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Abstract Background Studies have shown that Chinese Clinicians and nurses have positive attitudes toward ACP, but no local tools exist to assess their need for ACP knowledge and skills training. resulting in their inability to initiate ACP conversations as well as poor end-of-life care for patients. Therefore, this study aims to assess the needs of Chinese Clinicians and nurses for ACP knowledge and skills training and assess the validity and reliability of a questionnaire on the Training Needs for Advance Care Planning (TNACP) scale. Methods From October to November 2021, 170 clinicians and nurses were pre-surveyed using a preliminary draft of the questionnaire. The responses were screened using item analysis, Cronbach’s alpha coefficient, and the intraclass correlation coefficient (ICC) to describe the internal consistency and stability of the questionnaire. The Content validity index (CVI), Exploratory factor analysis (EFA) and Confirmatory factor analysis (CFA) were used to test the validity of the questionnaire. Results After independent samples t-test analysis, Except for the entry “A2”, the critical ratio between the two groups of the remaining 23 items was statistically significant (p 0.40). The results of confirmatory factor analysis showed that the Training Needs for Advance Care Planning (TNACP) scale model fit well(X2/df = 2.504, RMSEA = 0.092, GFI = 0.809, AGFI = 0.745, CFI = 0.931, IFI = 0.932, TLI = 0.916); the Cronbach’s α = 0.888 for the total questionnaire, and the three dimensions of Cronbach’s α were 0.729 to 0.959; and the ICC for the overall scores between the test-retest evaluations was 0.884 (p

The uninterrupted operation of the distribution network is crucial for enhancing the security of power supply. However, factors such as environmental and line conditions may impede uninterrupted operation of overhead lines. Hence, this study conducts an analysis of factors that influence the uninterrupted operation of 10 kV overhead lines in distribution networks. To accomplish this, the Interpretative Structural Model (ISM) is employed to establish a hierarchical structure of the factors. Important factors are selected from this structure for the demand analysis of uninterrupted operation, and an optimization scheme for the design of overhead lines is proposed based on technical requirements for uninterrupted operation. Finally, the model is applied to optimize a real overhead line in a distribution network, thus validating the applicability of the proposed model.

Abstract The increased penetration of renewable energy sources and the intensification of peak‐valley differences present challenges to peak regulation in the power system. Fulfilling the peak regulation needs of the power system solely through generation‐side resources proves to be challenging. Large‐scale fixed frequency air‐conditioning (FFAC) and inverter air‐conditioning (IAC) are high‐quality flexible load resources. This paper proposes a hierarchical coordinated control strategy of air‐conditioning (AC) loads for peak regulation service. In the first layer of the control strategy, the load aggregator collaborates with multiple AC groups to ensure the completion of peak regulation tasks with specific power‐constrained requirements. In the second layer of the control strategy, the control centre of each group optimizes the temperature adjustment values for each AC load, aiming to reduce incentive costs. Finally, the proposed method is validated through simulations, demonstrating its capability to achieve coordinated control of FFAC and IAC loads under various power‐constrained requirements. Furthermore, the simulation demonstrates the effectiveness of the control strategy in reducing user discomfort and the AC's incentive costs.

Abstract Background While observational studies and experimental data suggest a link between oral lichen planus (OLP) and oral cavity cancer (OCC), the causal relationship and the role of inflammatory cytokines remain unclear. Methods This study employed a univariable and multivariable Mendelian Randomization (MR) analysis to investigate the causal relationship between OLP and the risk of OCC. Additionally, the potential role of inflammatory cytokines in modulating this association was explored. Instrumental variables were derived from genetic variants associated with OLP (n = 377,277) identified in Finngen R9 datasets, with 41 inflammatory cytokines as potential mediators, and OCC (n = 4,151) as the outcome variable. Analytical methods including Inverse Variance Weighted (IVW), Weighted Median, MR-Egger, and MR-PRESSO were utilized to assess the causal links among OLP, inflammatory cytokines, and OCC risk. Multivariable MR (MVMR) was then applied to quantify the mediating effects of these cytokines in the relationship between OLP and increased OCC risk. Results MR analysis provided strong evidence of a causal relationship between OLP (OR = 1.417, 95% CI = 1.167–1.721, p

The process of energy decarbonization in island power systems is accelerated due to the swift integration of inverter-based renewable energy resources (IBRs). The unique features of such systems, including rapid frequency changes resulting from potential generation outages or imbalances due to the unpredictability of renewable power, pose a significant challenge in maintaining the frequency nadir without external support. This paper presents a unit commitment (UC) model with data-driven frequency nadir constraints, including either frequency nadir or minimum inertia requirements, helping to limit frequency deviations after significant generator outages. The constraints are formulated using a linear regression model that takes advantage of real-world, year-long generation scheduling and dynamic simulation data. The efficacy of the proposed UC model is verified through a year-long simulation in an actual island power system using historical weather data. The alternative minimum inertia constraint, derived from actual system operation assumptions, is also evaluated. Findings demonstrate that the proposed frequency nadir constraint notably improves the system’s frequency nadir under high photovoltaic (PV) penetration levels, albeit with a slight increase in generation costs, when compared to the alternative minimum inertia constraint.

BackgroundOral lichen planus (OLP) is a relatively common chronic T cell-mediated disease characterized by pain and inflammation. Clobetasol propionate (CLO) is the first-line drug in the treatment of OLP. The meta-analysis aimed to evaluate the efficacy and safety of CLO for treating patients with OLP.MethodsPubMed, Embase and Web of Science were systematically searched from the database inception date up to August 2023. There were no restrictions on language or date of publication. The outcomes of our interest were as follows: improvement of clinical signs and/or symptoms, total lesion size, relapse and adverse events.ResultsA total of 17 RCTs evaluating the effects of CLO were included in this study. The results revealed no significant difference in the clinical score (WMD = 0.14, 95% CI: −0.39, 0.66; p = 0.609) and pain score (WMD = 0.17, 95% CI: −0.44, 0.79; p = 0.582) between CLO and other treatments. However, clinical resolution (RR = 1.61, 95% CI: 1.17, 2.22; p = 0.003) and symptoms improvement (RR = 1.80, 95% CI: 1.17, 2.77; p = 0.008) were significantly different between CLO and other treatments. Moreover, there was a significant reduction in the total lesion size with CLO treatment (WMD = -0.58, 95% CI: −1.03, −0.13; p = 0.011). In addition, CLO showed no statistical incidence of adverse events (RR = 1.46, 95% CI: 0.86, 2.50; p = 0.161) and relapse (RR = 1.56, 95% CI: 0.66, 3.71; p = 0.314) than other therapies.ConclusionThis systematic review and meta-analysis of 17 randomized clinical trials supported the long-term application of CLO as an effective regimen in OLP patients.

