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This paper presents a systematic methodology for analyzing and optimizing an innovative antenna mount designed for phased array antennas, implemented through a novel 2-PSS&1-RR circular-rail parallel mechanism. Initially, a comparative motion analysis between the 3D model of the mount and its full-scale prototype is conducted to validate effectiveness. Given the inherent complexity, a kinematic mapping model is established between the mount and the crank-slider linkage, providing a guiding framework for subsequent analysis and optimization. Guided by this model, feasible inverse and forward solutions are derived, enabling precise identification of stiffness singularities. The concept of singularity distance is thus introduced to reflect the structural stiffness of the mount. Subsequently, also guided by the mapping model, a heuristic algorithm incorporating two backtracking procedures is developed to reduce the mount's mass. Additionally, a parametric finite-element model is employed to explore the relation between singularity distance and structural stiffness. The results indicate a significant reduction (about 16%) in the antenna mount's mass through the developed algorithm, while highlighting the singularity distance as an effective stiffness indicator for this type of antenna mount.

Platelet-rich plasma (PRP) has the capability of assisting in the recovery of damaged tissues by releasing a variety of biologically active factors to initiate a hemostatic cascade reaction and promote the synthesis of new connective tissue and revascularization. It is now widely used for tissue engineering repair. In addition, PRP has demonstrated nerve repair and pain relief, and has been studied and applied to the facial nerve, median nerve, sciatic nerve, and central nerve.These suggest that PRP injection therapy has a positive effect on nerve repair. This indicates that PRP has high clinical value and potential application in nerve repair. It is worthwhile for scientists and medical workers to further explore and study PRP to expand its application in nerve repair, and to provide a more reliable scientific basis for the opening of a new approach to nerve repair.

Abstract Limited information is available on the cardiovascular health (CVH) index and risk of high-normal blood pressure (HNBP) in elderly people. Randomized cluster sampling, multivariate logistic regression, and mediating effects analysis were used in this study analyze the relationship between CVH index and HNBP in the elderly. 1089 non-hypertensive residents aged 65 years or older completed the study. The positive rate of HNBP was 75.85% (male vs. female: 76.13% vs. 75.64%, P = 0.852); The ideal rate of CVH (ideal CVH index ≥ 5 items) was 14.51% (male vs. female: 15.91% vs. 13.46%, P = 0.256). Compared with people with 0–2 ideal CVH index, the risk of HNBP in people with 4 ideal indexes and ≥ 5 ideal indexes decreased by 50% and 63%, respectively, and their OR (95% CI) were 0.50 (0.31, 0.81) and 0.37 (0.21, 0.66), respectively. The results of the trend test showed that the risk of HNBP decreased by 32% for every increase in the ideal CVH index (trend P

Pragmatic impairment has become a critical aspect of language development in autistic children and has gained significant academic attention over the past two decades. This study leverages bibliometric methods to conduct an exhaustive analysis of literature derived from Web of Science database. Utilizing CiteSpace software, we construct a knowledge map to dissect the academic hotspots in research related to pragmatic impairment in autistic children. This enables us to delineate the evolutionary trajectory of this research domain, analyze the prevailing research dimensions, and anticipate potential future dimensions. Our findings indicate that research hotspots in this field over the past two decades predominantly concentrate on assessing and diagnosing pragmatic impairment in autistic children, intervention strategies, and theory of mind. The research scope on pragmatic impairment in autistic children has progressively broadened and deepened. Research has evolved from initial descriptions and interpretations of autism to exploring the theory of mind in high-functioning, school-aged children. The current emphasis is on examining the specific skills that these children possess.

Objective The arginase inhibitor INCB001158 was evaluated for safety (primary endpoint) in locally advanced or metastatic solid tumours; pharmacokinetics, pharmacodynamics and efficacy were also assessed.Methods and analysis In this non-randomised, open-label, three-part phase 1 study, INCB001158 was orally administered two times per day as monotherapy or in combination with intravenous pembrolizumab 200 mg every 3 weeks. Dose expansion was conducted in tumour-type cohorts (with or without prior anti−PD-1/PD-L1 (programmed death protein 1/programmed death ligand 1) therapy).Results A total of 107 patients received INCB001158 50–150 mg two times per day as monotherapy, and 153 patients, including 6 with moderate renal impairment, received INCB001158 50–100 mg two times per day combined with pembrolizumab. INCB001158 exposure was similar between groups (median, 56 days (monotherapy); 84 days (combination)). 49 patients (45.8%) on monotherapy and 76 (51.7%) on combination therapy experienced grade ≥3 treatment-emergent adverse events (AEs). The most common INCB001158-related AEs were fatigue (n=10/107 (9.3%)) and nausea (n=10/107 (9.3%)) with monotherapy and diarrhoea (n=24/147 (16.3%)) and fatigue (n=22/147 (15.0%)) with combination therapy. The highest response rate was seen in the anti–PD-1/PD-L1–naive combination therapy group with head/neck squamous cell carcinoma (overall response rate, 19.2%; 4/26 partial responses, 1/26 complete response). Consistent with arginase inhibition activity, plasma arginine dose-dependently increased. Arginase 1 expression in the tumour microenvironment did not correlate with response.Conclusions INCB001158 was generally well tolerated. Response rates did not exceed background for given tumour types despite demonstrable pharmacodynamic activity. Overall, the limited antitumour activity of arginase inhibition observed suggests that the role of arginine depletion in cancer is multifaceted.Trial registration number NCT02903914.

