bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of Multiscaled Pore Structure of Gas Shales using Nitrogen Adsorption and FE-SEM Imaging Experiments
Authors: Zheng Aiwei , Bao Hanyong , Liu Li , Tu Mingkai , Hu Changpeng , Yang Lei
Published: June 2022

Nanopore in shales is the place for hydrocarbon accumulation and migration. However, there is a lack of understanding of the nanopore structure with regard to their ultratight and multiscaled nature. Here, the porous morphology of gas shales from the Sichuan Basin of China was investigated using field emission-scanning electronic microscopy (FE-SEM) with high resolution. Low-pressure nitrogen adsorption experiments at 77 K were conducted to obtain the adsorption-desorption isotherms, BET-specific surface area, pore size distribution, pore volume, and average pore diameter values. Research results show that pores of the studied shales are at the nanometer scale, and the average pore diameter is between 3 and 5 nm. The pore structure of these shales is complicated, which is not only predominately mesopores (pore diameter at 2–50 nm) but also some micropores (

pore
 
diameter
<
2
 
nm

) and macropores (

pore
 
diameter
>
50
 
nm

). The specific surface area of shales ranges from 13 to 30 m2/g. The micropore volume and mesopore volume occupy the total pore volume highly up to 77%–92%, which indicates that micropores and mesopores are the main storage place for shale gas. Through the analysis of adsorption isotherms and hysteretic loops, there are mainly two kinds of pores in shales, including ink-bottle-like pores and slit pores. Micropores of these shales are mainly related to organic matter, while macropores are mainly related to clay minerals. The estimation about porosity using the combined physical model shows that organic matter and clay minerals contribute about 50% and 33% to the porosity of these shales, respectively.
Role of Microbes and Nanomaterials in the Removal of Pesticides from Wastewater
Authors: Roy Arpita , Roy Madhura , Alghamdi Saad , Dablool Anas S. , Almakki Angham Ahmed , Ali Ismat H. , Yadav Krishna Kumar , Islam Md. Rabiul , Cabral-Pinto Marina M. S.
Published: June 2022

Pesticides are a class of xenobiotic compounds that are recalcitrant and show persistence in the environment for a longer period of time. Research studies have linked their potential for mutagenicity, teratogenicity, and carcinogenicity. The accumulation of pesticides in water sources due to runoff from agricultural lands has posed a serious threat to the biota of the water ecosystem as well as to the human population. Long-term exposure to pesticides can cause neurological disorders, reproductive complications, cancer, immunological, and pulmonary diseases. The use of pesticides has dramatically surged in agricultural as well as nonagricultural practices. Tons of pesticides are applied in the fields, but a limited amount reaches to the target organism while the rest is wasted and gets accumulated in soil or ends up in water sources like groundwater or river, which results in eradication of nontarget organisms. A variety of pesticides are used for pest management, such as organochlorine (DDT), carbamates (carbaryl), organophosphates (malathion), and pyrethroids (pyrethrins). These chemicals are highly toxic to flora and fauna because of their nonbiodegradable and persistence nature. Biomagnification of pesticides usually leads to cause various problems in human beings. Organochlorines like DDT have been banned in many developed countries due to these reasons. Therefore, the removal of pesticides from wastewater and natural water sources is of utmost importance. Conventional methods possess various limitations; therefore, there is a requirement of an alternative method which can efficiently remove these pollutants from the wastewater. In this review, environmental impacts and health-related complications of pesticides and microbial remediation approaches and use of different nanomaterials in the pesticide removal have been discussed.
DS-SWIPT: Secure Communication with Wireless Power Transfer for Internet of Things
Authors: Gong Pu , Chen Thomas M. , Xu Peng , Chen Qianbin
Published: June 2022

