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Existing deep learning methods have shown outstanding performance in predicting drug–target interactions. However, they still have limitations: (1) the over-reliance on locally extracted features by some single encoders, with insufficient consideration of global features, and (2) the inadequate modeling and learning of local crucial interaction sites in drug–target interaction pairs. In this study, we propose a novel drug–target interaction prediction model called the Neural Fingerprint and Self-Attention Mechanism (NFSA-DTI), which effectively integrates the local information of drug molecules and target sequences with their respective global features. The neural fingerprint method is used in this model to extract global features of drug molecules, while the self-attention mechanism is utilized to enhance CNN's capability in capturing the long-distance dependencies between the subsequences in the target amino acid sequence. In the feature fusion module, we improve the bilinear attention network by incorporating attention pooling, which enhances the model's ability to learn local crucial interaction sites in the drug–target pair. The experimental results on three benchmark datasets demonstrated that NFSA-DTI outperformed all baseline models in predictive performance. Furthermore, case studies illustrated that our model could provide valuable insights for drug discovery. Moreover, our model offers molecular-level interpretations. [ABSTRACT FROM AUTHOR]

Cerebral aneurysms are abnormal dilations of blood vessels in the brain that have the potential to rupture, leading to subarachnoid hemorrhage and other serious complications. Early detection and prediction of aneurysm rupture are crucial for effective management and prevention of rupture-related morbidities and mortalities. This review aims to summarize the current knowledge on risk factors and predictive indicators of rupture in cerebral aneurysms. Morphological characteristics such as aneurysm size, shape, and location, as well as hemodynamic factors including blood flow patterns and wall shear stress, have been identified as important factors influencing aneurysm stability and rupture risk. In addition to these traditional factors, emerging evidence suggests that biological and genetic factors, such as inflammation, extracellular matrix remodeling, and genetic polymorphisms, may also play significant roles in aneurysm rupture. Furthermore, advancements in computational fluid dynamics and machine learning algorithms have enabled the development of novel predictive models for rupture risk assessment. However, challenges remain in accurately predicting aneurysm rupture, and further research is needed to validate these predictors and integrate them into clinical practice. By elucidating and identifying the various risk factors and predictive indicators associated with aneurysm rupture, we can enhance personalized risk assessment and optimize treatment strategies for patients with cerebral aneurysms. [ABSTRACT FROM AUTHOR]

Deuterium/Tritium (D/T) handling in defined proportions are pivotal to maintain steady-state operation for fusion reactors. However, the hydrogen isotope effect in metal-hydrogen systems always disturbs precise D/T ratio control. Here, we reveal the dominance of kinetic isotope effect during desorption. To reconcile the thermodynamic stability and isotope effect, we demonstrate a quantitative indicator of Tgap and further a local coordination design strategy that comprises thermodynamic destabilization with vibration enhancement of interstitial isotopes for isotope engineering. Based on theoretical screening analysis, an optimized Ti-Pd co-doped Zr0.8Ti0.2Co0.8Pd0.2 alloy is designed and prepared. Compared to ZrCo alloy, the optimal alloy enables consistent isotope delivery together with a three-fold lower Tgap, a five-fold lower energy barrier difference, a one-third lower isotopic composition deviation during desorption and an over two-fold higher cycling capacity. This work provides insights into the interaction between alloy and hydrogen isotopes, thus opening up feasible approaches to support high-performance fusion reactors. [ABSTRACT FROM AUTHOR]

Background: Questioned document examination (QDE) is a crucial sub-discipline of forensic science, and over the years, this discipline has developed a vast amount of research results and literature. However, the current studies have only reviewed the development of QDE for a period of time or a particular research direction, lacking a comprehensive review of this discipline since its origins. Aim: The aim of this study is to utilize bibliometric methods to review the history and development of QDE since 1934 and also to predict its future research trends. Materials: This study collects the literature of questioned document examination (QDE) from the Web of Science Core Collection database and uses four bibliometric analysis tools: CiteSpace, VOSviewer, SciMAT, and Bibliometric, to process relevant literature data. Methods: Through the analysis methods of journal co-citation analysis, keyword co-occurrence network analysis, literature cocitation analysis, and theme evolutionary analysis, the bibliometric data information in the QDE field is obtained, and a visualized knowledge mapping is constructed. Results: The results show that four research directions have been formed, basically. As far as the development trend of QDE research is concerned, the research field shows the change in content from cursory to detailed and in analysis from qualitative to quantitative, while the research field maintains a close relationship with chemical technology and computer science. Conclusions: The changes in QDE can be attributed to advancements in science and technology, which have influenced research methods. QDE also has a legal aspect, with a focus on enhancing scientific accuracy and evidentiary value. These developments aim to strengthen QDE's identification power and promote its scientific and standardized growth. This will gradually enhance the reliability and strength of QDE evidence, making it more valuable in judicial practice. [ABSTRACT FROM AUTHOR]

Objective: Inflammation is recognized as a contributor in the development of pulmonary arterial hypertension (PAH), and the recruitment and functional capacity of immune cells are well-orchestrated by chemokines and their receptors. This study is aimed at identification of critical chemokines in the progression of PAH via transcriptomic analysis. Methods: Differentially expressed genes (DEGs) from lungs of PAH patients were achieved compared to controls based on Gene Expression Omnibus (GEO) database. Gene set enrichment analysis (GSEA) was applied for functional annotation and pathway enrichement. The abundance of immune cells was estimated by the xCell algorithm. Weighted correlation network analysis (WGCNA) was used to construct a gene expression network, based on which a diagnostic model was generated to determine its accuracy to distinguish PAH from control subjects. Target genes were then validated in lung of hypoxiainduce pulmonary hypertension (PH) mouse model. Results: ACKR4 (atypical chemokine receptor 4) was downregulated in PAH lung tissues in multiple datasets. PAH relevant biological functions and pathways were enriched in patients with low-ACKR4 level according to GSEA enrichment analysis. Immuno-infiltration analysis revealed a negative correlation of activated dendritic cells, Th1 and macrophage infiltration with ACKR4 expression. Three gene modules were associated with PAH via WGCNA analysis, and a model for PAH diagnosis was generated using CXCL12, COL18A1 and TSHZ2, all of which correlated with ACKR4. The ACKR4 expression was also downregulated in lung tissues of our experimental PH mice compared to that of controls. Conclusions: The reduction of ACKR4 in lung tissues of human PAH based on transcriptomic data is consistent with the alteration observed in our rodent PH. The correlation with immune cell infiltration and functional annotation indicated that ACKR4 might serve as a protective immune checkpoint for PAH. [ABSTRACT FROM AUTHOR]

The autotetraploid Carassius auratus (4nRR, 4n=200, RRRR) is derived from whole-genome duplication of Carassius auratus red var. (RCC, 2n=100, RR). In the current study, we demonstrated that chromatophores and pigment changes directly caused the coloration and variation of 4nRR skin (red in RCC, brownish-yellow in 4nRR). To further explore the molecular mechanisms underlying coloration formation and variation in 4nRR, we performed transcriptome profiling and molecular functional verification in RCC and 4nRR. Results revealed that scarb1, associated with carotenoid metabolism, underwent significant down-regulation in 4nRR. Efficient editing of this candidate pigment gene provided clear evidence of its significant role in RCC coloration. Subsequently, we identified four divergent scarb1 homeologs in 4nRR: two original scarb1 homeologs from RCC and two duplicated ones. Notably, three of these homeologs possessed two highly conserved alleles, exhibiting biased and allele specific expression in the skin. Remarkably, after precise editing of both the original and duplicated scarb1 homeologs and/or alleles, 4nRR individuals, whether singly or multiply mutated, displayed a transition from brownish-yellow skin to a cyan-gray phenotype. Concurrently, the proportional areas of the cyan-gray regions displayed a gene-dose correlation. These findings illustrate the sub functionalization of duplicated scarb1, with all scarb1 genes synergistically and equally contributing to the pigmentation of 4nRR. This is the first report concerning the functional differentiation of duplicated homeologs in an autopolyploid fish, substantially enriching our understanding of coloration formation and change within this group of organisms. [ABSTRACT FROM AUTHOR]

