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In the treatment of uterine fibroids with ultrasound-guided high-intensity focused ultrasound (HIFU), water balloons are considered to be a valuable aid for improving safety and efficiency. However, the water balloons worsen the pathway for acoustic transmission, causing degraded performance both in ultrasound therapy and in ultrasound imaging. This study was aimed at establishing a protocol to evaluate the effects of the water balloon. Simulations and experiments were carefully conducted to quantitatively investigate the effects of water ballons on the efficiency of HIFU energy delivery and on the quality of ultrasound guiding images. More specifically, HIFU-induced temperature increases in the focal region, together with spatial resolution, contrast and signal-to-noise ratio in the ultrasound guiding images, were compared under the conditions with and without the water balloon. Experiment results revealed that the use of water balloons led to decreases in temperature up to 10ºC within the focal region in some specific situations, but the quality of the guiding images was relatively less affected. The study provided knowledge on what influence the water balloon could have in ultrasound-guided HIFU treatment; it also established a practical and standardized evaluation scheme for further optimizing the water balloon, for example, its material and internal liquid compositions. This study can potentially help improve the efficiency and safety of treating uterine fibroids with ultrasound-guided HIFU systems. [ABSTRACT FROM AUTHOR]

Aims Background Methods Results Conclusions Implications for nursing practice and health policy This study aims to explore the association between the implementation of the adverse event reporting system (AERS), burnout, and job satisfaction among psychiatric nurses, with a focus on examining the mediating effect of workplace violence from patients.Many organizational and personal factors contribute to burnout and job satisfaction experienced by nurses. AERS, serving as a key component of organizational‐level quality improvement system, impacts the overall workplace wellness of nurses.A national sample of 9,744 psychiatric nurses from 41 psychiatric hospitals across 29 provinces in China participated. Burnout was measured by the Maslach Burnout Inventory. Job satisfaction was measured using the Minnesota Satisfaction Questionnaire. Workplace violence was assessed by nurses’ experience of verbal and physical violence. Multilevel linear regression analyses were carried out to examine if AERS impacts burnout and job satisfaction and to identify the mediating role of workplace violence.AERS was positively associated with job satisfaction, but negatively with burnout and workplace violence. Workplace violence exhibited a positive association with burnout and a negative association with job satisfaction. Mediation analyses indicated that the associations between AERS, burnout, and job satisfaction were mediated by workplace violence.The application of AERS is associated with a reduction in workplace violence in hospitals, which contributes to the diminished burnout and heightened job satisfaction among psychiatric nurses.The study highlights the importance of organizational efforts and mechanisms in promoting nurses’ well‐being. It is necessary for hospital management to create a safe workplace through the implementation of AERS. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) frameworks are essential for development since they offer pre-built tools and libraries that speed up and simplify the production of AI models, leveraging symmetry to save time and effort. They guarantee effective computing by modifying code for particular hardware, facilitating quicker testing and deployment. The identification of a suitable and optimal AI framework for development is a multi-criteria decision-making (MCDM) dilemma, where the considered AI frameworks for development are evaluated by considering various criteria and these criteria may have dual aspects (positive and negative). Thus, in this manuscript, we diagnosed a technique of MCDM within the bipolar fuzzy set (BFS) for identification and selection of optimal AI framework for development. In this regard, we diagnosed probability aggregation operators (AOs) within BFS, such as probability bipolar fuzzy weighted averaging (P-BFWA), probability bipolar fuzzy ordered weighted averaging (P-BFOWA), immediate probability bipolar fuzzy ordered weighted averaging (IP-BFOWA), probability bipolar fuzzy weighted geometric (P-BFWG), probability bipolar fuzzy ordered weighted geometric (P-BFOWH), and immediate probability bipolar fuzzy ordered weighted geometric (IP-BFOWG) operators. The diagnosed technique would be based on these invented probably AOs. Afterward, in this manuscript, we took a case study and obtained the optimal AI framework for development by employing the diagnosed technique of MCDM. We also investigated the comparison of the devised theory with certain prevailing theories to reveal the dominance and significance of the devised theory. [ABSTRACT FROM AUTHOR]

Background: It is imperative to develop novel therapeutics to overcome chemoresistance, a significant obstacle in the clinical management of prostate cancer (PCa) and other cancers. Methods: A phenotypic screen was performed to identify novel inhibitors of chemoresistant PCa cells. The mechanism of action of potential candidate(s) was investigated using in silico docking, and molecular and cellular assays in chemoresistant PCa cells. The in vivo efficacy was evaluated in mouse xenograft models of chemoresistant PCa. Results: Nicardipine exhibited high selectivity and potency against chemoresistant PCa cells via inducing apoptosis and cell cycle arrest. Computational, molecular, and cellular studies identified nicardipine as a putative inhibitor of embryonic ectoderm development (EED) protein, and the results are consistent with a proposed mechanism of action that nicardipine destabilised enhancer of zeste homologue 2 (EZH2) and inhibited key components of noncanonical EZH2 signalling, including transducer and activator of transcription 3, S-phase kinase-associated protein 2, ATP binding cassette B1, and survivin. As a monotherapy, nicardipine effectively inhibited the skeletal growth of chemoresistant C4-2B-TaxR tumours. As a combination regimen, nicardipine synergistically enhanced the in vivo efficacy of docetaxel against C4-2 xenografts. Conclusion: Our findings provided the first preclinical evidence supporting nicardipine as a novel EED inhibitor that has the potential to be promptly tested in PCa patients to overcome chemoresistance and improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Understanding the transformation of accumulated phosphorus (P) is vital for P management. However, previous studies are limited to a few sites in Chinese agroecosystems. In this study, to investigate the temporal-spatial differences of transformation from accumulated P to available P (determined by the Olsen method), a dataset was assembled based on 91 national long-term experimental sites across China in the recent 31 years (1988–2018). A boosted regression tree (BRT) and a structural equation model (SEM) were used to analyze the factors influencing the transformation. The results showed that the transformation from accumulated P to available P in South China (1.97 mg kg−1) was significantly higher than that in other regions (0.69–1.22 mg kg−1). Soil properties were the main driving factors with a relative contribution of 81.8%, while climate and management practices explained 7.8% and 10.4% of the variations, respectively. Furthermore, SEM analysis revealed that the soil organic matter (SOM) could positively and directly affect the transformation, whereas the soil pH, soil silt content, and P fertilizer had negative and direct effects on it. For the first time, this study analyzed the transformation from soil accumulated P to available P at a national scale and at multiple sites and quantified the contribution of the main influencing factors. These results help to predict the soil available P content across different agroecosystems based on the input amount of P fertilizer, contributing to the regional precise management of P fertilizer application. [ABSTRACT FROM AUTHOR]

Introduction: Mental health symptoms are common among health professionals and the influence of lifestyle behaviors on psychiatrists' mental health is insufficiently understood. Based on a nationwide sample, we aimed to survey the lifestyle behaviors and mental health status among psychiatrists, and to identify the co-occurrence and gender differences in lifestyle behaviors.Methods: Data were collected through an anonymous questionnaire among psychiatrists in China. Depression, Anxiety and Stress Scale - 21 (DASS-21) was used to evaluate mental health symptoms. Latent class analysis (LCA) was used to explore the co-occurrence of lifestyle behaviors. The multivariate logistic regression model was used to examine the effects of demographic and lifestyle factors.Results: 4520 psychiatrists were included in the analysis with 11.5 % of them reporting smoking, 10 % reporting alcohol misuse, 35.2 % reporting physical inactivity, and 23.1 % reporting insomnia. The prevalence of depression, anxiety and stress symptoms were 29.2 %, 34.5 %, and 12.2 %, respectively. Significant gender differences were found in smoking (P < 0.001), alcohol misuse (P < 0.001), and physical inactivity (P < 0.001), but not in insomnia. Based on these four high-risk health behaviors above, three lifestyle behavior clusters with huge gender differences were identified through the LCA. Accordingly, the unhealthy lifestyle classes, though defined differently for males and females, were significantly associated with depression, anxiety, and stress.Conclusions: The co-occurrence and significant gender differences in multiple lifestyle behaviors exist in this group, highlighting the need for gender-specific comprehensive interventions against mental health symptoms and the urgency of promoting their well-being. [ABSTRACT FROM AUTHOR]

