bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Long-Term Exposure to PM2.5 on Oxidative Stress Injury and Expression of Inflammatory Factors, NF-κB p65 and Cx43 in Bone Marrow of Mice
Authors: Liu Li-Li , Yang Jing , Ye Zhong-Lv , Tian Chuan , Huang Xiu-Lan , Zhang Hui-Qin , Mo Xiao-Huan 
Published: June 2022

Objective: This study aims to explore the toxic effect of PM2.5 on the hematopoietic microenvironment of the bone marrow, and investigate the effect of PM2.5 on oxidative stress injury, the secretion of inflammatory cytokines and the expression of NF-κB p65 and C x 43 in the bone marrow of mice.Methods: A total of 615 mice were treated with normal saline, low dose (0.1 mg/ml) PM2.5 suspension, and high dose (0.2 mg/ml) PM2.5 suspension by intratracheal instillation, respectively. The ROS content, activity of total SOD (T-SOD), DNA injury, and the protein expression levels of IL-1 β, IL-6, TNF-α, NF-κB p65 and Cx43 in bone marrow cells (BMCs) of mice were detected in these three groups.Results: Compared with the normal saline control group, the expression level of reactive oxygen species (ROS) significantly increased in BMCs, while the activity of SOD enzymes significantly decreased in PM2.5 exposed mice. Furthermore, DNA injury significantly increased in PM2.5 exposed mice, and the expression of IL-1 β, IL-6, TNF-α and NF-κB p65 significantly increased, while the protein expression of Cx43 significantly decreased in the PM2.5 exposed mice. The differences were statistically significant (p &lt; 0.05). There were significant differences in ROS content, T-SOD activity, DNA injury (TL, TD and TM), protein expression of IL-1β, IL-6, TNF-α and Cx43 between the high-dose PM2.5 exposure group and low-dose PM2.5 exposure group (p &lt; 0.05), but there was no significant difference in the expression of NF-κB p65 between the high-dose and low-dose PM2.5 exposure groups (p &gt; 0.05).Conclusion: PM2.5 has toxic effects on the bone marrow of mice. Oxidative stress injury, inflammatory reaction and abnormal intercellular communication may be the underlying mechanism.
The Novel lncRNA ENST00000530525 Affects ANO1, Contributing to Blood–Brain Barrier Injury in Cultured hCMEC/D3 Cells Under OGD/R Conditions
Authors: Jiang Wen , Li Jie , Cai Yuefang , Liu Wenchen , Chen Mei , Xu Xiaoying , Deng Minzhen , Sun Jingbo , Zhou Lihua , Huang Yan , Wu Shuang , Cheng Xiao 
Published: June 2022

Ischemic stroke (IS) is a major neurological disease with high fatality and residual disability burdens. Long noncoding RNAs (lncRNAs) have been found to play an important role in IS. However, the roles and significance of most lncRNAs in IS are still unknown. This study was performed to identify differentially expressed (DE) lncRNAs using a lncRNA microarray in whole blood samples of patients suffering from acute cerebral ischemia. Bioinformatics analyses, including GO, KEGG pathway enrichment analysis, and proximity to putative stroke risk location analysis were performed. The novel lncRNA, ENST00000530525, significantly decreased after IS. Furthermore, we evaluated lncRNA ENST00000530525 expression in cultured hCMEC/D3 cells under oxygen-glucose deprivation/reoxygenation (OGD/R) conditions using fluorescent in situ hybridization (FISH) and quantitative real-time polymerase chain reaction (RT–qPCR) analysis. To investigate the function of lncRNA ENST00000530525, its over-expression (OE) and negative control (NC) plasmids were transfected into hCMEC/D3 cells, and cell viability was detected by a cell counting kit-8 (CCK-8) assay after OGD/R. LncRNA ENST00000530525 and ANO1 expression were investigated using RT–qPCR and immunofluorescence. For blood–brain barrier (BBB) permeability, FITC-dextran transendothelial permeability assay and tight junction (TJ) protein immunofluorescence assays were performed. There were 3352 DE lncRNAs in the blood samples of acute IS patients. The validation results were consistent with the gene chip data. The GO and KEGG results showed that these lncRNAs were mainly related to oxygen and glucose metabolism, leukocyte transendothelial migration, mitophagy and cellular senescence. Among these, lncRNA ENST00000530525 was the most highly downregulated lncRNA and it was mapped within the IS-associated gene anoctamin-1 (ANO1). We further found that lncRNA ENST00000530525 was downregulated in hCMEC/D3 cells under 4 h OGD and 20 h reoxygenation (OGD4/R20) conditions. Upregulating lncRNA ENST00000530525 by plasmid transfection decreased cell viability while increasing ANO1 expression and it contributed to BBB injury in hCMEC/D3 cells after OGD4/R20. The lncRNA ENST00000530525 might play deleterious roles in post-stroke pathogenesis. These results show that some DE lncRNAs in humans participate through characteristic roles in post-stroke pathogenesis; thus, the roles and significance of some novel lncRNAs in IS warrant further study.
Identification and Validation of Necroptosis-Related LncRNA Signature in Hepatocellular Carcinoma for Prognosis Estimation and Microenvironment Status
Authors: Chen Cong , Wu Yumeng , Chen Kang , Xia Zicong , Liu Xiaokan , Zhang Chaojie , Zhao Hui , Shen Aiguo 
Published: June 2022

