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Abstract Vitiligo is a skin disorder that is associated with a decreased risk of skin cancer, but it can lead to increased susceptibility to sunburn, psychological distress, and disruptions in daily life, consists of two primary subtypes: segmental and nonsegmental vitiligo, each with distinct underlying mechanisms. However, the reliable identification of diagnostic markers and the ability to differentiate between these subtypes have remained elusive challenges. This study aims to pioneer predictive algorithms for vitiligo diagnosis, harnessing the capabilities of AI (Artificial Intelligence) to amalgamate multisource data and uncover essential features for distinguishing vitiligo subtypes.An ensemble algorithm was thoughtfully developed for vitiligo diagnosis, utilizing a spectrum of machine learning techniques to evaluate the likelihood of vitiligo, whether segmental or nonsegmental. Diverse machine learning methodologies were applied to distinguish between healthy individuals and vitiligo patients, as well as to differentiate segmental from nonsegmental vitiligo. The ensemble algorithm achieved a remarkable AUC (Area Under the Curve) of 0.99 and an accuracy of 0.98 for diagnosing vitiligo. Furthermore, in predicting the development of segmental or nonsegmental vitiligo, the model exhibited an AUC of 0.79 and an accuracy of 0.73. Key parameters for vitiligo identification encompassed factors such as age, FBC (full blood count)-neutrophils, FBC-lymphocytes, LKF(liver and kidney function)-direct bilirubin, LKF-total bilirubin, and LKF-total protein levels. In contrast, vital indicators for monitoring the progression of segmental and nonsegmental vitiligo included FBC-B lymphocyte count, FBC-NK (Natural Killer) cell count, and LKF-alkaline phosphatase levels. This retrospective study underscores the potential of AI-driven analysis in identifying significant risk factors for vitiligo and predicting its subtypes at an early stage. These findings offer great promise for the development of effective diagnostic tools and the implementation of personalized treatment approaches in managing this challenging skin disorder.

Pediatric gliomas are highly heterogeneous and have unique molecular characteristics. They are not smaller versions of adult gliomas. This review emphasizes the basic points of surgery, radiotherapy, and chemotherapy for pediatric gliomas, introduces the similarities and differences with targeted therapy for adult gliomas, describes the important driver gene abnormalities involved in pediatric gliomas and the corresponding targeted therapy strategies, and focuses on the epigenetic treatment strategies for pediatric diffuse high-grade gliomas caused by histone H3 mutations, and looks forward to the future work of diagnosis and treatment of pediatric gliomas.

Medical biotechnology is at the forefront of scientific progress, with humanity facing a critical juncture during the pandemic. However, to maximize these benefits, governments face the complex challenge of reconciling innovation and risk. A sustainable balance is critical, as extreme measures such as blanket bans on biotechnology research could hamper progress, while unfettered research could pose an existential threat. The need for effective regulation has become apparent in the context of recent controversies surrounding pharmaceutical biotechnology. Governments face the challenge of reconciling precaution with innovation, necessitating a dual strategy fostering both principles. This paper explores the delicate dynamics of innovation and risk in pharmaceutical biotechnology, focusing on the evolving landscape in Europe, the U.S., and, notably, China. At the same time, we delve into the regulatory landscape and examine the role of the “right to science” in shaping Chinese policy. This paper further applies the right to science that has received the interests of medical biotechnology regulatory policymakers: understanding the role of scientific claims in regulating emerging technologies and analyzing the impact of major regulations on the ability to sustainably balance innovation and risk. We believe that a comprehensive global effort is needed to harmonize these two principles, highlighting the imperative of responsible governance in steering the trajectory of this powerful scientific frontier. The insights gained from the Chinese experience offer valuable implications for global policymakers facing similar challenges.

Abstract This study aims to explore the efficacy of a hybrid deep learning and radiomics approach, supplemented with patient metadata, in the noninvasive dermoscopic imaging-based diagnosis of skin lesions. We analyzed dermoscopic images from the International Skin Imaging Collaboration (ISIC) dataset, spanning 2016–2020, encompassing a variety of skin lesions. Our approach integrates deep learning with a comprehensive radiomics analysis, utilizing a vast array of quantitative image features to precisely quantify skin lesion patterns. The dataset includes cases of three, four, and eight different skin lesion types. Our methodology was benchmarked against seven classification methods from the ISIC 2020 challenge and prior research using a binary decision framework. The proposed hybrid model demonstrated superior performance in distinguishing benign from malignant lesions, achieving area under the receiver operating characteristic curve (AUROC) scores of 99%, 95%, and 96%, and multiclass decoding AUROCs of 98.5%, 94.9%, and 96.4%, with sensitivities of 97.6%, 93.9%, and 96.0% and specificities of 98.4%, 96.7%, and 96.9% in the internal ISIC 2018 challenge, as well as in the external Jinan and Longhua datasets, respectively. Our findings suggest that the integration of radiomics and deep learning, utilizing dermoscopic images, effectively captures the heterogeneity and pattern expression of skin lesions.

Abstract Background Auriculocondylar syndrome (ARCND) is an extremely rare autosomal dominant or recessive condition that typically manifests as question mark ears (QMEs), mandibular condyle hypoplasia, and micrognathia. Severe dental and maxillofacial malformations present considerable challenges in patients’ lives and clinical treatment. Currently, only a few ARCND cases have been reported worldwide, but most of them are related to genetic mutations, clinical symptoms, and ear correction; there are few reports concerning the treatment of dentofacial deformities. Case presentation Here, we report a rare case of ARCND in a Chinese family. A novel insertional mutation in the guanine nucleotide-binding protein alpha-inhibiting activity polypeptide 3 (GNAI3) was identified in the patient and their brother using whole-exome sequencing. After a multidisciplinary consultation and examination, sequential orthodontic treatment and craniofacial surgery, including distraction osteogenesis and orthognathic surgery, were performed using three-dimensional (3D) digital technology to treat the patient’s dentofacial deformity. A good prognosis was achieved at the 5-year follow-up, and the patient returned to normal life. Conclusions ARCND is a monogenic and rare condition that can be diagnosed based on its clinical triad of core features. Molecular diagnosis plays a crucial role in the diagnosis of patients with inconspicuous clinical features. We present a novel insertion variation in GNAI3, which was identified in exon 2 of chromosome 110116384 in a Chinese family. Sequential therapy with preoperative orthodontic treatment combined with distraction osteogenesis and orthognathic surgery guided by 3D digital technology may be a practical and effective method for treating ARCND.

The geological conditions of the North China-type coalfields are complicated, and a large number of water-conducting channels are formed by the tectonic cutting of the coal seam base plate, whose detection and identification have always been the key point and difficulty in water damage prevention and control. Based on the multi-branch directional long drilling overrun investigation, the water-conducting channel identification technology combining process analysis and fuzzy comprehensive evaluation was constructed. Firstly, in the process of overpassing exploration, six evaluation indexes were selected, named drilling time recording, drilling fluid consumption, γ recording, rock chip recording, water pressure test and injectability and the construction process was divided into 16 working conditions, according to which a comprehensive analysis flowchart was set up to make a qualitatively judgement on whether the sample points were water-conducting. Secondly, the six indicators are quantified and graded by drilling speed, drilling fluid consumption, γ value, non-tuff proportion, unit grouting volume, and grouting volume, the weights of the indicators were determined by using the over-weighting method, and a three-level quantitative identification was made based on the fuzzy theory and the maximum membership principle to determine whether the sample point was water-conducting. Lastly, the technique was used to carry out a comprehensive process analysis and fuzzy comprehensive evaluation of 13 points in the 15031 working face of Zhaogu No.1 mine, of which 10 points had a high probability of water conduction and 3 points had a low probability of water conduction. This technique constructed a system of indicators for identifying water-conducting channels, and carried out quantitative grading and comprehensive evaluation, which improved the identification of water-conducting channels in the coalbed base plate.

ObjectivesTo investigate the value of CT radiomics combined with radiological features in predicting pathological grade of stage I invasive pulmonary adenocarcinoma (IPA) based on the International Association for the Study of Lung Cancer (IASLC) new grading system.MethodsThe preoperative CT images and clinical information of 294 patients with stage I IPA were retrospectively analyzed (159 training set; 69 validation set; 66 test set). Referring to the IASLC new grading system, patients were divided into a low/intermediate-grade group and a high-grade group. Radiomic features were selected by using the least absolute shrinkage and selection operator (LASSO), the logistic regression (LR) classifier was used to establish radiomics model (RM), clinical-radiological features model (CRM) and combined rad-score with radiological features model (CRRM), and visualized CRRM by nomogram. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve and calibration curve were used to evaluate the performance and fitness of models.ResultsIn the training set, RM, CRM, and CRRM achieved AUCs of 0.825 [95% CI (0.735-0.916)], 0.849 [95% CI (0.772-0.925)], and 0.888 [95% CI (0.819-0.957)], respectively. For the validation set, the AUCs were 0.879 [95% CI (0.734-1.000)], 0.888 [95% CI (0.794-0.982)], and 0.922 [95% CI (0.835-1.000)], and for the test set, the AUCs were 0.814 [95% CI (0.674-0.954)], 0.849 [95% CI (0.750-0.948)], and 0.860 [95% CI (0.755-0.964)] for RM, CRM, and CRRM, respectively.ConclusionAll three models performed well in predicting pathological grade, especially the combined model, showing CT radiomics combined with radiological features had the potential to distinguish the pathological grade of early-stage IPA.

