a metallaazulene and a metal-free organic azulene intertwined by sharing the tropylium motif. The two azulene motifs in MDA exhibit distinct reactivities. The azulene motif readily undergoes nucleophilic addition, leading to N-, O- and S-substituted cycloheptanetrienyl species. Demetalation of the metallaazulene moiety occurs when it reacts with
n
Bu
4
NF, which enables highly selective recognition of fluoride anion and a noticeable color change. The practical 5 + 2 annulation methodology, facile functional-group modification, high and selective fluoride detection make this new π-conjugated polycyclic system very suitable for potential applications in photoelectric and sensing materials.
Immunotherapy is a practical therapeutic approach in breast cancer (BRCA), and the role of FLI1 in immune regulation has gradually been unveiled. However, the specific role of FLI1 in BRCA was ...conflicted; thus, additional convincing evidence is needed.
We explored the upstream regulation of FLI1 expression via summary data-based Mendelian randomization (SMR) analysis and ncRNA network construction centering on FLI1 using BRCA genome-wide association study (GWAS) summary data with expression quantitative trait loci (eQTLs) and DNA methylation quantitative trait loci (mQTLs) from the blood and a series of in silico analyses, respectively. We illuminated the downstream function of FLI1 in immune regulation by integrating a series of analyses of single-cell RNA sequence data (scRNA-seq).
We verified a causal pathway from FLI1 methylation to FLI1 gene expression to BRCA onset and demonstrated that FLI1 was downregulated in BRCA. FLI1, a transcription factor, served as myeloid and T cells' communication regulator by targeting immune-related ligands and receptor transcription in BRCA tissues. We constructed a ceRNA network centering on FLI1 that consisted of three LncRNAs (CKMT2-AS1, PSMA3-AS1, and DIO3OS) and a miRNA (hsa-miR-324-5p), and the expression of FLI1 was positively related to a series of immune-related markers, including immune cell infiltration, biomarkers of immune cells, and immune checkpoints.
Low-methylation-induced or ncRNA-mediated downregulation of FLI1 is associated with poor prognosis, and FLI1 might regulate the tumor immune microenvironment via a cell-type-specific target genes manner in BRCA.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In this study, a simple one-pot method was used to prepare a multifunctional platform for synergistic chemo- and photothermal therapy,, which is composed of zeolitic imidazolate framework-8 (ZIF-8) ...as drug nanocarriers and the embedded graphene quantum dots (GQDs) as local photothermal seeds. The structure, drug release behavior, photothermal effect, and synergistic therapeutic efficiency of the ZIF-8/GQD nanoparticles were systematically investigated. Using doxorubicin (DOX) as a model anticancer drug, the results showed that monodisperse ZIF-8/GQD nanoparticles with a particle size of 50–100 nm could encapsulate DOX during the synthesis procedure and trigger DOX release under acidic conditions. The DOX-loaded ZIF-8/GQD nanoparticles could efficiently convert near-infrared (NIR) irradiation into heat and thereby increase the temperature. More importantly, with breast cancer 4T1 cells as a model cellular system, the results indicated that the combined chemo- and photothermal therapy with DOX-ZIF-8/GQD nanoparticles exhibited a significant synergistic effect, resulting in a higher efficacy to kill cancer cells compared with chemotherapy and photothermal therapy alone. Hence, ZIF-8/GQD nanoparticles would be promising as versatile nanocarriers for synergistic cancer therapy.
Given the chronic inflammatory nature of Parkinson's disease (PD), T cell immunity may be important for disease onset. Here, we performed single-cell transcriptome and TCR sequencing, and conducted ...integrative analyses to decode composition, function and lineage relationship of T cells in the blood and cerebrospinal fluid of PD. Combined expression and TCR-based lineage tracking, we discovered a large population of CD8
T cells showing continuous progression from central memory to terminal effector T cells in PD patients. Additionally, we identified a group of cytotoxic CD4
T cells (CD4 CTLs) remarkably expanded in PD patients, which derived from Th1 cells by TCR-based fate decision. Finally, we screened putative TCR-antigen pairs that existed in both blood and cerebrospinal fluid of PD patients to provide potential evidence for peripheral T cells to participate in neuronal degeneration. Our study provides valuable insights and rich resources for understanding the adaptive immune response in PD.
Rubidium laser optically pumped magnetometers (OPMs) are widely used magnetic sensors based on the Zeeman effect, laser pumping, and magnetic resonance principles. They measure the magnetic field by ...measuring the magnetic resonance signal passing through a rubidium atomic gas cell. The quality of the magnetic resonance signal is a necessary condition for a magnetometer to achieve high sensitivity. In this research, to obtain the best magnetic resonance signal of rubidium laser OPMs in the Earth’s magnetic field intensity, the experiment system of rubidium laser OPMs is built with a rubidium atomic gas cell as the core component. The linewidth and amplitude ratio (LAR) of magnetic resonance signals is utilized as the optimization objective function. The magnetic resonance signals of the magnetometer experiment system are experimentally measured for different laser frequencies, radio frequency (RF) intensities, laser powers, and atomic gas cell temperatures in a background magnetic field of 50,765 nT. The experimental results indicate that optimizing these parameters can reduce the LAR by one order of magnitude. This shows that the optimal parameter combination can effectively improve the sensitivity of the magnetometer. The sensitivity defined using the noise spectral density measured under optimal experimental parameters is 1.5 pT/Hz1/2@1 Hz. This work will provide key technical support for rubidium laser OPMs’ product development.
SPTBN2 is a protein-coding gene that is closely related to the development of malignant tumors. However, its prognostic value and biological function in pan-cancer, especially pancreatic cancer ...(PAAD), have not been reported. In the present study, a novel exploration of the value and potential mechanism of SPTBN2 in PAAD was conducted using multi-omics in the background of pan-cancer. Via various database analysis, up-regulated expression of SPTBN2 was detected in most of the tumor tissues examined. Overexpression of SPTBN2 in PAAD and kidney renal clear cell cancer patients potentially affected overall survival, disease-specific survival, and progression-free interval. In PAAD, SPTBN2 can be used as an independent factor affecting prognosis. Mutations and amplification of SPTBN2 were detected, with abnormal methylation of SPTBN2 affecting its expression and the survival outcome of PAAD patients. Immunoassay results demonstrate that SPTBN2 was a potential biomarker for predicting therapeutic response in PAAD, and may influence the immunotherapy efficacy of PAAD by regulating levels of CD8 + T cells and neutrophil infiltration. Results from an enrichment analysis indicated that SPTBN2 may regulate the development of PAAD via immune pathways. Thus, SPTBN2 is a potential prognostic biomarker and immunotherapy target based on its crucial role in the development of PAAD.
In order to reveal the dynamics of brain network, we proposed a new research method based on the Hindmarsh–Rose model. In the method, a neural network model was developed by constructing a functional ...brain network topology based on functional magnetic resonance imaging resting-state data and using Hindmarsh–Rose neurons as nodes in place of the brain regions belonging to the functional brain network. The dynamics of the functional brain network were investigated using the dynamics model. The simulation results showed that the dynamic behaviors of the brain regions in the functional brain network could be divided into three types: stable, chaotic, and periodical bursts. A state space was introduced to analyze the dynamic behavior of the brain regions in the network. We find that increasing excitation and mutual connection strength among brain regions enhanced network communication capabilities in the state space. Both the periodic and stable modes exhibited stronger communication capabilities than the chaotic mode. Despite individual differences in the dynamics of brain regions among subjects, brain regions in the periodic mode were highly consistent and corresponded to key regions of the default mode network in the resting state.
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