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Flexible, stretchable and sensitive textile-based sensors play important roles in a wide variety of artificial intelligence because of its seamless integration with clothing and good comfort. Herein, MXene sensing layer is deposited on the surface of springlike helical core-sheath polyester yarns thanks to the capillarity effect and its intrinsic hydrophilic ability, and the resultant strain sensor and humidity sensor exhibit wide detection range from 0.3 to 120% strain and 30–100% relative humidity (RH) detection, owing to elastic core-sheath structures. The strain sensor shows excellent reproducibility (over 10000 cycles) and fast response time (120 ms). The core-sheath yarn sensor can detect various human motions such as walking, bending and twisting as well as physiological signal (pulse), which have great potential in real-time precise medicine and health care. The yarn sensor could also be an excellent humidity sensor because of the high specific area structure of yarn and intrinsic hydrophilic properties of MXene sensing layer.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases, whose severe form is associated with oxidative stress. Vitamin E as an antioxidant has a protective potential in NAFLD. Whether dietary intake of vitamin E, supplementary vitamin E use, and total vitamin E have a preventive effect on NAFLD requires investigation. A cross-sectional study used data from the National Health and Nutrition Examination Survey (2017–2020) was conducted. Vitamin E intake, including dietary vitamin E, supplementary vitamin E use, and total vitamin E, was obtained from the average of two 24-h dietary recall interviews. The extent of hepatic steatosis was measured by liver ultrasound transient elastography and presented as controlled attenuated parameter (CAP) scores. Participants were diagnosed with NAFLD based on CAP threshold values of 288 dB/m and 263 dB/m. The statistical software R and survey-weighted statistical models were used to examine the association between vitamin E intake and hepatic steatosis and NAFLD. Overall, 6122 participants were included for NAFLD analysis. After adjusting for age, gender, race, poverty level index, alcohol consumption, smoking status, vigorous recreational activity, body mass index, abdominal circumference, hyperlipidemia, hypertension, diabetes, and supplementary vitamin E use, dietary vitamin E was inversely associated with NAFLD. The corresponding odds ratios (OR) and 95% confidence intervals (CI) of NAFLD for dietary vitamin E intake as continuous and the highest quartile were 0.9592 (0.9340–0.9851, P  = 0.0039) and 0.5983 (0.4136–0.8654, P  = 0.0091) ( P trend  = 0.0056). Supplementary vitamin E was significantly inversely associated with NAFLD (fully adjusted model: OR = 0.6565 95% CI 0.4569–0.9432, P  = 0.0249). A marginal improvement in total vitamin E for NAFLD was identified. The ORs (95% CIs, P ) for the total vitamin E intake as continuous and the highest quartile in the fully adjusted model were 0.9669 (0.9471–0.9871, P  = 0.0029) and 0.6743 (0.4515–1.0071, P  = 0.0538). Sensitivity analysis indicated these findings were robust. The protective effects of vitamin E significantly differed in the stratum of hyperlipidemia ( P interaction  < 0.05). However, no statistically significant results were identified when the threshold value was set as 263 dB/m. Vitamin E intake, encompassing both dietary and supplemental forms, as well as total vitamin E intake, demonstrated a protective association with NAFLD. Augmenting dietary intake of vitamin E proves advantageous in the prevention of NAFLD, particularly among individuals devoid of hyperlipidemia.

