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Abstract EMT dysfunction is a dominant mechanisms of hypospadias. Thus, identification of EMT‐related lncRNAs based on transcriptome sequencing data of hypospadias might provide novel molecular markers and therapeutic targets for hypospadias. First, the microarray data related to hypospadias were downloaded from Gene Expression Omnibus (GEO). Besides, the differentially expressed lncRNAs and messenger RNAs (mRNAs) related to EMT were screened to construct lncRNA‐mRNA co‐expression interaction pairs. In addition, the microRNA (miRNA) prediction analysis was performed through bioinformatics methods to construct a ceRNA network. Moreover, function prediction and function enrichment and pathway analyses were also performed. Finally, the core EMT‐related lncRNAs were verified based on mRNA expression changes and cell functions. A total of 6 EMT‐related lncRNAs were identified and 123 mRNA‐lncRNA co‐expression interaction pairs were screened in this study. Additionally, a ceRNA regulatory network comprising 17 mRNAs, 4 lncRNAs, and 28 miRNAs was constructed based on the prediction of hypospadias‐related miRNAs. The validation results of the dataset GSE121712 revealed that only BEX1 was positively correlated with the expression of the lncRNA GNAS‐AS1 (r = 0.874, P < 0.01), both of which had high expression. The cell experiment results demonstrated that interfering with the expression of GNAS‐AS1 significantly promoted the proliferation, migration, and EMT of cells. Importantly, it was confirmed that GNAS‐AS1 can serve as a ceRNA and play an important role in the EMT of hypospadias. Hence, it may be considered as a potential target in the treatment of this disease.

Abstract A simple and flexible mass balance approach was applied to observations of XCH4 from TROPOMI to estimate CH4 emissions over Shanxi Province, including the impacts of advective transport, pressure transport, and atmospheric diffusion. High-frequency eddy-covariance flux observations were used to constrain the driving terms of the mass balance equation. This equation was then used to calculate day-to-day and 5 km × 5 km grided CH4 emissions from May 2018 to July 2022 based on TROPOMI RPRO column CH4 observations. The Shanxi-wide emissions of CH4, 126 ± 58.8 ug/m2/s, shows a fat tail distribution and high variability on a daily time scale (the 90th percentile is 2.14 times the mean and 2.74 times the median). As the number of days in the rolling average increases, the change in the variation decreases to 128 ± 35.7 ug/m2/s at 10-day, 128 ± 19.8 ug/m2/s at 30-day and 127 ± 13.9 ug/m2/s at 90-day. The range of values of the annual mean emissions on coal mine grids within Shanxi for the years 2018 to 2022 was 122 ± 58.2, 131 ± 71.2, 111 ± 63.6, 129 ± 87.1, and 138 ± 63.4 ug/m2/s, respectively. The 5-year average emissions from TROPOMI are 131 ± 68.0 ug/m2/s versus 125 ± 94.6 ug/m2/s on the grids where the EDGAR bottom-up database also has data, indicating that those pixels with mines dominate the overall emissions in terms of both magnitude and variability. The results show that high-frequency observation-based campaigns can produce a less biased result in terms of both the spatial and temporal distribution of CH4 emissions as compared with approaches using either low-frequency data or bottom-up databases, that coal mines dominate the sources of CH4 in Shanxi, and that the observed fat tail distribution can be accounted for using this approach.

Abstract Background Preoperative discrimination between non-muscle-invasive bladder cancer (NMIBC) and the muscle invasive bladder cancer (MIBC) is a determinant of management. The purpose of this research is to employ radiomics to evaluate the diagnostic value in determining muscle invasiveness of compressed sensing (CS) accelerated 3D T2-weighted-SPACE sequence with high resolution and short acquisition time. Methods This prospective study involved 108 participants who underwent preoperative 3D-CS-T2-weighted-SPACE, 3D-T2-weighted-SPACE and T2-weighted sequences. The cohort was divided into training and validation cohorts in a 7:3 ratio. In the training cohort, a Rad-score was constructed based on radiomic features selected by intraclass correlation coefficients, pearson correlation coefficient and least absolute shrinkage and selection operator . Multivariate logistic regression was used to develop a nomogram combined radiomics and clinical indices. In the validation cohort, the performances of the models were evaluated by ROC, calibration, and decision curves. Results In the validation cohort, the area under ROC curve of 3D-CS-T2-weighted-SPACE, 3D-T2-weighted-SPACE and T2-weighted models were 0.87(95% confidence interval (CI):0.73-1.00), 0.79(95%CI:0.63–0.96) and 0.77(95%CI:0.60–0.93), respectively. The differences in signal-to-noise ratio and contrast-to-noise ratio between 3D-CS-T2-weighted-SPACE and 3D-T2-weighted-SPACE sequences were not statistically significant(p > 0.05). While the clinical model composed of three clinical indices was 0.74(95%CI:0.55–0.94) and the radiomics-clinical nomogram model was 0.88(95%CI:0.75-1.00). The calibration curves confirmed high goodness of fit, and the decision curve also showed that the radiomics model and combined nomogram model yielded higher net benefits than the clinical model. Conclusion The radiomics model based on compressed sensing 3D T2WI sequence, which was acquired within a shorter acquisition time, showed superior diagnostic efficacy in muscle invasion of bladder cancer. Additionally, the nomogram model could enhance the diagnostic performance.

Drug testing has many test elements. It aims to prevent unqualified drugs from entering the market and ensure drug safety. The existing artificial intelligence (AI) online monitoring system identifies active ingredients in the process of use. Owing to their openness, data are easy to be lost, failing to meet user needs and inducing a specific impact on the use of the monitoring system. With the continuous development of computer and measurement technologies, various biochemical data are increasing at an unprecedented speed, and numerous databases are emerging. Extracting patterns from considerable known data and experimental facts is an essential task for a wide range of biological and chemical workers. Pattern recognition is one of the essential technologies for data mining. It is widely used in industry, agriculture, national defense, biomedicine, meteorology, astronomy, and other fields. To improve the effect of the online drug ingredient recognition system, this study used AI to design an online drug ingredient recognition-embedded monitoring system and applied AI to the teaching field to improve teaching efficiency. First, this study constructed the framework of the AI online drug ingredient recognition-embedded monitoring system and introduced the process of online drug ingredient recognition. Then, it introduced the pattern recognition method, constructed the pattern recognition system, and presented the pattern recognition algorithm and the algorithm evaluation index. Afterward, it used pattern recognition to conduct a qualitative analysis of the infrared spectrum of drug components and introduced the overall process of the qualitative analysis. In addition, this study employed AI to implement changes to the embedded system instruction in colleges and universities, summarizing the current issues. The impact of drug component recognition and the educational impact of embedded systems were investigated in the experimental portion. The experimental findings demonstrated the excellent accuracy, sensitivity, specificity, and Matthew correlation coefficient of the online drug component recognition-integrated monitoring system in this work. Compared with that of other systems, its average drug component recognition accuracy was above 0.85. Students in five majors reported high levels of satisfaction with the embedded system teaching, which is better for delivering college instruction.