ABSTRACTIn order to develop nutritious and healthy fermented fig juice, foure samples fermented were made using natural fermentation and fermentation by lactobacillus. Then the total acidity, total sugar, reducing sugar, total phenols, total flavones and characteristic organic acids, antioxidant activity, and inhibition of enzyme activity in fermented fig juice were compared. The results showed that natural fermentation could produce more reducing sugar, lactic acid, flavonoids, and exhibit stronger DPPH radical scavenging capacity and total reducing power. Inhibition of tyrosinase and pancreatic lipase was detected in fermented fig juice, of which the inhibition rate of tyrosinase by natural fermentation was 81.80%, and the inhibition rate of pancreatic lipase by mixed cultures was 38.72%, which was higher than that of other groups. The results indicated the functional activity of fermented fig juice could be improved by fermentation, and the natural fermentation method was found superior.

BackgroundPrevious neuroimaging studies have revealed structural and functional brain abnormalities in patients with cervical spondylosis (CS). However, the results are divergent and inconsistent. Therefore, the present study conducted a multi-modal meta-analysis to investigate the consistent structural and functional brain alterations in CS patients.MethodsA comprehensive literature search was conducted in five databases to retrieve relevant resting-state functional magnetic resonance imaging (rs-fMRI), structural MRI and diffusion tensor imaging (DTI) studies that measured brain functional and structural differences between CS patients and healthy controls (HCs). Separate and multimodal meta-analyses were implemented, respectively, by employing Anisotropic Effect-size Signed Differential Mapping software.Results13 rs-fMRI studies that used regional homogeneity, amplitude of low-frequency fluctuations (ALFF) and fractional ALFF, seven voxel-based morphometry (VBM) studies and one DTI study were finally included in the present research. However, no studies on surface-based morphometry (SBM) analysis were included in this research. Due to the insufficient number of SBM and DTI studies, only rs-fMRI and VBM meta-analyses were conducted. The results of rs-fMRI meta-analysis showed that compared to HCs, CS patients demonstrated decreased regional spontaneous brain activities in the right lingual gyrus, right middle temporal gyrus (MTG), left inferior parietal gyrus and right postcentral gyrus (PoCG), while increased activities in the right medial superior frontal gyrus, bilateral middle frontal gyrus and right precuneus. VBM meta-analysis detected increased GMV in the right superior temporal gyrus (STG) and right paracentral lobule (PCL), while decreased GMV in the left supplementary motor area and left MTG in CS patients. The multi-modal meta-analysis revealed increased GMV together with decreased regional spontaneous brain activity in the left PoCG, right STG and PCL among CS patients.ConclusionThis meta-analysis revealed that compared to HCs, CS patients had significant alterations in GMV and regional spontaneous brain activity. The altered brain regions mainly included the primary visual cortex, the default mode network and the sensorimotor area, which may be associated with CS patients' symptoms of sensory deficits, blurred vision, cognitive impairment and motor dysfunction. The findings may contribute to understanding the underlying pathophysiology of brain dysfunction and provide references for early diagnosis and treatment of CS.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, CRD42022370967.

Abstract Studies have suggested that serum testosterone levels may be strongly correlated with the pathogenesis of arthritis. Therefore, the aim of this study was to assess the relationship between serum testosterone levels and arthritis in US adults using the National Health and Nutrition Examination Survey (NHANES). We used the database from NHANES, 2013–2016 to perform a cross-sectional study. This study investigated the relationship between serum testosterone and arthritis using multivariate logistic regression models and also used smoothed curve fitting and generalized additivity models. A total of 10,439 adults were included in this analysis. A significant negative association between serum testosterone and arthritis was found in a linear regression analysis. The study showed that the arthritis group had lower testosterone levels than the non-arthritis group. The univariate multivariate analyses of Q4, using Q1 as a reference, all showed a significantly lower risk of developing arthritis. In subgroup analyses, the negative correlation between serum testosterone levels and arthritis was more significant in women and those with a body mass index (BMI) ≥ 30 kg/m2. After controlling for various variables, we found a significant association between serum testosterone and arthritis in this analysis. Further study of the relationship between testosterone and arthritis is necessary to clarify the specific mechanism of serum testosterone action on arthritis.

Abstract Objective The primary objective of this study is to elucidate the molecular mechanism underlying the reversal of peritoneal fibrosis (PF) by Danshenol C, a natural compound derived from the traditional Chinese medicine Salvia miltiorrhiza. By comprehensively investigating the intricate interactions and signaling pathways involved in Danshenol C's therapeutic effects on PF, we aim to unveil novel insights into its pharmacological actions. This investigation holds the potential to revolutionize the clinical application of Salvia miltiorrhiza in traditional Chinese medicine, offering promising new avenues for the treatment of PF and paving the way for evidence-based therapeutic interventions. Methods Firstly, we utilized the YaTCM database to retrieve the structural formula of Danshenol C, while the SwissTargetPrediction platform facilitated the prediction of its potential drug targets. To gain insights into the genetic basis of PF, we acquired the GSE92453 dataset and GPL6480-9577 expression profile from the GEO database, followed by obtaining disease-related genes of PF from major disease databases. R software was then employed to screen for DEG associated with PF. To explore the intricate interactions between Danshenol C's active component targets, we utilized the String database and Cytoscape3.7.2 software to construct a PPI network. Further analysis in Cytoscape3.7.2 enabled the identification of core modules within the PPI network, elucidating key targets and molecular pathways critical to Danshenol C's therapeutic actions. Subsequently, we employed R to perform GO and KEGG pathway enrichment analyses, providing valuable insights into the functional implications and potential biological mechanisms of Danshenol C in the context of PF. To investigate the binding interactions between the core active components and key targets, we conducted docking studies using Chem3D, autoDock1.5.6, SYBYL2.0, and PYMOL2.4 software. We applied in vivo and in vitro experiments to prove that Danshenol C can improve PF. In order to verify the potential gene and molecular mechanism of Danshenol C to reverse PF, we used quantitative PCR, western blot, and apoptosis, ensuring robust and reliable verification of the results. Results ① Wogonin, sitosterol, and Signal Transducer and Activator of Transcription 5 (STAT5) emerged as the most significant constituents among the small-molecule active compounds and gene targets investigated. ②38 targets intersected with the disease, among which MAPK14, CASP3, MAPK8 and STAT3 may be the key targets; The results of GO and KEGG analysis showed that there was a correlation between inflammatory pathway and Apoptosis. ④Real-time PCR showed that the mRNA expressions of MAPK8 (JNK1), MAPK14 (P38) and STAT3 were significantly decreased after Danshenol C treatment (P

