The mechanism of antigen‐specific regulatory T cell (Treg) induction is not yet fully understood. Curcumin has an immune regulatory function. This study aims to induce antigen‐specific Tregs by ...employing extracellular vesicles (EVs) that carry two types of T cell activators. Two types of T cell activators, ovalbumin (OVA)/major histocompatibility complex‐II (MHC‐II) and tetramethylcurcumin (FLLL31) (a curcumin analog) were carried by dendritic cell‐derived extracellular vesicles, designated OFexo. A murine model of allergic rhinitis (AR) was developed with OVA as the specific antigen. AR mice were treated with a nasal instillation containing OFexo. We observed that OFexo recognized antigen‐specific T cell receptors (TCR) on CD4+ T cells and enhanced Il10 gene transcription in CD4+ T cells. Administration of the OFexo‐containing nasal instillation induced antigen‐specific type 1 Tregs (Tr1 cells) in the mouse airway tissues. OFexo‐induced Tr1 cells showed immune suppressive functions on CD4+ T cell proliferation. Administration of OFexo efficiently alleviated experimental AR in mice. In conclusion, OFexo can induce antigen‐specific Tr1 cells that can efficiently alleviate experimental AR. The results suggest that OFexo has the translational potential to be employed for the treatment of AR or other allergic disorders.
Administration of OFexo can induce Ag‐specific Tr1 cells in the airway tissues, which efficiently alleviate experimental AR. The results suggest that OFexo has the translational potential to be employed for the treatment of AR or other allergic disorders.
A bioactive polysaccharide from microalga Chlorella pyrenoidosa (CPP) was successively prepared via DEAE-52 and G-100 columns. Nuclear magnetic resonance analysis showed that the main glycosidic ...bonds were composed of 1,2-linked-α-l-Fucp, 1,4-linked-α-l-Rhap, 1,4-linked-β-l-Araf, 1-linked-α-d-Glcp, 1,3-linked-β-d-GlcpA, 1,4-linked-β-d-Xylp, and 1,3,6-linked-β-d-Manp. Its molecular weight was 5.63 × 106 Da. The hypolipidemic effect and intestinal flora regulation of CPP on diet-induced rats were evaluated through histopathology and biochemistry analyses. CPP could improve plasma and liver lipid metabolism and accelerate the metabolism of the cecal total bile acids and short-chain fatty acids. CPP has also upregulated the adenosine-monophosphate-activated protein kinase α and downregulated the acetyl-CoA carboxylase, sterol regulatory element-binding protein 1c, and β-hydroxy β-methylglutaryl-CoA expressions. Moreover, with the 16S rRNA gene sequencing, it was revealed that the composition of intestinal flora changed drastically after treatment, such as the bloom of Coprococcus_1, Lactobacillus, and Turicibacter, whereas there was a strong reduction of the Ruminococcus_gauvreauii_group. The above results illustrated that CPP might be served as an effective ingredient to ameliorate lipid metabolism disorders and intestinal flora in hyperlipidemia rats.
Tea is the world's oldest and most popular caffeine-containing beverage with immense economic, medicinal, and cultural importance. Here, we present the first high-quality nucleotide sequence of the ...repeat-rich (80.9%), 3.02-Gb genome of the cultivated tea tree Camellia sinensis. We show that an extraordinarily large genome size of tea tree is resulted from the slow, steady, and long-term amplification of a few LTR retrotransposon families. In addition to a recent whole-genome duplication event, lineage-specific expansions of genes associated with flavonoid metabolic biosynthesis were discovered, which enhance catechin production, terpene enzyme activation, and stress tolerance, important features for tea flavor and adaptation. We demonstrate an independent and rapid evolution of the tea caffeine synthesis pathway relative to cacao and coffee. A comparative study among 25 Camellia species revealed that higher expression levels of most flavonoid- and caffeinebut not theanine-related genes contribute to the increased production of catechins and caffeine and thus enhance tea-processing suitability and tea quality. These novel findings pave the way for further metabolomic and functional genomic refinement of characteristic biosynthesis pathways and will help develop a more diversified set of tea flavors that would eventually satisfy and attract more tea drinkers worldwide.
Aetiologies of bronchiectasis in mainland China and their comparisons with those in western countries are unknown. We aimed to investigate bronchiectasis aetiologies in Guangzhou, southern China, and ...to determine ethnic or geographic differences with reports from western countries.
Consecutive patients with steady-state bronchiectasis were randomly recruited. Past history was meticulously extracted. Patients underwent physical examination, saccharine test, humoral immunity assays, gastroesophageal reflux scoring and sputum culture. Fiberoptic bronchoscopy, total immunoglobin E (IgE) and Aspergillus fumigatus-specific IgE measurement, 24-h gastroesophageal pH monitoring and miscellaneous screening tests were performed, if indicated. This entailed comparisons on aetiologies with literature reports.