Software vulnerability detection aims to proactively reduce the risk to software security and reliability. Despite advancements in deep-learning-based detection, a semantic gap still remains between learned features and human-understandable vulnerability semantics. In this paper, we present an XAI-based framework to assess program code in a graph context as feature representations and their effect on code vulnerability classification into multiple Common Weakness Enumeration (CWE) types. Our XAI framework is deep-learning-model-agnostic and programming-language-neutral. We rank the feature importance of 40 syntactic constructs for each of the top 20 distributed CWE types from three datasets in Java and C++. By means of four metrics of information retrieval, we measure the similarity of human-understandable CWE types using each CWE type’s feature contribution ranking learned from XAI methods. We observe that the subtle semantic difference between CWE types occurs after the variation in neighboring features’ contribution rankings. Our study shows that the XAI explanation results have approximately 78% Top-1 to 89% Top-5 similarity hit rates and a mean average precision of 0.70 compared with the baseline of CWE similarity identified by the open community experts. Our framework allows for code vulnerability patterns to be learned and contributing factors to be assessed at the same stage.

Abstract Objective This study aims to screen the differentially expressed long non-coding RNAs (DELncRNAs) related to the regulation of epithelial-mesenchymal transition (EMT) in hypospadias in mesenchymal stem cell-derived exosomes (MSC-Exons) and explore the potential mechanism of these lncRNAs for the EMT in hypospadias. Methods In this study, the microarray data related to MSC-Exos and hypospadias were downloaded from Gene Expression Omnibus (GEO). Besides, the lncRNAs highly expressed in MSC-Exos and the differentially expressed mRNAs and lncRNAs in children with hypospadias were screened, respectively. In addition, the lncRNAs enriched in MSC-Exos and differentially expressed lncRNAs in hypospadias were intersected to obtain the final DElncRNAs. Moreover, the co-expression interaction pairs of differentially expressed lncRNAs and mRNAs were analyzed to construct a Competing Endogenous RNA (ceRNA) network. Finally, the candidate lncRNAs in exosomes were subjected to in vitro cell function verification. Results In this study, a total of 4 lncRNAs were obtained from the microarray data analysis. Further, a ceRNA regulatory network of MSC-Exo-derived lncRNAs related to the regulation of EMT in hypospadias was constructed, including 4 lncRNAs, 2 mRNAs, and 6 miRNAs. The cell function verification results indicated that the exosomes secreted by MSCs may transport HLA complex group 18 (HCG18) into target cells, which promoted the proliferation, migration, and EMT of these cells. Conclusion MSC-Exo-derived lncRNA HCG18 can enter target cells, and it may be involved in the regulation of EMT in hypospadias through the ceRNA network.

Abstract Wilms tumor (WT) is the most common malignancy of the genitourinary system in children. Currently, the Integration of single-cell RNA sequencing (scRNA-Seq) and Bulk RNA sequencing (RNA-Seq) analysis of heterogeneity between different cell types in pediatric WT tissues could more accurately find prognostic markers, but this is lacking. RNA-Seq and clinical data related to WT were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. Small nucleolar RNA host gene 15 (SNHG15) was identified as a risk signature from the TARGET dataset by using weighted gene co-expression network analysis, differentially expressed analysis and univariate Cox analysis. After that, the functional mechanisms, immunological and molecular characterization of SNHG15 were investigated at the scRNA-seq, pan-cancer, and RNA-seq levels using Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), ESTIMATE, and CIBERSORT. Based on scRNA-seq data, we identified 20 clusters in WT and annotated 10 cell types. Integration of single-cell and spatial data mapped ligand-receptor networks to specific cell types, revealing M2 macrophages as hubs for intercellular communication. In addition, in vitro cellular experiments showed that siRNAs interfering with SNHG15 significantly inhibited the proliferation and migration of G401 cells and promoted the apoptosis of G401 cells compared with the control group. The effect of siRNAs interfering with SNHG15 on EMT-related protein expression was verified by Western blotting assay. Thus, our findings will improve our current understanding of the pathogenesis of WT, and they are potentially valuable in providing novel prognosis markers for the treatment of WT.

This research was to assess the dietary copper (Cu) requirement of broiler chickens fed a practical corn-soybean meal diet during 22–42 d of age. A total of 288 numbered Arbor Acres male broilers at 22 d of age were randomly allotted 6 treatments with 8 replicate cages (6 broilers per cage) per treatment. Broilers were fed a Cu-unsupplemented corn-soybean meal basal diet (control, containing 7.36 mg Cu/kg) or the basal diet added with 3, 6, 9, 12, or 15 mg Cu/kg from CuSO4·5H2O for 21 d. Quadratic, asymptotic and broken-line models were fitted and the best fitted models were selected to determine dietary Cu requirements. The results revealed that the contents of Cu in serum and liver, mRNA expression levels of Cu- and zinc-containing superoxide dismutase (CuZnSOD) in liver and monoamine oxidase b (MAO B) in heart, as well as protein expression level of CuZnSOD in liver were affected (P

Infectious bronchitis virus (IBV) is responsible for avian infectious bronchitis, a disease prevalent in countries with intensive poultry farming practices. Given the presence of multiple genotypic strains in China, identifying the regionally dominant genotypes is crucial for the implementation of effective prevention and control measures. This study focuses on the IBV strain CK/CH/WJ/215, isolated from a diseased commercial chicken flock in China in 2021. The CK/CH/WJ/215 isolate was genetically characterized through complete S1 sequence analysis. Phylogenetic comparisons were made with prevalent vaccine strains (H120, LDT3-A, and 4/91). Glycosylation patterns in the S1 protein were also analyzed. Pathogenicity was assessed in 7-day-old specific-pathogen-free chicks, monitoring morbidity, mortality, and tissue tropisms. Phylogenetic analysis clustered the CK/CH/WJ/215 isolate within the GI-19 lineage. Identity with the vaccination strains H120, LDT3-A, and 4/91 was low (75.7%, 78.6%, and 77.5% respectively). Novel glycosylation sites at positions 138 and 530 were identified compared to H120 and LDT-A. The isolate demonstrated nephropathogenic characteristics, causing 100% morbidity and 73.3% mortality in SPF chicks, with broader tropisms in tissues including trachea, lungs, kidneys, and bursa of Fabricius. Comprehensive genetic and pathological investigations revealed significant differences between the CK/CH/WJ/215 isolate and common vaccine strains, including novel glycosylation sites and a strong multiorgan infective capability. These findings are crucial for understanding the evolutionary dynamics of IBV and developing more effective prevention and control strategies.

This research investigates the dynamics of smoke dispersion in a subway train carriage with multiple lateral openings within a ventilated subway tunnel. Numerous extensive full-scale numerical simulations were conducted to analyze the thermal plume distribution within multiple lateral openings of a train carriage, and the longitudinal and transverse maximum excess ceiling temperature. The results reveal that the heat release rates have a greater impact on the airflow in the carriage than velocities ,even when the longitudinal ventilation velocity reaches 8 m/s or the heat release rate reaches 15 MW. The multiple lateral openings cause significant differences in smoke flow characteristics compared to tunnels with both ends open. Additionally, the transverse maximum ceiling excess temperature inclines towards the lateral opening side due to asymmetrical air entrainment. The analysis of longitudinal maximum ceiling excess temperature identified two regions based on the dimensionless heat release rate, showing a linear increase followed by a constant phase dependent on the heat release rate, with a maximum longitudinal excess gas temperature of 1242 K. Additionally, a relationship between the dimensionless heat release rate and the transverse dimensionless maximum ceiling excess temperature was established. This study can be used as a guide for smoke exhaust mitigation and fire safety measures in the event of subway train carriage fires.

