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Abstract Background Winter wheat undergoes vernalization, a process activated by prolonged exposure to low temperatures. During this phase, flowering signals are generated and transported to the apical meristems, stimulating the transition to the inflorescence meristem while inhibiting tiller bud elongation. Although some vernalization genes have been identified, the key cis-regulatory elements and precise mechanisms governing this process in wheat remain largely unknown. Results In this study, we construct extensive epigenomic and transcriptomic profiling across multiple tissues—leaf, axillary bud, and shoot apex—during the vernalization of winter wheat. Epigenetic modifications play a crucial role in eliciting tissue-specific responses and sub-genome-divergent expressions during vernalization. Notably, we observe that H3K27me3 primarily regulates vernalization-induced genes and has limited influence on vernalization-repressed genes. The integration of these datasets enables the identification of 10,600 putative vernalization-related regulatory elements including distal accessible chromatin regions (ACRs) situated 30Kb upstream of VRN3, contributing to the construction of a comprehensive regulatory network. Furthermore, we discover that TaSPL7/15, integral components of the aging-related flowering pathway, interact with the VRN1 promoter and VRN3 distal regulatory elements. These interactions finely regulate their expressions, consequently impacting the vernalization process and flowering. Conclusions Our study offers critical insights into wheat vernalization’s epigenomic dynamics and identifies the putative regulatory elements crucial for developing wheat germplasm with varied vernalization characteristics. It also establishes a vernalization-related transcriptional network, and uncovers that TaSPL7/15 from the aging pathway participates in vernalization by directly binding to the VRN1 promoter and VRN3 distal regulatory elements.

Although gastrointestinal stromal tumors (GISTs) has been reported in patients of all ages, its diagnosis is more common in elders. The two most common types of mutation, receptor tyrosine kinase (KIT) and platelet-derived growth factor receptor a (PDGFRA) mutations, hold about 75 and 15% of GISTs cases, respectively. Tumors without KIT or PDGFRA mutations are known as wild type (WT)-GISTs, which takes up for 15% of all cases. WT-GISTs have other genetic alterations, including mutations of the succinate dehydrogenase and serine–threonine protein kinase BRAF and neurofibromatosis type 1. Other GISTs without any of the above genetic mutations are named “quadruple WT” GISTs. More types of rare mutations are being reported. These mutations or gene fusions were initially thought to be mutually exclusive in primary GISTs, but recently it has been reported that some of these rare mutations coexist with KIT or PDGFRA mutations. The treatment and management differ according to molecular subtypes of GISTs. Especially for patients with late-stage tumors, developing a personalized chemotherapy regimen based on mutation status is of great help to improve patient survival and quality of life. At present, imatinib mesylate is an effective first-line drug for the treatment of unresectable or metastatic recurrent GISTs, but how to overcome drug resistance is still an important clinical problem. The effectiveness of other drugs is being further evaluated. The progress in the study of relevant mechanisms also provides the possibility to develop new targets or new drugs.

Abstract Background Myocardial injury after non-cardiac surgery (MINS) is a common and insidious postoperative complication. This study aimed to evaluate the relationship between the triglyceride-glucose index (TyG) and MINS in advanced-age patients. Methods We performed a single-center retrospective study including patients ≥ 65 years of age who underwent non-cardiac surgery. The relationship between TyG and MINS was investigated using univariate and multivariate logistic regression analyses. Multivariate logistic regression analysis involved three models: Model I adjusted for preoperative factors, Model II adjusted for surgery-related factors, and Model III adjusted for both preoperative and surgery-related factors. Propensity score matching (PSM) was used to reduce the confounding effects of covariates. Subgroup analyses were then performed to evaluate the relationship between TyG and MINS in various subsamples. Results A total of 7789 patients were studied, among whom 481 (6.2%) developed MINS. A cut-off value of TyG of 8.57 was determined using a receiver operating characteristic (ROC) curve to be associated with the best predictive performance. Participants with TyG ≥ 8.57 were at a higher risk of developing MINS than those with TyG

Abstract This study aimed to explore the link between various forms of obesity, including body mass index (BMI) and waist circumference (WC), and the risk of dyslipidemia among Chinese residents. We selected the study population through a multi-stage random sampling method from permanent residents aged 35 and older in Ganzhou. Obesity was categorized as non-obesity, general obesity, central obesity, or compound obesity according to established diagnostic criteria. We employed a logistic regression model to assess the relationship between different types of obesity and the risk of dyslipidemia. Additionally, we used the restricted cubic spline model to analyze the association between BMI, WC, and the risk of dyslipidemia. The study included 2030 residents aged 35 or older from Ganzhou, China. The prevalence of dyslipidemia was found to be 39.31%, with an age-standardized prevalence of 36.51%. The highest prevalence of dyslipidemia, 58.79%, was observed among those with compound obesity. After adjusting for confounding factors, we found that the risk of dyslipidemia in those with central and compound obesity was respectively 2.00 (95% CI 1.62–2.46) and 2.86 (95% CI 2.03–4.03) times higher than in the non-obese population. Moreover, the analysis using the restricted cubic spline model indicated a nearly linear association between BMI, WC, and the risk of dyslipidemia. The findings emphasize the significant prevalence of both dyslipidemia and obesity among adults aged 35 and above in Ganzhou, China. Notably, individuals with compound obesity are at a substantially increased risk of dyslipidemia. Therefore, it is crucial to prioritize the use of BMI and WC as screening and preventive measures for related health conditions.

Abstract BackgroundMyocardial injury after noncardiac surgery (MINS) is an easily overlooked complication but closely related to postoperative cardiovascular adverse outcomes; therefore, the early diagnosis and prediction are particularly important. ObjectiveWe aimed to develop and validate an explainable machine learning (ML) model for predicting MINS among older patients undergoing noncardiac surgery. MethodsThe retrospective cohort study included older patients who had noncardiac surgery from 1 northern center and 1 southern center in China. The data sets from center 1 were divided into a training set and an internal validation set. The data set from center 2 was used as an external validation set. Before modeling, the least absolute shrinkage and selection operator and recursive feature elimination methods were used to reduce dimensions of data and select key features from all variables. Prediction models were developed based on the extracted features using several ML algorithms, including category boosting, random forest, logistic regression, naïve Bayes, light gradient boosting machine, extreme gradient boosting, support vector machine, and decision tree. Prediction performance was assessed by the area under the receiver operating characteristic (AUROC) curve as the main evaluation metric to select the best algorithms. The model performance was verified by internal and external validation data sets with the best algorithm and compared to the Revised Cardiac Risk Index. The Shapley Additive Explanations (SHAP) method was applied to calculate values for each feature, representing the contribution to the predicted risk of complication, and generate personalized explanations. ResultsA total of 19,463 eligible patients were included; among those, 12,464 patients in center 1 were included as the training set; 4754 patients in center 1 were included as the internal validation set; and 2245 in center 2 were included as the external validation set. The best-performing model for prediction was the CatBoost algorithm, achieving the highest AUROC of 0.805 (95% CI 0.778‐0.831) in the training set, validating with an AUROC of 0.780 in the internal validation set and 0.70 in external validation set. Additionally, CatBoost demonstrated superior performance compared to the Revised Cardiac Risk Index (AUROC 0.636; P ConclusionsThe ML models can provide a personalized and fairly accurate risk prediction of MINS, and the explainable perspective can help identify potentially modifiable sources of risk at the patient level.

The islanded micro-grid is playing a more and more significant role to absorb more wind and solar energy because of its advantages such as flexibility, cleanliness and environmental friendliness. However, the randomness and transient of renewable energy result in many challenges for the economic operation of the islanded micro-grid. The load frequency control is the core influencing factor for the economic operation. A modified active disturbance rejection control (MADRC), combined with a compensation part and an amplitude limiter, is proposed for the load frequency control with high-proportional renewable energy. The convergence of the extended state observer is analyzed theoretically. Then a pragmatic tuning procedure is provided by examining the influence of MADRC’s parameters on the control performance. Finally, the proposed control strategy is applied to the load frequency control of the islanded micro-grid and simulations under different conditions are carried out. The simulation results compared with other comparative controller strategies show that MADRC can obtain the best control performance with good robustness. Quantitative data demonstrates the improvement of the proposed method in terms of economic operation and the proposed method also shows promising engineering application potential.