Surgical instrument packaging defects may affect the safety of medical care and patients and waste the hospital workforce, material resources, and financial resources. This study explored the application of healthcare failure mode and effect analysis in controlling surgical instrument packaging defects. We retrospectively evaluated the packaging process of 183,642 surgical instruments packaged in our hospital during January–June 2020 using the healthcare failure mode and effect analysis. Besides, we used a decision tree model to determine the steps requiring improvement and formulate the improvement measures. We applied the improvement measures to 190,231 surgical instrument packs packaged in our hospital during July–December 2020. Based on the healthcare failure mode and effect analysis, we compared the packaging defect rates before and after adopting the improvement measures. Of the 183,642 packs selected before adopting the improvement measures, 98 defects occurred, with a defect rate of 0.053%. However, of the 190,231 packs selected after adopting the improvement measures, 22 defects occurred, with a defect rate of 0.012%. The defect rate of surgical instrument packaging handled by the central sterile supply department staff was significantly reduced (χ2 = 50.822, P = 0.001) after adopting the improvement measures. Using the medical failure mode and effect analysis method to control the defects in surgical instrument packaging can effectively reduce the packaging defect rate, ensuring patient safety. [ABSTRACT FROM AUTHOR]

Aims: This study aims to investigate the association between stressors, coping strategies and intention to leave the nursing profession among nurses. Background: Job stressors and coping strategies are believed to affect turnover intention among nurses, but no large‐scale study has been conducted on these associations in China yet. Method: A cross‐sectional secondary analysis was conducted among 51,406 nurses from 1858 hospitals. Univariable and multivariable logistic regression analyses were carried out, and odds ratios were reported. Results: Overall, 49.58% nurses had an intention to leave the profession. It is found that stress from health condition, family, occupational injuries, nurse–patient tension, high job demands, strict leaders and colleague relationships were significantly associated with higher intention to leave. Coping strategies such as talking to family and friends, talking to leaders, doing outdoor activities, engaging in hobbies and attending on‐the‐job training were significantly associated with lower intention, but social gathering, psychological counselling and suffering in silence had an opposite effect. Conclusions: Our study provides new insights into the association between stressors, coping strategies and turnover intention among nurses in China. Implications for Nursing Management: Evidence from this study indicates that policies promoting a safe and supportive work environment should be developed to help nurses cope with stress. [ABSTRACT FROM AUTHOR]

The variable diapause features of bivoltine silkworm (Bombyx mori) strains regulated by environmental signals in the embryonic stage are closely related to epigenetics. Previously, we showed that the expression of YTHDF3 is significantly different in the pupae of the bivoltine silkworm Qiufeng developed from eggs incubated at a normal temperature (QFHT, diapause egg producer) compared to those from eggs incubated at a low temperature (QFLT, nondiapause egg producer), indicating that the expression of diapause-associated genes is regulated by the m6A modification level. However, how YTHDF3 regulates the expression of diapause-related genes remains unclear. In this study, we observed that the knockdown of B. mori YTHDF3 resulted in delayed embryo development, while the overexpression of YTHDF3 resulted in the transformation of nondiapause-destined eggs into a mixture of diapause and nondiapause eggs. Further studies showed that YTHDF3, as a reading protein, can recognize the m6A site of Cyp307a1 and Cyp18a1 genes in the ecdysone synthesis pathway (ESP), and the overexpression of YTHDF3 affects the diapause traits of the silkworm by decreasing the stabilities of mRNAs of Cyp307a1 and Cyp18a1 and inhibiting their translation. The above results demonstrate that m6A modification mediates YTHDF3 to affect the expression levels of its target genes, Cyp307a1 and Cyp18a1, in the ESP to regulate diapause in bivoltine B. mori. This is the first report of the m6A methylation regulation mechanism in diapause in B. mori and provides new experimental data for clarifying the diapause regulation network. [ABSTRACT FROM AUTHOR]

Objective. To screen CXC chemokines related to the risk of lung adenocarcinoma (LUAD) using bioinformatics and construct a CXC-based prognostic risk model to improve the diagnosis and treatment of LUAD patients. Methods. The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database were searched to obtain mRNA expression data and clinicopathological information of LUAD patients. CXC genes differentially expressed in LUAD were screened using the R packages. Further, risk factors significantly associated with the survival of LUAD patients were obtained by the univariate Cox proportional hazard regression, LASSO regression, and multivariate Cox proportional hazard regression analysis, following which a risk prediction model was constructed. The performance of the CXCL13-based model in predicting the prognosis of low-risk and high-risk effect LUAD patients was verified, and the association between the model and the degree of tumor immune cell infiltration was investigated. Results. CXCL13 was significantly highly expressed in the cancer tissues of LUAD patients. The risk of death in patients with highly expressed CXCL13 was about 1.5 times higher than in those with lowly expressed CXCL13 (HR = 1.5153357). CXCL13-based risk scoring showed that the high-risk score of LUAD patients was significantly correlated with poor prognosis, but no relation between the two was found in the GEO validation sets, suggesting that this risk model may not be accurate enough. In addition, activated B cells, CD4+ T cells, CD8+ T cells, and dendritic cells were significantly positively correlated with the high risk of LUAD. Conclusions. Although we found that a high expression of CXCL13 was associated with a high risk of death and immune cell infiltration and activation in LUAD patients, the CXCL13-based risk model was not accurate enough for predicting the prognosis of LUAD patients. [ABSTRACT FROM AUTHOR]

Objective. Red raspberry serves as a proven natural product to produce anti-inflammatory, antioxidant, and anticancer functions, but limited findings are available on its effects on depression. This study, by using a chronic unpredictable mild stress- (CUMS-) induced depression model, thus investigated the effects and underlying mechanism of red raspberry extract (RRE) on depressive behavior, inflammation, and oxidative stress. Methods. Different treatments were given after random grouping of Sprague-Dawley rats, including no intervention (control), CUMS induction, and CUMS+different concentrations of RRE, and subsequently, depression-like behavior tests were performed. HE staining was designed to observe the pathological damage of the hippocampal tissue in rats. The levels of oxidative stress, endocrine hormones, and inflammatory factors were determined by biochemical assay and ELISA, and gene expression (mRNA and protein) in the hippocampal tissue by qRT-PCR and Western blot. Results. On completion of CUMS treatment, the rats showed severe depression-like behavior, with obvious hippocampal tissue damage, oxidative inflammatory response, and endocrine imbalance. Importantly, RRE treatment significantly improved such depression-like behavior and attenuated histopathological damage in CUMS rats when reducing inflammation and oxidative stress and endocrine imbalance with upregulation of glutathione (GSH), superoxide dismutase (SOD), and interleukin- (IL-) 10 and downregulation of adrenocorticotropic hormone (ACTH), corticosterone (CORT), malondialdehyde (MDA), IL-1β, cyclooxygenase- (COX-) 2, and human macrophage chemoattractant protein- (MCP-) 1. In addition, for CUMS rats, RRE was a contributor to increasingly expressed brain-derived neurotrophic factor (BDNF), neurotrophic tyrosine receptor kinase 2 (TrkB), and p-mTOR but inhibited p-GSK-3β expression in the hippocampal tissue. All the above antidepressant effects of RRE were concentration-dependent. Conclusion. By regulating neuroinflammation, oxidative stress response, endocrine level, and BDNF/TrkB level, RRE showed potential efficacy in alleviating depression-like behavior and histopathological damage of hippocampal tissue in CUMS rats by regulating the GSK3β and mTOR signaling pathways. [ABSTRACT FROM AUTHOR]

Background: Surgical instrument packaging quality directly affects the safety and performance of surgery. We aimed to investigate the factors causing defects in surgical instrument packaging and recommend strategies to prevent defects in surgical instrument packaging.Methods: We collected surgical instrument packaging data regarding age, gender, length of service, educational background, number of staff dealing with packaging, time period of packaging, instrument specification, where the wrap was intact, whether the wrap reached the required quality of cleaning, and whether the instruments were satisfactorily cleaned in compliance with guidelines from 5000 surgical instrument packages during June-December 2018 at Central Sterile Supply Department of the West China Second University Hospital, Sichuan University. Meanwhile, a questionnaire survey completed by the operating room staff using surgical instruments was used to measure the level of their satisfaction with the instruments in the packages. We utilized single-factor analysis to investigate possible factors that might cause defects in surgical instrument packaging, and conducted multivariate logistic regression analysis of the factors associated with defects in packaging.Results: Length of service, educational background, number of staff dealing with packaging, time period of packaging, instrument structure, whether the wrap was intact, whether the wrap reached the required quality of cleaning, and whether the surgical instruments were satisfactorily cleaned in compliance with guidelines were the factors significantly (P < 0.05) associated with defects in surgical instrument packaging.Conclusion: This study reveals that various factors are associated with defects in surgical instrument packaging. Recommendations for reducing incidences of defects include improved scheduling of packaging workload, greater provision of training in packaging skills, and standardization of packaging procedure. [ABSTRACT FROM AUTHOR]