In recent years, with the rapidly aging population, alleviating the pressure on medical staff has become a critical issue. To improve the work efficiency of medical staff and reduce the risk of infection, we consider the multi-trip autonomous mobile robot (AMR) routing problem in a stochastic environment. Our goal is to minimize the total expected operating cost and maximize the total service quality for patients, ensuring that each route violates the vehicle capacity and the time window with only a minimal probability. The travel time of AMRs is stochastically affected by the surrounding environment; the demand for each ward is unknown until the AMR reaches the ward, and the service time is linearly related to the actual demand. We developed a population-based tabu search algorithm (PTS) that combines the genetic algorithm with the tabu search algorithm to solve this problem. Extensive numerical experiments were conducted on the modified Solomon instances to demonstrate the efficiency of the PTS algorithm and reveal the impacts of the confidence level on the optimal solution, providing insights for decision-makers to devise delivery schemes that balance operating costs with patient satisfaction.

Characterized by severe deficits in communication, most individuals with autism spectrum conditions (ASC) experience significant language dysfunctions, thereby impacting their overall quality of life. Wernicke's area, a classical and traditional brain region associated with language processing, plays a substantial role in the manifestation of language impairments. The current study carried out a mega-analysis to attain a comprehensive understanding of the neural mechanisms underpinning ASC, particularly in the context of language processing. The study employed the Autism Brain Image Data Exchange (ABIDE) dataset, which encompasses data from 443 typically developing (TD) individuals and 362 individuals with ASC. The objective was to detect abnormal functional connectivity (FC) between Wernicke's area and other language-related functional regions, and identify frequency-specific altered FC using Wernicke's area as the seed region in ASC. The findings revealed that increased FC in individuals with ASC has frequency-specific characteristics. Further, in the conventional frequency band (0.01–0.08 Hz), individuals with ASC exhibited increased FC between Wernicke's area and the right thalamus compared with TD individuals. In the slow-5 frequency band (0.01–0.027 Hz), increased FC values were observed in the left cerebellum Crus II and the right lenticular nucleus, pallidum. These results provide novel insights into the potential neural mechanisms underlying communication deficits in ASC from the perspective of language impairments.

PurposeSepsis-induced cardiomyopathy (SIC) is a major life-threatening condition in critically infected patients. Early diagnosis and intervention are important to improve patient prognosis. Recognizing the pivotal involvement of the glycolytic pathway in SIC, this study aims to establish a glycolysis-related ceRNA network and explore novel diagnostic avenues.Materials and methodsSIC-related datasets were carefully filtered from the GEO database. CytoHubba was used to identify differentially expressed genes (DEGs) associated with glycolysis. A predictive method was then used to construct an lncRNA-miRNA-mRNA network. Dual-luciferase reporter assays validated gene interactions, and the specificity of this ceRNA network was confirmed in peripheral blood mononuclear cells (PBMCs) from SIC patients. Logistic analysis was used to examine the correlation between the ceRNA network and SIC. Diagnostic potential was assessed using receiver operating characteristic (ROC) curves, and correlation analysis investigated any associations between gene expression and clinical indicators.ResultsIER3 was identified as glycolysis-related DEG in SIC, and a ceRNA network (SNHG17/miR-214-3p/IER3) was established by prediction. Dual luciferase reporter gene assay confirmed the presence of mutual binding between IER3, miR-214-3p and SNHG17. RT-qPCR verified the specific expression of this ceRNA network in SIC patients. Multivariate logistic analysis established the correlation between the ceRNA network and SIC. ROC analysis demonstrated its high diagnostic specificity (AUC > 0.8). Correlation analysis revealed a negative association between IER3 expression and oxygenation index in SIC patients (p

Metaphor affects how people focus, remember, and process information and significantly influences children’s language development. The study explored metaphorical comprehension by Chinese children of different ages (5–8 years). We collected response times and accuracy rates when they processed metaphorical and literal sentences with the graded salience. Linear mixed-effects modeling showed that Chinese children’s metaphorical ability improved with age. Subsequent analysis found that the perception period of metaphorical knowledge was at age 5, the development stage of metaphorical knowledge was at age 6 and 7, and the rational decision period of metaphorical ability was at age 8. After 8-year-old, children can invoke the knowledge of the intention schema while activating the source domain, and this knowledge can be automatically and quickly mapped to the target domain. Meanwhile, language development and cognitive processing influenced the metaphorical comprehension of Chinese children, especially children of 8 years of age who had the highest correct rate and the shortest reaction time to process low-saliency metaphorical sentences, while 5-year-old children had the highest accuracy in high-saliency metaphorical sentence and 6-year-old children got the longest reaction time to process sentence in high-saliency metaphor. This study may provide evidence for improving and training metaphor comprehension in children with special needs such as those with an autism spectrum disorder.