Metal organic frameworks(MOFs),as non-homogeneous Fenton oxidation catalysts,are difficult to be utilized multiple times and prone to secondary pollution in the treatment of printing and dyeing wastewater. To solve this problem, metal organic framework polypropylene melt blown composites (TA-APTES@MOF@PP) were prepared by modifying the surface of polypropylene melt blown nonwoven (PP) with polyphenol heterogeneous network coating, which resulted in excellent adhesion and secondary reactivity,and by in situ growth of MIL-88B (Fe) crystals on its surface. The catalytic degradation effect and recycling performance of the composites were tested with methylene blue dye (MB) as the target pollutant,and the catalyst delivery ratio and optimal reaction conditions were determined by single-factor optimization. The results showed that the degradation of MB by TA-APTES@MOF@PP (MOF 20 mg) under dark conditions was optimal at 3 h with a degradation rate of 95.3% when the pH of dye solution was 3 and the H2O2 concentration was 50 mmol/L. The composite material has no secondary pollution,easy to recycle, good stability, acid and alkali resistance, catalytic effect in the pH range of 2-11 of dying solution, and the 3 h degradation rate was still above 73.4% after 5 cycles. The composite material had a broad application prospect in printing and dyeing wastewater treatment and water environment management.

Abstract Current assessment methods for diabetic foot ulcers (DFUs) lack objectivity and consistency, posing a significant risk to diabetes patients, including the potential for amputations, highlighting the urgent need for improved diagnostic tools and care standards in the field. To address this issue, the objective of this study was to develop and evaluate the Smart Diabetic Foot Ulcer Scoring System, ScoreDFUNet, which incorporates artificial intelligence (AI) and image analysis techniques, aiming to enhance the precision and consistency of diabetic foot ulcer assessment. ScoreDFUNet demonstrates precise categorization of DFU images into “ulcer,” “infection,” “normal,” and “gangrene” areas, achieving a noteworthy accuracy rate of 95.34% on the test set, with elevated levels of precision, recall, and F1 scores. Comparative evaluations with dermatologists affirm that our algorithm consistently surpasses the performance of junior and mid-level dermatologists, closely matching the assessments of senior dermatologists, and rigorous analyses including Bland–Altman plots and significance testing validate the robustness and reliability of our algorithm. This innovative AI system presents a valuable tool for healthcare professionals and can significantly improve the care standards in the field of diabetic foot ulcer assessment.

Abstract Background Sublobar resection for ground-glass opacity became a recommend surgery choice supported by the JCOG0804/JCOG0802/JCOG1211 results. Sublobar resection includes segmentectomy and wedge resection, wedge resection is suitable for non-invasive lesions, but in clinical practice, when pathologists are uncertain about the intraoperative frozen diagnosis of invasive lesions, difficulty in choosing the appropriate operation occurs. The purpose of this study was to analyze how to select invasive lesions with clinic-pathological characters. Methods A retrospective study was conducted on 134 cases of pulmonary nodules diagnosed with minimally invasive adenocarcinoma by intraoperative freezing examination. The patients were divided into two groups according to intraoperative frozen results: the minimally invasive adenocarcinoma group and the at least minimally invasive adenocarcinoma group. A variety of clinical features were collected. Chi-square tests and multiple regression logistic analysis were used to screen out independent risk factors related to pathological upstage, and then ROC curves were established. In addition, an independent validation set included 1164 cases was collected. Results Independent risk factors related to pathological upstage were CT value, maximum tumor diameter, and frozen result of AL-MIA. The AUC of diagnostic mode was 71.1% [95%CI: 60.8-81.3%]. The independent validation included 1164 patients, 417 (35.8%) patients had paraffin-based pathology of invasive adenocarcinoma. The AUC of diagnostic mode was 75.7% [95%CI: 72.9-78.4%]. Conclusions The intraoperative frozen diagnosis was AL-MIA, maximum tumor diameter larger than 15 mm and CT value is more than − 450Hu, highly suggesting that the lung GGO was invasive adenocarcinoma which represent a higher risk to recurrence. For these patients, sublobectomy would be insufficient, lobectomy or complementary treatment is encouraged.

Abstract Purpose To investigate the relationship between multi-dimensional aspects of screen exposure and autistic symptoms, as well as neuropsychological development in children with ASD. Methods We compared the ScreenQ and Griffiths Development Scales-Chinese Language Edition (GDS-C) of 636 ASD children (40.79 ± 11.45 months) and 43 typically developing (TD) children (42.44 ± 9.61 months). Then, we analyzed the correlations between ScreenQ and Childhood Autism Rating Scale (CARS), and GDS-C. We further used linear regression model to analyze the risk factors associated with high CARS total scores and low development quotients (DQs) in children with ASD. Results The CARS of children with ASD was positively correlated with the ScreenQ total scores and “access, frequency, co-viewing” items of ScreenQ. The personal social skills DQ was negatively correlated with the “access, frequency, content, co-viewing and total scores” of ScreenQ. The hearing-speech DQ was negatively correlated with the “frequency, content, co-viewing and total scores” of ScreenQ. The eye-hand coordination DQ was negatively correlated with the “frequency and total scores” of ScreenQ. The performance DQ was negatively correlated with the “frequency” item of ScreenQ. Conclusion ScreenQ can be used in the study of screen exposure in children with ASD. The higher the ScreenQ scores, the more severe the autistic symptoms tend to be, and the more delayed the development of children with ASD in the domains of personal-social, hearing-speech and eye-hand coordination. In addition, “frequency” has the greatest impact on the domains of personal social skills, hearing-speech, eye-hand coordination and performance of children with ASD.

Abstract Background Recently, studies on behavioral interventions for autism have gained popularity. Naturalistic Developmental Behavior Interventions (NDBIs) are among the most effective, evidence-based, and widely used behavior interventions for autism. However, no research has been conducted on which of the several NDBI methods is most effective for parents and children with autism spectrum disorders. Therefore, we conducted a network meta-analysis to compare the specific effects of each type of parental-mediated NDBI on children’s developmental skills and parent fidelity. Methods PubMed, Embase, Cochrane Library, Medline, Web of Science, China National Knowledge Infrastructure (CNKI), CINAHL, and Wanfang databases were searched from inception to August 30, 2023. A total of 32 randomized controlled trial studies that examined the efficacy of different NDBIs were included. Results Parents of children with ASD who received Pivotal Response Treatment (PRT) reported significant improvements in their children’s social skills (SUCRA, 74.1%), language skills (SUCRA, 88.3%), and parenting fidelity (SUCRA, 99.5%). Moreover, parents who received Early Start Denver Model (ESDM) reported significant improvements in their children’s language (SMD = 0.41, 95% CI: 0.04, 0.79) and motor skills (SMD = 0.44, 95% CI: 0.09, 0.79). In terms of the efficacy of improving parent fidelity, the results showed that the Improving Parents as Communication Teachers (ImPACT) intervention significantly improved parent fidelity when compared with the treatment-as-usual group (TAU) (SMD = 0.90, 95% CI: 0.39, 1.42) and the parental education intervention (PEI) (SMD = 1.10, 95% CI:0.28, 1.91).There was a difference in parent fidelity among parents who received PRT(SMD = 3.53, 95% CI: 2.26, 4.79) or ESDM(SMD = 1.42, 95% CI: 0.76, 2.09) training compared with PEI. Conclusion In conclusion, this study revealed that parents can achieve high fidelity with the ImPACT intervention, and it can serve as an early first step for children newly diagnosed with ASD. It also showed that parent-mediated ESDM is effective in improving language and motor skills for children with ASD and can be used as part of the second stage of parent training. Parent-mediated PRT can also be used as a third stage of parent training with sufficient training intensity to further improve language, social, and motor skills.