We enrolled 148 patients (44.6 ± 13.8 years, 92 females), most of whom had mild to moderate bronchiectasis. Idiopathic (46.0%), post-infectious (27.0%) and immunodeficiency (8.8%) were the most common aetiologies. Miscellaneous aetiologies consisted of asthma (5.4%), gastroesophageal reflux (4.1%), aspergillosis (2.7%), congenital lung malformation (2.0%), Kartagener syndrome (1.4%), rheumatoid arthritis (1.4%), chronic obstructive pulmonary disease (0.7%), Young's syndrome (0.7%), yellow nail's syndrome (0.7%), eosinophilic bronchiolitis (0.7%) and foreign bodies (0.7%). No notable differences in clinical characteristics between idiopathic and known aetiologies were found. Ethnic or geographic variations of aetiologies were overall unremarkable.
Idiopathic, post-infectious and immunodeficiency constitute major bronchiectasis aetiologies in Guangzhou. Clinical characteristics of patients between known aetiologies and idiopathic bronchiectasis were similar. Ethnicity and geography only account for limited differences in aetiologic spectra. These findings will offer rationales for early diagnosis and management of bronchiectasis in future studies and clinical practice in China.
Gut acute graft-versus-host disease (aGVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is associated with high mortality. Mucosa-associated ...invariant T (MAIT) cells are a group of innate-like T cells enriched in the intestine that can be activated by riboflavin metabolites from various microorganisms. However, little is known about the function or mechanism of action of MAIT cells in the occurrence of gut aGVHD in humans. In our study, multiparameter flow cytometry (FCM) was used to evaluate the number of MAIT cells and functional cytokines. 16S V34 region amplicon sequencing analysis was used to analyze the intestinal flora of transplant patients.
stimulation and coculture assays were used to study the activation and function of MAIT cells. The number and distribution of MAIT cells in intestinal tissues were analyzed by immunofluorescence technology. Our study showed that the number and frequency of MAIT cells in infused grafts in gut aGVHD patients were lower than those in no-gut aGVHD patients. Recipients with a high number of MAITs in infused grafts had a higher abundance of intestinal flora in the early posttransplantation period (+14 days). At the onset of gut aGVHD, the number of MAIT cells decreased in peripheral blood, and the activation marker CD69, chemokine receptors CXCR3 and CXCR4, and transcription factors Rorγt and T-bet tended to increase. Furthermore, when gut aGVHD occurred, the proportion of MAIT17 was higher than that of MAIT1. The abundance of intestinal flora with non-riboflavin metabolic pathways tended to increase in gut aGVHD patients. MAIT cells secreted more granzyme B, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ under the interleukin (IL)-12/IL-18 stimulation non-T-cell receptor (TCR) signal and secreted most of the IL-17 under the cluster of differentiation (CD)3/CD28 stimulation (TCR signal). MAIT cells inhibited the proliferation of CD4+ T cells
. In conclusion, the lower number of MAIT cells in infused grafts was related to the higher incidence of gut aGVHD, and the number of MAIT cells in grafts may affect the composition of the intestinal flora of recipients early after transplantation. The flora of the riboflavin metabolism pathway activated MAIT cells and promoted the expression of intestinal protective factors to affect the occurrence of gut aGVHD in humans.
Postpartum osteoporosis (PO) is a rare condition characterized by low bone mineral density (BMD) and an increased risk of vertebral fragility fracture. We encountered a 34-year-old woman who ...developed back pain 1 week after delivery. Magnetic resonance imaging of the lumbar spine revealed three vertebral compression fractures. Pretreatment BMD evaluation by dual-energy X-ray absorptiometry revealed a low T-score and Z-score (−2.0 and −2.0, respectively; BMD, 0.876 g/cm2) in the affected region of the spine. The patient was diagnosed with PO and treated with subcutaneous injection of denosumab 60 mg (Prolia; Amgen, Inc., Thousand Oaks, CA, USA) every 6 months. After two treatments, the BMD had significantly increased and the back pain was improved; the patient therefore decided to terminate the treatment. Two months later, her back pain worsened and BMD decreased as measured by dual-energy X-ray absorptiometry examination of the lumbar spine. Therefore, the patient resumed treatment with denosumab, and the BMD of the lumbar spine increased after another two treatments. Therefore, we consider denosumab to be promising in the management of PO with respect to increased BMD and decreased pain.
Long non-coding RNA growth arrest-specific transcript 5 (lncRNA GAS5) is a well-known tumor suppressor in the pathogenesis of a variety of human cancers. The precise role of GAS5 in pancreatic cancer ...(PC) progression is currently unknown, so the aim of this study was to explore the functional participation of GAS5 in PC metastasis.