Internet of Things (IoT) is promptly spreading and reaching a series of domains, including many industrial applications designed for monitoring purposes. In such networks, sensitive information is being collected and transmitted by IoT devices with limited resources, which leads energy efficiency and cybersecurity to become critical. Therefore, this paper proposes a novel approach for wireless communications and power for IoT monitoring applications with the aim of achieving energy efficiency and security. The proposed solution combines the advantages of Simultaneous Wireless Information and Power Transfer (SWIPT) for wireless power transfer to remote IoT devices and Direct Sequence Spread Spectrum (DSSS) for data confidentiality. The proposed DS-SWIPT is a security improvement over the original SWIPT. Simulation results show that the proposed DS-SWIPT can achieve energy efficiency along with acceptable data confidentiality.
Dynamic Changes in Red Cell Distribution Width Can Predict Major Adverse Cardiovascular Events after PCI in Patients with Unstable Angina Pectoris: A Retrospective Cohort Study
Authors: Xiao Qiang , Yan Dekai , Qin Jian , Chen Wenwen , Jiang Ke , Zhao Jian , Zhang Chen , Li Yuanmin
Published: June 2022

Background. The increased red cell distribution width (RDW) is related to a higher risk for cardiovascular disease (CVD). However, it is yet unclear whether the dynamic change of RDW is associated with the major adverse cardiovascular events (MACEs) for individual with CVD. Methods and Results. A cohort study was conducted among 228 patients who had unstable angina (UA) and underwent PCI. RDW was measured preceding PCI and re-measured on the 16th week after PCI. The change of RDW values was defined as ΔRDW. The patients were divided into 3 groups in accordance with ΔRDW: improved, stable, and worsened RDW groups. The patients were followed up for 6 years, and MACE episodes were recorded. The survival analysis showed that the incidence of MACEs in stable RDW group was significantly lower than that in improved and worsened RDW groups. By the COX model, the risk of the occurrence of cardiovascular events in improved RDW group was 1.661 times higher than the risk in stable RDW group (HR =1.661, 95% CI: 1.583-2.880,

p
<
0.05

) and the same situation was 3.307 times higher in worsened RDW group (HR =3.307, 95% CI: 1.830-5.041,

p
<
0.05

). Conclusion. The measurement of ΔRDW has potential to predict the MACEs in UA patients underwent PCI. The dynamic changes in RDW are associated with the outcome of CVD.
MOOC Teaching Model of Basic Education Based on Fuzzy Decision Tree Algorithm
Authors: Yuanyuan Zhang
Published: June 2022

In recent years, the development of science and technology in China has greatly affected people’s ways of entertainment. In the traditional industrial model, new industries and Internet industries represented by the Internet have emerged, and the Internet video business is an emerging business that has been gradually emerging in the Internet industry in recent years. Moreover, this new teaching method has been gradually noticed in simple education, such as MOOC, I want to self-study network, and Smart Tree, and other online learning websites have sprung up. At present, the epidemic environment makes people pay more attention to this convenient and wide range of online video education. Therefore, we need to evaluate this kind of online video teaching model from the effectiveness of this kind of method and the quality of user experience. This paper takes this as the starting point and chooses the earliest online video platform, MOOC, as the model to establish a set of perfect user experience quality evaluation methods suitable for domestic online video education mode. Considering the data source, the accuracy of the results, and other factors, we chose the industry-leading platform MOOC network as an example. Through the exploration of the MOOC teaching mode in basic education, a member experience evaluation model is established based on fuzzy decision tree algorithm. The experimental results show that the model has high accuracy and high reliability.
Computed Tomography Images of Spontaneous Portosystemic Shunt in Liver Cirrhosis
Authors: Yi Fangfang , Guo Xiaozhong , Zeng Qing-Lei , Yang Benqiang , He Yanglan , Yuan Shanshan , Arora Ankur , Qi Xingshun
Published: June 2022

Spontaneous portosystemic shunt (SPSS) refers to collateral vessels that communicate between the portal vein system and systemic circulation. SPSS mainly includes esophageal varices, gastric varices, left gastric vein, recanalized paraumbilical vein, abdominal wall varices, and spontaneous splenorenal shunt. SPSS contributes to the development of hepatic encephalopathy caused by portal vein inflow bypassing and carries a higher risk of death in liver cirrhosis. Abdominal contrast-enhanced computed tomography is a major imaging approach to establish a diagnosis of SPSS and evaluate its location and feature. This review primarily describes the main contrast-enhanced CT features of SPSS in liver cirrhosis.
Cardiac Transplantation following Cobalt Cardiomyopathy from Bilateral Metal-on-Metal Hip Replacements
Authors: Szedlak Peter , Virdi Amrik , Cacciottolo Paul , Shepherd Stephen , Pettit Stephen , Falter Florian
Published: June 2022

