bluuebunny/crossref_metadata_2025 huggingface dataset:
lncRNA OIP5-AS1 Suppresses Cell Proliferation and Invasion of Endometrial Cancer by Regulating PTEN/AKT via Sponging miR-200c-3p
Authors: Liu Yun , Cai Xiaohui , Cai Yixuan , Chang Yue
Published: July 2021

Background. Endometrial carcinoma (EC) is one of the major gynecologic malignancy cancers affecting females with dismal prognosis and high mortality around the world. Numerous studies have proven that an aberrant level of long noncoding RNAs is present in many endometrial cancer patients, while the underlying molecular mechanism remains unclear. Method. The expression levels of lncRNA OIP5-AS1, miR200c-3p, and PTEN were measured by a quantitative real-time polymerase chain reaction in endometrial cancer tissue and endometrial cancer cells. CCK8 assay, wound-healing assay, and cell colony formation were applied to evaluate cell proliferation, cell migration, and cell colony formation ability. Cell cycle and cell apoptosis were detected by flow cytometry. The interactions between OIP5-AS1, miR200c-3p, and PTEN were explored by luciferase activity. Results. In the present study, we demonstrated that long noncoding RNA OIP5-AS1 was significantly reduced in EC tissue compared with normal tissue. The lower expression level of OIP5-AS1 was also confirmed in four kinds of EC cell lines compared with the normal endometrial cell line. Gain- and loss-of-function of experiments indicated that upregulation of OIP5-AS1 could inhibit the proliferation, migration, and invasion of EC cells in vitro. Meanwhile, overexpression of OIP5-AS1 could also suppress the growth of tumor in the xenograft model. Moreover, further study revealed that miR-200c-3p could bind to OIP5-AS1, and the loss function of miR-200c-3p could reverse the elevated OIP5-AS1’s inhibitory effect on the progression of EC. Furthermore, we found that downregulation of miR-200c-3p was inversely correlated with PTEN expression in EC cells. Reduced OIP5-AS1 could lead to the accumulation of miR-200c-3p, which could induce the upregulation of PTEN indirectly. Conclusion. Our study demonstrated a novel molecular mechanism that lncRNA OIP5-AS1 could modulate the progression of EC by combining competitively with miR-200c-3p to control the PTEN/AKT pathway in EC cells, which might supply important information for developing novel therapeutic strategies for EC patients.
A Novel Expression Signature from the Perspective of Mesenchymal-Epithelial Transition for Hepatocellular Carcinoma with Regard to Prognosis, Clinicopathological Features, Immune Cell Infiltration, Chemotherapeutic Efficacy, and Immunosuppressive Molecules
Authors: Xu Lijun , Zheng Qing
Published: July 2021

Purpose. Mesenchymal-epithelial transition (MET), a reverse biological process to epithelial-mesenchymal transition (EMT), is involved in tumor metastasis and invasion. However, the role of MET-related genes (MRGs) in hepatocellular carcinoma (HCC) prognosis remains unclear. Methods. In this research, we obtained MRGs data and clinical information from public databases. In the TCGA dataset, a prognostic signature for HCC was constructed by the least absolute shrinkage and selection operator (LASSO) method and externally verified using the ICGC dataset. Results. There were 148 differentially expressed MRGs (DEMRGs), out of which 37 MRGs were found associated with overall survival (OS) in the univariate Cox analysis. A novel signature integrating of 5 MRGs was constructed, which split patients into high- and low-risk groups. Kaplan–Meier analysis revealed that high-risk patients had unfavorable OS than those low-risk counterparts. Receiver operating characteristic curve (ROC) showed great performance of this signature in predictive ability. Multivariate Cox analysis confirmed that this signature could independently predict HCC prognosis. The analysis of immune cell infiltration demonstrated that immune status varied differently between high- and low-risk groups. The analysis of clinicopathological characteristics suggested that tumor grade, clinical stage, and T stage were different between risk groups. The analysis between this signature and chemotherapeutic efficacy and immunosuppressive molecules indicated that this signature could serve as a promising predictor. Conclusions. In conclusion, we constructed and verified a novel signature from the perspective of MET, which was significantly associated with HCC prognosis, clinicopathological features, immune status, chemotherapeutic efficacy, and immunosuppressive biomarkers.
Further Results about Seeking for the Exact Solutions of the Nonlinear

2
+
1

-Dimensional Jaulent-Miodek Equation
Authors: Hu Jingsen , Qi Jianming
Published: July 2021

Nonlinear science is a great revolution of modern natural science. As a result of its rise, the various branches of subjects characterized by nonlinearity have been developed vigorously. In particular, more attention to acquiring the exact solutions of a wide variety of nonlinear equations has been paid by people. In this paper, three methods for solving the exact solutions of the nonlinear

2
+
1

-dimensional Jaulent-Miodek equation are introduced in detail. First of all, the exact solutions of this nonlinear equation are obtained by using the exp

−
ϕ

z

-expansion method,

tanh

method, and sine-cosine method. Secondly, the relevant results are verified and simulated by using Maple software. Finally, the advantages and disadvantages of the above three methods listed in the paper are analyzed, and the conclusion was drawn by us. These methods are straightforward and concise in very easier ways.
AngioSuite‐Assisted Volume Calculation and Coil Use Prediction in the Endovascular Treatment of Tiny Volume Intracranial Aneurysms
Authors: Du Zhihua , Lv Bin , Cao Xiangyu , Liu Xinfeng , Zhang Rongju , Su Hui , Wang Jun
Published: July 2021