Abstract Background Early-onset bone dysplasia is a common manifestation of hypophosphatasia (HPP), an autosomal inherited disease caused by ALPL mutation. ALPL ablation induces prototypical premature bone ageing characteristics, resulting in impaired osteogenic differentiation capacity of human bone marrow mesenchymal stem cells (hBMMSCs). As angiogenesis is tightly coupled with osteogenesis, it also plays a necessary role in sustaining bone homeostasis. We have previously observed a decrease in expression of angiogenesis marker gene CD31 in the metaphysis of long bone in Alpl +/− mice. However, the role of ALPL in regulation of angiogenesis in bone has remained largely unknown. Methods Exosomes derived from Normal and HPP hBMMSCs were isolated and identified by ultracentrifugation, transmission electron microscopy, and nanoparticle size measurement. The effects of ALPL on the angiogenic capacity of hBMMSCs from HPP patients were assessed by immunofluorescence, tube formation, wound healing and migration assay. exo-ELISA and Western Blot were used to evaluate the exosomes secretion of hBMMSCs from HPP, and the protein expression of VEGF, PDGFBB, Angiostatin and Endostatin in exosomes respectively. Results We verified that ALPL ablation resulted in impaired pro-angiogenic capacity of hBMMSCs, accounting for reduced migration and tube formation of human umbilical vein endothelial cells, as the quantities and proteins composition of exosomes varied with ALPL expression. Mechanistically, loss of function of ALPL enhanced ATP release. Additional ATP, in turn, led to markedly elevated level of ATP receptor P2X7, which consequently promoted exosomes secretion, resulting in a decreased capacity to promote angiogenesis. Conversely, inhibition of P2X7 increased the angiogenic induction capacity by preventing excessive release of anti-angiogenic exosomes in ALPL deficient-hBMMSCs. Conclusion The ALPL–ATP axis regulates the pro-angiogenic ability of hBMMSCs by controlling exosomes secretion through the P2X7 receptor. Thus, P2X7 may be proved as an effective therapeutic target for accelerating neovascularization in ALPL–deficient bone defects.

Detection of specific antinuclear antibodies is very important in term of diagnosis, prognosis and management of patients with systemic autoimmune rheumatic diseases. Chemiluminescence microarray immunoassay (CLMIA) is a microdot array-based method that allows simultaneous detection of multiple antinuclear antibodies, which received increasing attention.

The limited folding resistance of continuous silicon carbide (SiC) fibres hinders their application as flexible, foldable materials. With this objective in mind, the folding endurance and damage properties of the second (2nd) and third (3rd) generation continuous SiC fibre tows were investigated through repeated folding tests, optical microscope observation and tensile tests. These SiC fibre tows were disassembled from two-dimensional (2D) SiC fibre braided fabrics with varying braiding angles. The braiding process can alleviate the force on fibre tows during the textile forming process. The investigation of damage mechanisms and analysis of force conditions are instrumental in optimizing structural parameters. The research findings suggested that, in comparison to the 3rd generation continuous SiC fibres, the 2nd generation SiC fibre tows demonstrated higher resistance to repeated folding. In contrast, the 2nd generation fabrics exhibited slightly lower folding endurance values. After repeated folding, the SiC fibre tows in fabrics showed the highest strength losses near the braiding angle of 37.8° to 38.3°. In comparison, the SiC fibre fabric demonstrated the lowest folding endurance values (approximately 760 times) near the braiding angle of 41° to 42°. Considering factors such as folding endurance value, the strength loss rate of fibre tows and fabric strength loss rate, it can be concluded that SiC fibres in fabrics with large braiding angles exhibit optimal performance in terms of folding endurance.

AbstractInterferon-beta (IFN-[Formula: see text]) is one of the classical drugs for immunomodulatory therapy in relapsing-remitting multiple sclerosis (RRMS) patients, but the drug responsiveness of different patients varies. Currently, there is no valid model to predict IFN-[Formula: see text] responsiveness. This research attempted to develop an IFN-[Formula: see text] responsiveness prediction model based on mRNA expression in RRMS patient peripheral blood mononuclear cells. Peripheral blood mononuclear cell mRNA expression datasets including 50 RRMS patients receiving IFN-[Formula: see text] treatment were obtained from GEO. Among the datasets, 24 cases from GSE24427 were included in a training set, and 18 and 9 cases from GSE19285 and GSE33464, respectively, were adopted as two independent test sets. In the training set, blood samples were collected immediately before first, second, month 1, 12, and 24 IFN-[Formula: see text] injection, and the mRNA expression data at four time points, namely, two days, one month, one year and two years after the onset of IFN-[Formula: see text] treatment, were compared with pre-treatment data to identify IFN-stimulated genes (ISGs). The ISGs at the one-month time point were used to construct the drug responsiveness prediction model. Next, the drug responsiveness model was verified in the two independent test sets to examine the performance of the model in predicting drug responsiveness. Finally, we used CIBERSORTx to estimate the content of cell subtypes in samples and evaluated whether differences in the proportions of cell subtypes were related to differences in IFN-[Formula: see text] responsiveness. Among the four time points, one month was the time point when the training set GSE24427 and test set GSE33464 had the highest number of ISGs. Functional analysis showed that these one-month ISGs were enriched in biological functions such as the innate immune response, type-I interferon signalling pathway, and other IFN-[Formula: see text]-associated functions. Based on these ISGs, we obtained a four-factor prediction model for IFN-[Formula: see text] responsiveness including MX1, MX2, XAF1, and LAMP3. In addition, the model demonstrated favourable predictive performance within the training set and two external test sets. A higher proportion of activated NK cells and lower naive CD4/total CD4 ratio might indicate better drug responsiveness. This research developed a polygene-based biomarker model that could predict RRMS patient IFN-[Formula: see text] responsiveness in the early treatment period. This model could probably help doctors screen out patients who would not benefit from IFN-[Formula: see text] treatment early and determine whether a current treatment plan should be continued.

Background: Diabetic cardiovascular complications are the leading cause of diabetes-related deaths. These complications place an enormous and growing burden on global health systems and economies. The objective of this study was to conduct a systematic review on the therapeutic mechanisms of Taohe Chengqi Decoction (THCQD) in the treatment of diabetic cardiovascular complications. To predict the potential mechanisms of action of THCQD on diabetic cardiovascular complications using network pharmacology, and to validate these predictions through molecular docking analysis. Methods: To collect relevant animal experiments, we searched a total of 6 databases. Eligibility for the study was determined based on inclusion and exclusion criteria. Data extraction was then performed on the literature. Methodological quality of animal studies was assessed using SYRCLE criteria. Based on network pharmacology, intersecting genes for THCQD and diabetic cardiovascular complications were obtained using Venny, PPI analysis and topology analysis of intersecting genes were performed; GO and KEGG were used for enrichment analysis and prediction of new targets of action. Molecular docking techniques were employed to model the interactions between drug components and target genes, thereby validating the results of network pharmacology predictions. Results: A total of 16 studies were finally identified that fit the direction of this review. Included 6 studies of the myocardium, 1 study of the aortic arch, 5 studies of the femoral artery, 4 studies of the thoracic aorta. THCQD exhibited anti-inflammatory, anti-fibrotic and anti-atherosclerotic effects on cardiovascular complications in diabetic rats. Network pharmacology results showed that C0363 (Resveratrol), C0041 (Emodin), and C1114 (Baicalein) were the key components in the treatment of diabetic cardiovascular complications by THCQD. PPI results showed that INS, AKT1, TNF, ALB, IL6, IL1B as the genes that interact with the top 6. KEGG enrichment analysis identified the AGE-RAGE signaling pathway in diabetic complications as the most prominent pathway enriched by THCQD for diabetic cardiovascular complications genes. The results of molecular docking showed that the key active components demonstrated favorable interactions with their corresponding target genes. Conclusion: In conclusion, the results of both basic and web-based pharmacological studies support the beneficial effects of the natural herbal formulation THCQD on diabetic cardiovascular complications. This decoction has anti-inflammatory and antifibrotic properties and is effective in ameliorating diabetic cardiovascular disease. The network pharmacology results further support these ideas and identify the AGE-RAGE signaling pathway in diabetic complications as possibly the most relevant pathway for THCQD in the treatment of diabetic cardiovascular complications. The extent of the therapeutic potential of all-natural herbal components in the treatment of diabetic cardiovascular disease merits further investigation.

BackgroundWhile observational epidemiological studies have suggested an association between gut microbiota and Behçet’s disease (BD), the causal relationship between the two remains uncertain.MethodsStatistical data were obtained from gut microbiome Genome-Wide Association Studies (GWAS) published by the MiBioGen consortium, and genetic variation points were screened as instrumental variables (IV). Mendelian randomization (MR) study was performed using inverse variance weighted (IVW), weighted median, MR-Egger regression, simple mode, and weighted mode methods to evaluate the causal relationship between gut microbiota (18,340 individuals) and BD (317,252 individuals). IVW was the main method of analysis. The stability and reliability of the results were verified using the leave-one-out method, heterogeneity test, and horizontal genetic pleiotropy test. Finally, a reverse MR analysis was performed to explore reverse causality.ResultsInverse variance weighted (IVW) results showed that the genus Parasutterella (OR = 0.203, 95%CI 0.055–0.747, p = 0.016), Lachnospiraceae NC2004 group (OR = 0.101, 95%CI 0.015–0.666, p = 0.017), Turicibacter (OR = 0.043, 95%CI 0.007–0.273, p = 0.001), and Erysipelatoclostridium (OR = 0.194, 95%CI 0.040–0.926, p = 0.040) were protective factors against BD, while Intestinibacter (OR = 7.589, 95%CI 1.340–42.978, p = 0.022) might be a risk factor for BD.ConclusionOur study revealed the causal relationship between gut microbiota and BD. The microbiota that related to BD may become new biomarkers; provide new potential indicators and targets for the prevention and treatment of BD.

