bluuebunny/crossref_metadata_2025 huggingface dataset:
Biosynthesis of Silver Nanoparticles from Rhododendron arboreum for Metal Sensing, Antibacterial Assessment, and Photocatalytic Degradation
Authors: Phuyal Sitaram , Lamichhane Ganesh , Gupta Aakash , Khadayat Karan , Adhikari Anup , Marahatha Rishab , Khadka Sujan , Parajuli Niranjan
Published: June 2022

The nanomaterial industry has focused on green synthetic methods to avoid unpleasant compounds produced during manufacturing, offering eco‐friendly, sustainable, and nature‐derived alternative methods. In this study, silver nanoparticles (Ag NPs) have been synthesized from an aqueous extract of the leaves of Rhododendron arboreum, where the pH of the reaction mixture is found to be crucial. The reaction progress monitored using the UV‐Vis spectrophotometer displayed a strong absorption band at 425 nm at pH 9, suggesting an optimum pH for the synthesis. The Ag NPs thus synthesized were characterized using instrumental techniques. The attenuated total reflectance‐Fourier transform infrared (ATR‐FTIR) spectroscopy showed the presence of phytoconstituents in the aqueous extract, which are believed to be responsible for reducing Ag+ ions to Ag NPs and capping agents on its surface for stability. X‐ray diffraction (XRD) showed a highly crystalline nature, and energy‐dispersive X‐ray (EDX) demonstrated the presence of metallic silver. The scanning and transmission electron microscopy (SEM and TEM, respectively) revealed crystalline morphology and monodisperse Ag NPs of sizes ranging from 23 to 41 nm. Furthermore, the metal‐sensing activity of biosynthesized Ag NPs was evaluated using various metal ions; they were utilized for highly selective and sensitive colorimetric detection of Hg2+ in an aqueous medium among various metal ion solutions tested with the detection limit of 0.5 mM using the UV‐Vis spectrophotometer. Similarly, they were also shown to be effective for the nanocatalytic activity for degradation of methylene blue dye up to 81%. These studies demonstrated Ag NPs as potential candidates for selective detection of mercury in water resources, a tool for sensing the heavy metals and degradation of synthetic dye from industrial effluents in wastewater treatment. Having the high surface‐to‐volume ratio and size‐dependent functionality of Ag NPs, further optimization studies at micromolar and nanomolar detection limits will avail its better industrial utilization. Moreover, biologically mediated Ag NPs can also exhibit good antimicrobial activity against Staphylococcus aureus and Escherichia coli.
An Enhanced Priori Knowledge GAN for CT Images Generation of Early Lung Nodules with Small-Size Labelled Samples
Authors: Wang Xun , Yu Zhiyong , Wang Lisheng , Zheng Pan
Published: June 2022

The small size of labelled samples is one of the challenging problems in identifying early lung nodules from CT images using deep learning methods. Recent literature on the topic shows that deep convolutional generative adversarial network (DCGAN) has been used in medical data synthesis and gained some success, but does not demonstrate satisfactory results in synthesizing CT images. It primarily suffers from the problem of model convergence and is prone to mode collapse. In this paper, we propose a generative adversarial network (GAN) model with prior knowledge to generate CT images of early lung nodules from a small-size of labelled samples, i.e., SLS-PriGAN. Particularly, a knowledge acquisition network and a sharpening network are designed for priori knowledge learning and acquisition, and then, a GAN model is developed to produce CT images of early lung nodules. To validate our method, a general fast R-CNN network is trained using the CT images generated by SLS-PriGAN. The experiment result shows that it achieved a recognizing accuracy of 91%, a recall rate of 81%, and

F
1

score of 0.85 in identifying clinic CT images of early lung nodules. This provides a promising way of identifying early lung nodules from CT images using deep learning with small-size labelled samples.
Effect of Fermentation Time on Physiochemical Properties of Kombucha Produced from Different Teas and Fruits: Comparative Study
Authors: Li Siying , Zhang Yang , Gao Jingrong , Li Tong , Li Huizhen , Mastroyannis Adele , He Shan , Rahaman Abdul , Chang Kun
Published: June 2022

This study aimed to investigate the impact of fermentation time on antioxidative activities and phenolic composition and sensory quality of kombucha fermented from different teas (green, black, and oolong) and fruits (grape, dragon, and guava). Results: the highest antioxidative activity was observed in kombucha from green tea and grapefruit fermented for 6-7 days at 25–30°C and 48 h at 37°C, respectively. Further analysis revealed that the antioxidative activity of grape kombucha was significantly improved due to an increase in polyphenols’ concentration as compared to original green tea kombucha. Furthermore, the sensory evaluation of grape kombucha suggested that grape-flavoured kombucha is more acceptable by the young-aged group. In conclusion, this study provides a potential and promising method for the first time to produce fruit-flavoured kombucha with increased bioactive compounds in very short fermentation time (48 h) which could fulfil the nutritional requirement for human health.
Manifestation of Urinary Tract Injury during Cervical Cancer Surgery Based on CT Urography Secretion Phase Images
Authors: Lin Song , Li Xiaoshan , Zhang Yan , Mao Xiaowen , Liang Xingchi , Cheng Shigang , Zhang Lingli
Published: June 2022

