bluuebunny/crossref_metadata_2025_split huggingface dataset:
The forgotten tonsils—does the immune active organ absorb nanoplastics?
Authors: Ekvall Mikael T. , Naidu Shanti , Lundqvist Martin , Cedervall Tommy , Värendh Maria 
Published: August 2022

Nanoplastics are defined as plastic particles broken down to extremely small sizes (1–100 nm) with unknown effects to the human body and immune system. Air and food exposure scenarios involving blood, lungs and intestine are considered in the literature. The fact that plastics also needs to pass the nose, oral cavity, and throat is so far ignored in the literature. The tonsils are immunologically important tissue in the oral cavity in which ingested and inhaled agents are incorporated through crypts with the capacity to capture agents and start early immunologic reactions. We argue that the tonsil is a very important tissue to study in regard to micro and nanoplastic human exposure and immunologic response. Nano-sized particles are known to be able to travel through the natural barriers and have different effects on biology compared to larger particle and the bulk material. It is therefore, although difficult, important to develop experimental methods to detect and identify nanoplastics in the tonsils. In preliminary experiments we have optimized the breakdown of tonsil tissues and tried to retrieve added polystyrene nanoparticles using density-based separation and concentration. The polystyrene was followed by FTIR spectrometry and could be detected in micro- and nano-size, in the tissue breakdown solution but not after density-based separation. When nanoplastics are incorporated in the human body, it is possible that the small plastic pieces can be detected in the tonsil tissue, in the lymph system and it is of importance for future studies to reveal the immunological effects for humans.
E2ENNet: An end-to-end neural network for emotional brain-computer interface
Authors: Han Zhichao , Chang Hongli , Zhou Xiaoyan , Wang Jihao , Wang Lili , Shao Yongbin 
Published: August 2022

ObjectveEmotional brain-computer interface can recognize or regulate human emotions for workload detection and auxiliary diagnosis of mental illness. However, the existing EEG emotion recognition is carried out step by step in feature engineering and classification, resulting in high engineering complexity and limiting practical applications in traditional EEG emotion recognition tasks. We propose an end-to-end neural network, i.e., E2ENNet.MethodsBaseline removal and sliding window slice used for preprocessing of the raw EEG signal, convolution blocks extracted features, LSTM network obtained the correlations of features, and the softmax function classified emotions.ResultsExtensive experiments in subject-dependent experimental protocol are conducted to evaluate the performance of the proposed E2ENNet, achieves state-of-the-art accuracy on three public datasets, i.e., 96.28% of 2-category experiment on DEAP dataset, 98.1% of 2-category experiment on DREAMER dataset, and 41.73% of 7-category experiment on MPED dataset.ConclusionExperimental results show that E2ENNet can directly extract more discriminative features from raw EEG signals.SignificanceThis study provides a methodology for implementing a plug-and-play emotional brain-computer interface system.
An integrated intervention of computerized cognitive training and physical exercise in virtual reality for people with Alzheimer's disease: The jDome study protocol
Authors: Gambella Elena , Margaritini Arianna , Benadduci Marco , Rossi Lorena , D'Ascoli Paola , Riccardi Giovanni R. , Pasquini Sara , Civerchia Patrizia , Pelliccioni Giuseppe , Bevilacqua Roberta , Maranesi Elvira 
Published: August 2022