Abstract Periodontitis is a chronic inflammatory disease that affects the tissues surrounding the teeth, including the gums and the bones supporting the teeth. Early detection and intervention are crucial for effective management of periodontitis. Our study aims to identify a diagnostic biomarker for periodontitis and explore the pathways associated with the occurrence and development of periodontitis. The expression of gingival tissue from periodontitis and healthy control were downloaded from the Gene Expression Omnibus. The weighted gene co-expression network analysis (WGCNA) were used to analyze module genes associated with periodontitis and DESeq2 were performed to identify differently expressed genes (DEGs) between periodontitis and healthy control. Then the candidate genes were obtained by intersecting the genes from interest modules and DEGs. Functional enrichment analysis was performed using gene ontology and kyoto encyclopedia of gene and genomes, followed by the protein–protein interaction (PPI) network analysis. The hub genes were identified by the cytoCNA plugin in Cytoscape. Finally, immunohistochemical staining of the hub genes was performed to validate the findings. WGCNA analysis found that the expression of the MEblack module was significantly higher in individuals with periodontitis compared to those in the healthy control group. A total of 888 DEGs, including 750 upregulated and 138 downregulated genes, were identified. Finally, 427 candidate genes were identified potentially associated with periodontitis after intersecting the DEGs and the black module genes. Several critical signaling pathways were identified associated with periodontitis by functional enrichment analysis, including cytokine–cytokine receptor interaction, neutrophil extracellular trap formation, Staphylococcus aureus infection, and Interleukin-17 signaling pathway. The PPI network analysis revealed that C-X-C motif chemokine ligand 5 (CXCL5) and C-X-C motif chemokine ligand 6 (CXCL6) could play an important role in the process of periodontitis. The gene expression level of CXCL5 and CXCL6 detected using immunohistochemical verified the findings. In conclusion, we found that CXCL5 and CXCL6 are closely associated with the occurrence of periodontitis. Our present pilot study suggests that CXCL5 and CXCL6 have the potential to be used as a diagnostic biomarker of periodontitis.

Abstract Introduction Recently, studies on behavioral tic suppression techniques have gained popularity as opposed to pharmacological alternatives that often have potentially dangerous side effects. Differential Reinforcement of Other Behaviors therapy (DRO) is one such behavioral technique whose efficacy in tic suppression has been experimentally demonstrated albeit in studies with very few patients, and lacking statistical power. Here, we conducted a meta-analysis of these studies to improve their overall power and explore whether DRO intervention is really effective for tic suppression. Materials and methods PubMed, Embase, PsycINFO, and Cochrane Library were searched from inception to August 30, 2023. Only original interventional studies that examined the efficacy of DRO for tic suppression were included. Results A total of 8 no control interventional studies involving 79 children with tic disorders were recruited. Most of the children had moderate tic severity. The pooled mean Yale Global Tic Severity Scale (YGTSS) score was 24.64 (95% CI: 21.99 – 30.12, p =

Abstract Background Uniparental disomy (UPD) is a rare genetic condition leading to potential disease risks. Maternal UPD of chromosome 6 upd(6)mat is exceptionally rare, with limited cases reported. This study reported two new cases of upd(6)mat and reviewed the literature of previous cases. Case presentation Both cases exhibited intrauterine growth restriction (IUGR), and genetic analysis confirmed upd(6)mat in each case. The literature review identified a total of 19 cases. IUGR and preterm labor were the most common two symptoms observed, and additional anomalies and genetic variations were also reported in some cases. Conclusion upd(6)mat is potentially associatied with IUGR, but the precise genotype–phenotype relationship remains unclear. The cases with upd(6)mat may present clinical features due to imprinting disorders.

With the increase of mine development depth, the problems such as high difficulty in plugging deep water inrush points and large quantities of work have become increasingly prominent. The surface multi branch horizontal directional drilling technology is an effective means to solve the above problems, and its construction technical difficulties are mainly well trajectory control, well wall stability control and grouting effect improvement. Based on the above problems, taking Wucun Mine in Jiaozuo Mining Area as an example, the optimal plugging scheme for water inrush points is proposed. The structure of PDM drill is improved by adding eccentric cushion block to improve the control of well trajectory; the potassium ammonium based polymer drilling fluid system is used to optimize the proportioning scheme of the treating agent to improve the wellbore stability control; variable frequency speed regulating grouting pump and secondary mixing process are adopted to improve the grouting effect. The results show that the maximum drop of water level in Wucun Mine shaft is 6.53 m after the completion of the project, and the water blocking effect is significant.

Amide bond is a ubiquitous and crucial functional group that serves as the linchpin for constructing proteins, peptides, and is also the central site in numerous drug molecules. Consequently, it is crucial to investigate the strategies and mechanisms of amidation reactions. In recent years, the use of electrochemistry for amidation has gained significant attention due to its exceptional qualities such as increased selectivity and eco-friendliness. However, due to the complexities of the reaction processes and the scarcity of relevant analytical tools, the studys of in-situ monitoring and mechanistic investigations on these electrochemical amidation reactions are rare. In response to this challenge, a novel coupling device was designed in this study. The main component of the coupling device was a glass capillary tube with a metal cover. The metal coating on the tip's outer surface was connected to a high voltage power supply to drive the electrospray ionization process. Additionally, the metal coating inside the tip was also connected to the metal coating on the tip's outer surface and served as the working electrode for an electrochemical reaction. When high voltage was applied, both the electrospray process and the electrochemical reaction on the tip could be driven simultaneously. The substances produced by the electrochemical reaction in the capillary tip could be quickly transfered to spray droplets, ionized via desolvation process, and finally detected via mass spectrometry. Based on this technique, a series of aromatic primary amines amidation reactions were observed in situ while using triphenylphosphine as the condensing agent. Numerous important intermediates were also discovered during these reactions. Remarkably, this novel approach not only facilitated continuous real-time monitoring of these reactions but also empowered scientists to unambiguously identify an array of key intermediates, including the elusive short-lived free radical intermediates. The electrochemical-mass spectrometry coupling device has numerous advantages, including short analysis delays, the ethical use of sample resources, and uncomplicated, simple preparation processes. It's potential to revolutionize the field of electroorganic synthesis reactions. This cutting-edge technique is poised to become an invaluable tool for rapid screening and in-depth investigations into the complex mechanisms of driving amidation reactions. The coupling device represents an exciting improvement forward in the context of drug investigations, where precision and efficiency are critical. Additionally, as society places increasing emphasis on environmental sustainability and the demand for precise chemical processes intensifies, this breakthrough coupling device is expected to become a formidable instrument in investigating the mechanism of electrochemical reactions.

In the novel power system of urban grid, the multiple resources increase and the data collection becomes more difficult, which lead to a higher random missing data rate. It is difficult to meet the demand for refined analysis and decision making. For the frequent missing data problem in the distribution network, a new missing data filling method for power systems based on fluctuation cross-correlation analysis (FCCA) and generative adversarial network (GAN) is proposed in this paper. Firstly, a multi-dimensional feature extraction method for strongly correlated grid data is proposed by fusing FCCA. Secondly, based on kernel principal component analysis (KPCA), the multi-dimensional feature dataset is dimensionally reduced. Finally, an improved GAN structure is designed, which integrates multi-dimensional features of power grid equipment data to reconstruct low dimensional vectors. The missing data is accurately filled in, and the integrity and availability of the new power system measurement data is improved. The algorithm is validated using real grid data, and the proposed method is also tested in a city grid. The results show that the proposed method has higher filling accuracy than the traditional data filling methods. Therefore, it is conformed that in the case of continuous and significant data environment, integrating strong correlation features for data filling has significant advantages in improving the integrity and availability of measurement data.

