Thermally induced residual stresses and residual distortions in the additive manufactured (AM) parts are two of the major obstacles that are preventing AM technology from gaining wide adoption. In ...this work, a three-dimensional thermo-elastic-plastic model is proposed to predict the thermomechanical behavior in the laser engineered net shaping (LENS) process of Ti-6Al-4V using Finite Element Method (FEM). It is shown that the computed thermal history and mechanical deformations are in good agreement with the experimental measurements. The main contributions of this study are: (I) in the past, a point-wise comparison between simulation results and experimental measurements is more favored to validate the employed model, where the general picture is lost; rather, to validate the proposed model, the simulated distortion of the bottom surface of a thin substrate is compared with experimental measurements using a 3D laser scanner, in terms of both magnitude and distribution map. (II) Rather few works have been done to show the effectiveness of widely employed quasi-static mechanical analysis in the transient LENS process; as such, both quasi-static and dynamic simulations are performed and compared mechanically to demonstrate the validity of using quasi-static modeling to save computational cost.
Experiments including electrical, mechanical and morphological aspects under compression in the range of 0-40% have been carried out on four potential materials for liquid diffusion layer (LDL) of ...vanadium redox flow battery (VRB) (including three widely used carbon felt and one recently utilized metal foam) in order to better understand the influence of the fundamental properties on the battery performance. We experimentally demonstrate that the electrical contact resistance is predominately determined by the clamping force. It is observed that increasing the stress applied on the carbon felt, which is of high interest for the durability of the membrane electrode assembly (MEA), has moreover a positive effect on their performance due to the reduced contact resistance. However, a simultaneously reduced porosity is also recorded and possibly detrimental to the mass transport of vanadium electrolyte. Moreover, the intrusion of carbon felts under compression is also characterized. Experimental results show that with the clamping force increases, both the porosity of the carbon felts underneath the rib and channel volume decrease, and this can be mainly attributed to the deformation of the carbon felts and resultant changed of the void volume as well as intrusion.
Conduction disturbances requiring permanent pacemaker implantation (PPI) are common following transcatheter aortic valve replacement (TAVR). There were conflicting data regarding the impact of new ...PPI on clinical outcomes after TAVR.
The study sought to evaluate the impact of new PPI on clinical outcomes in patients undergoing TAVR.
This study was a retrospective analysis of prospectively collected data. Data were from 210 consecutive patients without prior PPI who underwent TAVR due to severe symptomatic aortic stenosis at our center between June 2018 and July 2020. Clinical, echocardiographic, and pacing data were assessed at 30-day, 1- and 2-year follow-up.
New PPI was required in 35 (16.7%) patients within 30 days after TAVR. The median time from TAVR to PPI was 3 days. The most common indication for PPI was high-degree or complete atrioventricular block. The median follow-up was 798.0 (interquartile range, 669.0-1115.0) days. There were no differences in all-cause mortality (adjusted hazard ratio HR: 1.18; 95% confidence interval CI: 0.85-2.36; p = 0.415) and cardiovascular mortality (adjusted HR: 0.92; 95% CI: 0.57-1.89; p = 0.609) between groups. However, PPI group had a higher risk of heart failure (HF) rehospitalization (adjusted HR: 1.53; 95% CI: 1.26-2.28; p = 0.027). Echocardiography showed no significant improvement of LVEF over time in patients with PPI. At the latest follow-up, 31.3% of patients exhibited low (≤10%) pacing burdens, whereas 28.1% of patients had near constant (>90%) right ventricular pacing.
New PPI within 30 days following TAVR was not associated with an increased risk of all-cause or cardiovascular mortality. However, patients with PPI had a higher risk of HF rehospitalization and lack of LVEF improvement.
Aims. More than half of the patients with sepsis would develop cardiac dysfunction, which is termed as sepsis-induced myocardial dysfunction (SIMD). Previous studies suggest that autophagy may play ...an important role in SIMD. The present study investigated whether miR-214-3p could attenuate SIMD by inhibiting autophagy. Main Methods. In this article, we investigated the role of autophagy in a mouse model of cecal ligation and puncture (CLP). The structure and function of hearts harvested from the mice were evaluated. Myocardial autophagy levels were detected with immunohistochemical, immunofluorescent, and Western blot. Key Findings. miR-214-3p can alleviate SIMD in septic mice by inhibiting the level of cardiac autophagy to attenuate myocardial dysfunction. Moreover, this study showed that miR-214-3p inhibited autophagy by silencing PTEN expression in the myocardial tissues of septic mice. Significance. This study showed that miR-214-3p attenuated SIMD through myocardial autophagy inhibition by silencing PTEN expression and activating the AKT/mTOR pathway. The present findings supported that miR-214-3p may be a potential therapeutic target for SIMD.