Background: Hepatocellular carcinoma (HCC) is among malignancies with the highest fatality toll globally and minimal therapeutic options. Necroptosis is a programmed form of necrosis or inflammatory cell death, which can affect prognosis and microenvironmental status of HCC. Therefore, we aimed to explore the prognostic value of necroptosis-related lncRNAs (NRLs) in HCC and the role of the tumor microenvironment (TME) in immunotherapy.Methods: The RNA-sequencing data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). NRLs were identified by Pearson correlation analysis. The signature was constructed using the LASSO–Cox regression analysis and evaluated using the receiver operating characteristic curve (ROC) and the area under the Kaplan–Meier curve. The nomogram was built based on clinical information and risk score. Gene set enrichment analysis (GSEA), immunoassay, half-maximum inhibitory concentration (IC50) analysis of the risk group, and the HCC subtype identification based on NRLs were also carried out. Finally, we detected the expression of lncRNAs in HCC tissues and cell lines in vitro.Results: A total of 508 NRLs were screened out, and seven NRLs were constructed as a risk stratification system to classify patients into distinct low- and high-risk groups. Patients in the high-risk group had a significantly lower overall survival (OS) than those in the low-risk group. Using multivariate Cox regression analysis, we found that the risk score was an independent predictor of OS. Functional analysis showed that the immune status of different patients was different. The IC50 analysis of chemotherapy demonstrated that patients in the high-risk group were more sensitive to commonly prescribed drugs. qRT-PCR showed that three high-risk lncRNAs were upregulated in drug-resistant cells, and the expression in HCC tissues was higher than that in adjacent tissues.Conclusion: The prediction signature developed in this study can be used to assess the prognosis and microenvironment of HCC patients, and serve as a new benchmark for HCC treatment selection.
Prognostic Implication and Immunological Role of PSMD2 in Lung Adenocarcinoma
Authors: Zhao Huihui , Lu Guojun 
Published: June 2022