Introduction: In the Dongting water system, the Carassius auratus (Crucian carp) complex is characterized by the coexistence of diploid forms (2n=100, 2nCC) and polyploidy forms. The diploid (2nCC) and triploid C.auratus (3n=150, 3nCC) had the same fertility levels, reaching sexual maturity at one year. Methods: The nucleotide sequence, gene expression, methylation, and immunofluorescence of the gonadotropin releasing hormone 2(Gnrh2), Gonadotropin hormone beta(Gthb), and Gonadotropin-releasing hormone receptor(Gthr) genes pivotal genes of the hypothalamic-pituitary-gonadal (HPG) axis were analyzed. Results: The analysis results indicated that Gnrh2, follicle-stimulating hormone receptor(Fshr), and Lethal hybrid rescue(Lhr) genes increased the copy number and distinct structural differentiation in 3nCC compared to that in 2nCC. The transcript levels of HPG axis genes in 3nCC were higher than 2nCC (P<0.05), which could promote the production and secretion of sex steroid hormones conducive to the gonadal development of 3nCC. Meanwhile, the DNA methylation levels in the promoter regions of the HPG axis genes were lower in 3nCC than in 2nCC. These results suggested that methylation of the promoter region had a potential regulatory effect on gene expression after triploidization. Immunofluorescence showed that the localization of the Fshβ,Lhβ, and Fshr genes between 3nCC and 2nCC remained unchanged, ensuring the normal expression of these genes at the corresponding sites after triploidization. Discussion: Relevant research results provide cell and molecular biology evidence for normal reproductive activities such as gonad development and gametematuration in triploid C. auratus, and contribute to further understanding of the genetic basis for fertility restoration in triploid C. auratus. [ABSTRACT FROM AUTHOR]

Hydrogen storage alloys (HSAs) are attracting widespread interest in the nuclear industry because of the generation of stable metal hydrides after tritium absorption, thus effectively preventing the leakage of radioactive tritium. Commonly used HSAs in the hydrogen isotopes field are Zr2M (M = Co, Ni, Fe) alloys, metallic Pd, depleted U, and ZrCo alloy. Specifically, Zr2M (M = Co, Ni, Fe) alloys are considered promising tritium-getter materials, and metallic Pd is utilized to separate and purify hydrogen isotopes. Furthermore, depleted U and ZrCo alloy are well suited for storing and delivering hydrogen isotopes. Notably, all the aforementioned HSAs need to modulate their hydrogen storage properties for complex operating conditions. In this review, we present a comprehensive overview of the reported modification methods applied to the above alloys. Alloying is an effective amelioration method that mainly modulates the properties of HSAs by altering their local geometrical/electronic structures. Besides, microstructural modifications such as nano-sizing and nanopores have been used to increase the specific surface area and active sites of metallic Pd and ZrCo alloys for enhancing de-/hydrogenation kinetics. The combination of metallic Pd with support materials can significantly reduce the cost and enhance the pulverization resistance. Moreover, the poisoning resistance of ZrCo alloy is improved by constructing active surfaces with selective permeability. Overall, the review is constructive for better understanding the properties and mechanisms of hydrogen isotope storage alloys and provides effective guidance for future modification research. [ABSTRACT FROM AUTHOR]

Motivation Research on human microbiome has suggested associations with human health, opening opportunities to predict health outcomes using microbiome. Studies have also suggested that diverse forms of taxa such as rare taxa that are evolutionally related and abundant taxa that are evolutionally unrelated could be associated with or predictive of a health outcome. Although prediction models were developed for microbiome data, no prediction models currently exist that use multiple forms of microbiome–outcome associations. Results We developed MK-BMC, a M ulti- K ernel framework with B oosted distance M etrics for C lassification using microbiome data. We propose to first boost widely used distance metrics for microbiome data using taxon-level association signal strengths to up-weight taxa that are potentially associated with an outcome of interest. We then propose a multi-kernel prediction model with one kernel capturing one form of association between taxa and the outcome, where a kernel measures similarities of microbiome compositions between pairs of samples being transformed from a proposed boosted distance metric. We demonstrated superior prediction performance of (i) boosted distance metrics for microbiome data over original ones and (ii) MK-BMC over competing methods through extensive simulations. We applied MK-BMC to predict thyroid, obesity, and inflammatory bowel disease status using gut microbiome data from the American Gut Project and observed much-improved prediction performance over that of competing methods. The learned kernel weights help us understand contributions of individual microbiome signal forms nicely. Availability and implementation Source code together with a sample input dataset is available at https://github.com/HXu06/MK-BMC [ABSTRACT FROM AUTHOR]

Background: Self-directed learning (SDL) is one of the most important abilities for medical students in terms of their future clinical medical practice. During the blended teaching process, teachers can design a variety of learning activities to cultivate students’ SDL abilities. This study aimed to assess the differences between the SDL abilities of medical students using blended and traditional didactic teaching. Methods: This study included 239 medical students from eight administrative classes. The students were divided into two groups: (1) the experimental group (EG), which included 119 students from four administrative classes, and (2) the control group (CG), which included 120 students from the remaining four classes. From February to July 2022, blended teaching methods were applied to the EG group, and SDL abilities were assessed in comparison to the CG group receiving traditional didactic teaching methods. Results: At the end of the semester, significant differences (p < 0.05) were observed between EG and CG in all six SDL ability factors. Furthermore, when k-means cluster analysis was used to analyze the learning behavior of students in the EG after classifying them as comprehensive, interactive, and passive types, significant differences were observed in all six Self-directed learning factors of students with the comprehensive type, whereas significant differences were observed in four factors (setting learning goals and plans, self-monitoring and regulation, information processing, and communication and cooperation) of students with the interactive type. For students with passive type, only one factor of SDL (information processing) showed significant improvement. There were on differences between comprehensive, interactive, and passive types of CG. Conclusion: The blended teaching approach is better than the conventional didactic teaching for cultivating clinical medical students’ SDL abilities. [ABSTRACT FROM AUTHOR]

The symptoms of Behçet's disease (BD), a multisystemic condition with autoimmune and inflammation as hallmarks, include arthritis, recurring oral and vaginal ulcers, skin rashes and lesions, and involvement of the nervous, gastrointestinal, and vascular systems. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), may be important regulators of inflammation and autoimmune disease. These ncRNAs are essential to the physiological and pathophysiological disease course, and miRNA in particular has received significant attention for its role and function in BD and its potential use as a diagnostic biomarker in recent years. Although promising as therapeutic targets, miRNAs must be studied further to fully comprehend how miRNAs in BD act biologically. [ABSTRACT FROM AUTHOR]

Introduction: To analyze the impact of yoga and music intervention on child consumers, we selected 60 eligible child consumers from yoga and music companies. Methods: This preliminary study used a randomized controlled design to investigate whether a 16-week combined yoga and music intervention improves attention, hyperactivity/impulsivity, and oppositional defiant disorder (ODD) in 60 children with attention-deficit/hyperactivity disorder (ADHD) comorbid with ODD aged 4-6 years. It also preliminarily identified which intervention is best for these children among three types: combined yoga and music, yoga-only, and musiconly interventions. We used both the parent- and teacher-rated MTA SNAP-IV ADHD Rating Scale for data collection. Results: We found that the combined yoga and music intervention had a positive effect on inattention, hyperactivity/impulsivity, and ODD in children with comorbid ADHD and ODD. The combined yoga and music intervention was the most effective in reducing inattention (in repeated measures ANOVA effect size, 0.9; followed by the yoga- and the music-only interventions, respectively), hyperactivity/impulsivity (effect size, 0.92), and ODD behaviors (effect size, 0.93) in children with comorbid ADHD and ODD. Thus, the combined yoga and music intervention was the most effective and had a more comprehensive effect on children with combined ADHD and ODD compared with the two other interventions (i.e., yoga- and music-only interventions). Discussion: Our findings provide preliminary evidence for the use of combined yoga and music interventions on a daily basis as a safe and effective adjunctive treatment for children with comorbid ADHD and ODD. The children in the article refer to child consumers of yoga and music companies. [ABSTRACT FROM AUTHOR]

