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Background. The effect of GuizhiFuling Wan (GFW) on adenomyosis (AM) is definite. This study aimed to explore the mechanism and key therapeutic targets of GFW in treating AM through network pharmacology combined with molecular docking and experimental verification. Materials and Methods. In network pharmacology, firstly, the active components of GFW, its drug, and disease targets were screened through several related public databases, and GFW-AM common targets were obtained after the intersection. Then, the biological function (Gene Ontology, GO) and pathway (Kyoto Encyclopedia of Genes and Genomes, KEGG) of GFW in treating AM were enriched and analyzed. Finally, the interaction and binding force between key components and key targets of GFW were verified by molecular docking. In the animal part, the effect of GFW on the expression of matrix metallopeptidase 2 (MMP-2), matrix metallopeptidase 9 (MMP-9), and vascular endothelial growth factor (VEGF) in mice with AM was observed by HE staining, ELISA, and immunohistochemistry. Results. In this study, 89 active components of GFW, 102 related targets, and 291 targets of AM were collected. After the intersection, 26 common targets were finally obtained. The key active compounds were baicalein, sitosterol, and β-sitosterol, and the key targets were MMP-2, MMP-9, and VEGF. GO and KEGG enrichment analyses showed that biological processes such as the positive regulation of vascular endothelial migration and signaling pathways such as TNF and HIF-1 were involved in regulating angiogenesis, invasion, and metastasis in AM. The molecular docking results showed that baicalein, β-sitosterol, and stigmasterol had better binding potential with MMP-2, MMP-9, and VEGF. The results of in vivo analysis showed that GFW could decrease the serum content and protein expression of MMP-2, MMP-9, and VEGF in mice with AM. Conclusions. GFW could reduce the expression of MMP-2, MMP-9, and VEGF, which might be an essential mechanism for GFW to inhibit the invasion and metastasis of ectopic tissues of AM.

Vibration-based piezoelectric energy harvesting has received significant attention recently due to its ability to convert vibration energy from the surrounding environment into electric energy to power wireless sensors. In this work, two typical types of vibration sources, that is, engine-induced floor vibration and train-induced bridge vibration, are considered. The array of piezoelectric energy harvesters (PEHs) is adopted to harvest the energy of vibration with different frequencies. The aim of this work is to give a stable system-level modeling method and present a method to select operating point for designing energy harvesters connected with nonlinear energy harvesting circuits under complex excitations. The system-level modeling method is based on Krylov’s subspace model order reduction algorithm. With the help of this method, the harvester can be modeled using conventional finite element software and co-simulated with nonlinear circuits at a system-level. The proposed method is validated using equivalent circuit method, equivalent impedance method and experiment results, and then employed to investigate the performances of harvesters under typical real vibrations. Finally, design suggestions for PEHs under different types of vibration sources are presented.

Recent compelling results indicate possible links between neurotransmitters, intestinal mucosal IgA + B cell responses, and immunoglobulin A nephropathy (IgAN) pathogenesis. Here, we demonstrated that γ-amino butyric acid (GABA) transporter-2 (GAT-2) deficiency induces intestinal germinal center (GC) B cell differentiation and worsens the symptoms of IgAN in a mouse model. Mechanistically, GAT-2 deficiency enhances GC B cell differentiation through activation of GABA–mammalian target of rapamycin complex 1 (mTORC1) signaling. In addition, IgAN patients have lower GAT-2 expression but higher activation of mTORC1 in blood B cells, and both are correlated with kidney function in IgAN patients. Collectively, this study describes GABA signaling–mediated intestinal mucosal immunity as a previously unstudied pathogenesis mechanism of IgAN and challenges the current paradigms of IgAN.