As an essential component of the fungal cell wall, β-1,6-glucan has an important role in the growth and development of fungi, but its distribution has not been investigated in Magnaporthe oryzae. Here, a novel β-1,6-glucanase from M. oryzae, MoGlu16, was cloned and expressed in Pichia pastoris. The enzyme was highly active on pustulan, with a specific activity of 219.0 U/mg at pH 5.0 and 50°C, and showed great selectivity for continuous β-1,6-glycosidic bonding polysaccharides. Based on this, β-1,6-glucan was selectively visualized in the vegetative hyphae, conidia and bud tubes of M. oryzae using a hydrolytically inactive GFP-tagged MoGlu16 with point mutations at the catalytic position (His-MoGlu16E236A-Gfp). The spore germination and appressorium formation were significantly inhibited after incubation of 105/ml conidia with 0.03 μg/μl MoGlu16. Mycelia treated with MoGlu16 produced reactive oxygen species and triggered the cell wall integrity pathway, increasing the expression levels of genes involved in cell wall polysaccharide synthesis. These results revealed that MoGlu16 participated in the remodeling of cell wall in M. oryzae, laying a foundation for the analysis of cell wall structure.

Purpose: As the most common subset of breast cancer (BC), estrogen receptor positive (ER+) BC accounting for 80% of cases, has become a global public health concern. The female hormone estrogen (E2) unequivocally drives ER + breast malignancies. The reasons that estrogen affects BC development has long been considered, yet further study remains to be conducted of the molecular events in the E2-estrogen receptor α (ERα) signaling pathway in ER + BC progression, especially lipid metabolism, so providing more options for tailored and individualized therapy. Our aim is to find out new targets and clinical biomarkers for ER + breast cancer treatment from the perspective of lipid metabolism. Methods: Lipid metabolomics profiling was used to examine the membrane phospholipid stimulated by E2. Clinical BC samples were used to assess the association of CYP4F2, CYP4F11 expression with clinicopathological characteristics and patient outcomes. Some inhibitors of main enzymes in AA metabolism were used combined with E2 to assess roles of CYP4F2/CYP4F11 in the progression of ER + BC. CYP4F2, CYP4F11 overexpression and knockdown BC cell lines were employed to examine the effects of CYP4F2, CYP4F11 on cellular proliferation, apoptosis and tumor growth. Western blotting, qPCR, Immunohistochemical staining and flow cytometry were also conducted to determine the underlying mechanisms related to CYP4F2, CYP4F11 function. Results: The activation of the CYP450 signaling pathway in arachidonic acid metabolism contributed to ER + BC tumorigenesis. In ER + BC, CYP4F2 and CYP4F11 overexpression induced by E2 could promote cancer cell proliferation and resistance to apoptosis by producing the metabolite 20-HETE and activating the antiapoptotic protein Bcl-2. CYP4F2 and CYP4F11 elevation correlates with poorer overall survival and disease-free survival in ER + BC patients. Conclusion: CYP4F2, CYP4F11 and their metabolite 20-HETE could serve as effective prognostic markers and attractive therapeutic targets for novel anticancer drug development about ER + BC.

Background: The policy of merging remote rural elementary schools into centralized villages has led to the emergence of boarding schools as an essential means of providing compulsory education in rural areas of China. As boarding children reside in schools for extended periods, parents' influence on their human capital development is inevitably specificity. The development of rural boarding children is a serious social issue in China, and parent–child distance plays a crucial role in affecting the development of children's human capital. Objective: While previous studies have focused on the relationship between parental absence and the development of human capital in rural boarding children, this study examines the effects of both spatial and emotional distance between parents and children on the human capital of rural boarding children. Participants and setting: A stratified, multi-stage probabilities proportional to size (PPS) sampling method was used, and self-report questionnaires were completed by 2397 rural boarding children (54.2 % males; ages 12 to 18, M = 14.66, SD = 1.30). Methods: Children's background, family, and school and teacher characteristics were used as control variables. An OLS regression model was used to assess the effects of parent–child spatial and emotional distance on the human capital of rural boarding children, and a CMP–OLS regression model was used to address endogeneity using parents' self-assessed family economic conditions as instrumental variables. Results: Parent–child spatial distance had a significant positive effect (p

The airtightness of heated tobacco product (HTP) packs is a very important indicator for the product quality and is also of great importance during the conditioning process. A method for evaluation of the airtightness was developed based on the air pressure difference in a constant pumping configuration. The essential feature of this method is that the pressure difference between the inside and the outside of the HTP packs during the deflation process is used to characterize the sealing quality of HTP packs. The detailed setup, the principle as well as the determination procedure are described. The accuracy and the repeatability of the method were assessed, and the effect of airtightness on the conditioning process was also investigated. The developed method is proven to be reliable with a standard deviation less than 0.09 kPa and repeatability less than 0.30 kPa. In addition, it was found that, although the transmission of moisture between HTPs and atmosphere could not be entirely prevented by the packs, airtightness still plays a significant role during the conditioning process, especially if the airtightness was at a relatively low level (e.g., lower than 1.5 kPa under a pumping flow rate of 200 mL/min). The method provides a promising way to assess and monitor the sealing quality of HTP packs, and it is suggested that the airtightness of the pack should not be lower than 2 kPa under a pumping flow rate of 200 mL/min. [Contrib. Tob. Nicotine Res. 32 (2023) 140–145]

Microbial communities within oxygen minimum zones (OMZs) play crucial roles in the marine biogeochemical cycling. Arabian Sea (AS) has one of the largest OMZs among the global oceans, however, knowledge about the microbial ecology of the AS OMZ remained limited. In the present study, 44 water samples collected from six stations across the AS, spanning from the deep chlorophyll maximum (DCM) layer to 4000m depth were analyzed. High-throughput sequencing of 16S rRNA genes revealed the structural diversity of bacterial and archaeal communities, influenced primarily by depth and dissolved oxygen (DO) levels. Distinct community compositions were observed across different oxygen gradients, with shifts in the relative abundance of key taxa. Notably, Desulfosarcinaceae, UBA10353, Nitrospina, SUP05, Sva0996_marine_group, Microtrichaceae, and Nitrosopumilus emerged as bioindicator taxa in the AS hypoxic zones. Co-occurrence network analysis identified SAR324, Alteromonadaceae, and Sphingomonadaceae as keystone taxa. The spatial and depth-wise distribution patterns revealed that Desulfosarcinaceae was predominantly found in the hypoxic zones of the Arabian Sea, whereas UBA10353, Nitrospina, SUP05, Microtrichaceae and SAR324 were ubiquitous across AS, Bay of Bengal (BOB), and Eastern Tropical North Pacific (ETNP) OMZs, with OTU-level niche differentiation observed for the latter two. Functional profiling using FAPROTAX predicted higher metabolic potential for nitrogen and sulfur in the OMZ compared to other layers of the AS. Our findings provide valuable insights into the distribution, structure, and diversity of microbial communities in the AS OMZ, highlighting the ecological roles of key taxa in hypoxic environments. The established sequence database offers a foundation for further research into the complex interactions within these microbial ecosystems.

