bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deficient or R273H and R248W Mutations of p53 Promote Chemoresistance to 5-FU via TCF21/CD44 Axis-Mediated Enhanced Stemness in Colorectal Carcinoma
Authors: Gao Xiaolei , Zheng Xuan , Zhang Yixin , Dong Liying , Sun Liangjie , Zhao Na , Ding Chong , Ma Zeyun , Wang Yixiang 
Published: January 2022

Background: p53 mutations are highly frequent in various human cancers and are reported to contribute to tumor malignance and chemoresistance. In this study, we explored the mechanism by which mutant p53 promotes carcinogenesis and chemoresistance and provided novel insights into cancer therapy.Materials and methods: A total of 409 patients with colorectal carcinoma from TCGA database were subdivided into two groups according to the p53 status, namely, mutant p53 and wild-type p53, following with GSEA analysis. The differences of the clinicopathologic index were also analyzed. Two HCT116 cell lines containing hot spots at codons R273H and R248W of p53 were constructed based on HCT116 with knockout p53, respectively. Cell viability, mobility, clonogenesis, and stemness were detected by CCK8, transwell migration and invasion, colonogenic, and sphere formation assays. Resistance to 5-FU was examined by live-dead staining and flow cytometry. qPCR, Western blot, and luciferase reporter assay were performed to identify that deficient or mutant p53 promoted chemoresistance of the colorectal carcinoma cell line HCT116 through the TCF21/CD44 signaling pathway, with the following rescue assays by overexpression of TCF21 and knockdown of CD44.Results: Patients with recurrence harbor a higher frequency of mutant p53 than those without recurrence (p &lt; 0.05). The mutant p53 group developed a larger tumor than the wild-type one. GSEA analysis showed that oncogenic signatures were enriched in the mutant p53 group. Extracellular assays showed that cancer cells with deficient or mutant p53 (R273H and R248W, respectively) promoted colon cancer cell growth, migration, invasion, and stemness. The mutant cancer cells were also observed to be significantly resistant to 5-FU. Xenografts also confirmed that HCT116 cells harboring deficient or mutant p53 promoted cancer growth and 5-FU tolerance. Luciferase reporter assay showed that deficient or mutant p53 R237H and R248W endowed cancer cells with chemoresistance by activating CD44 via repressing the nuclear transcription factor TCF21 expression. Overexpression of TCF21 or knockdown of CD44 could rescue the sensitivity to 5-FU in deficient and mutant p53 HCT116 cell lines.Conclusion: Our results, for the first time, reveal a novel deficient or mutant p53/TCF21/CD44 signaling pathway which promotes chemoresistance in colorectal carcinoma. The axis could be an effective therapeutic strategy against deficient- or mutant p53-driven chemoresistance.
The Role of Fatty Acid Signaling in Islet Beta-Cell Adaptation to Normal Pregnancy
Authors: Kim Jee-Hye , Delghingaro-Augusto Viviane , Chan Jeng Yie , Laybutt D. Ross , Proietto Joseph , Nolan Christopher J. 
Published: January 2022

