Abstract
Background
Stroke affects 3–4% of adults and kills numerous people each year. Recovering blood flow with minimal reperfusion-induced injury is crucial. However, the mechanisms underlying ...reperfusion-induced injury, particularly inflammation, are not well understood. Here, we investigated the function of miR-19a/b-3p/SIRT1/FoxO3/SPHK1 axis in ischemia/reperfusion (I/R).
Methods
MCAO (middle cerebral artery occlusion) reperfusion rat model was used as the in vivo model of I/R. Cultured neuronal cells subjected to OGD/R (oxygen glucose deprivation/reperfusion) were used as the in vitro model of I/R. MTT assay was used to assess cell viability and TUNEL staining was used to measure cell apoptosis. H&E staining was employed to examine cell morphology. qRT-PCR and western blot were performed to determine levels of miR-19a/b-3p, SIRT1, FoxO3, SPHK1, NF-κB p65, and cytokines like TNF-α, IL-6, and IL-1β. EMSA and ChIP were performed to validate the interaction of FoxO3 with
SPHK1
promoter. Dual luciferase assay and RIP were used to verify the binding of miR-19a/b-3p with SIRT1 mRNA.
Results
miR-19a/b-3p, FoxO3, SPHK1, NF-κB p65, and cytokines were elevated while SIRT1 was reduced in brain tissues following MCAO/reperfusion or in cells upon OGD/R. Knockdown of SPHK1 or FoxO3 suppressed I/R-induced inflammation and cell death. Furthermore, knockdown of FoxO3 reversed the effects of SIRT1 knockdown. Inhibition of the miR-19a/b-3p suppressed inflammation and this suppression was blocked by SIRT1 knockdown. FoxO3 bound SPHK1 promoter and activated its transcription. miR-19a/b-3p directly targeted SIRT1 mRNA.
Conclusion
miR-19a/b-3p promotes inflammatory responses during I/R via targeting SIRT1/FoxO3/SPHK1 axis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
A lithium-sulfur (Li-S) battery is regarded as the most promising candidate for next generation energy storage systems, because of its high theoretical specific capacity (1675 mA h g
) and specific ...energy (2500 W h kg
), as well as the abundance, low cost and environmental benignity of sulfur. However, the soluble polysulfides Li
S
(4 ≤ x ≤ 8) produced during the discharge process can cause the so-called "shuttle effect" and lead to low coulombic efficiency and rapid capacity fading of the batteries, which seriously restrict their practical application. Using porous materials as hosts to immobilize the polysulfides is proved to be an effective strategy. In this article, a dual functional cage-like metal-organic framework (Cu-MOF), Cu-TDPAT, combining the Lewis basic sites from the nitrogen atoms of the ligand H
TDPAT with the Lewis acidic sites from Cu(ii) open metal sites (OMSs), was employed as the sulfur host in a Li-S battery for lithium ions and polysulfide anions (S
). In addition, the size of nano-Cu-TDPAT was also optimized by microwave synthesis to reduce the internal resistance of the batteries. The electrochemical test results showed that the optimized Cu-TDPAT material can efficiently confine the polysulfides within the MOF, and the resultant porous S@Cu-TDPAT composite cathode material with the size of 100 nm shows good cycling performance with a reversible capacity of about 745 mA h g
at 1C (1C = 1675 mA g
) after 500 cycles, to the best of our knowledge, which is higher than those of all reported S@MOF cathode materials. The DFT calculation and XPS data indicate that the good cycling performance mainly results from the dual functional binding sites (that is, Lewis acid and base sites) in nanoporous Cu-TDPAT, providing the comprehensive and robust interaction with the polysulfides to overcome their dissolution and diffusion into the electrolyte. Clearly, our work provides a good example of designing MOFs with suitable interaction sites for the polysulfides to achieve S@MOF cathode materials with excellent cycling performance by multiple synergistic effects between nanoporous host MOFs and the polysulfides.