IntroductionAlzheimer's disease is a neurodegenerative syndrome characterized by cognitive deficits, loss of daily functions, and mental and behavioral disorders, which cause stress and negatively affect the quality of life. Studies in the field suggest that combining cognitive training with physical activity can reduce the risk of developing the disease and, once neurodegeneration has begun, it slows its progress. In particular, virtual reality and augmented reality administer cognitive stimulation while providing a link to autobiographical memory through reminiscence, enabling the improvement of the person's quality of life. The present protocol aims to evaluate the effectiveness of cognitive and physical treatments, integrated with the addition of virtual reality and reminiscence elements, using the Brainer software, in which people will find cognitive training, and the jDome® BikeAround™ system, which will allow participants to pedal along a personalized path projected on a schematic, using an exercise bike connected to the system.Methods and analysisFor this study, 78 patients with mild Alzheimer's dementia were recruited and divided into the Experimental Group (EG) and Control Group (CG). Sixteen treatment sessions of 60 min each were conducted for both groups (2 training sessions per week, for 8 weeks), including 1 patient at a time. The EG received cognitive treatment with Brainer and physical training with jDome, while the CG received cognitive treatment with Brainer and physical training with a classic bicycle. The evaluation mainly focused on the assessment of the person's cognitive status. Other analyses were conducted on the quality of life, mood, behavioral disorders, and physical function, which were considered secondary outcomes.DiscussionsThe ultimate goal of the present study is to test the effectiveness of a treatment for people with mild Alzheimer's focused on the integration of cognitive training and aerobic physical activity, using an exercise bike, with the addition of virtual reality and reminiscence elements.Ethics and disseminationThe study was approved by the Ethics Committee of the IRCCS INRCA. It was recorded in ClinicalTrials.gov on 2 June 2022 with the number NCT05402423. The study findings will be used for publication in peer-reviewed scientific journals and presentations in scientific meetings.
Glycerol monolaurate ameliorates DSS-induced acute colitis by inhibiting infiltration of Th17, neutrophils, macrophages and altering the gut microbiota
Authors: He Ke-Jie , Dong Jia-Hui , Ouyang Xiao-Mei , Huo Ya-Ni , Cheng Xiao-Shen , Lin Ying , Li Yue , Gong Guoyu , Liu Jingjing , Ren Jian-Lin , Guleng Bayasi 
Published: August 2022

Background and aimsInflammatory bowel disease (IBD) places a heavy medical burden on countries and families due to repeated and prolonged attacks, and the incidence and prevalence of IBD are increasing worldwide. Therefore, finding an effective treatment is a matter of great urgency. Glycerol monolaurate (GML), which has a twelve-carbon chain, is a compound naturally found in human breast milk. Some studies have shown that GML has antibacterial and anti-inflammatory effects. However, the specific mechanism of action remains unclear.MethodsAcute colitis was established in mice using 3% DSS, and glycerol monolaurate (500 mg·kg−1) was administered for two weeks. QPCR and western blotting were performed to examine the inflammatory status. Mice described were subjected to flow cytometry analysis for immune cell activation.ResultsGML treated alleviated macroscopic symptoms such as shortened colons, increased spleen weight, and caused weight loss in mice with DSS-induced colitis. In addition, GML decreased the expression of pro-inflammatory factors (NF-α, IL-1β and IL-1α) and increased the expression of anti-inflammatory factors (IL-10 and TGF-β). GML inhibited the activation of the MAPK and NF-κB signalling pathways, improved tissue damage, and increased the expression of intestinal tight junction proteins. In addition, LPMCs extracted from intestinal tissue via flow cytometry showed that GML treatment led to a decrease of Th17 cells, Neutrophils and Macrophages. 16S rDNA sequencing showed that GML increased the abundance of commensal bacterium such as Akkermansia and Lactobacillus murinus.ConclusionsWe showed that oral administration of GML ameliorated DSS-induced colitis by inhibiting infiltration of Th17 cells, Neutrophils, and Macrophages, protecting the intestinal mucosal barrier and altered the abundance of commensal bacterium. This study provides new insights into the biological function and therapeutic potential of GML in the treatment of IBD.
Effective dissecting range and prognostic significance of lateral pelvic lymph node dissection for middle-low rectal cancer patients with lateral pelvic lymph node metastasis: Results of a large multicenter lateral node collaborative group in China
Authors: Zhou Sicheng , Tang Jianqiang , Liang Jianwei , Lou Zheng , Fu Wei , Feng Bo , Yang Yingchi , Xiao Yi , Liu Qian 
Published: August 2022