Background: The importance of N6-methyladenosine (m6A) modification in tumorigenesis and progression have been highlighted. This study aimed to investigate the modification of insulin receptor substrate 1 (IRS1) by m6A and its role in oral squamous cell carcinoma (OSCC). Methods: Bioinformatics was employed to predict differential genes related to epithelial-mesenchymal transition (EMT) in OSCC. Seventeen pairs of OSCC and paracancerous tissue samples were collected. The impact of IRS1 on OSCC cell growth and EMT was evaluated. The fluctuations in IRS1 enrichment and the involvement of p53/Line-1 were investigated. Results: IRS1 was highly expressed in OSCC. IRS1 silencing decreased OSCC cell proliferation and increased apoptosis. IRS1 silencing hindered EMT by regulating related markers. IRS1 silencing upregulated p53 and downregulated Line-1 ORF1p. The p53 inhibition reversed the effects of IRS1 silencing and induced EMT in OSCC cells. Furthermore, the m6A modification of IRS1 was increased in OSCC cells. IRS1 were positively regulated by the m6A regulators methyltransferase-like 14 (METTL14) and YTH domain-containing protein 1 (YTHDC1). IRS1 bound to YTHDC1, and YTHDC1 knockdown inhibited the IRS1 nuclear export. The obesity-associated protein (FTO) negatively regulated IRS1, and FTO overexpression reversed the IRS1-induced OSCC tumor growth. Conclusions: m6A methylation-mediated IRS1 regulated EMT in OSCC through p53/Line-1. These findings provide potential therapeutic strategies for managing OSCC.

Background and Objective. Oral submucous fibrosis (OSF) is a progressive and irreversible disorder of collagen metabolism, resulting in mucosal fibrosis, oral functional changes, and even malignant transformation. This study investigated the relationship between human leukocyte antigen (HLA)-DQB1 alleles and the susceptibility to OSF in a Hunan Han population, providing a new basis for clinical prevention and treatment of OSF. Methods. 44 OSF patients and 44 healthy volunteers were included in this study. To detect the expression frequency of HLA-DQB1 alleles in the two groups and analyze significant allelic subtypes and their relative risk, polymerase chain reaction (PCR) sequence-specific primers were used. Subsequently, based on the identification of differential genes, we compare the gene expression levels of OSF patients and healthy volunteers expressing differential genes by real-time quantitative PCR. Results. The expression frequency of the HLA-DQB1 ∗05 : 02 allele in the OSF group (36.4%) was significantly higher than in the controls (13.6%), and exposure to the HLA-DQB1 ∗05 : 02 allele was strongly related to OSF (OR (95% CI) = 3.619 (1.257,10.421), Wald χ2 = 5.681, P=0.017). However, there were no significant differences in the allele expression frequencies of DQB1 ∗02 : 01, DQB1 ∗03 : 03, DQB1 ∗05 : 01, DQB1 ∗05 : 03, DQB1 ∗06 : 02, DQB1 ∗06 : 03, and DQB1 ∗06 : 04 in the OSF group compared with the controls (all P>0.05). Furthermore, the relative expression level of the HLA-DQB1 ∗05 : 02 allele in the OSF group (3.98 ± 3.50) was significantly higher than in controls (0.70 ± 0.41). Conclusions. There are differences in the HLA-DQB1 allele polymorphisms between the healthy population and patients with oral submucosal fibrosis. Preliminarily, it is suggested that the HLA-DQB1 ∗05 : 02 allele, which has a strong correlation with OSF and great differential expression between patients with OSF and controls, might be a susceptibility gene for OSF in Hunan.

Abstract Background Alzheimer's disease (AD) is the most common neurodegenerative disease. Mitochondrial dysfunction and immune responses are important factors in the pathogenesis of AD, but their crosstalk in AD has not been studied. In this study, the independent role and interaction of mitochondria-related genes and immune cell infiltration in AD were investigated using bioinformatics methods. Methods The datasets of AD were obtained from NCBI Gene Expression Omnibus (GEO), and the data of mitochondrial genes was from MitoCarta3.0 database. Subsequently, differential expression genes (DEGs) screening and GSEA functional enrichment analysis were performed. The intersection of DEGs and mitochondrial related genes was used to obtain MitoDEGs. The MitoDEGs most relevant to AD were determined by Least absolute shrinkage and selection operator and multiple support vector machine recursive feature elimination, as well as protein–protein interactions (PPI) network and random forest. The infiltration of 28 kinds of immune cells in AD was analyzed by ssGSEA, and the relationship between hub MitoDEGs and the proportion of immune infiltration was studied. The expression levels of hub MitoDEGs were verified in cell models and AD mice, and the role of OPA1 in mitochondrial damage and neuronal apoptosis was investigated. Results The functions and pathways of DEGs were significantly enriched in AD, including immune response activation, IL1R pathway, mitochondrial metabolism, oxidative damage response and electron transport chain-oxphos system in mitochondria. Hub MitoDEGs closely related to AD were obtained based on PPI network, random forest and two machine learning algorithms. Five hub MitoDEGs associated with neurological disorders were identified by biological function examination. The hub MitoDEGs were found to be correlated with memory B cell, effector memory CD8 T cell, activated dendritic cell, natural killer T cell, type 17 T helper cell, Neutrophil, MDSC, plasmacytoid dendritic cell. These genes can also be used to predict the risk of AD and have good diagnostic efficacy. In addition, the mRNA expression levels of BDH1, TRAP1, OPA1, DLD in cell models and AD mice were consistent with the results of bioinformatics analysis, and expression levels of SPG7 showed a downward trend. Meanwhile, OPA1 overexpression alleviated mitochondrial damage and neuronal apoptosis induced by Aβ1-42. Conclusions Five potential hub MitoDEGs most associated with AD were identified. Their interaction with immune microenvironment may play a crucial role in the occurrence and prognosis of AD, which provides a new insight for studying the potential pathogenesis of AD and exploring new targets.

Abstract Intermittent hypoxia is the best predictor of developing cognitive decline and Alzheimer’s disease progression in patients with obstructive sleep apnea. The nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome has been poorly studied as a regulator of neuroinflammation in cognitive impairment caused by intermittent hypoxia. As critical inflammatory cells, exosomes secreted by microglia have been found to affect the spread of pathologic proteins and neuropathology in neurodegenerative diseases. However, the effects of microglial exosomes on neuroinflammation and cognitive outcomes after intermittent hypoxia remain unclear. In this study, the role of miRNAs in microglial exosomes in improving cognitive deficits in mice exposed to intermittent hypoxia was investigated. We demonstrated that miR-146a-5p fluctuated over time in microglial exosomes of mice exposed to intermittent hypoxia for different periods of time, which could regulate neuronal NLRP3 inflammasome and neuroinflammation. In primary neurons, we found that miR-146a-5p regulated mitochondrial reactive oxygen species by targeting HIF1α, thus affecting the NLRP3 inflammasome and secretion of inflammatory factors. Similarly, further studies showed that inhibition of NLRP3 by administering overexpressed miR-146a-5p in microglial exosomes and MCC950 has improved neuroinflammation and cognitive dysfunction in mice after intermittent hypoxia. In conclusion, NLRP3 inflammasome may be a regulatory target for ameliorating cognitive impairment caused by intermittent hypoxia, and microglial exosomal miR-146a-5p may be a promising therapeutic strategy.

In recent years, social media has emerged as an important channel for the dissemination of destination branding. Despite the fact that the dissemination of information through social media enables a broader audience to become acquainted with destinations, the dissemination process of trending events exhibits variances. Consequently, the precise impact of the underlying mechanisms that govern the spread of information on the efficacy of disseminating destination brand trending events remains ambiguous. In an endeavor to bridge this gap, an improved SEIR model was developed in this research to investigate the dynamic dissemination mechanisms and influencing factors of destination trending events within social media. The model was applied to simulate the diffusion mechanism of destinations’ trending events. The results show that during the dissemination process of destination trending events on social media, the proportion of users affected at different stages influences the ultimate effectiveness of information propagation. In light of these insights, this research proposes a social media trending event dissemination strategy to aid in enhancing the propagation efficiency of destination brands through existing resources.