To study the regulatory function of Bombyx mori (B. mori) miRNAs (bmo-miR) on the expression of fibroin light chain gene (BmFib-L), the 3'UTR of BmFib-L mRNA was used as the target for online prediction of miRNAs from miRBase using RNAhybrid Software, and miR-2845 was screened out. First, the expression profiles of miR-2845 and BmFib-L in larvae of the 5th instar were analyzed by Real-time quantitative PCR (RT-qPCR). Then recombinant plasmids (pcDNA3.0-pre-miR-2845 and pGL3.0-BmFib-L) were constructed to use for the expression of miR-2845 and BmFib-L 3'UTR, respectively. Cellular-level functional verification of miR-2845 on BmFib-L was carried out using multiple experimental methods (including dual luciferase reporter vectors, artificially synthesized mimics and inhibitors, and target site mutations). Finally, in vivo functional verification was performed by injecting the recombinant vector in 5th instar larvae. BmFib-L expression levels were detected using RT-qPCR in the posterior silk glands (PSG) of the injected larvae. Results showed that the expression of miR-2845 increased between the 1st and 5th day in 5th instar larvae, but began to decline on the 5th day, while the expression of the target gene BmFib-L increased sharply. This suggests that miR-2845 and BmFib-L expression levels show opposing trends, implying a negative regulatory relationship. In BmN cells, miR-2845 significantly down-regulated the expression of BmFib-L; the inhibitory effect of miR-2845 on BmFib-L was disappeared after mutation of the targeting site on 3'UTR of BmFib-L; in individuals, miR-2845 significantly down-regulated BmFib-L expression levels. Our results provide new experimental data for clarifying the molecular regulation mechanism of silk protein expression. [ABSTRACT FROM AUTHOR]

Background: Although great progress has been made in the prevention and treatment of AIDS, there are still a considerable number of new infections annually, especially in adolescents. With the advance of technology, game-based education has gradually become an important tool for changing healthy behaviors among youth.Methods: A protocol for conducting a randomized controlled trial to evaluate the "AIDS Fighter · Health Defense", a game-based AIDS education project aimed at improving the ability of adolescents to prevent AIDS. During the four-week intervention, participants will receive: 1) A virus combat game; 2) Goal setting to eliminate HIV; 3) Questions to be answered to be resurrected in the game; 4) Points ranking; 5) Recognition and Rewards. The primary outcomes include changes in participants' knowledge, stigma attitude, and risk behaviors attitude related to AIDS after four weeks of intervention. The secondary outcomes are the participants' AIDS-related risk behaviors three and six months after the intervention.Discussion: AIDS Fighter· Health Defense may be an innovative approach to help adolescents improve AIDS prevention capabilities, fill the gap in game-based AIDS prevention education in China, and gain experience of AIDS management.Trial Registration: Chinese Clinical Trial Registry: ChiCTR2000040195 . Registered 25 November 2020. [ABSTRACT FROM AUTHOR]

Understanding soil phosphorus (P) distribution and its key drivers is fundamental for sustainable P management. In this study, a 21-year fertilization experiment on black soil was carried out, setting up five fertilization treatments: unfertilized control (CK), nitrogen and potassium (NK), nitrogen, P and potassium (NPK), NPK plus straw (NPKS), and NPK plus manure (NPKM). The distribution and effecting factors of P pools within soil aggregates were investigated. Compared to CK, the NK and NPK treatments decreased calcium-associated P concentration in all aggregate fractions. Meanwhile, the NPK treatment significantly increased the organic P extracted from NaOH in unaggregated particles (<0.053 mm). This was mainly due to the reduction in soil pH. The NPKS and NPKM treatments increased almost all P forms in aggregates, especially Ca-P. For the NPKM treatment, inorganic P extracted from resin, NaHCO3, and NaOH increased as aggregate size increased. This was mainly because straw or manure addition promoted soil organic carbon (SOC) storage in aggregates, creating more sorption sites via association with amorphous metallic minerals, and, thus, facilitating P accumulation. In conclusion, decreasing soil pH by chemical fertilizers is an effective strategy for mobilizing soil P, whereas increasing SOC by straw or manure facilitates P accumulation. [ABSTRACT FROM AUTHOR]

Ground surface settlement induced by shallow tunnel construction is inevitable, and it is more complicated at the intersection area since the rock behavior is a complex, three-dimensional problem. This paper presented a case study of controlling the surface settlement during the tunneling of an urban shallow intersection between a double-arched tunnel and a connection tunnel in China. Various construction measures, including the sequence excavation, presupport, and primary support systems, were used to control the settlement. Furthermore, a three-dimensional analysis was conducted to investigate the settlement characteristics in different stages, the optimum excavation spacing among pilots, and the support effect of the presupport. The results showed that the settlement was mainly caused by the excavation of the upper steps. The deformation induced by transverse guide tunnel T3 was much larger than that of the others because the surrounding rock at the vault was plain fill. The three-pilot excavation methods can effectively control the surface settlement for a double-arched tunnel, and the optimum spacing values between the different steps were obtained. The reduced proportions of the advanced small pipes supporting construction tunnels T2 and T3 were approximately 27.0% and 17.2%, respectively, while the reduced proportion of the pipe roof supporting T4 was approximately 42.4%. The monitoring results showed that this project was successfully completed. [ABSTRACT FROM AUTHOR]

Fully memristive neuron learning framework, which uses drift and diffusion memristor models to build an artificial neuron structure, becomes a hot topic recently with the development of memristor. However, some other devices like resistor or capacitor are still necessary in recent works of fully memristive learning framework. Theoretically, if one neuron is built by memristors only, the technique process will be simpler and learning framework will be more like biological brain. In this paper, a fully memristive spiking-neuron learning framework is introduced, in which a neuron structure is just built of one drift and one diffusion memristive models and spikes are used as transmission signals. The learning framework and spiking coding mode are simple and direct without any complicated calculation on hardware. To verify its merits, a feedforward neural network for pattern recognition and a cellular neural network for edge detection are designed. Experimental results show that compared to other memristive neural networks, processing speed of the proposed framework is very high, and the hardware resource is saved in pattern recognition. Further, due to the dynamic filtering function of diffusion memristor model in our learning framework, its peak signal noise ratio (PSNR) is much higher than traditional algorithms in edge detection. [ABSTRACT FROM AUTHOR]

Anxi persimmon is a popular fruit because of its appealing flavor and rich nutrients such as polysaccharides. However, the harvested persimmon fruit softens and deteriorates quickly. This study explored the influences of the treatment of papers containing 1-methylcyclopropene (1-MCP) on the contents of cell wall polysaccharides and activities of cell wall-degrading enzymes in harvested Anxi persimmons, as well as its effect on fruit softening. The results demonstrated that, in comparison to the control Anxi persimmons, the Anxi persimmons treated with 1.35 μL/L 1-MCP manifested higher fruit firmness, higher contents of protopectin, cellulose, and hemicellulose, but a lower level of water-soluble pectin, lower activities of pectin methylesterase, polygalacturonase, cellulase, and β -galactosidase in Anxi persimmons during postharvest storage. These findings suggested that the treatment of papers containing 1.35 μL/L 1-MCP could retard softening of harvested Anxi persimmon fruit via inhibiting the degradation of cell wall polysaccharides. • Paper containing 1-MCP retarded fruit softening in harvested Anxi persimmons. • Paper containing 1-MCP reduced Anxi persimmon cell wall-degrading enzyme activities. • Paper containing 1-MCP kept higher levels of Anxi persimmon cell wall polysaccharides. • Paper containing 1-MCP inhibited Anxi persimmon cell wall polysaccharides disassembly. • Paper containing 1-MCP is a convenient method for keeping quality of Anxi persimmons. [ABSTRACT FROM AUTHOR]