Background and Purpose. Ruptured tiny volume intracranial aneurysms (TVIAs) are associated with high risk of intraprocedural perforation. Aneurysm volume measuring is important for treatment planning and packing density calculation. We aim to assess the ability of the AngioSuite software in calculating TVIAs and guiding the selection of suitable coil. Methods. Thirty‐three consecutive patients with 34 TVIAs were prospectively recruited and treated with endovascular techniques. The volume of TVIAs and the required length of coils were calculated by the AngioSuite software before embolization. The treatment efficacy of TVIAs was assessed using the Raymond scale (Rs) and the modified Rankin scale (mRs). Results. Of the 34 aneurysms with an average volume of 7.16 mm3, 13 aneurysms were treated with sole coil embolization, 19 by stent‐assisted embolization, and 2 by balloon‐assisted embolization. The average coil length was 5.32 cm, and the average packing density was 41.21%. The immediate DSA showed that total occlusion (Rs = 1) was achieved in 15 aneurysms, subtotal (Rs = 2) in 9, and partial (Rs = 3) in 11. Total occlusion was achieved in 30 aneurysms and subtotal in the other 4 aneurysms at 6‐month follow‐up. Baseline volume and diameter of aneurysms were significantly correlated with the coil length (r = 0.801, P < 0.001; r = 0.711, P < 0.001). Conclusions. Coil embolization of TVIAs was easy to achieve high packing density. According to the data from AngioSuite, relative few coils can increase the safety in procedure and stenting may reduce risk of aneurysmal recurrence.
Clinical Effect of Iodine-125 Seed Implantation in Patients with Primary Liver Cancer and Its Effect on Th1/Th2 Cells in Peripheral Blood
Authors: Chen Xiaoyan , Zhu Fan , Wang Bin , Zhou Yu , Xiong Hao , Fan Tao , Ke Wenjie
Published: July 2021

Objective. To investigate the clinical effect of iodine-125 seed implantation combined with chemotherapy in patients with primary liver cancer and the effect on peripheral blood Th1/Th2 cells. Methods. A total of 136 patients with primary liver cancer from April 2017 to June 2018 were selected as subjects and randomly divided into the control group and observation group with 68 cases in each group. The control group was treated with chemotherapy, and the observation group was treated with iodine-125 seed implantation on the basis of the control group. After 3 months of treatment, the curative effect was investigated. Serum tumor markers, peripheral blood Th1/Th2 cells, and side effects and recurrence rate were compared between the two groups. Results. The levels of serum tumor markers in both groups at 3 months after treatment were lower than before treatment (

P
<
0.05

). Three months after treatment, the levels of tumor markers AFP, AFP-L3, and GP73 in the observation group were 14.61 ± 3.49 μg/L, 3.29 ± 0.41 ng/mL, and 51.24 ± 4.51 μg/L, respectively, which were lower than those in the control group, 32.53 ± 4.59 μg/L, 5.63 ± 0.63 ng/mL, and 71.52 ± 6.05 μg/L (

P
<
0.05

). At 3 months after treatment, the level of including interleukin-2 (IL-2) and tumor necrosis factor-α (TNF-α) in Th1 cells of the observation group was higher than that of the control group (

P
<
0.05

), whereas the levels of IL-4, IL-6, and IL-10 in Th2 cells were lower than those in the control group (

P
<
0.05

). There was no statistical significance in the incidence of leukopenia, thrombocytopenia, and gastrointestinal reactions between the two groups (

P
>
0.05

). The recurrence rate of the observation group at 12, 24, and 36 months after treatment was lower than that of the control group (

P
<
0.05

). Conclusion. Iodine-125 seed implantation combined with chemotherapy in patients with primary liver cancer can reduce the level of serum tumor markers, improve the level of peripheral blood Th1/Th2 cells, and reduce the recurrence rate of patients without increasing the incidence of side effects, which is worthy of promoting the application of iodine-125 seed implantation.
Advanced Oxidation Protein Products Induce G1/G0‐Phase Arrest in Ovarian Granulosa Cells via the ROS‐JNK/p38 MAPK‐p21 Pathway in Premature Ovarian Insufficiency
Authors: Zhou Xing-Yu , Zhang Jun , Li Ying , Chen Ying-Xue , Wu Xiao-Min , Li Xin , Zhang Xiao-Fei , Ma Lin-Zi , Yang Yi-Zhen , Zheng Ke-Ming , Liu Yu-Dong , Wang Zhe , Chen Shi-Ling
Published: July 2021

The mechanism underlying the role of oxidative stress and advanced oxidation protein products (AOPPs) in the aetiology of premature ovarian insufficiency (POI) is poorly understood. Here, we investigated the plasma AOPP level in POI patients and the effects of AOPPs on granulosa cells both in vitro and in vivo. KGN cells were treated with different AOPP doses, and cell cycle distribution, intracellular reactive oxygen species (ROS), and protein expression levels were measured. Sprague–Dawley (SD) rats were treated daily with PBS, rat serum albumin, AOPP, or AOPP+ N‐acetylcysteine (NAC) for 12 weeks to explore the effect of AOPPs on ovarian function. Plasma AOPP concentrations were significantly higher in both POI and biochemical POI patients than in controls and negatively correlated with anti‐Müllerian hormone and the antral follicle count. KGN cells treated with AOPP exhibited G1/G0‐phase arrest. AOPP induced G1/G0‐phase arrest in KGN cells by activating the ROS‐c‐Jun N‐terminal kinase (JNK)/p38 mitogen‐activated protein kinase (MAPK)‐p21 pathway. Pretreatment with NAC, SP600125, SB203580, and si‐p21 blocked AOPP‐induced G1/G0‐phase arrest. In SD rats, AOPP treatment increased the proportion of atretic follicles, and NAC attenuated the adverse effects of AOPPs in the ovary. In conclusion, we provide mechanistic evidence that AOPPs may induce cell cycle arrest in granulosa cells via the ROS‐JNK/p38 MAPK‐p21 pathway and thus may be a novel biomarker of POI.
Pharmacological Preconditioning Improves the Viability and Proangiogenic Paracrine Function of Hydrogel-Encapsulated Mesenchymal Stromal Cells
Authors: Touani Francesco K. , Borie Melanie , Azzi Feryel , Trudel Dominique , Noiseux Nicolas , Der Sarkissian Shant , Lerouge Sophie
Published: July 2021

