Search

Abstract Epithelial ovarian cancer (EOC) presents considerable difficulties in prognostication and treatment strategy development. Bevacizumab, an anti-angiogenic medication, has demonstrated potential in enhancing progression-free survival (PFS) in EOC patients. Nevertheless, the identification of individuals at elevated risk of disease progression following treatment remains a challenging task. This study was to develop and validate a deep learning (DL) model using retrospectively collected computed tomography (CT) plain scans of inoperable and recurrent EOC patients receiving bevacizumab treatment diagnosed between January 2013 and January 2024. A total of 525 patients from three different institutions were retrospectively included in the study and divided into training set (N = 400), internal test set (N = 97) and external test set (N = 28). The model’s performance was evaluated using Harrell’s C-index. Patients were categorized into high-risk and low-risk group based on a predetermined cutoff in the training set. Additionally, a multimodal model was evaluated, incorporating the risk score generated by the DL model and the pretreatment level of carbohydrate antigen 125 as input variables. The Net Reclassification Improvement (NRI) metric quantified the reclassification performance of our optimal model in comparison to the International Federation of Gynecology and Obstetrics (FIGO) staging model. The results indicated that DL model achieved a PFS predictive C-index of 0.73 in the internal test set and a C-index of 0.61 in the external test set, along with hazard ratios of 34.24 in the training set (95% CI: 21.7, 54.1; P

Abstract Activin A and hepatic stellate cells (HSCs) are involved in tissue repair and fibrosis in liver injury. This study investigated the impact of activin A on HSC activation and migration. A microfluidic D4-chip was used for examining the cell migration of mouse hepatic stellate cell line MHSteC. The analysis of differentially expressed genes revealed that activin βA (Inhba), activin receptor type 1A (Acvr1a) and type 2A (Acvr2a) mRNAs were more significantly expressed in human HSCs than in the hepatocytes. Moreover, activin A promoted MHSteC proliferation and induced MHSteC migration. Furthermore, the MHSteCs treated with activin A exhibited increased levels of migration-related proteins, N-cadherin, Vimentin, α-SMA, MMP2 and MMP9, but a decreased level of E-cadherin. Additionally, activin A treatment significantly increased the p-Smad3 levels and p-Smad3/Smad3 ratio in the MHSteCs, and the Smad3 inhibitor SIS3 attenuated activin A-induced MHSteC proliferation and migration. Simultaneously, activin A increased the calcium levels in the MHSteCs, and the migratory effects of activin A on MHSteCs were weakened by the intracellular calcium ion-chelating agent BAPTA-AM. These data indicate that activin A can promote MHSteC activation and migration through the canonical Smad3 signaling and calcium signaling.

Abstract Background UNC5A had been reported to play crucial roles in multiple cancers. However, little was known about the associations among UNC5A and glioma. Therefore, we first combined scRNA-seq, proteomics, as well as bulk RNA-seq in order to investigate UNC5A’s functions in gliomas. Methods Online databases provided scRNA-seq, proteomics, as well as bulk RNA-seq data on UNC5A in gliomas. The following procedures were conducted in order: QRT-PCR, Norman chart, gene set enrichment analysis (GSEA), and univariate/multifactor Cox regression analyses. We further explored the associations among UNC5A and tumor immunity. Results By comparing gliomas with normal tissues, the TCGA dataset showed a significantly reduced expression of UNC5A, which was also confirmed by GSE50161, GSE4290, and QRT-PCR findings (p

Abstract Lignin, a natural organic polymer that is recyclable and inexpensive, serves as one of the most abundant green resources in nature. With the increasing consumption of fossil fuels and the deterioration of the environment, the development and utilization of renewable resources have attracted considerable attention. Therefore, the effective and comprehensive utilization of lignin has become an important global research topic, with the goal of environmental protection and economic development. This review focused on the bacteria and enzymes that can bio-transform lignin, focusing on the main ways that lignin can be utilized to produce high-value chemical products. Bacillus has demonstrated the most prominent effect on lignin degradation, with 89% lignin degradation by Bacillus cereus. Furthermore, several bacterial enzymes were discussed that can act on lignin, with the main enzymes consisting of dye-decolorizing peroxidases and laccase. Finally, low-molecular-weight lignin compounds were converted into value-added products through specific reaction pathways. These bacteria and enzymes may become potential candidates for efficient lignin degradation in the future, providing a method for lignin high-value conversion. In addition, the bacterial metabolic pathways convert lignin-derived aromatics into intermediates through the “biological funnel”, achieving the biosynthesis of value-added products. The utilization of this “biological funnel” of aromatic compounds may address the heterogeneous issue of the aromatic products obtained via lignin depolymerization. This may also simplify the separation of downstream target products and provide avenues for the commercial application of lignin conversion into high-value products.

