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In response to the common issues in practical training in vocational engineering construction courses, such as dangerous operation of training equipment, insufficient number of training equipment, and ineffective teaching, a vivid and interactive virtual simulation training system was developed using Unity3D software, taking the U-shaped bridge abutment in the course of Bridge Engineering as an example. Detailed introduction to the development and design process of 3D model establishment, ZSpace device adaptation, file format conversion, model rendering and disassembly, model zooming in and out, script writing and function implementation, UI interface design, etc., in order to achieve immersive interaction functions such as free observation, assembly disassembly, and ZSpace integrated VR virtual experience in the virtual simulation training system. The practical results show that the interactive effect simulated through the simulation training system is superior to that of the physical system, which can enhance the sense of experience, improve learning enthusiasm, and deepen the understanding of the knowledge points in Bridge Engineering Drawing Recognition. After the system is successfully established and applied in the training and teaching process, it will provide an important reference for the training and teaching of relevant courses for students majoring in road and bridge engineering, and also enhance the cultivation of high-quality skilled personnel in engineering majors in vocational colleges.

BackgroundThe effectiveness and safety of a novel class of hypoglycemic medications known as sodium-glucose cotransporter 2 (SGLT2) inhibitors have not been completely established in relation to acute heart failure (AHF). Consequently, we sought to compare the prognostic and safety outcomes of patients administered SGLT2 inhibitors for the treatment of AHF.MethodsAn extensive search of the Web of Science, PubMed, and EMBASE was conducted for randomized controlled trials and observational studies that have evaluated the use of SGLT2 inhibitors in AHF from the inception of these drugs to the present. We compiled data related to cardiovascular safety and prognosis. Aggregated risk ratios (RR), mean differences (MD), or standardized mean differences (SMD) were generated for all outcomes, with 95% confidence intervals (CIs), to evaluate the predictive significance of SGLT2 inhibitors in patients with AHF.ResultsWe identified 4,053 patients from 13 studies. Patients experienced a substantial reduction in all-cause mortality (RR = 0.82, 95% CI: 0.70–0.96, P = 0.01), readmission rates (RR = 0.85, 95% CI: 0.74–0.98, P = 0.02), the number of heart failure exacerbation events (RR = 0.69, 95% CI: 0.50–0.95, P = 0.02), and the number of rehospitalization events due to heart failure (RR = 0.71, 95% CI: 0.58–0.86, P

Abstract Lymphatic invasion (LI) is extremely aggressive and induces worse prognosis among patients with colorectal cancer (CRC). Thus, it is critical to characterize the cellular and molecular mechanisms underlying LI in order to establish novel and efficacious therapeutic targets that enhance the prognosis of CRC patients. RNA-seq data, clinical and survival information of colon adenocarcinoma (COAD) patients were obtained from the TCGA database. In addition, three scRNA-seq datasets of CRC patients were acquired from the GEO database. Data analyses were conducted with the R packages. We assessed the tumor microenvironment (TME) differences between LI+ and LI− based scRNA-seq data, LI+ cells exhibited augmented abundance of immunosuppression and invasive subset. Marked extracellular matrix network activation was also observed in LI+ cells within SPP1+ macrophages. We revealed that an immunosuppressive and pro-angiogenic TME strongly enhanced LI, as was evidenced by the CD4+ Tregs, CD8+ GZMK+, SPP1+ macrophages, e-myCAFs, and w-myCAFs subcluster infiltrations. Furthermore, we identified potential LI targets that influenced tumor development, metastasis, and immunotherapeutic response. Finally, a novel LIRS model was established based on the expression of 14 LI-related signatures, and in the two testing cohorts, LIRS was also proved to have accurate prognostic predictive ability. In this report, we provided a valuable resource and extensive insights into the LI of CRC. Our conclusions can potentially benefit the establishment of highly efficacious therapeutic targets as well as diagnostic biomarkers that improve patient outcomes.

Abstract Objective Prediction of lymph node metastasis (LNM) for intrahepatic cholangiocarcinoma (ICC) is critical for the treatment regimen and prognosis. We aim to develop and validate machine learning (ML)-based predictive models for LNM in patients with ICC. Methods A total of 345 patients with clinicopathological characteristics confirmed ICC from Jan 2007 to Jan 2019 were enrolled. The predictors of LNM were identified by the least absolute shrinkage and selection operator (LASSO) and logistic analysis. The selected variables were used for developing prediction models for LNM by six ML algorithms, including Logistic regression (LR), Gradient boosting machine (GBM), Extreme gradient boosting (XGB), Random Forest (RF), Decision tree (DT), Multilayer perceptron (MLP). We applied 10-fold cross validation as internal validation and calculated the average of the areas under the receiver operating characteristic (ROC) curve to measure the performance of all models. A feature selection approach was applied to identify importance of predictors in each model. The heat map was used to investigate the correlation of features. Finally, we established a web calculator using the best-performing model. Results In multivariate logistic regression analysis, factors including alcoholic liver disease (ALD), smoking, boundary, diameter, and white blood cell (WBC) were identified as independent predictors for LNM in patients with ICC. In internal validation, the average values of AUC of six models ranged from 0.820 to 0.908. The XGB model was identified as the best model, the average AUC was 0.908. Finally, we established a web calculator by XGB model, which was useful for clinicians to calculate the likelihood of LNM. Conclusion The proposed ML-based predicted models had a good performance to predict LNM of patients with ICC. XGB performed best. A web calculator based on the ML algorithm showed promise in assisting clinicians to predict LNM and developed individualized medical plans.

Abstract Background CREG1 (cellular repressor of E1A‐stimulated genes 1) is a protein involved in cellular differentiation and homeostasis regulation. However, its role in skeletal muscle satellite cells differentiation and muscle regeneration is poorly understood. This study aimed to investigate the role of CREG1 in myogenesis and muscle regeneration. Methods RNA sequencing data (GSE8479) was analysed from the Gene Expression Omnibus database (GEO, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi). We generated Creg1 knockdown and skeletal muscle satellite cells specific Creg1 overexpression mice mediated by adeno‐associated virus serotype 9 (AAV9), skeletal muscle mature myofibre Creg1 knockout mice (myoblast/Creg1MKO), and control mice Creg1flox/flox (Creg1fl/fl) as in vivo models. The mice were injected into tibialis anterior (TA) muscle with 100 μL of 10 μM cardiotoxin to establish a muscle regeneration model. Creg1fl/fl and Creg1MKO mice were treated with AAV‐sh‐C‐Cbl (2 × 1010 genomic copies/mouse) to silence C‐Cbl in the TA muscle. 293T and C2C12 cells were transfected with plasmids using lipofectamine RNAi MAX in vitro. Mass spectrometry analyses and RNA sequencing transcriptomic assay were performed. Results We analysed the transcriptional profiles of the skeletal muscle biopsies from healthy older (N = 25) and younger (N = 26) adult men and women in GSE8479 database, and the results showed that Creg1 was associated with human sarcopenia. We found that Creg1 knockdown mice regenerated less newly formed fibres in response to cardiotoxin injection (~30% reduction, P

Background Coronavirus disease 2019 (COVID-19) patients with pneumonia should receive the guidance of initial risk stratification and early warning as soon as possible. Whether the prehospital Pandemic Respiratory Infection Emergency System Triage (PRIEST) score can accurately predict the short-term prognosis of them remains unknown. Accordingly, we aimed to assess the performance of prehospital PRIEST in predicting the 30-day mortality of patients.Methods This retrospective study evaluated the accuracy of five physiological parameters scores commonly used in prehospital disposal for mortality prediction using receiver operating characteristic curves and decision curve analysis. Cox proportional hazard regression analysis was conducted to evaluate independent predictors associated with the 30-day mortality.Results A total of 231 patients were included in this study, among which 23 cases (10.0%) died within 30 days after admission. Compared with survivor patients, non-survivor patients had greater numbers of comorbidities, signs and symptoms, complications, and physiological parameters scores and required greater prehospital care (p 12, the sensitivity was 91.3%, and the specificity was 77.4%. We found that the area under the curve of the PRIEST score (0.887, p 12 (69.1%) (p 12 (HR = 7.409) was one of the independent predictors of the 30-day mortality.Conclusions The PRIEST can accurately, quickly, and conveniently predict the 30-day mortality of COVID-19 patients with pneumonia in the prehospital phase and can guide their initial risk stratification and treatment.