The efficacy of cell therapy is limited by low retention and survival of transplanted cells in the target tissues. In this work, we hypothesize that pharmacological preconditioning with celastrol, a natural potent antioxidant, could improve the viability and functions of mesenchymal stromal cells (MSC) encapsulated within an injectable scaffold. Bone marrow MSCs from rat (rMSC) and human (hMSC) origin were preconditioned for 1 hour with celastrol 1 μM or vehicle (DMSO 0.1%

v
/

v), then encapsulated within a chitosan-based thermosensitive hydrogel. Cell viability was compared by alamarBlue and live/dead assay. Paracrine function was studied first by quantifying the proangiogenic growth factors released, followed by assessing scratched HUVEC culture wound closure velocity and proliferation of HUVEC when cocultured with encapsulated hMSC. In vivo, the proangiogenic activity was studied by evaluating the neovessel density around the subcutaneously injected hydrogel after one week in rats. Preconditioning strongly enhanced the viability of rMSC and hMSC compared to vehicle-treated cells, with 90% and 75% survival versus 36% and 58% survival, respectively, after 7 days in complete media and 80% versus 64% survival for hMSC after 4 days in low serum media (

p
<
0.05

). Celastrol-treated cells increased quantities of proangiogenic cytokines compared to vehicle-pretreated cells, with a significant 3.0-fold and 1.8-fold increase of VEGFa and SDF-1α, respectively (

p
<
0.05

). The enhanced paracrine function of preconditioned MSC was demonstrated by accelerated growth and wound closure velocity of injured HUVEC monolayer (

p
<
0.05

) in vitro. Moreover, celastrol-treated cells, but not vehicle-treated cells, led to a significant increase of neovessel density in the peri-implant region after one week in vivo compared to the control (blank hydrogel). These results suggest that combining cell pretreatment with celastrol and encapsulation in hydrogel could potentiate MSC therapy for many diseases, benefiting particularly ischemic diseases.
Development of Single-Longitudinal-Mode Selection Technology for Solid-State Lasers
Authors: Zhang Xuanpu , Wang Zhihan , Liu Shi , Gou Siyu , Fan Rong , Jin Duo , Bai Zhenao , Bai Zhenxu
Published: July 2021

Lasers with narrow linewidths and single frequencies are widely used in fields such as radar detection, nonlinear optics, and precision measurements. The demand for such lasers has promoted the rapid development of single-longitudinal-mode (SLM) selection technology. Here, we highlight the working principles of current mainstream SLM selection technologies and the recent advances in the field. We compare the characteristics of different SLM selection methods and list the challenges faced by these technologies.
Prolonged Maternal Separation Induces the Depression‐Like Behavior Susceptibility to Chronic Unpredictable Mild Stress Exposure in Mice
Authors: Bian Yaoyao , Ma Yanting , Ma Qian , Yang Lili , Zhu Qinmei , Li Wenlin , Meng Lingdong
Published: July 2021

Early life stress is an important determinant for developing depression later in life. It is reported that maternal separation (MS) could trigger stress sensitivity in adulthood when exposed to stress again. However, it could also result in resilience to stress‐induced depression. The conclusions are contradictory. To address this issue, C57BL/6N newborn pups were exposed to either daily short MS (MS for 15 min per day; MS15) or prolonged MS (MS for 180 min per day; MS180) from the first day postpartum (PD1) to PD21. Adult mice were then subjected to chronic unpredictable mild stress (CUMS) exposure from PD64 to PD105. The behavior tests such as the forced swimming test (FST), tail suspension test (TST), and open‐field test were performed once a week during this time. Besides, the hippocampal neurosteroids, serum stress hormones, and hippocampal monoamine neurotransmitters were measured at PD106. We found that mice in the MS180 group displayed the reduced struggling time and the increased latency to immobility in both FST and TST. However, there was no significant difference in the MS15 group. The levels of hippocampal neurosteroids (progesterone and allopregnanolone) were decreased, and the serum levels of corticosterone, corticotropin‐releasing hormone, and adrenocorticotropic hormone were overexpressed in the MS180 group. Besides, the expressions of monoamine neurotransmitters such as 5‐hydroxytryptamine and 5‐hydroxy indole acetic acid significantly decreased in the MS180 group, but not in the MS15 group. All findings revealed that prolonged MS, rather than short MS, could increase the susceptibility to depression‐like behavior when reexposed to stress in adulthood. However, future studies are warranted to identify the underlying neuromolecular mechanism of the MS experience on the susceptibility to adult stress reexposure.
Inhibition of Fatty Acid Metabolism Increases EPA and DHA Levels and Protects against Myocardial Ischaemia‐Reperfusion Injury in Zucker Rats
Authors: Kuka Janis , Makrecka-Kuka Marina , Vilks Karlis , Korzh Stanislava , Cirule Helena , Sevostjanovs Eduards , Grinberga Solveiga , Dambrova Maija , Liepinsh Edgars
Published: July 2021