Abstract Treatment for anterior cruciate ligament (ACL) tears depends on the condition of the ligament. We aimed to identify different tear statuses from preoperative MRI using deep learning-based radiomics with sex and age. We reviewed 862 patients with preoperative MRI scans reflecting ACL status from Hunan Provincial People’s Hospital. Based on sagittal proton density-weighted images, a fully automated approach was developed that consisted of a deep learning model for segmenting ACL tissue (ACL-DNet) and a deep learning-based recognizer for ligament status classification (ACL-SNet). The efficacy of the proposed approach was evaluated by using the sensitivity, specificity and area under the receiver operating characteristic curve (AUC) and compared with that of a group of three orthopedists in the holdout test set. The ACL-DNet model yielded a Dice coefficient of 98% ± 6% on the MRI datasets. Our proposed classification model yielded a sensitivity of 97% and a specificity of 97%. In comparison, the sensitivity of alternative models ranged from 84 to 90%, while the specificity was between 86 and 92%. The AUC of the ACL-SNet model was 99%, demonstrating high overall diagnostic accuracy. The diagnostic performance of the clinical experts as reflected in the AUC was 96%, 92% and 88%, respectively. The fully automated model shows potential as a highly reliable and reproducible tool that allows orthopedists to noninvasively identify the ACL status and may aid in optimizing different techniques, such as ACL remnant preservation, for ACL reconstruction.

Abstract Virulence factor modulating (VFM) is a quorum sensing (QS) signal shared by and specific to Dickeya bacteria, regulating the production of plant cell wall degrading enzymes (PCWDEs) and virulence of Dickeya. High polarity and trace of VFM signal increase the difficulty of signal separation and structure identification, and thus limit the development of quorum quenching strategy to biocontrol bacterial soft rot diseases caused by Dickeya. In order to high‐throughput screen VFM quenching bacteria, a vfmE‐gfp biosensor VR2 (VFM Reporter) sensitive to VFM signal was first constructed. Subsequently, two bacterial strains with high quenching efficiency were screened out by fluorescence intensity measurement and identified as Pseudomonas chlororaphis L5 and Enterobacter asburiae L95 using multilocus sequence analysis (MLSA). L5 and L95 supernatants reduced the expression of vfm genes, and both strains also decreased the production of PCWDEs of D. zeae MS2 and significantly reduced the virulence of D. oryzae EC1 on rice seedlings, D. zeae MS2 on banana seedlings, D. dadantii 3937 on potato and D. fangzhongdai CL3 on taro. Findings in this study provide a method to high‐throughput screen VFM quenching bacteria and characterize novel functions of P. chlororaphis and E. asburiae in biocontrolling plant diseases through quenching VFM QS signal.

Abstract DNA barcodes enable Oxford Nanopore sequencing to sequence multiple barcoded DNA samples on a single flow cell. DNA sequences with the same barcode need to be grouped together through demultiplexing. As the number of samples increases, accurate demultiplexing becomes difficult. We introduce HycDemux, which incorporates a GPU-parallelized hybrid clustering algorithm that uses nanopore signals and DNA sequences for accurate data clustering, alongside a voting-based module to finalize the demultiplexing results. Comprehensive experiments demonstrate that our approach outperforms unsupervised tools in short sequence fragment clustering and performs more robustly than current state-of-the-art demultiplexing tools for complex multi-sample sequencing data.

Abstract Background Delayed healing of diabetic cutaneous wounds is one of the most common complications of type 2 diabetes mellitus (T2DM), which can bring great distress to patients. In diabetic patients, macrophages accumulate around skin wounds and produce NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasomes, which in turn undergo pyroptosis and produce inflammatory factors such as interleukin-1β that affect wound healing. Although our previous study revealed that apoptotic extracellular vesicles (ApoEVs) produced from mesenchymal stem cells (MSCs) improve cutaneous wound healing in normal C57BL/6 mice, whether ApoEVs can also improve diabetic wound healing remains unclear. Methods Umbilical cord mesenchymal stem cells (UCMSCs) were cultured in vitro and apoptosis was induced. ApoEVs were extracted and identified and used in a T2DM mouse cutaneous wound model to evaluate the efficacy. The inhibitory effect of ApoEVs on macrophage pyroptosis was verified in vivo and in vitro, and the level of oxidative stress in macrophages was assessed to explore the mechanism by which ApoEVs play a role. Results UCMSC-derived ApoEVs improved skin defect healing in T2DM mice. Moreover, UCMSC-derived ApoEVs inhibited macrophage pyroptosis in T2DM mice in vivo as well as in vitro under high-glucose culture conditions. In addition, we demonstrated that ApoEVs reduce oxidative stress levels, which is a possible mechanism by which they inhibit macrophage pyroptosis. Conclusions Our study confirmed that local application of UCMSC-derived ApoEVs improved cutaneous wound healing in T2DM mice. ApoEVs, as products of MSC apoptosis, can inhibit macrophage pyroptosis and regulate the death process by decreasing the level of oxidative stress.

Abstract Background Exosome-mediated interaction serves as a significant regulatory factor for M2 macrophage polarization in cancer. Methods All accessible data were acquired from The Cancer Genome Atlas (TCGA) database and analyzed using R software. Molecules implicated in exocrine secretion were amassed from the ExoCarta database. Our research initially quantified the immune microenvironment in Esophageal Squamous Cell Carcinoma (ESCC) patients based on the expression profile sourced from the TCGA database. Additionally, we delved into the biological role of M2 macrophages in ESCC via Gene Set Enrichment Analysis (GSEA). Results We observed that patients with high M2 macrophage infiltration typically have a poorer prognosis. Subsequently, a total of 1457 molecules were identified, with 103 of these molecules believed to function through exocrine mechanisms, as supported by data from the ExoCarta database. SNORD91A and SLC40A1 were ultimately pinpointed due to their correlation with patient prognosis. Moreover, we investigated their potential roles in ESCC, including biological enrichment, immune infiltration, and genomic instability analysis. Conclusions Our study identified exosome-associated molecules, namely SNORD91A and SLC40A1, which notably impact ESCC prognosis and local M2 macrophage recruitment, thereby presenting potential therapeutic targets for ESCC.

Ionizing radiation exposure can cause damage to diverse tissues and organs, with the hematopoietic system being the most sensitive. However, limited information is available regarding the radiosensitivity of various hematopoietic cell populations in the bone marrow due to the high heterogeneity of the hematopoietic system. In this study, we observed that granulocyte–macrophage progenitors, hematopoietic stem/progenitor cells, and B cells within the bone marrow showed the highest sensitivity, exhibiting a rapid decrease in cell numbers following irradiation. Nonetheless, neutrophils, natural killer (NK) cells, T cells, and dendritic cells demonstrated a certain degree of radioresistance, with neutrophils exhibiting the most pronounced resistance. By employing single-cell transcriptome sequencing, we investigated the early responsive genes in various cell types following irradiation, revealing that distinct gene expression profiles emerged between radiosensitive and radioresistant cells. In B cells, radiation exposure led to a specific upregulation of genes associated with mitochondrial respiratory chain complexes, suggesting a connection between these complexes and cell radiosensitivity. In neutrophils, radiation exposure resulted in fewer gene alterations, indicating their potential for distinct mechanisms in radiation resistance. Collectively, this study provides insights into the molecular mechanism for the heterogeneity of radiosensitivity among the various bone marrow hematopoietic cell populations.

Abstract Background There are overlapping effects of screen time and sleep on children’s behavior. The purpose of this study was to explore the relationship of screen time with behavior problems in children with autism spectrum disorder (ASD) and the probable mediating effects of sleep, in order to provide evidence for the need for clinical identification and intervention. Methods A sample of 358 preschoolers with ASD were included. We investigated the children’s basic characteristics of sex and age, ASD symptoms (ABC, CARS, and ADOS-2), neurodevelopment (GDS-C), sleep habits (CSHQ), and behavior (CBCL). Pearson correlation tests were used to determine the direct correlations among children’s screen time, CBCL, and CSHQ. Linear regression analysis was used to explore whether screen time predicted total score of CBCL. Multi-step linear regression analysis was used to investigate the mediating effect of sleep on the relationship between screen time and total score of CBCL. Results Screen time before bedtime was correlated with CBCL and CSHQ, which indicated that screen time before bedtime was correlated with sleep and behavior in children with ASD. Screen time before bedtime was a predictor of CBCL total score (indicating children’s behavior), and CSHQ total score (indicating children’s sleep habits) played a partial mediating role between screen time before bedtime and children’s behavior. Conclusion Clinicians should support and educate parents of children with ASD, which should focus on managing screen time, especially screen time before bedtime.