Abstract Background Cholangiocarcinoma (CCA) is a highly malignant and easily metastatic bile duct tumor with poor prognosis. We aimed at studying the associated risk factors affecting distal metastasis of CCA and using nomogram to guide clinicians in predicting distal metastasis of CCA. Methods Based on inclusion and exclusion criteria, 345 patients with CCA were selected from the Fifth Medical Center of Chinese PLA General Hospital and were divided into distal metastases (N = 21) and non-distal metastases (N = 324). LASSO regression models were used to screen for relevant parameters and to compare basic clinical information between the two groups of patients. Risk factors for distal metastasis were identified based on the results of univariate and multivariate logistic regression analyses. The nomogram was established based on the results of multivariate logistic regression, and we drawn the corresponding correlation heat map. The predictive accuracy of the nomogram was evaluated by receiver operating characteristic (ROC) curves and calibration plots. The utility of the model in clinical applications was illustrated by applying decision curve analysis (DCA), and overall survival(OS) analysis was performed using the method of Kaplan-meier. Results This study identified 4 independent risk factors for distal metastasis of CCA, including CA199, cholesterol, hypertension and margin invasion, and developed the nomogram based on this. The result of validation showed that the model had significant accuracy for diagnosis with the area under ROC (AUC) of 0.882 (95% CI: 0.843-0.914). Calibration plots and DCA showed that the model had high clinical utility. Conclusions This study established and validated a model of nomogram for predicting distal metastasis in patients with CCA. Based on this, it could guide clinicians to make better decisions and provide more accurate prognosis and treatment for patients with CCA.

Triboelectrification of powders and grains is deleterious in a large number of manufacturing operations, due to its adverse effect on process consistency and reliability. To mitigate it, charge neutralisers are commonly employed. However, their selection is often based on trial and error. This study is conducted to systematically examine the influence of the ionic polarity strength of a charge neutraliser, specifically aluminium stearate (AlSt), on charge transfer. AlSt has three types with different numbers of stearate chains, thereby influencing the electron exchange propensity of the molecule. The experiments involved surface-treated glass beads in the sieve size range of 90–150 µm (to make them hydrophilic by acid washing or hydrophobic by silanisation), then coated with the three forms of AlSt (mono-, di- and tri-) for charge mitigation. These coated beads were subjected to aerodynamic dispersion to cause triboelectrification, in order to quantitatively evaluate their charge neutralising effect. The experiments were conducted with four contact surfaces: stainless steel, copper, aluminium, and polytetrafluoroethylene (PTFE). Both acid-washed and silanised glass beads exhibited negative charging against aluminium, copper and stainless steel (typically around 22–44 nC/g), but positive charging against PTFE (around 90 nC/g and 19 nC/g for acid-washed and silanised, respectively), despite having significantly different surface functional groups. A complex trend is observed for the effect of the amount of AlSt present on the surfaces, the type of AlSt and the surface treatment. A relatively good charge reduction behaviour was seen for AlSt-coated acid washed glass beads, but for silanised glass beads, AlSt coating actually increases their charge level.

Abstract Benzopyrene (B[a]P) is a well-known carcinogen that can induce chronic inflammation and fibrosis in the liver, leading to liver disease upon chronic exposure. Nonalcoholic steatohepatitis (NASH) is a chronic liver condition characterized by fat accumulation, inflammation, and fibrosis, often resulting in hepatocellular carcinoma (HCC). In this study, we aimed to investigate the intricate connections between B[a]P exposure, NASH, and HCC. Through comprehensive bioinformatics analysis of publicly available gene expression profiles, we identified differentially expressed genes (DEGs) associated with B[a]P exposure, NASH, and liver cancer. Furthermore, network analysis revealed hub genes and protein–protein interactions, highlighting cellular metabolic dysfunction and disruption of DNA damage repair in the B[a]P-NASH-HCC process. Notably, HSPA1A and PPARGC1A emerged as significant genes in this pathway. To validate their involvement, we conducted qPCR analysis on cell lines and NASH mouse liver tissues and performed immunohistochemistry labeling in mouse and human HCC liver sections. These findings provide crucial insights into the potential regulatory mechanisms underlying benzopyrene-induced hepatotoxicity, shedding light on the pathogenesis of B[a]P-associated NASH and HCC. Moreover, our study suggests that HSPA1A and PPARGC1A could serve as promising therapeutic targets. Enhancing our understanding of their regulatory roles may facilitate the development of targeted therapies, leading to improved patient outcomes.

Abstract Background The gut mycobiome of patients with lung adenocarcinoma (LUAD) remains unexplored. This study aimed to characterize the gut mycobiome in patients with LUAD and evaluate the potential of gut fungi as non-invasive biomarkers for early diagnosis. Methods In total, 299 fecal samples from Beijing, Suzhou, and Hainan were collected prospectively. Using internal transcribed spacer 2 sequencing, we profiled the gut mycobiome. Five supervised machine learning algorithms were trained on fungal signatures to build an optimized prediction model for LUAD in a discovery cohort comprising 105 patients with LUAD and 61 healthy controls (HCs) from Beijing. Validation cohorts from Beijing, Suzhou, and Hainan comprising 44, 17, and 15 patients with LUAD and 26, 19, and 12 HCs, respectively, were used to evaluate efficacy. Results Fungal biodiversity and richness increased in patients with LUAD. At the phylum level, the abundance of Ascomycota decreased, while that of Basidiomycota increased in patients with LUAD. Candida and Saccharomyces were the dominant genera, with a reduction in Candida and an increase in Saccharomyces, Aspergillus, and Apiotrichum in patients with LUAD. Nineteen operational taxonomic unit markers were selected, and excellent performance in predicting LUAD was achieved (area under the curve (AUC) = 0.9350) using a random forest model with outcomes superior to those of four other algorithms. The AUCs of the Beijing, Suzhou, and Hainan validation cohorts were 0.9538, 0.9628, and 0.8833, respectively. Conclusions For the first time, the gut fungal profiles of patients with LUAD were shown to represent potential non-invasive biomarkers for early-stage diagnosis.

Abstract The six species of lungfish possess both lungs and gills and are the closest extant relatives of tetrapods. Here, we report a single-cell transcriptome atlas of the West African lungfish (Protopterus annectens). This species manifests the most extreme form of terrestrialization, a life history strategy to survive dry periods that can last for years, characterized by dormancy and reversible adaptive changes of the gills and lungs. Our atlas highlights the cell type diversity of the West African lungfish, including gene expression consistent with phenotype changes of terrestrialization. Comparison with terrestrial tetrapods and ray-finned fishes reveals broad homology between the swim bladder and lung cell types as well as shared and idiosyncratic changes of the external gills of the West African lungfish and the internal gills of Atlantic salmon. The single-cell atlas presented here provides a valuable resource for further exploration of the respiratory system evolution in vertebrates and the diversity of lungfish terrestrialization.