Long‐chain ω‐3 polyunsaturated fatty acids (PUFAs) are known to induce cardiometabolic benefits, but the metabolic pathways of their biosynthesis ensuring sufficient bioavailability require further investigation. Here, we show that a pharmacological decrease in overall fatty acid utilization promotes an increase in the levels of PUFAs and attenuates cardiometabolic disturbances in a Zucker rat metabolic syndrome model. Metabolome analysis showed that inhibition of fatty acid utilization by methyl‐GBB increased the concentration of PUFAs but not the total fatty acid levels in plasma. Insulin sensitivity was improved, and the plasma insulin concentration was decreased. Overall, pharmacological modulation of fatty acid handling preserved cardiac glucose and pyruvate oxidation, protected mitochondrial functionality by decreasing long‐chain acylcarnitine levels, and decreased myocardial infarct size twofold. Our work shows that partial pharmacological inhibition of fatty acid oxidation is a novel approach to selectively increase the levels of PUFAs and modulate lipid handling to prevent cardiometabolic disturbances.
The Influence of the Use of Whole Grain Flour from Sprouted Wheat Grain on the Rheological and Microstructural Properties of Dough and Bread
Authors: Naumenko Natalia , Potoroko Irina , Kalinina Irina , Fatkullin Rinat , Ivanisova Eva
Published: July 2021

Whole wheat flour from sprouted wheat grain is a full-fledged raw ingredient containing essential amino acids, easily digestible sugars, and dietary fiber, with increased digestibility and enzymatic activity. The use of this raw material in the production of food products will contribute to the creation of products for a healthy diet of the population. This study is aimed at studying the possibility of using whole grain flour from sprouted wheat in the production of bread and its effect on the rheological and microstructural properties of dough and finished products. It was found that whole wheat flour from sprouted wheat grain had an even particle size and was characterized by a uniform distribution of particles over the size range (from 53 to 209 microns—

61
±
3
%

); large particles from 297 to 497 microns were present in an amount of no more than

10
±
3
%

. The replacement of 20% refined flour with whole wheat flour from sprouted wheat grain resulted in better values of the farinograph quality index (

200
±
3

 mm). The bread obtained according to this recipe had a high specific volume (

4.21
±
0.62

 mL.g-1) and optimal rheological characteristics: total deformation

13.7
±
0.3

 mm, plastic

4.3
±
0.3

 mm, and elastic

9.4
±
0.3

 mm. The study of the microstructure of dough and bread also confirmed the established dependencies. This percentage of replacement of refined flour with whole wheat flour from sprouted wheat grain can be recommended as the best for obtaining bread of good quality with high rheological characteristics.
Optimized CSMRI Algorithm-Based MRI Image Analysis in the Active Rehabilitation Method for Patients with Acute Cerebral Infarction
Authors: Zeng Chao , Chen Jing , Liu Wenbing , Liang Kang , Li Hui , Wang Jing , Li Jingge , Xu Haibo
Published: July 2021

This paper combines optimized CSMRI algorithm (CS) and magnetic resonance imaging (MRI) to shorten the scanning time of MRI image data and improve the imaging quality. At the same time, the paper applies functional magnetic resonance imaging (BOLD-fMRI) based on the principle of blood oxygen level dependence to explore the application value of the nerve function reconstruction therapy system for the rehabilitation of active and passive motor functions in patients with acute cerebral infarction. Methods. In this paper, 20 patients with acute cerebral infarction were included. The random drawing method was used to divide them into active group and passive group, each with 10 cases. Both groups were treated with conventional medication and acupuncture. The active group used the active mode of the nerve function reconstruction treatment system to guide the patients’ limb active exercise; all training in the passive group is provided by the nerve function reconstruction treatment system to passively exercise the patients’ limbs; both groups undergo BOLD-fMRI examination before treatment and after 2 weeks of treatment and observe the activated parts of the brain functional area and corresponding parts of the two groups before and after treatment. We observe the activation volume and, at the same time, the ADL score. Results. After treatment, the activation volume and ADL scores of brain functional areas in the two groups were significantly improved compared with those before treatment, and the difference was statistically significant (

P
<
0.05

). Conclusion. The combination of optimized CSMRI algorithm (CS) and magnetic resonance imaging (MRI) can be used to evaluate the early rehabilitation efficacy of patients with acute cerebral infarction and has certain guiding value for clinical treatment.
Solvent Extraction of Jatropha Oil for Biodiesel Production: Effects of Solvent-to-Solid Ratio, Particle Size, Type of Solvent, Extraction Time, and Temperature on Oil Yield
Authors: Ntalikwa Justin W.
Published: July 2021

The aim of this study was to examine the effects of solvent-to-solid ratio, particle size, extraction time, and temperature on the extraction of Jatropha oil using three organic solvents, i.e., n-hexane, petroleum ether, and ethanol. The Soxhlet extraction method was used, and the parameters were varied in the following ranges: extraction temperature of 24–80°C, extraction time of 2 to 8 h, solvent-to-solid ratio of 4 : 1 to 7 : 1, and particle size of 0.5–0.8 mm. After obtaining optimal conditions, a large volume of Jatropha oil was prepared, purified, and subjected to analysis of quality parameters. It was found that the oil content of the Jatropha curcas L. seeds used was 48.2 ± 0.12% w/w. The highest oil yield of 47.5 ± 0.11% w/w corresponding to an oil recovery of 98.6 ± 0.3% w/w was obtained with n-hexane under the following conditions: solvent-to-solid ratio of 6 : 1, particle size of 0.5–0.8 mm, extraction time of 7 h, and extraction temperature of 68°C. This was followed by that of petroleum ether (46.2 ± 0.15% w/w) and lastly by ethanol (43 ± 0.18% w/w). The quality parameters of the oil extracted compared favorably well with most of the values reported in the literature, suggesting that the oil was of good quality for biodiesel production. Environmental and safety concerns over the use of hexane pose a great challenge. Thus, ethanol, which is environmentally benign, is recommended for application. The conditions for ethanol extraction that gave high oil yield were as follows: extraction temperature of 70°C, extraction time of 7 h, solvent-to-solid ratio of 6 : 1, particle size of 0.5–0.8 mm, and oil yield of 43 ± 0.18% w/w corresponding to an oil recovery of 89.2 ± 0.4% w/w.
A Novel Multivariable MGM (1, m) Direct Prediction Model and Its Optimization
Authors: Ding Yuanping , Li Ye
Published: July 2021