MicroRNAs (miRNAs) have been reported to be involved in the initiation and progression of human tumors including cervical cancer (CC). However, the mechanisms underlying of their actions in CC remain to be fully elucidated. Herein, the differentially expressed miRNAs that were screened based on GSE55940 microarray data retrieved from Gene Expression Omnibus (GEO), and miR-103a-3p was significantly upregulated in CC tissues which was selected as the target miRNA for further research. We also found that high expression of miR-103a-3p was closely associated with histological grades, FIGO stage and distant metastasis as well as reflected poor overall survival. Moreover, miR-103a-3p inhibition decreased the growth capacity of SiHa and HeLa cells by inducing cell apoptosis. And F-box and WD repeat-domain containing protein 7 (FBXW7), a well-known tumor suppressor in many cancer types, was identified as a direct target of miR-103a-3p. It was further found that FBXW7 was significantly downregulated in CC tissues, and it was inversely correlated with miR-103a-3p expression levels. Further investigation demonstrated that FBXW7 upregulation could simulate the roles of miR-103a-3p knockdown in cell viability and apoptosis. Moreover, FBXW7 knockdown efficiently abrogated the influences of CC cells proliferation caused by miR-103a-3p inhibition. Notably, miR-103a-3p could block FBXW7 mediated the downstream transcription factor pathways. Taken together, these findings suggest that miR-103a-3p functions as an oncogene in CC by targeting FBXW7.

Background: Hemorrhagic transformation (HT) is a common complication of acute ischemic stroke, often resulting from reperfusion therapy. Early prediction of HT can enable stroke neurologists to undertake measures to avoid clinical deterioration and make optimal treatment strategies. Moreover, the trend of extending the time window for reperfusion therapy (both for intravenous thrombolysis and endovascular treatment) further requires more precise detection of HT tendency. Summary: In this review, we summarized and discussed the neuroimaging markers of HT prediction of acute ischemic stroke patients, mainly focusing on neuroimaging markers of ischemic degree and neuroimaging markers of blood-brain barrier permeability. This review is aimed to provide a concise introduction of HT prediction and to elicit possibilities of future research combining advanced technology to improve the accessibility and accuracy of HT prediction under emergent clinical settings. Key Messages: Substantial studies have utilized neuroimaging, blood biomarkers, and clinical variables to predict HT occurrence. Although huge progress has been made, more individualized and precise HT prediction using simple and robust imaging predictors combining stroke onset time should be the future goal of development.

Background & Aims We aimed to compare safety and effectiveness of vedolizumab to tumor necrosis factor (TNF)-antagonist therapy in ulcerative colitis in routine practice. Methods A multicenter, retrospective, observational cohort study (May 2014 to December 2017) of ulcerative colitis patients treated with vedolizumab or TNF-antagonist therapy. Propensity score weighted comparisons for development of serious adverse events and achievement of clinical remission, steroid-free clinical remission, and steroid-free deep remission. A priori determined subgroup comparisons in TNF-antagonist–naive and –exposed patients, and for vedolizumab against infliximab and subcutaneous TNF-antagonists separately. Results A total of 722 (454 vedolizumab, 268 TNF antagonist) patients were included. Vedolizumab-treated patients were more likely to achieve clinical remission (hazard ratio [HR], 1.651; 95% confidence interval [CI], 1.229-2.217), steroid-free clinical remission (HR, 1.828; 95% CI, 1.135-2.944), and steroid-free deep remission (HR, 2.819; 95% CI, 1.496-5.310) than those treated with TNF antagonists. Results were consistent across subgroup analyses in TNF-antagonist–naive and −exposed patients, and for vedolizumab vs infliximab and vs subcutaneous TNF-antagonist agents separately. Overall, there were no statistically significant differences in the risk of serious adverse events (HR, 0.899; 95% CI, 0.502-1.612) or serious infections (HR, 1.235; 95% CI, 0.608-2.511) between vedolizumab-treated and TNF-antagonist−treated patients. However, in TNF-antagonist−naive patients, vedolizumab was less likely to be associated with serious adverse events than TNF antagonists (HR, 0.192; 95% CI, 0.049-0.754). Conclusions Treatment of ulcerative colitis with vedolizumab is associated with higher rates of remission than treatment with TNF-antagonist therapy in routine practice, and lower rates of serious adverse events in TNF-antagonist−naive patients.