Abstract Background Although spatial organization of compartments and topologically associating domains at large scale is relatively well studied, the spatial organization of regulatory elements at fine scale is poorly understood in plants. Results Here we perform high-resolution chromatin interaction analysis using paired-end tag sequencing approach. We map chromatin interactions tethered with RNA polymerase II and associated with heterochromatic, transcriptionally active, and Polycomb-repressive histone modifications in Arabidopsis. Analysis of the regulatory repertoire shows that distal active cis-regulatory elements are linked to their target genes through long-range chromatin interactions with increased expression of the target genes, while poised cis-regulatory elements are linked to their target genes through long-range chromatin interactions with depressed expression of the target genes. Furthermore, we demonstrate that transcription factor MYC2 is critical for chromatin spatial organization, and propose that MYC2 occupancy and MYC2-mediated chromatin interactions coordinately facilitate transcription within the framework of 3D chromatin architecture. Analysis of functionally related gene-defined chromatin connectivity networks reveals that genes implicated in flowering-time control are functionally compartmentalized into separate subdomains via their spatial activity in the leaf or shoot apical meristem, linking active mark- or Polycomb-repressive mark-associated chromatin conformation to coordinated gene expression. Conclusion The results reveal that the regulation of gene transcription in Arabidopsis is not only by linear juxtaposition, but also by long-range chromatin interactions. Our study uncovers the fine scale genome organization of Arabidopsis and the potential roles of such organization in orchestrating transcription and development.

Abstract Introduction In the aging process of the body, in addition to changes in fat and muscle content, there is also bone loss, implying the possibility of a strong muscle–bone–lipid link. In this study, we initially investigated the relationship between lumbar BMD and low muscle mass and the relationship between “muscle–bone–lipid.” Methods The datasets from the National Health and Nutrition Examination Survey (NHANES) 2011–2018 were used in a cross-sectional investigation. BMD and appendicular skeletal muscle (ASM) were measured by dual-energy X-ray absorptiometry (DXA), and appendicular skeletal muscle was adjusted by body mass index (BMI) as a marker of sarcopenia. Weighted multivariate regression and logistic regression analysis were used to explore the independent relationship between lumbar BMD and sarcopenia. Fitted smoothing curves and threshold effect analysis were used to describe the nonlinear relationship. Result In 8386 participants with ages 20–59 years, there was a negative association between lumbar BMD and sarcopenia. In the fully adjusted model, the risk of developing sarcopenia decreased by 93% for each 1-unit increase in lumbar BMD (OR = 0.07, 95%CI 0.03–0.20). The risk of sarcopenia was 58% lower in participants in the highest quartile of lumbar BMD than in those in the lowest quartile (OR = 0.42, 95%CI 0.27–0.64). This negative association was more pronounced in the population of women with BMI ≥ 25. Conclusion Our findings suggest that lumbar BMD is negatively associated with sarcopenia in US adults. The dynamic balance between “muscle–bone–lipid” is likely to be related to the pathogenesis of bone loss.

Abstract Background Type 2 diabetes mellitus (DM2) and osteoporosis (OP) are currently the two most significant causes of mortality and morbidity in older adults, according to clinical evidence. The intrinsic link between them is yet unknown, despite reports of their coexistence. By utilizing the two-sample Mendelian randomization (MR) approach, we sought to evaluate the causal impact of DM2 on OP. Methods The aggregate data of the whole gene-wide association study (GWAS) were analyzed. A two-sample MR analysis was performed using single-nucleotide polymorphisms (SNPs), which are strongly associated with DM2, as instrumental variables (IVs) to evaluate the causal analysis of DM2 on OP risk with OR values, using inverse variance weighting, MR-egger regression, and weighted median methods, respectively. Result A total of 38 single nucleotide polymorphisms were included as tool variables. According to the results of inverse variance-weighted (IVW), we found that there was a causal relationship between DM2 and OP, in which DM2 had a protective effect on OP. For each additional case of DM2, there is a 0.15% decrease in the odds of developing OP (OR = 0.9985;95%confidence interval:0.9974,0.9995; P value = 0.0056). There was no evidence that the observed causal effect between DM2 and the risk of OP was affected by genetic pleiotropy (P = 0.299). Using Cochran Q statistics and MR-Egger regression in the IVW approach, the heterogeneity was calculated; P > 0.05 shows that there is a significant amount of heterogeneity. Conclusion A causal link between DM2 and OP was established by MR analysis, which also revealed that DM2 decreased the occurrence of OP.