To solve the problem of high sintering temperature of vitrified bond, a novel low- temperature vitrified bond based on Bi2O3-B2O3 glass system was proposed. The effect of nano-SiC and nano-ZrO2 on the phase composition, fluidity and mechanical properties of the vitrified bond were analyzed. Additionally, the effect of adding walnut shell powder as a pore-forming agent on the microstructure of the vitrified bond diamond grinding wheel was explored. A vitrified bond diamond cup grinding wheel based on Bi2O3-B2O3 glass system was prepared, and its grinding performance on monocrystalline silicon wafer was tested. The results show that adding nano-SiC powder leads to the formation of Bi in the vitrified bond and destroys the [BiO4] glass network of vitrified bond. The fluidity of the vitrified bond decreases with the addition of nano-SiC and nano- ZrO2. Furthermore, the fluidity, flexural strength and hardness of the vitrified bond increase as the sintering temperature increases. The flexural strength and the hardness of the vitrified bond reach to their highest value at 560 ℃. With the increase of the content of the pore-forming agent, the amount of large pores in the grinding wheel increases significantly and the size becomes larger. The prepared Bi2O3-B2O3 vitrified bond diamond cup grinding wheel (800 mesh or M10/20) was used to grind monocrystalline silicon wafer under specific conditions (linear speed: 12.56 m/s, workpiece speed: 5.23 m/s, and feed speed: 0.1 μm/s). The grinding ratio reaches 790, and the surface roughness of the monocrystalline silicon wafer is 0.16 μm.

Background: Since cytokine receptor-like factor 1 (CRLF1) has been implicated in tissue regeneration, we hypothesized that CRLF1 released by mesenchymal stem cells can promote the repair of osteochondral defects. Methods: The degree of a femoral osteochondral defect repair in rabbits after intra-articular injections of bone marrow-derived mesenchymal stem cells (BMSCs) that were transduced with empty adeno-associated virus (AAV) or AAV containing CRLF1 was determined by morphological, histological, and micro computer tomography (CT) analyses. The effects of CRLF1 on chondrogenic differentiation of BMSCs or catabolic events of interleukin-1beta-treated chondrocyte cell line TC28a2 were determined by alcian blue staining, gene expression levels of cartilage and catabolic marker genes using real-time PCR analysis, and immunoblot analysis of Smad2/3 and STAT3 signaling. Results: Intra-articular injections of BMSCs overexpressing CRLF1 markedly improved repair of a rabbit femoral osteochondral defect. Overexpression of CRLF1 in BMSCs resulted in the release of a homodimeric CRLF1 complex that stimulated chondrogenic differentiation of BMSCs via enhancing Smad2/3 signaling, whereas the suppression of CRLF1 expression inhibited chondrogenic differentiation. In addition, CRLF1 inhibited catabolic events in TC28a2 cells cultured in an inflammatory environment, while a heterodimeric complex of CRLF1 and cardiotrophin-like Cytokine (CLC) stimulated catabolic events via STAT3 activation. Conclusion: A homodimeric CRLF1 complex released by BMSCs enhanced the repair of osteochondral defects via the inhibition of catabolic events in chondrocytes and the stimulation of chondrogenic differentiation of precursor cells.

Objective: Brown adipose tissue (BAT) plays a crucial role in regulating non-shivering thermogenesis under cold exposure. Proline hydroxylases (PHDs) were found to be involved in adipocyte differentiation and lipid deposition. However, the effects of PHDs on regulatory mechanisms of BAT thermogenesis are not fully understood. Methods: We detected the expression of PHDs in different adipose tissues by using immunoblotting and real-time PCR. Further, immunoblotting, real-time PCR, and immunostaining were performed to determine the correlation between proline hydroxylase 2 (PHD2) and UCP1 expression. Inhibitor of PHDs and PHD2-sgRNA viruses were used to construct the PHD2-deficiency model in vivo and in vitro to investigate the impacts of PHD2 on BAT thermogenesis. Afterward, the interaction between UCP1 and PHD2 and the hydroxylation modification level of UCP1 were verified by Co-IP assays and immunoblotting. Finally, the effect of specific proline hydroxylation on the expression/activity of UCP1 was further confirmed by site-directed mutation of UCP1 and mass spectrometry analysis. Results: PHD2, but not PHD1 and PHD3, was highly enriched in BAT, colocalized, and positively correlated with UCP1. Inhibition or knockdown of PHD2 significantly suppressed BAT thermogenesis under cold exposure and aggravated obesity of mice fed HFD. Mechanistically, mitochondrial PHD2 bound to UCP1 and regulated the hydroxylation level of UCP1, which was enhanced by thermogenic activation and attenuated by PHD2 knockdown. Furthermore, PHD2-dependent hydroxylation of UCP1 promoted the expression and stability of UCP1 protein. Mutation of the specific prolines (Pro-33, 133, and 232) in UCP1 significantly mitigated the PHD2-elevated UCP1 hydroxylation level and reversed the PHD2-increased UCP1 stability. Conclusions: This study suggested an important role for PHD2 in BAT thermogenesis regulation by enhancing the hydroxylation of UCP1.