Object. CT imaging can be processed by computer, and the absorption coefficient of each voxel to X‐ray can be obtained by calculation, which can effectively improve the efficiency of surgery. Traditional treatment is based on the patient’s age, fertility requirements, and general conditions, often using a comprehensive treatment plan with surgery and radiotherapy as the mainstay, supplemented by chemotherapy, which has great limitations and side effects, in order to alleviate the loss of various body functions, especially the urinary tract during cervical cancer surgery. Methods. We grouped the patients who had undergone cervical cancer surgery in a hospital in this article and compared the nanodrug carrier system under CT imaging with traditional laparoscopy. The postoperative physical parameters of surgical patients are collected from cervical cancer patients of different degrees, and the parameters and prognostic health of patients after different operations are compared. Results. The results of the study show that the postoperative patient’s body parameters of the nanodrug delivery system under the CT imaging technology used in this article are better than those of the traditional surgery group, and the average intraoperative blood loss is about 20% less than that of the traditional surgery. Postoperative complications occur. The situation is even lower, more than 30% lower than traditional surgery. Conclusion. This shows that the operation of the nanodrug delivery system based on CT imaging technology has broken through some of the limitations of the development of laparoscopic technology and has played an important role in the surgical treatment of cervical cancer.
Artificial Intelligence Technologies and Their Application for Reform and Development of Table Tennis Training in Complex Environments
Authors: Han Dong , Zhang Shengtao , Zhang Huanyu
Published: June 2022

The development of information technology has been deployed in almost all sectors and is making life easier. In this development, the sports sector has seen tremendous expansion. In traditional table tennis training, the coach and the players have to meet daily to take appropriate training for the game. This process is time-consuming in a complex environment, and it will have a significant impact on the reformation and development of table tennis training. The utilization of improved technologies can overcome this challenge by performing training of the game online with an intelligent wireless system with advanced training mechanisms. Carrying the traditional and heavier intelligent wireless devices will be difficult for the players. In this research, the fine-grained evaluation (FGE) system is incorporated into the deep learning model to analyze the player’s body postures during the training and event sessions and make them develop after each session through online training in any circumstance. The proposed FGE was compared with the traditional statistical model, and it was observed that the proposed FGE had obtained higher precision and recall values of 70% and 98.9% than the statistical model.
Optimization on Powder Metallurgy Process Parameters on Nano Boron Carbide and Micron Titanium Carbide Particles Reinforced AA 4015 Composites by Taguchi Technique
Authors: Alrebdi Tahani A. , Gopinathan R. , Sunagar Prashant , Prabu R. Thandaiah , Kivade Rajesh , Gous Mahmad Ziya , Alodhayb Abdullah , Tesemma Belachew Girma
Published: June 2022

Aluminium metal matrix composite is developed using powder metallurgy, with number of different operational factors considered. The three most important operational factors are sintering time, sintering temperature, and compaction pressure. Investigations are conducted using L9 orthogonal array as the experimental design. Density, Vickers hardness, and compressive strength are determined through experiments. The S/N ratio based on Taguchi’s law and a number of anomalies accomplished were used to determine the effect of individual input parameters (ANOVA). The main effect plots identified the optimal parameter settings for obtaining a less density, a higher hardness, and a higher compressive strength. In addition, the ANOVA analysis confirmed that the best metal matrix composite material is produced at the optimal sintering time and average temperature and compaction pressure for generally classified levels.
“Derived Multiple Allogeneic Protein Paracrine Signaling (d-MAPPS)” Enhances T Cell-Driven Immune Response to Murine Mammary Carcinoma
Authors: Harrell Carl Randall , Pavlovic Dragica , Miloradovic Dragana , Stojanovic Milica Dimitrijevic , Djonov Valentin , Volarevic Vladislav
Published: June 2022

Breast cancer is considered refractory to immunotherapy. Accordingly, there is an urgent need for the therapeutic use of new immunostimulatory agents which would enhance antitumor immune response against breast cancer cells. “Derived Multiple Allogeneic Protein Paracrine Signaling (d-MAPPS)” is a biological product whose activity is based on chemokines and cytokines that modulate homing and phenotype of immune cells. d-MAPPS contains high concentration of dendritic cell (DC) and T cell-attracting chemokine CXCL16 and potent T cell-activating cytokine IL-27 which enhance DC:T cell cross-talk in inflamed tissues. Herewith, we used 4T1 murine model of breast cancer to analyze d-MAPPS-dependent enhancement of T cell-driven antitumor immunity. 4T1+d-MAPPS-treated mice showed delayed mammary tumor appearance compared to 4T1+saline-treated animals. d-MAPPS significantly reduced tumor weight and volume and improved survival of 4T1-treated mice. Significantly increased concentration of CXCL16, IL-27, IFN-γ, and IL-17 and decreased concentration of immunosuppressive TGF-β and IL-10 were measured in serum samples and tumor tissues of 4T1+d-MAPPS-treated mice. d-MAPPS enhanced production of IL-12 and increased expression of MHC class II and costimulatory molecules on tumor-infiltrated DC, significantly improving their antigen-presenting properties. d-MAPPS in CXCL16-dependent manner promoted recruitment of antitumorigenic IFN-γ/IL-17-producing CD4+Th1/Th17 cells and in IL-27-dependent manner induced expansion of tumoricidal CD178+granzyme B-expressing CD8+CTLs and inhibited generation of tolerogenic DC, IL-10, and TGF-β-producing FoxP3-expressing T regulatory cells. In summing up, d-MAPPS, in CXL16- and IL-27-dependent manner, enhanced T cell-driven antitumor immune response and suppressed breast cancer growth in experimental mice.
University English Network Teaching Resource Bank Construction Based on Cooperative Filter Algorithm
Authors: Wei Jingyu
Published: June 2022

