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Abstract Background Research has suggested significant correlations among ageing, immune microenvironment, inflammation and tumours. However, the relationships among ageing, immune microenvironment, cystitis and bladder urothelial carcinoma (BLCA) in the bladder have rarely been reported. Methods Bladder single-cell and transcriptomic data from young and old mice were used for immune landscape analysis. Transcriptome, single-cell and The Cancer Genome Atlas Program datasets of BLCA and interstitial cystitis/bladder pain syndrome (IC/BPS) were used to analyse immune cell infiltration and molecular expression. Bladder tissues from mice, IC/BPS and BLCA were collected to validate the results. Results Eight types of immune cells (macrophages, B-cells, dendritic cells, T-cells, monocytes, natural killer cells, γδ T-cells and ILC2) were identified in the bladder of mice. Aged mice bladder tissues had a significantly higher number of T-cells, γδ T-cells, ILC2 and B-cells than those in the young group (P

Deposition pattern and path-planning deposition strategy have significant impacts on the deformation and residual stress of components during a wire-arc additive manufacturing (WAAM) process. This work comparatively addressed the influence of weaving and non-weaving deposition patterns on the distributions of residual stress and warping deformation during a single-bead-on-plate WAAM process. Further, four path strategies with different deposition sequences (in-out and out-in) and deposition directions (alternate and consistent) were designed for a weaving WAAM process of disc part, and their impacts on temperature history, warping deformation, and residual stress were comparatively analyzed through thermal-mechanical coupling finite element (FE) method. Simulation and experiment results manifest that, compared to the non-weaving pattern, the weaving deposition pattern results in more uniform deformation and lower residual stress on the deposited plate due to wider and shallower molten pool. Comparison results for the four deposition path strategies in the weaving WAAM process of disc part suggest that the out-in deposition sequence exhibits faster heat dissipation and uniform temperature field during the cooling stage, resulting in reduced warping deformation and residual stress on the workpiece. Moreover, uniform deformation is observed across path strategies employing alternate deposition direction. The out-in alternate deposition path strategy was identified as the optimal choice for the weaving WAAM process of disc part. Finally, physical experiments validated the simulated warping deformation of disc parts under different deposition path strategies. This work contributes to the design and optimization of weaving WAAM process for disc-shaped components.

Cell implantation offers an appealing avenue for heart repair after myocardial infarction (MI). Nevertheless, the implanted cells are subjected to the aberrant myocardial niche, which inhibits cell survival and maturation, posing significant challenges to the ultimate therapeutic outcome. The functional cardiac patches (CPs) have been proved to construct an elastic conductive, antioxidative, and angiogenic microenvironment for rectifying the aberrant microenvironment of the infarcted myocardium. More importantly, inducing implanted cardiomyocytes (CMs) adapted to the anisotropic arrangement of myocardial tissue by bioengineered structural cues within CPs are more conducive to MI repair. Herein, a functional Cig/(TA-Cu) CP served as biomimetic cardiac niche was fabricated based on structural anisotropic cigarette filter by modifying with tannic acid (TA)-chelated Cu2+ (TA-Cu complex) via a green method. This CP possessed microstructural anisotropy, electrical conductivity and mechanical properties similar to natural myocardium, which could promote elongation, orientation, maturation, and functionalization of CMs. Besides, the Cig/(TA-Cu) CP could efficiently scavenge reactive oxygen species, reduce CM apoptosis, ultimately facilitating myocardial electrical integration, promoting vascular regeneration and improving cardiac function. Together, our study introduces a functional CP that integrates multimodal cues to create a biomimetic cardiac niche and provides an effective strategy for cardiac repair.

Abstract Background/Purpose Risk factors for re-bleeding and death after acute variceal bleeding (AVB) in cirrhotic HCC patients are not fully understood.We aimed to (1) explore how the combination of high-risk esophageal varices, HCC status, and portal vein tumor thrombus (i.e., HCC Portal Hypertension Imaging Score [HCCPHTIS]) helps predict increased risk of variceal re-bleeding and mortality; (2) assess predictability and reproducibility of the identified variceal re-bleeding rules. Methods This prospective study included 195 HCC patients with first-time AVB and liver cirrhosis, and conducted multivariable Cox regression analysis and Kaplan-Meier analysis. Receiver operating characteristic curve analysis was calculated to find the optimal sensitivity, specificity, and cutoff values of the variables. The reproducibility of the results obtained was verified in a different but related group of patients. Results 56 patients (28.7%) had re-bleeding within 6 weeks; HCCPHTIS was an independent risk factor for variceal re-bleeding after AVB (Odd ratio, 2.330; 95% confidence interval: 1.728–3.142, p 3 was 66.2%, sensitivity 83.9%, and specificity 82.3%. HCCPHTIS area under the curve was higher than Child-Pugh score (89% vs. 75%, p 4 was associated with increased risk of death within 6 weeks after AVB (p 3 is a strong predictor of variceal re-bleeding within the first 6 weeks. However, patients with HCCPHTIS > 4 were at increased risk of death within 6 weeks.