Objectives To investigate sexual behaviours among HIV-discordant heterosexual couples and assess the correlates of condom use at the couple level.Design Cross-sectional study.Setting Seven prefectures along the Yangtze River in the Anhui Province, China.Participants We included 412 participants aged 18 years or older (206 married HIV-discordant couples).Primary and secondary outcome measures In this study, sexual behaviours included marital or extramarital sex in the past 6 months, as well as the frequency of marital sex and condom use (always, sometimes or never) if having marital sex in the past 6 months. We used stepwise ordinal logistic regression modelling to determine the correlates of condom use.Results In total, 63.1% (130 of 206) of couples had marital sex in the past 6 months, of which 89.2% (116 of 130) used condoms consistently. Couples with more marital duration (OR=1.15; 95% CI: 1.03, 1.28) were more inclined to adhere to condom use, whereas those lacking support and care (OR=0.25; 95% CI: 0.07, 0.94) and being remarried (OR=0.08; 95% CI: 0.02, 0.43) were associated with less condom use. In addition, HIV-positive respondents were more likely to have extramarital sex than HIV-negative respondents (p=0.015).Conclusions The extramarital sex of HIV-positive spouses should be considered. Implementation of interventions, such as increasing support and care between spouses to promote marital intimacy and stability, could reduce unprotected sexual behaviour.

The effect of the content and the size (0.2, 0.4, 0.6 mm) of the hollow corundum microspheres on the total porosity, the flexural strength, the hardness and the microstructure of vitrified bond was investigated. The ceramic bonded diamond grinding wheel with hollow alumina microspheres as pore forming agent was prepared, and the grinding performance of the grinding wheel on quartz glass was studied. The results show that with the increase of the content of hollow corundum microspheres, the porosity increases, and the flexural strength and the hardness decreases at the same time. With the same content of hollow corundum microspheres, addition the smaller size of microspheres could lead to the increase of the porosity and the decrease of flexural and hardness. The vitrified bond diamond wheel contained with hollow corundum microspheres can used to grind quartz glass, and the surface roughness can be reduced from 0.5113 μm to 0.0206 μm. Diamond wheel contained with hollow corundum microspheres can used to grind quartz glass, and the surface roughness can be reduced from 0.5113 μm to 0.0206 μm.

The grinding performance of micro-textured grinding wheel with arrayed micro-hole and common grinding wheel are compared through experiments on alumina, aluminum nitride, zirconia and silicon nitride ceramic materials. The grinding force, the specific grinding energy, the surface roughness and the surface chipping are analyzed. In comparison with common grinding wheel, micro-textured grinding wheel improves the grinding force and the specific grinding energy in grinding of alumina, aluminum nitride and zirconia ceramics, reduces the surface roughness of these ceramics, but has a little effect on the grinding force and the surface roughness of silicon nitride ceramics. Silicon nitride has higher grinding force and specific grinding energy than other ceramic materials do. The surface characteristics of alumina and aluminum nitride mainly imply brittle removal mode, while a ductile removal mode is characterized on the surface of zirconia and silicon nitride has both plastic and brittle removal characteristics. The surface chipping thickness processed by the micro-textured grinding wheel is larger than that of the common grinding wheel, while the surface chipping thickness of both alumina and aluminum nitride ceramics is larger than those of zirconia and silicon nitride ceramics.

Abstract Background Tauroursodeoxycholic acid (TUDCA), a hydrophilic bile acid, is the main medicinal component of bear bile and is commonly used to treat a variety of hepatobiliary diseases. Meanwhile, TUDCA has been shown to modulate the intestinal barrier function and alleviate DSS-induced colitis in mice. However, the effect of TUDCA on the intestinal barrier of weaned piglets remains largely unclear. Methods The weaned piglets and porcine IPEC-J2 intestinal epithelial cells were used to investigate the effects of TUDCA on intestinal barrier function in weaned piglets and explore the possible underlying mechanisms. In vivo, 72 healthy weaned piglets were randomly allocated into 2 groups according to their gender and body weight, and piglets were fed the basal diet with 0 (control, CON) and 200 mg/kg TUDCA for 30 d, respectively. Three female and three male piglets reflecting the average bodyweight were slaughtered in each group and samples were collected. In vitro, IPEC-J2 cells were subjected to 100 μmol/L TUDCA to explore the possible underlying mechanisms. Results Our results demonstrated that dietary TUDCA supplementation significantly reduced the diarrhea incidence of weaned piglets, possibly attributing to the TUDCA-enhanced intestinal barrier function and immunity. In addition, TUDCA supplementation altered serum metabolites and the relative abundance of certain gut bacteria, which might contribute to the improved intestinal barrier function. Furthermore, the in-vitro results showed that TUDCA improved the E. coli-induced epithelial barrier impairment of IPEC-J2 cells and increased Takeda G-coupled protein receptor 5 (TGR5) protein expression. However, knockdown of TGR5 and inhibition of myosin light chain kinase (MLCK) pathway abolished the TUDCA-improved epithelial barrier impairment in E. coli-treated IPEC-J2 cells, indicating the involvement of TGR5-MLCK in this process. Conclusions These findings showed that TUDCA improved intestinal barrier function associated with TGR5-MLCK pathway and the alteration of serum metabolites and gut bacteria in weaned piglets, suggesting the potential application of TUDCA in improving gut health in piglet production.