Prime editing is a revolutionary gene-editing method that is capable of introducing insertions, deletions and base substitutions into the genome. However, the editing efficiency of Prime Editor (PE) is limited by the DNA repair process. Here, we show that overexpression of the flap structure-specific endonuclease 1 (FEN1) and the DNA ligase 1 (LIG1) increases the efficiency of prime editing, which is similar to the dominant negative mutL homolog 1 (MLH1dn). In addition, MLH1 is still the dominant factor over FEN1 and LIG1 in prime editing. Our results help to further understand the relationship of proteins involved in prime editing and envisage future directions for the development of PE.

Abstract The complete regeneration of deer antlers is based on the proliferation and differentiation of stem cells. Mesenchymal stem cells (MSCs) of antlers have an important role in antler regeneration and rapid growth and development. HGF is mainly synthesized and secreted by mesenchymal cells. After binding to its receptor c-Met, which transduces signals into cells to stimulate cell proliferation and migration in various organs to promote tissue morphogenesis and angiogenesis. However, the role and mechanism of the HGF/c-Met signaling pathway on antler MSCs are still unclear. In this study, we established antler MSCs with overexpression and interference of HGF gene by lentivirus and small interference RNA, observed the effect of HGF/c-Met signal pathway on the proliferation and migration of antler MSCs, and detected the expression of downstream related signal pathway genes, to explore the mechanism of HGF/c-MET signal pathway on the proliferation and migration of antler MSCs. The results showed that the HGF/c-Met signal affects the expression of RAS, ERK and MEK genes, regulates the proliferation of pilose antler MSCs through Ras/Raf, MEK/ERK pathway, affects the expression of Gab1, Grb2, AKT and PI3K genes, and regulates the migration of MSCs of pilose antler through Gab1/Grb2 and PI3K/AKT pathway.

Biomarkers for classifying and grading gliomas have been extensively explored, whereas populations in public databases were mostly Western/European. Based on public databases cannot accurately represent Chinese population. To identify molecular characteristics associated with clinical outcomes of lower-grade glioma (LGG) and glioblastoma (GBM) in the Chinese population, we performed whole-exome sequencing (WES) in 16 LGG and 35 GBM tumor tissues. TP53 (36/51), TERT (31/51), ATRX (16/51), EFGLAM (14/51), and IDH1 (13/51) were the most common genes harboring mutations. IDH1 mutation (c.G395A; p.R132H) was significantly enriched in LGG, whereas PCDHGA10 mutation (c.A265G; p.I89V) in GBM. IDH1-wildtype and PCDHGA10 mutation were significantly related to poor prognosis. IDH1 is an important biomarker in gliomas, whereas PCDHGA10 mutation has not been reported to correlate with gliomas. Different copy number variations (CNVs) and oncogenic signaling pathways were identified between LGG and GBM. Differential genomic landscapes between LGG and GBM were revealed in the Chinese population, and PCDHGA10, for the first time, was identified as the prognostic factor of gliomas. Our results might provide a basis for molecular classification and identification of diagnostic biomarkers and even potential therapeutic targets for gliomas.

ObjectiveThe purpose of the study is to evaluate the effects of biologic therapy on cardiovascular risk factors in rheumatoid arthritis patients to determine its clinical efficacy.MethodsRelevant literature was systematically searched in PubMed, Embase, and Cochrane Library databases. Meta-analysis was conducted using standardized mean differences (SMDs) and 95% confidence intervals (CIs) to evaluate cardiovascular risk factors and atherosclerosis. Heterogeneity, sensitivity analysis, and publication bias were assessed. Statistical significance was set at PResultsThe meta-analysis revealed that biologic treatment in RA patients was associated with decreased high-density lipoprotein cholesterol (HDL-C) levels compared to controls (MD: -0.10, 95% CI: [-0.14, -0.05], PConclusionBiologic agents may improve lipid profiles in RA patients but could also have adverse effects on cardiovascular health. Further research is needed to comprehensively understand the impact of biologic therapy on lipid metabolism and cardiovascular outcomes in RA patients.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, CRD42024504911.

To identify candidate pathogenic genes of early-stage Crohn's disease (CD) and predict potential roles of genetic factors in CD, we performed whole exome sequencing on a child with early-stage Crohn's disease (CD) and her parents (core family), found that the patient carried heterozygous variants of 4 genes: NOD2 c. 2257 C > T, IL10RA c. 301 C > T, PLA2G6 c. 2029 C > T, COL7A1 c. 3190 G > A. Heterozygous variants of NOD2, IL10RA, PLA2G6 and COL7A1, intestinal inflammatory response is triggered, normal intestinal wall tissue damage, leading to CD phenotype.

BackgroundWith the rise and deepening of positive psychology research, theoretical research on job burnout is also deepening worldwide, and some new theoretical models are proposed, such as the burnout-engagement continuum, but there is still a lack of empirical research and application in China. ObjectiveTo analyze the current situation and influencing factors of five profiles in the burnout-engagement continuum in working populations of China: job engagement, ineffective, overextended, disengaged, and burnout. MethodsFrom August to October 2019 and June to September 2020, a total of 27344 subjects of key occupations in six typical industries, including teachers, firefighters, manufacturing workers, medical staff, flight attendants, and traffic police, were selected from 10 provinces (cities) in the eastern, middle, and western regions of China by multistage stratified cluster sampling method for cross-sectional investigation. Maslach Burnout Inventory-General Survey and Core Occupational Stress Scale were used to evaluate job burnout and occupational stress respectively. χ2 test was used to compare rates of count data. Binary logistic regression was used for multivariate analysis of the five profiles. ResultsAmong the subjects, 24.4%, 61.9%, 31.9%, 12.7%, and 11.8% were the prevalence rates of job engagement, ineffective, overextended, disengaged, and burnout, respectively. Flight attendants (35.7%), firefighters (29.0%), traffic police (28.5%), and manufacturing workers (26.5%) had high prevalence rates of job engagement profile. Medical stuff (62.9%) and manufacturing workers (61.8%) had high prevalence rates of ineffective profile. Teachers (39.2%), traffic police (37.2%), and medical stuff (35.5%) had high prevalence rates of overextended profile. Traffic police (17.9%), medical staff (14.3%), and teachers (13.4%) had high prevalence rates of disengaged profile. Traffic police (16.9%), medical staff (13.4%), and teachers (13.3%) had high prevalence rates of burnout profile. The results of multivariate analysis showed that gender, age, education level, marital status, weekly working hours, length of service, income per month, shift work, smoking, drinking, industry, and occupational stress entered into the regression equations of job engagement, ineffective, overextended, disengaged, and burnout. The risks of overextended (OR=1.456-2.970), disengaged (OR=1.306-4.092), and burnout (OR=1.302-4.102) among the high rating groups of the four factors of occupational stress were higher than those among the low rating groups. Flight attendants (OR=0.296) and firefighters (OR=0.329) had lower risks of burnout than teachers, and flight attendants (OR=0.392) and firefighters (OR=0.466) had lower risks of disengaged than teachers. ConclusionAmong the prevalence rates of the five profiles in the burnout-engagement continuum in the 6 typical occupational populations in China, ineffective profile is the highest, followed by overextended, and burnout is the lowest. Gender, age, education level, marital status, weekly working hours, length of service, income per month, shift work, smoking, drinking, industry, and occupational stress have different effects on the five profiles, but industry and occupational stress have greater impacts on job burnout.