BackgroundChinese visceral adiposity index (CVAI) is a reliable indicator of visceral obesity, but little is known about the association of CVAI with comorbidity of hypertension (HTN) and diabetes mellitus (DM). This study aimed to explore the associations of CVAI with HTN-DM comorbidity, HTN or DM, HTN, and DM in elderly people and evaluate the mediating role of insulin resistance in the associations.MethodsA total of 3,316 Chinese participants aged ≥60 years were included in this cross-sectional study. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Restricted cubic splines were applied to explore the dose–response associations. Mediation analyses were used to assess the mediating effect of triglyceride-glucose (TyG) index in the associations.ResultsThe prevalence rate of HTN-DM comorbidity, HTN or DM, HTN, and DM was 13.78%, 72.26%, 67.16%, and 18.88%, respectively. Linear associations between CVAI and HTN-DM comorbidity, HTN or DM, HTN, and DM were found, and ORs (95%CIs) were 1.45 (1.30–1.61), 1.39 (1.28–1.52), 1.36 (1.25–1.48), and 1.28 (1.16–1.41) for per SD increase in CVAI. Compared with quartile 1 of CVAI, the risk of HTN-DM comorbidity, HTN or DM, HTN, and DM increased 190%, 125%, 112%, and 96% for quartile 4. In addition, we found TyG index playing a key role in the associations of CVAI with HTN-DM comorbidity, HTN or DM, and DM.ConclusionCVAI is linearly and positively correlated with HTN-DM comorbidity, HTN or DM, HTN, and DM. The potential mechanism is insulin resistance largely mediating the associations.

Based on conversations between 15 clients and 5 therapists in the context of daily treatment, this study investigated therapist-client linguistic mitigation in a natural setting. The study found that (1) the therapists and clients mainly used three major types of mitigation, among which illocutionary mitigation and propositional mitigation were employed more frequently. Furthermore, direct dissuasion and disclaimers, as subtypes of mitigators, were the most regularly employed by therapists and clients, respectively. (2) Through cognitive-pragmatic interpretation under rapport management theory, it was found that mitigation in the therapist-client conversations mainly performed cognitive-pragmatic functions in giving the means to preserve positive face, maintaining social rights and concentrating on interactive goals, which were interpenetrated with each other in therapeutic conversations. (3) This study proposed that three cognitive-pragmatic functions jointly devoted to a rapport in therapeutic relationship to reduce therapeutic risk of conflicts.

This paper studies the scheduling of autonomous mobile robots (AMRs) at hospitals where the stochastic travel times and service times of AMRs are affected by the surrounding environment. The routes of AMRs are planned to minimize the daily cost of the hospital (including the AMR fixed cost, penalty cost of violating the time window, and transportation cost). To efficiently generate high-quality solutions, some properties are identified and incorporated into an improved tabu search (I-TS) algorithm for problem-solving. Experimental evaluations demonstrate that the I-TS algorithm outperforms existing methods by producing high-quality solutions. Based on the characteristics of healthcare requests and the AMR working environment, scheduling AMRs reasonably can effectively provide medical services, improve the utilization of medical resources, and reduce hospital costs.

The current study employed the event-related potential (ERP) technique to investigate predictive inference revision during Chinese narrative text reading among Chinese native speakers. Experiment 1 studied predictive inference revision by ensuring high contextual constraints for activation of the primary predictive inferences. Experiment 2 inspected the effects of the weaker inference alternatives on the revision process. Longer reading time and less positive mean average amplitude with two subcomponents of P300 (P3a and P3b) in the revise condition suggest that readers could detect inconsistent information and disconfirm the incorrect predictive inferences. However, they have difficulties in either integrating the alternative predictive inferences (N400) or revising the incorrect ones (P600), especially when the alternatives are of weaker activation levels. This study supports the Knowledge Revision Components (KReC) framework by verifying remaining activation of the disconfirmed primary inferences and extends it by considering effects of competitive alternatives on the predictive inference revision process.

Autonomous mobile robots (AMRs) play a crucial role in transportation and service tasks at hospitals, contributing to enhanced efficiency and meeting medical demands. This paper investigates the optimization problem of scheduling strategies for AMRs at smart hospitals, where the service and travel times of AMRs are stochastic. A stochastic mixed-integer programming model is formulated to minimize the total cost of the hospital by reducing the number of AMRs and travel distance while satisfying constraints such as AMR battery state of charge, AMR capacity, and time windows for medical requests. To address this objective, some properties of the solutions with time window constraints are identified. The variable neighborhood search (VNS) algorithm is adjusted by incorporating the properties of the AMR scheduling problem to solve the model. Experimental results demonstrate that VNS generates high-quality solutions. Both enhanced efficiency and the meeting of medical demands are achieved through intelligently arranging the driving routes of AMRs for both charging and service requests, resulting in substantial cost reductions for hospitals and enhanced utilization of medical resources.

BackgroundMyotonic dystrophy type 1 (DM1) is the most common and dominant inherited neuromuscular dystrophy disease in adults, involving multiple organs, including the brain. Although structural measurements showed that DM1 is predominantly associated with white-matter damage, they failed to reveal the dysfunction of the white-matter. Recent studies have demonstrated that the functional activity of white-matter is of great significance and has given us insights into revealing the mechanisms of brain disorders.Materials and methodsUsing resting-state fMRI data, we adopted a clustering analysis to identify the white-matter functional networks and calculated functional connectivity between these networks in 16 DM1 patients and 18 healthy controls (HCs). A two-sample t-test was conducted between the two groups. Partial correlation analyzes were performed between the altered white-matter FC and clinical MMSE or HAMD scores.ResultsWe identified 13 white-matter functional networks by clustering analysis. These white-matter functional networks can be divided into a three-layer network (superficial, middle, and deep) according to their spatial distribution. Compared to HCs, DM1 patients showed increased FC within intra-layer white-matter and inter-layer white-matter networks. For intra-layer networks, the increased FC was mainly located in the inferior longitudinal fasciculus, prefrontal cortex, and corpus callosum networks. For inter-layer networks, the increased FC of DM1 patients is mainly located in the superior corona radiata and deep networks.ConclusionResults demonstrated the abnormalities of white-matter functional connectivity in DM1 located in both intra-layer and inter-layer white-matter networks and suggested that the pathophysiology mechanism of DM1 may be related to the white-matter functional dysconnectivity. Furthermore, it may facilitate the treatment development of DM1.