Environmental issue is one of the public concerns pertaining to human welfare. English language education is supposed to take its part to contribute to the sustainable development. In this study, a corpus comprising 12 series of English language textbooks used in Chinese universities (48 volumes/books) was constructed to examine the extent to which the textbooks cover the content of environmental education, and how these topics are presented. The large volume dataset was explored by corpus linguistic tools and the in-depth discourse analysis and findings were reported and discussed within the theoretical framework of critical discourse analysis. The results suggested that some key environmental semantic domains, such as “Green issues” (e.g., nature, environment, ecology), “Substances and materials” (e.g., pesticide, chemical, carbon dioxide), “Science and technology” (e.g., technologies, nuclear, biotechnology), “Farming & Horticulture” (e.g., farming, crop, agriculture), “Living creatures” (e.g., endangered species, animals, wildlife) were evident. Some topics within these domains such as sustainable environmentalism, energy efficiency and sufficiency were presented and discussed critically. The textbooks are expected to help learners develop knowledge, competencies and futuristic attitudes needed to meet the sustainability challenges in various contexts.

BackgroundTraditional anthropometric measures, including body mass index (BMI), are insufficient for evaluating gallstone risk. This study investigated the association between novel anthropometric indices and gallstone risk among 6,848 participants from the National Health and Nutrition Examination Survey in the United States.MethodsMeasures calculated included weight (WT), BMI, waist circumference (WC), waist-to-height ratio (WtHR), conicity index (CI), A Body Shape Index (ABSI), Body Roundness Index (BRI), Abdominal Volume Index (AVI), and Weight-adjusted Waist Index (WWI). Logistic regression and smooth curve fitting assessed the relationships between these indices and gallstones, complemented by receiver operating characteristic (ROC) curve analysis to evaluate their discriminative power.ResultsThe results indicated significant differences between study groups, with a positive and independent correlation identified between gallstones and all measures except ABSI. Specifically, per 1 SD increase in WC, WT, BMI, WtHR, and AVI was associated with a 57%, 59%, 52%, 53%, and 53% increased risk of gallstones, respectively. Dose-response analysis confirmed a positive correlation between these indices and gallstone risk. ROC analysis highlighted WtHR and BRI as having superior discriminative abilities (AUC = 0.6703). Further, among participants with a BMI < 30 kg/m2, elevated levels of WT, WtHR, CI, BRI, and WWI significantly increased the risk of gallstones (P < 0.001). Likewise, elevated BMI heightened the risk at low levels of WT, WC, WtHR, BRI, AVI, and CI (P < 0.001).ConclusionThis study supports the positive association between various anthropometric indicators and gallstones, recommending that newer anthropometric indices be considered more extensively to enhance gallstone prevention and treatment strategies.

Abstract The Amplified Luminescent Proximity Homogenous Assay-linked Immunosorbent Assay (AlphaLISA) is known for detecting various protein targets; however, its ability to detect nucleic acid sequences is not well established. Here, the capabilities of the AlphaLISA technology were expanded to include direct detection of DNA (aka: oligo-Alpha) and was applied to the detection of Listeria monocytogenes. Parameters were defined that allowed the newly developed oligo-Alpha to differentiate L. monocytogenes from other Listeria species through the use of only a single nucleotide polymorphism within the 16S rDNA region. Investigations into the applicability of this assay with different matrices demonstrated its utility in both milk and juice. One remarkable feature of the oligo-Alpha is that greater sensitivity could be achieved through the use of multiple acceptor oligos compared to only a single acceptor oligo, even when only a single donor oligo was employed. Additional acceptor oligos were easily incorporated into the assay and a tenfold change in the detection limit was readily achieved, with detection limits of 250 attomole of target being recorded. In summary, replacement of antibodies with oligonucleotides allows us to take advantage of genotypic difference(s), which both expands its repertoire of biological markers and furthers its use as a diagnostic tool.

This conceptual article underscores the critical need for tailored supervision for school counselors-in-training (SCITs), emphasizing challenges arising from differences in training, role ambiguity, and limited understanding of pK-12 educational contexts when overseen by doctoral supervisors with clinical mental health counseling (CMHC) backgrounds. We advocate for enhanced training and support for doctoral students from CMHC backgrounds to more effectively supervise SCITs. Bridging the gap between SCITs and counselor education doctoral training, we emphasize adjustments to supervision training and implications for the supervision of school counselor trainees.

Abstract Background Our previous study has reported that supplementation of oligosaccharide-based polymer enhances gut health and disease resistance of pigs infected with enterotoxigenic E. coli (ETEC) F18 in a manner similar to carbadox. The objective of this study was to investigate the impacts of oligosaccharide-based polymer or antibiotic on the host metabolic profiles and colon microbiota of weaned pigs experimentally infected with ETEC F18. Results Multivariate analysis highlighted the differences in the metabolic profiles of serum and colon digesta which were predominantly found between pigs supplemented with oligosaccharide-based polymer and antibiotic. The relative abundance of metabolic markers of immune responses and nutrient metabolisms, such as amino acids and carbohydrates, were significantly differentiated between the oligosaccharide-based polymer and antibiotic groups (q 2.0). In addition, pigs in antibiotic had a reduced (P

ABSTRACT Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by social communication deficiencies and stereotypic behaviors influenced by hereditary and/or environmental risk factors. There are currently no approved medications for treating the core symptoms of ASD. Human fecal microbiota transplantation (FMT) has emerged as a potential intervention to improve autistic symptoms, but the underlying mechanisms are not fully understood. In this study, we evaluated the effects of human-derived FMT on behavioral and multi-omics profiles of the BTBR mice, an established model for ASD. FMT effectively alleviated the social deficits in the BTBR mice and normalized their distinct plasma metabolic profile, notably reducing the elevated long-chain acylcarnitines. Integrative analysis linked these phenotypic changes to specific Bacteroides species and vitamin B6 metabolism. Indeed, vitamin B6 supplementation improved the social behaviors in BTBR mice. Collectively, these findings shed new light on the interplay between FMT and vitamin B6 metabolism and revealed a potential mechanism underlying the therapeutic role of FMT in ASD.IMPORTANCEAccumulating evidence supports the beneficial effects of human fecal microbiota transplantation (FMT) on symptoms associated with autism spectrum disorder (ASD). However, the precise mechanism by which FMT induces a shift in the microbiota and leads to symptom improvement remains incompletely understood. This study integrated data from colon-content metagenomics, colon-content metabolomics, and plasma metabolomics to investigate the effects of FMT treatment on the BTBR mouse model for ASD. The analysis linked the amelioration of social deficits following FMT treatment to the restoration of mitochondrial function and the modulation of vitamin B6 metabolism. Bacterial species and compounds with beneficial roles in vitamin B6 metabolism and mitochondrial function may further contribute to improving FMT products and designing novel therapies for ASD treatment.

IntroductionFirst-line treatment with tislelizumab plus chemotherapy has shown clinical benefits for patients with advanced or metastatic esophageal squamous cell carcinoma (OSCC) in China, while its economic burden is unknown. This study aimed to evaluate the cost-effectiveness of tislelizumab plus chemotherapy from the perspective of the Chinese healthcare system.MethodsWe constructed a partitioned survival model to compare the cost-effectiveness of tislelizumab plus chemotherapy with chemotherapy in patients with advanced OSCC. Patient characteristics and clinical outcomes were extracted from RATIONALE-306. Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were selected as the study outcomes. Sensitivity analysis and subgroup analysis were conducted to test the stability of the results.ResultsTislelizumab plus chemotherapy provided additional 0.48 QALYs with the incremental cost of $16,587.2 than chemotherapy, of which ICER was $34,699.72 per QALY. When the willingness-to-pay threshold was set as $37,260, the novel therapy had a probability of 77% to be cost-effective. Our base-case analysis results were sensitive to utilities of progression-free survival and progression of disease. Our subgroup analysis showed that the novel therapy was associated with cost-effectiveness in patients with a high expression of PD-L1.ConclusionTislelizumab plus chemotherapy was likely to be more cost-effective compared with chemotherapy in the first-line therapy of advanced OSCC from the perspective of the Chinese healthcare system. Our findings can provide clinicians and decision-makers with evidence of the cost-effectiveness of tislelizumab.