The development of quantitative metabolomics approaches for future standardized and translational applications has become increasingly important. Data-independent targeted quantitative metabolomics (DITQM) is a newly proposed method providing ion pair information on 1324 metabolites. However, the quantification of more than 1000 metabolites in large sample sizes has still not been implemented. In this study, on the basis of the DITQM concept, scheduled multiple reaction monitoring (MRM) methods for both high-abundant and low-abundant metabolites were established to broaden the quantification coverage, and an open-source program "Quanter_1.0" was coded to facilitate efficient data handling. Our results demonstrated that 1015 metabolites in human plasma met the quantitative requirements and could be relatively determined in an effective manner. The method was then applied to a large-scale sample study of lung cancer consisting of three distinct analytical batches. It was obvious that data quality that originated from quantitative metabolomics was improved, with substantially lower intra- and inter-batch data variation, resulting in a more effective multivariate statistical model. Finally, 26 potential biomarkers of lung cancer were discovered. Collectively, our approach provides a promising tool for quantitative metabolomics research involving large-scale sample sizes and clinical application. Image 1 • A high-coverage metabolome quantitative method based on scheduled MRM was developed. • An in-house Python program Quanter_1.0 was coded to support large amount of computation in quantification efficiently. • 202 high-abundant and 813 low-abundant (1015 in total) metabolites in plasma sample could be determined relatively. • Quantitative metabolomics had smaller data variation and more effective statistical model vs. traditional metabolomics. • The approach was a useful tool for large-scale sample analysis, even in separated batches. [ABSTRACT FROM AUTHOR]

Background and Aims: Cirrhosis is characterized by extensive fibrosis of the liver and is a major cause of liver‐related mortality. Cirrhosis is partially heritable but genetic contributions to cirrhosis have not been systemically explored. Here, we carry out association analyses with cirrhosis in two large biobanks and determine the effects of cirrhosis associated variants on multiple human disease/traits. Methods: We carried out a genome‐wide association analysis of cirrhosis as a diagnosis in UK BioBank (UKBB; 1088 cases vs. 407 873 controls) and then tested top‐associating loci for replication with cirrhosis in a hospital‐based cohort from the Michigan Genomics Initiative (MGI; 875 cases of cirrhosis vs. 30 346 controls). For replicating variants or variants previously associated with cirrhosis that also affected cirrhosis in UKBB or MGI, we determined single nucleotide polymorphism effects on all other diagnoses in UKBB (PheWAS), common metabolic traits/diseases and serum/plasma metabolites. Results: Unbiased genome‐wide association study identified variants in/near PNPLA3 and HFE, and candidate variant analysis identified variants in/near TM6SF2, MBOAT7, SERPINA1, HSD17B13, STAT4 and IFNL4 that reproducibly affected cirrhosis. Most affected liver enzyme concentrations and/or aspartate transaminase‐to‐platelet ratio index. PheWAS, metabolic trait and serum/plasma metabolite association analyses revealed effects of these variants on lipid, inflammatory and other processes including new effects on many human diseases and traits. Conclusions: We identified eight loci that reproducibly associate with population‐based cirrhosis and define their diverse effects on human diseases and traits. See Editorial on Page 281 [ABSTRACT FROM AUTHOR]

• This paper proposed a novel wind speed forecasting algorithm. • A new dataset division mechanism based on the moving window is used in this paper. • In order to improve the accuracy and stability simultaneously, the multi-objective particle swarm optimization is applied. • We compared the proposed MOPSO-Combined method with the combined model that published before in the paper. Accurate wind speed forecasting is important in power grid security, power system management, operation and market economics. However, most research has focused only on improving either accuracy or stability, with few studies addressing the two issues, simultaneously. Therefore, we proposed a novel combined model based on multi-objective particle swarm optimization, which is applied to optimize the key parameters of the echo state network. Most combined wind speed forecasting methods just use the combination theory to combine individual methods, this paper uses echo state network to combine the intermediate wind speed forecasting results of three artificial neural networks. Moreover, a new dataset division mechanism based on the moving window is applied in this paper. Firstly, the length of the input data is changed from 5 to 15 for 1-step, 2-step and 3-step wind speed forecasting, after that, the optimal length of the input vector can be got. And then we apply this optimal length of the input vector to another dataset for further verifying the proposed method. In order to verify the forecasting effectiveness of the proposed forecasting model, the 80/min wind speed data of M2 tower of the National Wind Power Technology Center of the United States were taken as an example. The experimental results indicate that the proposed algorithm is superior to the other ten comparative models in prediction accuracy and stability, and it also performs better than the combined model that we have proposed before. [ABSTRACT FROM AUTHOR]

[Display omitted] • The expression levels of BmINR and BmAC6 are significantly higher in NDEPs compared to DEPs. • Knockdown of BmINR upregulates the 3-hydroxykynurenine synthesis pathway and results in a change in the diapause phenotype. • Overexpression of BmINR or BmAC6 highly upregulates the expression levels of key genes related to carbohydrate metabolism. • BmINR and BmAC6 play a crucial role in regulating embryonic diapause via the insulin/IGF signaling pathway. Diapause of the silkworm (Bombyx mori) is an important ecological adaptation strategy regulated by multiple signaling pathways. As an evolutionarily conserved signaling pathway, the insulin/IGF signaling (IIS) pathway is essential in regulating lifespan, energy accumulation, and stress resistance in diapause insects. However, the regulatory mechanism of IIS on diapause in B. mori is still not fully understood. To investigate the role of the IIS pathway in regulating diapause, we first analyzed the transcription levels of the insulin receptor (BmINR) and its downstream gene adenylate cyclase 6 (BmAC6). The diapause-terminated eggs of a bivoltine strain QiuFeng (V2-QF) were incubated at 25 °C in natural room light for preparing diapause egg producers (DEPs) and at 17 °C in total darkness for preparing non-diapause egg producers (NDEPs), respectively. Then we investigated the effects of BmINR and BmAC6 on diapause phenotype and expression of diapause-related genes by RNA interference (RNAi) and overexpression techniques. The results showed that the mRNA expression levels of BmINR and BmAC6 in the head and ovary of NDEPs were higher than those in DEPs during the early and middle pupal stages. Furthermore, when BmINR was knocked down in the NDEPs, approximately 14.43% of eggs were in light red color and subsequently changed into gray-purple color after 48 h post-oviposition, then stayed in a diapause state. On the other hand, overexpression of BmINR or BmAC6 via recombinant baculoviruses did not cause any obvious phenotypic alterations in NDEPs, but it upregulated the expression of genes related to carbohydrate metabolism, which provides energy for embryonic growth and development. Therefore, it can be concluded that BmINR and BmAC6 genes regulate embryonic diapause in bivoltine B. mori. [ABSTRACT FROM AUTHOR]

Bone metastasis is a major cause of prostate cancer (PCa) mortality. Although docetaxel chemotherapy initially extends patients' survival, in most cases PCa becomes chemoresistant and eventually progresses without a cure. In this study, we developed a novel small-molecule compound BKM1972, which exhibited potent in vitro cytotoxicity in PCa and other cancer cells regardless of their differences in chemo-responsiveness. Mechanistic studies demonstrated that BKM1972 effectively inhibited the expression of anti-apoptotic protein survivin and membrane-bound efflux pump ATP binding cassette B 1 (ABCB1, p-glycoprotein), presumably via signal transducer and activator of transcription 3 (Stat3). BKM1972 was well tolerated in mice and as a monotherapy, significantly inhibited the intraosseous growth of chemosensitive and chemoresistant PCa cells. These results indicate that BKM1972 is a promising small-molecule lead to treat PCa bone metastasis and overcome docetaxel resistance. [ABSTRACT FROM AUTHOR]

Abstract This study investigated the water resource potential for bioenergy production from sweet sorghum (Sorghum bicolor (L.)) in Northern China according to the distribution of water resources, climate conditions and the total water consumption of bioenergy based on sweet sorghum, which consisted of blue water, green water and grey water. At a case study site in Inner Mongolia, simulation with a plant phenological model was used to determine whether sweet sorghum could reach the harvestable stage for sugar juice production. The blue water in the agricultural phase was estimated according to the potential crop evapotranspiration (ET c), the drought sensitivity of sweet sorghum in different stages and the precipitation during the growing season. The results showed that the irrigation water was significantly different among the districts, ranging from 730 to 5500 m3/ha and 2060 to 6680 m3/ha for early-maturing and late-maturing varieties, respectively. To avoid the water pressure level to be exacerbated and the severe reallocation of water resources resulting in negative effects on other sectors, the maximal annual water withdrawal was set to not surpass the upper threshold of water stress level of 40%. That makes the maximum area for the production of sweet sorghum cannot exceed 1.95 × 104 ha, representing only 0.24% of the total marginal land area in Inner Mongolia. However, the economic benefits of bioenergy production from sweet sorghum would be negative due to the high labour input. Therefore, not only the availability of marginal land, the climate conditions and local water resources but also the improvement of mechanisation and agricultural production techniques should be considered to attain the sustainable development of bioenergy production and address global energy and environmental crises. Graphical abstract Unlabelled Image Highlights • We evaluated irrigation water of sweet sorghum based on phenological characteristics. • The total water consumption of bioenergy and regional water stress were estimated. • We can use 0.24% of the marginal land to produce bioenergy from a water perspective. [ABSTRACT FROM AUTHOR]