BackgroundMaintenance of a normal fetal nutrient supply requires major adaptations in maternal metabolic physiology, including of the islet beta-cell. The role of lipid signaling processes in the mechanisms of islet beta-cell adaptation to pregnancy has been minimally investigated.ObjectiveTo determine the effects of pregnancy on islet fatty acid (FA) metabolic partitioning and FA augmentation of glucose-stimulated insulin secretion (GSIS).MethodsAge matched virgin, early pregnant (gestational day-11, G11) and late pregnant (G19) Sprague-Dawley rats were studied. Fasted and fed state biochemistry, oral glucose tolerance tests (OGTT), and fasted and post-OGTT liver glycogen, were determined to assess in vivo metabolic characteristics. In isolated islets, FA (BSA-bound palmitate 0.25 mmol/l) augmentation of GSIS, FA partitioning into esterification and oxidation processes using metabolic tracer techniques, lipolysis by glycerol release, triacylglycerols (TG) content, and the expression of key beta-cell genes were determined.ResultsPlasma glucose in pregnancy was lower, including during the OGTT (glucose area under the curve 0-120 min (AUC0-120); 655±24 versus 849±13 mmol.l-1.min; G19 vs virgin; P&lt;0.0001), with plasma insulin concentrations equivalent to those of virgin rats (insulin AUC0-120; 97±7 versus 83±7 ng.ml-1.min; G19 vs virgin; not significant). Liver glycogen was depleted in fasted G19 rats with full recovery after oral glucose. Serum TG increased during pregnancy (4.4±0.4, 6.7±0.5; 17.1±1.5 mmol/l; virgin, G11, G19, P&lt;0.0001), and islet TG content decreased (147±42, 172±27, 73±13 ng/µg protein; virgin, G11, G19; P&lt;0.01). GSIS in isolated islets was increased in G19 compared to virgin rats, and this effect was augmented in the presence of FA. FA esterification into phospholipids, monoacylglycerols and TG were increased, whereas FA oxidation was reduced, in islets of pregnant compared to virgin rats, with variable effects on lipolysis dependent on gestational age. Expression of Ppargc1a, a key regulator of mitochondrial metabolism, was reduced by 51% in G11 and 64% in G19 pregnant rat islets compared to virgin rat islets (P&lt;0.001).ConclusionA lowered set-point for islet and hepatic glucose homeostasis in the pregnant rat has been confirmed. Islet adaptation to pregnancy includes increased FA esterification, reduced FA oxidation, and enhanced FA augmentation of glucose-stimulated insulin secretion.
Exploration of the Molecular Mechanism of Polygonati Rhizoma in the Treatment of Osteoporosis Based on Network Pharmacology and Molecular Docking
Authors: Zhao Jinlong , Lin Fangzheng , Liang Guihong , Han Yanhong , Xu Nanjun , Pan Jianke , Luo Minghui , Yang Weiyi , Zeng Lingfeng 
Published: January 2022

ObjectiveTo explore the effective components and mechanism of Polygonati Rhizoma (PR) in the treatment of osteoporosis (OP) based on network pharmacology and molecular docking methods.MethodsThe effective components and predicted targets of PR were obtained through the Traditional Chinese Medicine Systems Pharmacology and Analysis Platform (TCMSP) database. The disease database was used to screen the disease targets of OP. The obtained key targets were uploaded to the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database for protein-protein interaction (PPI) network analysis. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of key targets. Analysis and docking verification of chemical effective drug components and key targets were performed with IGEMDOCK software.ResultsA total of 12 chemically active components, 84 drug target proteins and 84 common targets related to drugs and OP were obtained. Key targets such as JUN, TP53, AKT1, ESR1, MAPK14, AR and CASP3 were identified through PPI network analysis. The results of enrichment analysis showed that the potential core drug components regulate the HIF-1 signaling pathway, PI3K-Akt signaling pathway, estrogen signaling pathway and other pathways by intervening in biological processes such as cell proliferation and apoptosis and estrogen response regulation, with an anti-OP pharmacological role. The results of molecular docking showed that the key targets in the regulatory network have high binding activity to related active components.ConclusionsPR may regulate OP by regulating core target genes, such as JUN, TP53, AKT1, ESR1, AR and CASP3, and acting on multiple key pathways, such as the HIF-1 signaling pathway, PI3K-Akt signaling pathway, and estrogen signaling pathway.
The Influence of Humidity on Electron Transport Parameters and Insulation Performance of Air
Authors: An Yunzhu , Su Menghan , Hu Yuanchao , Hu Shangmao , Huang Tao , He Baina , Yang Minghao , Yin Kaiqiang , Lin Yitong 
Published: January 2022

The environmental conditions affect the external insulation performance of power equipment. In order to study the physical characteristics of air discharge, the microscopic process of electron–molecule collision in the air based on the Boltzmann equation has been studied in this paper. The influence of humidity on the air gap insulation performance was also analyzed. The calculation results show that with the temperature 300 K and the pressure 1.0 atm, the electron energy distribution function and electron transport parameters varied with the air relative humidity. As the air relative humidity is increased by each 30%, the average electron energy decreases by about 0.2 eV, the reduced electron mobility decreases by about 0.25 × 1023 [1/(V·m·s)], the reduced electron diffusion coefficient decreases by about 0.2 × 1024 [1/(m s)], and the effective ionization coefficient decreases by about 4 × 10−24 m2. As the air relative humidity increases from 0% to 60%, the critical breakdown electric field increases by 1.22 kV/cm.
Multi-Omics Analysis Based on Genomic Instability for Prognostic Prediction in Lower-Grade Glioma
Authors: Cao Yudong , Zhu Hecheng , Liu Weidong , Wang Lei , Yin Wen , Tan Jun , Zhou Quanwei , Xin Zhaoqi , Huang Hailong , Xie Dongcheng , Zhao Ming , Jiang Xingjun , Peng Jiahui , Ren Caiping 
Published: January 2022