Pears carry a gametophytic self-incompatibility (SI) system. In this system, S-RNase is the SI pistil determinant, and S-locus F-box brothers (SFBBs) are candidate pollen determinants. However, compared with apple, fewer SFBB genes were identified from pear, possibly caused by the lack of economic and effective methods. Here, we used transcriptome sequencing on 'Yali' (Pyrus bretschneideri) to obtain sequence fragments of SFBB genes and then used polymerase chain reaction (PCR) to amplify the whole sequence of SFBB genes. Twenty-seven SFBB genes, including 22 full-length and five nonfull-length SFBB genes, were identified in 'Yali' (P. bretschneideri). SFBBs linkage analysis by PCR-enzyme-linked immunoassay (ELISA) showed that 12 SFBB genes belong to the S21 locus, and 15 SFBB genes belong to the S34 locus. Phylogenetic analysis showed that SFBB genes from Pyrus were divided into 26 types, more than the original eight types. The intrahaplotypic divergence of SFBBs is high and comparable to the allelic diversity of S-RNase, which is consistent with a nonself-recognition SI system. In addition, the expression level of PbrSFBBs in 'Jinzhui', the only known haploid pollen of a self-compatible mutant, was mostly approximately two times higher than in 'Yali', which may be the reason for the self-compatible mutant. [ABSTRACT FROM AUTHOR]

We aimed to investigate the genetic defects related to pollen development and infertility in NY2, a novel tetraploid rice germplasm known as Neo-tetraploid rice. This rice variety was created through the crossbreeding and selective breeding of various autotetraploid rice lines and has previously shown high fertility. Our previous research has revealed that the NY2 gene, encoding a eukaryotic translation initiation factor 3 subunit E, regulates pollen fertility. However, the underlying mechanism behind this fertility is yet to be understood. To shed light on this matter, we performed a combined cytological and transcriptome analysis of the NY2 gene. Cytological analysis indicated that ny2 underwent abnormal tapetal cells, microspore, and middle layer development, which led to pollen abortion and ultimately to male sterility. Genetic analysis revealed that the F1 plants showed normal fertility and an obvious advantage for seed setting compared to ny2. Global gene expression analysis in ny2 revealed a total of 7545 genes were detected at the meiosis stage, and 3925 and 3620 displayed upregulation and downregulation, respectively. The genes were significantly enriched for the gene ontology (GO) term "carbohydrate metabolic process. Moreover, 9 genes related to tapetum or pollen fertility showed downregulation, such as OsABCG26 (ATP Binding Cassette G26), TMS9-1 (Thermosensitive Male Sterility), EAT1 (Programmed cell death regulatory), KIN14M (Kinesin Motor), OsMT1a (Metallothionein), and OsSTRL2 (Atypical strictosidine synthase), which were validated by qRT-PCR. Further analyses of DEGs identified nine down-regulated transcription factor genes related to pollen development. NY2 is an important regulator of the development of tapetum and microspore. The regulatory gene network described in this study may offer important understandings into the molecular processes that underlie fertility control in tetraploid rice. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is the most frequent musculoskeletal disease and the major contributor to disability worldwide. Metabolic syndrome (MetS) has been recognized as being associated with the pathogenesis of osteoarthritis. However, the exact mechanisms and links between the two are not clear. Methods: We downloaded clinical information data and gene expression profiles for OA and MetS from the database of Gene Expression Omnibus (GEO), and immune related gene (IRG) from the database of Immunology Database and Analysis Portal (IMMPORT). After screening OA-DEG and MetS-DEG, we identified the common immune hub gene by screening the overlapping genes between OA-DEG, MetS-DEG and IRG. Then we conducted single-gene analysis of S100A8, assessed the correlation of S100A8 with immune cell infiltration, and verified the diagnostic value of S100A8 in OA and MetS database respectively. Results: 323 OA-DEGs, 101 MetS-DEGs and an immune-related hub gene, S100A8, were identified. In single gene analysis of S100A8 in OA samples, GSEA suggested that immune-related biological processes were more significantly enriched. The results of immune cell infiltration analysis showed that the enrichment fraction of M2 macrophages was significantly higher in the high S100A8-expressing group, and the level of S100A8 expression was positively correlated with M2 macrophage infiltration. The results of the dataset validation showed that S100A8 expression levels were significantly upregulated in the OA group and performed well in the diagnosis of OA. In single gene analysis of S100A8 in MetS samples, immune cell infiltration analysis showed that monocyte infiltration was higher in the S100A8 high expression samples and that there was a positive correlation between the two. Dataset validation showed that S100A8 is of high value for the diagnosis of MetS. In the validation of the dataset for the four metabolism-related diseases (obesity, diabetes, hypertension and hyperlipidaemia), S100A8 was expressed at higher levels in the disease group and also had a higher diagnostic value for the four metabolism-related diseases. Conclusion: S100A8 is a common hub gene and diagnostic biomarker for OA and MetS, and the immune regulation involved in S100A8 may play a central role in the pathogenesis of OA and MetS. [ABSTRACT FROM AUTHOR]

Introduction: Servant leadership has long been associated with maintaining employee's affective commitment, yet the underlying mechanism remains unclear. Research from non-western cultures remains scarce. Methods: This study sought to fill in such research gap by introducing insights from social exchange theory perspective, and examined two potential mediators (viz., psychological safety and job burnout) with a largescale, representative Chinese sample. Results: A total of 931 staffs in a Chinese hospital were surveyed, and structural equation models revealed that psychological safety (indirect effect = 0.052, 95% Bootstrap CI = [0.002, 0.101]) and job burnout (indirect effect = 0.277, 95% Bootstrap CI = [0.226, 0.331]) parallelly (and partially) mediated the effect of servant leadership on affective commitment. Moreover, these effects held the same between permanent and temporary staffs, as well as between male and female staffs. Discussion: Results suggested that a leader's orientation to care, validate, and respond to their followers' needs was effective in creating a psychological safe environment and downplaying job burnout in workplace, in exchange to which, followers remained affectively committed to their organization in a long term. Not only did this study contribute to existing literature by providing non-western data for service leadership research, it also provided a deeper understanding of associated mechanisms of how servant leadership might cast on talent retain and organizational development in a long term. These mechanisms shed light on how serving helps leading and advocate servant leadership for hospitals, as well as other serving organizations. [ABSTRACT FROM AUTHOR]