Background Resting-state functional magnetic resonance imaging has been widely used for the assessment of brain functional network, yet with inconsistent results. The present study aimed to investigate intranetwork and internetwork connectivity differences between patients with major depressive disorder (MDD) and healthy controls at the integrity, network and edge levels of 8 well-defined resting state networks. Methods Thirty patients with MDD and sixty-three healthy control subjects were recruited in this study. Results Compared with healthy controls, patients with MDD showed increased node degree in the right amygdala and putamen, increased connectivity strength in the deep gray matter network (DGN) and increased functional connectivity in intranetwork and internetwork. Meanwhile, MDD showed decreased connectivity strength in visual network-DGN pair. Limitations The sample size was small, and all patients in this study were of Asian ethnicity, especially Han individuals. Conclusions These findings demonstrate that MDD cases and healthy controls may have divergent intranetwork and internetwork connectivity at an early stage without confounding influence of medication. These differences may underlie cognitive and behavioral alterations in patients with MDD. And these differences may help with the discrimination of patients and healthy people at an early stage of MDD. More studies in the future are warranted to assist in the diagnosis of this burdensome disease.

A series of high-efficiency CuBx-based bifunctional flexible polyurethane plastic electrodes are fabricated by mild electroless plating for durable electrolysis over 1 A cm−2 in seawater, which also promotes the degradation of polyurethane plastics.

Objective: To explore the association of baseline venous outflow from the occluded cerebral territory and futile recanalization (FR) in patients with acute ischemic stroke due to large vessel occlusion (LVO) in the anterior circulation. Methods: Consecutive patients from a prospectively maintained stroke database were included in this study if they presented with a multimodal CT-confirmed LVO in the anterior circulation and underwent thrombectomy within 24 hours after stroke onset. Excellent recanalization of the occluded artery, defined as final mTICI 2c-3 on digital subtraction angiography, was considered to be futile if patients fail to achieve functional independence (modified Rankin Scale of 0-2) at 90 days. Baseline venous outflow profile was determined by a 7-point semi-quantitative scoring system which assessed ipsilateral venous opacification of the vein of Labbe, Trolard and superficial middle cerebral vein on single-phase CTA source images. Hypoperfusion intensity ratio (HIR, defined as delay time >6 seconds/delay time >3 seconds) was applied to evaluate tissue-level collateral status. Results: 145 patients met the inclusion criteria. Multivariable logistic regression analysis showed that malignant venous outflow (OR 4.30 [95% CI 1.41-14.57]; p =0.013) was independently associated with functional dependence regardless of age, glucose, HIR, early neurologic deterioration, hemorrhagic transformation and final infarct volume. FR was observed in 24/52 (46%) recanalized patients. Stepwise logistic regression revealed a poor venous outflow profile at presentation as an independent predictor of FR (OR 7.04 [95% CI 1.29-50.16]; p =0.03) adjusted for baseline NIH Stroke Scale score, HIR and presence of hemorrhagic transformation. Conclusion: A malignant venous outflow profile at baseline is associated with FR in patients with LVO. The mechanism by which poor venous outflow from the occluded territory hinders clinical recovery despite prompt successful thrombectomy remains to be determined.

Summary. The purpose of the article is to reveal the cultural connotation and axiological characteristics of the concepts "left" and "right", which make up one of the universal binary oppositions, in Russian and Chinese stable word combinations and paremias in order to determine the differences between the Russian and Chinese language worldviews in the cognitive zone of the presence of these concepts. The object of the research is Russian and Chinese phraseological units with the key words left and right. The subject of the study is the determination of common and distinctive features in the perception of traditional views and habits by Chinese and Russians regarding the use of the above-mentioned concepts in their national language worldviews. The procedures of semantic, connotative, phraseological, linguocultural, conceptual, cognitive, comparative and quantitative analysis, as well as the descriptive method, were used in the research process. The results of the study were the identification of 74 Russian and 62 Chinese phraseological units with different structures, containing indicators of the concepts "left" and "right". They are classified according to their discursive meaning, sphere of functioning, and axiological characteristics. A comparative analysis of the linguocultural principles of their use in the Russian and Chinese languages was carried out. Conclusions are made regarding the asymmetry of the traditional perception and functioning of the conceptual meanings of left and right in the compared languages.