BackgroundLateral pelvic lymph node (LPN) metastasis causes increased lateral local recurrence and poor prognosis. We aimed to investigate the prognostic significance and effective range of dissection for the LPN dissection (LPND) in rectal cancer patients with LPN metastasis.Materials and methodsThrough this large, multicenter retrospective cohort study, we evaluated the therapeutic effect of LPND. From January 2012 to December 2019, 387 rectal cancer patients with clinical evidence of LPN metastasis who underwent total mesorectal excision with LPND were included in the study. According to pathological findings, they were divided into negative (n = 296) and positive (n = 91) LPN groups. Primary endpoints were 3-year overall survival (OS), recurrence-free survival (RFS), and local recurrence-free survival (LRFS).ResultsThe OS, RFS, and LRFS in the positive group were significantly worse than those in the negative group; However, LPN metastases were not independent prognostic risk factors for LRFS (hazard ratio [HR]: 2.42; 95% confidence interval [CI], 0.77–7.64; P=0.132). Among patients with pathological LPN metastases, LPN metastases to the common and external iliac arteries were independent prognostic risk factors both for OS (HR: 4.74; 95% CI, 1.74–12.90; P=0.002) and RFS (HR: 2.70; 95% CI, 1.16–6.29; P=0.021). No significant difference was observed in the 3-year OS (72.3% vs. 70.2%, P=0.775) and RFS rates (60.9% vs. 52.6%, P=0.408) between patients with metastases to the obturator or internal iliac arteries and patients at N2b stage.ConclusionsLPND may be effective in controlling local recurrence in patients with LPN metastasis but not systemic metastases. Patients with LPN metastasis limited to the internal iliac and obturator regions achieve a long-term survival benefit from LPND, and their prognoses may be comparable to those at the N2b stage. Further metastasis to the external iliac or common iliac region should be considered systemic disease, and LPND should be avoided.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT04850027.
Fucosylated exosomal miRNAs as promising biomarkers for the diagnosis of early lung adenocarcinoma
Authors: Chen Xiongfeng , Yu Lili , Hao Kun , Yin Xiaoqing , Tu Mingshu , Cai Liqing , Zhang Liangming , Pan Xiaojie , Gao Qi , Huang Yi 
Published: August 2022

BackgroundConsidering the absence of apparent symptoms at the early stage, most patients with lung adenocarcinoma (LUAD) present at an advanced stage, leading to a dismal 5-year survival rate of &lt;20%. Thus, finding perspective non-invasive biomarkers for early LUAD is very essential.MethodsWe developed a fucose-captured strategy based on lentil lectin-magnetic beads to isolate fucosylated exosomes from serum. Then, a prospective study was conducted to define the diagnostic value of serum exosomal miRNAs for early LUAD. A total of 310 participants were enrolled, including 146 LUAD, 98 benign pulmonary nodules (BPNs), and 66 healthy controls (HCs). Firstly, exosome miRNAs in the discovery cohort (n = 24) were profiled by small RNA sequencing. Secondly, 12 differentially expressed miRNAs (DEmiRs) were selected for further screening in a screening cohort (n = 64) by qRT-PCR. Finally, four candidate miRNAs were selected for further validation in a validating cohort (n = 222).ResultsThis study demonstrated the feasibility of a fucose-captured strategy for the isolation of fucosylated exosomes from serum, evidenced with exosomal characteristics identified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting, as well as rapid and convenient operation of &lt;10 min. Furthermore, a miRNA panel for early LUAD composed of miR4732-5p, miR451a, miR486-5p, and miR139-3p was defined with an AUC of 0.8554 at 91.07% sensitivity and 66.36% specificity.ConclusionsThe fucose-captured strategy provides a reliable, as well as rapid and convenient, approach for the isolation of tumor-derived exosomes from serum. A four-fucosylated exosomal miRNA panel presents good performance for early LUAD diagnosis.
HMOX1 promotes lung adenocarcinoma metastasis by affecting macrophages and mitochondrion complexes
Authors: Chen Bo , Zhang Liyang , Zhou Hongshu , Ye Wenrui , Luo Cong , Yang Liting , Fang Ning , Tang Anliu 
Published: August 2022