In recent years, with the rapid development of the network, related applications have also been greatly developed. Online-based online learning systems allow learners to ignore the difference in time and more convenient learning. It does not stick to the characteristics of classroom learning, which greatly meets the characteristics of contemporary education, and also enriches the diversity of education. This paper optimizes the recommendation technology of the personalized recommendation system of college English network teaching resource library, which is to propose a recommended model for the synergistic filtering algorithm using a combination of project properties and user attributes. Based on the detailed analysis of the network teaching resource construction platform, the algorithm is applied to the network teaching system, filled into the original matrix to obtain a dense pseudocomment matrix, and then find the user’s own attribute information and rating information in the pseudocommentary matrix. The recent neighbor of the target user calculates the target user’s preevaluation project for the nonscore item based on the nearest neighboring rating information and finally receives the highest recommendation list. After experimental analysis, the collaborative filtering algorithm proposed in this article was significantly higher than that of the remaining two, and the precision and recall values were also slightly more than about 0.2 in the

F

-measure evaluation criteria, bounded about 2%.
Calculation of the Overall Coordination Internal Force of the Grille Beam-Column under the Impact of Debris Flow
Authors: Wang Yongsheng , Zhu Hao , Wang Bing
Published: June 2022

At present, the research on the new ground anchor counterfort grille dam is not perfect. In order to analyze and design the new grille dam accurately and reasonably, it is necessary to carry out theoretical research on the internal force calculation of the overall coordination of the grille beam-column under the impact of debris flow. Under the condition of full reservoir of debris flow, the grille beam-column meets the working principle of elastic foundation beam; therefore, the equation of the overall cooperative work of the grille beam-column is derived based upon Winkler’s theory of elastic foundation beam. Finally, combined with the engineering example, this calculation method is used for analysis; the results show that the bending moment of the grille beam-column increases compared with that regardless of considering the overall coordination, and the increased value of the bending moment at the bottom of the grille column and the middle of the grille beam is the largest. Therefore, from the perspective of safety, the overall coordination cannot be ignored when designing a blocking dam.
Research on Painting Image Classification Based on Transfer Learning and Feature Fusion
Authors: Yong Qian
Published: June 2022

In order to effectively solve the problems of high error rate, long time consuming, and low accuracy of feature extraction in current painting image classification methods, a painting image classification method based on transfer learning and feature fusion was proposed. The global characteristics of the painting picture, such as color, texture, and form, are extracted. The SIFT method is used to extract the painting’s local features, and the global and local characteristics are normalized and merged. The painting images are preliminarily classified using the result of feature fusion, the deterministic and nondeterministic samples are divided, and the estimated Gaussian model parameters are transferred to the target domain via a transfer learning algorithm to alter the distribution of nondeterministic samples, completing the painting image classification. Experimental results show that the proposed method has a low error rate and low feature extraction time and a high accuracy rate of painting image classification.
Changes of Dance Sports in Air Equipment Dance Performance Using Convolutional Neural Network
Authors: Jia Chao
Published: June 2022

Dance is an artistic form that relies on human body to interpret the beauty. The expression of the character image in dance works through the display of the actor’s limb language and their expression of intrinsic emotions, making dance works aesthetic and delivering delicate emotions and profound ideas. This article aims to study the change of dance form in the air equipment dance performance by convolutional neural network technology. This paper also proposes to track the position and scale of the dancer in convolutional neural network. When estimating the position and scale of the dancer, the discriminant correlation filter is used to obtain a training sample around the initial area. The experimental results show that the recognition rate of HOG characteristics in the combination of the follower and the combination of the inner flower was 42.8%, 40%, respectively, which was 3.33%, 29.2% higher than the combination of the flower. At the same time, only the identification rate of 53.3% in this paper in the combination of the inner flowers was lower than 60% of the reference method. The algorithm herein can maintain a certain identification for complicated dance actions, and it is still able to ensure a certain accuracy in the case of confusion in the background and target. The effectiveness of this action recognition algorithm for dance action recognition algorithm is verified.
Huaier Inhibits Gastric Cancer Growth and Hepatic Metastasis by Reducing Syntenin Expression and STAT3 Phosphorylation
Authors: Shi Yunfu , Yuan Li , Xu Jingli , Xu Handong , Wang Lijing , Huang Ling , Xu Zhiyuan , Cheng Xiangdong
Published: June 2022