Abstract Objective The purpose of this study was to provide evidence for early life care by meta-analyzing the relationship between infection during pregnancy and up to 2 years of age and the risk of subsequent allergic rhinitis (AR). Methods Published studies up to April 2022 were systematically searched in PubMed, Embase, Web of Science, Cochrane Library, SinoMed, CNKI, Wanfang Database, and VIP. Literature screening, including quality assessment, was performed, and the effect values (OR, HR, RR) and 95% confidence intervals (95% CI) of infection during pregnancy and up to 2 years of age and allergic rhinitis were extracted from each qualified study. Results In total, 5 studies with a sample size of 82,256 reported the relationship between infection during pregnancy and offspring AR. Meta-analysis showed that maternal infection during pregnancy was associated with an increased risk of childhood AR in offspring (OR = 1.34, 95% CI: 1.08–1.67). Altogether, 13 studies with a sample size of 78,426 reported evidence of an association between infection within 2 years of age and subsequent AR in children. A pooled meta-analysis of all studies showed that early infection within 2 years of age was closely associated with childhood AR (OR = 1.25, 95% CI: 1.12–1.40), especially upper respiratory tract infection (OR = 1.32, 95% CI: 1.06–1.65) and gastrointestinal infections (OR = 1.37, 95% CI: 1.01–1.86), but ear infection showed similar results in the cohort study (OR = 1.13, 95% CI: 1.04–1.22). Conclusion Current evidence suggests that infection during pregnancy, early upper respiratory infection, gastrointestinal infections and ear infection within 2 years of age would increase the risk of AR in children. Therefore, the prevention of infection during pregnancy and in infancy and young children needs to be emphasized.

Introduction Exploring the experiences and perspectives of healthcare professionals, patients and caregivers toward serious illness conversations based on the Serious Illness Care Program is vital for improving communication with patients who are seriously ill, as has been shown in previous studies. However, few studies have carried out a systematic review to examine common themes, strengthen conclusions and identify gaps in the literature, the findings of which could help steer further research, policies and practice to improve more timely and person-centred conversations about the values and priorities of patients with serious illnesses. The objective of this qualitative meta-synthesis is to explore how healthcare professionals, patients and caregivers described their own experiences of the processes of serious illness communication through a secondary analysis of published qualitative data.Methods and analysis Meta-aggregation will be used to conduct a systematic review of qualitative studies. We conducted an initial search on 10 October 2023; papers published in English will be searched using electronic databases, including PubMed (MEDLINE), Web of Science, Embase, Ovid and CINAHL. Studies that satisfy the eligibility criteria will be evaluated for methodological quality using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Qualitative Research. The meta-aggregative review will consist of the following: (1) extraction of findings of all included studies; (2) categorisation of the findings, with at least two findings per category; and (3) synthesis of one or more findings from at least two categories. Study eligibility screening, data extraction, analysis and JBI Critical Appraisal Checklist and Grading of Recommendations Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative research assessments will be undertaken independently by two authors.Ethics and dissemination Secondary data analysis of published literature does not require ethical approval. The results will be disseminated in peer-reviewed journals and presented in conference papers and elsewhere.PROSPERO registration number CRD42022330859.

Due to the characteristics of low porosity, low permeability and serious anisotropy in tight reservoirs, it is difficult for conventional hydraulic fracturing theory to accurately guide the efficient exploitation of tight reservoirs. It has been shown that the reservoir rock mechanical properties are the key factor impacting the fracturing effect, but the current research on the damage properties of tight reservoir rocks is not comprehensive enough. Therefore, in order to improve the fracturing theory of tight reservoirs, this paper first explores the evolution mechanism of rock fractures through uniaxial compression experiments. Secondly, based on the particle discrete element method, the damage and failure process of tight sandstone under uniaxial compression is simulated from the microscopic scale. The test results show that the rock failure mainly includes tensile failure, shear failure, and tensile-shear failure; Internal micro-fractures will interconnect during rock destruction to form primary fractures through the rock mass, while secondary micro-fractures will also be generated. The numerical simulation results show that when the rock is subjected to tensile-shear failure, with the increase of load, tensile micro-fractures are mainly produced in the specimen, accompanied by a few shear fractures. Under the joint action of shear failure and tensile failure, V-shaped cracks are easily formed in rock. The tensile strength of rock is mainly affected by the microscopic tensile strength, and the cohesive force, modulus, stiffness ratio, friction coefficient and friction angle have significant effects on the compressive strength of rock. Therefore, a reasonable choice of microscopic parameters can realistically simulate the compression-tensile strength ratio of the rock. The research results of this paper can provide the theoretical basis of rock mechanics for the efficient exploitation of tight reservoirs.

Crocus sativus L. (C. sativus), known as “plant gold ”, has numerous functions in traditional Chinese medicine, including promoting blood circulation, removing blood stasis, cooling blood, detoxifying, relieving depression, and calming the nerves. Its stigma, the main medicinal part, performs extremely low yield and high price, thus the scarce resources, while its petals, the by-product, are usually discarded or employed as fertilizer or feed, resulting in huge waste, as the petals have been proved to contain various chemical components covering terpenoids, flavonoids, and glycosides, which exhibits pharmacological activities of analgesia, anti-inflammatory, cardiovascular protection, liver protection, and antidepressant. This paper aims to compare the material basis of the pharmacological similarities or differences between stigmas and petals, clarify their research status, and evaluate the potential application value of petals. As a by-product of a precious traditional herbal medicine, the petals of C. sativus have been elucidated in previous studies. This review explores the chemical constituents and pharmacological effect of stigma and petals of C. sativus, confirming their similar material bases, and the application prospect of petals.

Abstract Water constitutes the largest energy carrier on earth, absorbing more than 70% of the solar energy received by the earth's surface, yet its low exploitation has been a constant concern. The hydrovoltaic effect is an emerging technology that generates electricity through the direct interaction between nanomaterials and water of various forms (raindrops, waves, flows, moisture, and natural evaporation). Especially, the evaporation‐driven hydrovoltaic effect is a spontaneous and ubiquitous process that can directly convert thermal energy from the surrounding environment into electricity without the demand for additional mechanical work, which shows unique advantages compared with other hydrovoltaic effects. A variety of nanostructured materials have been steadily developed for evaporation‐driven hydrovoltaic devices (EHDs) in recent years. However, there has been a lack of a clear specification on the selection and design of materials for improving device performance. Herein, we first analyze the mechanisms of EHDs followed by a summarization of the recent advances in materials, including carbon materials, biomass‐based materials, metal oxides, composite materials, and others. We then discuss the strategies for improving the energy conversion efficiency and the output power in terms of structural design, surface modification, and interface treatment. Finally, we provide an outlook on the potential applications of electricity generation, sensors, and desalination technology, as well as the challenges and prospects for the development of this emerging technology in the future.