To achieve the uniform and fine-grained microstructures during thermal deformation of nickel-based superalloys, a novel two-stage deformation approach was employed, involving prior cold deformation treatment (PCDT) and subsequent thermal deformation. Experimental investigations concerning this two-stage deformation method were carried out on Ni80A superalloy, encompassing various combinations of cold and thermal compression parameters. The analysis of microstructures revealed that PCDT significantly enhances dynamic recrystallization (DRX) process, resulting in fine-grained microstructures during thermal compression and expanding the processing-parameter domains for grain refinement. To clarify the shift of DRX kinetics in thermal compression induced by PCDT, the DRX kinetics models considering this pre-treatment were derived. These models demonstrated a linear inverse correlation between the activation energy within DRX kinetics models and prior stored energy from PCDT. This suggested that PCDT promotes the DRX process by reducing the activation energy during thermal compression. Following, the kinetics curves depicting DRX volume fraction during thermal deformation were drawn. Results indicated that under an identical thermal compression condition, the kinetics curve shifts towards decreasing strain with increasing of prior cold deformation. Under various thermal compression conditions, these kinetics curves for Ni80A superalloy processed with PCDT get shifted to the direction of decreasing strain when compared to the alloy without PCDT. These shifts underscore a pronounced acceleration of DRX process induced by PCDT. Finally, a finite element model incorporating DRX kinetics models was developed to further illustrate the influence of PCDT on the shift of DRX in an upsetting process, which shows a promising potential for theoretical calculations.

IntroductionAlternol is a natural compound isolated from the fermentation of a mutated fungus. We have demonstrated its potent anti-cancer effect via the accumulation of radical oxygen species (ROS) in prostate cancer cells in vitro and in vivo. In this study, we tested its anti-cancer spectrum in multiple platforms.MethodsWe first tested its anti-cancer spectrum using the National Cancer Institute-60 (NCI-60) screening, a protein quantitation-based assay. CellTiter-Glo screening was utilized for ovarian cancer cell lines. Cell cycle distribution was analyzed using flow cytometry. Xenograft models in nude mice were used to assess anti-cancer effect. Healthy mice were tested for the acuate systemic toxicity.ResultsOur results showed that Alternol exerted a potent anti-cancer effect on 50 (83%) cancer cell lines with a GI50 less than 5 µM and induced a lethal response in 12 (24%) of those 50 responding cell lines at 10 µM concentration. Consistently, Alternol displayed a similar anti-cancer effect on 14 ovarian cancer cell lines in an ATP quantitation-based assay. Most interestingly, Alternol showed an excellent safety profile with a maximum tolerance dose (MTD) at 665 mg/kg bodyweight in mice. Its therapeutic index was calculated as 13.3 based on the effective tumor-suppressing doses from HeLa and PC-3 cell-derived xenograft models.ConclusionTaken together, Alternol has a broad anti-cancer spectrum with a safe therapeutic index in vivo.

Background: Alternol is a small molecular compound isolated from the fermentation of a mutant fungus obtained from Taxus brevifolia bark. Our previous studies showed that Alternol treatment induced reactive oxygen species (ROS)-dependent immunogenic cell death. This study conducted a comprehensive investigation to explore the mechanisms involved in Alternol-induced immunogenic cell death.Methods: Prostate cancer PC-3, C4-2, and 22RV1 were used in this study. Alternol interaction with heat shock proteins (HSP) was determined using CETSA assay. Alternol-regulated ER stress proteins were assessed with Western blot assay. Extracellular adenosine triphosphate (ATP) was measured using ATPlite Luminescence Assay System.Results: Our results showed that Alternol interacted with multiple cellular chaperone proteins and increased their expression levels, including endoplasmic reticulum (ER) chaperone hypoxia up-regulated 1 (HYOU1) and heat shock protein 90 alpha family class B member 1 (HSP90AB1), as well as cytosolic chaperone heat shock protein family A member 8 (HSPA8). These data represented a potential cause of unfolded protein response (UPR) after Alternol treatment. Further investigation revealed that Alternol treatment triggered ROS-dependent (ER) stress responses via R-like ER kinase (PERK), inositol-requiring enzyme 1α (IRE1α). The double-stranded RNA-dependent protein kinase (PKR) but not activating transcription factor 6 (ATF6) cascades, leading to ATF-3/ATF-4 activation, C/EBP-homologous protein (CHOP) overexpression, and X-box binding protein XBP1 splicing induction. In addition, inhibition of these ER stress responses cascades blunted Alternol-induced extracellular adenosine triphosphate (ATP) release, one of the classical hallmarks of immunogenic cell death.Conclusion: Taken together, our data demonstrate that Alternol treatment triggered multiple ER stress cascades, leading to immunogenic cell death.