Public participation in river basin ecological compensation is one of the effective means to adjust the multi stakeholder relationship and promote low-carbon development. This paper takes the upper Yellow River basin section as the research area, adds ecological compensation policy variables to the Theory of Planned Behavior (TPB). An integrated theoretical framework is established from the two levels of personal psychological cognition and policy environment, which can comprehensively consider multiple factors that affect individual behavior. This paper uses the Structural Equation Modeling (SEM) to empirically analyze the impact of psychological factors and river basin ecological compensation policy on the public's willingness and behavior to participate in river basin ecological compensation. The results showed that the three psychological cognitive factors of behavior attitude, subjective norm and perceived behavior control had a significant impact on the public's willingness to participate in ecological compensation. The ecological compensation policy also has a significant impact on the willingness and behavior of the public to participate in ecological compensation. The impact coefficient of ecological compensation policy on the participation willingness is 0.085, and the impact coefficient on the participation behavior is 0.551. The existing ecological compensation policies in carbon neutral contexts have a stronger effect on the public participation behavior, but a weaker impact on the public's willingness to participate. The existing policies in carbon neutral contexts play a small role in mobilizing the public's enthusiasm from the psychological cognitive level, but the willingness to participate has a significant direct impact on the participation behavior. The research conclusions of this paper can help to broaden the theoretical framework of public participation and provide new ideas and methods for improving the ecological compensation mechanism of the river basin.

Uncertainty and randomness in demand and supply bring significant challenges to the stable operation of the grid and the scheduling planning of multi-energy sources. To solve these challenges, we propose and analyze a multi-energy dispatching model which minimizes the total cost and enhances the efficiency of supplying power. Specifically, we design matching algorithms that simulate an appropriately scaled sequence of stochastic EV demand. We also analyze four different energy dispatching scenarios proving that the scheduling model and the multi-energy synergistic microgrid structure can bring higher efficiency and lower costs. Our main contribution is using a simulation approach to take EVs into account for demand-side uncertainty, which significantly improves the efficiency of grid dispatch.

Nutritional diarrhea and subsequent performance degradation in weaned piglets are major challenges for the pig industry. Bile acids (BA) can be added to the diet as emulsifiers. This experiment was conducted to investigate the effects of chenodeoxycholic acid (CDCA), a major primary BA, on growth performance, serum metabolic profiles and gut health in weaned piglets. A total of 72 healthy weaned piglets were randomly assigned to the control (CON) and the CDCA groups, which were feed a basal diet and the basal diet supplemented with 200 mg/kg CDCA for 30 d, respectively. Our results demonstrated that CDCA significantly increased final BW and average daily gain (ADG), decreased feed-to-gain (F:G) ratio and tended to reduce diarrhea incidence. In addition, CDCA increased the villus height-to-crypt depth (V:C) ratio, elevated goblet cell numbers and the expression of tight junction proteins, suggesting the enhancement of intestinal barrier function. As an emulsifier, CDCA increased jejunal lipase activity and the mRNA expression of pancreatic lipases. CDCA supplementation also altered the serum metabolic profiles, including increasing the levels of indole 3-acetic acid, N′-formylkynurenine and theobromine that were beneficial for gut health. Moreover, the relative abundance of 2 beneficial gut bacteria, Prevotella 9 and Prevotellaceae TCG-001, were increased, whereas the relative abundance of a harmful bacteria, Dorea, was decreased in the gut of weaned piglets supplemented with CDCA. Importantly, the altered serum metabolic profiles showed a strong correlation with the changed gut bacteria. In conclusion, CDCA improved the growth performance of weaned piglets by improving intestinal morphology and barrier function, and enhancing lipid digestion, accompanied by alterations of serum metabolic profiles, and changes in relative abundance of certain gut bacteria.