BackgroundThe rise in e-cigarette use among youth is a significant global public health issue. It is important to identify those at increased risk and implement effective strategies to reduce e-cigarette popularity among the youth.ObjectiveThis study aims to identify predictors of e-cigarette uptake in youths with no prior tobacco use, considering individual, familial and the broader societal environmental factors.MethodsFor this investigation, a group of 2,487 tobacco-free youths was selected from 15 high schools in Shenzhen, China. Susceptibility to e-cigarettes was determined by assessing the possibility of future use and the openness to trying e-cigarettes if presented by friends. Both chi-square tests and logistic regression were applied to identify factors linked to susceptibility to e-cigarette use.ResultsAmong the respondents, 5.5% (n = 136) were found to be susceptible to e-cigarette use. The analysis revealed factors tied to this risk: perceptions of e-cigarettes, the impact of vaping peers, paternal parenting styles, the extent of social support, exposure to messages both for and against e-cigarettes use, and secondhand smoke (SHS) exposure. Youths who downplayed the addictive nature of e-cigarettes (aOR = 2.01; 95% CI: 1.14–3.55; p = 0.016), those with friends who engaged in vaping (aOR = 3.43–7.64; 95%CI: 2.36–20.42; p

Uncrewed aerial vehicle (UAV) aerial photography technology is widely used in both industrial and military sectors, but remote sensing for small target detection still faces several challenges. Firstly, the small size of targets increases the difficulty of detection and recognition. Secondly, complex aerial environmental conditions, such as lighting changes and background noise, significantly affect the quality of detection. Rapid and accurate identification of target categories is also a key issue, requiring improvements in detection speed and accuracy. This study proposes an improved remote sensing target detection algorithm based on the YOLOv5 architecture. In the YOLOv5s model, the Distribution Focal Loss function is introduced to accelerate the convergence speed of the network and enhance the network’s focus on annotated data. Simultaneously, adjustments are made to the Cross Stage Partial (CSP) network structure, modifying the convolution kernel size, adding a new stack-separated convolution module, and designing a new attention mechanism to achieve effective feature fusion between different hierarchical structure feature maps. Experimental results demonstrate a significant performance improvement of the proposed algorithm on the RSOD dataset, with a 3.5% increase in detection accuracy compared to the original algorithm. These findings indicate that our algorithm effectively enhances the precision of remote sensing target detection and holds potential application prospects.

Abstract Background Autoimmune hepatitis (AIH) is a T-cell-mediated autoimmune liver disease that can lead to liver injury and has a poor long-term prognosis. Mesenchymal stromal cells (MSCs) have immunosuppressive effects and can treat AIH. CD4+ T cells express the unique inhibitory Fcγ receptor (FcγRIIB), which is the only receptor for the immunosuppressive factor soluble fibrinogen-like protein 2 (sFgl2). This study aimed to examine the therapeutic effect of sFgl2 gene-modified MSCs (sFgl2-MSCs) on AIH. Methods MSCs were obtained from the inguinal fat of mice and cocultured with CD4+ T cells sorted from mouse spleens. FcγRIIB expression on CD4+ T cells was determined by flow cytometry. sFgl2 expression in MSCs transfected with lentiviral vectors carrying the Fgl2 gene and a green fluorescent protein-encoding sequence was determined by enzyme-linked immunosorbent assay. The percentages of Th1 cells Th17 cells and regulatory T cells (Tregs) were determined by flow cytometry And the levels of p-SHP2 and p-SMAD2/3 were detected by Western blotting after the cells were cocultured with MSCs for 72 h. After locating MSCs by in vivo imaging Con A-induced experimental AIH mice were randomly divided into 4 groups and administered different treatments. After 24 h histopathological scores liver function and cytokine levels were examined and the proportions of CD4+ T cells CD8+ T cells Tregs Th17 cells and Th1 cells in the spleen and liver were determined by flow cytometry. In addition immunohistochemical staining was used to detect the liver infiltration of T-bet-, Foxp3- and RORγ-positive cells. Results FcγRIIB expression on CD4+ T cells was upregulated after coculture with MSCs. After coculture with sFgl2-MSCs, the proportion of Tregs among CD4+ T cells increased, the proportion of Th17 and Th1 cells decreased, and the levels of p-SHP2 and p-SMAD2/3 increased. In vivo, sFgl2-MSCs significantly improved liver function, decreased liver necrosis area, decreased tumor necrosis factor-α, interleukin (IL)-1β and IL-6 expression, increased IL-10 expression, reduced liver infiltration of CD4+ T and CD8+ T cells, increased the proportion of Tregs and reduced the proportions of Th17 and Th1 cells in mice. Conclusion By promoting Tregs differentiation and inhibiting Th17 and Th1 cell differentiation, sFgl2 gene-modified MSCs have a more powerful therapeutic effect on Con A-induced experimental AIH and may represent a strategy for the clinical treatment of AIH.

This paper presents a fast focusing inversion algorithm of magnetic data based on the conjugate gradient method, which can be used to describe the underground target geologic body efficiently and clearly. The proposed method realizes an effect similar to matrix compression by changing the computation order, calculating the inner product of vectors and equivalent expansion of expressions. Model tests show that this strategy successfully reduces the computation time of a single iteration of the conjugate gradient method, so the three-dimensional magnetic data inversion is realized under a certain number of iterations. In this paper, the detailed calculation steps of the proposed inversion method are given, and the effectiveness and high efficiency of the proposed fast focusing inversion method are verified by three theoretical model tests and a set of measured data. Finally, the fast focus inversion algorithm is applied to the magnetic data of Gonghe Basin, Qinghai Province, to describe the spatial distribution range of deep hot dry rock, which provides a direction for the continuous exploration of geothermal resources in this area.

Salmonella enterica Typhimurium DT104 (S. Typhimurium DT104) is an important foodborne pathogen that is associated with poultry and poultry products. Currently, there is very little information on the underlying molecular mechanisms that allow DT104 to survive and propagate in poultry meat and the poultry processing environment. The current study assessed the global gene expression of DT104 in ground chicken extract (GCE) compared to brain heart infusion (BHI) medium using RNA-Seq technology. DT104 was grown to the early stationary phase (ESP), inoculated into GCE or BHI, and then re-grown to the log phase before RNA was extracted and transcripts were quantified by RNA-Seq. Gene expression for DT104 grown in GCE was then compared to that of DT104 grown in BHI for samples grown to the ESP. Growth in GCE resulted in the up-regulated expression of genes related to translation, carnitine metabolism (23–283-fold change), and cobalamin (vitamin B12) biosynthesis (14-fold change). In particular, the presence of carnitine in chicken meat, and thus, in GCE, which lacks carbohydrates, may allow Salmonella to utilize this compound as a carbon and nitrogen source. This study demonstrates that RNA-Seq data can provide a comprehensive analysis of DT104 gene expression in a food model for poultry products. This study also provides additional evidence for the importance of metabolic adaptation in the ability of S. enterica to successfully adapt to and occupy niches outside of its host and provides potential targets that could be used to develop intervention strategies to control Salmonella in poultry.