Objective: To achieve rapid, quantitative and high-throughput detection of aminoglycoside antibiotic residues in pork. Methods: Square-array aligned SERS substrates based on Au nanoflowers （AuNFs） were prepared using PP synthetic paper as a substrate. Pork samples were pre-treated by QuEChERs method and subjected to SRES. Results: Using 4-mercaptobenzoic acid as the SERS probe molecule, the substrate exhibited good homogeneity, SERS enhancement effect, reproducibility and stability. the SERS signal intensities at the characteristic peaks at 475, 619 cm-1 showed good linear relationships with the logarithms of the concentrations of gentamicin sulphate and neomycin sulphate, respectively （R2 of 0.991 6 and 0.990 7, respectively）. The limits of detections （LODs） were as low as 1×10-9, 1×10-8 mol/L, respectively, and were successfully applied to the rapid, quantitative and high-throughput determination of aminoglycoside antibiotics in pork. Conclusion: The experimental method provides an economical, efficient, time-saving and highly sensitive way for the application of SERS technology for the detection of antibiotic residues in real meat samples.

ObjectiveThis study was conducted to explore the risk factors for the prognosis and recurrence of ureteropelvic junction obstruction (UPJO).MethodsThe correlation of these variables with the prognosis and recurrence risks was analyzed by binary and multivariate logistic regression. Besides, a nomogram was constructed based on the multivariate logistic regression calculation. After the model was verified by the C-statistic, the ROC curve was plotted to evaluate the sensitivity of the model. Finally, the decision curve analysis (DCA) was conducted to estimate the clinical benefits and losses of intervention measures under a series of risk thresholds.ResultsPreoperative automated peritoneal dialysis (APD), preoperative urinary tract infection (UTI), preoperative renal parenchymal thickness (RPT), Mayo adhesive probability (MAP) score, and surgeon proficiency were the high-risk factors for the prognosis and recurrence of UPJO. In addition, a nomogram was constructed based on the above 5 variables. The area under the curve (AUC) was 0.8831 after self cross-validation, which validated that the specificity of the model was favorable.ConclusionThe column chart constructed by five factors has good predictive ability for the prognosis and recurrence of UPJO, which may provide more reasonable guidance for the clinical diagnosis and treatment of this disease.

ABSTRACT: Excessive corticosterone (CORT) exposure could cause hepatic cholesterol accumulation in chickens and maternal betaine supplementation could decrease hepatic cholesterol deposition through epigenetic modifications in offspring chickens. Nevertheless, it remains uncertain whether providing betaine to laying hens could protect CORT-induced hepatic cholesterol accumulation via epigenetic mechanisms. This study aimed to examine the effects of dietary betaine on plasma and hepatic cholesterol contents, expression of cholesterol metabolic genes, as well as DNA methylation on their promoters in the liver of laying hens exposed to CORT. A total of 72 laying hens at 130 d of age were randomly divided into 3 groups: control (CON), CORT, and CORT+betaine (CORT+BET) groups. The experiment lasted for 35 d. Chickens in CON and CORT groups were fed a basal diet, whereas the CORT+BET group chickens were fed the basal diet supplemented with 0.1% betaine for 35 d. On d 28 of the experiment, chickens in CORT and CORT+BET groups received daily subcutaneous injections of CORT (4.0 mg/kg body weight), whereas the CON group chickens were injected with an equal volume of solvent for 7 d. The results showed that CORT administration led to a significant increase (P < 0.05) in the contents of cholesterol in plasma and liver, associated with activation (P < 0.05) of sterol regulatory element binding transcription factor 2 (SREBP2), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), lecithin-cholesterol acyltransferase (LCAT) and low-density lipoprotein receptor (LDLR) genes expression, and inhibition of cholesterol-7-alpha hydroxylase (CYP7A1) and sterol 27-hydroxylase (CYP27A1) genes expression in the liver compared to the CON. In contrast, CORT-induced up-regulation of HMGCR mRNA and protein abundances and downregulation of CYP7A1 mRNA and protein abundances were completely normalized (P < 0.05) by betaine supplementation. Besides, CORT injection led to significant hypomethylation (P < 0.05) on HMGCR promoter and hypermethylation (P < 0.05) on CYP7A1 promoter. Moreover, dietary betaine rescued (P < 0.05) CORT-induced changes in methylation status of HMGCR and CYP7A1 genes promoters. These results indicate that dietary betaine addition protects laying hens from CORT-induced hepatic cholesterol accumulation via epigenetic modulation of HMGCR and CYP7A1 genes.

Magnesium-based materials not only exhibit desirable characteristics such as low density and high specific strength, but also possess exceptional functional properties, including high damping capacity, high thermal conductivity, high electromagnetic interference shielding capacity, flame retardancy, and dissolvability. However, achieving a balance between strength and functional properties remains a significant challenge in Mg alloys community. Typically, strength depends on the pinning effect of defects, such as solute atoms and second phases, which hinder dislocation motion. On the other hand, optimal functional properties usually necessitate relative perfect crystal structures, as the presence of solute atoms and second phases can have adverse effects on damping capacity and thermal conductivity. Balancing these conflicting requirements is difficult. The trade-off between strength and functional properties of the Mg alloys should be broken to meet the urgent need in aerospace, automotive, 3C (computers, communications, and consumer electronics) and energy industries for high performance structural-functional integrated Mg-based materials. This review summarizes recent progress in understanding the mechanisms and influencing factors for the functional properties of Mg alloys. The mechanisms underlying the trade-off between strength and functional properties of Mg alloys is discussed. The latest developed structural-functional integrated Mg alloys and their composites are summarized, including high strength Mg-based materials with high damping capacity / high thermal conductivity / strong electromagnetic shielding capability / excellent flame-resistance / high dissolution rate. The future works of developing structure-function integrated Mg-based materials are proposed.

Raman scattering is an inelastic light scattering that occurs in a manner reflective of the molecular vibrations of molecular structures and chemical conditions in a given sample of interest. Energy changes in the scattered light can be assessed to determine the vibration mode and associated molecular and chemical conditions within the sample, providing a molecular fingerprint suitable for sample identification and characterization. Raman spectroscopy represents a particularly promising approach to the molecular analysis of many diseases owing to clinical advantages including its instantaneous nature and associated high degree of stability, as well as its ability to yield signal outputs corresponding to a single molecule type without any interference from other molecules as a result of its narrow peak width. This technology is thus ideally suited to the simultaneous assessment of multiple analytes. Neurodegenerative diseases represent an increasingly significant threat to global public health owing to progressive population aging, imposing a severe physical and social burden on affected patients who tend to develop cognitive and/or motor deficits beginning between the ages of 50 and 70. Owing to a relatively limited understanding of the etiological basis for these diseases, treatments are lacking for the most common neurodegenerative diseases, which include Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. The present review was formulated with the goal of briefly explaining the principle of Raman spectroscopy and discussing its potential applications in the diagnosis and evaluation of neurodegenerative diseases, with a particular emphasis on the research prospects of this novel technological platform.