Gastric cancer (GC) is a common malignant tumor worldwide and poses a serious threat to human health. As a traditional Chinese medicine, Huaier (Trametes robiniophila Murr.) has been used in the clinical treatment of GC. However, the mechanism underlying the anticancer effect of Huaier remains poorly understood. In this study, we used in vivo imaging technology to determine the anticancer effect of the Huaier n-butanol extract (HBE) on orthotopic and hepatic metastasis of GC mouse models. We found that HBE suppressed tumor growth and metastasis without causing apparent host toxicity. Proteomic analysis of GC cells before and after HBE intervention revealed syntenin to be one of the most significantly downregulated proteins after HBE intervention. We further demonstrated that HBE suppressed the growth and metastasis of GC by reducing the expression of syntenin and the phosphorylation of STAT3 at Y705 and reversing the epithelial-mesenchymal transition (EMT). In addition, we confirmed that syntenin was highly expressed in GC tissue and correlated with metastasis and poor prognosis. In conclusion, our results suggest that Huaier, a clinically used anticancer drug, may inhibit the growth and liver metastasis of GC by inhibiting the syntenin/STAT3 signaling pathway and reversing EMT.
A Case of Delayed Hepatic Injury Associated with Teriflunomide Use as Assessed for Causality Using the Updated RUCAM
Authors: Wurzburger Riana
Published: June 2022

Teriflunomide is a pyrimidine synthesis inhibitor used in the treatment of multiple sclerosis that has in rare instances been associated with liver toxicity, though there are few documented cases. Here, we report a case of probable teriflunomide-induced liver injury as assessed for causality using the updated RUCAM. The liver injury occurred approximately nine months after teriflunomide initiation and improved with discontinuation of the drug and treatment with cholestyramine.
Effect of Standardized Nutritional Intervention in Patients with Nasopharyngeal Carcinoma Receiving Radiotherapy Complicated with Diabetes Mellitus
Authors: Ge Yuhong
Published: June 2022

Objective. To evaluate the effect of standardized nutritional intervention in patients with nasopharyngeal carcinoma receiving radiotherapy complicated with diabetes mellitus and the impact on quality of life. Methods. From January 2019 to December 2020, 100 diabetic patients with nasopharyngeal carcinoma receiving radiotherapy were assessed for eligibility and recruited. They were concurrently and randomly assigned (1 : 1) to receive either conventional nursing (control group) or standardized nutritional intervention (observation group). The outcomes include clinical efficacy and quality of life. Results. Standardized nutritional intervention was associated with significantly lower levels of fasting blood glucose (FBG), 2 h postprandial blood glucose (2hPBG), and glycated hemoglobin (HbA1c) versus conventional nursing (

P
<
0.001

). The patients given standardized nutritional intervention showed significantly higher hemoglobin (Hb), prealbumin (PA), and albumin (ALB) levels versus those given conventional nursing at 4 weeks after the start of radiotherapy and at the end of radiotherapy (

P
<
0.001

). The two groups showed similar Morisky scores before intervention (

P
>
0.05

). After intervention, the observation group outperformed the control group in terms of treatment compliance (

P
<
0.05

). Standardized nutritional intervention provided patients with a significantly better quality of life versus conventional nursing (

P
<
0.05

). Standardized nutritional intervention was associated with a significantly lower incidence of adverse events and higher nursing satisfaction versus conventional nursing (

P
<
0.05

). Conclusion. Standardized nutritional intervention for patients with nasopharyngeal carcinoma given radiotherapy complicated with diabetes mellitus can efficiently restore the normal nutritional status of patients, reduce the complications of radiotherapy, and improve the quality of life of patients, so it is worthy of wide clinical application.
Analysis on Spatial Disturbance Influence of Surrounding Rock Stress in the Staggered Roadways and Its Control Countermeasures
Authors: Bu Qingwei , Yuan Benqing , Ye Meng , Xu Nuo
Published: June 2022

Combined with specific engineering examples, the spatial disturbance influence characteristics and laws of the surrounding rock stress in the staggered roadways are analyzed by numerical simulation. This paper concludes that (1) compared with the surrounding rock pressure behavior of the general roadway, the surrounding rock stability of the staggered roadway is relatively poor, showing the characteristics of the local serious roadway rock pressure behavior, such as the intensified destruction of the roadway side, the failure and fracture penetration of the surrounding rock between the roadways, and the relatively serious deformation of the surrounding rock. The reason is that the stress of the surrounding rock at the staggered roadway position is obviously superimposed and disturbed by each other; (2) the influencing factors of the failure and instability of the surrounding rock between interlaced roadways are as follows: the greater the buried depth and the smaller the distance between roadways, the more intense the superposition disturbance of the surrounding rock stress between roadways; the smaller the horizontal azimuth, the greater the influence range of superposition disturbance of surrounding rock stress between roadways; the more unbalanced the original rock stress field, the worse the stability of the surrounding rock between roadways, resulting in the more serious failure and instability of the surrounding rock between roadways; (3) for the staggered roadway layout, increasing the distance between roadways, the closer to the orthogonal layout and selecting the arch section of the lower roadway is conducive to the bearing stability of the surrounding rock between roadways; (4) constrained by the space conditions of staggered roadway, the role of bolt and cable support is limited. Passive support is the key to realize the safety and stability of surrounding rock of staggered roadway, so the control technical scheme of active and passive combined support in staggered roadway position is put forward, the combined support of the upper roadway “bolt + cable + shotcrete + concrete cushion of floor” and lower roadway “bolt + cable + U-shaped steel support passive reinforcement + shotcrete” within the spatial disturbance influence the range of surrounding rock stress in the staggered roadways, and the technical scheme can achieve satisfactory supporting effect.
Evaluation of Ecological Environment Quality in Chongqing Main City Area Based on Principal Component Analysis
Authors: Chen Chunyang , Ge Quansheng , Tao Zexing , Liang Liang
Published: June 2022