Objective: Inflammation is recognized as a contributor in the development of pulmonary arterial hypertension (PAH), and the recruitment and functional capacity of immune cells are well-orchestrated by chemokines and their receptors. This study is aimed at identification of critical chemokines in the progression of PAH via transcriptomic analysis. Methods: Differentially expressed genes (DEGs) from lungs of PAH patients were achieved compared to controls based on Gene Expression Omnibus (GEO) database. Gene set enrichment analysis (GSEA) was applied for functional annotation and pathway enrichement. The abundance of immune cells was estimated by the xCell algorithm. Weighted correlation network analysis (WGCNA) was used to construct a gene expression network, based on which a diagnostic model was generated to determine its accuracy to distinguish PAH from control subjects. Target genes were then validated in lung of hypoxiainduce pulmonary hypertension (PH) mouse model. Results: ACKR4 (atypical chemokine receptor 4) was downregulated in PAH lung tissues in multiple datasets. PAH relevant biological functions and pathways were enriched in patients with low-ACKR4 level according to GSEA enrichment analysis. Immuno-infiltration analysis revealed a negative correlation of activated dendritic cells, Th1 and macrophage infiltration with ACKR4 expression. Three gene modules were associated with PAH via WGCNA analysis, and a model for PAH diagnosis was generated using CXCL12, COL18A1 and TSHZ2, all of which correlated with ACKR4. The ACKR4 expression was also downregulated in lung tissues of our experimental PH mice compared to that of controls. Conclusions: The reduction of ACKR4 in lung tissues of human PAH based on transcriptomic data is consistent with the alteration observed in our rodent PH. The correlation with immune cell infiltration and functional annotation indicated that ACKR4 might serve as a protective immune checkpoint for PAH. [ABSTRACT FROM AUTHOR]

We aimed to assess general fluid management in China and evaluate the association between fluid balance and survival outcomes in acute respiratory distress syndrome (ARDS) patients. A retrospective, multicenter study including ARDS patients was conducted. We described the fluid management of ARDS patients in China. Furthermore, clinical characteristics and outcomes of patients subdivided by cumulative fluid balance were also analyzed. Multivariable logistic regression analysis was performed with hospital mortality as the outcome. From June 2016 to February 2018, 527 ARDS patients were included in our study. The mean cumulative fluid balance was 1669 (-1101 to 4351) mL in the first 7 day after intensive care unit (ICU) admission. Patients were divided into four groups based on cumulative fluid balance of the first 7 day after ICU admission: Group I (≤0 L), Group II (>0 L, ≤3L), Group III (>3L, ≤5 L), and Group IV (>5 L). Significantly lower hospital mortality was observed in patients with a lower cumulative fluid balance on day 7 of ICU admission (20.5% in Group I vs. 32.8% in Group II, 38.5% in Group III, and 50% in Group IV, p < 0.001). A lower fluid balance is associated with lower hospital mortality in patients with ARDS. However, a large-scale and well-designed randomized controlled trial is needed in the future. [ABSTRACT FROM AUTHOR]

The nerve trunk healing process of a transected peripheral nerve trunk is composed of angiogenesis, nerve fiber regeneration, and scarring. Nerve trunk healing and neuroma formation probably share identical molecular mediators and similar regulations. At the nerve transection site, angiogenesis is sufficient and necessary for nerve fiber regeneration. Angiogenesis and nerve fiber regeneration reveal a positive correlation in the early time. Scarring and nerve fiber regeneration show a negative correlation in the late phase. We hypothesize that anti-angiogenesis suppresses neuromas. Subsequently, we provide potential protocols to test our hypothesis. Finally, we recommend employing anti-angiogenic small-molecule protein kinase inhibitors to investigate nerve transection injuries. [ABSTRACT FROM AUTHOR]

The gastrointestinal symptom of diabetes mellitus, chronic constipation, seriously affects patients’ life. Whereas, the mechanism of chronic constipation is still ambiguous, resulting in a lack of effective therapies for this symptom. As a part of the smooth muscle cells, interstitial cells of Cajal, and platelet-derived growth factor receptor alpha-positive (PDGFRα+) cells syncytium (SIP syncytium), PDGFRα+ cells play an important role in regulating colonic motility. According to our previous study, in PDGFRα+ cells in colons of diabetic mice, the function of the P2Y1 purinergic receptor/type 3 small-conductance calcium-activated potassium (SK3) channel signaling pathway is strengthened, which may lead to colonic dysmotility. The purpose of this study is to investigate the changes in SK3 channel properties of PDGFRα+ cells in diabetic mice. Methods Whole-cell patch clamp, Western blotting, superoxide dismutase activity measurement, and malondialdehyde measurement were main methods in the present study. Results The present study revealed that when dialysed with low calcium ion (Ca2+) solution, the SK3 current density was significantly decreased in PDGFRα+ cells from diabetic mice. However, the SK3 current density in PDGFRα+ cells was enhanced from diabetic mice when dialysed with high Ca2+ solution. Moreover, hydrogen peroxide-treatment mimicked this phenomenon in SK3 transgenic HEK293 cells. The subunit of SK3 channels, protein kinase CK2, was up-regulated in colonic muscle layers and hydrogen peroxide treated HEK293 cells. Additionally, protein phosphatase 2A, the subunit of SK3 channels, was not changed in streptozotocin-treated mouse colons or hydrogen peroxide-treated HEK293 cells. Conclusion The diabetic oxidative stress-induced upregulation of CK2 contributed to modulating SK3 channel sensitivity to Ca2+ in colonic PDGFRα+ cells, which may result in colonic dysmotility in diabetic mice. [ABSTRACT FROM AUTHOR]

Anomaly detectors are used to distinguish differences between normal and abnormal data, which are usually implemented by evaluating and ranking the anomaly scores of each instance. A static unsupervised streaming anomaly detector is difficult to dynamically adjust anomaly score calculation. In real scenarios, anomaly detection often needs to be regulated by human feedback, which benefits adjusting anomaly detectors. In this paper, we propose a human-machine interactive streaming anomaly detection method, named ISPForest, which can be adaptively updated online under the guidance of human feedback. In particular, the feedback will be used to adjust the anomaly score calculation and structure of the detector, ideally attaining more accurate anomaly scores in the future. Our main contribution is to improve the tree-based streaming anomaly detection model that can be updated online from perspectives of anomaly score calculation and model structure. Our approach is instantiated for the powerful class of tree-based streaming anomaly detectors, and we conduct experiments on a range of benchmark datasets. The results demonstrate that the utility of incorporating feedback can improve the performance of anomaly detectors with a few human efforts. [ABSTRACT FROM AUTHOR]

With the rapid development of modern computing techniques, high-dimensional data are increasingly encountered in many studies. In this paper, we propose a three-step method to study the mean testing problem. The proposed test is based on the p-values calculated from the univariate tests and the dimension reduction method. Since it does not require explicit conditions of data dimension and sample size, we can use it to solve the mean testing problem of high-dimensional data, especially when the data dimension is much larger than the sample size. The new method can be implemented for the normal and non-normal distribution, which has a wide application. Various simulations are conducted to compare the testing power of the new method and the existing tests. The comparison shows that the new method has higher testing power. We also apply the proposed method to a real example of gene expression data. [ABSTRACT FROM AUTHOR]

Established autotetraploids often have a highly stable meiosis with high fertility compared with neo-autotetraploids. The autotetraploid Carassius auratus (4n = 200, RRRR) (4nRR), which stemmed from whole-genome duplication of Carassius auratus red var. (2n = 100, RR) (RCC), produces diploid gametes with an adopted diploid-like chromosome pairing in meiosis and maintains the formation of autotetraploid lineages. In this study, we focused on Dmc1, a meiosis-specific recombinase during the prophase of meiosis I, and elaborated on the genetic variation, alternative transcription, expression characterization, and epigenetic modification of Dmc1 in RCC and 4nRR. Two original Dmc1 from RCC were identified in 4nRR, and two duplicated Dmc1 differences in genetic composition were observed in 4nRR. Furthermore, we only noticed that one original and one duplicated Dmc1 were expressed in RCC and 4nRR, respectively. However, both possessed identical gene expression profiles, differential expression of sexual dimorphism, and hypomethylation levels. These results indicated that the specific expression of duplicated Dmc1 may be involve in the progression of meiosis of the diploid-like chromosome pairing in autotetraploid Carassius auratus. Herein, the findings significantly increase knowledge of meiosis of autopolyploid fish and provide meaningful insights into genetic breeding in polyploidy fish. [ABSTRACT FROM AUTHOR]