BackgroundManufacturing industry is the main body of China's national economy, and manufacturing employees provide solid guarantee and support for the vigorous development of China's manufacturing industry. The research on job burnout of manufacturing employees is helpful to prevent or alleviate the health damage and economic loss caused by job burnout. ObjectiveTo investigate the status and influencing factors of job burnout among manufacturing employees in China, and evaluate the potential mediating effect of job burnout between job stress and depressive symptoms. MethodsA cross-sectional study was performed from August to October 2019 and from June to September 2020 in seven provinces of China. Study participants were recruited from 21 manufacturing companies covering 11 manufacturing subdivisions using multistage stratified cluster sampling. General Burnout Scale, Core Occupational Stress Scale, and Patient Health Questionnaire-9 were used to evaluate job burnout, job stress, and depressive symptoms. Mann-Whitney U test and Kruskal-Wallis H test were used to compare data between two independent samples and multiple independent samples of measurement data; Pearson χ2 test was used to compare the rate of enumeration data; Spearman rank correlation analysis was used to evaluate correlation between selected variables; binary logistic regression was used for multivariate analysis; stepwise regression and bias-corrected Bootstrap method were used to test potential mediating effect. ResultsA total of 10973 valid questionnaires were collected. The M (P25, P75) scores of exhaustions, cynicism, professional efficacy, job burnout, job stress, and depressive symptoms were 1.6 (0.4, 3.0), 1.0 (0.2, 2.2), 4.8 (3.2, 5.7), 1.6 (0.8, 2.5), 45.0 (40.0, 50.0), and 7.0 (4.0, 11.0), respectively. The positive rates of job burnout, job stress, and depressive symptoms were 53.4% (5865/10973), 28.4% (3116/10973), and 29.4% (3231/10973), respectively. The influencing factors of job burnout were gender (versus male; OR for female=0.852), age (versus≤25 years old; ORs for 26-30, 31-40, 41-50, 51-60 years old=0.824, 0.819, 0.738, 0.677), education level (versus junior high school or below; ORs for senior high school/technical secondary school, junior college/vocational college, graduate school or above=1.119, 1.345, 1.331), income per month (versus＜3000 yuan; ORs for 3000-4999, 5000-6999, 7000-8999, 9000-10999, ≥11000 yuan=0.513, 0.470, 0.430, 0.375, 0.411), position (versus assembly line; OR for non-assembly line=0.814), average weekly working hours (versus ≤40 h; ORs for 61-70, ＞70 h=1.199, 1.519), and drinking (versus non-drinking; OR for drinking=1.261). Job burnout was positively correlated with job stress and depressive symptoms (r=0.556, 0.508, P

Background: The efficacy of anti-programmed cell death (PD)-1 monotherapy in advanced hepatocellular carcinoma (aHCC) is limited, and combination therapy with lenvatinib and pembrolizumab has shown promising results. However, comparative studies between immune monotherapies and combination therapies are lacking. Objectives: To investigate the efficacy and safety of anti-PD-1 monotherapy (PD-1) and anti-PD-1 plus lenvatinib (PD-1 + L ) in patients with aHCC to guide clinical treatment decisions. Design: A retrospective study was conducted on a cohort of patients with aHCC who received either PD-1 monotherapy or PD-1 + L combination therapy between January 2018 and January 2020. Methods: The study retrospectively reviewed the medical records of 94 eligible patients with aHCC, with 39 in the PD-1 group and 55 in the PD-1 + L group. The efficacy outcomes, including objective response rate (ORR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety, were assessed. Results: With a median follow-up of 30.1 months, the PD-1 + L group demonstrated a significantly higher ORR (32.7% versus 10.3%, p = 0.013), better DCR (80.0% versus 53.8%, p = 0.012), longer median PFS (10.6 versus 4.4 months, p < 0.001) and longer median OS (18.4 versus 8.5 months, p = 0.013) than PD-1 group. For the responders, the efficacy of the two groups was durable (DOR was 11.6 versus 3.5 months, p = 0.009). Subgroup analyses based on prior tyrosine kinase inhibitor (TKI) treatment and the presence or absence of macrovascular tumor thrombosis or extrahepatic metastases favored the PD-1 + L group. The combination therapy was a good predictor of PFS and OS in multivariate analysis. Grade 3/4 treatment-related adverse events were more common in PD-1 + L group, with higher incidences of hypertension and hand–foot skin reactions. Conclusions: PD-1 monotherapy and PD-1 plus lenvatinib combination therapy were well-tolerated in patients with aHCC. PD-1 + L showed significantly better survival benefits than PD-1 monotherapy.

Industrial cyber-physical systems (ICPS) are a key element that acts as the backbone infrastructure for realizing innovative systems compliant with the fourth industrial revolution vision and requirements to realize it. Several architectures, such as the reference architectural model industry 4.0 (RAMI4.0), the industrial Internet reference architecture (IIRA), and the smart grid architecture model (SGAM), have been proposed to develop and integrate ICPS, their services, and applications for different domains. In such architectures, the digitization of assets and interconnection to relevant industrial processes and business services is of paramount importance. Different technological solutions have been developed that overwhelmingly focus on the integration of the assets with their cyber counterpart. In this context, the adoption of standards is crucial to enable the compatibility and interoperability of these network-based systems. Since industrial agents are seen as an enabler in realizing ICPS, this work aims to provide insights related to the use and alignment of the recently established IEEE 2660.1 recommended practice to support ICPS developers and engineers to integrate assets in the context of each one of the three referred reference architectures. A critical discussion also points out some noteworthy aspects that emerge when using the IEEE 2660.1 in these architectures and discusses limitations and challenges ahead.

Abstract Background Both hyperuricaemia and hyperlipidaemia are common metabolic diseases that are closely related to each other, and both are independent risk factors for the development of a variety of diseases. HUA combined with hyperlipidaemia increases the risk of nonalcoholic fatty liver disease and coronary heart disease. This study aimed to investigate the relationship between HUA and hyperlipidaemia and study the metabolic pathway changes in patients with HUA associated with hyperlipidaemia using metabolomics. Methods This was a case‒control study. The prevalence of hyperlipidaemia in HUA patients in the physical examination population of Tianjin Union Medical Centre in 2018 was investigated. Metabolomics analysis was performed on 308 HUA patients and 100 normal controls using Orbitrap mass spectrometry. A further metabolomics study of 30 asymptomatic HUA patients, 30 HUA patients with hyperlipidaemia, and 30 age-and sex-matched healthy controls was conducted. Differential metabolites were obtained from the three groups by orthogonal partial least-squares discrimination analysis, and relevant metabolic pathways changes were analysed using MetaboAnalyst 5.0 software. Results The prevalence of hyperlipidaemia in HUA patients was 69.3%. Metabolomic analysis found that compared with the control group, 33 differential metabolites, including arachidonic acid, alanine, aspartate, phenylalanine and tyrosine, were identified in asymptomatic HUA patients. Pathway analysis showed that these changes were mainly related to 3 metabolic pathways, including the alanine, aspartate and glutamate metabolism pathway. Thirty-eight differential metabolites, including linoleic acid, serine, glutamate, and tyrosine, were identified in HUA patients with hyperlipidaemia. Pathway analysis showed that they were mainly related to 7 metabolic pathways, including the linoleic acid metabolism pathway, phenylalanine, tyrosine and tryptophan biosynthesis pathway, and glycine, serine and threonine metabolism pathway. Conclusions Compared to the general population, the HUA population had a higher incidence of hyperlipidaemia. HUA can cause hyperlipidaemia. by affecting the metabolic pathways of linoleic acid metabolism and alanine, aspartate and glutamate metabolism. Fatty liver is closely associated with changes in the biosynthesis pathway of pahenylalanine, tyrosine, and tryptophan in HUA patients with hyperlipidaemia. Changes in the glycine, serine and threonine metabolism pathway in HUA patients with hyperlipidaemia may lead to chronic kidney disease.