With the rapid development of social productive forces in China, the process of urbanization has been accelerating, resulting in the deterioration of urban environmental quality and the destruction of ecosystems, such as debris flow, drought, water bloom, large-scale haze weather, and other ecological and environmental problems. The quality of the urban ecological environment is not only related to the stability of urban ecological function but also affects the sustainable development of the city. Many scholars have studied the problem of ecoenvironmental quality assessment, but there are still some shortcomings in the evaluation process, such as the construction of the index system and the application of related methods. Taking Chongqing as the research object, after referring to the representative evaluation index system in China, the evaluation index system of ecological environment quality in Chongqing was constructed from three aspects of nature, economy, and society. In this article, the principal component analysis (PCA) method is used to construct the ecoenvironmental quality evaluation system of Chongqing, and the economic development, pollutant control, natural protection and pollution reduction investment, urban and rural cooperation, land area, and other aspects are comprehensively evaluated. The relationship between simulated variables and the regression equation was also assessed. Through the comparative analysis of the two evaluation methods, it can be seen that the evaluation results of the PCA method and the fuzzy comprehensive evaluation method are basically the same in the longitudinal trend, which shows that the application of this method in the field of ecological environment quality evaluation has certain scientific rationality.
Implementation of Sustainable Supply Chain Management considering Barriers and Hybrid Multiple-Criteria Decision Analysis in the Healthcare Industry
Authors: Karbassi Yazdi Amir , Wanke Peter , Ghandvar Maryam , Hajili Marjan , Mehdikarami Mousa
Published: June 2022

This research aims to find the barriers that affect the implementation of sustainable supply chain management (SSCM) and rank them using hybrid multiple-criteria decision analysis (MCDA) methods in the healthcare industry. As companies seek to earn revenue by providing goods or services to customers, they must also consider social responsibility, economics, and the environment as other multiple external factors. One of the most crucial factors is the company’s stewardship of the environment, but economic factors must be regarded when keeping the environment clean by balancing the economic situation to make a profit. This study extracts the barriers to implementing SSCM from previous studies, adapts these barriers to the healthcare industry, and ranks them using a hybrid best-worst method (BWM) and combined compromise solution (CoCoSo) method. The result indicates that hospital 7 should rank SSCM higher than the other six healthcare centers evaluated. Moreover, among the barriers, high disposal costs is the most crucial factor when considering implementing SSCM.
Improved Siamese Network-Based 3D Motion Tracking Algorithm for Athletes
Authors: Lan Tao
Published: June 2022

For the last few years, the application of Siamese network in athletes’ three-dimensional motion tracking has greatly improved the efficiency of sports training. However, the accuracy of the Siamese network tracking algorithm is limited to a large extent. To solve the above problems, based on the channel attention mechanism, the key feature information perception module is innovatively proposed to promote the discriminant ability of the network model and make the network focus on the convolution feature changes of the target. On this basis, an online adaptive mask strategy is proposed, which adapts the subsequent frames according to the output state of the cross-correlation layer learned online to highlight the foreground object. Compared with other algorithms in annotated data set and MOT17 data set, this algorithm has more stable initial tracking performance, significantly improved accuracy compared with the benchmark, and high robustness tracking effect in complex scenes.
Convolutional Neural Network with Multiscale Fusion and Attention Mechanism for Skin Diseases Assisted Diagnosis
Authors: Li Zhong , Wang Hongyi , Han Qi , Liu Jingcheng , Hou Mingyang , Chen Guorong , Tian Yuan , Weng Tengfei
Published: June 2022

Melanoma segmentation based on a convolutional neural network (CNN) has recently attracted extensive attention. However, the features captured by CNN are always local that result in discontinuous feature extraction. To solve this problem, we propose a novel multiscale feature fusion network (MSFA-Net). MSFA-Net can extract feature information at different scales through a multiscale feature fusion structure (MSF) in the network and then calibrate and restore the extracted information to achieve the purpose of melanoma segmentation. Specifically, based on the popular encoder-decoder structure, we designed three functional modules, namely MSF, asymmetric skip connection structure (ASCS), and calibration decoder (Decoder). In addition, a weighted cross-entropy loss and two-stage learning rate optimization strategy are designed to train the network more effectively. Compared qualitatively and quantitatively with the representative neural network methods with encoder-decoder structure, such as U-Net, the proposed method can achieve advanced performance.
Investigating the AC079305/DUSP1 Axis as Oxidative Stress-Related Signatures and Immune Infiltration Characteristics in Ischemic Stroke
Authors: Fan Jiaxin , Cao Shuai , Chen Mengying , Yao Qingling , Zhang Xiaodong , Du Shuang , Qu Huiyang , Cheng Yuxuan , Ma Shuyin , Zhang Meijuan , Huang Yizhou , Zhang Nan , Shi Kaili , Zhan Shuqin
Published: June 2022