BackgroundMetastasis is the leading cause of lung adenocarcinoma (LUAD) patient death. However, the mechanism of metastasis is unclear. We performed bioinformatic analyses for HMOX1 (Heme oxygenase-1), aiming to explore its role in LUAD metastasis.MethodsPan-cancer analysis was first used to identify the metastasis-associated role of HMOX1 in LUAD. HMOX1-related genomic alterations were then investigated. Based on functional enrichment, we systematically correlated HMOX1 with immunological characteristics and mitochondrial activities. Furthermore, weighted gene co-expression network analysis (WGCNA) was applied to construct the HMOX1-mediated metastasis regulatory network, which was then validated at the proteomic level. Finally, we conducted the survival analysis and predicted the potential drugs to target the HMOX1 network.ResultsHMOX1 expression was significantly associated with epithelial-mesenchymal transition (EMT) and lymph and distant metastasis in LUAD. High HMOX1 levels exhibited higher macrophage infiltration and lower mitochondrial complex expression. WGCNA showed a group of module genes co-regulating the traits mentioned above. Subsequently, we constructed an HMOX1-mediated macrophage-mitochondrion-EMT metastasis regulatory network in LUAD. The network had a high inner correlation at the proteomic level and efficiently predicted prognosis. Finally, we predicted 9 potential drugs targeting HMOX1-mediated metastasis in LUAD, like chloroxine and isoliquiritigenin.ConclusionsOur analysis elaborates on the role of HMOX1 in LUAD metastasis and identified a highly prognostic HMOX1-mediated metastasis regulatory network. Novel potential drugs targeting the HMOX1 network were also proposed, which should be tested for their activity against LUAD metastasis in future studies.
Exogenous Urokinase Inhibits Proteasomal Degradation of Its Cognate Urokinase Plasminogen Activator Receptor
Authors: Zhu Ran , Liu Ting-Wei , Liu Fan 
Published: August 2022

Acute pulmonary embolism (APE) is a debilitating condition with high incidence and mortality rates. APE is widely treated with the serine protease urokinase or urokinase-type plasminogen activator (uPA) that functions by resolving blood clots via catalyzing the conversion of plasminogen to plasmin. Treatment with recombinant uPA has been shown to increase endogenous expression of uPA and its cognate receptor, uPAR; however, the mechanisms for this induction are not known. Using an in vitro hypoxia/reoxygenation model in bronchial epithelial BEAS-2B cells, we show that induction of hypoxia/reoxygenation induces apoptosis and increases secretion of tumor necrosis factor–alpha, brain natriuretic peptide, and fractalkine, which are attenuated when treated with exogenous uPA. Induction of hypoxia/reoxygenation resulted in decreased expression of uPAR on cell surface without any significant changes in its messenger RNA expression, highlighting post-transcriptional regulatory mechanisms. Determination of uPAR protein half-life using cycloheximide showed treatment with uPA significantly increased its half-life (209.6 ± 0.2 min from 48.2 ± 2.3 min). Hypoxia/reoxygenation promoted the degradation of uPAR. Inhibition of proteasome-mediated degradation using MG-132 and lactacystin revealed that uPAR was actively degraded when hypoxia/reoxygenation was induced and that it was reversed when treated with exogenous uPA. Determination of the proteolytic activity of 20S proteasome showed a global increase in ubiquitin–proteasome activation without an increase in proteasome content in cells subjected to hypoxia/reoxygenation. Our results cumulatively reveal that uPAR is actively degraded following hypoxia/reoxygenation, and the degradation was significantly weakened by exogenous uPA treatment. Given the importance of the uPA/uPAR axis in a multitude of pathophysiological contexts, these findings provide important yet undefined mechanistic insights.
Investigation of the mechanism of the anti-cancer effects of Astragalus propinquus Schischkin and Pinellia pedatisecta Schott (A&P) on melanoma via network pharmacology and experimental verification
Authors: Wang Fang , Bai Juan , Li Feng , Liu Jing , Wang Yanli , Li Ning , Wang Yaqi , Xu Jin , Liu Wanbao , Xu Liting , Chen Lin 
Published: August 2022