Glioma, one of the most common malignant tumors in the nervous system, is characterized by limited treatment, high mortality and poor prognosis. Numerous studies have shown that lncRNAs play an important role in the onset and progression of glioma by acting on various classical signaling pathways of tumors through signaling, trapping, guiding, scaffolding and other functions. LncRNAs contribute to the malignant progression of glioma via proliferation, apoptosis, epithelial-mesenchymal transformation, chemotherapy resistance, ferroptosis and other biological traits. In this paper, relevant lncRNA signaling pathways involved in glioma progression were systematically evaluated, with emphasis placed on the specific molecular mechanism of lncRNAs in the process of ferroptosis, in order to provide a theoretical basis for the application of lncRNAs in the anticancer treatment of glioma.

Bisphenol A (BPA) pollution poses an increasingly serious problem. BPA has been detected in a variety of environmental media and human tissues. Microbial degradation is an effective method of environmental BPA remediation. However, BPA is also biotoxic to microorganisms. In this study, Rhodococcus equi DSSKP-R-001 (R-001) was used to degrade BPA, and the effects of BPA on the growth metabolism, gene expression patterns, and toxicity-resistance mechanisms of Rhodococcus equi were analyzed. The results showed that R-001 degraded 51.2% of 5 mg/L BPA and that 40 mg/L BPA was the maximum BPA concentration tolerated by strain R-001. Cytochrome P450 monooxygenase and multicopper oxidases played key roles in BPA degradation. However, BPA was toxic to strain R-001, exhibiting nonlinear inhibitory effects on the growth and metabolism of this bacterium. R-001 bacterial biomass, total protein content, and ATP content exhibited V-shaped trends as BPA concentration increased. The toxic effects of BPA included the downregulation of R-001 genes related to glycolysis/gluconeogenesis, pentose phosphate metabolism, and glyoxylate and dicarboxylate metabolism. Genes involved in aspects of the BPA-resistance response, such as base excision repair, osmoprotectant transport, iron-complex transport, and some energy metabolisms, were upregulated to mitigate the loss of energy associated with BPA exposure. This study helped to clarify the bacterial mechanisms involved in BPA biodegradation and toxicity resistance, and our results provide a theoretical basis for the application of strain R-001 in BPA pollution treatments.

In the context of international carbon neutrality, energy prices are affected by several nonlinear and nonstationary factors, making it challenging for traditional forecasting models to predict energy prices effectively. The existing literature mainly uses linear models or a combination of multiple models to forecast energy prices. For the nonlinear relationship between variables and the mining of historical data information, the prediction strategy and accuracy of the existing literature need to be improved. Thus, this paper improves the prediction accuracy of energy prices by developing a “decomposition-reconstruction-integration” thinking strategy that affords medium- and short-term energy price prediction based on carbon constraint, eigenvalue transformation and deep learning neural networks. Considering 2011–2020 as the research period, the prices for traditional energy resources and polysilicon in clean photovoltaic energy raw materials are selected as representatives. Based on energy price decomposition using the Singular Spectrum Analysis (SSA) method, and combining it with Learning Vector Quantization (LVQ) cluster technology, the decomposed quantities are aggregated into price sequences with different characteristics. Additionally, the carbon intensity is considered the leading market’s overall constraint, which is input with the processed price data into a Long Short-Term Memory network (LSTM) model for training. Thus, the SSA-LSTM combined forecasting model is developed to predict the energy price under carbon neutrality. Four indices are employed to evaluate the prediction accuracy: Root Mean Squared Error (RMSE), Mean Absolute Error (MAE), Mean Absolute Percentage Error (MAPE) and R-squared. The results highlight the following observations. (1) Using a sequence decomposition clustering strategy significantly improves the model’s prediction accuracy. This strategy enhances predicting the overall trend of the price series and the changes in different periods. For coal price, the RMSE value decreased from 0.135 to 0.098, the MAE value decreased from 0.087 to 0.054, the MAPE value decreased from 0.072 to 0.064, and the R-squared value increased from 0.643 to 0.725. Regarding the polysilicon price, the RMSE value decreased from 0.121 to 0.096, the MAE value decreased from 0.068 to 0.064, the MAPE value decreased from 0.069 to 0.048, and the R-squared value increased from 0.718 to 0.764. (2) The prediction effect is better in the case of carbon constraint. Considering “carbon emission intensity” as the overall constraint of the leading market, it can effectively explore the typical characteristics of energy price information. Four evaluation indicators show that the accuracy of the model prediction can be improved by more than 3%. (3) When the proposed SSA-LSTM model is used to predict both prices, the results show that the evaluation index of the prediction error remained at about 1%, while the model’s accuracy was high. This also proves that the proposed model can predict traditional energy prices and new energy sources such as solar energy.