Propylene glycol (PG) and vegetable glycerin (VG) are the most common solvents used in electronic cigarette liquids. No long-term inhalation toxicity assessments have been performed combining conventional and multi-omics approaches on the potential respiratory effects of the solvents in vivo. In this study, the systemic toxicity of aerosol generated from a ceramic heating coil-based e-cigarette was evaluated. First, the aerosol properties were characterized, including carbonyl emissions, the particle size distribution, and aerosol temperatures. To determine toxicological effects, rats were exposed, through their nose only, to filtered air or a propylene glycol (PG)/ glycerin (VG) (50:50, %W/W) aerosol mixture at the target concentration of 3 mg/L for six hours daily over a continuous 28-day period. Compared with the air group, female rats in the PG/VG group exhibited significantly lower body weights during both the exposure period and recovery period, and this was linked to a reduced food intake. Male rats in the PG/VG group also experienced a significant decline in body weight during the exposure period. Importantly, rats exposed to the PG/VG aerosol showed only minimal biological effects compared to those with only air exposure, with no signs of toxicity. Moreover, the transcriptomic, proteomic, and metabolomic analyses of the rat lung tissues following aerosol exposure revealed a series of candidate pathways linking aerosol inhalation to altered lung functions, especially the inflammatory response and disease. Dysregulated pathways of arachidonic acids, the neuroactive ligand-receptor interaction, and the hematopoietic cell lineage were revealed through integrated multi-omics analysis. Therefore, our integrated multi-omics approach offers novel systemic insights and early evidence of environmental-related health hazards associated with an e-cigarette aerosol using two carrier solvents in a rat model.

Research on the flexible hybrid epidermal electronic system (FHEES) has attracted considerable attention due to its potential applications in human–machine interaction and healthcare. Through material and structural innovations, FHEES combines the advantages of traditional stiff electronic devices and flexible electronic technology, enabling it to be worn conformally on the skin while retaining complex system functionality. FHEESs use multimodal sensing to enhance the identification accuracy of the wearer’s motion modes, intentions, or health status, thus realizing more comprehensive physiological signal acquisition. However, the heterogeneous integration of soft and stiff components makes balancing comfort and performance in designing and implementing multimodal FHEESs challenging. Herein, multimodal FHEESs are first introduced in 2 types based on their different system structure: all-in-one and assembled, reflecting totally different heterogeneous integration strategies. Characteristics and the key design issues (such as interconnect design, interface strategy, substrate selection, etc.) of the 2 multimodal FHEESs are emphasized. Besides, the applications and advantages of the 2 multimodal FHEESs in recent research have been presented, with a focus on the control and medical fields. Finally, the prospects and challenges of the multimodal FHEES are discussed.

Abstract The exponentially increasing heat generation in electronic devices, induced by high power density and miniaturization, has become a dominant issue that affects carbon footprint, cost, performance, reliability, and lifespan. Liquid metals (LMs) with high thermal conductivity are promising candidates for effective thermal management yet are facing pump‐out and surface‐spreading issues. Confinement in the form of metallic particles can address these problems, but apparent alloying processes elevate the LM melting point, leading to severely deteriorated stability. Here, we propose a facile and sustainable approach to address these challenges by using a biogenic supramolecular network as an effective diffusion barrier at copper particle‐LM (EGaIn/Cu@TA) interfaces to achieve superior thermal conduction. The supramolecular network promotes LM stability by reducing unfavorable alloying and fluidity transition. The EGaIn/Cu@TA exhibits a record‐high metallic‐mediated thermal conductivity (66.1 W m−1 K−1) and fluidic stability. Moreover, mechanistic studies suggest the enhanced heat flow path after the incorporation of copper particles, generating heat dissipation suitable for computer central processing units, exceeding that of commercial silicone. Our results highlight the prospects of renewable macromolecules isolated from biomass for the rational design of nanointerfaces based on metallic particles and LM, paving a new and sustainable avenue for high‐performance thermal management.

With the continuous development of the pharmaceutical industry, people have always paid attention to the safety and effectiveness of drugs, including innovative drugs and generic drugs. For pharmaceutical companies as manufacturers, drug development is a very lengthy process that requires high costs, millions of man-hours, thousands of trials, and the mobilization of hundreds of researchers. Therefore, efforts need to be made to develop drugs with high safety and effectiveness. Drug research and development plays an important role today. Based on this, this article applied computer molecular simulation embedded technology and artificial intelligence technology to drug research and development. First, the problems faced in the research and development of anti-inflammatory disease-dependent tumor drugs were introduced, and then the applications of computer molecular simulation embedded technology and artificial intelligence technology in drug research and development were analyzed. Subsequently, the application of artificial intelligence in drug research and development teaching was analyzed, and a teaching system based on computer molecular simulation embedded technology and artificial intelligence was designed. Finally, the application effects of computer molecular simulation embedded technology and artificial intelligence technology were analyzed, and a feasible conclusion was drawn. The use of computer molecular simulation embedded technology and artificial intelligence technology can greatly improve the efficiency of drug research and development, and the research and development safety of imatinib mesylate has been improved by 7%. On the other hand, it can improve students’ learning interest and stimulate their learning interest, and students’ drug research and development capabilities have been improved. Drug research and development for inflammatory-dependent tumors has good application prospects.

Abstract Natural medicines plants are significant considerable attention as potential therapeutic agents for bone tissue engineering. Cissus quadrangularis L (CQ). is a potent therapeutic plant known for its own osteogenic properties. In this research work, a phytoconstituents-filled composite was produced by incorporating CQ extract with gelatin (Gel) and pectin (Pec) polymers collective through β- tricalcium phosphate (β-TCP) bioceramic via a green template method. The effect of CQ-filled composite morphology and chemical structural properties, in vitro cytotoxicity, cell proliferation, and differentiation was investigated. FTIR spectroscopic results indicated the prepared materials’ structural confirmation. The CQ extract was the alcoholic -OH merge with the hydroxyl and -NH groups in the range of 3000 cm−1 to 3500 cm−1. Scanning electron microscopy images showed that the β-TCP ceramic was perfectly embedded in Gel-Pec polymeric matrix, which is important for bone regeneration. In vitro cell culture results indicated that β-TCP/Gel-Pec/CQ composite provided 92.0% of a favorable substrate for mesenchymal stem cell viability. The gene expression and RT-PCR studies represent the materials with good osteogenic expression, especially the β-TCP/Gel-Pec/CQ composite is observed at 168.0% and 188.0% for RUNx2 and OCN, respectively. The result of the physicochemical characterizations and cell viability studies suggest that CQ-loaded β-TCP/Gel-Pec composite can serve as a potential biomaterial for bone tissue repair and regeneration. Graphical Abstract

Agricultural chemicals with multifunctional applications in crop protection have attracted increasing attention. Herein, two new series of thiazole and imidazo[1,2-a]pyridine derivatives containing a hydrazone substructure were designed and synthesized via a concise synthesis route. Bioassay results showed that most of the thiazole derivatives exhibited broad-spectrum fungistatic activities, which were exemplified by compounds 1c, 1e, 1g, 1h and 1j. In particular, compound 1e displayed excellent in vitro inhibitory effects with the EC50 values of 5.00, 18.24, 6.94, and 3.03 μg/mL against the fungi Botrytis cinerea, Cytospora sp, Fusarium graminearum, and Fusarium solani, respectively. Detached fruit experiments against tomato gray mold (caused by B. cinerea) in vivo revealed that the control efficiency of compound 1e at 10, 20 and 40 μg/mL for 5 days was 35.05%, 54.14% and 81.83%, respectively, which was comparable and even superior to that of the fungicide carbendazim. Additionally, the title compounds also showed remarkable larvicidal activity against M. separata and some compounds exhibited good aphicidal activity. In a word, the bioassay indicated that a certain number of title compounds had multiple biological activities. Given their excellent antifungal and larvicidal characteristics, these interesting derivatives based on the title compounds could be served as new scaffolds for the development of pesticide with multifunctional applications.