In this study, we investigate the transferability of the process-property relationship between two Inconel alloys for laser powder bed fusion (LPBF). By developing a Bayesian learning approach, the process-property model of Inconel 625 learned from Inconel 718 demonstrates high accuracy with R of 0.95, which verifies the feasibility of this innovative concept. It is further found that the accuracy of the knowledge transfer model of Inconel 625 is increased if the data on Inconel 625 is more abundant. In this regard, the mean RMSE and MAE on relative density are decreased by about 0.45% and 0.35% when the Inconel 625 dataset size is increased from 15 to 60. In addition, both accuracy and robustness of the Inconel 625 model are increased with transferred knowledge from Inconel 718 regardless of the dataset size of Inconel 625, in which the mean RMSE and MAE are decreased by up to 0.7% and 0.5%, respectively.

To reveal the deep seismogenic environment and mechanism of earthquakes in Songyuan City, Northeastern China, 59 broadband magnetotelluric sites in the Songyuan area were arranged in this study at a spacing of 5 km. In addition, two intersecting magnetotelluric profiles, with a total of 23 measuring sites and a spacing of 2 km, were established near the Ningjiang earthquake swarm. Using a nonlinear conjugate gradient (NLCG) algorithm, resistivity structures in the lithosphere were obtained at different scales using three-dimensional (3D) inversion. The research results show that: a deep high-conductivity system (

Abstract Although the SARS-CoV-2 vaccine has been widely used worldwide, not all individuals can produce neutralization antibodies, so it is still urgent to find and prepare neutralization antibodies for COVID-19 prevention or treatment. In this study, we created a new strategy to effectively obtain neutralizing antibodies or complementary determining region 3 (CDR3) of neutralizing antibodies against SARS-CoV-2. We first predicted and synthesized several B cell epitopes on RBD and adjacent RBD of S protein, then the B cell epitopes were used to prepare affinity chromatography columns respectively and purify the binding IgG from serum samples of convalescent COVID-19 patients. After these IgGs were identified to have neutralizing activity, the peptide sequences of the antigen-binding regions (variable region) of neutralizing antibodies were analyzed by protein mass spectrometry. Subsequently, the B cells from the same individual were sorted and used to obtain their full BCR repertoire by 5′ RACE combined with high-throughput of PacBio sequencing method. Then, the peptide sequence of neutralizing antibody variable region by protein mass spectrometry was mapped to the full BCR repertoire and found the full variable region sequence of neutralizing antibodies. Finally, we obtained and synthesized numerous CDR3 peptides of neutralizing antibodies to confirm the neutralizing activity for SARS-CoV-2 infection. Our results indicate that the novel scheme will be suitable for rapid screening of neutralizing antibodies, including screening neutralizing antibodies against SARS-CoV-2 and other pathogenic microorganisms.

Abstract. Objective:. Pressure overload-induced myocardial apoptosis is a critical pathologically initiated process leading to heart failure (HF). Growth differentiation factor 15 (GDF15) dramatically increases during cardiac hypertrophy and dysfunction, but its functions and mechanisms are barely known. This study aims to elucidate the role and mechanism of GDF15 in HF. Methods:. Between January 2017 and August 2018, 57 patients diagnosed with chronic HF (aged >18 years, with left ventricular ejection fraction (LVEF) ≤35%) and 57 non-HF patients (aged >18 years, LVEF >35%) were prospectively enrolled in this study based on the balance of the baseline characteristics. Other acute or chronic diseases and pregnant/lactating women were excluded. The serum concentrations of GDF15 were detected. Isoproterenol (ISO)-induced HF mouse model was established by pumping with ISO (30 mg/(kg·day)) for 4 weeks, and the GDF15 expression in serum and heart tissue was evaluated in vivo. Primary cardiomyocytes were cultured and treated with ISO to induce cardiomyocytes damage. The apoptosis of cardiomyocytes and the effect of GDF15 on ISO-induced cardiomyocytes injury was evaluated in vitro. Results:. After adjusting the baseline characteristic, serum levels of GDF15 were significantly higher in HF subjects than in non-HF patients. Similarly, in the ISO-induced HF mouse model, the significant increase in GDF15 was associated with the process of HF in vivo. Moreover, the elevation of GDF15 occurred prior to heart remodeling in the ISO-induced HF mouse model. Furthermore, using primary cardiomyocytes, we demonstrated that the GDF15 was remarkably enhanced in serum from pathological HF patients and cardiac tissue from the ISO-induced mouse model. Reducing GDF15 exaggerated the ISO-induced cell apoptosis by blocking mitochondrial fusion and increasing oxidative stress. In contrast, the silence of GDF15 aggravated the ISO-induced cardiomyocytes damage. Conclusions:. GDF15 acts as a protective factor against cardiomyocyte apoptosis by improving mitochondria fusion during HF. These findings indicate that GDF15 may be a potential therapeutic target for HF.

An efficient Cu-catalyzed strategy for the direct C–H amination of arenes in high yields using N-hydroxyphthalimide as the amidyl radical precursor under air is reported. A possible mechanism is proposed that proceeds via a radical reaction in the presence of CuBr and triethyl phosphite.

Abstract Rivaroxaban is an oral anticoagulant that inhibits thrombin and blocks coagulation cascade through directly inactivating factors Xa. Despite rivaroxaban is widely used for prevention and treatment of venous thrombosis, and its common adverse reactions have been reported, including abnormal coagulation, mucosal hemorrhage, hematuria, and intracranial hemorrhage. To explore potential drivers of individual differences in adverse reactions induced by rivaroxaban, we performed whole‐exome sequencing and found that AKR7A3 rs1738023/rs1738025 and ABCA6 rs7212506 are susceptible sites for rivaroxaban‐related bleeding in aged patients treated with rivaroxaban. Gene functional annotation and signaling pathway enrichment indicated that homozygous mutations in AKR7A3 and ABCA6 might alter normal rivaroxaban transport and metabolism, and lead to continuous accumulation of activated drugs and toxic substances in vivo. Our results suggested that interindividual differences in bleeding events induced by rivaroxaban may be potentially driven by genetic alterations related to abnormal metabolism and transport of rivaroxaban.

The effects of inorganic micro powder particle size and type on the water stability, low-temperature crack resistance, and fatigue performance of asphalt and its mixtures were evaluated through various tests, including asphalt foundation, freeze–thaw splitting, low-temperature bending beam, and indirect tensile fatigue tests. The evaluation results show that the addition of inorganic micro powder particles, specifically, hydrated lime and cement, resulted in significant improvement of the asphalt mixture splitting strengths and freeze–thaw splitting strength ratio. Moreover, a decrease in the additive particle size increased its specific surface area, further enhancing the asphalt mixture splitting strength and freeze–thaw splitting strength ratio. Under the same stress level, the smaller the additive particle size, the better the fatigue performance of the asphalt mixture. Although micro powder particles have an adverse effect on the low-temperature performance of asphalt mixtures, this effect gradually decreases with the micro powder particle size. Furthermore, compared with cement, hydrated lime exhibited better fatigue performance but poor water stability.