The aim of this study is to examine the thiol species for the high cadmium (Cd) tolerance of spinach and provide information for the improvement of soil utilization. The spinach was cultured in aqueous solution with concentrations of Cd ranging from 1 to 9 mg/L. The time responses of glutathione (GSH) and phytochelatins (PCs, PC2-PC4) in the tissues of spinach were monitored via HPLC–MS/MS, and the concentrations of Cd in the roots, shoots and leaves were detected by ICP–OES. Data were analyzed via one-way ANOVA and Spearman correlation to assess the relationships among the types of thiols and the changes between types of thiols and Cd. As Cd stress increased, Cd concentrations in tissues also increased. The total thiol contents responded to Cd stresses with correlations r ranging from 0.394 (root), 0.520 (shoot) to 0.771 (leaf) (p < 0.01). GSH and PC3 were dominant on most of the days under Cd stress. The correlation r between improvements in GSH and increments of Cd concentration in roots was −0.808 (p < 0.01), and r between changes in PC3 and changes in Cd concentrations in leaves was −0.503 (p < 0.01). No correlation can be found between GSH and the subtypes of PCs in shoots, but strong positive correlations within the subtypes of PCs. Thiols can be produced in different tissues of spinach, while the shoots are only a transport tissue for GSH.

BackgroundGlioma is one of the highly fatal primary tumors in the central nervous system. As a major component of tumor microenvironment (TME), immune cell has been proved to play a critical role in the progression and prognosis of the diffuse lower-grade gliomas (LGGs). This study aims to screen the key immune-related factors of LGGs by investigating the TCGA database.MethodsThe RNA-sequencing data of 508 LGG patients were downloaded in the TCGA database. ESTIMATE algorithm was utilized to calculate the stromal, immune, and ESTIMATE scores, based on which, the differentially expressed genes (DEGs) were analyzed by using “limma” package. Cox regression analysis and the cytoHubba plugin of Cytoscape software were subsequently applied to screen the survival-related genes and hub genes, the intersection of which led to the identification of SERPINE1 that played key roles in the LGGs. The expression patterns, clinical features, and regulatory mechanisms of SERPINE1 in the LGGs were further analyzed by data mining of the TCGA database. What’s more, the above analyses of SERPINE1 were further validated in the LGG cohort from the CGGA database.ResultWe found that stromal and immune cell infiltrations were strongly related to the prognosis and malignancy of the LGGs. A total of 54 survival-related genes and 46 hub genes were screened out in the DEGs, within which SERPINE1 was identified to be significantly overexpressed in the LGG samples compared with the normal tissues. Moreover, the upregulation of SERPINE1 was more pronounced in the gliomas of WHO grade III and IDH wild type, and its expression was correlated with poor prognosis in the LGG patients. The independent prognostic value of SERPINE1 in the LGG patients was also confirmed by Cox regression analysis. In terms of the functions of SERPINE1, the results of enrichment analysis indicated that SERPINE1 was mainly enriched in the immune‐related biological processes and signaling pathways. Furthermore, it was closely associated with infiltrations of immune cells in the LGG microenvironment and acted synergistically with PD1, PD-L1, PD-L2.ConclusionThese findings proved that SERPINE1 could serve as a prognostic biomarker and potential immunotherapy target of LGGs.

Nanodiamonds (NDs) have the characteristics of both diamonds and nanomaterials. However, it is difficult to disperse NDs, and this is why there is less research regarding NDs in the field of aluminum matrix composites. In the present work, NDs were modified via surface oxidation, and ND/Al matrix composites were successfully prepared via mechanical ball milling and vacuum sintering. The effects of different volume fraction of NDs (1%, 3%, 5%, 7%) after surface oxidation on the ND/Al matrix composite were analyzed using a metallographic microscope, scanning electron microscope, infrared spectrometer, X-ray diffractometer, microhardness tester, and universal testing machine. The results show that the optimal temperature of surface oxidation treatment is 673 K, which effectively purifies the surface of ND and introduces appropriate C=O functional groups. NDs are uniformly distributed in the aluminum matrix, and no harmful Al 4 C 3 phase is formed. With an increase in the volume fraction of NDs, the grain size of the matrix first decreases and then increases, and the ultimate compressive strength first increases and then decreases. The volume fraction of ND with better comprehensive performance is 3% and the yield strength increased by 19%.