Introduction: Stroke is the second leading cause of death globally and a primary factor contributing to disability. Unilateral limb motor impairment caused by stroke is the most common scenario. The bilateral movement pattern plays a crucial role in assisting stroke survivors on the affected side to relearn lost skills. However, motion compensation often lead to decreased coordination between the limbs on both sides. Furthermore, muscle fatigue resulting from imbalanced force exertion on both sides of the limbs can also impact the rehabilitation outcomes.Method: In this study, an assessment method based on muscle synergy indicators was proposed to objectively quantify the impact of motion compensation issues on rehabilitation outcomes. Muscle synergy describes the body’s neuromuscular control mechanism, representing the coordinated activation of multiple muscles during movement. 8 post-stroke hemiplegia patients and 8 healthy subjects participated in this study. During hand-cycling tasks with different resistance levels, surface electromyography signals were synchronously collected from these participants before and after fatigue. Additionally, a simulated compensation experiment was set up for healthy participants to mimic various hemiparetic states observed in patients.Results and discussion: Synergy symmetry and synergy fusion were chosen as potential indicators for assessing motion compensation. The experimental results indicate significant differences in synergy symmetry and fusion levels between the healthy control group and the patient group (p ≤ 0.05), as well as between the healthy control group and the compensation group. Moreover, the analysis across different resistance levels showed no significant variations in the assessed indicators (p > 0.05), suggesting the utility of synergy symmetry and fusion indicators for the quantitative evaluation of compensation behaviors. Although muscle fatigue did not significantly alter the symmetry and fusion levels of bilateral synergies (p > 0.05), it did reduce the synergy repeatability across adjacent movement cycles, compromising movement stability and hindering patient recovery. Based on synergy symmetry and fusion indicators, the degree of bilateral motion compensation in patients can be quantitatively assessed, providing personalized recommendations for rehabilitation training and enhancing its effectiveness.

Gastric cancer has a high incidence rate worldwide; it is particularly important to determine the therapeutic efficacy of available treatments and to determine the prognosis of gastric cancer due to its insidious onset and lack of specific symptoms in the early stage (most patients are diagnosed in the middle or late stage). Recent studies have revealed that altered expression of microRNAs plays a pivotal role in immune checkpoints and various cellular processes in gastric cancer. miRNAs have gradually become biomarkers and therapeutic targets in cancer because of their specificity and high sensitivity. In this article, we review the expression of miR-15a/16 and its therapeutic efficacy in gastric cancer and discuss its impact on signaling pathways and its prognostic importance to provide better clinical treatment options for patients.

Objective: To construct and compared the short-term prognosis prediction models of acute ischemic stroke (AIS) by machine learning (ML). Methods: Retrospectively study. The group W (mRS≤3) was clustered, and combined with group P (mRS>3) to form the post-clustering dataset for modeling. The “glmnet”, “rpart”, “xgboost”, “randomForest”, “neuralnet” packages were used to construct ML models. The accuracy, sensitivity, specificity, positive predict value (PPV), negative predict value (NPV) among the models were compared. Four external clinical datasets were used for external clinical validation. The optimal prediction model was determined by variable screening ability, model visualization, and external clinical validation performance. Results: The post-clustering dataset contains 139 patients (group W) and 122 patients (group P). The neutrophil multiplied by D-dimer (NDM) has predictive value in all ML prediction models in this study. In the decision tree model, NDMQ occupies the first tree node, When NDM≤5.62 and the age5.62 and accompanied by pneumonia, the incidence of poor prognosis of AIS is about 90 %. In the Random Forest (RF) model, NDMQ had the highest Gini index. The variable combination screened by the RF model had the best performance in the neural network, and the accuracy, sensitivity, specificity, PPV, and NPV of the external validation were 0.800, 0.774, 0.833, 0.857, and 0.741, respectively. The RF model had the best performance in the external clinical validation datasets, with accuracies of 0.646, 0.697, 0.695, and 0.713, respectively. Conclusions: NDM shows predictive value for AIS short-term prognosis in all ML models in this study. The optimal model in screening characteristic variables and the performance of in external clinical datasets was RF model. In the analysis of medical data with small sample size and outcome as categorical variables, RF could be used as the main algorithm to build a model.

Trace elements (TEs) are essential for the treatment of rheumatoid arthritis (RA). This study aimed to prepare a TEs solution enriched with various organic states to evaluate its preventive, therapeutic effects, and mechanism of action in RA and to provide a treatment method for RA treatment. The TEs in natural ore were extracted and added to 0.5% (W/V) L-alanyl-L-glutamine (LG) to obtain a TEs solution (LG-WLYS), which was examined for its concentration and quality. The antioxidant properties and effects of LG-WLYS on cell behavior were evaluated at the cellular level. The preventive and therapeutic effects and mechanism of action of LG-WLYS in rats with RA were explored. The LG-WLYS solution was clear, free from visible foreign matter, and had a pH of 5.33 and an osmolality of 305.67 mOsmol/kg. LG-WLYS inhibited cell migration and angiogenesis. LG-WLYS solution induced macrophages to change from M1-type to M2-type, increased the content of antioxidant enzymes (glutathione, superoxide dismutase, and IL-10), decreased the levels of nitric oxide, malondialdehyde, TNF-α, IL-1β, IL-6, COX-2, and iNOs, scavenging reactive oxygen species from the lesion site, inhibiting the apoptosis of chondrocytes, regulating inflammatory microenvironment, and decreasing inflammation response to exert the therapeutic effect for RA. In conclusion, LG-WLYS has outstanding therapeutic and preventive effects against RA and has enormous potential for further development.

Peptide‒drug conjugates (PDCs) are drug delivery systems consisting of a drug covalently coupled to a multifunctional peptide via a cleavable linker. As an emerging prodrug strategy, PDCs not only preserve the function and bioactivity of the peptides but also release the drugs responsively with the cleavable property of the linkers. Given the ability to significantly improve the circulation stability and targeting of drugs in vivo and reduce the toxic side effects of drugs, PDCs have already been extensively applied in drug delivery. Herein, we review the types and mechanisms of peptides, linkers and drugs used to construct PDCs, and summarize the clinical applications and challenges of PDC drugs.

Load frequency regulation (LFR) is regarded as a significant method for the stable operation of modern power grids. However, the LFR is facing many challenges such as communication delays in the area control error, and external disturbances caused by renewable energy integrating into power grids. This paper presents a cascaded improved active disturbance rejection control (ADRC) to handle these control challenges, where the inner and outer controllers are the improved ADRC and regular ADRC, respectively. The advantages of the improved ADRC to reject external disturbances and system uncurtains are discussed by simulations. Then a practical parameter tuning method is provided to guide the selection of controller parameters. Finally, comparative simulations are implemented to illustrate the abilities of the proposed control scheme in different cases. The proposed control structure can handle the communication delay well and have a strong ability to reject the disturbances of uncertain consumed power and wind power. The simulation results imply that the cascaded improved ADRC may have broad application prospects for the LFR.

The extremely low bioavailability of oral paclitaxel (PTX) mainly due to the complicated gastrointestinal environment, the obstruction of intestinal mucus layer and epithelium barrier. Thus, it is of great significance to construct a coordinative delivery system which can overcome multiple intestinal physicochemical obstacles simultaneously. In this work, a high-density PEGylation-based glycocholic acid-decorated micelles (PTX@GNPs) was constructed by a novel polymer, 9-Fluorenylmethoxycarbonyl-polyethylene glycocholic acid (Fmoc-PEG-GCA). The Fmoc motif in this polymer could encapsulate PTX via π‒π stacking to form the core of micelles, and the low molecular weight and non-long hydrophobic chain of Fmoc ensures the high-density of PEG. Based on this versatile and flexible carriers, PTX@GNPs possess mucus trapping escape ability due to the flexible PEG, and excellent intestine epithelium targeting attributed to the high affinity of GCA with apical sodium-dependent bile acid transporter. The in vitro and in vivo results showed that this oral micelle could enhance oral bioavailability of PTX, and exhibited similar antitumor efficacy to Taxol injection via intravenous route. In addition, oral PTX@GNPs administered with lower dosage within shorter interval could increase in vivo retention time of PTX, which supposed to remodel immune microenvironment and enhance oral chemotherapy efficacy by synergistic effect.