Lithium-ion (Li+) batteries suffer from problems caused by the chemical instability of their organic electrolytes. Solid-state electrolytes that exhibit high ionic conductivities and are stable to ...lithium metal are potential replacements for flammable organic electrolytes. Garnet-type Li7La3Zr2O12 is a promising solid-state electrolyte for next-generation solid-state Li batteries. In this study, we prepared mono-, dual-, and ternary-doped lithium (Li) garnets by doping tantalum (Ta), tantalum–barium (Ta–Ba), and tantalum–barium–gallium (Ta–Ba–Ga) ions, along with an undoped Li7La3Zr2O12 (LLZO) cubic garnet electrolyte, using a conventional solid-state reaction method. The effect of multi-ion doping on the Li+ dynamics in the garnet-type LLZO was studied by combining joint Rietveld refinement against X-ray diffraction and high-resolution neutron powder diffraction analyses with the results of Raman spectroscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy, and multinuclear magic angle spinning nuclear magnetic resonance. Our results revealed that Li+ occupancy in the tetrahedrally coordinated site (24d) increased with increased multi-ion doping in LLZO, whereas Li+ occupancy in the octahedrally coordinated site (96h) remained constant. Among the investigated compounds, the ternary-doped garnet structure Li6.65Ga0.05La2.95Ba0.05Zr1.75Ta0.25O12 (LGLBZTO) exhibited the highest total ionic conductivity of 0.72 and 1.24 mS cm−1 at room temperature and 60 °C, respectively. Overall, our findings revealed that the dense microstructure and increased Li+ occupancy in the tetrahedral-24dLi1 site played a key role in achieving the maximum room-temperature Li-ion conductivity in the ternary-doped LGLBZTO garnet, and that the prepared ternary-doped LGLBZTO was a potential solid electrolyte for Li-ion batteries without polymer adhesion.
Here, a facile approach to constructing efficiently segregated conductive networks in the poly(lactic acid)/silver (PLA/Ag) nanocomposites were developed by coating Ag particles on PLA microfibers ...and then compression molding. The electrical conductivity and electromagnetic interference shielding effectiveness (EMI SE) of the nanocomposites were obviously enhanced by these efficiently conductive networks because of the well Ag coating layers on PLA microfibers. Furthermore, the electrical conductivity and the EMI SE of the nanocomposites increased with increasing the coating amount of Ag particles, which can be easily tuned by controlling the coating time. It was found that the chain-structured PLA/Ag nanocomposites with coating time of 7 min with 5.89 vol% Ag particles possessed the remarkable electrical conductivity of 254 S/m and outstanding EMI SE of 50 dB at 8.2–12.4 Hz when the testing samples with the thickness of 1.5 mm, which far surpassed the targeted value of 20 dB for commercial applications. The excellent EMI shielding properties of the nanocomposites were ascribed to the unique segregated chain-structures, which provide enormous interfaces to reflect, scatter and adsorb the electromagnetic waves many times. The PLA/Ag nanocomposites with segregated networks were also found to be an absorption dominated EMI shielding mechanism.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Electrically conductive segregated networks were built in poly(
l
-lactide)/multi-walled carbon nanotube (PLLA/MWCNT) nanocomposites without sacrificing their mechanical properties
via
simply ...choosing two different PLLA polymers with different viscosities and crystallinities. First, the MWCNTs were dispersed in PLLA with low viscosity and crystallinity (L-PLLA) to obtain the L-PLANT phase. Second, the PLLA particles with high viscosity and crystallinity (H-PLLA) were well coated with the L-PLANT phase at 140 °C which was below the melting temperature of H-PLLA. Finally, the coated H-PLLA particles were compressed above the melting temperature of H-PLLA to form the PLLA/MWCNT nanocomposites with segregated structures. The morphological observation showed the successful location of MWCNTs in the continuous L-PLLA phase, resulting in an ultralow percolation threshold of 0.019 vol% MWCNTs. The electrical conductivity and the electromagnetic interference (EMI) shielding effectiveness (SE) of the composites with the segregated structure are 25 S m
−1
and ∼30 dB, showing three orders and 36% higher than that of the samples with a random distribution of MWCNTs with 0.8 vol% of MWCNT loading, respectively. High-performance electromagnetic interference (EMI) shielding was also observed mainly dependent on the highly efficient absorption shielding, which can be achieved by the densely continuous MWCNT networks and the abundant interfaces induced by the segregated structures. Furthermore, the composites with segregated structures not only showed higher Young's modulus and tensile strength than the corresponding conventional composites, but also maintained high elongation at break because of the continuous and dense MWCNT networks induced by the segregated structures and the high interfacial interaction between H-PLLA and L-PLLA.