Currently, for ovarian cancer, which has the highest mortality rate among all gynecological cancers, the standard treatment protocol is initial tumor cytoreductive surgery followed by platinum-based combination chemotherapy. Although the survival rate after standard treatment has improved, the therapeutic effect of traditional chemotherapy is very limited due to problems such as resistance to platinum-based drugs and recurrence. With the advent of the precision medicine era, molecular targeted therapy has gradually entered clinicians’ view, and individualized precision therapy has been realized, surpassing the limitations of traditional therapy. The detection of genetic mutations affecting treatment, especially breast cancer susceptibility gene (BRCA) mutations and mutations of other homologous recombination repair defect (HRD) genes, can guide the targeted drug treatment of patients, effectively improve the treatment effect and achieve a better patient prognosis. This article reviews different sites and pathways of targeted therapy, including angiogenesis, cell cycle and DNA repair, and immune and metabolic pathways, and the latest research progress from preclinical and clinical trials related to ovarian cancer therapy. [ABSTRACT FROM AUTHOR]

Dimension prediction of robotic wire and arc additive manufacturing (WAAM) part is fundamentally dependent on the modelling accuracy of single-bead profile and its subsequent overlapping ones. Current multi-bead overlapping models are still not capable of describing the flatten valley area of WAAM parts. This paper proposes a new recursive model, based on coordinate transformation and axisymmetric drop shape analysis (ADSA), to predict multi-bead overlapping profiles. First, a single-bead profile model for WAAM is established based on ADSA, followed by detailed description of conventional and proposed modified recursive ADSA profile model. The properties of developed recursive ADSA model are then investigated to reveal the effects of overlapping ratio and single-bead aspect ratio. Finally, multi-bead overlapping deposition experiment is carried out to validate the model feasibility. The results show that the modified recursive ADSA model is more accurate than the conventional one for its better accountability of valley areas. It is also indicated that the modified recursive ADSA model is suitable for the robotic WAAM process. The research outcome is beneficial to improving the forming accuracy of WAAM parts and geometry prediction of other additive manufactured products. [ABSTRACT FROM AUTHOR]

(1) Background: DNA double strand breaks (DSBs) are the most serious form of DNA damage that affects oocyte maturation and the physiological state of follicles and ovaries. Non-coding RNAs (ncRNAs) play a crucial role in DNA damage and repair. This study aims to analyze and establish the network of ncRNAs when DSB occurs and provide new ideas for next research on the mechanism of cumulus DSB. (2) Methods: Bovine cumulus cells (CCs) were treated with bleomycin (BLM) to construct a DSB model. We detected the changes of the cell cycle, cell viability, and apoptosis to determine the effect of DSBs on cell biology, and further evaluated the relationship between the transcriptome and competitive endogenous RNA (ceRNA) network and DSBs. (3) Results: BLM increased γH2AX positivity in CCs, disrupted the G1/S phase, and decreased cell viability. Totals of 848 mRNAs, 75 long noncoding RNAs (lncRNAs), 68 circular RNAs (circRNAs), and 71 microRNAs (miRNAs) in 78 groups of lncRNA–miRNA–mRNA regulatory networks, 275 groups of circRNA–miRNA–mRNA regulatory networks, and five groups of lncRNA/circRNA–miRNA–mRNA co-expression regulatory networks were related to DSBs. Most differentially expressed ncRNAs were annotated to cell cycle, p53, PI3K-AKT, and WNT signaling pathways. (4) Conclusions: The ceRNA network helps to understand the effects of DNA DSBs activation and remission on the biological function of CCs. [ABSTRACT FROM AUTHOR]

The findings regarding changes in renal function in patients with hepatitis C virus (HCV) infection treated with direct-acting antivirals (DAAs) are controversial. This study attempted to identify the factors associated with the large decline in renal function following DAA treatment. This retrospective cohort study included patients treated with DAAs at Chiayi and Yunlin Chang Gung Hospitals, Taiwan, from 1 January 2017 to 31 October 2020. Estimated glomerular filtration rate (eGFR) data were collected within 90 days prior to DAA therapy and 2 years after the confirmation of a sustained virologic response (SVR). We performed multiple logistic regression to evaluate the clinical or laboratory parameters associated with a large eGFR decline (≥10%). Among the enrolled 606 patients, the mean eGFR at the baseline and endpoint were 84.11 ± 24.38 and 78.88 ± 26.30 mL/min/1.73 m2, respectively (p < 0.001). The factors associated with a large eGFR decline 2 years after the SVR included hypertension (OR: 1.481; 95% CI: 1.010–2.173, p = 0.044) and a higher baseline eGFR (OR: 1.016; 95% CI: 1.007–1.024, p < 0.001). A higher albumin level reduced the risk of a large eGFR decline (OR: 0.546; 95% CI: 0.342–0.872, p = 0.011). In the patients with HCV treated with DAAs, a larger renal function decline was more commonly observed in those with hypertension, a lower (but within normal range) albumin level, and a higher baseline eGFR, while DAA treatment had no effect. The clinical significance of these findings has to be further defined. Although some risk factors associated with chronic kidney disease may be alleviated after DAA treatment, the regular control and follow-up of risk factors and renal function are still recommended in at-risk patients after HCV eradication. [ABSTRACT FROM AUTHOR]

Background: Although hemoglobin A1c (HbA1c) is closely related to diabetes, its relationship with the incidence of hypertension is still unknown, so we aimed to evaluate the relationship between HbA1c and the incidence of hypertension in the general population. Method: In this large prospective cohort study with a median follow-up of 2 years, we included 4,074 participants from the China Health and Nutrition Survey (CHNS). Multivariate COX regression, subgroup analysis, receiver operator characteristic (ROC) curve and restricted cubic spline (RCS) were used to evaluate the relationship between HbA1c and incidental hypertension. Results: Compared with participants without incident hypertension, participants with incident hypertension had higher levels of HbA1c (P < 0.05). In univariate COX regression analysis, HbA1c was associated with the risk of hypertension (HR: 1.161, 95% CI: 1.105-1.221, P < 0.001). In multivariate COX regression analysis adjusted for confounding variables, HbA1c was still closely related to the risk of hypertension (HR: 1.102, 95% CI: 1.006-1.206, P = 0.037). And subgroup analysis showed that the relationship between HbA1c and hypertension remained significant in female, lower than high school and non-obese subgroups (P < 0.05). ROC curve also showed that HbA1c could predict the risk of hypertension (AUC = 0.583, 95% CI: 0.568-0.598, P < 0.001). Further RCS analysis showed that HbA1c was positively correlated with the risk of hypertension (P for nonlinearity = 0.642). Conclusion: HbA1c was linearly and positively associated with the incidence of hypertension. [ABSTRACT FROM AUTHOR]