With regard to the traditional MGM (1, m) model having jumping error in solving process, an MGM (1, m) direct prediction model (denoted as DMGM (1, m) model) is proposed and its solution method is put forward at first. Second, considering the inherent time development trend of system behavior sequence is ignored in the DMGM (1, m) model, the DMGM (1, m) model is optimized by introducing a time polynomial term, and the optimized model can be abbreviated as TPDMGM (1, m,

φ

) model. Subsequently, it is theoretically proved that the TPDMGM (1, m,

φ

) model can achieve mutual transformation with the traditional MGM (1, m) model and the DMGM (1, m) model by adjusting the parameter values. Finally, two case studies about predicting the deformation of foundation pit and Henan’s vehicle ownership have been carried out to validate the effectiveness of proposed models. Meanwhile, the MGM (1, m) model and Verhulst model are established for comparison. Results show that the modeling performance of four models from superior to inferior is ranked as TPDMGM (1, m,

φ

) model, DMGM (1, m) model, MGM (1, m) model, and Verhulst model, which on the one hand testifies the correctness of defect analysis of the MGM (1, m) model and on the other hand verifies that the TPDMGM (1, m,

φ

) model has advantages in predicting the system variables with mutual relation, mutual restriction, and time development trend characteristic.
Aldosterone Induces the Proliferation of Renal Tubular Epithelial Cells In Vivo but Not In Vitro
Authors: Hao Juan , Liu Lingjin , Liu Ziqian , Chen Gege , Xiong Yunzhao , Wang Xiangting , Ma Xuelian , Xu Qingyou
Published: July 2021

Objective. To investigate the proliferation effect of aldosterone on renal tubular epithelial cells in vivo and in vitro. Methods. Thirty-two male C57BL/6J mice (20–22 g) were divided randomly into four groups: sham, unilateral nephrectomy (UN), unilateral nephrectomy plus aldosterone infusion (UA), and UA plus eplerenone (UAE). The kidneys were removed 6 weeks after treatment. Expression of proliferating cell nuclear antigen (PCNA) was detected by immunohistochemistry and western blotting. Human kidney proximal tubular epithelial (HK2) and mouse distal convoluted tubule (mDCT) cell lines were stimulated by aldosterone (0, 10−9, 10−8, 10−7, and 10−6 mol/L) in vitro. Cells were collected after 3, 6, 12, 24, 36, and 48 h, and proliferation of each group detected by western blotting, flow cytometry, live imaging, and the MTT assay. In addition, mDCT cells were costimulated with a medium containing a final concentration of 161 mmol/L Na+ and different concentrations of aldosterone, and the number of cells and cellular DNA content was measured by the MTT assay and flow cytometry. Results. Aldosterone could induce a significant increase in the number of PCNA-positive cells in mouse kidneys accompanied by increased deposition of collagen fibers. Eplerenone could inhibit aldosterone-induced cell proliferation and collagen deposition. HK2 cells and mDCT cells administered different concentrations, and different times of aldosterone stimulation failed to cause cell proliferation, and costimulation of aldosterone and salt did not cause proliferation changes in mDCT cells. Conclusions. Aldosterone perfusion can induce proliferation of mouse kidney cells in vivo, and eplerenone can inhibit this change, but aldosterone stimulates HK2 cells and mDCT in vitro without causing their proliferation.
Commutators of Multilinear Calderón-Zygmund Operator on Weighted Herz-Morrey Spaces with Variable Exponents
Authors: Meng Jin , Wang Shengrong , Zhang Jing
Published: July 2021

In this paper, we acquire the boundedness of commutators generated by multilinear Calderón-Zygmund operator and BMO functions on products of weighted Herz-Morrey spaces with variable exponents.
Evaluation and Analysis of a Method to Real-Name Check Train Tickets during the COVID-19 Pandemic
Authors: Yao Jiao , Tang Qingyun , He Jiaping
Published: July 2021

COVID-19 has swept the world for more than one year. Public transport, especially railway passenger transport for long distance and extensive areas, is the most potential risk source of the pandemic. In railway passenger transport, real-name train ticket check can effectively track the propagation path of the pandemic, which is of most significance for spread prevention of COVID-19. In this study, the evaluation index system of real-name check of ticket in trains was first established, in which 22 indexes in 4 levels were included, and their weights were determined by the Method of Kantiray Weighting. Furthermore, a comprehensive evaluation model of real-name system check was proposed, in which normalized work of different indexes was done, and key factors affecting the evaluation were founded. Finally, typical data of 8 trains check were collected, and from the evaluation analysis, we can find out that most factors affecting results of real-name ticket check are attendant management, train organization level, train service, and real-name ticket check proportion, based on which corresponding countermeasures and suggestions are given oriented to short-, medium-, and long-distance trains, respectively, all of which can reduce the risk of pandemic propagation in railway system.
Metformin Increases Protein Phosphatase 2A Activity in Primary Human Skeletal Muscle Cells Derived from Lean Healthy Participants
Authors: Mestareehi Aktham , Zhang Xiangmin , Seyoum Berhane , Msallaty Zaher , Mallisho Abdullah , Burghardt Kyle Jon , Kowluru Anjaneyulu , Yi Zhengping
Published: July 2021

