The discovery of microRNA (miRNA) sorting into extracellular vesicles (EVs) revealed a novel mode of intercellular communication and uncovered a link between cellular endomembrane compartments and ...small RNAs in EV-secreting cells. Using a two-step ultracentrifugation procedure to isolate EVs released by T cells, we found that 45% of tRNA fragments (tRFs), but fewer than 1% of miRNAs, were significantly enriched in EVs compared with the corresponding cellular RNA. T cell activation induced the EV-mediated release of a specific set of tRFs derived from the 5′ end and 3′-internal region of tRNAs without variable loops. Inhibition of EV biogenesis pathways specifically led to the accumulation of these activation-induced EV-enriched tRFs within multivesicular bodies (MVBs). Introducing antisense oligonucleotides to inhibit these tRFs enhanced T cell activation. Taken together, these results demonstrate that T cells selectively release tRFs into EVs via MVBs and suggest that this process may remove tRFs that repress immune activation.
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•Specific tRFs are enriched in extracellular vesicles released by T cells•T cell activating signals regulate tRF secretion•Activation enhances multivesicular body formation and cellular tRF downregulation•Activation-induced, extracellular-vesicle-enriched tRFs inhibit T cell activation
Chiou et al. show that T cells release extracellular vesicles that carry RNA cargo enriched in tRNA fragments. Immune activating signals enhance multivesicular body formation and the secretion of vesicles containing specific tRNA fragments. Within cells, these tRNA fragments inhibit T cell activation and cytokine production.
Objectives/Hypothesis
Transformer‐2 protein homolog beta (Tra2β) generally plays an important role in various human cancers, but its role and the underlying mechanisms in laryngeal squamous cell ...carcinoma (LSCC) remained unknown. So this study aimed to assess the clinical significance and regulatory mechanisms of Tra2β in LSCC.
Study Design
Laboratory analysis.
Methods
Expression of Tra2β was compared in human LSCC tissue samples and paired adjacent normal tissue samples. The in vitro effects of Tra2β expression in Hep‐2 cells on their proliferation, invasion, and migration were assessed by CCK‐8 assays, Matrigel invasion, and transwell migration assays. In addition, the effects of downregulation of Tra2β on the activation of PI3K/AKT signaling pathway were measured using Western blot analysis. The effect of Tra2β on the growth of tumors was detected in the Hep‐2–injected xenograft models in vivo.
Results
Reverse‐transcription quantitative polymerase chain reaction analysis and immunochemistry analysis indicated that the increased expression of Tra2β in LSCC was significantly associated with poor differentiation, lymph node metastasis, and advanced clinical stage. In vitro knockdown of Tra2β caused a significant decrease in the proliferation, invasion, and migration of Hep‐2 cells. Tra2β silencing decreased the expression of Bcl‐2 but increased Bax and Caspase‐3 both in mRNA and protein levels. Furthermore, knockdown of Tra2β eliminated the suppressive effects of activation of PI3K/AKT signaling. In vivo knockdown of Tra2β significantly inhibited the tumor growth of Hep‐2–injected xenograft mice.
Conclusions
The results of the present study demonstrated that knockdown of Tra2β inhibits the proliferation and invasion of LSCC cells, at least partly via inhibiting PI3K/AKT signaling.
Level of Evidence
NA
Laryngoscope, 129:E318–E328, 2019
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•Strong electronic metal-support interactions (EMSI) between Pt and CeO2 nanorods.•Efficient and selective hydrogenation of quinolines by Pt/CeO2 at room temperature.•Strong EMSI ...enables the enhanced electronic density of Pt anchored on CeO2 nanorods.•Modulated electronic structures of Pt deliver high capability for hydrogen cleavage.•Modulated electronic structures of Pt improve the chemoselectivity.
Selectively catalytic hydrogenation of various quinolines in the presence of other reducible groups into the 1,2,3,4-tetrahydroquinoline compounds under mild conditions is a particular challenge for the heterogeneous catalysts due to the natural chemical stability of quinolines and poor chemoselectivity. Pt-based catalysts generally deliver good catalytic activity and selectivity for hydrogenation of quinolines with other reducible groups. However, the over-hydrogenated by-products are also often observed. Herein, Pt nanoparticles supported on CeO2 nanorods (Pt/NR-CeO2) realized highly efficient and chemoselective hydrogenation of various functionalized quinolines at room temperature. The unusual catalytic performance can be attributed to the strong electronic metal-support interactions (EMSI) between Pt and NR-CeO2 with the abundant surface oxygen vacancy, resulting in the enhanced electronic density of Pt nanoparticles. Subsequently, the modulated electronic structure of Pt enables the efficient hydrogen activation at room temperature, leading to a TOF of 546 h−1 of Pt/NR-CeO2 for the selective hydrogenation of 6-chloroquinolines. Density functional theory calculations also reveal that the high electron density of Pt benefits the desorption of the hydrogenated products and thus avoids the over-hydrogenation effectively.