This paper presents a metamaterial biosensor composed of dual-cut wires (DCWs) and quadruple split-ring resonators (QSRs), achieving polarization-independent plasmon-induced transparency (PIT) effects in the terahertz range. By leveraging the coupling between bright and dark modes, we observe a transparent window with a minimal loss at 1.22 THz. We investigate the physical mechanism of the PIT effect by analyzing the surface current distribution and electric fields. Simulations reveal that the PIT transparency shows a peak shift of up to 146.7 GHz with an analyte thickness of 14 μm. Moreover, as the refractive index of the analyte increases from 1.0 to 1.6, the biosensor’s theoretical sensitivity is calculated to be 281.25 GHz/RIU. Furthermore, we explore the application of the proposed DCW/QSR biosensor for the detection of bacteriophage viruses. Our simulation results demonstrate that the DCW/QSR biosensor serves as an effective sensing platform for detecting viruses such as PRD1 and MS2. These findings underscore the potential of our high-sensitivity metamaterial biosensor, which holds great promise in the field of biosensing, offering a practical and cost-effective approach to label-free biomedical detection.

Electric Vehicles (EVs) have become a trending topic in recent years due to the industry’s race for competitive pricing as well as environmental awareness. These concerns have led to increased research into the development of both affordable and environmentally friendly EV technology. This paper aims to review EV-related issues beginning with the component level, through the system level, based on intelligent maintenance aspects. The paper will also clarify the existing gaps in practical applications and highlight the potential opportunities related to the current issues in EVs for the EV industry moving forward. More specifically, we will briefly start with an overview of the fast-growing EV market, showing the urgent demand for Prognostics and Health Management (PHM) applications in the EV industry. At the component level, the issues of the major components such as the motor, battery, and charging system in EVs are elaborated, and the relevant PHM research of these components is surveyed to show the development in the era of EV expansion. Moreover, the impact of an increasing number of EVs at the system level such as power distribution systems and power grid are explored to uncover possible research in the future. The combination of existing PHM techniques and robust measurement or feature extraction methods can provide better solutions to address the motor, battery, or transformer issues at the component level. A comprehensive optimization and cybersecurity strategy will help to address the issues of the whole network at a system level. Four aspects of vision in the overall charging network – battery innovation, charging optimization, infrastructure evolution, and sustainability – that cover the demands of research in new battery materials, innovative charging techniques, new architectures of the charging network, and reliable waste treatment mechanisms are outlined. A conclusion is reached in this paper by summarizing the opportunities for future EV research and development.

An effective way to improve the rutting resistance of asphalt pavement is to increase the modulus of the middle surface layer of the asphalt mixture. However, the fatigue performance of high-modulus asphalt mixtures hinders this development. In this study, we enhanced the fatigue property of high-modulus asphalt mixtures by adding basalt fiber. Marshall tests were performed to evaluate the effect of the basalt fiber and a high-modulus modifier on various Marshall test results. The results were analyzed and compared with the performance of SBS-modified (Styrene-Butylene-Styrene) asphalt mixes. Adding basalt fiber increased the asphalt-aggregate ratio, decreased the density, and reduced air voids in the mixture. The stability also slightly increased, and the flow slightly decreased. Moreover, 0.2% basalt fiber increased the fatigue resistance of high-modulus asphalt mixture 1.9 times, and this improvement increases with the increasing basalt content. The elastic modulus of basalt fiber is considerably higher than that of asphalt; therefore, the proportion of stiffer components in the asphalt mastic was higher after mixing. Furthermore, basalt fiber absorbs oil (asphalt); accordingly, the increased asphalt content slightly enhanced the fatigue resistance of the mixture.

Backgrounds. Cardiovascular disease (CVD) is a serious condition that poses threats to patients’ quality of life and life expectancy. Cardiac rehabilitation is a crucial treatment option that can improve outcomes for CVD patients. Hybrid comprehensive telerehabilitation (HCTR) is a relatively new approach. In the context of pandemics, HCTR can minimize the risk of cluster infections by reducing hospital visits while delivering effective rehabilitation care. This study is aimed at assessing the efficacy and safety of HCTR as a secondary prevention measure for CVD patients compared to usual rehabilitation care. Methods. We searched PubMed, Embase, The Web of Science, The Cochrane Library, and PsychINFO for all related studies up to January 20, 2023. Two reviewers independently screened the titles and abstracts of potentially eligible articles based on the predefined search criteria. Data were analyzed using a comprehensive meta-analysis software (RevMan5.3). Results. Eight trials, involving 1578 participants, were included. HCTR and usual rehabilitation care provide similar effects on readmission rates (odds ratio OR=0.90 (95% CI 0.69-1.17), P=0.43) and mortality (odds ratio OR=1.06 (95% CI 0.72-1.57), P=0.76). Effects on Short Form-36 Health Status Questionnaire (SF-36) score were also similar (SMD: 1.32 (95% CI-0.48-3.11), P=0.15). Compared with usual rehabilitation care, HCTR can improve peak oxygen uptake (VO2 peak) (SMD: 0.99 (95% CI 0.23-1.74), P=0.01) and 6-minute walking test (6MWT) (SMD: 10.02 (95% CI 5.44-14.60), P

Manufacturers of nanomaterial-enabled products need models of endpoints that are relevant to human safety to support the “safe by design” paradigm and avoid late-stage attrition. Increasingly, embryonic zebrafish (Danio Rerio) are recognised as a key human safety relevant in vivo test system. Hence, machine learning models were developed for identifying metal oxide nanomaterials causing lethality to embryonic zebrafish up to 24 hours post-fertilisation, or excess lethality in the period of 24–120 hours post-fertilisation, at concentrations of 250 ppm or less. Models were developed using data from the Nanomaterial Biological-Interactions Knowledgebase for a dataset of 44 diverse, coated and uncoated metal or, in one case, metalloid oxide nanomaterials. Different modelling approaches were evaluated using nested cross-validation on this dataset. Models were initially developed for both lethality endpoints using multiple descriptors representing the composition of the core, shell and surface functional groups, as well as particle characteristics. However, interestingly, the 24 hours post-fertilisation data were found to be harder to predict, which could reflect different exposure routes. Hence, subsequent analysis focused on the prediction of excess lethality at 120 hours-post fertilisation. The use of two data augmentation approaches, applied for the first time in nano-QSAR research, was explored, yet both failed to boost predictive performance. Interestingly, it was found that comparable results to those originally obtained using multiple descriptors could be obtained using a model based upon a single, simple descriptor: the Pauling electronegativity of the metal atom. Since it is widely recognised that a variety of intrinsic and extrinsic nanomaterial characteristics contribute to their toxicological effects, this is a surprising finding. This may partly reflect the need to investigate more sophisticated descriptors in future studies. Future studies are also required to examine how robust these modelling results are on truly external data, which were not used to select the single descriptor model. This will require further laboratory work to generate comparable data to those studied herein.