Background: Lower-grade gliomas (LGGs) are a heterogeneous set of gliomas. One of the primary sources of glioma heterogeneity is genomic instability, a novel characteristic of cancer. It has been reported that long noncoding RNAs (lncRNAs) play an essential role in regulating genomic stability. However, the potential relationship between genomic instability and lncRNA in LGGs and its prognostic value is unclear.Methods: In this study, the LGG samples from The Cancer Genome Atlas (TCGA) were divided into two clusters by integrating the lncRNA expression profile and somatic mutation data using hierarchical clustering. Then, with the differentially expressed lncRNAs between these two clusters, we identified genomic instability-related lncRNAs (GInLncRNAs) in the LGG samples and analyzed their potential function and pathway by co-expression network. Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were conducted to establish a GInLncRNA prognostic signature (GInLncSig), which was assessed by internal and external verification, correlation analysis with somatic mutation, independent prognostic analysis, clinical stratification analysis, and model comparisons. We also established a nomogram to predict the prognosis more accurately. Finally, we performed multi-omics-based analyses to explore the relationship between risk scores and multi-omics data, including immune characteristics, N6-methyladenosine (m6A), stemness index, drug sensitivity, and gene set enrichment analysis (GSEA).Results: We identified 52 GInLncRNAs and screened five from them to construct the GInLncSig model (CRNDE, AC025171.5, AL390755.1, AL049749.1, and TGFB2-AS1), which could independently and accurately predict the outcome of patients with LGG. The GInLncSig model was significantly associated with somatic mutation and outperformed other published signatures. GSEA revealed that metabolic pathways, immune pathways, and cancer pathways were enriched in the high-risk group. Multi-omics-based analyses revealed that T-cell functions, m6A statuses, and stemness characteristics were significantly disparate between two risk subgroups, and immune checkpoints such as PD-L1, PDCD1LG2, and HAVCR2 were significantly highly expressed in the high-risk group. The expression of GInLncSig prognostic genes dramatically correlated with the sensitivity of tumor cells to chemotherapy drugs.Conclusion: A novel signature composed of five GInLncRNAs can be utilized to predict prognosis and impact the immune status, m6A status, and stemness characteristics in LGG. Furthermore, these lncRNAs may be potential and alternative therapeutic targets.
Prediction of the RNA Tertiary Structure Based on a Random Sampling Strategy and Parallel Mechanism
Authors: Liu Zhendong , Yang Yurong , Li Dongyan , Lv Xinrong , Chen Xi , Dai Qionghai 
Published: January 2022

Background: Macromolecule structure prediction remains a fundamental challenge of bioinformatics. Over the past several decades, the Rosetta framework has provided solutions to diverse challenges in computational biology. However, it is challenging to model RNA tertiary structures effectively when the de novo modeling of RNA involves solving a well-defined small puzzle.Methods: In this study, we introduce a stepwise Monte Carlo parallelization (SMCP) algorithm for RNA tertiary structure prediction. Millions of conformations were randomly searched using the Monte Carlo algorithm and stepwise ansatz hypothesis, and SMCP uses a parallel mechanism for efficient sampling. Moreover, to achieve better prediction accuracy and completeness, we judged and processed the modeling results.Results: A benchmark of nine single-stranded RNA loops drawn from riboswitches establishes the general ability of the algorithm to model RNA with high accuracy and integrity, including six motifs that cannot be solved by knowledge mining–based modeling algorithms. Experimental results show that the modeling accuracy of the SMCP algorithm is up to 0.14 Å, and the modeling integrity on this benchmark is extremely high.Conclusion: SMCP is an ab initio modeling algorithm that substantially outperforms previous algorithms in the Rosetta framework, especially in improving the accuracy and completeness of the model. It is expected that the work will provide new research ideas for macromolecular structure prediction in the future. In addition, this work will provide theoretical basis for the development of the biomedical field.
Effect of Annealing on the Magnetic Properties of FeCoNiCuNbSiB Soft Magnetic Alloys
Authors: Li Z. , Yao K. F. , Liu T. C. , Li X. , Wang S. 
Published: January 2022