Context. Skeletal muscle insulin resistance is one of the primary contributors of type 2 diabetes (T2D). Metformin is the first-line drug for the treatment of T2D. The primary effects of metformin include decreasing glucose production in the liver and decreasing insulin resistance in the skeletal muscle. However, the molecular mechanism of metformin’s action in skeletal muscle is not well understood. Protein phosphatase 2A (PP2A), a major serine/threonine protein phosphatase, plays a pivotal role in cellular processes, such as signal transduction, cell proliferation, and apoptosis, and acts through dephosphorylating key signaling molecules such as AKT and AMPK. However, whether PP2A plays a role in metformin-induced insulin sensitivity improvement in human skeletal muscle cells remains to be elucidated. Objective. To investigate if PP2A plays a role in metformin-induced insulin sensitivity improvement in human skeletal muscle cells. Participants. Eight lean insulin-sensitive nondiabetic participants (4 females and 4 males; age:

21.0
±
1.0

years; BMI:

22.0
±
0.7
 
kg
/

m

2

; 2-hour OGTT:

97.0
±
6.0
 
mg
/
dl

; HbA1c:

5.3
±
0.1
%

; fasting plasma glucose:

87.0
±
2.0
 
mg
/
dl

;

M

value;

11.0
±
1.0
 
mg
/
kgBW
/
min

). Design. A hyperinsulinemic-euglycemic clamp was performed to assess insulin sensitivity in human subjects, and skeletal muscle biopsy samples were obtained. Primary human skeletal muscle cells (shown to retain metabolic characteristics of donors) were cultured from these muscle biopsies that included 8 lean insulin-sensitive participants. Cultured cells were expanded, differentiated into myotubes, and treated with 50 μM metformin for 24 hours before harvesting. PP2Ac activity was measured by a phosphatase activity assay kit (Millipore) according to the manufacturer’s protocol. Results. The results indicated that metformin significantly increased the activity of PP2A in the myotubes for all 8 lean insulin-sensitive nondiabetic participants, and the average fold increase is

1.54

±

0.11

(

P
<
0.001

). Conclusions. These results provided the first evidence that metformin can activate PP2A in human skeletal muscle cells derived from lean healthy insulin-sensitive participants and may help to understand metformin’s action in skeletal muscle in humans.
Reproduction of the Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG) Gastric Cancer Molecular Classifications and Their Association with Clinicopathological Characteristics and Overall Survival in Moroccan Patients
Authors: Nshizirungu Jean Paul , Bennis Sanae , Mellouki Ihsane , Sekal Mohammed , Benajah Dafr-Allah , Lahmidani Nada , El Bouhaddouti Hicham , Ibn Majdoub Karim , Ibrahimi Sidi Adil , Celeiro Sónia Pires , Viana-Pereira Marta , Munari Fernanda Franco , Ribeiro Guilherme Gomes , Duval Vinicius , Santana Iara , Reis Rui Manuel
Published: July 2021

Introduction. The Cancer Genome Atlas (TCGA) project and Asian Cancer Research Group (ACRG) recently categorized gastric cancer into molecular subtypes. Nevertheless, these classification systems require high cost and sophisticated molecular technologies, preventing their widespread use in the clinic. This study is aimed to generating molecular subtypes of gastric cancer using techniques available in routine diagnostic practice in a series of Moroccan gastric cancer patients. In addition, we assessed the associations between molecular subtypes, clinicopathological features, and prognosis. Methods. Ninety-seven gastric cancer cases were classified according to TCGA, ACRG, and integrated classifications using a panel of four molecular markers (EBV, MSI, E-cadherin, and p53). HER2 status and PD-L1 expression were also evaluated. These markers were analyzed using immunohistochemistry (E-cadherin, p53, HER2, and PD-L1), in situ hybridization (EBV and HER2 equivocal cases), and multiplex PCR (MSI). Results. Our results showed that the subtypes presented distinct clinicopathological features and prognosis. EBV-positive gastric cancers were found exclusively in male patients. The GS (TCGA classification), MSS/EMT (ACRG classification), and E-cadherin aberrant subtype (integrated classification) presented the Lauren diffuse histology enrichment and tended to be diagnosed at a younger age. The MSI subtype was associated with a better overall survival across all classifications (TCGA, ACRG, and integrated classification). The worst prognosis was observed in the EBV subtype (TCGA and integrated classification) and MSS/EMT subtype (ACRG classification). Discussion/Conclusion. We reported a reproducible and affordable gastric cancer subtyping algorithms that can reproduce the recently recognized TCGA, ACRG, and integrated gastric cancer classifications, using techniques available in routine diagnosis. These simplified classifications can be employed not only for molecular classification but also in predicting the prognosis of gastric cancer patients.
Two Novel Mutations Associated with Polymyxin-B Resistance in a Pandemic Lineage of Uropathogenic Escherichia coli of the Sequence Type 69
Authors: dos Santos Carla Adriana , Hernandes Rodrigo Tavanelli , Cunha Marcos Paulo Vieira , Nagamori Filipe Onishi , Gonçalves Claudia Regina , Sacchi Claudio Tavares , Tiba-Casas Monique Ribeiro , Camargo Carlos Henrique
Published: July 2021

Background: Uropathogenic Escherichia coli (UPEC) are frequent pathogens worldwide, impacting on the morbidity and economic costs associated with antimicrobial treatment. Objectives: We report two novel mutations associated with polymyxin-B resistance in an UPEC isolate collected in 2019. Methods: Isolate was submitted to antimicrobial susceptibility testing including broth microdilution for polymyxin B. Whole genome was sequenced and analyzed. Results: Polymyxin-B total inhibition occurred at 16 mg/L (resistant). UPEC isolate was assigned to the phylogroup D, serotype O117:H4, and Sequence Type 69. mcr genes were not detected, but two novel mutations in the pmrA/basS (A80S) and pmrB/basR (D149N) genes were identified. Conclusions: The occurrence of non-mcr polymyxin resistance in E. coli from extraintestinal infections underscores the need of a continuous surveillance of this evolving pathogen.
Use of the Montreal Cognitive Assessment Thai Version to Discriminate Amnestic Mild Cognitive Impairment from Alzheimer’s Disease and Healthy Controls: Machine Learning Results
Authors: Hemrungrojn Solaphat , Tangwongchai Sookjaroen , Charoenboon Thammanard , Panasawat Muthita , Supasitthumrong Thitiporn , Chaipresertsud Pisit , Maleevach Pacharaporn , Likitjaroen Yuttachai , Phanthumchinda Kammant , Maes Michael
Published: July 2021