Diapause is an important characteristic of insects used to adapt to extreme changes in environmental conditions. Embryonic diapause of the bivoltine silkworm (Bombyx mori) is determined by environmental conditions experienced by the mother while in the embryo stage. If they are incubated at 25°C with natural light, their progenies will be diapause‐destined. If they are incubated at 17°C in darkness, their progenies will be non‐diapause‐destined. The molecular mechanism of diapause remains unknown. In the present study, we analyzed two downregulated genes (BGIBMGA003835, BGIBMGA012335) and two upregulated genes (BGIBMG012996, BGIBMG002426) related to carbohydrate metabolism, verified differentially expressed in ovaries and heads of 1‐day‐old fifth‐instar larvae to 6‐day pupae by quantitative real‐time reverse transcription polymerase chain reaction (qRT‐PCR). In line with published data, the expression level of these genes in larvae were generally lower than in pupae. We further analyzed the expression levels of the four genes in BmN cells that had been treated with various concentrations of diapause hormone (DH). It demonstrated that the expression of these genes was affected by DH. Knockdown of the selected genes in non‐diapause‐destined female pupae changed the fate of the progeny from non‐diapause‐ to daipause‐destined, as seen by the appearance of diapause eggs. Our study provides insight into the molecular mechanism of diapause in B. mori. The expression levels of BGIBMGA003835, BGIBMGA012335, BGIBMG012996 and BGIBMG002426 were different at diverse developmental stages. They can also be influenced by Bmo‐DH. RNAi if several genes can turn over the fate of non‐diapause eggs. [ABSTRACT FROM AUTHOR]

Highlights • This paper proposed a novel combined model based on echo state network. • A new dataset division mechanism is applied in this paper. • ESN is initially applied to combine the intermediate forecasting results of four hybrid models. • The proposed model is tested comprehensively in different wind speed sites. Abstract Accurate wind speed forecasting plays a crucial role in wind power plants and wind systems. Numerous studies that dedicated to enhance wind speed forecasting accuracy have been proposed. Nevertheless, some classical models are not good at dealing with nonlinear time sequence, and artificial intelligence are easy fall into local optimum. Based on this, this paper proposed a novel combined model for wind speed forecasting, which combined hybrid models based on decomposition method and optimization algorithm. In this approach, four distinct hybrid models are proposed and to additionally enhance the forecasting performance, ESN (Echo state network) is initially applied to integrate all the results obtained by each hybrid model and achieve the ultimate forecasting results. Besides, a distinct data set division mechanism is adopted in the multi-step wind speed forecasting. To verify the effectiveness and versatility of the proposed combined model, the wind speed data of 20 m, 50 m, 80 m per minute of the M2 tower from the National Wind Power Technology Center, United States, are utilized as case studies. The experimental results indicate that the proposed combined model performs better than other conventional methods. [ABSTRACT FROM AUTHOR]

Abstract Targeted quantification and untargeted global profiling are the two mainstream approaches, a merging of which could provide enhanced analytical potential in metabolomics research. Here, a simultaneous targeted quantification and untargeted metabolomics (STQUM) strategy was developed for more efficient, accurate and comprehensive metabolomics research by using ultra-high-performance liquid chromatography coupled with high-resolution tandem mass spectrometry (UPLC-HRMS/MS). First, we selected 110 cancer-related metabolites as targets and established a dual LC sequential separation method for simultaneous analysis of strong and weak polar metabolites. In order to achieve efficient acquisition for synchronous qualitative and quantitative analysis, high-resolution, data-dependent parallel reaction monitoring (PRM) method and data-independent all ion fragmentation (AIF) method were established. Their performance in targeted confirmation and quantification, and untargeted analysis were systematically investigated and assessed. In total, 78 metabolites were confidently confirmed in positive ion mode in both PRM and AIF assays, in which 73 metabolites can be accurately quantified. In addition, simultaneously untargeted profiling of 4651 features of high reliability and validity were achieved. Both AIF and PRM methods revealed high confidence, sensitivity and accuracy. In the STQUM approach, another 15 metabolites could be accurately quantified in negative ion mode. The method offers a new perspective for merging the hypothesis-based targeted quantitative validation and untargeted biomarkers discovery in one run for improved analysis efficiency and integrity. Graphical abstract Image 1 Highlights • A simultaneous targeted quantification and untargeted metabolomics (STQUM) strategy based on dual LC-MS/MS was developed. • Efficient separation for both strong and weak polar metabolites was achieved in one injection. • PRM and AIF methods were respectively established and systematically evaluated. • The STQUM approach contributes to improved efficiency and comprehensiveness in metabolomics study. [ABSTRACT FROM AUTHOR]

The expression level of vitamin D receptor in patients with asthma was investigated to study the association between vitamin D receptor and inflammatory changes in asthma. Thirty patients with bronchial asthma treated in the Tianjin Hospital of ITCWM Nankai Hospital were selected as the experimental group, while 30 healthy individuals were selected as the control group. The mRNA expression level of vitamin D receptor in blood was detected via reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The protein expression level of vitamin D receptor in blood was detected via western blot analysis and the levels of inflammatory factors were detected via enzyme-linked immune sorbent assay (ELISA). Correlations between the expression level of vitamin D and inflammatory factors were studied via Pearsons analysis. Finally, the prognoses of patients were recorded and analyzed. The results showed that the mRNA and protein expression levels of vitamin D receptor in the experimental group were significantly lower than those in control group (P<0.01). The content of 25-(OH) D3 in serum in the experimental group was significantly lower than that in the control group (P<0.01). The contents of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in serum in the experimental group were obviously higher than those in the control group, but the contents of IL-10 and transforming growth factor-β (TGF-β) were obviously lower than those in the control group (P<0.01). Moreover, the correlation analysis revealed that IL-6 and TNF-α were negatively correlated with the expression of vitamin D receptor (P<0.05), whereas IL-10 and TGF-β were positively correlated with the expression of vitamin D receptor (P<0.05). In conclusion, the expression of vitamin D receptor is positively correlated with the levels of pro-inflammatory factors. Moreover, the vitamin D receptor affects the prognosis and recovery of lung function of patients with asthma. [ABSTRACT FROM AUTHOR]

Short term electric load forecasting, as an important tool in the electricity market, plays a critical role in the management of electric systems. Proposing an accuracy and optimization method is not only a challenging task but also an indispensable part of the energy system. More and more accurate forecasting methods are needed by different people in different areas. This paper proposes a novel short-term electric load forecasting method EMD-Mixed-ELM which based on empirical mode decomposition (EMD) and extreme learning machine (ELM). EMD-Mixed-ELM first uses the empirical mode decomposition to decompose the load series for capturing the complicated features of the electric load and de-noising the data. Considering that the performance of extreme learning machine (ELM) is greatly influenced by the choice of kernel, the mixed kernel method is proposed for ELM. The mixed kernel combines the RBF kernel and the UKF kernel. The forecasting results of the EMD-Mixed-ELM are proved to be better than all the other three methods (RBF-ELM, UKF-ELM and Mixed-ELM) and other existing methods (MFES, ESPLSSVM and Combined method). To verify the forecasting ability of the EMD-Mixed-ELM, half-hourly electric load data from the state of New South Wales, Victoria and Queensland in Australia are used in this paper as a case study. The experimental results clearly indicate that for this three datasets, the forecasting accuracy of the proposed method is superior to other methods. [ABSTRACT FROM AUTHOR]