A series of nanocrystalline soft magnetic alloys with nominal compositions of Fe66.8-xCo10NixCu0.8Nb2.9Si11.5B8 (x = 1–15 at%) were developed and studied. Effects of annealing on the soft magnetic properties, crystallization behavior, and domain structure were investigated. The alloys with higher Ni content were prone to exhibit stronger magnetic anisotropy. The Fe66.8Co10Ni10Cu0.8Nb2.9Si11.5B8 alloy exhibited excellent soft magnetic properties, including the low permeability of 2000, low coercivity of about 0.6 A/m, and low remanence of 2.4 mT, together with a temperature gap of 128 K between two crystallization onset temperatures. It has been found that the Ni content and the annealing process possess significant effects on the soft magnetic property of the nanocrystalline alloys. It shows that the developed Fe66.8Co10Ni10Cu0.8Nb2.9Si11.5B8 nanocrystalline alloy exhibits great potentials for applying in the field of common mode chokes or current transformers, due to its ability to resist the direct current.
Improvement of Calcium Aluminate Cement Containing Blast Furnace Slag at 50°C and 315°C
Authors: Zhiqiang Wu , Hengjie Liu , Xiong Qu , Guangai Wu , Xuesong Xing , Xiaowei Cheng , Xiucheng Ni 
Published: January 2022

During the thermal recovery of heavy oil thermal recovery wells, improving the mechanical properties and integrity of the cement ring is of great significance for the safe and efficient exploitation of heavy oil resources. This paper studies the relative properties of calcium aluminate cement and three kinds of slags under the conditions of 50°C × 1.01 MPa and 315°C × 20.7 MPa. CAC-slag composite material performance was evaluated using the cement paste compressive strength and permeability tests to study the physical properties of CAC with blast furnace slag. X-ray diffraction analysis, scanning electron microscopy (SEM), and thermal analysis (DSC/TG) were carried out to investigate the mineralogical composition of CAC with blast furnace slag. Results show that adding blast furnace slag did not affect the performance of cement slurry. Moreover, C2ASH8 curing occurred at low temperature, the microstructure of CAC paste was compact, and the permeability resistance was improved, thus improving the low-temperature properties of neat CAC. When cured at a high temperature, the CAC paste was mainly hydrated with C3ASH4 and AlO(OH), which had a well-developed crystal structure. Adding blast furnace slag can improve the CAC resistance to high temperature.
Vitreomacular Interface Abnormalities in Myopic Foveoschisis: Correlation With Morphological Features and Outcome of Vitrectomy
Authors: Fang Dong , Wang Li , Chen Lu , Liang Jia , Li Kunke , Mao Xingxing , Xie Ting , Zhang Shaochong 
Published: January 2022

Purpose: To compare the morphologic characteristics and response to surgery of myopic foveoschisis (MF) with different patterns of vitreomacular interface abnormalities (VMIAs).Methods: In this observational case series, 158 eyes of 121 MF patients with epiretinal membrane (ERM) or vitreomacular traction (VMT) based on optical coherence tomography (OCT) were enrolled. All the eyes were divided into two groups by the pattern of VMIAs: ERM and VMT group. Sixty-one eyes underwent pars plana vitrectomy (PPV) and were followed up for at least 6 months. The morphologic characteristics based on OCT and the surgical outcome were evaluated.Outcome: ERM and VMT were found in 47.47 and 52.53% of the cases, respectively. A higher rate of foveal detachment (61.4 vs. 26.7%; p &lt; 0.001) and a higher rate of outer lamellar macular hole (45.8 vs. 21.3%; p = 0.001) were detected in the eyes with VMT compared with those with ERM. In contrast, a lower rate of inner lamellar macular hole (28.9 vs. 60.0%; p = 0.001) was detected in the eyes with VMT compared with those with ERM. The disruption of the external limiting membrane (ELM) was more common in the eyes with VMT than in those with ERM (45.8 vs. 21.3%; p = 0.001). PPV was performed in 61 eyes with a mean follow-up time of 23.55 ± 19.92 months. After surgery, anatomical resolution was achieved in 51 eyes (83.6%). At the final visit, the mean central foveal thickness (CFT) decreased significantly from 547.83 to 118.74 μm, and the mean LogMAR BCVA improved significantly from 0.92 to 0.57. The VMT group was associated with a higher proportion of eyes with visual acuity improvement postoperatively (p = 0.02) and had more a decrease of CFT (P = 0.007) compared with the ERM group.Conclusion: In the eyes with MF, outer retinal lesions occurred more frequently in the eyes with VMT, whereas inner retinal lesions occurred more frequently in the eyes with ERM. Tangential force generated by ERM may act as a causative factor for the inner retinal lesions in MF, and inward-directed force resulting from VMT may act as a causative factor for outer retinal lesions in MF.
Clinical Characteristics and Follow-Up of Seizures in Children With Anti-NMDAR Encephalitis
Authors: Zhang Jianzhao , Sun Jing , Zheng Ping , Feng Shuo , Yi Xiaoli , Ren Haitao , Chen Qian 
Published: January 2022