Abstract Aims/Introduction Obstructive sleep apnea (OSA) is related to prediabetes and diabetes. Whether patients with OSA have a higher risk of prediabetes/diabetes remains unclear. We aimed to carry out a meta‐analysis of published studies to evaluate the relationships between OSA and prediabetes and diabetes, and the impact of the severity of OSA on diabetes. Materials and Methods The PubMed, EMBASE and Cochrane databases were searched from January 2011 to July 2021. The associations between OSA and impaired fasting glucose, impaired glucose tolerance, impaired glucose regulation and diabetes mellitus were analyzed. We estimated the pooled odds ratios using fixed or random effects models. We included 25 studies comprising a total of 154,948 patients with OSA and risk factors for prediabetes/diabetes (20 and 16, respectively) in the analysis. Results OSA was associated with a higher risk of impaired fasting glucose, impaired glucose tolerance, impaired glucose regulation and diabetes mellitus in the cohort studies and cross‐sectional studies. The pooled odds ratios were 2.34 (95% confidence interval [CI] 1.16–4.72), 1.58 (95% CI 1.15–2.15), 1.65 (95% CI 1.12–2.42), 2.15 (95% CI 1.68–2.75) and 3.62 (95% CI 2.75–4.75), respectively. Subgroup analyses were based on the proportions of men and women. The results showed that OSA was a risk factor, and there was no significant difference between the two groups. The risk of diabetes increased with the severity of OSA. Conclusions The risk of developing prediabetes and diabetes was higher in patients with OSA.

Generating electricity from air opens a promising way for green energy harvesting. Here, authors present a prototype driven by the integration of moisture adsorption with evaporation to generate continuous electricity for a long duration.

The failure types of bedding determine the penetration behavior of hydraulic fracture. A stratum model containing bedding was established based on the 3D block distinct element method to explore the penetration behavior of hydraulic fractures with different types of bedding. The mechanics of hydraulic fractures penetrating the shear- failure bedding plane and tensile-failure bedding plane were analyzed. The results showed that the shear-failure bedding plane was more difficult to expand than the tensile-failure bedding plane after the hydraulic fracture turns to bedding plane. The initial stress magnitude controls the expansion difficulty of hydraulic fractures, and the high stress magnitude attenuated penetration behavior. The vertical stress affected the shear failure by increasing the shear strength of the bedding plane. It affected the tensile failure by increasing the initiation stress of the bedding plane. The effect of horizontal stress on the penetration behavior included the influence on the initiation stress of vertical joints and the enhancement of the interference stress on the horizontal bedding plane. The conclusions can provide the guidance for hydraulic fracturing in reservoir with bedding planes.

Abstract Large‐scale power systems exhibit more complex dynamics due to the increasing integration of inverter‐based resources (IBRs). Therefore, there is an urgent need to enhance the situational awareness capability for better monitoring and control of power grids dominated by IBRs. As a pioneering Wide‐Area Measurement System, FNET/GridEye has developed and implemented various advanced applications based on the collected synchrophasor measurements to enhance the situational awareness capability of large‐scale power grids. This study provides an overview of the latest progress of FNET/GridEye. The sensors, communication, and data servers are upgraded to handle ultra‐high density synchrophasor and point‐on‐wave data to monitor system dynamics with more details. More importantly, several artificial intelligence (AI)‐based advanced applications are introduced, including AI‐based inertia estimation, AI‐based disturbance size and location estimation, AI‐based system stability assessment, and AI‐based data authentication.

EV-miRNAs regulate the polarization phenotype of macrophages and promote the release of inflammation-related cytokines through a variety of signaling pathways under hypoxia, ultimately affect the development of inflammation.

Natural edible fungal polysaccharides are of research and application value for the prevention of diseases by improving the microenvironment within the intestine. Inonotus obliquus polysaccharide (IOP) extracts have strong antioxidant, anti-inflammatory, and other biological activities, and as such, it could be used as prebiotics to improve the viability of intestinal microbes, maintain intestinal homeostasis and improve intestinal immunity. The effects of sex on intestinal microbiota after IOP absorption was determined. In this study, IOP had different effects on the intestinal flora of male and female rats, with the diversity and richness showing opposite changes. At the same time, after IOP intervention, changes in the dominant intestinal flora of female rats was less compared with that of males. In addition, while Clostridia, Lactobacillus and Roseburia were the dominant intestinal microbes in female rats, males had mainly Bacteroidota from different families and genera, along with an increasing proportion of Muribaculaceae from different families and genera. IOP could further regulate the intestinal microenvironment of male and female SD rats by enhancing the vitality of their dominant microorganisms, and for both sexes, this enabled the screening of dominant microflora that were conducive to the balance of the intestinal flora. These results help to understand the effects of sex-related differences on the composition of the intestinal microbiota as well as on diseases.

Abstract Hypoxia is a pathological condition common to many diseases, although multiple organ injuries induced by hypoxia are often overlooked. There is increasing evidence to suggest that the hypoxic environment may activate innate immune cells and suppress adaptive immunity, further stimulating inflammation and inhibiting immunosurveillance. We found that dysfunctional immune regulation may aggravate hypoxia-induced tissue damage and contribute to secondary injury. Among the diverse mechanisms of hypoxia-induced immune dysfunction identified to date, the role of programmed death-ligand 1 (PD-L1) has recently attracted much attention. Besides leading to tumour immune evasion, PD-L1 has also been found to participate in the progression of the immune dysfunction which mediates hypoxia-induced multiple organ injury. In this review, we aimed to summarise the role of immune dysfunction in hypoxia-induced multiple organ injury, the effects of hypoxia on the cellular expression of PD-L1, and the effects of upregulated PD-L1 expression on immune regulation. Furthermore, we summarise the latest information pertaining to the involvement, diagnostic value, and therapeutic potential of immunosuppression induced by PD-L1 in various types of hypoxia-related diseases, including cancers, ischemic stroke, acute kidney injury, and obstructive sleep apnoea. Video Abstract

In the forming process of galvanized sheet, the friction between the die and the blank often causes the zinc coating of galvanized sheet to peel off, scratch, and crack. The aim of this study is to evaluate and calculate the fractal characteristics of the surface morphology of galvanized sheet and the effect of pressure on the interfacial friction behavior. Two steel plates, GA and GI, produced by Shanghai Baosteel Company, were used as materials to conduct tribological experiments, measure the surface profile and three-dimensional shape of the galvanized sheet, and calculate the fractal dimension and fractal roughness parameters. According to the analysis results of friction surface damage of galvanized sheet, the damage failure parameters of galvanized sheet are calculated. On this basis, according to the adhesive friction theory, the total surface friction value of galvanized sheet is obtained, and the fractal calculation model of galvanized sheet friction is established. The simulation results show that the galvanized sheet has fractal characteristics. The average values of fractal dimension and scale factor of SP781BQ alloy hot-dip galvanized sheet are 1.52 and 0.23 µm, respectively. The average fractal dimension and scale coefficient of HC420/780DPD + Z hot-dip galvanized sheet are 1.60 and 0.11 µm, respectively. The friction coefficient calculated by the proposed method is consistent with the theoretical value, and the error is less than 10%, which proves the accuracy and feasibility of the friction fractal calculation method.