Objective To investigate the role and molecular mechanism of poly (ADP-ribose) polymerase 1 (PARP1) in mitosis of HeLa cells. Methods Flow cytometry, immunofluorescent assay and live cell imaging were used to detect the effect of PARP1 on mitosis of HeLa cells. Chromosome karyotype analysis and immunofluorescent assay were used to detect the effect of PARP1 on chromosome stability. Western blotting and co-immunoprecipitation assay were used to analyze the protein expression and enzyme activity of PARP1 in HeLa cells during mitosis. Proteome mass spectrometry was used to identify proteins that interacted specifically with PARP1 in mitosis, which was verified by co-immunoprecipitation and poly(ADP-ribosyl)ation assay. Results Flow cytometry and immunofluorescence staining showed that the response of HeLa cells to nocodazole-induced mitotic arrest was significantly decreased after genetic manipulation (knockdown) or pharmacological inhibition (olaparib) of PARP1 (P < 0.05). The results of live cell imaging showed the mean mitotic time of HeLa cells was shortened after the knockdown of PARP1(P < 0.01). Chromosome karyotype analysis and immunofluorescence staining showed that the proportion of aneuploid and multipolar spindle cells was increased significantly after the knockdown of PARP1 (P < 0.05). Western blotting showed no significant difference in the protein level of PARP1 during the process of mitosis, while the co-immunoprecipitation assay showed the enzyme activity was increased significantly. Proteome mass spectrometry and co-immunoprecipitation assay showed that PARP1 specifically interacted with BUB3, a major component of the mitotic checkpoint complex (MCC), and BUB3 is poly(ADP-ribosyl)ated in mitosis. Conclusion DNA damage repair protein PARP1 may regulate the mitosis of HeLa cells and maintain its chromosome stability by upregulating enzyme activity and poly(ADP-ribosyl)ating mitotic BUB3.

Objective To explore the mechanism of FGFR3⁃TACC3 (F3⁃T3) fusion gene mediating DNA damage repair through promoting pyruvate kinase M2 (PKM2)'s nuclear translocation in glioblastoma. Methods The lentiviral transfection technology was used to constructed stable transitional cell lines U87MG cells and U251MG cells that stably expressing F3 ⁃ T3 and empty vector. In vivo glioblastoma model was constructed by intracranial in situ tumor implantation in athymic mice, and the tumorigenic ability of F3⁃T3 transfected cells in athymic mice of each treatment group was observed by small⁃animal in vivo imaging system. Bioinformatics analysis was performed to analyze gene microarray data exploring the possible biological functions of F3 ⁃ T3 mediating chemoresistance and identify the relationship between survival expectations and PKM2 expression levels in glioblastoma patients from The Cancer Genome Atlas (TCGA) database. Transient transfection of small interference RNA (siRNA) was used to knock down the expression of PKM2 in the F3 ⁃ T3 transfected cells. Proliferative activity of U87MG and U251MG cells treated with different concentrations of temozolomide (TMZ), transfected with siRNA, and TMZ in combination with Compound 3k, a PKM2 inhibitor, was observed in CCK ⁃ 8 cell proliferation assays. Nuclear and cytoplasmic proteins were extracted separately and PKM2 protein expression was observed in whole cell extract, cytoplasmic extract and cytosolic extract after TMZ treatment. Relative expression of PKM2, relative expression of cytosolic phosphorylated histone H2AX (p⁃H2AX) and relative expression of siRNA knockdown PKM2 gene in U87MG and U251MG cells stably expressing the F3 ⁃ T3 fusion gene, detected by Western blotting. Results 1) CCK⁃8 cell proliferation assay showed that the survival rate of U87MG cells in the F3 ⁃ T3 transfected group was higher than that in the empty vector transfected group after treatment with TMZ 640, 320, 160, 80, 40 μmol/L (P = 0.000, 0.000, 0.000, 0.000, 0.004, 0.010), and the survival rate of U251MG cells in the F3 ⁃ T3 transfected group was also higher than that in the empty vector transfected group after TMZ 640, 320, 160, 80, 40, 20, 5 μmol/L (P = 0.000, 0.000, 0.000, 0.002, 0.001, 0.002); the survial rate of U87MG cells in the si⁃PKM2⁃1009 transfected group was lower than that of F3 ⁃ T3 transfected group after TMZ 640, 320, 160, 80, 40, 20, 10, 5, 2.50 μmol/L, the survival rate of U251MG cells in the si⁃PKM2⁃1377 transfected group was also lower than that in F3⁃T3 transfected group after TMZ 640, 320, 160, 80, 40, 20, 5 μmol/L (P = 0.000, 0.000, 0.002, 0.000, 0.002, 0.048, 0.042); and the survival rate of U87MG cells in TMZ + Compound 3k group was lower than TMZ group after TMZ 640, 320, 160, 80, 40, 20 μmol/L (P = 0.000, 0.000, 0.000, 0.000, 0.001, 0.002), and the survival rate of U251MG cells in TMZ + Compound 3k group after treatment with high concentrations of TMZ (640, 320, 160, 80 and 40 μmol/L) was also lower than TMZ group (P = 0.000, 0.000, 0.000, 0.000, 0.003), while the survival rate of U251MG cells in TMZ + Compound 3k group after treatment with low concentrations of TMZ (10, 5 and 2.50 μmol/L) was higher than that of TMZ group (P = 0.000, 0.000, 0.006). 2) An animal model of glioblastoma showed the presence of TMZ resistance in homozygous mice. 3) Bioinformatic analysis showed that the biological function of F3⁃T3 was significantly enriched in the DNA repair pathway (P = 0.000). Survival and overall survival of glioblastoma patients in the TCGA database were lower in the PKM2 high expression group than in the low expression group (P < 0.05). 4) Western blotting showed that the relative expression of p⁃H2AX in U87MG (P = 0.000, 0.000, 0.004) and U251MG (P = 0.000, 0.007, 0.005) cells in the F3 ⁃ T3 transfected group were lower than those in the empty vector transfected group after TMZ treatment for 48 h and then medium change for 24, 36 and 48 h. PKM2 protein incorporation into the nucleus was observed in both U87MG and U251MG cells in the F3⁃T3 transfected group after TMZ treatment, whereas it was not observed in cells in the empty vector transfected group; si⁃PKM2⁃1009 and si⁃ PKM2⁃1377 knocked down the relative expression of p⁃H2AX in U87MG (P = 0.000, 0.001, 0.006) and U251MG (P = 0.000, 0.000, 0.000) cells, respectively. Conclusions In the presence of TMZ, F3 ⁃ T3 promotes PKM2's nuclear translocation and activates DNA damage repair pathways, which in the eventually results resistance of glioblastoma cell to TMZ. PKM2 inhibitors can compromise the resistance glioblastoma cells stably expressing F3⁃T3 fusion gene to TMZ.

In this paper, the transformation of the green service industry is regarded as an intermediate variable based on the TPB model. Green service innovation can be divided into application type and exploration type. The function mechanism of enterprise green innovation guidance mechanism on enterprise operating performance is established. The empirical analysis of several service companies in East China shows that “green innovation” has an apparent positive effect on service innovation. It will only have a pronounced positive development in the research-based green service-based innovation. These factors have no evident positive impact on creating environmental services for use. Green service innovation and the use of green service innovation have a noticeable positive impact on the business performance of enterprises. This research result provides a new idea for the development of enterprises.

Short chain fatty acid (SCFA), a class of fatty acids with six or less carbon atoms, have important physiological functions for human health. As metabolites of the intestinal flora, SCFA can maintain intestinal health. Furthermore, accumulating research has proved that SCFA have many functions such as maintaining brain and bone functions, participating in regulating the immune response, antibacterial and antitumor activity, and alleviating obesity and diabetes. In this paper, recent literature on the production, absorption and functions of SCFA in the body are reviewed to provide a theoretical reference for the research and application of SCFA in nutrition.

Adhesive bonding is the preferred method for joining dissimilar materials owing to the low weight of adhesives. To evaluate the application of adhesive bonding to multi-materialization, in this study, we used conical cup testing as an integrated formability test method to assess the forming limit of bonded multi-layered metal sheets, comparing them with the equivalent unitary sheets. The conical cup testing equipment used in this study was designed and produced based on JIS Z 2249, with a viewing port that can be used to observe the deformed bottom of the specimens during the conical cup test. Multi-layered specimens composed of aluminum (Al) and steel (steel plate cold-rolled commercial (SPCC) steel) layers were produced using acrylic and epoxy adhesives, and single-(material)-layered specimens composed of layers of the same material were also produced. In addition, the unitary specimens of the materials without any bonding were examined as reference materials. The experimental results showed that the forming limits of the single-(material)-layered Al specimens (pure aluminum A1050 and aluminum alloy A5052) were nearly identical to those of the unitary specimens. Therefore, the use of the adhesive improved the formability of the Al sheet to that of the corresponding unitary specimen with twice the thickness. The results of the A5052-SPCC multi-layered specimen bonded by acrylic adhesive were compared with those of the SPCC unitary specimen, and its forming limit increased by 35% with a notable 33% reduction in weight, demonstrating the enhanced performance of the multi-layer structure. The reason for the improvement in formability may be the suppression of the abrupt increase in surface roughness, which otherwise leads to plastic instability.

Based on artificial intelligence technology, this paper integrates ideological and political education with “Sanxin” party building and uses mean density center estimation to get the correlation degree between user data metric words and educational documents. Combined with the fuzzy genetic algorithm to calculate the corresponding positional weights of various words, the information matching is realized through the similarity function, and the K-means clustering algorithm is used to effectively predict the learning behavior of party members. The highest number of course visits to the intelligent ideological and political education platform reached 880, and the highest number of readers of educational articles with party building reached 4,700. The integration of ideological and political education and the “Sanxin” party building enables the party members to establish the correct value of life and promotes the long-term development of new economic organizations, new social organizations, and new employment groups.