Objective: To analyze the seizure characteristics of children with anti-NMDAR encephalitis.Methods: This was a retrospective analysis of 50 children with anti-NMDAR encephalitis between July 1, 2013, and July 1, 2019.Results: Fifty children with anti-NMDAR encephalitis were included in this study, of which 34 (68.0%) had seizures. During the follow-up, three patients with anti-NMDAR encephalitis secondary to herpes simplex virus encephalitis had persistent seizures. The average duration of seizures in the remaining patients was 14.6 days (range 1–47 days). Compared to patients without seizures, those with seizures were more likely to experience consciousness disturbances (p = 0.008) and epileptic form discharge on electroencephalograms (p = 0.002). The Glasgow coma scale scores (p = 0.014), and Rankin scale scores (p = 0.019) were also different. The cranial MRI findings of children were reviewed, and clinical characteristics were compared between children without cranial lesions and those with lesions in the limbic system and neocortex. Compared to children in the non-lesion group, children with lesions in the limbic system and neocortex had a higher incidence of status epilepticus. Further, children in the limbic system and neocortical lesions groups were more likely to be taking anti-seizure medications (ASMs) and receive second-line drugs.Conclusion: Long-term oral ASMs are not recommended for most children with anti-NMDAR encephalitis. Children with involvement of the limbic system and neocortex are prone to status epilepticus, and sequelae of epilepsy may remain when the neocortex is involved.
Vertebrobasilar Junction Angle Over 90°: A Potential Imaging Marker Associated With Vertebrobasilar Atherosclerosis
Authors: Li Jia , Yang Wen-Jie , Zheng Lu , Du Heng , Chu Winnie Chiu-Wing , Leung Thomas Wai-Hong , Chen Xiang-Yan 
Published: January 2022

Objective: Whether the cerebral vascular variations play an important role in the progression of intracranial atherosclerosis is yet largely unclear. We aimed to investigate the relationship between the magnitude of the vertebrobasilar junction (VBJ) angle and the imaging features of vertebrobasilar artery atherosclerosis.Methods: Adult patients with acute ischemic stroke or transient ischemic attack undergoing a 3.0-tesla vessel wall magnetic resonance imaging (VW-MRI) scanning were consecutively included. Imaging features of vertebrobasilar artery atherosclerosis were assessed on the reconstructed short axis of VW-MRI at the most stenotic site. The VBJ angle degree was measured on magnetic resonance angiography and classified into the angle ≥90° or &lt;90°.Results: Among 68 patients (mean age = 63.5 ± 9.4 years old; 63.2% were male) with vertebrobasilar atherosclerosis, 33 had a VBJ angle ≥90° and 35 had a VBJ angle &lt;90°. Compared to the vertebrobasilar plaques with VBJ angle &lt;90°, those with VBJ angle ≥90° had a heavier plaque burden (84.35 vs. 70.58%, p &lt; 0.001) and higher prevalence of intraplaque hemorrhage (17.1 vs. 3.3%, p = 0.01). In the regression analyses, the VBJ angle ≥90° was also robustly associated with plaque burden (odds ratio, 1.11; 95% confidential interval, 1.043–1.18; p = 0.001) and intraplaque hemorrhage (odds ratio, 5.776; 95% confidential interval, 1.095–30.46; p = 0.039) of vertebrobasilar atherosclerosis.Conclusion: The VBJ angle over 90° might aggravate the vessel wall condition of the atherosclerotic vertebrobasilar arteries, which might serve as a potential risk factor for vertebrobasilar atherosclerosis.