The endeavor to enhance utility of organic molecular cages involves the evolution of them into higher-level chiral superstructures with self-similar, presenting a meaningful yet challenging. In this ...work, 2D tri-bladed propeller-shaped triphenylbenzene serves as building blocks to synthesize a racemic 3D tri-bladed propeller-shaped helical molecular cage. This cage, in turn, acts as a building block for a pair of higher-level 3D tri-bladed chiral helical molecular cages, featuring multilayer sandwich structures and displaying elegant characteristics with self-similarity in discrete superstructures at different levels. The evolutionary procession of higher-level cages reveals intramolecular self-shielding effects and exclusive chiral narcissistic self-sorting behaviors. Enantiomers higher-level cages can be interconverted by introducing an excess of corresponding chiral cyclohexanediamine. In the solid state, higher-level cages self-assemble into supramolecular architectures of L-helical or D-helical nanofibers, achieving the scale transformation of chiral characteristics from chiral atoms to microscopic and then to mesoscopic levels.
Inflammation and immune dysfunction play significant roles in the pathogenesis of Alzheimer's disease (AD)-related dementia. Changes in peripheral blood cell profiles are a common manifestation of ...inflammation and immune dysfunction and have been reported in patients with AD or mild cognitive impairment (MCI). We systematically evaluated the association of peripheral blood cell counts and indices with AD or MCI through a meta-analysis.
We electronically searched sources to identify all case-control trials comparing peripheral blood cell counts and/or lymphocyte subsets between patients with AD or MCI and healthy controls (HCs). Meta-analyses were used to estimate the between-group standardized mean difference (SMD) and 95% confidence interval (CI).
A total of 36 studies involving 2,339 AD patients, 608 MCI patients, and 8,352 HCs were included. AD patients had significantly decreased lymphocyte counts (SMD -0.345, 95% CI -0.545, -0.146,
= 0.001) and significantly increased leukocyte counts (0.140 0.039, 0.241,
= 0.006), neutrophil counts (0.309 0.185, 0.434,
= 0.01), and neutrophil-lymphocyte ratio (NLR) (0.644 0.310, 0.978,
< 0.001) compared to HCs. Similarly, significantly increased leukocyte counts (0.392 0.206, 0.579,
< 0.001), NLR (0.579 0.310, 0.847,
< 0.001), and neutrophil counts (0.248 0.121, 0.376,
< 0.001) were found in MCI patients compared with HCs. A significantly decreased percentage of B lymphocytes (-1.511 -2.775, -0.248,
= 0.019) and CD8
T cells (-0.760 -1.460, -0.061,
= 0.033) and a significantly increased CD4/CD8 ratio (0.615 0.074, 1.156,
= 0.026) were observed in AD patients compared to HCs. Furthermore, significant changes in hemoglobin level and platelet distribution width were found in patients with AD or MCI compared with HCs. However, no significant difference was found between AD or MCI patients and HCs in terms of platelet counts, mean corpuscular volume, red cell distribution width, mean platelet volume, and CD4
T, CD3
T, or natural killer cell counts.
Changes in peripheral blood cell profiles, particularly involving leukocyte, lymphocyte, neutrophil, and CD8
T cell counts, as well as the NLR and the CD4/CD8 ratio, are closely associated with AD. The diagnostic relevance of these profiles should be investigated in future.
Gram-negative bacterial infection causes an excessive inflammatory response and acute organ damage or dysfunction due to its outer membrane component, lipopolysaccharide (LPS). Protectin conjugates ...in tissue regeneration 1 (PCTR1), an endogenous lipid mediator, exerts fundamental anti-inflammation and pro-resolution during infection. In the present study, we examined the properties of PCTR1 on the systemic inflammatory response, organic morphological damage and dysfunction, and serum metabolic biomarkers in an LPS-induced acute inflammatory mouse model. The results show that PCTR1 reduced serum inflammatory factors and ameliorated morphological damage and dysfunction of the lung, liver, kidney, and ultimately improved the survival rate of LPS-induced acute inflammation in mice. In addition, metabolomics analysis and high performance liquid chromatography-mass spectrometry revealed that LPS-stimulated serum linoleic acid (LA), arachidonic acid (AA), and prostaglandin E2 (PGE2) levels were significantly altered by PCTR1. Moreover, PCTR1 upregulated LPS-inhibited fatty acid desaturase 1 (FADS1), fatty acid desaturase 2 (FADS2), and elongase of very long chain fatty acids 2 (ELOVL2) expression, and downregulated LPS-stimulated phospholipase A2 (PLA2) expression to increase the intrahepatic content of AA. However, these effects of PCTR1 were partially abrogated by a lipoxin A4 receptor (ALX) antagonist (BOC-2). In summary, via the activation of ALX, PCTR1 promotes the conversion of LA to AA through upregulation of FADS1, FADS2, and ELOVL2 expression, and inhibits the conversion of bound AA into free AA through downregulation of PLA2 expression to decrease the serum AA and PGE2 levels.