Background. Oxidative stress (OS) and immune inflammation play complex intersections in the pathophysiology of ischemic stroke (IS). However, a competing endogenous RNA- (ceRNA-) based mechanism linked to the intersections in IS has not been explored. We aimed to identify potential OS-related signatures and analyze immune infiltration characteristics in IS. Methods. Three datasets (GSE22255, GSE110993, and GSE140275) from the GEO database were extracted. Differentially expressed long noncoding RNAs, microRNAs, and messenger RNAs (DElncRNAs, DEmiRNAs, and DEmRNAs) between IS patients and controls were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were explored. Moreover, a triple ceRNA network was constructed to reveal transcriptional regulation mechanisms. A comprehensive strategy among least absolute shrinkage and selection operator (LASSO) regression, DEmRNAs, uprelated DEmRNAs, and OS-related genes was adopted to select the best signature. Then, we evaluated and verified the discriminant ability of the signature via receiver operating characteristic (ROC) analysis. Immune infiltration characteristics were explored via the CIBERSORT algorithm. Moreover, the best signature was verified via qPCR and western blot methods in rat brain tissues and PC12 cells. Results. 11 DEmRNAs were identified totally. Enrichment analysis showed that the DEmRNAs were primarily concentrated in MAPK-associated biological processes and immune or inflammation-involved pathways. DUSP1 was identified as the best signature with an area under the ROC curve of 73.5% (

95
%
CI
=
57.02

-89.98,

sensitivity
=
95
%

, and

specificity
=
60
%

) in GSE22255 and 100.0% (

95
%
CI
=
100.00

-100.00,

sensitivity
=
100
%

, and

specificity
=
100
%

) in GSE140275. Importantly, we also identified the AC079305/DUSP1 axis in the ceRNA network. Immune infiltration showed that resting mast cells infiltrate less in IS patients compared with controls. And DUSP1 was negatively correlated with resting mast cells (

r
=
−
0.703

,

P
<
0.01

), whereas it was positively correlated with neutrophils (

r
=
0.339

,

P
<
0.05

). Both in vivo and in vitro models confirmed the upregulated expression of DUSP1 and the downregulated expression of miR-429. Conclusion. This study identified the ceRNA-based AC079305/DUSP1 axis as a promising OS-related signature for IS. Immune infiltrating cells, especially mast cells, may exert a pivotal role in IS progression. Pharmacological agents targeting signatures, their receptors, or mast cells may shed a novel light on therapeutic targets for IS.
Entropy Generation Analysis for MHD Flow of Hybrid Nanofluids over a Curved Stretching Surface with Shape Effects
Authors: Ullah Basharat , Khan Umar , Wahab Hafiz Abdul , Khan Ilyas , Alam Md. Nur
Published: June 2022

The characteristic of magnetohydrodynamic flow of viscous fluids is explained here. The energy equation behavior is studied in the presence of heat, viscous dissipation, and joule heating. The major emphasis of this study is the physical behavior of the entropy optimization rate. Based on the implementation of curvilinear coordinates, the basic flow equations are established. Nonlinear partial differential expressions are reduced by appropriate transformation to the ordinary differential system. In the engineering and industrial processes, nanoparticles and their shape have practical consequences. For this reason, we give a detailed investigation of the shape impacts on the flow through the curved stretching surface of nanoparticles. The flow equations are reduced into a number of nonlinear differential equations which are solved numerically using a useful numerical approach called Runge‐Kutta‐4 (RK‐4). The shooting method is first used to reduce the equations to a number of problems of first order, and then the RK‐4 approach is used for solution. Impacts for entropy optimization, Bejan number, velocity, concentration, and temperature of several physical parameters are graphically studied.
Circulating DNA and Liquid Biopsies in the Management of Patients with Cancer
Authors: Joosse Simon A. , Pantel Klaus
Published: June 2022

Forty-five years ago, Cancer Research published the study by Leon and colleagues in which the authors described the observation of increased levels of cell-free DNA (cfDNA) in the serum of patients with cancer as compared with healthy individuals, with the highest serum levels in patients with metastatic cancer. Most interestingly was the correlation between serum DNA concentrations and therapy outcome: Increased serum DNA levels were associated with poor response to treatment, whereas decreases in DNA levels during treatment appeared to be a sign of better prognosis. Since the discovery of the prognostic value of blood DNA, much research has been focused on the characterization of cfDNA to understand its origins and increase the sensitivity and specificity of using cfDNA as a prognostic and predictive marker in the battle against cancer. Tumor-specific cfDNA markers that were discovered include genetic alterations, chromosomal aberrations, epigenetic modifications, and DNA fragmentation size. In recent years, due to the development of highly sensitive molecular technologies, cfDNA-based assays are now being introduced into the clinic as the so called “liquid biopsy.” The advantages of a liquid biopsy over traditional biopsy and imaging have led to the implementation in the clinic for early cancer detection, improved cancer staging, early detection of relapse, real-time monitoring of therapeutic efficacy, and detection of therapeutic targets and resistance mechanisms. Despite Leon and colleagues’ initial skepticism about the potential diagnostic value of serum DNA, cfDNA-based liquid biopsy has become one of the most important tools for personalized cancer treatment.