Background: The Montreal Cognitive Assessment (MoCA) is an effective and applicable screening instrument to confirm the diagnosis of amnestic mild cognitive impairment (aMCI) from patients with Alzheimer’s disease (AD) and healthy controls (HCs). Objectives: This study aimed to determine the reliability and validity of the following: (a) Thai translation of the MoCA (MoCA-Thai) and (b) delineate the key features of aMCI based on the MoCA subdomains. Methods: This study included 60 HCs, 61 aMCI patients, and 60 AD patients. The MoCA-Thai shows adequate psychometric properties including internal consistency, concurrent validity, test-retest validity, and inter-rater reliability. Results: The MoCA-Thai may be employed as a diagnostic criterion to make the diagnosis of aMCI, whereby aMCI patients are discriminated from HC with an area under the receiver-operating characteristic (AUC-ROC) curve of 0.813 and from AD patients with an AUC-ROC curve of 0.938. The best cutoff scores of the MoCA-Thai to discriminate aMCI from HC is ≤24 and from AD > 16. Neural network analysis showed that (a) aberrations in recall was the most important feature of aMCI versus HC with impairments in language and orientation being the second and third most important features and (b) aberrations in visuospatial skills and executive functions were the most important features of AD versus aMCI and that impairments in recall, language, and orientation but not attention, concentration, and working memory, further discriminated AD from aMCI. Conclusions: The MoCA-Thai is an appropriate cognitive assessment tool to be used in the Thai population for the diagnosis of aMCI and AD.
Repeated Intravenous Thrombolysis in Patients with Recurrent Ischemic Stroke in the Vertebrobasilar Territory
Authors: Černík David , Ospalík Dušan , Šaňák Daniel , Cihlář Filip
Published: July 2021

Acute ischemic vertebrobasilar stroke (AIVBS) is usually associated with poor outcome and prognosis and in case of basilar artery occlusion (BAO) with high mortality. Intravenous thrombolysis (IVT), as a standard recanalization therapy of acute ischemic stroke (IS) within first 4.5 h, can be administrated beyond this therapeutic time window in case of symptomatic BAO. Repeated IVT is generally contraindicated in case of early recurrent IS, despite a risk of poor outcome or death after recurrent IS. The aim was to present 2 cases of repeated IVT for recurrent AIVBS and discuss specific situations where repeated IVT may be considered. Up to now, repeated IVT has been reported only in recurrent stroke in anterior circulation.
Retinal Sensitivity and Structural Changes after Focal Photocoagulation for Diabetic Macular Edema: A Multisectorial Comparison
Authors: Marques João , Marta Ana , Baptista Pedro Manuel , José Diana , Almeida Daniel , Ribeiro António , Barbosa Irene
Published: July 2021

Introduction: The hindrance of a macular laser treatment for diabetic macular edema (DME) remains unclear. Our purpose was to evaluate macular functional and structural changes after focal macular photocoagulation for DME. Methods: This is a prospective cohort study that included patients with mild diabetic retinopathy, submitted to focal macular laser treatment as monotherapy for DME. Patients underwent optical coherence tomography and microperimetry after the necessary number of treatment sessions for complete resolution of DME. Eyes were compared in each macular sector (superior, temporal, and inferior 1- to 3-mm parafoveal ring) according to the presence of laser spots. Relative sensitivity was calculated as sectorial sensitivity divided by general sensitivity. Results: Sixty-four eyes were included. In sectors submitted to focal photocoagulation, we observed a significant reduction in absolute sensitivity (−1.0 to −0.4 dB, depending on the sector analyzed) and relative sensitivity (−2.1 to −0.6%) together with a reduction in the outer nuclear layer (ONL) thickness (−8 to −3 μm). The number of laser spots correlated with both functional and structural changes. Conclusion: In macular sectors that underwent photocoagulation, we found a small reduction in retinal sensitivity together with a reduction in the corresponding ONL thickness.
The Inhibitory Effect of miR-345 on Glioma Progression Is Closely Related to circRNA-hsa_circ_0073237 and HDGF
Authors: Xu Wu , Che Dan-dan , Liu Qing , Pan Ya-wen , Lv Sheng-qing , Chen Bao-dong
Published: July 2021

Glioma is the most common primary malignant tumor of the central nervous system and has a poor prognosis. Therefore, exploring the key molecular targets is a new opportunity for basic research and clinical treatment of glioma. Previous studies found that circRNA-hsa_circ_0073237 was upregulated in gliomas. Our further analyses of the biological function and molecular mechanism of hsa_circ_0073237 showed that hsa_circ_0073237 was also upregulated in glioma cell lines and could combine with miR-345 to inhibit its expression. miR-345 was downregulated in glioma tissues and cells, and targeted to regulate the expression of hepatoma-derived growth factor (HDGF), while HDGF expression was enhanced in glioma. Hsa_circ_0073237 promoted the expression of HDGF in glioma cells by adsorbing miR-345. Hsa_circ_0073237 siRNA, miR-345, and HDGF siRNA effectively inhibited cell viability and invasion and promoted cell apoptosis. When expression of hsa_circ_0073237 and miR-345 was inhibited simultaneously, cell viability, apoptosis, and invasion did not change significantly; however, after transfection with HDGF overexpression vector, the effects of hsa_circ_0073237 siRNA and miR-345 on glioma cell viability, apoptosis, and invasion were obviously reversed. Further construction of glioma xenograft models in nude mice confirmed that the introduction of miR-345 in vivo effectively inhibited tumor growth, significantly reduced tumor diameter and weight, and obviously decreased the expression of HDGF. Therefore, hsa_circ_0073237 can regulate the biological functions of glioma cells through miR-345/HDGF, thereby affecting the progression of tumors, indicating that the hsa_circ_0073237/miR-345/HDGF pathway may be a key target for the treatment of glioma.
Produção e circulação internacionais do conhecimento sociológico: uma análise do conceito de dependência acadêmica
Authors: Braga Filho Edmar Machado
Published: July 2021