BackgroundBoth domestic and foreign studies on the diet quality of patients with thyroid nodules are rare at present, and the relationship between thyroid nodules and diet quality is still unclear.ObjectiveThis study aims to evaluate the diet quality of thyroid nodules with the China Healthy Diet Index (CHDI) and to explore the relationship between diet quality and thyroid nodules.MethodsWe conducted a hospital-based case-control study in which 387 patients with thyroid nodules were matched individually (1∶1) by gender and age (±3 years) to the controls who ordered a routine physical examine and with negative thyroid nodules reported by B-ultrasound in the same hospital. A structured questionnaire was applied to collect data on general characteristics and diet. CHDI was employed to evaluate the diet quality of the two groups. CHDI is based on the Dietary Guidelines for Chinese Residents and the recommended food intake in the balanced diet pagoda, combined with the dietary nutritional status of Chinese population. The index contains 13 scoring components, and the highest total score is 100, with a higher score representing better dietary quality. CHDI scores < 60, 60-

BackgroundPapillary thyroid cancer is the result of a variety of pathogenic factors. The prevalence of papillary thyroid cancer varies greatly in different regions, and the disease is more harmful to women.ObjectiveThis study aims to explore the relationship between reproductive factors and papillary thyroid cancer, and to provide basic data for prevention and control of the disease.MethodsA 1∶1 age (±3 years) matched case-control study was conducted in 331 pairs of newly confirmed papillary thyroid cancer cases and controls from two hospitals in Shanghai from November 2012 to December 2013. Comparisons were made in the history of menstruation, pregnancy, gynecological and breast diseases, and other variables between the two groups.ResultsThe results of univariate analysis indicated that the proportions of education below bachelor degree, married, and mainly manual workers in the case group were significantly higher than those in the control group (P1 time (OR =2.490, 95%CI: 1.196-5.184; P=0.015), and the history of using oral contraceptive or hormone drugs (OR=2.389, 95%CI: 1.338-4.268; P=0.003) were the risk factors of papillary thyroid cancer.ConclusionIrregular menstruation, surgical menopause, history of pregnancy, and history of using oral contraceptive or hormone drugs might be the risk factors of papillary thyroid cancer. To reduce the incidence of papillary thyroid cancer, strengthened health education and rational use of contraceptives are recommended.

A composite electrode of carbon nanotube CNT@Mn3O4 nanocable was successfully synthesized via direct electrophoretic deposition onto a copper foil, followed by calcination. By uniformly depositing Mn3O4 nanoparticles on CNTs, a nanocable structure of CNT@Mn3O4 can be formed, where the CNT acts as a “highway” for electrons and ions to facilitate fast transportation. Moreover, capacitive energy storage processes play a crucial role in lithium (Li) storage, especially during high scan rates. The significant contribution of capacitance is highly advantageous for the rapid transfer of Li+ ions, which ultimately results in an improved reversible capacity and prolonged cycle stability of the battery. A high specific capacity of 1367 mAh g−1 was maintained over 300 charge–discharge cycles at a current density of 1 A g−1, indicating excellent capacity retention and an extended cycle life. Furthermore, the synthesis process was facile and cost-effective, obviating the need for complex procedures such as mixing and pasting. Additionally, no binder was required, thereby enhancing battery quality efficiency.

Objective: Hepatocellular carcinoma (HCC), the main type of liver cancer, has a high morbidity and mortality, and a poor prognosis. RNA helicase DDX5, which acts as a transcriptional co-regulator, is overexpressed in most malignant tumors and promotes cancer cell growth. Heat shock protein 90 (HSP90) is an important molecular chaperone in the conformational maturation and stabilization of numerous proteins involved in cell growth or survival. Methods: DDX5 mRNA and protein expression in surgically resected HCC tissues from 24 Asian patients were detected by quantitative real-time PCR and Western blot, respectively. The interaction of DDX5-HSP90 was determined by molecular docking, immunoprecipitation, and laser scanning confocal microscopy. The autophagy signal was detected by Western blot. The cell functions and signaling pathways of DDX5 were determined in 2 HCC cell lines. Two different murine HCC xenograft models were used to determine the function of DDX5 and the therapeutic effect of an HSP90 inhibitor. Results: HSP90 interacted directly with DDX5 and inhibited DDX5 protein degradation in the AMPK/ULK1-regulated autophagy pathway. The subsequent accumulation of DDX5 protein induced the malignant phenotype of HCC by activating the β-catenin signaling pathway. The silencing of DDX5 or treatment with HSP90 inhibitor both blocked in vivo tumor growth in a murine HCC xenograft model. High levels of HSP90 and DDX5 protein were associated with poor prognoses. Conclusions: HSP90 interacted with DDX5 protein and subsequently protected DDX5 protein from AMPK/ULK1-regulated autophagic degradation. DDX5 and HSP90 are therefore potential therapeutic targets for HCC.

Abstract Background Hepatocellular carcinoma (HCC) is a common cause of cancer mortality worldwide. Recent studies have shown that the polytopic enzyme membrane associated ring-CH-type finger 6 (MARCH6) participates in tumorigenesis, but its function in HCC development needs to be investigated. This study aimed to explore the role of MARCH6 in HCC. Methods Expression of MARCH6 in human HCC samples was checked by immunohistochemical staining assay. Clinical relevance of MARCH6 and activating transcription factor 2 (ATF2) was analyzed from TCGA database. CCK-8, EdU staining, colony formation and transwell were performed to assess cell proliferation, growth and migration. Xenografted tumorigenesis was used to examine in vivo role MARCH6. Immunoblotting was applied to detect protein abundance. Results We found that MARCH6 expression was elevated in human HCC samples. Over-expression of MARCH6 was associated with poor prognosis of HCC patients. Up-expression of MARCH6 promoted cell growth and migration of HCC cells. In contrast, the HCC cell growth and migration were suppressed by MARCH6 knockdown. Furthermore, the DNA synthesis was enhanced by MARCH6. The expression of ATF2 was potentiated by MARCH6 over-expression, while it was suppressed by MARCH6 silencing. TCGA database showed positive correlation between the expression of MARCH6 and ATF2. Importantly, ATF2 expression contributed to the oncogenic function of HCC cells. Conclusion Our findings suggest that MARCH6-mediated ATF2 up-regulation contributes to HCC development. MARCH6 may be a promising target for the diagnosis and treatment of HCC.

BackgroundGamma-aminobutyric acid transaminase (ABAT) catalyzes the conversion of gamma-aminobutyric acid (GABA) into succinic semialdehyde. Although some evidence supports a key role of ABAT in the progression of hepatocellular carcinoma (HCC), no systematic analysis is available. Thus, this study aimed to investigate the possible mechanisms related to low ABAT expression and the prognostic value and potential functions of ABAT in HCC.MethodsWe obtained relevant datasets from the Encyclopedia of RNA Interactomes, MethSurv, cBioPortal, TISIDB and The Cancer Genome Atlas and used bioinformatic methods to analyze DNA methylation, copy number variation, gene mutation, and upstream microRNAs (miRNAs) of ABAT, exploring the potential relationship between ABAT expression and the prognosis, glycolysis, and immune infiltration in HCC.ResultsThe results indicated that ABAT expression was lower in HCC tumor tissues than in normal tissues or adjacent tissues. Low ABAT expression was related to patient age, T stage classification, pathologic stage, histological grade, and alpha-fetoprotein level of HCC. Kaplan-Meier survival analyses indicated that low ABAT expression was correlated with poor HCC prognosis. ABAT was also verified as an independent risk factor in HCC via Cox multivariate analysis. Gene set enrichment analysis showed enrichment in various signaling pathways. Furthermore, DNA methylation, copy number variation, and gene mutation potentially induced low ABAT expression; miR-135a-5p was a potential upstream miRNA of ABAT. Additionally, ABAT expression was associated with glycolysis-related genes, infiltrated immune cells, immunoinhibitors, and immunostimulators in HCC.ConclusionsOur study reveals that deficient ABAT expression is correlated with disease progression and poor prognosis in HCC because of its role in tumorigenesis and tumor immunity.