Supporting Ontario’s diverse multilingual learners (MLs) requires more than “just good teaching” (de Jong & Harper, 2005, p. 102). MLs’ success is tied to specific teacher knowledge, attitudes, and pedagogical moves based on linguistically responsive teaching (Lucas & Villegas, 2013). This study investigated the perspectives of teachers, curriculum leaders, and consultants regarding how MLs can best be supported, their challenges and successes in working with MLs, and what needs to change in teacher education to achieve the goal of supporting MLs across their curricula. Semi-structured interviews were conducted with 11 teachers currently working with MLs in Ontario, organized around their personal and professional backgrounds and experiences, issues faced in supporting MLs, perspectives on how Ontario’s policies impact their work, and opinions about how to enable future teachers to develop necessary skills to support MLs. Findings from an inductive thematic analysis of the interviews suggest the need for teachers to connect with MLs through shared language learning experiences, use assetbased, linguistically responsive and translanguaging approaches, and involve parents and communities. The findings also highlight issues around policy accessibility, the lack of specialized training, and inadequate resources. Finally, the study makes recommendations for preparing future teachers with practical strategies to support MLs in K–12 classrooms. Le soutien des divers apprenants multilingues de l’Ontario exige plus que « just good teaching » (de Jong et Harper, 2005, p. 102). La réussite des multilingues est liée à la connaissance spécifique des enseignants, aux attitudes et aux mouvements pédagogiques fondés sur un enseignement répondant aux besoins linguistiques (Lucas et Villegas, 2013). Cette étude examine les perspectives des enseignants, des responsables de programmes et des consultants sur la façon dont on peut optimiser le soutien aux multilingues, les défis et les réussites rencontrés en travaillant avec les multilingues et ce qui a besoin de changer dans la formation des enseignants pour qu’ils parviennent à apporter du soutien aux multilingues dans tous leurs programmes. On a effectué des entrevues semi-structurées auprès de 11 enseignants travaillant avec des multilingues en Ontario. Ces entrevues étaient organisées autour de leurs antécédents et expériences personnels et professionnels, des problèmes auxquels ils avaient fait face dans le soutien des multilingues, de leurs perspectives sur la manière dont les politiques ontariennes influencent leur travail et de leur opinion sur la façon de permettre aux futurs enseignants d’acquérir les habiletés nécessaires pour soutenir les multilingues. Les résultats tirés d’une analyse thématique inductive des entrevues suggèrent que les enseignants doivent établir des liens avec les multilingues en partageant leurs expériences d’apprentissage linquistique, en utilisant des approches fondées sur les atouts, adaptées sur le plan linguistique et du translanguaging, et en faisant participer les parents et les communautés. Les résultats soulignent également les problèmes concernant les politiques d’accessibilité, le manque de formation et les ressources inadéquates. Pour finir, l’étude propose des recommandations pour préparer les futurs enseignants à l’aide de stratégies pratiques afin de soutenir les multilingues dans les salles de classe de la maternelle à la 12e année.

The aim of this study was to explore the interaction between reperfusion and treatment time on the outcomes of patients undergoing endovascular treatment presenting within 24 h of last known well, and to compare the predictive ability of different reperfusion measurements on outcomes.Eligible patients from a single-center cohort were enrolled in this study. Reperfusion was assessed using reperfusion index (decreased volume of hypoperfusion lesion compared with baseline) measured by repeated perfusion imaging, and modified treatment in cerebral ischemia score measured by digital subtraction angiography, respectively. The interactions between reperfusion measurements and treatment time on outcomes were explored using multivariate-adjusted logistic and linear regression models. The predictive abilities of reperfusion measurements on outcomes were compared using area under the receiver operating characteristic curve (ROC-AUC) and values of R-square.Reperfusion index and treatment time had significant interactions on 3-month modified Rankin Scale (mRS) 0-2 and infarct growth (p for interaction0.05). Although the AUCs were statistically similar (AUCs of mRS 0-2 prediction, mTICI≥2b:0.63, mTICI≥2c:0.59, reperfusion index≥0.5:0.66, reperfusion index ≥0.9:0.73, P value of any of the two AUCs0.05), reperfusion index≥0.9 showed the highest R-square values in outcome prediction (R-square values of 3-month mRS 0-2 and infarct growth = 0.21) among all the reperfusion measurements.Treatment time mitigated the effect of reperfusion on outcomes of patients receiving endovascular treatment within 24 h of last known well. Reperfusion index≥0.9 might serve as a better proxy of good outcomes compared with other reperfusion measurements.