BackgroundAlzheimer's disease (AD) is a progressive neurodegenerative disease that leads to cognitive impairment and memory loss. Currently, the pathogenesis and underlying causative genes of AD remain unclear, and there exists no effective treatment for this disease. This study explored AD-related diagnostic and therapeutic biomarkers from the perspective of immune infiltration by analyzing public data from the NCBI Gene Expression Omnibus database.MethodIn this study, weighted gene co-expression network analysis (WGCNA) was conducted to identify modules and hub genes contributing to AD development. A protein–protein interaction network was constructed when the genes in the modules were enriched and examined by Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Furthermore, a gene network was established using topological WGCNA, from which five hub genes were selected. Logistic regression analysis and receiver operating characteristic curve analysis were performed to explore the clinical value of genes in AD diagnosis. The genes in the core module intersected with the hub genes, and four intersection genes (ATP2A2, ATP6V1D, CAP2, and SYNJ1) were selected. These four genes were enriched by gene set enrichment analysis (GSEA). Finally, an immune infiltration analysis was performed.ResultsThe GO/KEGG analysis suggested that genes in the core module played a role in the differentiation and growth of neural cells and in the transmission of neurotransmitters. The GSEA of core genes showed that these four genes were mainly enriched in immune/infection pathways (e.g., cholera infection and Helicobacter pylori infection pathways) and other metabolic pathways. An investigation of immune infiltration characteristics revealed that activated mast cells, regulatory T cells, plasma cells, neutrophils, T follicular helper cells, CD8 T cells, resting memory CD4 T cells, and M1 macrophages were the core immune cells contributing to AD progression. qRT-PCR analysis showed that the ATP6V1D is upregulated in AD.ConclusionThe results of enrichment and immuno-osmotic analyses indicated that immune pathways and immune cells played an important role in the occurrence and development of AD. The selected key genes were used as biomarkers related to the pathogenesis of AD to further explore the pathways and cells, which provided new perspectives on therapeutic targets in AD.

Abstract Mitochondria are indispensable organelles for maintaining cell energy metabolism, and also are necessary to retain cell biological function by transmitting information as signal organelles. Hypoxia, one of the important cellular stresses, can directly regulates mitochondrial metabolites and mitochondrial reactive oxygen species (mROS), which affects the nuclear gene expression through mitochondrial retrograde signal pathways, and also promotes the delivery of signal components into cytoplasm, causing cellular injury. In addition, mitochondria can also trigger adaptive mechanisms to maintain mitochondrial function in response to hypoxia. Extracellular vesicles (EVs), as a medium of information transmission between cells, can change the biological effects of receptor cells by the release of cargo, including nucleic acids, proteins, lipids, mitochondria, and their compositions. The secretion of EVs increases in cells under hypoxia, which indirectly changes the mitochondrial function through the uptake of contents by the receptor cells. In this review, we focus on the mitochondrial regulation indirectly through EVs under hypoxia, and the possible mechanisms that EVs cause the changes in mitochondrial function. Finally, we discuss the significance of this EV-mitochondria axis in hypoxic diseases.

Lavender ( Lavandula angustifolia ) is an important medicinal and aromatic plant. However, the application of lavender essential oil (LEO) is limited by its instability, low solubility and high volatility. Therefore, to improve the stabilities and antioxidant activities of LEO and thereby expand the applications, LEO was microencapsulated by metal-organic frameworks based on β-cyclodextrin and potassium cation (K-βCD-MOFs) with different mass core/wall ratios. The results showed that the best inclusion rate was 96.67% with the ratio of 1:10. Then, the optimum inclusion product was characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM). The thermal and pH stabilities and the intracellular antioxidant activities were also studied. The results showed that the stabilities of the oil with K-βCD-MOFs inclusions and their abilities to resist acid and alkali were significantly stronger than those of LEO itself. In addition, the intracellular antioxidant activities of LEO were also enhanced by the K-βCD-MOFs inclusion. These results suggested the potential of K-βCD-MOFs as carriers for essential oils in food industry applications.

Background: The long-term prognosis of current treatments for anal sphincter incontinence (ASI) is poor. Here, we explored the efficacy of tissue adipose stromal vascular fraction SVF (tSVF) on ASI and compared it to that of cellular SVF (cSVF). We then investigated possible mechanisms. Methods: Rat cSVF and tSVF were isolated and labeled with DIL. One day after modeling, three groups received phosphate-buffered saline (PBS), cSVF, tSVF, respectively. The control group received nil modeling nor any treatments. The effect was assessed by function test for anal pressure and electromyography, and staining for fiber content, proliferation and differentiation at day 5 and day 10. Results: cSVF injection resulted in faster healing than tSVF. The cSVF group showed significant improvement on anal pressure on day 10. For the electromyography test, cSVF showed significant improvement for the frequencies on day 10, and for the peak values on both time points, while tSVF showed significant improvement for the peak values on day 10. The two SVF both alleviated fibrosis. Immunofluorescence tracing identified differentiation of some injected cells towards myosatellite cells and smooth muscle cells in both SVF groups. For all the tests, the tSVF group tends to have similar or lower effects than the cSVF group with no significant difference. Conclusion: cSVF and tSVF are both safe and effective in treating ASI, while the effect of cSVF is slighter higher than tSVF.

A series of periodic mesoporous organosilica supported benzotriazolium ionic liquids were synthesized and tested as effective and practical heterogeneous catalysts in the condensation reaction of diphenylethanedione, aromatic aldehydes and ammonium acetate. The catalyst PMO@ILBF4(1.0) showed brilliant catalytic activity for the synthesis of 2,4,5-trisubstituted imidazoles with good to high yields. We also found that the catalytic activity could be significantly influenced by the loading levels and functional anions of the benzotriazolium-cation ionic liquid, probably due to an intensification of intramolecular synergistic effect. Furthermore, the multifunctional catalyst PMO@ILBF4(1.0) could be easily recovered by filtration and recycled for six times with no significant loss in activity, indicating its excellent stability and reusability. This method provides an efficient and environmentally-friendly procedure for the production of 2,4,5-trisubstituted imidazoles.

Mitochondria are double membrane organelles within eukaryotic cells, which act as cellular power houses, depending on the continuous availability of oxygen. Nevertheless, under hypoxia, metabolic disorders disturb the steady-state of mitochondrial network, which leads to dysfunction of mitochondria, producing a large amount of reactive oxygen species that cause further damage to cells. Compelling evidence suggests that the dysfunction of mitochondria under hypoxia is linked to a wide spectrum of human diseases, including obstructive sleep apnea, diabetes, cancer and cardiovascular disorders. The functional dichotomy of mitochondria instructs the necessity of a quality-control mechanism to ensure a requisite number of functional mitochondria that are present to fit cell needs. Mitochondrial dynamics plays a central role in monitoring the condition of mitochondrial quality. The fission–fusion cycle is regulated to attain a dynamic equilibrium under normal conditions, however, it is disrupted under hypoxia, resulting in mitochondrial fission and selective removal of impaired mitochondria by mitophagy. Current researches suggest that the molecular machinery underlying these well-orchestrated processes are coordinated at mitochondria–endoplasmic reticulum contact sites. Here, we establish a holistic understanding of how mitochondrial dynamics and mitophagy are regulated at mitochondria–endoplasmic reticulum contact sites under hypoxia.