Acute high-intensity interval training (HIIT) is a time-efficient strategy to improve physical health; however, the effect of acute HIIT on executive function (EF) is unclear. The aim of this study ...was to systematically review the existing evidence and quantify the effect of acute HIIT on overall EF and the factors affecting the relationship between acute HIIT and EF. Standard databases (i.e., the PubMed, Medline, Scopus, and CENTRAL databases) were searched for studies that examined the effect of acute HIIT on EF and were published up until January 2021. The overall EF and factors grouped by three categories, namely, EF assessment characteristics, exercise intervention characteristics, and sample and study characteristics, were analyzed by percentage of comparison for positive or null/negative effects. Overall, 35 of 57 outcomes (61%) across 24 studies revealed that acute HIIT has a positive effect on overall EF. In terms of factors, the results indicated that among EF assessment characteristics, groups, inhibition, updating, and the assessment occurring within 30 min may moderate the effect of acute HIIT on EF, while among exercise intervention characteristics, total time within 11 to 30 min may moderate the effect. Finally, among sample characteristics, age under 40 years may moderate the effect. Acute HIIT is generally considered a viable alternative for eliciting EF gains, with factors related to EF components, timing of the assessment, exercise total time, and age potentially moderating the effect of HIIT on EF.
Recent studies have shown that myocardial ischemia/reperfusion (I/R)-induced necrosis can be controlled by multiple genes. In this study, we observed that both strands (5p and 3p) of miR-223 were ...remarkably dysregulated in mouse hearts upon I/R. Precursor miR-223 (pre-miR-223) transgenic mouse hearts exhibited better recovery of contractile performance over reperfusion period and lesser degree of myocardial necrosis than wild type hearts upon ex vivo and in vivo myocardial ischemia. Conversely, pre-miR-223 knock-out (KO) mouse hearts displayed opposite effects. Furthermore, we found that the RIP1/RIP3/MLKL necroptotic pathway and inflammatory response were suppressed in transgenic hearts, whereas they were activated in pre-miR-223 KO hearts upon I/R compared with wild type controls. Accordingly, treatment of pre-miR-223 KO mice with necrostatin-1s, a potent necroptosis inhibitor, significantly decreased I/R-triggered cardiac necroptosis, infarction size, and dysfunction. Mechanistically, we identified two critical cell death receptors, TNFR1 and DR6, as direct targets of miR-223-5p, whereas miR-223-3p directly suppressed the expression of NLRP3 and IκB kinase α, two important mediators known to be involved in I/R-induced inflammation and cell necroptosis. Our findings indicate that miR-223-5p/-3p duplex works together and cooperatively inhibits I/R-induced cardiac necroptosis at multiple layers. Thus, pre-miR-223 may constitute a new therapeutic agent for the treatment of ischemic heart disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Background
Downstaging of hepatocellular carcinoma (HCC) makes it possible for patients beyond the criteria to have the chance of liver transplantation (LT) and improved outcomes. Thus, a ...procedure to predict the prognosis of the treatment is an urgent requisite. The present study aimed to construct a comprehensive framework with clinical information and radiomics features to accurately predict the prognosis of downstaging treatment.