Background Cholangiocarcinoma refers to an epithelial cell malignancy with poor prognosis. Yinchenhao decoction (YCHD) showed positive effects on cancers, and associations between YCHD and cholangiocarcinoma remain unclear. This study aimed to screen out the effective active components of Yinchenhao decoction (YCHD) using network pharmacology, estimate their potential targets, screen out the pathways, as well as delve into the potential mechanisms on treating cholangiocarcinoma. Methods By the traditional Chinese medicine system pharmacology database and analysis platform (TCMSP) as well as literature review, the major active components and their corresponding targets were estimated and screened out. Using the software Cytoscape 3.6.0, a visual network was established using the active components of YCHD and the targets of cholangiocarcinoma. Based on STRING online database, the protein interaction network of vital targets was built and analyzed. With the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server, the gene ontology (GO) biological processes and the Kyoto encyclopedia of genes and genomes (KEGG) signaling pathways of the targets enrichment were performed. The AutoDock Vina was used to perform molecular docking and calculate the binding affinity. The PyMOL software was utilized to visualize the docking results of active compounds and protein targets. In vivo experiment, the IC 50 values and apoptosis rate in PI-A cells were detected using CCK-8 kit and Cell Cycle Detection Kit. The predicted targets were verified by the real-time PCR and western blot methods. Results 32 effective active components with anti-tumor effects of YCHD were sifted in total, covering 209 targets, 96 of which were associated with cancer. Quercetin, kaempferol, beta-sitosterol, isorhamnetin, and stigmasterol were identified as the vital active compounds, and AKT1, IL6, MAPK1, TP53 as well as VEGFA were considered as the major targets. The molecular docking revealed that these active compounds and targets showed good binding interactions. These 96 putative targets exerted therapeutic effects on cancer by regulating signaling pathways (e.g., hepatitis B, the MAPK signaling pathway, the PI3K-Akt signaling pathway, and MicroRNAs in cancer). Our in vivo experimental results confirmed that YCHD showed therapeutic effects on cholangiocarcinoma by decreasing IC 50 values, down-regulating apoptosis rate of cholangiocarcinoma cells, and lowering protein expressions. Conclusions As predicted by network pharmacology strategy and validated by the experimental results, YCHD exerts anti-tumor effectsthrough multiple components, targets, and pathways, thereby providing novel ideas and clues for the development of preparations and the treatment of cholangiocarcinoma.

The histone methyltransferase DOT1L, the sole enzyme catalyzing H3K79 methylation, is increasingly implicated in cancer progression, yet its role in shaping the tumor immune microenvironment (TME) remains unclear. Here, we demonstrate that DOT1L orchestrates immune evasion in lung adenocarcinoma (LUAD) through epigenetic activation of multiple immune checkpoints. Integrative analysis of TCGA and single-cell RNA-seq data revealed that high DOT1L expression correlates with poor prognosis, diminished cytotoxic immune-cell infiltration, and upregulation of inhibitory checkpoints (PD-L1, PD-1, LAG3, CD276, etc.). Mechanistically, ChIP-seq identified DOT1L-mediated H3K79me2 enrichment at promoters of JAK1/STAT3 genes, and some immune checkpoints, including LAG3, CD276, etc. Pharmacological DOT1L inhibition (SGC0946) suppressed the JAK1/STAT3/PD-L1 axis, reduced PD-1+ T cells in a vitro immune microenvironment. In vivo , SGC0946 attenuated lung metastasis, improved survival, and remodeled the TME by downregulating PD-L1, LAG3, and CD276 expression, reduced PD-1+ T cells subsets, and alongside with enhanced TNF-α, IFN-γ production. Clinical LUAD specimens further validated the correlation between DOT1L expression, STAT3 activation, and checkpoint upregulation, particularly in metastatic disease. Our findings identify DOT1L as an epigenetic linchpin of immune suppression.

Background. Copper (Cu) metabolism is strongly associated with liver disease. Cuproptosis is a novel format of cell death, and cuproptosis-related genes (CRGs) were identified. However, the role of CRGs in Hepatocellular Carcinoma (HCC) remains unknown. Method. The mRNA transcriptome profiling data, somatic mutation data, and copy number gene level data of The Cancer Genome Atlas-Liver Hepatocellular Carcinoma project (TCGA-LIHC) were downloaded for subsequent analysis. Molecular characterization analysis of CRGs, including differential gene expression analysis, mutation analysis, copy number variation (CNV) analysis, Kaplan-Meier analysis, and immune regulator prioritization analysis, was implemented. The nonnegative matrix factorization (NMF) approach was used to identify the CRG-related molecular subtypes. Principal component analysis was adopted to verify the robustness and reliability of the molecular subtype. The least absolute shrinkage and selection operator regression analysis was performed to construct the prognostic signature based on differentially expressed genes between molecular subtypes. The survival characteristics of the molecular subtype and the signature were analyzed. The Gene Set Variation Analysis was performed for functional annotation. The immune landscape analysis, including immune checkpoint gene analysis, single sample gene set enrichment analysis, tumor immune dysfunction and exclusion (TIDE) analysis, immune infiltration cell, and tumor mutation burden analysis (TMB), was conducted. The ability of the signature to predict conventional anti-HCC agent responses was evaluated. The signature was validated in the LIRI-JP cohort and the IMvigor210 cohort. Result. A total of 13 CRGs are differentially expressed between the tumor and normal samples, while the mutation of CRGs in HCC is infrequent. The expression of CRGs is associated with the CNV level. Fourteen CRGs are associated with the prognosis of HCC. Two clusters were identified and HCC patients were divided into 2 groups with a cutoff risk score value of 1.570. HCC patients in the C1 cluster and high-risk have a worse prognosis. The area under the receiver operating characteristic curve for predicting 1-, 2-, and 3-year overall survival is 0.775, 0.768, and 0.757 in the TCGA-LIHC cohort, and 0.811, 0.741, and 0.775 in the LIRI-JP cohort. Multivariate Cox regression analysis indicates that the signature is an independent prognostic factor. Pathways involved in metabolism and gene stability and immune infiltration cells are significantly enriched. Immune checkpoint genes are highly expressed in the C1 cluster. TMB is positively correlated with the risk score. HCC patients in the high-risk group are more likely to benefit from conventional anti-HCC agents and immune checkpoint inhibitor therapies. Conclusion. The molecular characterization of CRGs in HCC is presented in this study, and a successful prognostic signature for HCC based on the cuproptosis-related molecular subtype was constructed.