Second-harmonic-generation (SHG) efficiency and birefringence are two crucial parameters for nonlinear optical (NLO) crystals. However, the simultaneous optimization of these two key parameters rem...

The developed Ni-La/Al2O3-CeO2-Bamboo charcoal (ACB) catalyst was applied to the co-pyrolysis of straw and plastic to produce hydrogen in a horizontal quartz tube pyrolysis furnace. In this study, the effects of the mixing ratio of straw and plastic, the presence and stability of the catalyst on the co-pyrolysis hydrogen production were investigated. Experiment showed that the addition of PE can increase the yield of H2 within a certain range, and the best mass ratio of 5:5 was found. In the co-pyrolysis process with the participation of the catalysts, the macromolecular tar can be cracked into combustible gases such as H2, and the H2 yield could be increased to 332.2ml/g (Ni-La/ACB) is much higher than 68.87ml/g without catalyst. Compared with Ni/ACB, Ni-La/ACB had been increased the alkalinity by adding La element and enhanced the carbon deposition resistance of the catalyst, which makes the catalyst maintain higher stability. This was also confirmed in stability test experiments.

BACKGROUND Existing therapeutic efficacy of chemotherapy and photodynamic therapy (PDT) is always affected by some resistance factors from tumour environment (TME), such as hypoxia and the antioxidant defense system. PURPOSE This study aims at developing a cascaded intelligent multifunctional nanoplatforms to modulate the TME resistance for synergistically enhanced chemo- and photodynamic therapies. METHODS In this study, we synthesised hollow manganese dioxide nanoparticles (HMDNs) loaded with the hydrophilic chemotherapeutic drug (acriflavine, ACF) and the hydrophobic photosensitizer (chlorine6, Ce6), which was further encapsulated by pH-sensitive liposome to form core-shell nanocomposite, with surface modified with arginine-glycine-aspartic acid (RGD) peptide to achieve tumour targeting. RESULTS After uptake by tumour cells, the liposome shell was rapidly degraded by the low pH, and the inner core could be released from the liposome. Then, the released HMDNs/ACF/Ce6 would be dissociated by low pH and high levels of intracellular GSH within TME to release encapsulated drugs, thereby resulting in synergistic effects of chemotherapy and PDT. Meanwhile, the released ACF could bind with HIF-1a and then inhibit the expression levels of HIF-1's downstream signalling molecules P-gp and VEGF, which could further strengthen the antitumor effects. As a result, HMDNs/ACF/Ce6@Lipo-RGD NPs with laser irradiation exhibited superior anti-tumour therapeutic efficiency.

Background Although lower temperature ( Methods and results In this work, a core–shell nanoplatform with an appropriate size composed of arginine–glycine–aspartate (RGD) functioned polydopamine (PDA) as a shell and a triphenylphosphonium (TPP) modified hollow mesoporous manganese dioxide (H-mMnO2) as a core was designed and fabricated for the first time. This nanostructure endows a size-controllable hollow cavity mMnO2 and thickness-tunable PDA layers, which effectively prevented the pre-matured release of encapsulated azo initiator 2,2′-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIBI) and revealed pH/NIR dual-responsive release performance. With the mitochondria-targeting ability of TPP, the smart nanocomposites (AIBI@H-mMnO2-TPP@PDA-RGD, AHTPR) could efficiently induce mitochondrial associated apoptosis in cancer cells at relatively low temperatures ( Conclusions The synergistic therapy efficacy was confirmed by effectively inducing cancer cell death in vitro and completely eradicating the tumors in vivo. Additionally, the excellent biosafety and biocompatibility of the nanoplatforms were confirmed both in vitro and in vivo. Taken together, the current study provides a novel paradigm toward oxygen-independent free-radical-based cancer therapy, especially for the treatment of hypoxic solid tumors. Graphical Abstract

Traditional centralized cloud services face challenges, such as high communication delay, single point of failure, etc. Edge computing is one of distributed computing services in which resources are placed closer to users, and thus is more robust and can reduce communication delay. Although outsourcing data to the edge servers can bring great convenience, it also brings serious security threats. In order to provide image retrieval while ensuring users’ data privacy, a privacy-preserving content-based image retrieval scheme in edge environment is proposed. Considering the distributed characteristics of edge environment and the requirement of lightweight computing, we design a secure interaction protocol completed through the collaborative cooperation of two or more edge servers. This scheme not only protects data privacy, but also has low communication overhead and delay as well as low computing complexity, therefore it is more suitable for edge computing environment. Theoretical analysis and experiments show that our scheme has high security, retrieval accuracy and efficiency.