ObjectiveThe aim of this study was to investigate the spontaneous regional neural activity abnormalities in patients with acute basal ganglia ischemic stroke (BGIS) using a multifrequency bands regional homogeneity (ReHo) method and to explore whether the alteration of ReHo values was associated with clinical characteristics.MethodsIn this study, 34 patients with acute BGIS and 44 healthy controls (HCs) were recruited. All participants were examined by resting-state functional magnetic resonance imaging (rs-fMRI). The ReHo method was used to detect the alterations of spontaneous neural activities in patients with acute BGIS. A two-sample t-test comparison was performed to compare the ReHo value between the two groups, and a Pearson correlation analysis was conducted to assess the relationship between the regional neural activity abnormalities and clinical characteristics.ResultsCompared with the HCs, the patients with acute BGIS showed increased ReHo in the left caudate and subregions such as the right caudate and left putamen in conventional frequency bands. In the slow-5 frequency band, patients with BGIS showed decreased ReHo in the left medial cingulum of BGIS compared to the HCs and other subregions such as bilateral caudate and left putamen. No brain regions with ReHo alterations were found in the slow-4 frequency band. Moreover, we found that the ReHo value of left caudate was positively correlated with the NIHSS score.ConclusionOur findings revealed the alterations of ReHo in patients with acute BGIS in a specific frequency band and provided a new insight into the pathogenesis mechanism of BGIS. This study demonstrated the frequency-specific characteristics of ReHo in patients with acute BGIS, which may have a positive effect on the future neuroimaging studies.

Herein, the quercetin-human serum albumin (HSA) nano-complex was formulated and its capability to decrease H2O2-stimulated cytotoxicity against spinal cord neurons as a model of preventive care study was investigated by cellular assays. Quercetin molecules were first encapsulated into HSA as a shell and the loading efficiency along with drug release and different properties of formulated nano-complex were determined using TEM, SEM, and DLS approaches. Afterwards using CD spectroscopic method and theoritical analysis, the structural changes and binding redisues of HSA after interaction with quercetin were investigated, respectively. Finally, the antioxidant activity of quercetin-HSA nano-complex against H2O2 (200 µM)-stimulated cytotoxicity in spinal cord neurons was explored by MTT, SOD and CAT activity, and morphological changes assays. It was shown that the fabrication of quercetin-HSA nano-complex resulted in the improved bioavailability of quercetin with an entrapment efficiency of 68.99% and percent yield of 53.19%. Also, molecular docking study showed that quercetin molecules spontaneously bind to HSA through hydrogen bonds and van der Waals interactions. Furthermore, CD data indicated that the quercetin did not change the secondary structure of HSA. Finally, cellular assays displayed that the pre-treatments of spinal cord neurons with quercetin-HSA nano-complex attenuated the H2O2-triggerd neuron mortality through a significant increase in the activity of SOD and CAT and prevention of morphological changes. In conclusion, it may be suggested that the formulation of quercetin into nano-complex can improve its medical properties and this new developed drug formulation may hold a great promise in the advancement of antioxidant compounds in preventive care services.

Objectives Vaccinations can prevent COVID-19 and control its spread quickly and efficiently. This study aimed to investigate knowledge and willingness of geriatric care facility staff to receive a COVID-19 vaccine, and to provide a basis for the government to promote the COVID-19 vaccine and guide people to get vaccinated. Study design A cross-sectional study. Methods Data on characteristics of the participants, knowledge about the COVID-19 vaccine, and willingness to get vaccinated for COVID-19 were collected through an online survey from May 19 to June 18, 2021. Statistical analyses were conducted with ANOVA, chi-square, logistic regression. Results The survey illustrated that the highest score of COVID-19 vaccine knowledge was 50, the lowest 20, and the average 44.22. It also demonstrated that 91.3% of the participants had a good knowledge of COVID-19 vaccine, and that 97.3% participants were willing to receive the COVID-19 vaccine. The results showed that geriatric care facility staff had varied level of the COVID-19 vaccine knowledge depending upon their age, educational background, and other factors, and correspondingly, their willingness to receive COVID-19 vaccine was affected by their knowledge level of COVID-19 vaccine. Conclusions In general, the participants, the staff of geriatric care facilities in Anhui Province, had good mastery of the COVID-19 vaccine, and they were willing to get vaccinated. However, there still existed a few participants with poor knowledge, who were unwilling to get vaccinated against COVID-19. Government can guide people to accept vaccination by enhancing publicity about the effects and adverse reactions of COVID-19 vaccines.