Background: An early diagnosis model with clinical phenotype classification is key for the early identification and precise treatment of sepsis-associated acute respiratory distress syndrome (ARDS). This study aimed to: 1) build a machine learning diagnostic model for patients with sepsis-associated ARDS using easily accessible early clinical indicators, 2) conduct rapid classification of clinical phenotypes in this population, and 3) explore the differences in clinical characteristics, outcomes, and treatment responses of different phenotypes. Methods: This study is based on data from the Telehealth Intensive Care Unit (eICU) and Medical Information Mart for Intensive Care IV (MIMIC-IV). We trained and tested the early diagnostic model of sepsis-associated ARDS patients in the eICU. We used key predictive indicators to cluster sepsis-associated ARDS patients and determine the characteristics and clinical outcomes of different phenotypes, as well to explore the differences of in-hospital mortality among different the positive end-expiratory pressure (PEEP) levels in different phenotypes. These results are verified in MIMIC-IV to evaluate whether they are repeatable. Results: Among the diagnostic models constructed in 19,249 sepsis patients and 5,947 sepsis-associated ARDS patients, the AdaBoost (Decision Tree) model achieved the best performance with an area under the receiver operating characteristic curve (AUC) of 0.895, which is higher than that of the traditional Logistic Regression model (Z = -2.40,p = 0.013), and the accuracy of 70.06%, sensitivity of 78.11% and specificity of 78.74%. We simultaneously identified three sepsis-associated ARDS phenotypes. Cluster 0 (n = 3,669) had the lowest in-hospital mortality rate (6.51%) and fewer laboratory abnormalities (lower WBC (median:15.000 K/mcL), lower blood glucose (median:158.000 mg/dl), lower creatinine (median:1.200 mg/dl), lower lactic acid (median:3.000 mmol/L); p < 0.001). Cluster 1 (n = 1,554) had the highest in-hospital mortality rate (75.29%) and the most laboratory abnormalities (higher WBC (median:18.300 K/mcL), higher blood glucose (median:188.000 mg/dl), higher creatinine (median:2.300 mg/dl), higher lactic acid (median:3.900 mmol/L); p < 0.001). Cluster 2 (n = 724) had the most complex condition, with a moderate in-hospital mortality rate (29.7%) and the longest intensive care unit stay. In Clusters 0 and 1, patients with high PEEP had higher in-hospital mortality rate than those with low PEEP, but the opposite trend was seen in Cluster 2. These results were repeatable in 11,935 patients with sepsis and 2,699 patients with sepsis-associated ARDS patients in the MIMIC-IV cohort. Conclusion: A machine learning diagnostic model of sepsis-associated ARDS patients was established. Three phenotypes with different clinical features and outcomes were clustered, and these had different therapeutic responses. These findings are helpful for the early and rapid identification of sepsis-associated ARDS patients and their precise individualized treatment. [ABSTRACT FROM AUTHOR]

Tyrosine kinase 2 (TYK2) is a member of the Janus kinase (JAK) family and is involved in immune and inflammatory signaling. TYK2 is overexpressed in several types of cancers and promotes the invasion and proliferation of cancer cells. Nevertheless, the roles of TYK2 in the prognosis and immune infiltration of head and neck squamous cell carcinoma (HNSCC) remain to be elucidated. In this study, the expression of TYK2 in HNSCC was evaluated based on the data retrieved from multiple databases and quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The prognostic potential of TYK2 in patients with HNSCC was analyzed by Kaplan-Meier curves and Cox regression analysis. A TYK2-related risk assessment model was subsequently constructed by Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis and stepwise multivariate Cox regression analysis. The association between the expression of TYK2 and the tumor immune microenvironment, immune checkpoints, and drug sensitivity was explored various packages in R. Cell function assays were finally used for exploring the effects of TYK2 on the growth and metastasis of HNSCC tumors. The expression of TYK2 was significantly upregulated in HNSCC and was found to be closely correlated with HPV status, gender, clinical grade, and TP53 mutation status. Survival analysis suggested that TYK2 is associated with better survival outcomes and acts as an independent prognostic indicator of HNSCC. The model constructed herein also performed well in terms of predicting patient prognosis. The expression of TYK2 was positively associated with the population of tumor-infiltrating immune cells, expression of immune checkpoint genes, and antitumor drug susceptibility. Functionally, TYK2 knockdown significantly promoted the proliferation, migration, and invasion of HNSCC cell lines in vitro. The findings demonstrated that TYK2 could serve as a suppressor of tumor growth and holds significant promise as a novel biomarker for assessing the prognosis of patients with HNSCC and aid in immunotherapy against HNSCC. [ABSTRACT FROM AUTHOR]

Germplasm conservation strongly depends on the desiccation tolerance (DT) of seeds. Xerophytic seeds have strong desiccation resistance, which makes them excellent models to study DT. Although some experimental strategies have been applied previously, most methods are difficult to apply to xerophytic seeds. In this review, we attempted to synthesize current strategies for the study of seed DT and provide an in-depth look at Caragana korshinskii as an example. First, we analyze congenital advantages of xerophytes in the study of seed DT. Second, we summarize several strategies used to study DT and illustrate a suitable strategy for xerophytic species. Then, based on our previous studies work with C. korshinskii, a feasible technical strategy for DT re-establishment is provided and we provide illustrate some special molecular mechanisms seen in xerophytic seeds. Finally, several steps to unveil the DT mechanism of xerophytic seeds are suggested, and three scientific questions that the field should consider are listed. We hope to optimize and utilize this strategy for more xerophytic species to more systematically decipher the physiological and molecular processes of seed DT and provide more candidate genes for molecular breeding. [ABSTRACT FROM AUTHOR]

Background: Although studies have shown that higher waist-hip ratio (WHR) is closely related to higher risk of metabolism-related diseases, the relationship between WHR and subclinical myocardial injury (SC-MI) is unknown. This study was to evaluate the effect of WHR on SC-MI in the general population free from cardiovascular disease. Methods: The cross-sectional study included 6253 participants without cardiovascular disease (CVD) from the third National Health and Nutrition Examination Survey (NHANES III) for further analysis. Restricted cubic spline, multivariable logistic regression models and subgroup analyses were performed to assess the association between WHR and SC-MI. Results: The multivariate logistic regression showed that after adjusting for potential confounding factors, participants in the higher quartiles had higher risk of developing SC-MI than those in the first quartile of WHR [Q3, OR (95% CI): 1.523 (1.159, 2.000), P = 0.002; Q4, OR (95% CI): 1.719 (1.279, 2.311), P < 0.001], and this relationship was robust among the participants aged ≥ 50 years, with hypertension and without diabetes. Every 0.1 unit increase in WHR, as a continuous variable, increased the risk of SC-MI by more than 20% [OR (95% CI): 1.233 (1.092, 1.392), P = 0.001]. And restricted cubic spline analysis showed that there was a linear positive correlation between WHR and the risk of SC-MI. Conclusions: WHR may be an independent risk factor for SC-MI in the general population free from CVD. [ABSTRACT FROM AUTHOR]

Background: The thalamus plays a crucial role in transmitting nociceptive information to various cortical regions involving migraine-related allodynia and photophobia. Abnormal structural and functional alterations related to the thalamus have been well established. However, it is unknown whether the brain structure and function of the thalamic subregions are differentially affected in this disorder. In this study, we aimed to clarify this issue by comparing the structure and function of 16 thalamic subregions between patients with episodic migraine (EM) and healthy controls (HCs). Methods: Twenty-seven patients with EM and 30 sex-, age- and education-matched HCs underwent resting-state functional and structural magnetic resonance imaging scans. Functional connectivity (rsFC), grey matter volume (GMV), and diffusion tensor imaging (DTI) parameters of each subregion of the thalamus were calculated and compared between the two groups. Furthermore, correlation analyses between neuroimaging changes and clinical features were performed in this study. Results: First, compared with HCs, patients with EM exhibited decreased rsFC between the anterior-medial-posterior subregions of the thalamus and brain regions mainly involved in the medial system of the pain processing pathway and default mode network (DMN). Second, for the whole thalamus and each of its subregions, there were no significant differences in GMV between patients with EM and HCs (P > 0.05, Bonferroni corrected). Third, there was no significant difference in DTI parameters between the two groups (P > 0.05). Finally, decreased rsFC was closely related to scores on the Hamilton Rating Scale for Anxiety (HAMA) and Big Five Inventory (BFI) scales. Conclusion: Selective functional hypoconnectivity in the thalamic subregions provides neuroimaging evidence supporting the important role of thalamocortical pathway dysfunction in episodic migraine, specifically, that it may modulate emotion and different personality traits in migraine patients. [ABSTRACT FROM AUTHOR]