With the continuous development of the global electricity market, the electricity market needs the electricity price forecasting result to be accurate, and electricity price forecasting also has more profound practical significance. Accurate price forecasting can not only better reflect the operation of the electricity market but also help to make better decisions about the electricity market. However, the electricity price is affected by a variety of uncertain subjective and objective factors, as well as the constraints of the power system, making it more difficult to obtain accurate electricity price forecasting than electricity load forecasting. The kernel function occupies a very important position in a support vector machine (SVM), which is the key to the mature development of SVM theory. When using SVM for classification and regression, the appropriate kernel function is the basis and precondition for obtaining better classification and approximation effects. In this paper, a new combinatorial kernel function that combines RBF and UKF kernel functions is proposed and is applied to a least squares support vector machine (LSSVM), and based on this, a new hybrid model empirical mode (EMD)-Mixed-LSSVM is proposed to forecast electricity price. The hybrid model puts the electricity price data after the noise reduction by the EMD into the LSSVM with the combined kernel function for calculation. In this paper, we forecast the electricity price in Australia and compare the results of EMD-Mixed-LSSVM with other methods. The results show that EMD-Mixed-LSSVM can effectively improve the accuracy of electricity price forecasting. [ABSTRACT FROM AUTHOR]

Contemporary therapy for advanced castration-resistant prostate cancer (CRPC) employs reagents such as enzalutamide and abiraterone acetate targeting the androgen receptor (AR) transcription axis only provide a temporary response and rapidly develop resistance. Additionally, neuroendocrine prostate cancer (NEPC) is an AR pathway-independent and lethal-stage prostate cancer with no standard therapy. Qingdai Decoction (QDT), a traditional Chinese medicine formula, has various pharmacological activities and was widely used for the treatment of different diseases including prostatitis which may contribute to prostate cancer development. This study aims to explore the anti-tumor role and potential mechanism of QDT on prostate cancer. CRPC prostate cancer cell models and xenograft mice models were established for research. The effect of TCMs on cancer growth and metastasis were determined by CCK-8, wound-healing assays and the PC3-xenografted mice model. The toxicity of QDT in the major organs was investigated by H&E staining. The compound-target network was analyzed with network pharmacology. The correlation of QDT targets with prostate cancer patient's prognosis was analyzed with multiple prostate cancer patient cohorts. The expression of related proteins and mRNA were detected by western blot and real-time PCR. The gene knockdown was achieved with CRISPR-Cas13 technology. By integrating functional screening, network pharmacology analysis, CRISPR-Cas13 directed RNA targeting, and molecular biology validation in different prostate cancer models and clinical prostate cancer cohorts, we found that Qingdai Decoction (QDT), a Traditional Chinese Medicine, can repress cancer growth in advanced prostate cancer models in vitro and in vivo in an AR independent manner by targeting NOS3, TGFB1 , and NCOA2. This study not only identified QDT as a novel drug for lethal-stage prostate cancer treatment but also provided an extensive Integrative research paradigm for investigating the roles and mechanisms of TCMs for the treatment of other diseases. [Display omitted] • QDT efficiently represses multiple prostate cancer cells growth in vitro and in vivo. • QDT targets are closely related to prostate cancer progression and patient survival. • NOS3, TGFB1 and NCOA2 mediate the antitumor effect of QDT. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD), and its progressive form steatohepatitis (NASH), represent a genetically and phenotypically diverse entity for which there is no approved therapy, making it imperative to define the spectrum of pathways contributing to its pathogenesis. Rare variants in genes encoding nuclear envelope proteins cause lipodystrophy with early-onset NAFLD/NASH; we hypothesized that common variants in nuclear envelope-related genes might also contribute to hepatic steatosis and NAFLD. Using hepatic steatosis as the outcome of interest, we performed an association meta-analysis of nuclear envelope-related coding variants in three large discovery cohorts (N >120,000 participants), followed by phenotype association studies in large validation cohorts (N >600,000) and functional testing of the top steatosis-associated variant in cell culture. A common protein-coding variant, rs6461378 (SUN1 H118Y), was the top steatosis-associated variant in our association meta-analysis (p <0.001). In ancestrally distinct validation cohorts, rs6461378 associated with histologic NAFLD and with NAFLD-related metabolic traits including increased serum fatty acids, type 2 diabetes, hypertension, cardiovascular disease, and decreased HDL. SUN1 H118Y was subject to increased proteasomal degradation relative to wild-type SUN1 in cells, and SUN1 H118Y-expressing cells exhibited insulin resistance and increased lipid accumulation. Collectively, these data support a potential causal role for the common SUN1 variant rs6461378 in NAFLD and metabolic disease. Non-alcoholic fatty liver disease (NAFLD), with an estimated global prevalence of nearly 30%, is a growing cause of morbidity and mortality for which there is no approved pharmacologic therapy. Our data provide a rationale for broadening current concepts of NAFLD genetics and pathophysiology to include the nuclear envelope, and particularly Sad1 and UNC84 domain containing 1 (SUN1), as novel contributors to this common liver disease. Furthermore, if future studies confirm causality of the common SUN1 H118Y variant, it has the potential to become a broadly relevant therapeutic target in NAFLD and metabolic disease. [Display omitted] • Association meta-analysis identified a strong positive association between a coding variant in SUN1 (rs6461378-T) and hepatic steatosis. • SUN1 variant positively associated with histologic NAFLD and NAFLD-related metabolic traits in separate validation cohorts. • This variant increased SUN1 degradation compared to the wild-type protein under nutrient-limited conditions (serum starvation). • The SUN1 variant increased lipid droplet accumulation and blunted insulin signaling in human hepatoma cell lines. [ABSTRACT FROM AUTHOR]

14 C-containing dissolved organic compounds may significantly contribute to the calculated annual overall dose emanated from a deep geological repository for radioactive waste. To date, there is a general lack of knowledge concerning the transport behaviour of low molecular weight organic compounds in the geosphere. The present work is aiming at a generic approach to measure weak adsorption of such compounds onto selected clay minerals. Percolation experiments were employed to sensitively measure the retardation of low molecular weight carboxylates and alcohols in compacted illite and kaolinite as a function of the ionic strength. Detection limits of ∼10 −5  m 3  kg −1 for the involved sorption distribution coefficients were attained thereby. The adsorption of alcohols on clays was near the detection limit and assumed to occur predominately via H-bonding. The adsorption of organic anions was influenced by several factors such as molecular structure, type of clay surfaces and the chemical composition of the aqueous phase. It was found that the relative position of neighbouring hydroxyl groups strongly influenced the retardation behaviour. Alpha-hydroxylated carboxylates, such as lactate, were found to be most retarded. Ligand exchange at the edge aluminol sites is the most probable explanation for the uptake of the negatively charged organic test compounds by the clay surface. The breakthrough behaviour of organic anions was additionally impacted by anion exclusion in illite. The demonstrated weak retardation of the test compounds can be robustly introduced in transport models, leading thus to a much lower contribution of 14 C to the expected long-term overall dose. [ABSTRACT FROM AUTHOR]

Background: Inherited eye diseases are major causes of vision loss in both children and adults. Inherited eye diseases are characterized by clinical variability and pronounced genetic heterogeneity. Genetic testing may provide an accurate diagnosis for ophthalmic genetic disorders and allow gene therapy for specific diseases. Methods: A targeted gene capture panel was designed to capture exons of 283 inherited eye disease genes including 58 known causative retinitis pigmentosa (RP) genes. 180 samples were tested with this panel, 68 were previously tested by Sanger sequencing. Systematic evaluation of our method and comprehensive molecular diagnosis were carried on 99 RP patients. Results: 96.85% targeted regions were covered by at least 20 folds, the accuracy of variants detection was 99.994%. In 4 of the 68 samples previously tested by Sanger sequencing, mutations of other diseases not consisting with the clinical diagnosis were detected by next-generation sequencing (NGS) not Sanger. Among the 99 RP patients, 64 (64.6%) were detected with pathogenic mutations, while in 3 patients, it was inconsistent between molecular diagnosis and their initial clinical diagnosis. After revisiting, one patient’s clinical diagnosis was reclassified. In addition, 3 patients were found carrying large deletions. Conclusions: We have systematically evaluated our method and compared it with Sanger sequencing, and have identified a large number of novel mutations in a cohort of 99 RP patients. The results showed a sufficient accuracy of our method and suggested the importance of molecular diagnosis in clinical diagnosis. [ABSTRACT FROM AUTHOR]