Background: Antibody-drug conjugate (ADC) is a promising therapy for solid cancer that has raised global concern. Although several papers have reviewed the current state of ADCs in different solid cancers, a quantitative analysis of the publications in this field is scarce. Methods: Publications related to ADC in the field of solid cancer were obtained from the Web of Science Core Collection. Data analyses were performed with VOSviewer 1.6.9, HistCite 2.1, CiteSpace V and R package Bibliometrix. Results: A total of 3,482 records were obtained in the holistic field and 1,197 in the clinical field. Steady growth in the number of publications was observed. The United States was the leading contributor in this field. Krop IE was the most influential author. The most productive institution was Genentech Inc., while Mem Sloan Kettering Canc Ctr was the most cited one. The most impactful journal was the Journal of Clinical Oncology . A total of 37 burst references and five burst references were identified between 2017–2022 in the holistic and clinical fields, respectively. Keywords analysis indicated that ADCs research mainly involved breast cancer, triple-negative breast cancer, ovarian cancer, small cell lung cancer, prostate cancer, gastric cancer, and urothelial carcinoma. ADC agents including trastuzumab emtansine, trastuzumab deruxtecan, sacituzumab govitecan, enfortumab vedotin, and rovalpituzumab tesirine were highly studied. Targets including HER2, trophoblast cell-surface antigen, mesothelin, delta-like ligand 3, and nectin-4 were the major concerns. Conclusion: This study analyzed publications concerning ADCs in the field of solid cancer with bibliometric analysis. Further clinical trials of ADCs and designs of the next generation of ADCs are the current focuses of the field. Acquired resistance of ADCs and biomarkers for ADC therapy efficacy monitoring are future concerns.

This study investigated the expression and role of Synaptosome associated protein 25 (SNAP25) in high-grade neuroendocrine carcinoma (HGNEC). We used differentially expressed analysis and weighted gene co-expression network analysis (WGCNA) to identify key genes and modules in HGNEC. KEGG and GO analyses helped understand these genes' roles, and ROC curves assessed their diagnostic value. We also studied SNAP25's relation to immune infiltration and confirmed findings with and vivo experiments and datasets. WGCNA identified 595 key genes related to pathways like MAPK signaling, GABAergic synapse, and cancer-related transcriptional misregulation. Top genes included SNAP25, MYC, NRXN1, GAD2, and SYT1. SNAP25 was notably associated with M2 macrophage infiltration. Dataset GSE40275 confirmed SNAP25's high expression and poor prognosis in HGNEC. qRT-PCR and WB analyses showed increased SNAP25 and c-MYC levels in HGNEC, promoting MEK/ERK pathway activity. Reducing SNAP25 decreased H1299 cell proliferation, migration, invasion, and levels of c-MYC, MEK, and ERK. Finally, experiments further confirmed that SNAP25 knockout can inhibit tumor growth. SNAP25 regulates c-MYC activation by stimulating the MEK/ERK pathway, ultimately influencing the development of HGNEC.