Acute myelocytic leukemia (AML) is a malignancy of the stem cell precursors of the myeloid lineage. CD4+ and CD8+ T cells play pivotal roles in influencing AML progression but are functionally suppressed in the bone marrow microenvironment. We aimed to find hub genes related to T cell exhaustion and suppression, thereby providing evidence for immunotherapy. In this study, gene transcriptome expression data from TCGA and TARGET databases were utilized to find key genes. Firstly, CIBERSORT immune cell infiltration algorithm and WGCNA method were used to identify CD4+ and CD8+ T cells-related genes. Univariate and multivariate cox regression analyses were then introduced to construct the overall survival prognosis model and included hub genes. The ESTIMATE and ssGSEA scoring methods were used to analyze the correlation between the hub genes and immune activity. Single-cell transcriptome analysis was applied to detect the immune cells expressing hub genes, hence, to detect exact mechanisms. Consequently, FLT3LG and IFITM3P6 were determined to be positively correlated with patients' overall survival and microenvironment immune activity. Further study suggested FLT3-FLT3LG and IFITM3P6-miR-6748-3p-CBX7 signaling axes were involved in CD4+ and CD8+ T cells activation. This may be one of the mechanisms of T cells suppression in AML. [ABSTRACT FROM AUTHOR]

Background: Laryngeal mask airway(LMA) have been widely used in clinical practice. Irritation to the patient during the insertion of a laryngeal mask can cause hemodynamic fluctuations, which is particularly unsafe for geriatric patients. We used probit regression analysis to determine the median effective dose of sufentanil to inhibit the response to LMA insertion in geriatric patients. Methods: A total of 90 patients were selected for the study using the following inclusion criteria: age ≥ 65 years old, ASA grade I–III, and scheduled to undergo intravenous general anesthesia with LMA insertion. Each patient received a dose of sufentanil for anesthesia induction in one of six levels: 0.05, 0.1, 0.15, 0.2, 0.25, or 0.3 μg kg−1. LMA insertion was scored with a 3-point, 6-category scale, with scores ≥ 16 indicating effective LMA insertion, and < 16 indicating ineffective LMA insertion. Mean arterial blood pressure (MAP), heart rate (HR), and bispectral index (BIS) were recorded 1 min before induction (T1), 1 min after induction (T2), 1 min after LMA insertion (T3), and 5 min after LMA insertion (T4) in each group. In addition, the plasma norepinephrine (NE) levels and adverse reactions were measured at T2 and T3 in each dosage group. Results: Probit regression analysis showed that the ED50 of sufentanil inhibiting the response to LMA insertion in geriatric patients was 0.18 μg kg−1 (95% CI: 0.16–0.21 μg kg−1), and the ED95 was 0.31 μg kg−1 (95% CI: 0.27–0.38 μg kg−1), and the probit(p) = -2.34 + 12.90 × ln(Dose)( χ 2 = 0.725, p = 0.948). Among all the patients, the number of effective LMA insertions was 57 (group A), and the number of ineffective LMA insertions was 33 (group B). The MAP, HR, and NE in group B were significantly higher than in group A at T3. Conclusions: Sufentanil can effectively inhibit the patient's response to LMA insertion, with stable hemodynamics and small stress response. The ED50 and ED95 were 0.18 μg kg−1 (95% CI: 0.16–0.21 μg kg−1) and 0.31 μg kg−1(95% CI: 0.27–0.38 μg kg−1), respectively. Trial registration: This study was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2100051827) on October 6, 2021. [ABSTRACT FROM AUTHOR]

Background: Laryngeal mask airway(LMA) have been widely used in clinical practice. Irritation to the patient during the insertion of a laryngeal mask can cause hemodynamic fluctuations, which is particularly unsafe for geriatric patients. We used probit regression analysis to determine the median effective dose of sufentanil to inhibit the response to LMA insertion in geriatric patients. Methods: A total of 90 patients were selected for the study using the following inclusion criteria: age ≥ 65 years old, ASA grade I–III, and scheduled to undergo intravenous general anesthesia with LMA insertion. Each patient received a dose of sufentanil for anesthesia induction in one of six levels: 0.05, 0.1, 0.15, 0.2, 0.25, or 0.3 μg kg−1. LMA insertion was scored with a 3-point, 6-category scale, with scores ≥ 16 indicating effective LMA insertion, and < 16 indicating ineffective LMA insertion. Mean arterial blood pressure (MAP), heart rate (HR), and bispectral index (BIS) were recorded 1 min before induction (T1), 1 min after induction (T2), 1 min after LMA insertion (T3), and 5 min after LMA insertion (T4) in each group. In addition, the plasma norepinephrine (NE) levels and adverse reactions were measured at T2 and T3 in each dosage group. Results: Probit regression analysis showed that the ED50 of sufentanil inhibiting the response to LMA insertion in geriatric patients was 0.18 μg kg−1 (95% CI: 0.16–0.21 μg kg−1), and the ED95 was 0.31 μg kg−1 (95% CI: 0.27–0.38 μg kg−1), and the probit(p) = -2.34 + 12.90 × ln(Dose)( χ 2 = 0.725, p = 0.948). Among all the patients, the number of effective LMA insertions was 57 (group A), and the number of ineffective LMA insertions was 33 (group B). The MAP, HR, and NE in group B were significantly higher than in group A at T3. Conclusions: Sufentanil can effectively inhibit the patient's response to LMA insertion, with stable hemodynamics and small stress response. The ED50 and ED95 were 0.18 μg kg−1 (95% CI: 0.16–0.21 μg kg−1) and 0.31 μg kg−1(95% CI: 0.27–0.38 μg kg−1), respectively. Trial registration: This study was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2100051827) on October 6, 2021. [ABSTRACT FROM AUTHOR]

The center and edge of the hot-rolled low-carbon steel plate reflect the inhomogeneity. Five positions along the transverse direction of the steel plate are taken as the research object. This study reveals the root cause of the inhomogeneity of transverse microstructure and properties of hot-rolled low-carbon steel plates. The grain size in the center of the hot-rolled low-carbon steel plate is relatively large, and the grain size at the edge is relatively small. The mechanical properties test shows that the closer the edge, the higher the hardness. The strength along the transverse direction is similar to the shape of W. The finite element simulation results show that the central cooling is slow, and the deformation degree is different in different transverse positions. In conclusion, the main reason for the inhomogeneous microstructure are the various cooling rates of different parts in the transverse direction. The synergistic effect of grain size and alloying elements is the main reason that causes the transverse strength distribution to show a "W" shape. [ABSTRACT FROM AUTHOR]

Background: Autotetraploid Carassius auratus (4n = 200, RRRR) (abbreviated as 4nRR) is derived from whole genome duplication of Carassius auratus red var. (2n = 100, RR) (abbreviated as RCC). Ribosome DNA (rDNA) is often used to study molecular evolution of repeated sequences because it has high copy number and special conserved coding regions in genomes. In this study, we analysed the sequences (5S, ITS1-5.8S-ITS2 region), structure, methylation level (NTS and IGS), and expression level (5S and 18S) of 5S and 45S ribosomal RNA (rRNA) genes in 4nRR and RCC in order to elucidate the effects of autotetraploidization on rDNA in fish. Results: Results showed that there was high sequence similarity of 5S, 5.8S and ITS1 region between 4nRR and RCC. This study also identified two different types of ITS2 region in 4nRR and predicted the secondary structure of ITS2. It turns out that both secondary structures are functional. Compared with RCC, there was no significant difference in NTS (5S rRNA) methylation level, but the expression level of 5S rRNA was lower in 4nRR, indicating that methylation had little effect on the expression level in 4nRR. IGS (45S rRNA) was hypermethylated in 4nRR compared to RCC, but the expression of 18S rRNA gene was no significantly different from that in RCC, indicating that methylation regulation affected gene expression in 4nRR. Conclusion: The above studies initially revealed the effects of autotetraploidization on the structure and function of 5S and 45S rRNA in Carassius auratus, and provided a theoretical support for the systematic study of the evolution pattern and characteristics of rDNA in vertebrates. [ABSTRACT FROM AUTHOR]