Catalytic oxidation of organic sulfides is of considerable significance in industrial chemistry and fuel industry. Therefore, numerous methods have been developed for the oxidation. Metal-containing ionic liquid-based catalysts can catalyze the selective oxidation reactions and are highly used in chemical processes, which have also been used as effective solvents, reaction media, extractants, and catalysts for the oxidation of organic sulfides including oxidative desulfurization of fuel oil. Recently, much attention is being drawn to the preparation of heterogenous catalysts based on the immobilization of metal- or nonmetal-containing ILs on diverse solid supports, which can be easily separated after the completion reaction and recycled. Therefore, there is still an increasing interest in developing new and efficient catalytic procedures for the oxidation of organic sulfides. In this review, we have outlined the recent advances in catalytic oxidation of organic sulfides including oxidative desulfurization of fuel oil. The versatilities and adaptabilities of metal–ionic liquid catalytic systems in the selective oxidation of sulfides are considered a powerful research field in these transformations.

A rapid method for simultaneous determination of five synthetic edible pigments (SEPs) including tartrazine (TA), ponceau 4R (PO), sunset yellow (SY), brilliant blue (BB) and erythrosine (ER) in beverages with titania-based RP-HPLC has been developed. The good linear relationships were obtained in the concentration ranges of 2.5–40 μg mL−1 for TA, PO and SY, 0.75–12 μg mL−1 for BB, and 1.25–20 μg mL−1 for ER, respectively. The detection limits (LODs) of five SEPs were 0.042, 0.021, 0.042, 0.0005, and 0.021 μg mL−1, respectively. The average recoveries were between 92.2% and 106.3%. Relative standard deviations (RSD, n = 7) for five SEPs were less than 1.18%. The precision and accuracy of the method can meet the requirements of HPLC analysis. In addition, the thermodynamic parameters of retention of the pigments in the titania column such as enthalpy (ΔHο), entropy (ΔSο) and Gibbs free energy (ΔGο) were also determined. Keywords: Titania-based stationary phase, RP-HPLC, Synthetic edible pigments (SEPs), Beverages

Previous Convolutional Neural Networks (CNNs) based multi-focus image fusion methods rely primarily on local information of images. In this paper, we propose a novel deep network architecture for multi-focus image fusion that is based on a non-local image model. The motivation of this paper stems from local and non-local self-similarity widely shown in nature images. We build on this concept and introduce a recurrent neural network (RNN) that performs non-local processing. The RNN captures global and local information by retrieving long distant dependencies, hence augmenting the representation of each pixel with contextual representations. The augmented representation is beneficial to detect accurately focused and defocused pixels. In addition, we design a regression loss to address the influences of texture information. Experimental results demonstrate that the proposed method outperforms the state-of-the-art methods, both qualitatively and quantitatively.

A type of multifunctional periodic mesoporous organosilica supported dual imidazolium ionic liquids PMO-IL-anion have been designed and prepared, characterized and evaluated as heterogeneous catalysts for the Knoevenagel condensation. The as-fabricated supported ionic liquids show good catalytic performances in the Knoevenagel condensation at room temperature, especially the supported ionic liquids PMO-IL-NTf2 and PMO-IL-PF6, based on a synergetic effect between the Lewis-base-type sites of dual functionalized imidazolium ionic liquids and active sites of periodic mesoporous organosilica. The best catalytic performance over PMO-IL-NTf2 was observed with excellent yields of 93∼99% in a short time of 20∼30 min. In addition, the heterogeneous catalyst offers simple operation for recovery and the recycling test showed that it could be reused for five times without significant loss of catalytic activity, thus making this process economical and environmental-friendly. Keywords: Ionic liquid, Periodic mesoporous organosilica, Knoevenagel condensation, Heterogeneous catalysis, Environmental-friendly

The current study aimed to explore the mechanism of Guizhi Shaoyao Zhimu Decoction in the treatment of gouty arthritis based on the combination of Vanquish Ultra High Performance Liquid Chromatography Q Exactive IV Pole-electrostatic field orbital trap high resolution mass spectrometer (UHPLC-Q-Orbitrap HRMS) and network pharmacology. Firstly, UHPLC-Q-Orbitrap HRMS was established and applied to separation and identification of the chemical components of GSZD. Then, using network pharmacology analysis to obtain the potential active components and candidate targets underlying the effect of GSZD on gouty arthritis (GA). Through targeted and untargeted analysis, a total of 79 components, including 3 chromones, 26 flavonoids, 10 alkaloids, 10 phenolic acids, 7 nucleosides and nucleobases, and 23 other components, were characterized from GSZD. 11 compounds were considered to potentially key active compounds against GA which may be via interacting with multiple inflammatory factors and multiple inflammatory pathways.

Ethnopharmacological Relevance: Pepper essential oils have potential immunomodulatory, anti-tumor, and anti-cancer activities. Pepper exhibits the potential to prevent or attenuate carcinogenesis as therapeutic tools. However, the related mechanism remains unelucidated.Aim of the Study: The present study aims to provide reasonable information for the explanation of the dissimilarity of the essential oils from white (WPEO) and black pepper (BPEO).Materials and Methods: WPEO, BPEO, and their single active component, as well as synthetic antioxidants, were compared by the cell model methods and chemical methods, including intracellular antioxidant activity (CAA), total antioxidant activities (TAA), superoxide radical (SR), hydroxyl radical (HR), DPPH radical (DR) scavenging activities and inhibition ability of lipoprotein lipid peroxidation (ILLP).Results: The median effective concentration (EC50) values (mg/mL) of the WPEO and BPEO of SR, HR, DR, and ILLP were 0.437 and 0.327, 0.486 and 0.204, 7.332 and 6.348, 0.688, and 0.624 mg/mL, respectively. The CAA units of WPEO and BPEO were 50.644 and 54.806, respectively. CAA, DR, and TAA of BPEO were significantly higher than those of WPEO (p < 0.05). The BPEO and WPEO can be differentiated as the former have higher correlations with 3-carene, α-pinene, β-pinene, and limonene while the latter has a higher caryophyllene correlation. The WPEO and BPEO show a good intracellular scavenging ability of reactive oxygen species in HeLa cells.Conclusion: Generally, pepper oil has stronger activities than single components, indicating that pepper is a broad-spectrum natural antioxidant.

Background: Anal sphincter incontinence (ASI) can cause a serious decline in the quality of life and can cause a socioeconomic burden. Studies have shown that bone marrow mesenchymal stem cells (MSC) have significant therapeutic effects on ASI, but the cost and risk of MSC harvest limit their further application. In contrast, adipose tissue derived stem cells (ADSC) and cellular stromal vascular fraction (CSVF) as stem cell sources have multipotency and the advantage of easy harvest. Objective: Here we aim to investigate the effects of ADSC and CSVF on treating ASI and compare them to that of bone marrow MSC. Methods: Bone marrow MSC, ADSC, and CSVF were obtained and labeled with green fluorescent protein (GFP), and CSVF was labeled with DIL. Sprague Dawley (SD) rats were divided into 5 groups. Four groups were injected with 0.2 mL phosphate buffer saline (PBS), 1 × 107/0.2 mL of MSC, ADSC, or CSVF, respectively, after model establishment. The control group received no treatment. The repair was assessed by anal functional tests and immunostaining on day 5 and day 10 after injection. Results: MSC, ADSC, and CSVF significantly promoted tissue repair and the recovery of muscle contraction and electromyographic activity in ASI. The generation of myosatellite cells by injected MSC, ADSC, and CSVF was found in the wounded area. On day 5, CSVF showed highest therapeutic effect, while on day 10, MSC and ADSC showed higher therapeutic effects than CSVF. When comparing the effects of MSC and ADSC, ADSC was slightly better than MSC in the indexes of anal pressure, etc. Conclusion: ADSC and CVSF are alternative stem cell sources for ASI repair.