A new lignan, named (8S, 8′S)-2,2',3,3'-tetramethoxy-4'-hydroxy-epoxylignan-4-O-β-D-glucoside (1), together with eight known compounds (2-9), was isolated from the leaves of P. tectorius. Their ...structures were elucidated on the basis of spectral characteristics and comparison with the data of literatures. Besides, the absolute configuration of 1 was established by using ECD calculations. The cytotoxicity of 1 in vitro against three selected tumor cell lines (A549, HeLa and MCF-7) was evaluated by MTT assay. The results showed that compound 1 exhibited moderate cytotoxicity against HeLa cell with IC
50
value of 19.30 ± 4.46 μM.
MicroRNAs (miRs) have been identified as critical regulatory molecules in myocardial ischemia/reperfusion injury; however, the exact expression profile of miR‑199a‑5p in reperfusion injury and the ...underlying pathogenic mechanisms remain unclear. In the present study, it was revealed that miR‑199a‑5p expression was significantly increased in the plasma of patients with acute myocardial infarction and in a H9c2 cell model of oxygen‑glucose deprivation and reperfusion (OGD/R) via reverse transcription‑quantitative PCR. H9c2 cells were transfected with miR‑199a‑5p mimic or inhibitor, or short interfering RNA (siRNA) specific to hypoxia‑inducible factor‑1α (HIF‑1α). MTS, lactate dehydrogenase (LDH), TUNEL staining and flow cytometry assays were performed to determine the proliferation, LDH activity, apoptosis and mitochondrial membrane potential (ΔΨm) of H9c2 cells, respectively. The overexpression of miR‑199a‑5p in the OGD/R cell model significantly decreased the viability and increased the lactate dehydrogenase leakage of cells; whereas knockdown of miR‑199‑5p induced the opposing effects. Additionally, inhibition of miR‑199‑5p significantly attenuated OGD/R‑induced alterations to the mitochondrial transmembrane potential (ΔΨm) and increases in the apoptosis of cells. Furthermore, the overexpression or knockdown of miR‑199a‑5p decreased or increased the expression of HIF‑1α and phosphorylation of glycogen synthase kinase 3β (GSK3β) in OGD/R‑treated H9c2 cells. Additionally, siRNA‑mediated downregulation of HIF‑1α decreased phosphorylated (p)‑GSK3β (Ser9) levels and reversed the protective effects of miR‑199a‑5p inhibition on OGD/R‑injured H9c2 cells. Similarly, treatment with LiCl (a specific inhibitor of p‑GSK3β) also attenuated the protective effects of miR‑199a‑5p knockdown on OGD/R‑injured H9c2 cells. Mechanistic studies revealed that HIF‑1α was a target of miR‑199a‑5p, and that HIF‑1α downregulation suppressed the expression of p‑GSK3β in OGD/R‑injured H9c2 cells. Furthermore, an miR‑199a‑5p inhibitor increased the interaction between p‑GSK3β and adenine nucleotide transferase (ANT), which was decreased by OGD/R. Additionally, miR‑199a‑5p inhibitor reduced the OGD/R‑induced interaction between ANT and cyclophilin D (Cyp‑D), potentially leading to the increased mitochondrial membrane potential in inhibitor‑transfected OGD/R‑injured H9c2 cells. Collectively, the present study identified a novel regulatory pathway in which the upregulation of miR‑199a‑5p reduced the expression of HIF‑1α and p‑GSK3β, and potentially suppresses the interaction between p‑GSK3β and ANT, thus promoting the interaction between ANT and Cyp‑D and potentially inducing cytotoxicity in OGD/R‑injured H9c2 cells.
Recent studies have revealed the functional roles of cell membrane coated-nanoparticles (CMNPs) in tackling urological diseases, including cancers, inflammation, and acute kidney injury. Cells are a ...fundamental part of pathology to regulate nearly all urological diseases, and, therefore, naturally derived cell membranes inherit the functional role to enhance the biopharmaceutical performance of their encapsulated nanoparticles on drug delivery. In this review, methods for CMNP synthesis and surface engineering are summarized. The application of different types of CMNPs for tackling urological diseases is updated, including cancer cell membrane, stem cell membrane, immune cell membrane, erythrocytes cell membranes, and extracellular vesicles, and their potential for clinical use is discussed.
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