Methods
Specifically, three-dimensional (3D) tumor segmentation from contrast-enhanced computed tomography (CT) is employed to extract spatial information of the lesions. Then, the radiomics features within the segmented region are calculated. Combining radiomics features and clinical data prompts the development of feature selection to enhance the robustness and generalizability of the model. Finally, we adopt the support vector machine (SVM) algorithm to establish a classification model for predicting HCC downstaging outcomes.
Results
Herein, a comparative study was conducted on three different models: a radiomics features-based model (R model), a clinical features-based model (C model), and a joint radiomics clinical features-based model (R-C model). The average accuracy of the three models was 0.712, 0.792, and 0.844, and the average area under the receiver-operating characteristic (AUROC) of the three models was 0.775, 0.804, and 0.877, respectively.
Conclusions
The novel and practical R-C model accurately predicted the downstaging outcomes, which could be utilized to guide the HCC downstaging toward LT treatment.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Systemic inflammation and cachexia are associated with adverse clinical outcomes in elderly patients with cancer. The Geriatric Nutritional Risk Index (GNRI) is a simple and useful tool to ...assess these conditions, but its predictive ability for elderly patients with cancer cachexia (EPCC) is unknown.
Methods
This multicentre cohort study included 746 EPCC with an average age of 72.00 ± 5.24 years, of whom 489 (65.5%) were male. The patients were divided into two groups (high GNRI group ≥91.959 vs. low GNRI group <91.959) according to the optimal cut‐off value of the ROC curve. The calibration curves were performed to analyse the prognostic, predictive ability of GNRI. Comprehensive survival analyses were utilized to explore the relationship between GNRI and the overall survival (OS) of EPCC. Interaction analysis was used to investigate the comprehensive effects of low GNRI and subgroup parameters on the OS of EPCC.
Results
In this study, a total of 2560 patients were diagnosed with cancer cachexia, including 746 cases of EPCC. During the 3.6 year median follow‐up, we observed 403 deaths. The overall mortality rate for EPCC at 12 months was 34.3% (95% CI: 62.3% to 69.2%), and resulting in rate of 278 events per 1000 patient‐years. The GNRI score of EPCC was significantly lower than those of young patients with cancer cachexia (P < 0.001). The 1, 3, and 5 year calibration curves showed that the GNRI score had good survival prediction in the OS of EPCC. The GNRI could predict the OS of EPCC, whether as a continuous variable or a categorical variable. Particularly, we also found that low GNRI score (<91.959) of EPCC had a worse prognosis than those with a high GNRI score (≥91.959, P = 0.001, HR = 1.728, 95% CI: 1.244–2.401). Consistent results were observed in the tumour subgroups of gastric cancer and colorectal cancer. Notably, similar results were observed in the sensitivity analysis. In the subgroup analysis, the low GNRI has a combined effect with age (<70 years) on poor OS of EPCC. The results of the prognostic risk model found that the lower the GNRI score, the greater the prognostic risk score, and the greater the risk of death in EPCC.
Conclusions
For the first time, this study found that the GNRI score can serve as an independent prognostic factor for the OS of EPCC.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The current study assessed the effects of acute exercise on three core executive functions in preadolescents and controlled for the moderating role of age.
A true experimental design.
Thirty-four ...third-grade children and 53 fifth-grade preadolescents were randomly assigned into either an acute exercise group or a control group. The exercise protocol was designed for ecological validity and involved group jogging at moderate intensity for 30 min. Participants completed inhibition, working memory, and shifting-related executive function tasks prior to and following the treatment.
Acute exercise facilitated performance in three executive function tasks in children in both grade groups; nevertheless, better performance was observed among the fifth graders in inhibition and working memory, but not in shifting, when compared with the third graders.
These findings suggest that acute exercise benefited three primary aspects of executive function in general, regardless of the preadolescent age group, whereas the distinct components of executive function had different developmental trajectories.
•To examine the acute exercise effect on multiple aspects of executive function in preadolescents.•To determine whether age group moderates the relationship.•Acute exercise facilitates three core aspects of executive function in both aged preadolescents.•Older preadolescents demonstrate better inhibition and working memory, but not shifting.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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