Abstract Geniposide as the major active component of Gardenia jasminoides Ellis has neuroprotective activity. This study elucidated the potential antidepressant-like effect of geniposide and its ...related mechanisms using a depression rat model induced by 3 consecutive weeks of chronic unpredictable mild stress (CUMS). Sucrose preference test, open field test (OFT) and forced swimming test (FST) were applied to evaluate the antidepressant effect of geniposide. Adrenocorticotropic hormone (ACTH) and corticosterone (CORT) serum levels, adrenal gland index and hypothalamic corticotrophin-releasing hormone (CRH) mRNA expression were measured to assess the activity of hypothalamus–pituitary–adrenal (HPA) axis. Hypothalamic glucocorticoid receptor α (GRα) mRNA expression and GRα protein expression in hypothalamic paraventricular nucleus (PVN) were also determined by real-time PCR and immunohistochemistry, respectively. We found that geniposide (25, 50, 100 mg/kg) treatment reversed the CUMS-induced behavioral abnormalities, as suggested by increased sucrose intake, improved crossing and rearing behavior in OFT, shortened immobility and prolonged swimming time in FST. Additionally, geniposide treatment normalized the CUMS-induced hyperactivity of HPA axis, as evidenced by reduced CORT serum level, adrenal gland index and hypothalamic CRH mRNA expression, with no significant effect on ACTH serum level. Moreover, geniposide treatment upregulated the hypothalamic GRα mRNA level and GRα protein expression in PVN, suggesting geniposide could recover the impaired GRα negative feedback on CRH expression and HPA axis. These aforementioned therapeutic effects of geniposide were essentially similar to fluoxetine. Our results indicated that geniposide possessed potent antidepressant-like properties that may be mediated by its effects on the HPA axis.
Circular RNAs （circRNAs）, a kind of covalently closed RNA molecule, were used to be considered a type of byproducts of mis-splicing events and were discovered sporadically due to the technological ...limits in the early years. With the great technological progress such as high-throughput next-generation sequencing, numerous circRNAs have recently been detected in many species. CircRNAs were expressed in a spatio-temporally specific manner, suggesting their regulatory functional potentials were overlooked previously. Intriguingly, some circRNAs were indeed found with critical physiological functions in certain circumstances. CircRNAs have a more stable molecular st;＇ucture that can resist to exoribonuclease comparing to those linear ones, and their molecular functions include microRNA sponge, regulatory roles in transcription, mRNA traps that compete with linear splicing, templates for translation and possibly other presently unknown roles. Here, we review the discovery and characterization of circRNAs, the origination and formation mechanism, the physiological functions and the molecular roles, along with the methods for detection of circRNAs. We further look into the future and propose key questions to be answered for these magical RNA molecules.
In this study, poly(lactic acid) (PLA)/thermoplastic polyester elastomer (TPEE) (70/30) blend and blend‐based nanocomposites with carbon nanotube (CNT) as a nanofiller were fabricated by conventional ...melt mixing. Scanning electron microscopy results showed that the blend had a biphasic morphology, and CNTs were selectively distributed in the dispersed TPEE domains in the composites. The presence of CNTs induced the agglomeration and shape modification of TPEE domains, consequently influencing the examined properties. Differential scanning calorimetry results revealed that the crystallizability of PLA was improved after blending with TPEE, and further CNT incorporation increased the crystallization temperature of TPEE during cooling. The elongation at break (EB) and notched impact strength (IS) of PLA were evidently improved in the blend and composites. In particular, the EB and IS in the composites increased by up to 290% and 43%, respectively. The electrical resistivity of neat components and the blend decreased by up to eight orders of magnitude after 3 phr CNT loading due to double percolation in TPEE domains and dispersed CNTs. A percolation threshold at ca. 1 phr CNT loading for electrical conductivity was determined. Rheological property analysis suggested the formation of a pseudo‐network structure, which was attributed to the CNTs increasing the viscosity of the TPEE domains in the composites.