Background: Although previous studies reported that 26S proteasome non-ATPase regulatory subunit 2 (PSMD2) is involved in many human cancers. However, its clinical significance and function in lung adenocarcinoma remain unclear. Here, we examined the prognostic and immunological role of PSMD2 in lung adenocarcinoma.Methods: The Cancer Genome Atlas (TCGA) was conducted to analyze PSMD2 expression and verified using UALCAN. PrognoScan and Kaplan-Meier curves were utilized to assess the effect of PSMD2 on survival. cBioPortal database was conducted to identify the mutation characteristics of PSMD2. Functional enrichment was performed to determine PSMD2-related function. Cancer Single-cell State Atlas (CancerSEA) was used to explore the cancer functional status of PSMD2 at single-cell resolution. PSMD2-related immune infiltration analysis was conducted. Tumor-Immune system interaction database (TISIDB) was performed to verify the correlation between PSMD2 expression and tumor-infiltrating lymphocytes (TILs).Results: Both mRNA and protein expression of PSMD2 were significantly elevated in lung adenocarcinoma. High expression of PSMD2 was significantly correlated with high T stage (p = 0.014), lymph node metastases (p &lt; 0.001), and TNM stage p = 0.005). Kaplan-Meier curves indicated that high expression of PSMD2 was correlated with poor overall survival (38.2 vs. 59.7 months, p &lt; 0.001) and disease-specific survival (59.9 months vs. not available, p = 0.004). Multivariate analysis suggested that PSMD2 was an independent biomarker for poor overall survival (HR 1.471, 95%CI, 1.024–2.114, p = 0.037). PSMD2 had a high mutation frequency of 14% in lung adenocarcinoma. The genetic mutation of PSMD2 was also correlated with poor overall survival, disease-specific survival, and progression-free survival in lung adenocarcinoma. Functional enrichment suggested PSMD2 expression was involved in the cell cycle, RNA transport, and cellular senescence. CancerSEA analysis indicated PSMD2 expression was positively correlated with cell cycle, DNA damage, and DNA repair. Immune infiltration analysis suggested that PSMD2 expression was correlated with immune cell infiltration levels and abundance of TILs.Conclusion: The upregulation of PSMD2 is significantly correlated with poor prognosis and immune infiltration levels in lung adenocarcinoma. Our findings suggest that PSMD2 is a potential biomarker for poor prognosis and immune therapeutic target in lung adenocarcinoma.
Correlation Between Immune-Related Genes and Tumor-Infiltrating Immune Cells With the Efficacy of Neoadjuvant Chemotherapy for Breast Cancer
Authors: Zhou Yan , Tian Qi , Gao Huan , Zhu Lizhe , Yang Jiao , Zhang Juan , Yang Jin 
Published: June 2022

Background: In the absence of targeted therapy or clear clinically relevant biomarkers, neoadjuvant chemotherapy (NAC) is still the standard neoadjuvant systemic therapy for breast cancer. Among the many biomarkers predicting the efficacy of NAC, immune-related biomarkers, such as immune-related genes and tumor-infiltrating lymphocytes (TILs), play a key role.Methods: We analyzed gene expression from several datasets in the Gene Expression Omnibus (GEO) database and evaluated the relative proportion of immune cells using the CIBERSORT method. In addition, mIHC/IF detection was performed on clinical surgical specimens of triple-negative breast cancer patients after NAC.Results: We obtained seven immune-related genes, namely, CXCL1, CXCL9, CXCL10, CXCL11, IDO1, IFNG, and ORM1 with higher expression in the pathological complete response (pCR) group than in the non-pCR group. In the pCR group, the levels of M1 and γδT macrophages were higher, while those of the M2 macrophages and mast cells were lower. After NAC, the proportions of M1, γδT cells, and resting CD4 memory T cells were increased, while the proportions of natural killer cells and dendritic cells were decreased with downregulated immune-related genes. The results of mIHC/IF detection and the prognostic information of corresponding clinical surgical specimens showed the correlation of proportions of natural killer cells, CD8-positive T cells, and macrophages with different disease-free survival outcomes.Conclusion: The immune-related genes and immune cells of different subtypes in the tumor microenvironment are correlated with the response to NAC in breast cancer, and the interaction between TILs and NAC highlights the significance of combining NAC with immunotherapy to achieve better clinical benefits.
Multi-Technique Approach to Enhance the Properties of Fine Recycled Aggregate Concrete
Authors: Amadi I. G. , Beushausen H. , Alexander M.G. 
Published: June 2022

This study investigated the properties of fine recycled aggregates (FRA), with a view to enhancing their properties for structural concrete applications. The study explored several approaches including mixing; curing; systematic screening of FRA particles below 1.18 mm to reduce the adhered cement paste (ACP) content; and the use of fly ash as 30% cement replacement to modify the microstructure of FRA concrete. To test these approaches, two series of concrete mixes were prepared at 0.45 and 0.55 w/b ratio, with FRA replacing natural sand at 0, 25, and 50% by mass, and tests were carried out after 3, 28, and 180 days of curing. Results show that the combination of ACP reduction and fly ash treatment significantly enhanced the compressive strength and elastic modulus of FRA concrete, especially at 180 days, through microstructure modification and pozzolanic reactions.
Impact of BNT162b2 mRNA Vaccination on the Development of Short and Long-Term Vaccine-Related Adverse Events in Inflammatory Bowel Disease: A Multi-Center Prospective Study
Authors: Shehab Mohammad , Alrashed Fatema , Abdullah Israa , Alfadhli Ahmad , Ali Hamad , Abu-Farha Mohamed , Channanath Arshad Mohamed , Abubaker Jehad Ahmed , Al-Mulla Fahd 
Published: June 2022

IntroductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination has been effective in protecting against severe COVID-19 infections and related mortality. It is recommended for all individuals including patients with inflammatory bowel disease (IBD). However, safety data are lacking in this group of patients. Therefore, we aim to evaluate the short- and long-term vaccine related adverse events (AEs) in patients with IBD.MethodsThis is a prospective, observational cohort study investigating short- and long-term AEs related to the BNT162b2 vaccine in patients with IBD (study group) after the first and second dose compared to healthy participants (control group). Patients were recruited at the time of attendance to the clinic or infusion rooms. Short term (&lt;3 weeks) localized and systemic AEs were assessed via questionnaire. Follow-up phone-based survey was made to collect data on long term (up to 24 weeks) AEs.ResultsA total of 408 patients answered the questionnaires, 204 patients in each group, the study and control group. No serious adverse events were reported in either the study or the control group after the first or the second dose. Participants in the control group reported more frequent pain at the injection site than those in the study group after the first dose [58 (57%) vs. 38 (37%) respectively, P = 0.005]. After the second dose, tiredness was reported more frequently in the control group [49 (48%)] compared to the study group [25 (24%) (P &lt; 0.001)]. At 20–24 weeks post vaccination, 386 out of 408 (94.6%) patients were willing to participate in the follow-up phone based questionnaire [196 (96.1%) in the study group vs. 190 (93.1%) in the control group]. In both groups, none of the patients reported local, systemic, or severe adverse events (0 out of 386) at week 20–24 post second dose.ConclusionThe BNT162b2 vaccine is safe in patients with IBD. No severe or long-term adverse events were reported in our study. The frequency of local and systemic adverse events after the second dose was generally higher among healthy participants compared to patients with IBD. Further studies including a larger cohort with a longer follow-up duration are needed to assess for possible rare adverse events.
Exosomal miR-4800-3p Aggravates the Progression of Hepatocellular Carcinoma via Regulating the Hippo Signaling Pathway by Targeting STK25
Authors: Lin Haoming , Peng Jicai , Zhu Taifeng , Xiong Meihong , Zhang Rui , Lei Liming 
Published: June 2022

BackgroundEmerging evidence has shown that exosome microRNAs (miRNAs) regulate the development of hepatocellular carcinoma (HCC). Here, the influences of miR-4800-3p on the progression of HCC were explored.Materials and MethodsThe expression of miR-4800-3p in the exosome derived by transforming growth factor beta 1 (TGF-β1)-treated HCC cells and the serum exosome isolated from HCC patients were identified by real-time PCR. The effects of TGF-β1 and the influences of Huh7-secreted exosomes and the effects of miR-4800-3p combined with/without STK25 on cell functions were explored using the EdU assay cloning experiments, wound healing assay, and Transwell assay. The corresponding molecular mechanisms were further detected using Western blot and real-time PCR assays. The combination of miR-4800-3p and STK25 was verified by the dual-luciferase and RNA pulldown assays. The influences of miR-4800-3p on the growth and epithelial–mesenchymal transformation (EMT) of implanted tumors were tested in vivo and further confirmed by Western blot.ResultsThe miR-4800-3p expression was highly expressed in both exosomes derived by TGF-β1-treated HCC cells and the serum exosomes of HCC patients. In the cases of treatment with both Huh7-derived exosomes, the level of miR-4800-3p expression was highest, and the treatment of TGF-β1 could greatly promote the proliferation, stemness, migration, and invasion of HCC cells via upregulating the markers of stemness and EMT, including CD44, CD133, OCT4, N-cadherin, E-cadherin, and ZO-1. Similar results could be obtained when miR-4800-3p was overexpressed in HCC cells. Furthermore, downregulation of STK25 expression, a direct target gene of miR-4800-3p, could greatly rescue the malignant biological behaviors aggravated by overexpression of miR-4800-3p. This was achieved by suppressing the expression of CD44, CD133, OCT4, N-cadherin, and PCNA and activating the Hippo pathway while increasing E-cadherin and ZO-1. Similar results were also obtained in vivo that knockdown of miR-4800-3p expression suppressed tumor growth induced by Huh7-derived exosomes by mediating the EMT markers and the Hippo signaling pathway.ConclusionExosomal miR-4800-3p could accelerate HCC development by regulating the Hippo signal by targeting STK25, which could be used as a new therapeutic target for HCC treatment.
Deep Learning Model for Predicting the Pathological Complete Response to Neoadjuvant Chemoradiotherapy of Locally Advanced Rectal Cancer
Authors: Lou Xiaoying , Zhou Niyun , Feng Lili , Li Zhenhui , Fang Yuqi , Fan Xinjuan , Ling Yihong , Liu Hailing , Zou Xuan , Wang Jing , Huang Junzhou , Yun Jingping , Yao Jianhua , Huang Yan 
Published: June 2022