Organic semiconductor power devices have been attracting increasing attention due to their advantages such as flexibility, low fabrication cost, and sustainability. They have found wide applications in fields such as flexible electronic devices and biomedical devices. However, in the field of power applications, the lack of reliable organic semiconductor power devices is mainly attributed to the limited thermal stability and electrical stability of organic materials. This article provides a detailed review of the development status of organic semiconductor power devices from three aspects: device structure, organic materials, and fabrication methods. It clarifies that the future development goal is to enhance the voltage resistance and thermal stability of organic transistors through higher-performance structure design, higher-mobility materials, and higher-quality fabrication methods. The continuous innovation and development of the structures, materials, and fabrication of these devices will generate more novel devices, offering more possibilities for the application of organic semiconductor power devices. This information is of great reference value and guidance significance for engineers in related fields.

Background. Moyamoya disease (MMD) leads to nerve injury. Exosomes are touted as bio-shuttles for the delivery of distinct biomolecules inside the cells. Recently, UCH-L1 was shown to play a vital role in nerve injury. However, it is still unknown whether UCH-L1 can improve the nerve injury of MMD. Materials and Methods. Exosomes were isolated from the serum of patients with MMD and healthy controls. The total RNA was extracted from the exosomes, and the level of GFAP and UCH-L1 between the serum exosomes of the two groups was analyzed by a quantitative reverse transcription-polymerase chain reaction and western blot. Exosome labeling and uptake by SH-SY5Y cells were observed by confocal laser microscopy. Cell counting kit-8 assay and flow cytometry were used to determine the viability and apoptosis of SH-SY5Y cells, respectively. Results. Exosomes were successfully isolated and identified from serum. The expression of GFAP and UCH-L1 was significantly higher in the serum-derived exosomes from MMD patients compared with the healthy controls (P

Flexible electronic products, with their characteristics of flexibility and wearability, have attracted significant attention and have become an important direction in the research and development of the electronics industry. Planar micro-supercapacitors (MSCs) with flexible composite electrodes can provide reliable energy support for these products, propelling their further development. The research employed a quick, effective, and environmentally friendly method of laser scribing to create shape-controllable flexible composite electrodes on composite films of Poly(3,4-ethylenedioxythiophene) and graphene oxide (PEDOT/GO), which were subsequently assembled into MSCs. An analysis of the composite electrode morphology, structure, and elemental distribution was conducted through the utilization of SEM, TEM, and XPS techniques. Following this, a comprehensive evaluation of the electrochemical performance of the flexible MSCs was carried out, which included cyclic voltammetry (CV), galvanostatic charge/discharge (GCD), and assessment of cyclic stability. The analysis of the CV results indicated that the MSCs achieved the areal capacitance of 5.78 mF/cm2 at 5 mV/s. After 5000 cycles at a current density of 0.05 mA/cm2, the capacitance retention rate was 85.4%. The high areal capacitance and strong cycle stability of MSCs highlight the potential of PEDOT/reduced graphene oxide (PEDOT/rGO) electrodes in electrode applications.

A simple proof using Birkhoff theorem is given for the result that the spectral norm of a doubly stochastic matrix is 1. We also show that the result generalizes the results of İpek, Bozkurt, and Jiang and Zhou on circulant matrices and rr-circulant matrices. Spectral norm of level-kk circulant matrix and applications are given.

Background: In recent years, with benefits from the continuous improvement of clinical technology and the advantage of fertility preservation, the application of embryo cryopreservation has been growing rapidly worldwide. However, amidst this growth, concerns about its safety persist. Numerous studies have highlighted the elevated risk of perinatal complications linked to frozen embryo transfer (FET), such as large for gestational age (LGA) and hypertensive disorders during pregnancy. Thus, it is imperative to explore the potential risk of embryo cryopreservation and its related mechanisms. Methods: Given the strict ethical constraints on clinical samples, we employed mouse models in this study. Three experimental groups were established: the naturally conceived (NC) group, the fresh embryo transfer (Fresh-ET) group, and the FET group. Blastocyst formation rates and implantation rates were calculated post-embryo cryopreservation. The impact of FET on fetal growth was evaluated upon fetal and placental weight. Placental RNA-seq was conducted, encompassing comprehensive analyses of various comparisons (Fresh-ET vs. NC, FET vs. NC, and FET vs. Fresh-ET). Results: Reduced rates of blastocyst formation and implantation were observed post-embryo cryopreservation. Fresh-ET resulted in a significant decrease in fetal weight compared to NC group, whereas FET reversed this decline. RNA-seq analysis indicated that the majority of the expression changes in FET were inherited from Fresh-ET, and alterations solely attributed to embryo cryopreservation were moderate. Unexpectedly, certain genes that showed alterations in Fresh-ET tended to be restored in FET. Further analysis suggested that this regression may underlie the improvement of fetal growth restriction in FET. The expression of imprinted genes was disrupted in both FET and Fresh-ET groups. Conclusion: Based on our experimental data on mouse models, the impact of embryo cryopreservation is less pronounced than other in vitro manipulations in Fresh-ET. However, the impairment of the embryonic developmental potential and the gene alterations in placenta still suggested it to be a risky operation. [ABSTRACT FROM AUTHOR]