Stroke is a brain system disease with a high fatality rate and disability rate. About 80% of strokes are ischemic strokes. Cerebral ischemia-reperfusion injury (CIRI) caused by ischemic stroke seriously affects the prognosis of stroke patients. The purpose of this study is to investigate the effect of sufentanil (SUF) on CIRI model rats. We used middle cerebral artery occlusion (MCAO) to make the CIRI model in rats and monitored region cerebral blood flow (rCBF) to ensure that blood flow was blocked and recanalized. We used ELISA and RT-PCR to detect the expression of inflammatory factors in rat serum and brain tissue. In addition, we detected the expression of metalloproteinase (MMP) 2, MMP9 and collagen IV in brain tissues and performed Evans blue (EB) assay to determine the permeability of the blood-brain barrier (BBB). Finally, we clarified the apoptosis of brain tissue through the TUNEL staining and the detection of caspase3, Bcl2 and Bax. Various concentrations of SUF, especially 5, 10 and 25 μg/kg of SUF, all alleviated the infarct size, neurological function and brain edema of MCAO rats. SUF pretreatment also effectively reduced the expression of inflammatory cytokines in MCAO rats, including interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α. In addition, SUF also inhibited MMP2 and MMP9 and promoted the expression of collagen IV, indicating that SUF attenuated the destruction of the BBB. SUF also inhibited caspase3 and Bax rats and promoted Bcl2 in MCAO rats, thus inhibiting cell apoptosis. SUF pretreatment effectively improved the neurological function and cerebral infarction of MCAO rats, inhibited excessive inflammation in rats, protected the BBB, and inhibited cell apoptosis in brain tissue.

Objective. The purpose of this study was to investigate the characteristics of different frequency bands in the spontaneous brain activity among patients with acute basal ganglia ischemic stroke (BGIS). Methods. In the present study, thirty-four patients with acute BGIS and forty-four healthy controls were examined by resting-state functional magnetic resonance imaging (rs-fMRI) from May 2019 to December 2020. Two amplitude methods including amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) calculated in three frequency bands (conventional frequency band: 0.01-0.08 Hz; slow-5 frequency band: 0.01-0.027 Hz; and slow-4 frequency band: 0.027-0.073 Hz) were conducted to evaluate the spontaneous brain activity in patients with acute BGIS and healthy controls (HCs). Gaussian Random Field Theory (GRF, voxel p

Purpose. Several functional magnetic resonance imaging (fMRI) studies have investigated the resting-state functional connectivity (rs-FC) changes in the primary motor cortex (M1) in patients with acute basal ganglia ischemic stroke (BGIS). However, the frequency-specific FC changes of M1 in acute BGIS patients are still unclear. Our study was aimed at exploring the altered FC of M1 in three frequency bands and the potential features as biomarkers for the identification by using a support vector machine (SVM). Methods. We included 28 acute BGIS patients and 42 healthy controls (HCs). Seed-based FC of two regions of interest (ROI, bilateral M1s) were calculated in conventional, slow-5, and slow-4 frequency bands. The abnormal voxel-wise FC values were defined as the features for SVM in different frequency bands. Results. In the ipsilesional M1, the acute BGIS patients exhibited decreased FC with the right lingual gyrus in the conventional and slow-4 frequency band. Besides, the acute BGIS patients showed increased FC with the right medial superior frontal gyrus (SFGmed) in the conventional and slow-5 frequency band and decreased FC with the left lingual gyrus in the slow-5 frequency band. In the contralesional M1, the BGIS patients showed lower FC with the right SFGmed in the conventional frequency band. The higher FC values with the right lingual gyrus and left SFGmed were detected in the slow-4 frequency band. In the slow-5 frequency band, the BGIS patients showed decreased FC with the left calcarine sulcus. SVM results showed that the combined features (slow-4+slow-5) had the highest accuracy in classification prediction of acute BGIS patients, with an area under curve (AUC) of 0.86. Conclusion. Acute BGIS patients had frequency-specific alterations in FC; SVM is a promising method for exploring these frequency-dependent FC alterations. The abnormal brain regions might be potential targets for future researchers in the rehabilitation and treatment of stroke patients.

Objective To explore the expression of HIF-1α, neuronal apoptosis and the influence of traditional Chinese medicine Sanqi on hematoma after brain injury in rats. Methods Ninety SD rats were divided into 3 groups randomly: blank control group, traumatic brain injury (TBI) group and Sanqi intervention group, and they were decapitated after brain injury at different time points: 6 h, 1 d, 2 d, 3 d, 5 d, 7 d. The model of cerebral hemorrhage was made by autologous non-coagulation in stereotactic locator, the expression of HIF-1α and TUNEL-positive cells (apoptotic cells) in the perihematomal area was detected by immunohistochemistry. Results In blank control group, a small amount of HIF-1α was expressed and apoptotic cells were observed. The expression of HIF-1α was up-regulated in the brain injury group from 6 h, and the apoptotic cells increased in abundance. The peak of HIF-1α was reached at 3 d, then decreased, and remained at the high level on the 7 d. Compared with blank control group, the TBI group was statistically significant (P