Soils play a dominant role in supporting the survival and growth of crops and they are also extremely important for human health and food safety. At present, the contamination of soil by heavy metals remains a globally concerning environmental issue that needs to be resolved. In the environment, iron plaque, naturally occurring on the root surface of wetland plants, is found to be equipped with an excellent ability at blocking the migration of heavy metals from soils to plants, which can be further developed as an environmentally friendly strategy for soil remediation to ensure food security. Because of its large surface-to-volume porous structure, iron plaque exhibits high binding affinity to heavy metals. Moreover, iron plaque can be seen as a reservoir to store nutrients to support the growth of plants. In this review, the formation process of iron plaque, the ecological role that iron plaque plays in the environment and the interaction between iron plaque, plants and microbes, are summarized.

In the context of a burgeoning knowledge economy, enterprise intellectual capital has emerged as a pivotal asset for organizational growth. Evaluating it requires a comprehensive and robust index, yet there is no standard methodology for such assessments. Here, we propose an index for evaluating enterprise intellectual capital. We use the Delphi method to delineate a scientific decision structure. A grey-based decision-making trial and evaluation laboratory (DEMATEL) is coupled with an analytic network process (ANP)—i.e., grey DEMATEL-based ANP (GDANP)—to determine the relative weight of indicators. Then, we use the technique for order preference by similarity to an ideal solution to validate the effectiveness and applicability of the proposed evaluation index based on data on thirty new-technology companies in China. This study bridges a critical gap in academic discourse, and we discuss the practical implications for the strategic management of intellectual capital in corporate settings.

Abstract Background ABO blood groups has been associated with risk of several cancers; however, the results for an association with ovarian cancer are inconsistent and little is known about the expression of histo‐blood group (ABH) antigens and ABO gene in ovarian tumor tissues. Methods To assess the impact of genotype‐derived ABO blood types on the risk of EOC, we conducted a case–control study in 1,870 EOC and 4,829 controls. Expression of A and B antigen in 70 pairs of ovarian tumor tissues and adjacent normal tissues were detected by immunohistochemistry. Gene expression and DNA methylation profiling was conducted in ovarian tumor tissues. Results We identified that blood group A was associated with increased risk for EOC compared to blood group O (OR = 1.18, 95% CI = 1.03–1.36, p = 0.019). Increased frequency of aberrant expression of histo‐blood group antigens was observed in patients with blood group A (76.5%) compared to patients with blood group O (21.1%) and B (5.0%) by immunohistochemistry (p

BackgroundAs a severe hematological malignancy in adults, acute myeloid leukemia (AML) is characterized by high heterogeneity and complexity. Emerging evidence highlights the importance of the tumor immune microenvironment and lipid metabolism in cancer progression. In this study, we comprehensively evaluated the expression profiles of genes related to lipid metabolism and immune modifications to develop a prognostic risk signature for AML.MethodsFirst, we extracted the mRNA expression profiles of bone marrow samples from an AML cohort from The Cancer Genome Atlas database and employed Cox regression analysis to select prognostic hub genes associated with lipid metabolism and immunity. We then constructed a prognostic signature with hub genes significantly related to survival and validated the stability and robustness of the prognostic signature using three external datasets. Gene Set Enrichment Analysis was implemented to explore the underlying biological pathways related to the risk signature. Finally, the correlation between signature, immunity, and drug sensitivity was explored.ResultsEight genes were identified from the analysis and verified in the clinical samples, including APOBEC3C, MSMO1, ATP13A2, SMPDL3B, PLA2G4A, TNFSF15, IL2RA, and HGF, to develop a risk-scoring model that effectively stratified patients with AML into low- and high-risk groups, demonstrating significant differences in survival time. The risk signature was negatively related to immune cell infiltration. Samples with AML in the low-risk group, as defined by the risk signature, were more likely to be responsive to immunotherapy, whereas those at high risk responded better to specific targeted drugs.ConclusionsThis study reveals the significant role of lipid metabolism- and immune-related genes in prognosis and demonstrated the utility of these signature genes as reliable bioinformatic indicators for predicting survival in patients with AML. The risk-scoring model based on these prognostic signature genes holds promise as a valuable tool for individualized treatment decision-making, providing valuable insights for improving patient prognosis and treatment outcomes in AML.

IntroductionLaser interstitial thermal therapy (LITT) at 1064 nm is widely used to treat epilepsy and brain tumors; however, no numerical model exists that can predict the ablation region with careful in vivo validation.MethodsIn this study, we proposed a model with a system of finite element methods simulating heat transfer inside the brain tissue, radiative transfer from the applicator into the brain tissue, and a model for tissue damage.ResultsTo speed up the computation for practical applications, we also validated P1-approximation as an efficient and fast method for calculating radiative transfer by comparing it with Monte Carlo simulation. Finally, we validated the proposed numerical model in vivo on six healthy canines and eight human patients with epilepsy and found strong agreement between the predicted temperature profile and ablation area and the magnetic resonance imaging-measured results.DiscussionOur results demonstrate the feasibility and reliability of the model in predicting the ablation area of 1,064 nm LITT, which is important for presurgical planning when using LITT.

The Beibu Gulf (Gulf of Tonkin, Vinh Bac Bo in Vietnamese), located midway along the East Asian-Australasian Flyway (EAAF), is a critical stopover and wintering region for migratory waterbirds. This transboundary coastal region, spanning between China and Vietnam, harbors diverse wetland habitats that provide refuge to waterbird species, including highly threatened species such as the spoon-billed sandpiper (CR) and the black-faced spoonbill (EN). However, the scarcity of comprehensive assessments regarding waterbird abundances, distribution, key wetland habitats, and regional threats hinders our understanding of its conservation significance at the flyway level. Further research is needed to address these knowledge gaps and facilitate effective conservation efforts in the Beibu Gulf. By synthesizing accessible citizen science datasets and published records from wetland sites in south China and northeast Vietnam, we concluded that at least 97 waterbird species used the Gulf’s wetlands during their annual cycle. Among surveys conducted from 2014 to 2022, 5 and 11 waterbird species were considered as first and second class protected species under the National Key Protected Wild Animal List in China; 2 species were listed as Critically Endangered on the IUCN Red List, 4 as Endangered and 2 as Vulnerable, underlying the critical importance of the Beibu Gulf for the survival of these species. Our study identified 25 sites in the Beibu Gulf that met the criteria for designation as internationally important wetlands. Alarmingly, less than a quarter (n = 5, or 20%) of these sites benefit from national or international protection. Localized threats, including aquatic resource harvesting, hunting, and aquaculture/fisheries, were widespread in the region. This study provides a crucial scientific baseline for continued waterbird monitoring, site prioritization, and the development of effective habitat management plans to conserve vital coastal wetland habitats in the Beibu Gulf in China and Vietnam.