Ischemic stroke (IS), a leading cause of disability and death worldwide, lacks effective biomarkers for early diagnosis and therapeutic intervention. This study aims to explore the potential miRNA-mRNA regulatory network in IS using clinical samples and bioinformatics methods, providing insights into its pathophysiology and identifying novel biomarkers. We analyzed plasma samples from IS patients and controls collected at Ningbo No. 2 Hospital between May 2022 and February 2023, alongside data from the Gene Expression Omnibus (GEO) database. Bioinformatics analyses, including differential expression analysis and machine learning algorithms, were employed to identify key miRNAs and their target mRNAs. The findings were validated using four-dimensional data-independent acquisition (4D-DIA) quantitative proteomics. Our analysis revealed differentially expressed miRNAs and mRNAs in IS patients compared to controls. We constructed a potential miRNA-mRNA regulatory network and confirmed the differential expression of proteins associated with this network by proteomic validation, suggesting that they play a role in IS pathophysiology. The results of data analysis and clinical sample validation emphasized Integrin alpha M (ITGAM) as a key gene associated with IS. In addition, ROC curve analysis reflected the good performance of ITGAM as a potential biomarker for the diagnosis of IS and for differentiating between early- and late-onset stroke. The area under curve (AUC) of ITGAM in diagnosing IS was 0.750, and the AUC of ITGAM in distinguishing early-onset stroke from late-onset stroke was 0.759, with a sensitivity of 93.8%. This study identifies a novel miRNA-mRNA regulatory network in IS, offering potential biomarkers for diagnosis and targets for therapeutic intervention. Our findings bridge the gap between clinical observations and molecular mechanisms, paving the way for improved IS management.

Background: Anlotinib is used as a third-line treatment for advanced non-small-cell lung cancer (NSCLC), but has limited clinical benefits and several side effects, such as diarrhea and acneiform skin rash. Traditional Chinese Medicine (TCM) is commonly used to treat cancers in China. Chinese herbal medicines may have the potential as adjuvant therapies to reduce toxicity and improve the efficacy of treatments for NSCLC. Given the positive outcomes of basic research, we plan to evaluate whether the addition of the Chinese herbal medicine Yifei Sanjie formula (YFSJF) to anlotinib can improve the progression-free survival (PFS) of advanced NSCLC patients. Methods: A multicenter, randomized, double-blind, placebo-controlled parallel-group controlled pilot trial will be performed. Forty eligible patients will be randomized in a ratio of 1:1 to the intervention (YFSJF + anlotinib) and control (placebo + anlotinib) groups. Participants will be advised to take 12 mg/day of anlotinib on days 1 to 14 of each 21-day cycle. YFSJF or placebo will be administered (15 g twice daily) during each cycle until progression of disease (PD). The primary outcome will be progression-free survival (PFS), and the secondary outcomes will be overall survival (OS), the objective response rate (ORR), and patient-reported outcomes (PRO). Tumors will be assessed based on RECIST v. 1.1 after every 2 cycles of treatment. The M. D. Anderson Symptom Inventory-Lung Cancer (MDASI-LC) will be used to evaluate PRO at baseline and weekly thereafter until PD. Discussion: This will be the first trial to evaluate the effectiveness and safety of TCM combined with anlotinib for the treatment of NSCLC. The results of this randomized controlled trial will fill a gap in the research by showing whether YFSJF combined with anlotinib can improve PFS in NSCLC patients. Trial Registration: The study was registered on June 8th, 2021 on Chinese Clinical Registry; registration number ChiCTR2100047143. (https://www.chictr.org.cn/index.aspx). Ethics and Dissemination: The Ethics Committee of the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine approved the study protocol (approval no.: K2020151, 2021/08/19). The study will also be supervised and managed by the Ethics Committee.

In order to explore how to change the singularity of the existing public physical education teaching mode, this paper introduces Internet multimedia technology to analyze physical education. Firstly, the characteristics of Internet multimedia technology were analyzed to construct a fuzzy evaluation model based on Internet multimedia technology divided into index weights, primary fuzzy evaluation, and secondary fuzzy evaluation. Secondly, some teaching indicators were statistically categorized through the method of a statistical survey, and the results of the survey were calculated to eliminate indicators lower than 85%, and the evaluation system of public physical education mixed teaching indicators was constructed. Finally, it was concluded through the experiment that 52.11% of the experts think the application level of Internet multimedia technology in public physical education hybrid teaching is now advanced and in an acceptable state. There are 36.27% of experts think that the application level is now intermediate and needs to be reduced to an acceptable level according to the program regulations. 11.82% of the experts believe that the application level is now low, unacceptable, and needs to be rectified immediately. Thus, it is concluded that public physical education based on Internet technology can enrich the existing physical education model and increase the diversity of physical education models.