Background: Proteinuria is an important symptom of chronic kidney disease irrespective of its initial pathogenesis. Mitochondrial dysfunction is an early pathophysiological event in proteinuria-induced tubular damage. Mitophagy, the selective degradation of damaged mitochondria targeted by autophagy, contributes to mitochondrial homeostasis and is primarily regulated by the PTEN-induced kinase 1 (PINK1)/Parkin pathway. In this study, we evaluated the function of mitophagy in proteinuria-induced tubular injury and mechanism. Methods: HK-2 cells were transfected with Parkin siRNA or Parkin overexpression plasmids for 48 h followed by treatment with albumin (8 mg/mL) for 8 h. JC-1 staining, ATP detection, and reactive oxygen species (ROS) detection were used to determine mitochondrial function. Immunoblot, LC3/mitochondria co-localization analyses, and Mito-Keima were employed to detect mitophagy. Immunoblot analysis and TUNEL were used to detect apoptosis. Results: Albumin overload induced mitochondrial dysfunction and mitophagy activation in HK-2 cells. Parkin knockdown inhibited albumin overload induced-mitophagy. Parkin overexpression further upregulated albumin overload induced-mitophagy. Parkin deficiency aggravated albumin overload-induced mitochondrial dysfunction and the overproduction of ROS, resulting in increased cell injury. Contrarily, Parkin overexpression helped maintain mitochondrial function and attenuate ROS generation, contributing to cell protection. Conclusions: Our results suggest that by clearing damaged mitochondria and maintaining mitochondrial function, PINK1/Parkin-mediated mitophagy contributed to tubular cell survival during albumin overload. PINK1/Parkin-mediated mitophagy may be a potential therapeutic target for proteinuria in tubular epithelial cells.

ABSTRACT Polycomb group (PcG) ring finger protein 6 (PCGF6), though known as a member of the transcription-repressing complexes, PcG, also has activation function in regulating pluripotency gene expression. However, the mechanism underlying the activation function of PCGF6 is poorly understood. Here, we found that PCGF6 co-localizes to gene activation regions along with pluripotency factors such as OCT4. In addition, PCGF6 was recruited to a subset of the super-enhancer (SE) regions upstream of cell cycle-associated genes by OCT4, and increased their expression. By combining with promoter capture Hi-C data, we found that PCGF6 activates cell cycle genes by regulating SE-promoter interactions via 3D chromatin. Our findings highlight a novel mechanism of PcG protein in regulating pluripotency, and provide a research basis for the therapeutic application of pluripotent stem cells.

Data from Phasor Measurement Units (PMUs) inform powerful diagnostic tools that can help avert catastrophic failures in the power grid. Because of this, PMU measurement errors are particularly problematic, and it is critical to understand their impact. However, there is limited understanding of how much the PMU measurement errors affect the performance of various synchrophasor-based applications, and thus the ability of these applications to fulfill the users' requirements effectively is also unclear. This paper examines internal and external factors contributing to PMU phase angle and frequency measurement errors. A generic method is proposed to evaluate the impact of measurement errors on application performance. The impact of measurement errors on several synchrophasor-based Wide Area Monitoring System (WAMS) applications are analyzed as examples. These applications include power system disturbance location, oscillation detection, islanding detection, and dynamic line rating. The analysis demonstrated that the proposed method can be used to quantify the measurement error impact and analyze the performance degradation of these applications due to the measurement error. It also reveals that the impact of measurement error depends on the type, algorithm, and parameters of applications.

Context: Kangfuxin (KFX) is widely used for the treatment of gastric and duodenal ulcer; however, more research is needed to determine the protective mechanisms of KFX in ameliorating gastric ulcer. Objective: To investigate the efficacy and potential mechanism of Kangfuxin liquid (KFX) in water-immersion and restraint stress (WIRS)-induced gastric ulcer. Materials and methods: Seventy rats were randomly divided into seven groups (n = 10) as follows: the control group (normal saline, i.g.), the model group (normal saline, i.g.), the KFX groups (2.5, 5 and 10 mL/kg, i.g.), the omeprazole group (20 mg/kg, i.p.) and Sanjiuweitai Granules group (1850 mg/kg, i.g.). The WIRS model was applied to induce stress ulcers after 7 days of drug administration. Afterwards, rats were sacrificed at 10 h induced by WIRS. Results: Pre-treatment with KFX (5,10 mL/kg) could effectively reduce the area of gastric ulcers and improve the pathological changes of ulcerated tissue. Moreover, KFX (5,10 mL/kg) increased the prostaglandin E2 (52%) and cyclooxygenase-1 (30%) levels, and improved malondialdehyde (54%), superoxide dismutase (58%), catalase (39%), and nitric oxide (11%) and TNF-α (9%), IL-6 (11%), MMP-9 (54%) and MMP-2 (53%) of ulcer tissue. Furthermore, pre-treatment with KFX dramatically increased IGF-1, PTEN, and Akt protein expression. Conclusions: Our results suggest that KFX has protective effects on WIRS-induced gastric ulcer via inflammatory reactions, oxidative stress inhibition, and pro-survival action, which were the results of activating the IGF-1/PTEN/Akt signalling pathway. Our results provide evidence of KFX for treating gastric ulcer.

Background/Aims: Intermittent hypoxia (IH) causes apoptosis in pancreatic β-cells, but the potential mechanisms remain unclear. Endoplasmic reticulum (ER) stress, autophagy, and apoptosis are interlocked in an extensive crosstalk. Thus, this study aimed to investigate the contributions of ER stress and autophagy to IH-induced pancreatic β-cell apoptosis. Methods: We established animal and cell models of IH, and then inhibited autophagy and ER stress by pharmacology and small interfering RNA (siRNA) in INS-1 cells and rats. The levels of biomarkers for autophagy, ER stress, and apoptosis were evaluated by immunoblotting and immunofluorescence. The number of autophagic vacuoles was observed by transmission electron microscopy. Results: IH induced autophagy activation both in vivo and in vitro, as evidenced by increased autophagic vacuole formation and LC3 turnover, and decreased SQSTM1 level. The levels of ER-stress-related proteins, including GRP78, CHOP, caspase 12, phosphorylated (p)-protein kinase RNA-like ER kinase (PERK), p-eIF2α, and activating transcription factor 4 (ATF4) were increased under IH conditions. Inhibition of ER stress with tauroursodeoxycholic acid or 4-phenylbutyrate partially blocked IH-induced autophagy in INS-1 cells. Furthermore, inhibition of PERK with GSK2606414 or siRNA blocked the ERstress-related PERK/eIF2α/ATF4 signaling pathway and inhibited autophagy induced by IH, which indicates that IH-induced autophagy activation is dependent on this signaling pathway. Promoting autophagy with rapamycin alleviated IH-induced apoptosis, whereas inhibition of autophagy with chloroquine or autophagy-related gene (Atg5 and Atg7) siRNA aggravated pancreatic β-cell apoptosis caused by IH. Conclusion: IH induces autophagy activation through the ER-stress-related PERK/eIF2α/ATF4 signaling pathway, which is a protective response to pancreatic β-cell apoptosis caused by IH.