See related article by Leon and colleagues, Cancer Res 1977;37:646–50
Abstract 1009: A novel C-terminal HSP90 inhibitor NCT-58 targets cancer stem-like properties and suppresses migratory ability in triple-negative breast cancer cells
Authors: Park Soeun , Park Jung Min , Park Minsu , Ko Dongmi , Kim Seongjae , Seo Juyeon , Nam Kee Dal , Kim Yoon-Jae , Kim Ji Young , Seo Jae Hong
Published: June 2022

Background: Although several N-terminal HSP90 inhibitors have been investigated in clinical trials, none have yet been approved for clinical use due to issues including induction of the heat shock response (HSR), off-target effects and toxicity. A major issue for N-terminal inhibitors is induction of the heat shock response (HSR) which triggers cell survival. In the present study, we investigated the effects of NCT-58, a rationally-designed novel HSP90 inhibitor that instead targets the C-terminal domain, and evaluated its capacity to induce apoptosis and target cancer stem-like properties in triple-negative breast cancer.

Materials and Methods: The effect of NCT-58 on TNBC cell lines in vitro was evaluated with cell viability, apoptosis, heat shock response and cell migration. Cancer stem-like properties were examined by Aldefluor positivity, CD44+/CD24- stem-like population and mammosphere formation assays.

Results: NCT-58 induces apoptosis in TNBC cells without triggering the heat shock response (HSR) due to its targeting of the C-terminal region. This is accompanied by potent and simultaneous degradation of AKT, MEK and STAT3. Importantly, NCT-58 kills not only the rapidly proliferating tumor cells and but also effectively eradicates the breast cancer stem-like population (BCSCs). The latter phenomena are accompanied by reductions in the activity of stem/progenitor marker ALDH1 and the CD44+/CD24- stem-like population and as well as impairment of mammosphere formation. Furthermore, NCT-58 markedly impairs cell migratory ability, coinciding with collapse of HSP90 client cytoskeletal proteins including vimentin and F-actin in TNBC cells in vitro. It is noteworthy that NCT-58 exhibits more cytotoxic to tumor cells but minimally cytotoxicity to non-malignant cells.

Conclusion: These findings suggest that NCT-58 may represent an effective therapeutic approach for the simultaneous targeting of HSP90 and its client oncoproteins for the treatment of molecularly heterogeneous TNBC.

Citation Format: Soeun Park, Jung Min Park, Minsu Park, Dongmi Ko, Seongjae Kim, Juyeon Seo, Kee Dal Nam, Yoon-Jae Kim, Ji Young Kim, Jae Hong Seo. A novel C-terminal HSP90 inhibitor NCT-58 targets cancer stem-like properties and suppresses migratory ability in triple-negative breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1009.
Abstract 102: IGFBP6 modulates estrogen receptor alpha phosphorylation and transcriptional activity in breast cancer cells
Authors: Lariz Francisco Javier , Houston Kevin D.
Published: June 2022

Insulin-like growth factors (IGFs) are signaling proteins which bind to insulin-like growth factor 1 receptor (IGF-1R) and induce a signaling cascade to promote proliferation and survival in breast cancer cells. Insulin-Like Growth Factor Binding Protein 6 (IGFBP-6) induces apoptosis by inhibiting IGF-1R upon binding to both IGF-1 and IGF-2, however, the role of IGFBP-6 in breast cancer has not been adequately studied. While IGFBP-6 can bind to both IGF-1 and IGF-2, the binding affinity for IGF2 is 20-fold higher compared to IGF1. To determine if IGFBP-6 modulates breast cancer cells, MCF-7 and T-47D cells were stably transfected with an IGFBP-6 expression plasmid. IGFBP6 over-expression resulted in decreased proliferation rates in both cell lines when compared to empty vector controls. To identify a mechanism of decreased proliferation rates, the activation of the IGF-1R-dependent AKT and MAPK mediators was measured. Reduced phosphorylation of MAPK and AKT was observed in both cell lines over-expressing IGFBP-6 compared to empty vector controls. MAPK and AKT phosphorylate ERα at serine 118 and serine 167 respectively, therefore, ERα phosphorylation at these residues was determined in the presence of IGFBP6 expression. Reduction in phosphorylation was greater in MCF-7 cells than T-47D cells when IGFBP6 was constitutively expressed. To determine if reduced ERα phosphorylation altered expression of known targets of ERα-modulated expression, such as IGF-1R and Progesterone Receptor (PR) was measured. Unexpectedly, IGF-1R and PR protein and transcript levels were greater in IGFBP6 over-expressing cells. Studies have shown that differences in ERα phosphorylation change the recruitment of transcriptional modulators associated with ERα-mediated transcription. These results suggest that despite reducing IGF-1R-dependent cell signaling, compensatory mechanisms may be induced to enhance ERα-mediated expression.