In this study, we assess the dynamic evolution of short-term correlation, long-term cointegration and Error Correction Model (hereafter referred to as ECM)-based long-term Granger causality between each pair of US, UK, and Eurozone stock markets from 1980 to 2015 using the rolling-window technique. A comparative analysis of pairwise dynamic integration and causality of stock markets, measured in common and domestic currency terms, is conducted to evaluate comprehensively how exchange rate fluctuations affect the time-varying integration among the S&P 500, FTSE 100 and EURO STOXX 50 indices. The results obtained show that the dynamic correlation, cointegration and ECM-based long-run Granger causality vary significantly over the whole sample period. The degree of dynamic correlation and cointegration between pairs of stock markets rises in periods of high volatility and uncertainty, especially under the influence of economic, financial and political shocks. Meanwhile, we observe the weaker and decreasing correlation and cointegration among the three developed stock markets during the recovery periods. Interestingly, the most persistent and significant cointegration among the three developed stock markets exists during the 2007–09 global financial crisis. Finally, the exchange rate fluctuations, also influence the dynamic integration and causality between all pairs of stock indices, with that influence increasing under the local currency terms. Our results suggest that the potential for diversifying risk by investing in the US, UK and Eurozone stock markets is limited during the periods of economic, financial and political shocks. [ABSTRACT FROM AUTHOR]

A superhydrophilic and antibacterial surface with silver nanoparticles (AgNPs) was fabricated on the blend membranes of poly(vinylidene fluoride) (PVDF) and poly(styrene- co-maleic anhydride) (SMA). The PVDF/SMA blend membranes were surface-modified firstly by coating polydopamine (PDA) in aqueous solution for 24 h. Subsequently, AgNPs were immobilized in situ. Lastly, the AgNP-loaded membranes were second coating PDA. Scanning electronic microscopy (SEM) was carried out to characterize both the micro- and nanoscale hierarchical structures. The results of X-ray photoelectron spectroscopy (XPS) indicated that metallic silver was formed and more Ag loaded might be apt to deposit more PDA during the second coating PDA procedure. The membrane surface hydrophilicity was characterized by water contact angle measurement; AgNPs and PDA had provided an excellent hydrophilicity. Meanwhile, AgNPs imparted outstanding antibacterial activity to the modified membranes which was confirmed by halo zone test. All of the results demonstrated that the modified surface possessed superhydrophilic and excellent antibacterial properties. [ABSTRACT FROM AUTHOR]

Phosphorus (P) leaching from excessive P application is the primary pathway of P losses in agricultural soils. Different P fertilizer practices have mixed effects on P leaching. We conducted a meta-analysis of the relevant literature regarding the response of crop yields, soil-available P (AP), and total P (TP) leaching to reduced P input (RP) and an inorganic-organic combination fertilizer (NPKM) for different agricultural land-use types. Compared to conventional P application (CP), RP (10~90% reduction) did not reduce crop yields in vegetable fields (experiments were 1~4 years) but significantly reduced cereal yields by 4.57%. Compared to chemical fertilizer (NPK), NPKM significantly increased cereal yields by 12.73%. Compared to CP, RP significantly reduced AP at 0~60 cm in vegetable and cereal fields. The greatest reduction occurred at 20~40 cm in vegetable fields (40.29%) and 0~20 cm in cereal fields (34.45%). Compared to NPK, NPKM significantly increased the AP at 0~60 cm in vegetable fields, with the greatest increase (52.44%) at 20~40 cm. The AP at 0~40 cm in cereal fields significantly increased under the NPKM treatment, with the greatest increase at 0~20 cm (76.72%). Compared to CP, RP significantly decreased TP leaching by 16.02% and 31.50% in vegetable and cereal fields, respectively. Compared to NPK, NPKM significantly increased TP leaching in vegetable fields (30.43%); no significant difference in leaching occurred in cereal fields. P leaching, in response to RP, was influenced by the P amounts applied (34.49%); soil organic matter (14.49%); and TP (12.12%). P leaching in response to NPKM was influenced by multiple factors: rainfall (16.05%); soil organic matter (12.37%); soil bulk density (12.07%); TP (11.65%); pH (11.41%). NPKM was more beneficial for improving yields in cereal fields with low soil fertility and lower P-leaching risks. [ABSTRACT FROM AUTHOR]

Quantitative metabolomics approaches can significantly improve the repeatability and reliability of metabolomics investigations but face critical technical challenges, owing to the vast number of unknown endogenous metabolites and the lack of authentic standards. The present study contributes to the development of a novel method known as "data-independent targeted quantitative metabolomics" (DITQM), which was used to investigate the label-free quantitative metabolomics of multiple known and unknown metabolites in biofluid samples. This approach initially involved the acquisition of MS/MS data for all metabolites in biosamples using a sequentially stepped targeted MS/MS (sst-MS/MS) method, in which multiple product ion scans were performed by selecting all ions in the targeted mass ranges as the precursor ions. Subsequently, scheduled multiple reaction monitoring (MRM) by LC-MS/MS of the metabolome was established for 1658 characteristic ion pairs of 1324 metabolites. For sensitive and accurate quantification of these metabolites, mixed calibration curves were generated using sequentially diluted standard reference plasma samples using established MRM methods. Relative concentrations of all metabolites in each sample were calculated without using individual authentic standards. To evaluate the reliability and applicability of this new method, the performance of DITQM was validated by comparison to absolute quantification of 12 acylcarnitines using authentic standards and traditional metabolomics analysis for lung cancer. The results proved that the DITQM protocol is more reliable and can significantly improve clustering effects and repeatability in biomarker discovery. In this study, we established a novel methodology to standardize and quantify large-scale metabolome, providing a new choice for metabolomics research and its clinical applications. [ABSTRACT FROM AUTHOR]

The authors have developed a surface-enhanced Raman spectroscopic (SERS) method for the determination of pyrophosphate ion (PPi). It is based on the competitive coordination of Cu(II) between cysteine (Cys) and PPi using silver nanoparticles (AgNPs) modified with Cys and Rhodamine 6G (R6G). Cys was attached to the surface of the AgNPs via Ag−S bond, and the amino acid unit in Cys bind to Cu(II) to form a chelate complex. This results in the aggregation of AgNPs and a strong SERS signal for the probe R6G. However, in the presence of PPi, the aggregated AgNPs are solubilized because of the stronger affinity between PPi and Cu(II). This leads to a decrease of the SERS signal and forms the basis for the quantitation of PPi. The amount of AgNPs, the concentration of Cu(II), and the mixing time were optimized. The method displays a linear response in the 0.1 to 80 μM PPi concentration range, and the limit of detection is as low as 20 nM. The method was applied to the determination of PPi in spiked serum samples and urine samples, with recoveries between 95.2 to 100.5% and relative standard deviations of <4.4%. [ABSTRACT FROM AUTHOR]

A simple and rapid method based on multi-throughput dynamic microwave-assisted extraction coupled online with salting-out-assisted liquid–liquid extraction was developed for the analysis of chlorpyrifos in soil. First, the chlorpyrifos was extracted with acetonitrile aqueous (50%, v/v) under the action of microwave energy. Then the obtained extract was separated clearly and easily into an acetonitrile phase and an aqueous phase with the assistance of ammonium acetate. The acetonitrile phase containing chlorpyrifos was concentrated and determined by liquid chromatography–tandem mass spectrometry. The effects of parameters on extraction efficiency including microwave power, extraction solvent, volumes and flow rate of extraction solvent, sample pH, types and amount of salt were studied and optimised. To eliminate the matrix effect, validation of the method was carried out using the matrix-based calibration curve. The limits of detection and quantification for chlorpyrifos were 0.17 and 0.5 ng g−1, respectively. The proposed method was applied to analyse chlorpyrifos in five soil samples and verified by the recovery test. The recoveries of chlorpyrifos at three spiked levels (5, 50, 200 ng g−1) were in the range of 90.0–100.5%, with relative standard deviations varying from 1.3% to 5.7%. Compared with the methods reported previously, the proposed method can simplify the operation procedure and reduce solvent consumption in sample pretreatment. [ABSTRACT FROM PUBLISHER]

Neurotransmitters (NTs) and their metabolites play crucial roles in the regulation of the sleep-wake cycle. Thus, a comprehensive quantitative analysis of NTs would be useful in elucidating the potential mechanisms involved in sedative-hypnotic activities. In this study, we developed a high-throughput quantitative method based on a two-dimensional chromatography-mass spectrometry technique to simultaneously analyze 63 NTs and their metabolites in rat plasma, brain homogenate, and microdialysis samples from five different sleep-associated regions of the brain. Moreover, this method was used to study the neurochemical mechanism of an adenosine analog sedative-hypnotic candidate YZG-331. Most of the correlations between NTs were lost after the administration of the sedative, particularly in the caudate putamen (CPu) and dorsal raphe nucleus (DRN), indicating that the sleep-wake balance was affected. Administration of the adenosine analog YZG-331 could act similar as accumulation of adenosine, inducing adenosine and its metabolite adenine were decreased significantly in the CPu, accompanying with GABA, aspartate, and glutamate changed slightly by the communications between different neurons to further promote sleep. In addition, YZG-331 affected the metabolism of tryptophan and serotonin (5-HT) in the DRN and orbital frontal cortex (OFC). Melatonin and 5-hydroxyindole-3-acetic acid (a metabolite of 5-HT) were significantly increased in the OFC, and the levels of glutamate/glutamine, asparagine, and adrenaline were altered. Sleep homeostasis is a balance between the duration of sleep and wakefulness and is coordinated by all NTs. The high-throughput quantitative method introduced in this study may aid in revealing the temporal cohesion among NTs, evaluating sleep homeostasis, and determining the effects of sedative-hypnotic drugs. [Display omitted] • Quantify 63 NTs/NTs' metabolites in plasma and brain • YZG-331 interrupts sleep homeostasis by acting similar as accumulation of adenosine in CPU [ABSTRACT FROM AUTHOR]