In today’s society, under the demand for high-quality talents, the professionals cultivated in colleges and universities should not only master professional skills but also need to have the spirit of innovation and entrepreneurial ability in professional aspects. In this paper, firstly, the multivariate statistical analysis method is explained, and the basic principles of the factor analysis model, principal component analysis method and systematic clustering method are given to analyze the data in the following article. Secondly, starting from the necessity of the integration of bi-initiative education and professional education of teacher training majors in colleges and universities, we constructed the 4344 specialized and innovative integrated talent cultivation model of teacher training majors and constructed an evaluation system to evaluate the effectiveness. Finally, based on the evaluation system, the data analysis of the specialized and creative integrated talent cultivation model was carried out using factor analysis, principal component analysis and systematic clustering method. The results show that in the factor analysis, the highest loading value of the first principal factor is 0.917, the contribution rate of the first principal factor is 39.67%, and the loading value of the principal component factor reaches the highest value of 0.925. The clustering analysis is based on the results of the factor analysis, and the respondents are divided into 4 clusters. The number of people in the 2nd category is more than 30 people, which accounts for about 31.41% of the total number of people. The method of multivariate statistical analysis can be used to analyze the data effectively for the specialized and integrated personnel training mode of teacher training in colleges and universities and also gives the path of specialized and integrated personnel training for teacher training.

Abstract Background Dental treatment associated with unadaptable occlusal alteration can cause chronic primary myofascial orofacial pain. The serotonin (5-HT) pathway from the rostral ventromedial medulla (RVM) exerts descending modulation on nociceptive transmission in the spinal trigeminal nucleus (Sp5) and facilitates chronic pain. The aim of this study was to investigate whether descending 5-HT modulation from the RVM to the Sp5 is involved in the maintenance of primary myofascial orofacial hyperalgesia after persistent experimental occlusal interference (PEOI) or after delayed removal of experimental occlusal interference (REOI). Methods Expressions of 5-HT3A and 5-HT3B receptor subtypes in the Sp5 were assessed by immunofluorescence staining and Western blotting. The release and metabolism of 5-HT in the Sp5 were measured by high-performance liquid chromatography. Changes in the pain behavior of these rats were examined after specific pharmacologic antagonism of the 5-HT3 receptor, chemogenetic manipulation of the RVM 5-HT neurons, or selective down-regulation of 5-HT synthesis in the RVM. Results Upregulation of the 5-HT3B receptor subtype in the Sp5 was found in REOI and PEOI rats. The concentration of 5-HT in Sp5 increased significantly only in REOI rats. Intrathecal administration of Y-25130 (a selective 5-HT3 receptor antagonist) dose-dependently reversed the hyperalgesia in REOI rats but only transiently reversed the hyperalgesia in PEOI rats. Chemogenetic inhibition of the RVM 5-HT neurons reversed the hyperalgesia in REOI rats; selective down-regulation of 5-HT in advance also prevented the development of hyperalgesia in REOI rats; the above two manipulations did not affect the hyperalgesia in PEOI rats. However, chemogenetic activation of the RVM 5-HT neurons exacerbated the hyperalgesia both in REOI and PEOI rats. Conclusions These results provide several lines of evidence that the descending pathway from 5-HT neurons in the RVM to 5-HT3 receptors in the Sp5, plays an important role in facilitating the maintained orofacial hyperalgesia after delayed EOI removal, but has a limited role in that after persistent EOI. Graphical Abstract

Abstract To solve the problem of low accuracy of the previous electricity theft detection methods, the authors propose a multi‐domain feature (MDF) fusion electricity theft detection method based on improved tensor fusion (ITF). Firstly, the original electricity consumption series is transformed by gram angle field (GAF) to obtain the time‐domain matrix. The original electricity consumption series is converted into frequency‐domain by Maximal Overlap Discrete Wavelet Transform (MODWT) to obtain the frequency‐domain matrix. Then, the convolutional neural networks (CNN) are used to extract features of the time‐domain matrix and frequency‐domain matrix, respectively. Next, in order to fuse single‐domain feature information and MDF interaction information while reducing redundant information, the authors propose an ITF method to obtain a multi‐domain fusion tensor. Finally, the multi‐domain fusion tensor is input into the electricity theft inference module to judge whether the user implements electricity theft behaviour. The authors simulate six electricity theft types and evaluate the method's performance separately for each electricity theft type. The results show that the proposed method outperforms other methods.

ObjectiveTo sort out and analyze the research progress of adolescent psychological resilience， and to grasp the research hotspots and frontiers in this field.MethodsCiteSpace was used to make a visual analysis of the number of publications， authors and institution， and co-occurrence， clustering and burst terms of keywords in literatures related to adolescent psychological resilience collected in CNKI database from January 1， 2012 to December 31， 2021.Results① For almost a decade， the research on adolescent psychological resilience was divided into a slow growth stage （2012-2018） and a rapid growth stage （2018-2021）. ② The cooperation between authors were relatively close， and most of them were small and medium-sized cooperative organizations. There was less cooperation in scientific research institutions and most of them were normal universities. ③ In terms of co-occurrence analysis， hot keywords could be roughly divided into three categories： mental health status， influencing factors， and prevention and intervention research. ④ The related high-frequency keywords generate ten clusters， including academic emotions， learning burnout， adolescents， migrant children， mental health， internalized problems， social support， coping style， self-esteem and happiness. ⑤ The keywords with high burst intensity were coping style， mental health， mediation， regression analysis， social work， mental health and anxiety.ConclusionIn the future， cooperation between research institutions can be strengthened to improve the quality of the research on psychological resilience of adolescents. In addition， intervention research related to psychological resilience may become a hotspot in this field in the future.

ObjectiveTo investigate the mediating role of loneliness and social anxiety in the relationship between basic psychological needs satisfaction and smartphone addiction among high school students， and to provide references for the intervention to smartphone addiction for high school students.MethodsIn April 2022， a total of 14 666 high school students from 5 middle schools in a county of Sichuan Province were included by random sampling method. Basic Psychological Needs Scales （BPNS）， the UCLA Loneliness Scale-3 edition （UCLA-3）， Interaction Anxiousness Scale （IAS） and the Mobile Phone Addiction Index （MPAI） were used for cross-sectional investigation. Bootstrap method was used to analyze the mediating role of loneliness and social anxiety in the relationship between the basic psychological needs satisfaction and smartphone addiction.Results① In this study， 14 036 valid questionnaires were returned， and 1 752 （12.48%， 95% CI： 0.114~0.136） high school students were found to be addicted to smartphone phone. The BPNS score was negatively correlated with UCLA-3， IAS and MPAI scores （r=-0.771， -0.486， -0.417， P

Abstract Background This study evaluated vitamin A (VA), copper (Cu), and zinc (Zn) levels in the population with autism spectrum disorder (ASD) in Jilin Province, China. Furthermore, we examined their links to core symptoms and neurodevelopment, as well as gastrointestinal (GI) comorbidities and sleep disorders. Methods This study included 181 children with autism and 205 typically developing (TD) children. The participants had not taken vitamin/mineral supplements in the prior three months. High-performance liquid chromatography was used to measure serum VA levels. By using inductively coupled plasma–mass spectrometry, Zn and Cu concentrations in plasma were determined. Importantly, the Childhood Autism Rating Scale, the Social Responsiveness Scale, and the Autism Behavior Checklist were used to measure core ASD symptoms. However, the Griffith Mental Development Scales-Chinese were used to measure neurodevelopment. GI comorbidities and sleep abnormalities were assessed with the 6 Item-Gastrointestinal Severity Index and Children’s Sleep Habits Questionnaire, respectively. Children with ASD with GI issues were grouped according to severity (low GI severity and high GI severity groups). Results (i) The difference in VA, Zn, Cu levels and the Zn/Cu ratio between ASD and TD children is small. But children with ASD had lower VA levels and Zn/Cu ratio, higher Cu levels than TD children. Cu levels in children with ASD were associated with the severity of core symptoms. (ii) Children with ASD were much more likely than their TD counterparts to suffer from GI comorbidities or sleep problems. Furthermore, it was observed that high GI severity was associated with lower levels of VA, whereas low GI severity was associated with higher levels of VA. (iii) The children with ASD who had both lower VA and lower Zn/Cu ratio had more severe scores on the Autism Behavior Checklist, but not on other measures. Conclusion Children with ASD had lower VA and Zn/Cu ratio, and higher Cu levels. Cu levels in children with ASD were weakly correlated with one subscale on social or self-help. ASD children with lower VA levels may face more serious GI comorbidities. Children with ASD combined VA-Zn/Cu lower had more severe core symptoms. Trial registration Registration number: ChiCTR-OPC-17013502. Date of registration: 2017-11-23.