The expression changes of GAS5, miR-32-5p and PTEN in human PC specimens and cell lines were compared by means of molecular biology methods. Transfection of the recombinant plasmid was applied to modulate the expression levels of the target genes. RIP and RNA pull-down assays were designed to investigate the interaction between GAS5 and miR-32-5p. The effect of GAS5 and miR-32-5p on PC progression was assessed with cell proliferation, migration, invasion and apoptosis in vitro.
GAS5 and PTEN protein were decreased in human PC tissues and cells, but miR-32-5p was increased. GAS5 induction greatly inhibited the proliferation, migration and invasion of PC cells PANC-1 and BxPC-3 in vitro and simultaneously induced cell apoptosis. Moreover, GAS5 positively regulated the expression of PTEN through miR-32-5p. Furthermore, GAS5 suppressed the proliferation, migration and invasion of PC cells through regulating miR-32-5p/PTEN axis. Additionally, this finding was further supported by the results of in vivo experiments.
GAS5 could positively regulate PTEN-induced tumor-suppressor pathway via miR-32-5p, thereby suppressing PC metastasis.
Low-temperature coal tar (LTCT) is a sticky liquid mixture produced mainly from coal pyrolysis, which contains various value-added chemicals (VACs). Liquid-liquid extraction is considered as one of ...the green and effective ways to explore the organic composition and separate the VACs from LTCT. Herein, petroleum ether, methanol, and carbon disulfide were used to extract arenols from a LTCT. As a result, the relative content and absolute content of arenols extracted from the LTCT are
ca
. 96.3% and 85.9%, respectively. Among them,
p
-cresol is predominant, accounting for 22.2%. The isolated contents of arenols are up to 84.6%. Moreover, a kilogram-scale operation was carried out under the same conditions, which offers a potential application in industrial production.
Abstract
Recently, some gamma-ray bursts (GRBs) whose light curves consist of repeating emission episodes with similar temporal profiles have attracted extensive attention. They are proposed to be ...candidates of millilensing events, although smoking gun evidence is lacking, since there are no redshift measurements and no angular offset detections for any of these candidates. Here we show that without invoking gravitational lensing, the repeating light-curve properties of these GRBs could also be interpreted under the jet precession model, as long as the detectable period in every precession circle is less than the precession period, and the precession period is close to the jet emission duration. By fitting the gamma-ray light curves of these GRBs, we suggest that the jet precession angle for these bursts should be relatively small (e.g.,
θ
p
< 5.°3), and the jet structure for these bursts are more likely Gaussian. The results suggest us to be careful when identifying millilensing GRBs. Multiband afterglow data and especially angular offset detections are essential to provide comprehensive justification for this identification.
Annual gross primary productivity (AGPP) is the basis for grain production and terrestrial carbon sequestration. Mapping regional AGPP from site measurements provides methodological support for ...analysing AGPP spatiotemporal variations thereby ensures regional food security and mitigates climate change. Based on 641 site-year eddy covariance measuring AGPP from China, we built an AGPP mapping scheme based on its formation and selected the optimal mapping way, which was conducted through analysing the predicting performances of divergent mapping tools, variable combinations, and mapping approaches in predicting observed AGPP variations. The reasonability of the selected optimal scheme was confirmed by assessing the consistency between its generating AGPP and previous products in spatiotemporal variations and total amount. Random forest regression tree explained 85 % of observed AGPP variations, outperforming other machine learning algorithms and classical statistical methods. Variable combinations containing climate, soil, and biological factors showed superior performance to other variable combinations. Mapping AGPP through predicting AGPP per leaf area (PAGPP) explained 86 % of AGPP variations, which was superior to other approaches. The optimal scheme was thus using a random forest regression tree, combining climate, soil, and biological variables, and predicting PAGPP. The optimal scheme generating AGPP of Chinese terrestrial ecosystems decreased from southeast to northwest, which was highly consistent with previous products. The interannual trend and interannual variation of our generating AGPP showed a decreasing trend from east to west and from southeast to northwest, respectively, which was consistent with data-oriented products. The mean total amount of generated AGPP was 7.03 ± 0.45 PgC yr−1 falling into the range of previous works. Considering the consistency between the generated AGPP and previous products, our optimal mapping way was suitable for mapping AGPP from site measurements. Our results provided a methodological support for mapping regional AGPP and other fluxes.
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•Random forest was the best tool in mapping annual gross primary productivity (AGPP).•Mapping AGPP should incorporate climate, soil, and biological variables.•Mapping AGPP by predicting AGPP per leaf area (PAGPP) outperformed other ways.•The generated AGPP was consistent with previous products in spatiotemporal variations.