A novel Cr (VI) removal material was designed and produced comprising multi-walled carbon nanotubes (MWCNTs) as a support with a high specific surface area and the loaded Fe–Ni bimetallic particles as catalytic reducing agents. Such a design permits the composite particle to perform the adsorption, reduction, and immobilisation of Cr (VI) quickly and efficiently. Due to MWCNTs’ physical adsorption, Cr (VI) in solution aggregates in the vicinity of the composite, and Fe rapidly reduces Cr (VI) to Cr (III) catalysed by Ni. The results demonstrated that the Fe–Ni/MWCNTs exhibits an adsorption capacity of 207 mg/g at pH = 6.4 for Cr (VI) and 256 mg/g at pH 4.8, which is about twice those reported for other materials under similar conditions. The formed Cr (III) is solidified to the surface by MWCNTs and remains stable for several months without secondary contamination. The reusability of the composites was proven by retaining at least 90% of the adsorption capacity for five instances of reutilization. Considering the facile synthesis process, low cost of raw material, and reusability of the formed Fe–Ni/MWCNTs, this work shows great potential for industrialisation.

Accurate battery capacity prediction is important to ensure reliable battery operation and reduce the cost. However, the complex nature of battery degradation and the presence of capacity regeneration phenomenon render the prediction task very challenging. To address this problem, this paper proposes a novel and efficient algorithm to predict the battery capacity trajectory in a multi-cell setting. The proposed method is a new variant of Gaussian process regression (GPR) model, and it utilizes similar trajectories in the historical data to enhance the prediction of desired capacity trajectory. More importantly, the proposed method adds no extra computation cost to the standard GPR. To demonstrate the effectiveness of the proposed method, validation tests on two different battery datasets are implemented in the case studies. The prediction results and the computation cost are carefully benchmarked with cutting-edge GPR approaches for battery capacity prediction.

Hepatocellular carcinoma (HCC), a primary liver cancer, is closely associated with the gut microbiota. However, the role of gut fungi in the development of HCC remains unclear. The aim of this study was to explore the influence of intestinal Candida albicans on HCC. Here, We found that patients with HCC showed significantly decreased diversity of the gut mycobiome and increased abundance of C. albicans, compared to the patients with liver cirrhosis. The gavage of C. albicans in the WT models increased the tumor size and weight and influenced the plasma metabolome, which was indicated by alterations in 117 metabolites, such as L-carnitine and L-acetylcarnitine, and several KEGG enriched pathways, such as phenylalanine metabolism and citrate cycle. Moreover, the expression of nucleotide oligomerization domain-like receptor family pyrin domain containing 6 (NLRP6) in the intestinal tissues and primary intestinal epithelial cells of the WT mice interacted with C. albicans increased. Notably, the colonization of C. albicans had no effect on tumor growth in Nlrp6–/– mice. In conclusion, the abnormal colonization of C. albicans reprogrammed HCC metabolism and contributed to the progression of HCC dependent on NLRP6, which provided new targets for the treatment of HCC.

The advent of the Industry 4.0 initiative has made it so that manufacturing environments are becoming more and more dynamic, connected but also inherently more complex, with additional inter-dependencies, uncertainties and large volumes of data being generated. Recent advances in Industrial Artificial Intelligence have showcased the potential of this technology to assist manufacturers in tackling the challenges associated with this digital transformation of Cyber-Physical Systems, through its data-driven predictive analytics and capacity to assist decision-making in highly complex, non-linear and often multistage environments. However, the industrial adoption of such solutions is still relatively low beyond the experimental pilot stage, as real environments provide unique and difficult challenges for which organizations are still unprepared. The aim of this paper is thus two-fold. First, a systematic review of current Industrial Artificial Intelligence literature is presented, focusing on its application in real manufacturing environments to identify the main enabling technologies and core design principles. Then, a set of key challenges and opportunities to be addressed by future research efforts are formulated along with a conceptual framework to bridge the gap between research in this field and the manufacturing industry, with the goal of promoting industrial adoption through a successful transition towards a digitized and data-driven company-wide culture. This paper is among the first to provide a clear definition and holistic view of Industrial Artificial Intelligence in the Industry 4.0 landscape, identifying and analysing its fundamental building blocks and ongoing trends. Its findings are expected to assist and empower researchers and manufacturers alike to better understand the requirements and steps necessary for a successful transition into Industry 4.0 supported by AI, as well as the challenges that may arise during this process.

The continuous monitoring and real-time feedback on the uniformity of the mixture after paving and compaction is important to guide the construction and improve the life of the asphalt pavement. Thus, in this study, the latest digital image technology was used to collect images of asphalt pavement after paving and compaction according to the set parameters. The images collected were preprocessed in steps such as binary grayscale, filtering, histogram, and small particle filtering, which established the method for calculating the construction depth HP of the digital images of pavement. Moreover, a method was proposed to evaluate the uniformity of asphalt pavement using the construction depth coefficient of variation. The coefficients of variation were computed based on 100 images of the dependent project and compared with the actual images. The results indicated that the construction depth coefficient of variation of the digital images obtained by the developed calculation procedure was in agreement with the actual situation and combined the correlation degree of the calculation results. Small areas of 42 are recommended as the division of the asphalt pavement compaction uniformity evaluation method based on construction depth variation, and the use of Cv4≥8.0 as the evaluation standard for the segregation of asphalt pavement is recommended. The method proposed is a new and rapid test to evaluate and detect the asphalt pavement uniformity.

Background: Antibodies induced by viral infection can not only prevent subsequent virus infection, but can also mediate pathological injury following infection. Therefore, understanding the B-cell receptor (BCR) repertoire of either specific neutralizing or pathological antibodies from patients convalescing from Coronavirus disease 2019 (COVID-19) infection is of benefit for the preparation of therapeutic or preventive antibodies, and may provide insight into the mechanisms of COVID-19 pathological injury. Methods: In this study, we used a molecular approach of combining 5’ Rapid Amplification of cDNA Ends (5’-RACE) with PacBio sequencing to analyze the BCR repertoire of all 5 IgH and 2 IgL genes in B-cells harvested from 35 convalescent patients after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Results: We observed numerous BCR clonotypes within most COVID-19 patients, but not in healthy controls, which validates the association of the disease with a prototypical immune response. In addition, many clonotypes were found to be frequently shared between different patients or different classes of antibodies. Conclusions: These convergent clonotypes provide a resource to identify potential therapeutic/prophylactic antibodies, or identify antibodies associated with pathological effects following infection with SARS-CoV-2.

The rolling correction process can eliminate machining distortions of aluminum alloy 7075-T651 structural parts. The thermal stability of the corrected structural parts under the action of temperature loading, especially the macroscopic shape stability, is key to ensure the safe service of mechanical equipment. In this study, different thermal loads were used to postprocess aluminum alloy 7075-T651 structural parts after rolling correction. The thermal stability of the rolled samples was analyzed by characterizing the microstructure and physical and mechanical properties. The results show no obvious change compared to rolling in the distortion of the parts after temperature treatments at 120 °C, 160 °C, 230 °C and 300 °C; the distortion changes were only 10.48%, 2.74%, 8.13% and 8.70%, respectively. The residual stresses in the rolling areas of the samples decreased by 35.58%, 26.08%, 75.97% and 83.13%, respectively. The microhardness also showed a decreasing trend. There was no obvious change after treatment at 120 °C, but the hardness decreased by approximately 5%, 23% and 56%, respectively, after treatments at other temperatures. However, the rolling stress relaxed under thermal stress. The microstructure change analysis shows that the material microstructure is mainly dominated by static reversion at lower thermal loads. With increasing thermal load, the samples are mainly affected by the static recrystallization effect, the microstructure is gradually blurred, and the hardness decreases significantly. In conclusion, although the residual stresses introduced by rolling would occur in different degrees of stress relaxation under the thermal load, the microstructure changes caused by thermal load did not significantly affect the macroscopic distortion of the samples, and the macroscopic shape of the structural parts after rolling correction had good thermal stability.