Abstract Background The prognostic nutritional index (PNI) is a nutritional indicator and predictor of various diseases. However it is unclear whether PNI can be a predictor of perioperative ischemic stroke. This study aims to evaluate the association of the preoperative PNI and ischemic stroke in patients undergoing non-cardiac surgery. Methods The retrospective cohort study included patients who underwent noncardiac surgery between January 2008 and August 2019. The patients were divided into PNI ≥ 38.8 and PNI

Abstract Background Hip fractures are common in elderly patients, and almost all the patients undergo surgery. This study aimed to develop a novel modified lymphocyte C-reactive protein (CRP) score (mLCS) to simply and conveniently predict 3-year mortality in elderly patients undergoing intertrochanteric fracture surgery. Methods A retrospective study was conducted on elderly patients who underwent intertrochanteric fracture surgery between January 2014 and December 2017. The mLCS was developed according to the value of CRP and lymphocyte counts. Univariate and multivariate Cox regression analyses were used to identify independent risk factors for 3-year mortality after surgery. The performances of the lymphocyte CRP score (LCS) and mLCS to predict 3-year mortality were then compared using C-statistics, decision curve analysis (DCA), net reclassification index (NRI) and integrated discrimination improvement (IDI). Results A total of 291 patients were enrolled, of whom 52 (17.9%) died within 3 years after surgery. In the multivariate Cox regression analysis, mLCS (hazard ratio (HR), 5.415; 95% confidence interval (CI), 1.743–16.822; P = 0.003) was significantly associated with postoperative 3-year mortality. The C-statistics of LCS and mLCS for predicting 3-year mortality were 0.644 and 0.686, respectively. The NRI (mLCS vs. LCS, 0.018) and IDI (mLCS vs. LCS, 0.017) indicated that the mLCS performed better than the LCS. DCA also showed that mLCS had a higher clinical net benefit. Conclusions mLCS is a promising predictor that can simply and conveniently predict 3-year mortality in elderly patients undergoing intertrochanteric fracture surgery.

Cattle rumination behavior is strongly correlated with its health. Current methods often rely on manual observation or wearable devices to monitor ruminating behavior. However, the manual monitoring of cattle rumination is labor-intensive, and wearable devices often harm animals. Therefore, this study proposes a non-contact method for monitoring cattle rumination behavior, utilizing an improved YOLOv8-pose keypoint detection algorithm combined with multi-condition threshold peak detection to automatically identify chewing counts. First, we tracked and recorded the cattle’s rumination behavior to build a dataset. Next, we used the improved model to capture keypoint information on the cattle. By constructing the rumination motion curve from the keypoint information and applying multi-condition threshold peak detection, we counted the chewing instances. Finally, we designed a comprehensive cattle rumination detection framework to track various rumination indicators, including chewing counts, rumination duration, and chewing frequency. In keypoint detection, our modified YOLOv8-pose achieved a 96% mAP, an improvement of 2.8%, with precision and recall increasing by 4.5% and 4.2%, enabling the more accurate capture of keypoint information. For rumination analysis, we tested ten video clips and compared the results with actual data. The experimental results showed an average chewing count error of 5.6% and a standard error of 2.23%, verifying the feasibility and effectiveness of using keypoint detection technology to analyze cattle rumination behavior. These physiological indicators of rumination behavior allow for the quicker detection of abnormalities in cattle’s rumination activities, helping managers make informed decisions. Ultimately, the proposed method not only accurately monitors cattle rumination behavior but also provides technical support for precision management in animal husbandry, promoting the development of modern livestock farming.

Extensive research has been conducted to identify key proteins governing stress responses, virulence, and antimicrobial resistance, as well as to elucidate their interactions within Listeria monocytogenes. While these proteins hold promise as potential targets for novel strategies to control L. monocytogenes, given their critical roles in regulating the pathogen’s metabolism, additional analysis is needed to further assess their druggability—the chance of being effectively bound by small-molecule inhibitors. In this work, 535 binding pockets of 46 protein targets for known drugs (mainly antimicrobials) were first analyzed to extract 13 structural features (e.g., hydrophobicity) in a ligand–protein docking platform called Molsoft ICM Pro. The extracted features were used as inputs to develop a logistic regression model to assess the druggability of protein binding pockets, with a value of one if ligands can bind to the protein pocket. The developed druggability model was then used to evaluate 23 key proteins from L. monocytogenes that have been identified in the literature. The following proteins are predicted to be high-potential druggable targets: GroEL, FliH/FliI complex, FliG, FlhB, FlgL, FlgK, InlA, MogR, and PrfA. These findings serve as an initial point for future research to identify specific compounds that can inhibit druggable target proteins and to design experimental work to confirm their effectiveness as drug targets.

The manipulation of trap states plays a crucial role in the development of efficient photocatalysts. An ultrathin-shelled Zn-AgIn5S8/ZnS quantum dots (QDs) photocatalyst was synthesized via in situ growth using a low-temperature hydrothermal method. The optical properties of the samples coated with ZnS shell were studied vis UV-vis absorption and fluorescence spectra. The ultrathin ZnS shell plays an important role in the Zn-AgIn5S8/ZnS core–shell heterostructure photocatalytic water splitting system, which could reduce surface defects, prolong the carrier lifetime and improve the photo-generated electron–hole pair separation effectively, resulting in the improved photocatalytic efficiency and enhanced stability of the catalyst. The results provide an effective guideline for shell thickness design in future constructions of the core–shell heterostructure photocatalyst.

To prepare molecularly imprinted polymers (MIPs) with specific selectivity for steranes, the prepolyme-rization system was screened by UV spectroscopy to determine the type, proportion and mode of action of functional monomers. In this study, the interaction intensities between three template molecules (cholesterol, β-sitosterol, deoxycholic acid) and four functional monomers (acrylic acid (AA), methacrylic acid (MAA), methyl methacrylate (MMA), and acrylamide (AM)) are compared respectively. The results show that the functional monomer AA can interact strongly with the three template molecules and form a stable prepolymerization system, so AA is selected as the functional monomer of MIPs. In addition, the UV spectral absorbance change and differential UV spectral analysis of different proportions of AA show that the optimal concentration ratios of the three template molecules to functional monomer AA are all 1:4, and the stable complex configurations formed are cholesterol-1AA, β-sitosterol-1AA and deoxycholic acid-3AA, respectively. The MIPs are successfully synthesized by precipitation polymerization using EDGMA as dispersant and AIBN as initiator, and the results of FTIR show that MIPs are well prepared. Therefore, this method can be used for the screening and preparation of MIPs functional monomers with specific selectivity for steranes, and provide technical support for the study of oil-source correlation between deep and ultra-deep source rocks.

Abstract Background African swine fever (ASF) is a highly fatal disease in domestic pigs caused by ASF virus (ASFV), for which there is currently no commercial vaccine available. The genome of ASFV encodes more than 150 proteins, some of which have been included in subunit vaccines but only induce limited protection against ASFV challenge. Methods To enhance immune responses induced by ASFV proteins, we expressed and purified three fusion proteins with each consisting of bacterial lipoprotein OprI, 2 different ASFV proteins/epitopes and a universal CD4+ T cell epitope, namely OprI-p30-modified p54-TT, OprI-p72 epitopes-truncated pE248R-TT, and OprI-truncated CD2v-truncated pEP153R-TT. The immunostimulatory activity of these recombinant proteins was first assessed on dendritic cells. Then, humoral and cellular immunity induced by these three OprI-fused proteins cocktail formulated with ISA206 adjuvant (O-Ags-T formulation) were assessed in pigs. Results The OprI-fused proteins activated dendritic cells with elevated secretion of proinflammatory cytokines. Furthermore, the O-Ags-T formulation elicited a high level of antigen-specific IgG responses and interferon-γ-secreting CD4+ and CD8+ T cells after stimulation in vitro. Importantly, the sera and peripheral blood mononuclear cells from pigs vaccinated with the O-Ags-T formulation respectively reduced ASFV infection in vitro by 82.8% and 92.6%. Conclusions Our results suggest that the OprI-fused proteins cocktail formulated with ISA206 adjuvant induces robust ASFV-specific humoral and cellular immune responses in pigs. Our study provides valuable information for the further development of subunit vaccines against ASF.