The value of power data credit reporting in the social credit system continues to increase, and the government, users and the whole society have deep expectations and support for power data credit reporting. This paper will combine the data labeling theory as the support, define the power data label and explain its labeling implementation. Based on the construction of knowledge graph, the method of labeling power data is introduced in detail: demand analysis method, index selection method, data cleaning method and data desensitization method. Use the sorted data labels to establish a label system for power data, and through its system, visualize the comprehensive situation of enterprise power data credit information to meet the development of power data credit business. This paper takes shell enterprises as the main representatives of credit risk enterprises, analyzes the power data in the three stages before and after loans, and builds a value mining model for power credit data. In the future, the data labeling technology and value mining model of the power data credit business will be comprehensively applied, and the power data label library and credit model library will be established and continuously improved, so as to facilitate the evaluation of the operation of the enterprise at different stages.

TRPCs, nonselective cation channels, are involved in cardiac contraction and conduction. Here, the authors show that Trpc1/6 deficiency or pharmacological inhibition improves endotoxemic cardiac dysfunction and prolongs survival by prominently suppressing cardiac inflammation and ER Ca2+ release.

E2-Spy (abbreviated as ES) plays a vital role as a component in the Bacterial-Like Particles (BLPs) vaccine against classical swine fever virus (CSFV). This vaccine demonstrates remarkable immunoprotection, highlighting the importance of augmenting ES production in the development of CSFV subunit vaccines. In this study, a Pichia pastoris strain capable of high-yield secretory production of ES was developed through signal peptide engineering, gene dosage optimization and co-expression of molecular chaperones. Initially, a hybrid signal peptide cSP3 was engineered, leading to a 3.38-fold increase in ES production when compared to the control strain 1-α-ES. Subsequently, cSP3 was evaluated for its expression efficiency alongside different commonly used signal peptides under multicopy conditions. SDS-PAGE analysis revealed that 2-αd14-ES exhibited the highest ES production, displaying a 4.38-fold increase in comparison to 1-α-ES. Afterwards, SSA1, YDJ1, BIP, LHS1, and their combinations were integrated into 2-αd14-ES, resulting in a 1.92-fold rise in ES production compared to 2-αd14-ES (equivalent to a 6.18-fold increase compared to 1-α-ES). The final yield of ES was evaluated as 168.3 mg/L through comparison with serially diluted BSA protein bands.

At present, there is a research gap concerning the specific functions and mechanisms of the Notch gene family and its signaling pathway in jawless vertebrates. In this study, we identified a Notch1 homologue (Lr. Notch1) in the Lethenteron reissneri database. Through bioinformatics analysis, we identified Lr. Notch1 as the likely common ancestor gene of the Notch gene family in higher vertebrates, indicating a high degree of conservation in the Notch gene family and its signaling pathways. To validate the biological function of Lr. Notch1, we conducted targeted silencing of Lr. Notch1 in L. reissneri and analyzed the resultant gene expression profile before and after silencing using transcriptome analysis. Our findings revealed that the silencing of Lr. Notch1 resulted in differential expression of pathways and genes associated with signal transduction, immune regulation, and metabolic regulation, mirroring the biological function of the Notch signaling pathway in higher vertebrates. This article systematically elucidated the origin and evolution of the Notch gene family while also validating the biological function of Lr. Notch1. These insights offer valuable clues for understanding the evolution of the Notch signaling pathway and establish a foundation for future research on the origin of the Notch signaling pathway, as well as its implications in human diseases and immunomodulation.

In recent years, nanobodies have played an increasingly crucial role in virus neutralization, ELISA detection, and medical imaging. This study aimed to explore a universal expression strategy in Pichia pastoris using three nanobodies, denoted Va, Vb, and Vc, as model proteins. Initially, plasmids pLD-AOXα and pLD-AOX were engineered to minimize the risk of antibiotic resistance gene drift. Optimization of promoters and signal peptides resulted in a 1.38-fold and 1.89-fold increase in Va production. Further optimization of gene dosage led to an additional 1.39-fold enhancement in Va yield. Subsequently, 25 molecular chaperones were co-expressed with Va under the control of the wild-type AOX1 promoter, with HAC1 further increasing Va yield by 1.5-fold. By fine-tuning the promoter strength for HAC1, Va production was increased by 2.41-fold under the control of the 55p promoter. Finally, through high-density fermentation, the Va yield reached 2.13 g/L, representing a 49.8-fold increase compared to the initial strain 1-AOXα-Va in shake-flask culture. Integration of pLD-55p-HAC1 into the GS115 genome resulted in the H55 host, and the transformation of multicopy plasmids into this host led to a 1.98-fold increase in Vb yield and a 2.34-fold increase in Vc yield, respectively. The engineering of antibiotic-free parental plasmids, modification of expression components, gene dosage optimization, and the H55 host are regarded as a composite strategy which will pave the way for efficient expression of nanobodies in the future.

In many applications, data streams are indispensable to describe the relationships between nodes in networks, such as social networks, computer networks, and hyperlink networks. Fundamentally, a graph stream is a dynamic representation of a graph, which is usually composed of a sequence of edges, where each edge is represented by two endpoints and a weight. As a result of its large volume and highly dynamic nature, several graph sketches were proposed for the purposes of summarizing large-scale graph streams and enabling fast query processing. By using a compact data structure with hash functions, the graph sketches sequentially store the edges. Nevertheless, the existing graph sketches suffer from low performance on graph query tasks as a result of unpredictable collisions between heavy edges and light edges. To store heavy edges and light edges, this paper introduces a novel learning-based Dichotomy Graph Sketch (DGS) mechanism that uses two separate graph sketches, a heavy sketch and a light sketch. During a graph stream session, DGS obtains heavy edges and light edges, and uses these edges as training samples for a deep neural network (DNN) based binary classifier. The DNN-based classifier is then used to determine whether the upcoming edges are heavy or not. We will store the edges that are classified as heavy edges in the heavy sketch, and those that are classified as light edges in the light sketch. By combining the learnable classifier and Dichotomy Graph Sketches, the proposed mechanism resolves the hashing collision problem in conventional graph sketches and significantly improves graph query accuracy. The DGS algorithm outperforms the state-of-the-art graph sketches in a variety of graph query tasks based on extensive experiments that were conducted on four real-world graph stream datasets.