This article undertakes a theoretical discussion on the concept of academic dependence, as debated by recent literature in the field of sociology. Starting from a thematic contextualization, three different perspective of the phenomenon are analyzed: 1) as a colonial heritage; 2) as an analytical model of center-periphery; and 3) as structural heterogeneity of peripheral fields. Then, a model of analysis is elaborated, focusing on the dialogue between national fields, on the one hand, and on the international field of sociology, on the other. This article argues for relational academic dependence model, which takes into account the dynamics imposed by this interdependence
Inhibition of HIPK2 Alleviates Thoracic Aortic Disease in Mice With Progressively Severe Marfan Syndrome
Authors: Caescu Cristina I. , Hansen Jens , Crockett Brittany , Xiao Wenzhen , Arnaud Pauline , Spronck Bart , Weinberg Alan , Hashimoto Takeshi , Murtada Sae-Il , Borkar Roshan , Gallo James M. , Jondeau Guillaume , Boileau Catherine , Humphrey Jay D. , He John Cijiang , Iyengar Ravi , Ramirez Francesco
Published: July 2021

Objective:

Despite considerable research, the goal of finding nonsurgical remedies against thoracic aortic aneurysm and acute aortic dissection remains elusive. We sought to identify a novel aortic PK (protein kinase) that can be pharmacologically targeted to mitigate aneurysmal disease in a well-established mouse model of early-onset progressively severe Marfan syndrome (MFS).

Approach and Results:

Computational analyses of transcriptomic data derived from the ascending aorta of MFS mice predicted a probable association between thoracic aortic aneurysm and acute aortic dissection development and the multifunctional, stress-activated HIPK2 (homeodomain-interacting protein kinase 2). Consistent with this prediction,
Hipk2
gene inactivation significantly extended the survival of MFS mice by slowing aneurysm growth and delaying transmural rupture. HIPK2 also ranked among the top predicted PKs in computational analyses of DEGs (differentially expressed genes) in the dilated aorta of 3 MFS patients, which strengthened the clinical relevance of the experimental finding. Additional in silico analyses of the human and mouse data sets identified the TGF (transforming growth factor)-β/Smad3 signaling pathway as a potential target of HIPK2 in the MFS aorta. Chronic treatment of MFS mice with an allosteric inhibitor of HIPK2-mediated stimulation of Smad3 signaling validated this prediction by mitigating thoracic aortic aneurysm and acute aortic dissection pathology and partially improving aortic material stiffness.

Conclusions:

HIPK2 is a previously unrecognized determinant of aneurysmal disease and an attractive new target for antithoracic aortic aneurysm and acute aortic dissection multidrug therapy.
HE4 Predicts Progressive Fibrosis and Cardiovascular Events in Patients With Dilated Cardiomyopathy
Authors: Yamamoto Masahiro , Hanatani Shinsuke , Araki Satoshi , Izumiya Yasuhiro , Yamada Toshihiro , Nakanishi Nobuhiro , Ishida Toshifumi , Yamamura Satoru , Kimura Yuichi , Arima Yuichiro , Nakamura Taishi , Takashio Seiji , Yamamoto Eiichiro , Sakamoto Kenji , Kaikita Koichi , Matsushita Kenichi , Morimoto Sachio , Ito Takaaki , Tsujita Kenichi
Published: July 2021

Background

Cardiac fibrosis plays a crucial role in the pathogenesis of dilated cardiomyopathy (DCM). HE4 (human epididymis protein 4) is a secretory protein expressed in activated fibroblasts that exacerbates tissue fibrosis. In the present study, we investigated the clinical utility of HE4 measurement in patients with DCM and its pathophysiological role in preclinical experiments in vivo and in vitro.

Methods and Results

We measured serum HE4 levels of 87 patients with DCM. Endomyocardial biopsy expressed severe fibrosis only in the high HE4 group (
P
<0.0001). Echocardiography showed that left ventricular end‐diastolic diameter tends to decrease over time (58±7.3 to 51±6.6 mm;
P
<0.0001) in the low HE4 group (<59.65 pmol/L [median value]). HE4 was significantly associated with risk reduction of mortality and cardiovascular hospitalization in multivariate Cox model. In vivo, HE4 was highly expressed in kidney and lung tissue of mouse, and scarcely expressed in heart. In genetically induced DCM mouse model, HE4 expression increased in kidney but not in heart and lung. In vitro, supernatant from HE4‐transfected human embryonic kidney 293T cells enhanced transdifferentiation of rat neonatal fibroblasts and increased expression of fibrosis‐related genes, and this was accompanied by the activation of extracellular signal‐regulated kinase signaling in cardiac fibroblasts. Treatment with an inhibitor of upstream signal of extracellular signal‐regulated kinase or a neutralizing HE4 antibody canceled the profibrotic properties of HE4.

Conclusions

HE4 functions as a secretory factor, activating cardiac fibroblasts, thereby inducing cardiac interstitial fibrosis. HE4 could be a promising biomarker for assessing ongoing fibrosis and a novel therapeutic target in DCM.

Registration

URL:
https://upload.umin.ac.jp/cgi‐open‐bin/ctr
; Unique identifier: UMIN000043062.