Background Since most infants are usually discharged before age 48–72 hours, peak bilirubin levels will almost always occur after discharge. Parents may be the first to observe the onset of jaundice after discharge, but visual assessment is unreliable. The jaundice colour card (JCard) is a low-cost icterometer designed for the assessment of neonatal jaundice. The objective of this study was to evaluate parental use of JCard to detect jaundice in neonates.Methods We conducted a multicentre, prospective, observational cohort study in nine sites across China. A total of 1161 newborns ≥35 weeks of gestation were enrolled in the study. Measurements of total serum bilirubin (TSB) levels were based on clinical indications. The JCard measurements by parents and paediatricians were compared with the TSB.Results JCard values of parents and paediatricians were correlated with TSB (r=0.754 and 0.788, respectively). The parents’ and paediatricians’ JCard values 9 had sensitivities of 95.2% vs 97.6% and specificities of 84.5% vs 71.7% for identifying neonates with TSB ≥153.9 µmol/L. The parents’ and paediatricians’ JCard values 15 had sensitivities of 79.9% vs 89.0% and specificities of 66.7% vs 64.9% for identifying neonates with TSB ≥256.5 µmol/L. Areas under the receiver operating characteristic curves of parents for identifying TSB ≥119.7, ≥153.9, ≥205.2, and ≥256.5 µmol/L were 0.967, 0.960, 0.915, and 0.813, respectively, and those of paediatricians were 0.966, 0.961, 0.926 and 0.840, respectively. The intraclass correlation coefficient was 0.933 between parents and paediatricians.Conclusion The JCard can be used to classify different levels of bilirubin, but it is less accurate with high bilirubin levels. The JCard diagnostic performance of parents was slightly lower than that of paediatricians.

Objective This study was to assess the safety and effectiveness of immunosuppressive agents, specifically Voclosporin, when used in conjunction with mycophenolate mofetil (MMF) induction therapy for the management of lupus nephritis (LN).Methods A systematic review and network meta-analysis (NMA) was conducted on randomized controlled trials investigating the efficacy of immunosuppressant-induced therapy for LN. The random effects model was used in the analysis. I2 was used to evaluate the heterogeneity of the model. Odds ratios (OR) and 95% credible intervals (CrI) were computed to assess and compare the relative effectiveness and safety of various treatment protocols.Results The study included a total of 16 randomized controlled trials (RCTs) involving 2444 patients with LN. The analysis results indicated that there was no significant difference in terms of partial remission (PR) between the drugs. However, when considering complete remission (CR), the combination of Voclosporin with MMF showed the highest remission rate, followed by Tacrolimus (TAC). Unfortunately, Voclosporin in combination with MMF had the highest risk of infection and serious infection, indicating a lower safety profile.Conclusions Voclosporin in combination with MMF demonstrated the highest efficacy as an induction therapy for LN. However, it should be noted that the risk of infection and serious infection was found to be high with this regimen. On the other hand, TAC not only showed efficacy but also had a lower risk of infection and serious infection, making it a favorable option in terms of safety. This study did’ not include results on other adverse events.

Platelet microparticles (PMPs) are vesicles that are released by platelets into the extracellular space and play a role in antiphospholipid antibody syndromes. PMPs have recently been recognized as a new and viable cell. There is growing evidence that the anti-β2 glycoprotein (GPI)/β2GPI complex is associated with aberrant activation of PMPs. Although studies suggest that aberrant activation of PMPs may lead to inflammatory necrosis of endothelial cells, the underlying mechanisms remain unclear. We found that although the difference in the number of PMPs was not statistically significant, NLR family pyrin domain containing 3 (NLRP3) within PMPs was increased during stimulation of anti-β2GPI/β2GPI complexes. Furthermore, we demonstrated that anti-β2GPI/β2GPI complex-induced PMPs effectively stimulated endothelial cell pyroptosis via the NLRP3/nuclear factor (NF)-κB/gasdermin D (GSDMD) signaling pathway as well as the NLRP3/Caspase-1 signaling pathway. Additionally, inhibition of NLRP3 expression in PMPs effectively reduced the inflammatory response and pyroptosis in endothelial cells. Our data suggest that PMPs aberrantly activated by anti-β2GPI/β2GPI complexes play a vital role in endothelial cell pyroptosis, and these studies provide major insights into the mechanisms of thrombosis during the treatment of antiphospholipid antibody syndrome.

Abstract Modulating the inflammatory microenvironment can inhibit the process of inflammatory diseases (IDs). A tri‐cross‐linked inflammatory microenvironment‐responsive hydrogel with ideal mechanical properties achieves triggerable and sustained drug delivery and regulates the inflammatory microenvironment. Here, this study develops an inflammatory microenvironment‐responsive hydrogel (OD‐PP@SeNPs) composed of phenylboronic acid grafted polylysine (PP), oxidized dextran (OD), and selenium nanoparticles (SeNPs). The introduction of SeNPs as initiators and nano‐fillers into the hydrogel results in extra cross‐linking of the polymer network through hydrogen bonding. Based on Schiff base bonds, Phenylboronate ester bonds, and hydrogen bonds, a reactive oxygen species (ROS)/pH dual responsive hydrogel with a triple‐network is achieved. The hydrogel has injectable, self‐healing, adhesion, outstanding flexibility, suitable swelling capacity, optimal biodegradability, excellent stimuli‐responsive active substance release performance, and prominent biocompatibility. Most importantly, the hydrogel with ROS scavenging and pH‐regulating ability protects cells from oxidative stress and induces macrophages into M2 polarization to reduce inflammatory cytokines through PI3K/AKT/NF‐κB and MAPK pathways, exerting anti‐inflammatory effects and reshaping the inflammatory microenvironment, thereby effectively treating typical IDs, including S. aureus infected wound and rheumatoid arthritis in rats. In conclusion, this dynamically responsive injectable hydrogel with a triple‐network structure provides an effective strategy to treat IDs, holding great promise in clinical application.

Water, in ultra-deep layers of the earth and in layers receiving abnormally high heat, can exist in a supercritical state. Supercritical water (SCW) can participate in the transformations of organic compounds not only as a solvent but also as a reactant, influencing petroleum formation and the evolution of sedimentary organic matter. Here, we carried out hydrous pyrolysis experiments in both SCW and water vapor (WV) using two organic-rich marine rocks under closed conditions, to quantitatively evaluate the generation potential of hydrocarbons in a supercritical state and to clarify the effect of water phase on hydrous pyrolysis experiments. The results showed that SCW promoted gaseous and liquid hydrocarbon generation and facilitated the cracking of aliphatic hydrocarbons. For gaseous hydrocarbons, the action of SCW became stronger as the temperature increased. For liquid hydrocarbons, the peak yields of bitumen were enhanced by the SCW, and the temperature corresponding to peak yield in SCW was lower than that in WV. These results were attributed to the supply of hydrogen and oxygen from SCW for the petroleum formation and cracking. The δ13C and δD values of gases were also influenced by SCW. However, these values obtained in SCW did not always become positive as their yields increased. Generally, methane (CH4) was enriched in 12C and 1H. The influence of SCW on the isotopic fractionation of ethane (C2H6) and propane (C3H8) was more complex. The water phase is an important factor affecting the experimental results of hydrous pyrolysis. From these findings, it can be concluded that SCW allowed for increased conversion of sedimentary organic matter to gaseous and liquid hydrocarbons in ultra-deep layers and layers affected by volcanic-hydrothermal activity.