Parahydrogen-induced polarization (PHIP) technique can greatly enhance the sensitivity of nuclear magnetic resonance (NMR) signals, and has been applied in the fields of magnetic resonance imaging, in situ chemical reaction monitoring, etc. In addition to improving the sensitivity of different molecules in the PHIP, it is also crucial to extend and preserve the high polarization state. To achieve this, a possible approach is to transfer the polarized state into a nuclear spin singlet state. Here, we focus on the singlet states preparation in hexene molecule that can be polarized by PHIP. By designing optimal control pulses, a five-spin system in hexene molecule was manipulated, and various quantum states were prepared respectively. Our results show that three different nuclear spin singlet states could be prepared with the group CH2=CH- in hexene. The three different nuclear spin singlet states have longer lifetime than that of the initial state polarized by PHIP, and thus can be utilized as the intermediate states to delay the decay of the polarization state. By comparing the lifetime of the singlet state with the longitudinal relaxation time of the corresponding spin, it is deduced that converting the state of the polarized hexene to longitudinal magnetization may also be an effective way to preserve the polarizability.

ABSTRACT: Lipopolysaccharide (LPS) is an important stimulus of inflammation via binding to toll-like receptor 4 (TLR4), but the role of TLR4 in LPS-induced cellular homeostasis disruption indicated by the increased level of endoplasmic reticulum (ER) stress, autophagy, and apoptosis is unknown in the liver of dairy cows. Previous studies show that forkhead box protein A2 (FOXA2) is an important transcriptional factor to maintain cellular metabolic homeostasis, but the mechanisms by which FOXA2 mediates cellular homeostasis disruption in response to LPS remains unclear. To achieve the aims, hepatocytes separated from dairy cows at ∼160 d in milk were pretreated with a specific TLR4 inhibitor TAK-242 for 12 h, followed by LPS treatment for another 12 h to investigate the role of TLR4 in LPS-induced disruption of cellular homeostasis. The results indicated that LPS-induced nuclear factor-κB (NF-κB)-mediated inflammatory cascades, ER stress, autophagy, and apoptosis via activating TLR4 and downregulating FOXA2 expression in bovine hepatocytes. The application of TLR4 inhibitor alleviated LPS-induced inflammation through inactivating NF-κB proinflammatory pathway, restored cell homeostasis by decreasing the level of ER stress, autophagy, and apoptosis, and upregulated FOXA2 expression. Furthermore, we also elevated FOXA2 expression with an overexpression plasmid to clarify its molecular role in response to LPS challenge. FOXA2 overexpression reduced LPS-caused inflammation by inhibiting NF-κB signaling pathway. Also, FOXA2 could alleviate ER stress to block unfolded protein response and suppress autophagic flux. In addition, FOXA2 enhanced mitochondrial membrane potential via reducing pro-apoptotic protein BAX, CASPASE3, and Cleaved CASPASE3 expression and elevating anti-apoptotic protein BCL-2 expression to mitigate LPS-induced apoptosis. Taken together, these findings suggested that FOXA2 is a mediator to alleviate TLR4-controlled inflammation, ER stress, autophagy, and apoptosis in LPS-treated bovine hepatocytes, it could serve as a potential target to intervene cell homeostasis disruption caused by LPS in the liver of dairy cows.

ABSTRACT: The purpose of this experiment was to investigate high-concentrate feeding-induced changed status of oxidative and autophagy in the livers of dairy cows. Hepatocyte nuclear factor 3β (FOXA2) was reported in cases of liver fibrosis, glucolipid metabolism, and hepatocyte differentiation, but not in cases liver damage in cows fed a high-concentrate diet. Therefore, we also aimed to explore the potential role of FOXA2 in SARA-induced liver damage. We divided 12 mid-lactating Holstein cows into 2 groups and fed them a high-concentrate (HC group, forage:concentrate = 4:6) and a low-concentrate (forage:concentrate = 6:4) diet. After a 2-wk adaptation period and a 3-wk experimental period, peripheral blood was collected for determination of antioxidant enzyme activity, and liver tissue was collected to examine genes and proteins. On d 20 and 21 of the experiment, rumen fluid was collected, and the pH was measured. A significant difference in rumen fluid pH was found between the 2 groups (low-concentrate: 6.10 ± 0.07 vs. HC: 5.59 ± 0.09). The rumen fluid pH in the HC group was less than 5.6 at 2 time points, indicating that SARA was successfully induced. Lipopolysaccharide (0.24 ± 0.10 vs. 0.42 ± 0.12) and malondialdehyde (1.46 ± 0.25 vs. 2.94 ± 0.65) increased, whereas superoxide dismutase (14.06 ± 0.63 vs. 11.71 ± 0.64), reduced glutathione (14.48 ± 2.25 vs. 6.82 ± 0.67), and the total antioxidant capacity (0.43 ± 0.03 vs. 0.30 ± 0.03) decreased in the peripheral blood of the HC group. Moreover, in liver tissue from the HC group, catalase (0.71 ± 0.03 vs. 0.49 ± 0.03) and superoxide dismutase (27.46 ± 1.90 vs. 20.32 ± 1.54) were decreased, whereas malondialdehyde (0.21 ± 0.03 vs. 0.28 ± 0.03) was elevated. Meanwhile, we observed lower gene expression of CAT (1.00 ± 0.15 vs. 0.64 ± 0.17), NAD(P)H quinone dehydrogenase 1 (NQO1; 1.00 ± 0.09 vs. 0.47 ± 0.14), glutathione peroxidase 1 (GPX1; 1.03 ± 0.27 vs. 0.55 ± 0.09), SOD1 (1.01 ± 0.17 vs. 0.76 ± 0.17), and SOD3 (1.02 ± 0.21 vs. 0.55 ± 0.16) in the liver tissue of the HC group. Furthermore, western blot analysis showed that high-concentrate feeding led to decreased sirtuin-1 (SIRT1) (1.00 ± 0.10 vs. 0.62 ± 0.15) and FOXA2 (1.02 ± 0.19 vs. 0.68 ± 0.18), elevated autophagy-related protein microtubule associated protein 1 light chain 3 II (MAP1LC3-II; 1.00 ± 0.32 vs. 1.98 ± 0.83) and autophagy related 5 (ATG5; 1.00 ± 0.30 vs. 1.80 ± 0.27), and suppressed antioxidant signaling pathway-related protein nuclear factor erythroid 2-like 2 (NFE2L2; 1.00 ± 0.18 vs. 0.61 ± 0.30) and heme oxygenase 1 (HMOX1; 1.00 ± 0.48 vs. 0.38 ± 0.25) in liver tissue. Overall, these data indicated that SARA elevated systematic oxidative status and enhanced autophagy in the liver, and suppressed SIRT1 and FOXA2 may mediate enhanced oxidative damage and autophagy in the livers of dairy cows fed a high-concentrate diet.

Objective To investigate the outcomes of a novel direct pulp capping agent containing platelet-rich fibrin (PRF) and mineral trioxide aggregate (MTA). Methods A total of 32 New Zealand rabbits were randomly divided into 4 groups, namely, the PRF+MTA group (P+M group), PRF group (P group), MTA group (M group) and blank control group (BC group), with 8 rabbits per group. Dental pulp exposure and direct pulp capping were performed, and complete crown square sealing was performed on 2 mandibular central incisor teeth of each rabbit. Four rabbits from each group were euthanized after each observation period (7 and 28 days). The experimental teeth were subjected to HE staining. Inflammatory cell infiltration, calcified bridge formation and pulp tissue disorganization were observed and graded. Results Inflammatory cell infiltration: on the 7th day, group P+M and group M were lighter than group BC (P0.05). Calcified bridge formation: on the 7th and 28th days, group P+M was lighter than group P, group M and group BC (P0.05). Conclusion The combination of PRF and MTA for direct pulp capping provided light inflammatory cell infiltration, stable pulp status and a strong ability of pulp tissue to form calcified bridge, and the calcified bridge resembled certain points of osteodentin.

ObjectiveTo establish a rapid and nondestructive identification method for human body fluid stains and non-biological stains using three-dimensional fluorescence spectroscopy.MethodsThe collected three-dimensional fluorescence spectrum data of human saliva, 3% blood, coffee and Fanta® stains were processed with dimensionality reduction. After wavelet transform, spectral denoising and feature extraction, the classification formula was established. The Fisher discriminant was used for spectrum matching and recognition to establish the analysis method to distinguish stain types.ResultsAccording to the results of data training and comparison, all the recognition accuracies of Fanta®, coffee, saliva and blood were more than 91.39%. Among them, saliva reached 100% recognition accuracy.ConclusionThree-dimensional fluorescence spectroscopy is a potential method for rapid and nondestructive identification of biological and non-biological stains.