Piezoelectrets, a new type of electromechanical transducer material with low acoustic impedance and high piezoelectric d33 and g33 coefficients, are promising candidates for developing high-performance air-coupled ultrasonic transducers. In this work, we design polypropylene-piezoelectret-film based air-coupled transducers (ACTs) with two different structures and investigate the influence of boundary conditions of the film with experimental measurement, electromechanical equivalent circuit modeling (EECM), and finite element analysis (FEA) for both inverse and direct piezoelectric effects. The experimental data are in great agreement with the results of EECM and FEA. The resonant frequency of the ACT with a free-front-clamped-back (FFCB) film is about half of that of the device with a free-front-free-back (FFFB) film, the response peak of the FFCB device is higher than that of the FFFB device, and the −3dB bandwidth of the former is much narrower than that of the latter. The results show that the experimental measurements can be predicted by EECM and FEA, which can provide the basis for the development of high-performance air-coupled ultrasonic transducers based on piezoelectret films.

Imbalances of proatherogenic inflammatory and antiatherogenic inflammatory mediators were involved in the pathogenesis of atherosclerosis. This study sought to investigate the effects of proatherogenic inflammatory and antiatherogenic inflammatory mediators on the proximal, middle, and distal coronary artery reocclusions in elderly patients after coronary stent implantations. We measured the expression levels of proatherogenic inflammatory/antiatherogenic inflammatory cytokines. This included interleukin-1 β (IL-1 β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), high-sensitivity C-reactive protein (hs-CRP), interleukin-10 (IL-10), interleukin-17 (IL-17), interleukin-13 (IL-13), and interleukin-37 (IL-37) in the elderly patients with the proximal, middle, and distal coronary artery reocclusions after coronary stent implantations. Levels of IL-1 β, IL-6, IL-8, TNF-α, and hs-CRP were remarkably increased (P

Background/Aims: It has been implicated that calcium supplementation is involved in reducing body weight/fat and improving glucose homeostasis. However, the underlying mechanisms are still not fully understood. Here, we investigated the effects of calcium supplementation on adipogenesis and glucose homeostasis in porcine bone marrow mesenchymal stem cells (pBMSCs) and high fat diet (HFD)-fed mice and explored the involved signaling pathways. Methods: In vitro, pBMSCs were treated with 4 mM extracellular calcium ([Ca2+]o) and/or 1 μM nifedipine, 0.1 μM BAPTA-AM, 1 μM KN-93, 50 nM wortmannin for 10 days. The intracellular calcium ([Ca2+]i) levels were measured using Fluo 3-AM by flow cytometry. The adipogenic differentiation of pBMSCs was determined by Oil Red-O staining and triglyceride assay. The expression of marker genes involved in adipogenesis (peroxisome proliferator activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα)) and glucose uptake (glucose transporter 4 (GLUT4)), as well as the activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and PI3K/Akt-FoxO1/AS160 signaling pathways were determined by Western blotting. Glucose uptake and utilization were examined using 2-NBDG assay and glucose content assay, respectively. In vivo, C57BL/6J male mice were fed a HFD (containing 1.2% calcium) without or with 0.6% (w/w) calcium chloride in drinking water for 13 weeks. The adipogenesis, glucose homeostasis and the involvement of CaMKII and PI3K/Akt signaling pathway were also assessed. Results: In vitro, [Ca2+]o stimulated pBMSCs adipogenesis by increasing [Ca2+]i level and activating CaMKII and PI3K/Akt-FoxO1 pathways. In addition, [Ca2+]o promoted glucose uptake/utilization by enhancing AS160 phosphorylation, GLUT4 expression and translocation. However, the stimulating effects of [Ca2+]o on pBMSCs adipogenesis and glucose uptake/utilization were abolished by L-VGCC blocker Nifedipine, [Ca2+]i chelator BAPTA-AM, CaMKII inhibitor KN-93, or PI3K inhibitor Wortmannin. In vivo, calcium supplementation decreased body weight and fat content, increased adipocyte number, and improved glucose homeostasis, with elevated PPARγ and GLUT4 expression and PI3K/Akt activation in iWAT. Conclusion: calcium supplementation enhanced adipogenesis and glucose uptake in pBMSCs, which was coincident with the increased adipocyte number and improved glucose homeostasis in HFD-fed mice, and was associated with activation of CaMKII and PI3K/Akt-FoxO1/AS160 pathways. These data provided a broader understanding of the mechanisms underlying calcium-induced body weight/fat loss and glycemic control.

AlMgB14 hot pressed under different environments from the elemental powders was investigated. The microstructure of the products was analyzed by scanning electron microscopy (SEM) with energy dispersive X-ray spectroscopy (EDX) and X-ray diffractometer (XRD). The density, hardness and fracture toughness of AlMgB14 were also examined. The results show that single phase of MgAl2O4 is formed in hot pressed Al-Mg-B system in air. The addition of carbon powder cannot reduce the formation of MgAl2O4. Additional Al (10 wt.%) and Mg (10 wt.%) can effectively compensate for their loss in the formation of MgAl2O4 and enhance the production of AlMgB14 under agron atmosphere. The AlMgB14 with 10 vol.% spinel MgAl2O4 owns a hardness of 28.42 GPa and a fracture toughness of 2.92 MPa•m1/2.