The generalized Zakharov equation is a widely used and crucial model in plasma physics, which helps to understand wave particle interactions and nonlinear wave propagation in plasma. The solitary wave solution of this equation provides insights into phenomena such as electron and ion acoustic waves, as well as magnetic field disturbances in plasma. The numerical simulation of solitary wave solutions to the generalized Zakharov equation is an interesting problem worth studying. This is crucial for plasma-based technology, as well as for understanding nonlinear wave propagation in plasma physics and other fields. In this study, a numerical investigation of the generalized Zakharov equation using the lattice Boltzmann method has been conducted. The lattice Boltzmann method is a new modeling and simulating method at the mesoscale. A lattice Boltzmann model was constructed by performing Taylor expansion, Chapman–Enskog expansion, and time multiscale expansion on the lattice Boltzmann equation. By defining the moments of the equilibrium distribution function appropriately, the macroscopic equation can be restored. Furthermore, the numerical experiments for the equation are carried out with the parameter lattice size m=100, time step Δt=0.001, and space step size Δx=0.4. The solitary wave solution of the equation is numerically simulated. Numerical results under different parameter values are compared, and the convergence and effectiveness of the model are numerically verified. It is obtained that the model is convergent in time and space, and the convergence orders are all 2.24881. The effectiveness of our model was also verified by comparing the numerical results of different numerical methods. The lattice Boltzmann method demonstrates advantages in both accuracy and CPU time. The results indicate that the lattice Boltzmann method is a good tool for computing the generalized Zakharov equation.

Bark is vital for woody plants, providing protection, transporting nutrients and water, and storing essential resources. For fire-prone ecosystems, bark thickness is a key adaptive trait conferring fire resistance. Few studies have been conducted on the drivers of variation in bark thickness of the widely distributed Larix gmelinii (Rupr.) Kuzen in the Great Xing’an Mountains region, on the southern edge of East Siberia, where surface fire disturbances are frequent. To elucidate the relationships between variation in bark thickness (inner vs. outer bark) of L. gmelinii and plant size, environmental factors, and co-variation with other fire-tolerance traits, we selected 26 sites to set up plots and carried out a survey and bark sampling. Results showed that stem diameter primarily determines variation in bark thickness, especially outer bark. The proportion of outer bark to total bark increased accordingly as the tree increased in size. We also observed stronger correlated variation in outer bark thickness, tree height, and self-pruning capacity, implying that larger trees have thicker protective outer bark and taller heights with greater self-pruning, mitigating crown fire risks. Environmental factors appear to have a relatively limited effect on changes in bark thickness in L. gmelinii. Mean air temperature, annual precipitation, and total soil nitrogen content had some effect on outer bark thickness, and mean air temperature had some effect on inner bark thickness.

IntroductionNew poultry feed valorization pathways for recovered household food could be enabled by commercially available household devices that dry uneaten food material, arrest spoilage, and preserve nutrient content. However, the nutrient composition, safety, and feed incorporation potential of dried recovered household food (DRHF) is presently unknown.MethodsThirty-eight households spanning 31 states participated in a 4-to-6-week survey to generate and collect food residues that were dried using an in-home device. The DRHF samples were evaluated for chemical composition, digestibility of energy and amino acids, and safety to determine their potential for inclusion in chicken feed.Results and discussionThe DRHF had average levels of 15.9% crude protein, 13.3% crude fat, and 22.6% neutral detergent fiber, and 3.18 kcal/g of nitrogen-adjusted true metabolizable energy (by dry weight). The Windows User-Friendly Feed Formulation 2.1 modeler was used to perform linear programming and develop chicken feed rations for broilers and layers that incorporated DRHF alongside conventional feed ingredients, including corn, soybean meal, dicalcium phosphate, limestone, synthetic amino acids, salt, vitamin premix, and mineral premix. The feed formulation results showed that, on average, DRHF incorporation rates of up to 33 and 37% (by weight) are predicted to avoid any nutrient deficiencies or electrolyte imbalances in the broiler and layer rations, respectively. In the broiler ration, DRHF displaced corn, soybean meal, and limestone to varying degrees, while corn, soybean meal, animal fat, dicalcium phosphate, and limestone were substantially displaced in the layer rations. Addition of vitamin premix was predicted as necessary to facilitate DRHF inclusion in the layer rations. Furthermore, foodborne pathogens, mycotoxins, and heavy metals were either absent or below United States regulatory threshold levels. Measured levels of biogenic amines and fat/oil oxidation were consistent with prior research showing compatibility with chickens. These results can inform future in vivo feeding trials to validate the use of DRHF with varying properties in poultry feed.

To analyze the specific effects of prolonged computer use on oculomotor function, we propose an oculomotor function evaluation system to analyze changes in oculomotor movement function by using an eye tracker to record eye movement data when performing gaze, smooth pursuit, and saccade under normal condition, after one hour and one and a half hours of continuous working at a computer. The captured eye movement data is pre-processed, and then data features are calculated and analyzed to understand the specific effects of continuously using the computer on the oculomotor function. The results show that the oculomotor function decreases as we gaze at the computer screen for longer periods, as evidenced by a decrease in the stability of the gaze function, a reduction in the gaze focus, a reduction in the speed of eye saccades, and a decrease in the smooth pursuit function. In short, the oculomotor function worsens after prolonged working at a computer. This paper presents the effects of continuously using the computer quantificationally for the first time. The proposed oculomotor function evaluation system could also be used to assess patients who have a disability in oculomotor function and specific individuals, e.g. pilots.

The safe operation of multi-area power systems (MPS) is facing great challenges with the explosive growth of renewable energy, where the load frequency regulation (LFR) may be disturbed due to the unpredictability and uncertainty of renewable energy. This paper considers the communication delays in the area control error signals for the LFR of MPS, where a cascaded proportional–integral–derivative (PID) control scheme optimized by genetic algorithms is proposed to handle the communication delays. By comparing the stability boundaries of PI parameters with/without different time delays, the adverse effects caused by communication delays are discussed. Based on the proposed cascaded control scheme, its parameters are optimized by the genetic algorithms. Simulation results in different scenarios validate the superiorities of the proposed control scheme, where it can reject disturbances of the load variance most quickly and obtain a small overshoot. The proposed cascaded PI control scheme optimized by the genetic algorithms shows great promising potential in load frequency regulation.

The suturing of the southern Altaids and final closure of the Paleo Asian Ocean within Pangea occurred during the early Triassic, according to geochemical and detrital zircon provenance analyses of sandstones in the Muzitekexie fore-arc accretionary basin

Abstract Human health has been seriously endangered by arsenic pollution in drinking water. In this paper, iron hydroxide nanopetalines were synthesized through a precipitation method using KBH4 and their performance and mechanism of As(V) and As(III) removal were investigated. The prepared material was characterized by SEM–EDX, XRD, BET, zeta potential and FTIR analyses. Batch experiments indicated that the iron hydroxide nanopetalines exhibited more excellent performance for As(V) and As(III) removal than ferrihydrite. The adsorption processes were very fast in the first stage, followed a relatively slower adsorption rate and reached equilibria after 24 h, and the reaction could be fitted best by the pseudo-second order model, followed by the Elovich model. The adsorption isotherm data followed to the Freundlich model, and the maximal adsorption capacities of As(V) and As(III) calculated by the Langmuir model were 217.76 and 91.74 mg/g at pH 4.0, respectively, whereas these values were 187.84 and 147.06 mg/g at pH 8.0, respectively. Thermodynamic studies indicated that the adsorption process was endothermic and spontaneous. The removal efficiencies of As(V) and As(III) were significantly affected by the solution pH and presence of PO4 3– and citrate. The reusability experiments showed that more than 67% of the removal efficiency of As(V) could be easily recovered after four cycles. The SEM and XRD analyses indicated that the surface morphology and crystal structure before and after arsenic removal were stable. Based on the analyses of FTIR, XRD and XPS, the predominant adsorption mechanism was the formation of inner-sphere surface complexes by the surface hydroxyl exchange reactions of Fe–OH groups with arsenic species. This research provides a new strategy for the development of arsenic immobilization materials and the results confirm that iron hydroxide nanopetalines could be considered as a promising material for removing arsenic from As-contaminated water for their highly efficient performance and stability.