Melanoma is a commonly malignant cutaneous tumor in China. Astragalus propinquus Schischkin and Pinellia pedatisecta Schott (A&amp;P) have been clinically used as adjunctive drugs in the treatment of malignant melanoma. However, the effect and mechanism of A&amp;P on melanoma have yet to be explored. The current investigation seeks to characterize the active components of A&amp;P and their potential roles in treating malignant melanoma using network pharmacology and in vitro and in vivo experiments. We first used the traditional Chinese medicine systems pharmacology (TCMSP) database and high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) to identify a total of 13 effective compounds within A&amp;P. 70 common genes were obtained by matching 487 potential genes of A&amp;P with 464 melanoma-related genes, and then we built up protein-protein interaction (PPI) network of these 70 genes, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The results revealed that A&amp;P might influence the pathobiology of melanoma through the PI3K/Akt pathway. Molecular docking also confirmed that higher content of ingredients in A&amp;P, including hederagenin, quercetin, beta-sitosterol and stigmasterol, had a strong binding activity (affinity &lt; −5 kcal/mol) with the core targets AKT1, MAPK3 and ESR1. Furthermore, we confirmed A&amp;P could inhibit melanoma cells proliferation and induce cells apoptosis through suppressing the PI3K/Akt signaling pathway by in vitro and in vivo xenograft model experiments. These findings indicate that A&amp;P may function as a useful therapy for melanoma through the PI3K/Akt pathway.
Kanglaite (Coix Seed Extract) as Adjunctive Therapy in Cancer: Evidence Mapping Overview Based on Systematic Reviews With Meta-Analyses
Authors: Lu Cuncun , Wu Shuilin , Ke Lixin , Liu Fumei , Shang Wenru , Deng Xiuxiu , Huang Yanli , Zhang Qiang , Cui Xin , Mentis Alexios-Fotios A. , Xie Yanming , Wang Zhifei 
Published: August 2022

Background: Several quantitative systematic reviews of Kanglaite (KLT), an herb preparation used to treat cancer and malignant pleural effusion, have been published in recent years. However, the clinical evidence reported in these studies has not been pursued further and the methodological quality of these meta-analyses remains unknown. Therefore, an overview was designed to map the evidence landscape based on the published meta-analyses on KLT in cancer treatment.Methods: Two bibliographic databases (PubMed and Embase) were searched from inception to 25 November 2021. Two independent reviewers were involved in study selection, data abstraction, and methodological quality assessment using AMSTAR 2. The principal features of publications and the clinical outcomes of efficacy and safety were synthesized narratively, and results of methodological quality were reported as frequencies and percentages with the corresponding 95% confidence intervals. The evidence map was used to visualize the overall quality. Excel 2016 and Stata 17/SE were used for data analysis.Results: Thirteen meta-analyses published in English were included for in-depth analysis. Among them, the year of publication ranged from 2008 to 2021, and the number of included patients ranged from 488 to 2,964. Regarding the cancer type, seven articles focused on non-small cell lung cancer, two on malignant pleural effusion, and four reviews on digestive system malignancies, such as hepatocellular carcinoma and pancreatic cancer. Almost all included meta-analyses reported that KLT as adjunctive therapy could improve various efficacy outcomes (such as disease response rates, quality of life, immune indicators) and reduce the rate of occurrence of adverse reactions, such as nausea and vomiting, leukopenia, and anemia. In terms of their methodological quality, three meta-analyses were of low quality, whereas 10 studies were critically low in quality. The methodological flaws main involved items 2 (“predesigned protocol and registration informatio’’), 3 (“rationale of study design for inclusion”), 4 (“comprehensive search strategy’’), 5 (“literature selection in duplicate’’), 7 (“list of excluded studies with reasons’’), 8 (“adequate information on included studies’’), 10 (“funding support for included primary studies’’), and 12 (“evaluation of the potential impact of risk of bias’’) based on the AMSTAR 2 tool.Conclusion: Current evidence reveals that KLT is effective and safe as an adjunctive treatment for non-small cell lung cancer, malignant pleural effusion, and digestive system malignancies (such as hepatocellular carcinoma). However, the results assessed in this overview should be further verified using well-designed and clearly reported clinical trials and meta-analyses of KLT.