ObjectiveThis study aimed to develop an artificial intelligence model for predicting the pathological complete response (pCR) to neoadjuvant chemoradiotherapy (nCRT) of locally advanced rectal cancer (LARC) using digital pathological images.BackgroundnCRT followed by total mesorectal excision (TME) is a standard treatment strategy for patients with LARC. Predicting the PCR to nCRT of LARC remine difficulty.Methods842 LARC patients treated with standard nCRT from three medical centers were retrospectively recruited and subgrouped into the training, testing and external validation sets. Treatment response was classified as pCR and non-pCR based on the pathological diagnosis after surgery as the ground truth. The hematoxylin &amp; eosin (H&amp;E)-stained biopsy slides were manually annotated and used to develop a deep pathological complete response (DeepPCR) prediction model by deep learning.ResultsThe proposed DeepPCR model achieved an AUC-ROC of 0.710 (95% CI: 0.595, 0.808) in the testing cohort. Similarly, in the external validation cohort, the DeepPCR model achieved an AUC-ROC of 0.723 (95% CI: 0.591, 0.844). The sensitivity and specificity of the DeepPCR model were 72.6% and 46.9% in the testing set and 72.5% and 62.7% in the external validation cohort, respectively. Multivariate logistic regression analysis showed that the DeepPCR model was an independent predictive factor of nCRT (P=0.008 and P=0.004 for the testing set and external validation set, respectively).ConclusionsThe DeepPCR model showed high accuracy in predicting pCR and served as an independent predictive factor for pCR. The model can be used to assist in clinical treatment decision making before surgery.
Relationship Between Thyroid Autoantibodies and Recurrence of Papillary Thyroid Carcinoma in Children and Adolescents
Authors: Huang Dongmei , Zhi Jingtai , Zhang Jinming , Qin Xuan , Zhao Jingzhu , Zheng Xiangqian , Gao Ming 
Published: June 2022

BackgroundNumerous studies reported connection between papillary thyroid carcinoma (PTC) and thyroid autoantibody in adults, but few of them have investigated whether there is a similar link in children and adolescents. The purpose of this research was to explore the relationship between clinicopathological features, prognosis and preoperative thyroid peroxidase antibody (TPOAb) as well as thyroglobulin antibody (TgAb) status in children and adolescents with PTC.MethodsThis study retrospectively reviewed 179 patients of PTC who underwent a thyroidectomy from January 2000 to June 2021 at Tianjin Medical University Cancer Hospital. We compared preoperative TgAb and TPOAb status with the clinicopathological features and prognosis of children and adolescents with PTC in different age groups.ResultsPatients with positive preoperative TPOAb and TgAb had lower recurrence rate in the younger group (P = 0.006, 0.047, respectively). Patients with positive TPOAb preoperatively had normal level of preoperative Tg and less cervical LNM than patients with negative TPOAb in children and adolescents (P &lt; 0.05). Positive TPOAb preoperatively of PTC patients had a longer median DFS (113.4 months) than negative TPOAb (64.9 months) (P = 0.009, log-rank). Univariate analyses showed age, maximal tumor size, T stage, multifocality, lateral LNM and N staging were predictors for cancer recurrence in children and adolescents (P&lt;0.05). Cox regression analysis found younger age (HR 0.224, P &lt; 0.001), lateral LNM (HR 0.137, P = 0.010), N stage (HR 30.356, P &lt; 0.001) were independent risk factors for recurrence.ConclusionsOur study found that presence of preoperative TPOAb and TgAb could serve as novel prognostic factors for predicting recurrence of PTC in children.