Voriconazole is widely used in the treatment and prevention of invasive fungal diseases. Common drug-induced liver injuries increase the economic burdens and the risks of premature drug withdrawal and disease recurrence. This study estimated the disposal cost of voriconazole-related liver injury, explored the risk factors of voriconazole-related liver injury in hospitalized patients, and established a predictive model of liver injury to assist clinicians and pharmacists in estimating the probability or risk of liver injury after voriconazole administration to allow for early identification and intervention in patients at high risk of liver injury. A retrospective study was conducted on the selected inpatients whose blood concentration of voriconazole was measured in the West China Hospital of Sichuan University from September 2016 to June 2020. The incidence and disposal cost of voriconazole-related liver injuries were calculated. The incidence of voriconazole-related liver injury was 15.82% (217/1372). The disposal cost has been converted to 2023 at a discount rate of 5%. The median (P25, P75) disposal cost of severe liver injury (n = 42), general liver injury (n = 175), and non-liver injury (n = 1155) was 993.59 (361.70, 1451.76) Chinese yuan, 0.00 (0.00, 410.48) yuan, and 0.00 (0.00, 0.00) yuan, respectively, with a statistically significant difference (p < 0.001). Single factor analysis and multiple factor logistic regression were used to analyze the risk factors of voriconazole-related liver injury. The voriconazole-related liver injury was related to the trough concentration (Cmin, OR 1.099, 95% CI 1.058–1.140), hypoproteinemia (OR 1.723, 95% CI 1.126–2.636), and transplantation status (OR 0.555, 95% CI 0.325–0.948). The prediction model of liver injury was Logit (P)= −2.219 + 0.094 × Cmin + 0.544 × Hydroproteinemia − 0.589 × Transplantation, and the prediction model nomogram was established. The model validation results showed that the C-index of the derivation set and validation set was 0.706 and 0.733, respectively. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was 0.705 and 0.733, respectively, indicating that the model had good prediction ability. The prediction model will be helpful to develop clinical individualized medication of voriconazole and to identify and intervene in the cases of patients at high risk of voriconazole-related liver injury early on, in order to reduce the incidence of voriconazole-related liver injuries and the cost of treatment. [ABSTRACT FROM AUTHOR]

Introduction: It has been acknowledged in China that actions should be taken immediately to ease the critical shortage of psychiatric nurses. However, with national data lacking, little is known about nurses' mental health status. Aim: To evaluate psychiatric nurses' mental health status by measuring their burnout, depression, anxiety and stress. Methods: All psychiatric nurses in the 41 selected hospitals in China were invited to participate in the survey. The Maslach Burnout Inventory‐Human Service Survey and Depression Anxiety Stress Scale were used to assess variables of interest. Results: 38.6% of psychiatric nurses met the criteria for burnout. The rates of depression, anxiety and stress were 26.3%, 36.4% and 12.5%, respectively. It was found that workplace region, educational level, working years, longer working hours and night shifts were associated with risk of burnout and DASS. Conclusions: More than a quarter of psychiatric nurses are suffering from burnout, depression or anxiety in China. Policymakers and hospital administrators should design a flexible schedule and restrict working hours for psychiatric nurses to achieve work‐life balance. Implications for Practice: The study informs policymakers and administrators on addressing the nursing shortage by identifying nurses immersed in negative emotions and preventing mental health problems. [ABSTRACT FROM AUTHOR]

Refractive indexes and thermal conductivities at room temperature of an Er:Yb:Lu 2 Si 2 O 7 crystal were measured to be 1.745, 1.730, 1.695 around 1550 nm and 9.08, 6.98, 7.29 W m−1K−1 along three optical indicatrix X , Y , Z axes, respectively. Room-temperature polarized absorption spectra, fluorescence decay curves and unpolarized up-conversion fluorescence spectrum of the crystal were investigated. Some spectroscopic parameters related to the 1.55 μm laser operation were calculated. End-pumped by a 975 nm laser diode, a 1565 nm continuous-wave laser with maximum output power of 2.18 W and slope efficiency of 21.8% was realized in an Er:Yb:Lu 2 Si 2 O 7 crystal. • The refractive index, thermal and spectroscopic properties of an Er:Yb:LPS crystal were investigated in detail. • Polarized spectra in 1400–1680 nm were investigated when considering the contribution of the magnetic dipole transition. • A 1565 nm continuous-wave laser with maximum output power of 2.18 W and slope efficiency of 21.8% was realized. [ABSTRACT FROM AUTHOR]

In this study, microbes were isolated from the rice slurry of a fermented rice cake to obtain lactic acid bacteria and yeast species. These species were identified using microbial physiology and gene sequence analyses. As the growth of the lactic acid bacterial strain R-2b and the yeast J-3a strains were found to be the best, a composite starter comprising these microbes was used for the preparation of fermented rice cakes. Based on single factor and orthogonal experiments, when the proportion of Lactobacillus plantarum , Saccharomyces cerevisiae , and Candida humilis was 1:3:6, the optimal fermentation conditions were addition of sugar and starter amounts of 20% and 6%, respectively, a fermentation temperature of 32 °C, and fermentation time of 8 h. The fermented rice cake with this optimum ratio had the most abundant volatile components and qualified physicochemical and microbial indexes. Additionally, the overall quality was better than that of commercially available products. • We isolated the yeast and bacteria from the rice slurry of a fermented rice steamed cake. • The starters comprising these three microbes were used for fermented rice cake preparation. • The fermented rice cake had the most abundant volatile components and overall quality. • The physicochemical and microbial indexes were better than that of commercial rice cake. [ABSTRACT FROM AUTHOR]

Accurate electric load forecasting could prove to be a very useful tool for all market participants in electricity markets. Because it can not only help power producers and consumers make their plans but also can maximize their profits. In this paper, a new combined forecasting method (ESPLSSVM) based on empirical mode decomposition, seasonal adjustment, particle swarm optimization (PSO) and least squares support vector machine (LSSVM) model is proposed. In the electric market, noise signals usually affect the forecasting accuracy, which were caused by different erratic factors. First of all, ESPLSSVM uses an empirical mode decomposition-based signal filtering method to reduce the influence of noise signals. Secondly, ESPLSSVM eliminates the seasonal components from the de-noised resulting series and then it models the resultant series using the LSSVM which is optimized by PSO (PLSSVM). Finally, by multiplying the seasonal indexes by the PLSSVM forecasts, ESPLSSVM acquires the final forecasting result. The effectiveness of the presented method is examined by comparing with different methods including basic LSSVM (LSSVM), empirical mode decomposition-based signal filtering method processed by LSSVM (ELSSVM) and seasonal adjustment processed by LSSVM (SLSSVM). Case studies show ESPLSSVM performed better than the other three load forecasting approaches. [ABSTRACT FROM AUTHOR]

A new organic small molecule, DCA3TBDF, with a 2D benzo[1,2-b:4,5-b']difuran (BDF) moiety as the central core and octyl cyanoacetate units as the end-capped blocks, was designed and synthesized for solution-processed bulk heterojunction solar cells. DCA3TBDF possesses good solubility in common organic solvents such as toluene, CH2Cl2, chlorobenzene, and CHCl3 and good thermal stability with an onset decomposition temperature with 5% weight-loss occurring at 361 °C. The DCA3TBDF thin film showed a broad absorption at λ=320-700 nm and high crystallinity. Small-molecule organic solar cells based on DCA3TBDF and [6,6]- phenyl-C61-butyric acid methyl ester demonstrated promising power conversion efficiency with a high fill factor under the illumination of AM 1.5G (100 mWcm-2). [ABSTRACT FROM AUTHOR]