Summary Objective Nucleus pulposus (NP) plays a central role in disc degeneration pathogenesis, however, as a heterogeneous tissue, cell subsets in NP and their corresponding biological process in intervertebral disc degeneration (IVDD) are unreported. Method Nucleus pulposus were isolated from normal control and IVDD, and then subjected to single-cell RNA sequencing (scRNA-seq). Unsupervised clustering of the cells based on the gene expression profiles using the Seurat package and passed to tSNE for clustering visualization. Rat model of disc degeneration was built to validate the pathways identified by scRNA-Seq. Results Seven chondrocyte subsets were revealed in NP based on differential gene expression, among which 4 subsets (C1–C4) were reported for the first time. Furthermore, GO and KEGG analyses discovered that ferroptosis pathways were enriched. Rat model of disc degeneration was built (n = 6/group, control vs. model) to validate the pathways identified by scRNA-Seq. Iron levels of NP were significantly higher in model group than control group (means 0.712 vs. 0.248, respectively, mg/gpro, p = 0.0026), and the levels of Heme Oxygenase 1 (HO-1) were also elevated in model group (means 14.33 vs. 5.16 IOD, respectively, p = 0.0002). However, the levels of ferritin light chain (FTL) were significantly decreased in model group compared to control group (means 26.17 vs. 9.00 FTL+ cell number, respectively, p = 0.0011). Conclusions Novel chondrocyte subsets in nucleus pulposus were discovered through scRNA-Seq, which provided novel insight to understand the pathological change during the development of IVDD. Ferroptosis participated in disc degeneration pathogenesis and it might serve as a new target for intervening IVDD.

This study showed that the use of social networking sites would deepen individuals' unhealthy restrictions on their own diet, and the use of social networking sites will further deepen individuals' restrictive diet through their tendency to pursue appearance perfection. However, increased self-focus by individuals may discourage appearance perfectionists from adopting unhealthy eating control behaviors.

Huntingtin-associated protein 1 (HAP1) is the first identified protein whose function is affected by its abnormal interaction with mutant huntingtin (mHTT), which causes Huntington disease. However, the expression patterns of Hap1 and Htt in the rodent brain are not correlated. Here we found that the primate HAP1, unlike the rodent Hap1, is correlatively expressed with HTT in the primate brains. CRISPR/Cas9 targeting revealed that HAP1 deficiency in the developing human neurons did not affect neuronal differentiation and gene expression as seen in the mouse neurons. However, deletion of HAP1 exacerbated neurotoxicity of mutant HTT in the organotypic brain slices of adult monkeys. These findings demonstrate differential HAP1 expression and function in the mouse and primate brains, and suggest that interaction of HAP1 with mutant HTT may be involved in mutant HTT-mediated neurotoxicity in adult primate neurons.

Parkinson's disease (PD) is a common neurodegenerative disease with the exact etiology still unclear, but gut microbial disorders are thought to be related to the initiation and progression of it. Exercise training has a significant effect on the intestinal flora, so to investigate the promotion effect of exercise training on Parkinson's disease, we performed a rotarod walking training (5 times a week at 25 rpm for 20 min for 8 weeks) on a chronic mouse model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and observed the locomotor function of mice, function of dopaminergic neurons, intestinal mucosal barrier condition, intestinal inflammation and the structure and composition of intestinal flora. The results showed in these PD mice, exercise training improved their motility, increased the dopamine (DA) content in the striatum, along with promoted the gene expression of tyrosine hydroxylase and brain-derived neurotrophic factor in the striatum, which suggests this exercise training might protect striatal dopaminergic neurons from MPTP damage; the results also showed exercise training promoted recovery from ileal pathology, reduced the gene expression of intestinal inflammatory factors, and significantly altered the composition and structure of the intestinal flora in these mice.