Aims: Several studies suggested that diabetes mellitus (DM) was associated with the risk of glioma. However, other studies did not confirm the result. Therefore, I conducted this meta-analysis.
...Materials and Methods: I retrieved the PubMed, Embase, and Web of Science database, by adopting keywords "glioma," and "diabetes," "DM." The strength of the associations between DM and the risk of glioma was measured by odds ratios (ORs) with 95% confidence intervals (95% CIs).
Results: Ten relevant studies were identified in the final analysis. A statistically significant association between DM and glioma risk was fond (OR = 0.84; 95% CI, 0.73-0.97; P = 0.02). In the subgroup analysis of age group, young population with DM showed decreased glioma risk (OR = 0.83; 95% CI, 0.70-0.98; P = 0.02), whereas old population with DM did not show a significant association (OR = 0.87; 95% CI, 0.65-1.16; P = 0.34). In the subgroup analysis of gender, male patients with DM showed decreased glioma risk (OR = 0.82; 95% CI, 0.68-0.99; P = 0.04), whereas female population with DM did not show a significant association (OR = 0.93; 95% CI, 0.70-1.24; P = 0.63).
Conclusions: This meta-analysis suggested that DM may be associated with the reduced glioma risk.
Natural gas distributed energy is recognized as a pivotal means to enhance energy efficiency and mitigate carbon dioxide emissions through localized energy cascading. Positioned as a key option for ...advancing the Sustainable Development Goals, this system optimizes energy utilization near end-users. While maximizing energy efficiency, it is imperative to address potential environmental challenges. A thorough, comprehensive environmental assessment, facilitated by the life cycle assessment method, proves instrumental in meeting this standard. Employing this method enables an intuitive grasp of the environmental strengths and weaknesses inherent in natural gas distributed energy within the power structure. This insight serves as a foundation for informed project decision-making, fostering the growth of the industry. We selected six environmental impact assessment categories based on the CML 2001 method, and conducted the life cycle analysis across four stages. China's inaugural natural gas distributed energy demonstration project was chosen as a model case, and an environmental impact assessment inventory was established, utilizing survey data and literature for comprehensive data collection and analysis. Results from case testing yield environmental impact assessment outcomes, with a specific sensitivity analysis for stages with notable environmental impact factors. The study underscores that the operation phase has the highest environmental impact, comprising 78.37% of the total combined environmental impact, followed by the fuel production phase. Comparative analyses with coal-fired and conventional natural gas power generation, based on dimensionless literature data, reveal that abiotic resources depletion potential is the primary contributor to the environmental impact of 1 kWh of electricity product, constituting 52.76% of the total impact value, followed by global warming potential. Concrete strategies have been outlined for decision-making in both the operational and planning phases of natural gas distributed energy projects. The strengthening of policies is pinpointed towards grid connection and scale expansion.
Release of promoter-proximal paused RNA polymerase II (Pol II) during early elongation is a critical step in transcriptional regulation in metazoan cells. Paused Pol II release is thought to require ...the kinase activity of cyclin-dependent kinase 9 (CDK9) for the phosphorylation of DRB sensitivity–inducing factor, negative elongation factor, and C-terminal domain (CTD) serine-2 of Pol II. We found that Pol II–associated factor 1 (PAF1) is a critical regulator of paused Pol II release, that positive transcription elongation factor b (P-TEFb) directly regulates the initial recruitment of PAF1 complex (PAF1C) to genes, and that the subsequent recruitment of CDK12 is dependent on PAF1C. These findings reveal cooperativity among P-TEFb, PAF1C, and CDK12 in pausing release and Pol II CTD phosphorylation.
High-strength or long-duration exercise can lead to significant fatigue, oxidative stress, and muscle damage. The purpose of this study was to examine the effect of mangosteen concentrate drink (MCD) ...supplementation on antioxidant capacity and lactate clearance in rats after running exercise. Forty rats were divided into five groups: N, non-treatment; C, control; or supplemented with MCD, including M1, M5, and M10 (0.9, 4.5, and 9 mL/day) for 6 weeks. The rats were subjected to 30 min running and exhaustive-running tests using a treadmill. The blood lactate; triglyceride; cholesterol and glucose levels; hepatic and muscular malonaldehyde (MDA) levels; and antioxidant enzymes, including superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT), were analyzed. The results of this study demonstrated that MCD supplementation can increase GPx and CAT activities, alleviate oxidative stress in muscle, and increase lactate clearance, and is thereby beneficial to reduced muscle fatigue after exercise.
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