Objective: To analyze the key targets and potential mechanisms underlying the volatile components of Scutellaria baicalensis Georgi acting on gliomas through network pharmacology combined with biological experiments.Methods: We have extracted the volatile components of Scutellaria baicalensis by gas chromatography-mass spectrometry (GC-MS) and determined the active components related to the onset and development of gliomas by combining the results with the data from the Traditional Chinese Medicine Systems Pharmacology database. We screened the same targets for the extracted active components and gliomas through network pharmacology and then constructed a protein-protein interaction network. Using a Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, we analyzed the protein effects and regulatory pathways of the common targets. Lastly, we employed ELISA and Western blot in verifying the key targets in the regulatory pathway.Results: We ultimately determined that the active component in S. baicalensis Georgi related to the onset and development of gliomas was Wogonin. The results of the network pharmacology revealed 85 targets for glioma and Wogonin. We used gene ontology to analyze these target genes and found that they involved 30 functions, such as phosphatidylinositol phosphokinase activation, while the KEGG analysis showed that there were 10 regulatory pathways involved. Through the following analysis, we found that most of the key target genes are distributed in the PI3K-Akt and interleukin 17 signaling pathways. We then cultured U251 glioma cells for the experiments. Compared with the control group, no significant change was noted in the caspase-3 expression; however, cleaved caspase-3 expression increased significantly and was dose-dependent on Wogonin. The expression of Bad and Bcl-2 with 25 μM of Wogonin has remained unchanged, but when the Wogonin dose was increased to 100 μM, the expression of Bad and Bcl-2 was noted to change significantly (Bad was significantly upregulated, while Bcl-2 was significantly downregulated) and was dose-dependent on Wogonin. The ELISA results showed that, compared with the control group, the secretion of tumor necrosis factor alpha, IL-1β, and IL-6 decreased as the Wogonin concentration increased. Tumor necrosis factor alpha downregulation had no significant dose-dependent effect on Wogonin, the inhibitory effect of 25 μM of Wogonin on IL-6 was not significant, and IL-1β downregulation had a significant dose-dependent effect on Wogonin.Conclusion: Wogonin might promote the apoptosis of glioma cells by upregulating proapoptotic factors, downregulating antiapoptotic factors, and inhibiting the inflammatory response, thereby inhibiting glioma progression.

Children's language development can reflect the developmental process of children's cognition and social emotions. The present study focuses on preschool children's conversational competence and narrative competence, aiming at exploring developmental features of preschool children's pragmatic competence through analyzing data from self-built oral language corpora using the INCA-A coding system and CLAN. Results show that with respect to using pragmatic indicators, frequency increases significantly with age in the dimensions of knowledge and language. In the language dimension, frequency is highest in the middle group and in the behavior dimension, frequency gradually decreases. Results are taken to indicate that preschool children's language competence improves continually, and gradually displaces the use of behavior-assisted language. Meanwhile, children can initiate conversation or discourse narration by using knowledge and language. Based on the findings, this study analyzes the development of preschool children's pragmatic competence at different ages within the framework of perlocutionary acts. Finally, corresponding educational suggestions are suggested.

Metallic gratings have drawn great attention over the past few years due to effective light trapping and power conversion efficiency enhancement in organic solar cells (OSCs). Novel OSCs incorporated short-pitch metallic grating into the conventional OSCs as the back electrode is presented. The optical and electrical properties of OSCs are investigated by applying the finite-difference frequency-domain method. It is found that the light absorption at 400-650 nm in the active layer is strongly improved, compared with the standard structure without metallic grating. The underlying physical mechanism is due to the surface plasmon resonance and the interaction between two neighbor gratings, which undoubtedly enhances the electrical properties such as short-circuit current (JSC), fill factor, and power conversion efficiency. Meanwhile, the optical and electrical properties of OSCs with different groove widths are also investigated. With an optimal groove width of 4 nm, the overall performance of OSCs is enhanced. This paper indicates that OSCs incorporated short-pitch metallic grating are promising candidates for high-performance OSCs.

X-linked juvenile retinoschisis (XLRS) is a retinal disease caused by mutations in the gene encoding retinoschisin (RS1), which leads to a significant proportion of visual impairment and blindness. To develop personalized genome editing based gene therapy, knock-in animal disease models that have the exact mutation identified in the patients is extremely crucial, and that the way which genome editing in knock-in animals could be easily transferred to the patients. Here we recruited a family diagnosed with XLRS and identified the causative mutation (RS1, p.Y65X), then a knock-in mouse model harboring this disease-causative mutation was generated via TALEN (transcription activator-like effector nucleases). We found that the b-wave amplitude of the ERG of the RS1-KI mice was significantly decreased. Moreover, we observed that the structure of retina in RS1-KI mice has become disordered, including the disarray of inner nuclear layer and outer nuclear layer, chaos of outer plexiform layer, decreased inner segments of photoreceptor and the loss of outer segments. The novel knock-in mice (RS1-KI) harboring patient-specific mutation will be valuable for development of treatment via genome editing mediated gene correction.

Genomic studies have provided insights into molecular subgroups and oncogenic drivers of pediatric brain tumors (PBT) that may lead to novel therapeutic strategies. Participants of the cohort Pediatric Brain Tumor Atlas: CBTTC (CBTTC cohort), were randomly divided into training and validation cohorts. In the training cohort, Kaplan-Meier analysis and univariate Cox regression model were applied to preliminary screening of prognostic genes. The LASSO Cox regression model was implemented to build a multi-gene signature, which was then validated in the validation and CBTTC cohorts through Kaplan-Meier, Cox, and receiver operating characteristic curve (ROC) analyses. Also, gene set enrichment analysis (GSEA) and immune infiltrating analyses were conducted to understand function annotation and the role of the signature in the tumor microenvironment. An eight-gene signature was built, which was examined by Kaplan-Meier analysis, revealing that a significant overall survival difference was seen, either in the training or validation cohorts. The eight-gene signature was further proven to be independent of other clinic-pathologic parameters via the Cox regression analyses. Moreover, ROC analysis demonstrated that this signature owned a better predictive power of PBT prognosis. Furthermore, GSEA and immune infiltrating analyses showed that the signature had close interactions with immune-related pathways and was closely related to CD8 T cells and monocytes in the tumor environment. Identifying the eight-gene signature (CBX7, JADE2, IGF2BP3, OR2W6P, PRAME, TICRR, KIF4A, and PIMREG) could accurately identify patients' prognosis and the signature had close interactions with the immunodominant tumor environment, which may provide insight into personalized prognosis prediction and new therapies for PBT patients.