Alarm systems are commonly deployed in complex industries to monitor the operation status of the production process in real time. Actual alarm systems generally have alarm overloading problems. One of the major factors leading to excessive alarms is the presence of many correlated or redundant alarms. Analyzing alarm correlations will not only be beneficial to the detection of and reduction in redundant alarm configurations, but also help to track the propagation of abnormalities among alarm variables. As a special problem in correlated alarm detection, the research on first-out alarm detection is very scarce. A first-out alarm is known as the first alarm that occurs in a series of alarms. Detection of first-out alarms aims at identifying the first alarm occurrence from a large number of alarms, thus ignoring the subsequent correlated alarms to effectively reduce the number of alarms and prevent alarm overloading. Accordingly, this paper proposes a new first-out alarm detection method based on association rule mining and correlation analysis. The contributions lie in the following aspects: (1) An association rule mining approach is presented to extract alarm association rules from historical sequences based on the FP-Growth algorithm and J-Measure; (2) a first-out alarm determination strategy is proposed to determine the first-out alarms and subsequent alarms through correlation analysis in the form of a hypothesis test on conditional probability; and (3) first-out rule screening criteria are proposed to judge whether the rules are redundant or not and then consolidated results of first-out rules are obtained. The effectiveness of the proposed method is tested based on the alarm data generated by a public simulation platform.

In this study, we introduce an arthroscopic acromioplasty technique based on original bony landmarks, namely biplanar acromioplasty. This technique focuses on smoothing both the coronal and transverse plane of acromion, corresponding to the anterior and inferior acromial surface, and restores the acromion to its original shape. We believe this technique is effective, time-saving, and reproducible.

Three rat sarcoma (RAS) gene isoforms, KRAS, NRAS, and HRAS, constitute the most mutated family of small GTPases in cancer. While the development of targeted immunotherapies has led to a substantial improvement in the overall survival of patients with non-KRAS-mutant cancer, patients with RAS-mutant cancers have an overall poorer prognosis owing to the high aggressiveness of RAS-mutant tumors. KRAS mutations are strongly implicated in lung, pancreatic, and colorectal cancers. However, RAS mutations exhibit diverse patterns of isoforms, substitutions, and positions in different types of cancers. Despite being considered “undruggable”, recent advances in the use of allele-specific covalent inhibitors against the most common mutant form of RAS in non-small-cell lung cancer have led to the development of effective pharmacological interventions against RAS-mutant cancer. Sotorasib (AMG510) has been approved by the FDA as a second-line treatment for patients with KRAS-G12C mutant NSCLC who have received at least one prior systemic therapy. Other KRAS inhibitors are on the way to block KRAS-mutant cancers. In this review, we summarize the progress and promise of small-molecule inhibitors in clinical trials, including direct inhibitors of KRAS, pan-RAS inhibitors, inhibitors of RAS effector signaling, and immune checkpoint inhibitors or combinations with RAS inhibitors, to improve the prognosis of tumors with RAS mutations.

Renewable energy DC hydrogen production has become a new development trend. Due to the interaction between the weak damping of DC network and the negative impedance characteristics of power supply of hydrogen production, the actual available power of renewable and hydrogen energy DC interconnection system will be lower than its rated setting value. To solve this problem, this paper proposes an intelligent damping control to realize the rated power operation of hydrogen generation power source and significantly improve the hydrogen generation performance. In this paper, the nonlinear model under typical control strategies is established in order to adapt to different degrees of disturbance, and the damping controller is designed based on state feedback, including feedback control law and damping generation formula. On this basis, an intelligent method of damping control is proposed to support rapid decision-making. Finally, the intelligent damping control method is verified by simulation analysis. It realizes rated power of power supply of hydrogen production by generating only a small amount of damping power and superimposing it on the hydrogen production power.

With lower construction costs and power losses, the DC wind farm (DCWF) based on series-connected DC wind turbines (DCWT) is a potential collection scheme for large-scale offshore wind power. However, energy curtailment caused by unequal wind speed exists in DCWTs and results in energy waste, weakening the advantages of DCWTs. The energy curtailment mechanism is analyzed for DCWF, where single active bridge (SAB) is used as DC/DC converter in DCWTS and a full-bridge modular multilevel converter (FB-MMC) as the receiving end converter. The linear relationship between input and output of single active bridge (SAB) is interpreted, and a novel coordinate control strategy for DCWF is proposed to solve the wind energy curtailment caused by unequal wind speed. In addition, an auxiliary control strategy for receiving end converter is proposed to reduce the loss on HVDC link. A complete DCWF is built in PSCAD/EMTDC software package, and the results show that the proposed control strategy makes DCWF can operate well without energy curtailment under unequal wind speeds.

Abstract With the aging of society and the increase in people’s concern for personal health, long-term physiological signal monitoring in daily life is in demand. In recent years, electronic skin (e-skin) for daily health monitoring applications has achieved rapid development due to its advantages in high-quality physiological signals monitoring and suitability for system integrations. Among them, the breathable e-skin has developed rapidly in recent years because it adapts to the long-term and high-comfort wear requirements of monitoring physiological signals in daily life. In this review, the recent achievements of breathable e-skins for daily physiological monitoring are systematically introduced and discussed. By dividing them into breathable e-skin electrodes, breathable e-skin sensors, and breathable e-skin systems, we sort out their design ideas, manufacturing processes, performances, and applications and show their advantages in long-term physiological signal monitoring in daily life. In addition, the development directions and challenges of the breathable e-skin are discussed and prospected.

High lignin content of tobacco stem has been addressed as a drawback for its utilization on manufacture of reconstituted tobacco sheet. Therefore, the solvothermal method using ethylene glycol was investigated for the removal of lignin from tobacco stem. It was found that the removal efficiency of ethylene glycol on tobacco stem is much lower than that achieved on wheat straw and corncob, i.e., 13.9% vs. 39.3% and 44.1%, respectively. This can be rationalized in terms of the presence of solanesol in tobacco stem, which retards the strong hydrogen bond interaction between ethylene glycol and the free hydroxyl groups present in lignin. When solanesol was eliminated by applying an n-hexane extraction procedure, 40.5% of lignin was successfully dissolved from tobacco stem. The successful removal of lignin was further confirmed by the characterizing results of SEM, FT-IR and N2-sorption. The developed method provides a promising way to attenuate the negative effects of lignin on utilization of the otherwise wasted tobacco stem for production of reconstituted tobacco sheet.

Chronic rotator cuff tears are debilitating diseases which significantly affect patients’ quality of life and pose substantial financial burden to the society. The intraoperative reparability of injured tendon and postoperative probability of tendon retear are highly associated with the quality of torn muscles, specifically, the severity of muscle atrophy and fatty infiltration. Animal models that reproduce the characteristic muscle pathology after rotator cuff injury have been developed and used to provide insight into the underlying biology and pathophysiology. In this review, we briefly summarize the current information obtained from preclinical animal studies regarding the degenerative change of cuff muscle subsequent to tendon release and/or suprascapular nerve denervation. Importantly, we focus on the potential translational therapeutic targets or agents for the prevention or reversal of muscle atrophy and fatty infiltration. While further studies are warranted to assess the safety and efficacy of novel therapies derived from these preclinical animal research, we believe that their clinical translation for the treatment of rotator cuff disorders is on the horizon. The Translational potential of this article: Novel therapeutic strategies described in this review from preclinical animal studies hold a great translational potential for preventing or reversing rotator cuff muscle pathology, while further assessments on their safety and efficacy are warranted.