Citation Format: Francisco Javier Lariz, Kevin D. Houston. IGFBP6 modulates estrogen receptor alpha phosphorylation and transcriptional activity in breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 102.
Abstract 1028: Phosphate dysregulation as a novel therapeutic strategy in ovarian and uterine cancers
Authors: Bondeson Daniel , Paolella Brenton , Asfaw Adhana , Rothberg Michael , Skipper Thomas , Mesa Gabriel , Gonzalez Alfredo , Surface Lauren E. , Ito Kentaro , Kazachkova Mariya , Colgan William N. , Warren Allie , Dempster Joshua , Krill-Burger J Michael , Ericsson Maria , Tang Andrew , Fung Iris , Chambers Emily S. , Abdusamad Mai , Dumont Nancy , Doench John , Piccioni Federica , Root David , Boehm Jesse , Hahn William C. , Mannstadt Michael , McFarland James , Vazquez Francisca , Golub Todd
Published: June 2022

Precision medicine promises to improve the treatment of cancer patients, but a lack of therapeutic targets and associated predictive biomarkers limit this reality. To identify novel strategies, we integrate genome-scale CRISPR viability screens across many cancer models with cellular and molecular features to systematically define The Cancer Dependency Map. Using this data, we have identified that XPR1, an inorganic phosphate exporter protein, is a highly selective dependency gene in ovarian and uterine cancers. These cancers are sensitive to loss of XPR1 due to over-expression of SLC34A2, a phosphate importer protein. These data suggest a synthetic lethal relationship in which intracellular phosphate homeostasis is dysregulated in cancer. As proof-of-concept of pharmacological inhibition of XPR1, we have developed protein ligands based on the receptor binding domain of viruses which use XPR1 for cellular entry. These ligands inhibit XPR1 and kill cancer cells in an on-mechanism manner, but may be limited in their clinical utility. As such, we are deepening our understanding of the mechanisms of XPR1-dependent phosphate efflux, and have identified a novel partner protein that is integral to phosphate efflux, possibly revealing functional domains that small molecule inhibitors might target. Overall, these data highlight a novel mechanism to treat cancers by leveraging cancer-specific phosphate dysregulation and further reinforce the Cancer Dependency Map as a powerful engine to uncover novel therapeutic vulnerabilities.

Citation Format: Daniel Bondeson, Brenton Paolella, Adhana Asfaw, Michael Rothberg, Thomas Skipper, Gabriel Mesa, Alfredo Gonzalez, Lauren E. Surface, Kentaro Ito, Mariya Kazachkova, William N. Colgan, Allie Warren, Joshua Dempster, J Michael Krill-Burger, Maria Ericsson, Andrew Tang, Iris Fung, Emily S. Chambers, Mai Abdusamad, Nancy Dumont, John Doench, Federica Piccioni, David Root, Jesse Boehm, William C. Hahn, Michael Mannstadt, James McFarland, Francisca Vazquez, Todd Golub. Phosphate dysregulation as a novel therapeutic strategy in ovarian and uterine cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1028.
Abstract 1051: Combination of senaparib with temozolomide for the treatment of cancer
Authors: Cai Sui Xiong , Ma Ning , Wang Xiaozhu , Ma Jie , Guo Mingchuan , Zhou Ruiyu , Liu Lan , Hsieh Chih-Yi , Tian Ye Edward
Published: June 2022

Poly (ADP-ribose) polymerase (PARP) is a critical enzyme for DNA repair and PARP inhibitors have been found to be efficacious against cancers with defects in DNA repair pathways such as with BRCA mutations. In addition, in vitro and in vivo studies have found that for PARP inhibitors with good trapping activity, combination with temozolomide (TMZ) produced the best synergetic effects among different types of chemotherapies. Several clinical combination studies of PARP inhibitors with TMZ have been reported, such as the combination of olaparib with TMZ in small cell lung cancer (SCLC). In this presentation, we will report in vitro and in vivo studies of PARP inhibitor senaparib (IMP4297) in combination with TMZ. Synergetic effects were observed when senaparib was combined with TMZ in vitro against human SCLC NCI-H209 cells. In vivo studies of high-dose senaparib in combination with low-dose TMZ once a day continuously in human SCLC NCI-H209 xenograft model was found to be highly synergetic and well tolerated. A clinical study of senaparib in combination with TMZ in patients with advanced solid tumors and SCLC is ongoing (ClinicalTrials.gov Identifier: NCT04434482).

Citation Format: Sui Xiong Cai, Ning Ma, Xiaozhu Wang, Jie Ma, Mingchuan Guo, Ruiyu Zhou, Lan Liu, Chih-Yi Hsieh, Ye Edward Tian. Combination of senaparib with temozolomide for the treatment of cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1051.