Background: The incidence of obstructive sleep apnea (OSA) in the elderly is high, and the disorder is associated with a variety of chronic diseases. Microvesicles (MVs) are extracellular vesicles secreted by various cells during stimulation or apoptosis that play an important role in the pathogenesis of OSA. However, concentrations of circulating MVs in elderly patients with OSA remain unclear.Methods: Patients aged >60 years old were recruited and underwent polysomnography. Circulating plasma MV concentrations, including annexin V+MVs, endothelial MVs (EMVs), platelet MVs (PMVs), and leukocyte MVs (LMVs) levels, were measured using a flow cytometer with different labeling methods. Potential factors affecting the concentration of circulating MVs in elderly patients with OSA were determined via Spearman's correlation and multiple linear regression analysis.Results: Levels of circulating MVs, including both single- (annexin V+MVs, CD144+EMVs, CD41a+PMVs, and CD45+LMVs) and dual-labeled MVs (annexin V+CD144+EMVs), were elevated in elderly patients with OSA. Circulating MVs were positively correlated with OSA severity (AHI, ODI, and SPO2min). To some extent, obesity affected the MV concentrations in elderly patients with OSA. In addition, age and comorbidities may be associated with MV levels, but the correlations between the MV levels and age or comorbidities were not significant.Conclusion: Concentrations of circulating MVs in elderly patients with OSA are associated with the labeling method used, OSA severity, and obesity. The effects of age and comorbidities on circulating MV levels require further verification using a larger sample size.

Although hemorrhagic sepsis caused by Aeromonas hydrophila infection is the dominant disease in the aquaculture of Chinese soft-shelled turtle, information on its molecular pathology is seriously limited. In this study, ninety turtles intraperitoneally injected with A. hydrophila exhibited two different phenotypes based on the pathological symptoms, referred to as active and inactive turtles. Comparative transcriptomes of liver and spleen from these two groups at 6, 24, and 72 h post-injection (hpi) were further analyzed. The results showed that cytokine–cytokine receptor interaction, PRRs mediated signaling pathway, apoptosis, and phagocytosis enriched in active and inactive turtles were significantly different. Pro-inflammatory cytokines, the TLR signaling pathway, NLR signaling pathway, and RLR signaling pathway mediating cytokine expression, and apoptosis-related genes, were significantly up-regulated in inactive turtles at the early stage (6 hpi). The significant up-regulation of phagocytosis-related genes occurred at 24 hpi in inactive turtles and relatively lagged behind those in active turtles. The anti-inflammatory cytokine, IL10, was significantly up-regulated during the tested periods (6, 24, and 72 hpi) in active turtles. These findings offer valuable information for the understanding of molecular immunopathogenesis after A. hydrophila infection, and facilitate further investigations on strategies against hemorrhagic sepsis in Chinese soft-shelled turtle T. sinensis.

The Remedial Action Scheme (RAS) is designed to take corrective actions after detecting predetermined conditions to maintain system transient stability in large interconnected power grids. However, since RAS is usually designed based on a few selected typical operating conditions, it is not optimal in operating conditions that are not considered in the offline design, especially under frequently and dramatically varying operating conditions due to the increasing integration of intermittent renewables. The deep learning-based RAS is proposed to enhance the adaptivity of RAS to varying operating conditions. During the training, a customized loss function is developed to penalize the negative loss and suggest corrective actions with a security margin to avoid triggering under-frequency and over-frequency relays. Simulation results of the reduced United States Western Interconnection system model demonstrate that the proposed deep learning–based RAS can provide optimal corrective actions for unseen operating conditions while maintaining a sufficient security margin.

Traditionally, 5-hydroxymethylfurfural (HMF) is produced by using a water-organic solvent medium, which inevitably increases production costs and adds subsequent separation processes. To minimize cost and/or toxic organic solvent usage, this study presents an effective pathway for producing HMF from cellulose. The process uses a fixed bed reactor with a steam stripping process in which the cellulose is converted into HMF and other products in the presence of acidic inorganic salts. In the process, the cellulose was hydrolyzed to glucose, which was followed by isomerization to fructose and fructose dehydration into HMF. The produced HMF was easily vaporized into the gas phase, which avoided its conversion into undesired byproducts. An acceptable HMF yield of 28.2 mol% was obtained using KH2PO4 as the catalyst at 270 °C. This technology could be used to obtain both HMF and furfural (FF) from different lignocellulosic biomasses. This stripping technology has advantages such as the lack of organic solvents, showing an alternative and green HMF and/or FF production from lignocellulosic biomass.

This study addresses two puzzles in the IPO markets in China: whether underpricing in the IPO market is affected by earlier market information, especially the volume and number of IPOs in the prior period, and whether underpricing in the previous period leads to a subsequent hot period in the IPO markets in China. The main results of this study are as follows. First, while that the magnitudes of weighted (equally or value weighted) IPO volumes in the past have a positive effect on the magnitude of IPO returns in the future, the IPO volume itself has a negative effect on the magnitude of IPO returns in the future. Second, the magnitude of weighted IPO returns in the past has a positive effect on the magnitude of IPO returns, while simultaneously reflecting the effects of both time-span and magnitude in returns and volume. Third, as higher market returns and larger numbers of IPOs only result in more IPOs in the subsequent period during the period before 2004, whereas this phenomenon has since reversed.

In order to improve the lightning withstand level of ±660 kV DC transmission line in China, the authors had begun to develop the ±660 kV DC line arrester since 2014, which was developed successfully in 2016. The structure, technical parameters, protection performance, and installation of line arrester are analysed in detail. The arrester adopts the structure of polymer housing with an external series air gap and a four-section body. The technical parameters and protection performance are designed and calculated according to the relevant standards. The results show that the arrester has good electrical and mechanical performances, and it meets the requirement of insulation coordination. Pillar insulator supporting installation is used in the arrester application. Up to now, the ±660 kV DC line arrester has been used in the ±660 kV DC transmission line in China, which works safely and reliably over a long time. The successful operation can accumulate operating experience and provide a basis for the large-scale application of the line arrester on the ±660 kV DC transmission line in the future.

Background. To study the expression and clinical significance of long noncoding RNA- (lncRNA-) MIAT in patients with coronary atherosclerotic heart disease (CAD). Methods. Serum MIAT, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in 106 CAD patients and 89 healthy donors were detected. Correlations between serum MIAT and serum IL-6 and TNF-α were analyzed. Risk factors for patients with CAD were analyzed by multiple factor analysis. Results. Compared with healthy donors, serum lncRNA-MIAT was significantly increased in CAD patients. Serum MIAT was positively correlated with serum IL-6 and TNF-α in CAD. Multivariate analysis found that hypertension (OR (95% CI) = 3.471 (2.180–4.091), P=0.011), diabetes (OR (95% CI) = 3.682 (1.698–4.897), P=0.003), HDL-C (OR (95% CI) = 3.372 (1.760–6.920), P=0.001), and serum MIAT expression (OR (95% CI) = 2.687 (1.683–7.468), P=0.001) were independent risk factors for CAD. Conclusions. Serum lncRNA-MIAT in CAD patients was significantly increased, which may be a potential marker for diagnosis and prognosis of CAD.