The launch of the United Nations (UN) 17 Sustainable Development Goals (SDGs) in 2015 was a historic event, uniting countries around the world around the shared agenda of sustainable development with a more balanced relationship between human beings and the planet. The SDGs affect or impact almost all aspects of life, as indeed does the technological revolution, empowered by Big Data and their related technologies. It is inevitable that these two significant domains and their integration will play central roles in achieving the 2030 Agenda. This research aims to provide a comprehensive overview of how these domains are currently interacting, by illustrating the impact of Big Data on sustainable development in the context of each of the 17 UN SDGs. [ABSTRACT FROM AUTHOR]

Drawing on implicit leadership theory (Brown & Lord, 2001; Eden & Leviatan, 1975), we hypothesize that the relationship between participative leadership and employee performance is curvilinear (J-shaped), suggesting that participative leadership is unrelated to employee performance when participative leadership is below a moderate level (i.e., a threshold). Above this threshold, increased participative leadership is related to higher employee performance. Building on adaptive resonance theory (Grossberg, 1999), a variant of implicit leadership theory, we further hypothesize that leaders' information-sharing behavior will moderate this curvilinear relationship. We test this model using two independent samples: office and call-center employees (Study 1) and factory workers (Study 2). Results from Study 1 reveal that this curvilinear relationship is stronger when leaders' information sharing is high and weaker when information sharing is low. Furthermore, in Study 2, we find that leadership effectiveness mediates the interactive effect of participative leadership and information sharing on objective work performance. [ABSTRACT FROM AUTHOR]

Transition‐metal dichalcogenides PtTe2, PdTe2, and NiTe2 deserve particular attention, due to the presence of type‐II Dirac fermions. As a matter of fact, tilted Dirac cones afford a suitable platform for optoelectronics of dissipation‐less carrier‐transport, favored by their ultrahigh carrier mobility, and large nonsaturating magnetoresistance. Herein, it is shown that PtTe2, PdTe2, and NiTe2 display high‐speed terahertz (THz) detection capability at room temperature, which originates from their peculiar band structure with topologically protected electronic states. Furthermore, photodetectors based on their heterostructures are able to suppress dark current with high‐performance detection of THz light. Furthermore, these crystals are stable in air and they can be easily exfoliated in nanosheets by liquid‐phase exfoliation, due to the weak interlayer van der Waals bonds. The obtained results clearly establish that the type‐II Dirac semimetals based on transition‐metal ditellurides have immense research potential for addressing application‐oriented issues for remote sensing and telecommunications. [ABSTRACT FROM AUTHOR]

Bundle adjustment (BA) is a technique for refining sensor orientations of satellite images, while adjustment accuracy is correlated with feature matching results. Feature matching often contains high uncertainties in weak/repeat textures, while BA results are helpful in reducing these uncertainties. To compute more accurate orientations, this article incorporates BA and feature matching in a unified framework and formulates the union as the optimization of a global energy function so that the solutions of the BA and feature matching are constrained with each other. To avoid a degeneracy in the optimization, we propose a comprised solution by breaking the optimization of the global energy function into two-step suboptimizations and compute the local minimums of each suboptimization in an incremental manner. Experiments on multi-view high-resolution satellite images show that our proposed method outperforms state-of-the-art orientation techniques with or without accurate least-squares matching. [ABSTRACT FROM AUTHOR]

Clinical trials showed pangenotypic direct-acting antivirals' (DAAs) excellent efficacy and safety when treating hepatitis C virus (HCV). Two pangenotypic regimens were examined, glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir (SOF/VEL), in a real-world Taiwanese setting, including all HCV patients treated with GLE/PIB or SOF/VEL from August 2018 to April 2020. The primary endpoint was sustained virologic response 12 weeks after treatment cessation (SVR12), including adverse events (AEs). A total of 1,356 HCV patients received pangenotypic DAA treatment during the study: 742 and 614 received GLE/PIB and SOF/VEL, respectively. The rates of SVR12 for GLE/PIB and SOF/VEL were 710/718 (98.9%) and 581/584 (99.5%), respectively, by per-protocol analysis, and 710/742 (95.7%) and 581/614 (94.6%), respectively, by evaluable population analysis. Eleven (GLE/PIB: 8, SOF/VEL: 3) did not achieve SVR12. The most common AEs for GLE/PIB and SOF/VEL were pruritus (17.4% vs. 2.9%), abdominal discomfort (5.8% vs. 4.4%), dizziness (4.2% vs. 2%), and malaise (3.1% vs. 2.9%). Laboratory abnormalities were uncommon; only < 1% exhibited elevated total bilirubin or aminotransferase levels with both regimens. Five drug discontinuations occurred due to AEs (bilirubin elevation: 3; dermatological issues: 2). Pangenotypic DAAs GLE/PIB and SOF/VEL are effective and well tolerated, achieving high SVR12 rates for patients with all HCV genotypes. [ABSTRACT FROM AUTHOR]

Although all murine MDSCs are defined as Gr1+CD11b+, their true immunophenotype remains elusive. In this study, we found murine Gr1+CD11b+ cells can be divided into two subsets: Gr1+CD11b+B220- and Gr1+CD11b+B220+, especially in the spleen tissues. Unlike the dominant B220- subset, the B220+ sub-population was not induced by tumor in vivo. Moreover, Gr1+CD11b+B220+ cells from tumor-bearing mice spleens were unable to induce arginase 1 and inducible nitric oxide synthase expression, inhibit T cell proliferation, or promote tumor growth in primary tumor site. Nevertheless, these cells suppressed tumor metastasis in vivo and reduced cancer cell motility in vitro, while Gr1+CD11b+B220- cells from tumor-bearing mice spleens promoted tumor metastasis and enhanced cancer cell motility. Furthermore, both the polymorphonuclear (PMN-MDSCs) and monocytic MDSCs (Mo-MDSCs) could be further divided into B220- and B220+ subsets; interestingly, tumor only induced the expansion of B220- PMN-MDSCs and B220- Mo-MDSCs, but not the B220+ counterparts. Compared with B220- PMN-MDSCs and B220- Mo-MDSCs, the Ly6G+Ly6C-CD11b+B220+ and Ly6G-Ly6C+CD11b+B220+ cells from tumor-bearing mice spleens exhibited a more mature phenotype without immunosuppressive activity. Additionally, IL-6 deficiency attenuated the tumor-induced accumulation of MDSCs, B220- MDSCs and B220- PMN-MDSCs but increased the percentages of Gr1+CD11b+B220+, Ly6G+Ly6C-CD11b+B220+, and Ly6G-Ly6C+CD11b+B220+ cells, indicating the opposing roles of the IL-6 signaling pathway in the expansion of B220- MDSCs and their B220+ counterparts. Taken together, our findings indicate that the B220+ subset is a distinct subset of Gr1+CD11b+ cells functionally different from the B220- subpopulation during tumorigenesis and induction of MDSCs to B220+ cells may be helpful for cancer therapy. [ABSTRACT FROM AUTHOR]

Duplex kidney is a common congenital malformation appeared as duplication of pelvis and ureter. However, renal duplication within sinus renalis is an extremely rare variation of the renal collecting system. In this study, we report a case of an asymptomatic kidney disease in a 33-year-old man, who demonstrates abnormal echo of renal sinus anomaly discovered incidentally in ultrasound examination. Computed tomography urography (CTU) exhibited the other small duplex kidney located in renal sinus. In the excretory phase images, the contrast medium within its small renal pelvis could be seen to flow into the right major renal calices. This case exhibited a very rare anatomical variation of duplicated renal malformation. [ABSTRACT FROM AUTHOR]