Background. Severe coronary stenosis and multiple coronary chronic total occlusions are serious side effects of coronary stent implantation in elderly patients. This research sought to investigate the side effects of coronary stenting such as severe coronary stenosis and multiple coronary chronic total occlusions in elderly patients via induced proinflammatory and prooxidative stress. Methods. We evaluated the expression levels of tumor necrosis factor-α (TNF-α), toll-like receptor 4 (TLR4), acrolein (ACR), malondialdehyde (MDA), high-sensitivity C-reactive protein (hs-CRP), stromal cell-derived factor-1α (SDF-1α), superoxide dismutase 3 (SOD3), and endothelial nitric oxide synthase (eNOS) in elderly patients with severe coronary stenosis and multiple coronary chronic total occlusions. Results. Levels of TNF-α, TLR4, ACR, MDA, and hs-CRP were remarkably increased (P

It has been shown that IGF-1 secretion is influenced by dietary protein or amino acid. However, whether the dipeptides elicit regulatory effects on IGF-1 secretion remains largely unclear. Thus, this study aimed to investigate the effects of the dipeptide Pro-Gly on IGF-1 expression and secretion in HepG2 cells and mice, and explore the underlying mechanisms. The in vitro results indicated that Pro-Gly, but not Pro plus Gly, promoted the expression and secretion of IGF-1 in HepG2. Meanwhile, the expression of the peptide transporter 1 (PepT1) was elevated by Pro-Gly, whereas knockdown of PepT1 with siRNA eliminated the increase of IGF-1 expression induced by Pro-Gly. In addition, Pro-Gly activated JAK2/STAT5 signaling pathway in a PepT1-dependent manner. Furthermore, Pro-Gly enhanced the interaction between JAK2 and STAT5, and the translocation of phospho-STAT5 to nuclei. Moreover, inhibition of JAK2/STAT5 blocked the promotive effect of Pro-Gly on IGF-1 expression and secretion. In agreement with the in vitro results, the in vivo findings demonstrated that Pro-Gly, but not Pro plus Gly, stimulated the expression and secretion of IGF-1 and activated JAK2/STAT5 signaling pathway in the liver of mice injected with Pro-Gly or Pro+Gly acutely or chronically. Besides, acute injection of JAK2/STAT5 inhibitor abolished the elevation of IGF-1 expression and secretion induced by Pro-Gly in mice. Collectively, these findings suggested that the dipeptide Pro-Gly promoted IGF-1 expression and secretion in HepG2 cells and mice by activating JAK2/STAT5 signaling pathway through PepT1. These data provided new insights to the regulation of IGF-1 expression and secretion by the dipeptides.

Porcine bone marrow mesenchymal stem cells (pBMSCs) have the potential for application in regenerative medicine. This study aims to investigate the effects of extracellular calcium (Ca2+o) on pBMSCs proliferation and to explore the possible underlying mechanisms. The results demonstrated that 4 mM Ca2+o significantly promoted pBMSCs proliferation by reducing the G0/G1 phase cell percentage and by increasing the S phase cell proportion and the proliferation index of pBMSCs. Accordingly, Ca2+o stimulated the expression levels of proliferative genes such as cyclin A2, cyclin D1/3, cyclin E2, and PCNA and inhibited the expression of p21. In addition, Ca2+o resulted in a significant elevation of intracellular calcium and an increased ratio of p-ERK/ERK. However, inhibition of calcium-sensing receptor (CaSR) by its antagonist NPS2143 abolished the aforementioned effects of Ca2+o. Moreover, Ca2+o-induced promotion of pBMSCs proliferation, the changes of proliferative genes expression levels, and the activation of ERK1/2 signaling pathway were effectively blocked by U0126, a selective ERK kinase inhibitor. In conclusion, our findings provided evidence that the enhanced pBMSCs proliferation in response to Ca2+o was associated with the activation of CaSR and ERK1/2 signaling pathway, which may be useful for the application of pBMSCs in future clinical studies aimed at tissue regeneration and repair.

Pressure has a direct effect on metal deposition behavior, but it has been not clear for Zn metal in rechargeable aqueous Zn batteries due to the lack of suitable battery configuration. Here, we investigate the effect of stacking pressure on Zn electrodeposition and elucidate the role of pressure in stabilizing interphasial chemistry and enhancing Zn2+ transport at the electrode-electrolyte interface. Zn nucleation and growth processes can thus be guided by controlling the axial pressure of Zn-based batteries. Dendrite-free and compact Zn deposition is achieved under optimal applied pressure with enhanced cycle life and reaction kinetics. This work provides new insights into enhancing the performance of Zn batteries by regulating mechanical pressure. [ABSTRACT FROM AUTHOR]