Abstract Background Postoperative delirium (POD) is a common complication among elderly patients after surgery. It is unclear whether the systemic immune-inflammation index (SII) can be a predictor of POD. We explored the prognostic value of the SII in predicting POD in elderly patients undergoing non-neurosurgery and non-cardiac surgery in a large retrospective cohort. Methods We enrolled elderly patients undergoing non-neurosurgery and non-cardiac surgery between January 2014 and August 2019. Univariate and multivariate logistic regression analyses were performed to explore the correlation between POD and the SII value as both a continuous and categorical variable. Then, propensity score matching (PSM) analysis was applied to eliminate the confounding effect of covariates and prove our results. Subgroup analyses were then performed to discover the association between the SII and POD in different subgroups. Results A total of 29,608 patients with a median age of 70 years (IQR: 67–74) were enrolled in the retrospective cohort. The cut-off value of the SII was 650, which was determined by the receiver operating characteristic (ROC) curve. The ORs of an SII value > 650 was 2.709 (95% CI:2.373–3.092, P 650 was 1.301 (95% CI: 1.062–1.598, P = 0.011). The subgroup analysis indicated that the SII indicates a significantly increased risk of POD in patients with Hb

The stability and reliability of the power grid are facing great challenges caused by the intermittency and randomness of renewable energy, for example, the frequency variations induced by the load variance. To handle these challenges, the load frequency regulation is becoming a powerful feasible alternative. This paper focuses on the load frequency regulation for multi-area power systems with renewable sources via a cascaded active disturbance rejection control (ADRC) approach. By introducing a multi-area power system with renewable sources, a cascaded ADRC structure is structured for a multi-area power system, which contains a photovoltaic system, a thermal system and a wind system. Based on the ADRC principle and the parameter stability region, a practical and effective design procedure for the proposed cascaded ADRC is provided. Simulations illustrate that the proposed cascaded ADRC can ensure the stronger ability to reject the consumed power compared with other comparative control strategies under different scenarios. Besides, it needs the shortest time to return to the stable state with the smallest overshoot under all operating conditions when the load variance occurs. The successful application of the multi-area power system indicates a promising potential of the proposed cascaded ADRC in the power industry.

Abstract Background Metabolic dysregulation and disruption of immune homeostasis have been widely associated with perioperative complications including perioperative ischemic stroke. Although immunometabolite S-2-hydroxyglutarate (S-2HG) is an emerging regulator of immune cells and thus triggers the immune response, it is unclear whether and how S-2HG elicits perioperative ischemic brain injury and exacerbates post-stroke cognitive dysfunction. Methods Perioperative ischemic stroke was induced by transient middle cerebral artery occlusion for 60 min in C57BL/6 mice 1 day after ileocecal resection. CD8+ T lymphocyte activation and invasion of the cerebrovascular compartment were measured using flow cytometry. Untargeted metabolomic profiling was performed to detect metabolic changes in sorted CD8+ T lymphocytes after ischemia. CD8+ T lymphocytes were transfected with lentivirus ex vivo to mobilize cell proliferation and differentiation before being transferred into recombination activating gene 1 (Rag1−/−) stroke mice. Results The perioperative stroke mice exhibit more severe cerebral ischemic injury and neurological dysfunction than the stroke-only mice. CD8+ T lymphocyte invasion of brain parenchyma and neurotoxicity augment cerebral ischemic injury in the perioperative stroke mice. CD8+ T lymphocyte depletion reverses exacerbated immune-mediated cerebral ischemic brain injury in perioperative stroke mice. Perioperative ischemic stroke triggers aberrant metabolic alterations in peripheral CD8+ T cells, in which S-2HG is more abundant. S-2HG alters CD8+ T lymphocyte proliferation and differentiation ex vivo and modulates the immune-mediated ischemic brain injury and post-stroke cognitive dysfunction by enhancing CD8+ T lymphocyte-mediated neurotoxicity. Conclusion Our study establishes that S-2HG signaling-mediated activation and neurotoxicity of CD8+ T lymphocytes might exacerbate perioperative ischemic brain injury and may represent a promising immunotherapy target in perioperative ischemic stroke.

ABSTRACT Bacteria are known to cope with amino acid starvation by the stringent response signaling system, which is mediated by the accumulation of the (p)ppGpp alarmones when uncharged tRNAs stall at the ribosomal A site. While a number of metabolic processes have been shown to be regulatory targets of the stringent response in many bacteria, the global impact of amino acid starvation on bacterial metabolism remains obscure. This work reports the metabolomic profiling of the human pathogen Streptococcus pneumoniae under methionine starvation. Methionine limitation led to the massive overhaul of the pneumococcal metabolome. In particular, methionine-starved pneumococci showed a massive accumulation of many metabolites such as glutamine, glutamic acid, lactate, and cyclic AMP (cAMP). In the meantime, methionine-starved pneumococci showed a lower intracellular pH and prolonged survival. Isotope tracing revealed that pneumococci depend predominantly on amino acid uptake to replenish intracellular glutamine but cannot convert glutamine to methionine. Further genetic and biochemical analyses strongly suggested that glutamine is involved in the formation of a “prosurvival” metabolic state by maintaining an appropriate intracellular pH, which is accomplished by the enzymatic release of ammonia from glutamine. Methionine starvation-induced intracellular pH reduction and glutamine accumulation also occurred to various extents under the limitation of other amino acids. These findings have uncovered a new metabolic mechanism of bacterial adaptation to amino acid limitation and perhaps other stresses, which may be used as a potential therapeutic target for infection control. IMPORTANCE Bacteria are known to cope with amino acid starvation by halting growth and prolonging survival via the stringent response signaling system. Previous investigations have allowed us to understand how the stringent response regulates many aspects of macromolecule synthesis and catabolism, but how amino acid starvation promotes bacterial survival at the metabolic level remains largely unclear. This paper reports our systematic profiling of the methionine starvation-induced metabolome in S. pneumoniae. To the best of our knowledge, this represents the first reported bacterial metabolome under amino acid starvation. These data have revealed that the significant accumulation of glutamine and lactate enables S. pneumoniae to form a “prosurvival” metabolic state with a lower intracellular pH, which inhibits bacterial growth for prolonged survival. Our findings have provided insightful information on the metabolic mechanisms of pneumococcal adaptation to nutrient limitation during the colonization of the human upper airway.

Tularemia is a highly contagious disease caused by infection with Francisella tularensis (Ft), a pathogenic intracellular gram-negative bacterium that infects a wide range of animals and causes severe disease and death in people, making it a public health concern. Vaccines are the most effective way to prevent tularemia. However, there are no Food and Drug Administration (FDA)-approved Ft vaccines thus far due to safety concerns. Herein, three membrane proteins of Ft, Tul4, OmpA, and FopA, and a molecular chaperone, DnaK, were identified as potential protective antigens using a multifactor protective antigen platform. Moreover, the recombinant DnaK, FopA, and Tul4 protein vaccines elicited a high level of IgG antibodies but did not protect against challenge. In contrast, protective immunity was elicited by a replication-defective human type 5 adenovirus (Ad5) encoding the Tul4, OmpA, FopA, and DnaK proteins (Ad5-Tul4, Ad5-OmpA, Ad5-FopA, and Ad5-DnaK) after a single immunization, and all Ad5-based vaccines stimulated a Th1-biased immune response. Moreover, intramuscular and intranasal vaccination with Ad5-Tul4 using the prime-boost strategy effectively eliminated Ft lung, spleen and liver colonization and provided nearly 80% protection against intranasal challenge with the Ft live vaccine strain (LVS). Only intramuscular, not intranasal vaccination, with Ad5-Tul4 protected mice from intraperitoneal challenge. This study provides a comprehensive comparison of protective immunity against Ft provided by subunit or adenovirus-vectored vaccines and suggests that mucosal vaccination with Ad5-Tul4 may yield desirable protective efficacy against mucosal infection, while intramuscular vaccination offers greater overall protection against intraperitoneal tularemia.