A fifty-two-year-old man underwent heart transplantation at our centre after four years of developing progressive heart failure symptoms due to cobalt toxicity-related cardiomyopathy. Between the ages of forty and forty-two, he underwent bilateral metal-on-metal hip arthroplasties for early onset osteoarthritis. Six years later, he developed increasing fatigue and pericardial effusions. Following a prolonged period of deterioration without a clear cause, the diagnosis of cobalt toxicity-related cardiomyopathy due to cobalt-chromium alloy hip prostheses was eventually made. He underwent bilateral revision hip arthroplasties and was listed for heart transplantation. Metal-on-metal joint replacement is a rare cause of iatrogenic cobalt toxicity. Anaesthetists may encounter patients with unexplained symptoms of heart failure, having a high index of suspicion presenting an opportunity for early diagnosis and intervention before end-stage disease develops.
Some Fractional Integral Inequalities for a Generalized Class of Nonconvex Functions
Authors: Xiao Yeliang , Saleem Muhammad Shoaib , Batool Faiza
Published: June 2022

Fractional integral inequalities help to solve many difference equations. In this paper, we present some fractional integral inequalities for generalized harmonic nonconvex functions. Moreover, we also present applications of developed inequalities.
Cold Atmospheric Plasma Inhibits the Proliferation of CAL-62 Cells through the ROS-Mediated PI3K/Akt/mTOR Signaling Pathway
Authors: Liu Fang , Zhou Yuanyuan , Song Wencheng , Wang Hongzhi
Published: June 2022

This study aimed to investigate the inhibitory effects of cold atmospheric plasma (CAP) on anaplastic thyroid cancer cells (CAL-62 cells) and to reveal the molecular mechanism. The effects of CAP on CAL-62 cells were evaluated by cell viability, superoxide dismutase activity, apoptosis, cell cycle, and protein expression level, and the role of reactive oxygen species (ROS) produced by plasma was also investigated. The results showed that CAP dose-dependently inhibited cell viability and promotes cell apoptosis and G2/M arrest by increasing cell ROS levels. The activity of superoxide dismutase (SOD) was enhanced by CAP which indicated that the antioxidant system of the cell was activated. Additionally, the ROS produced by CAP can inhibit CAL-62 cell proliferation by inhibiting the PI3K/Akt/mTOR signaling pathway. Therefore, these findings will provide useful support for the application of CAP for treating anaplastic thyroid cancer.
Exponentiated Gull Alpha Exponential Distribution with Application to COVID‐19 Data
Authors: Khogeer Hazar A. , Alrumayh Amani , El-Raouf M. M. Abd , Kilai Mutua , Aldallal Ramy
Published: June 2022

In this paper, the main aim is to define a statistical distribution that can be used to model COVID‐19 data in Mexico and Canada. Using the method of exponentiation on the gull alpha exponential distribution introduces a new distribution with three parameters called the exponentiated gull alpha power exponential (EGAPE) distribution. The distribution has the benefit of being able to represent monotonic and nonmonotonic failure rates, both of which are often seen in dependability issues. It is possible to determine the quantile function as well as the skewness, kurtosis, and order statistics of the suggested distribution. The approach of maximum likelihood is used in order to calculate the parameters of the model, and the RMSE and average bias are utilised in order to evaluate how successful the strategy is. In conclusion, the flexibility of the new distribution is demonstrated by modeling COVID‐19 data. From the practical application, we can conclude that the proposed model outperformed the competing models and therefore can be used as a better option for modeling COVID‐19 and other related datasets.
Hainan Port Logistics Supply Chain and Its Flexible Operation Mechanism considering Digital Visual Remote Control
Authors: Wen Lei , Ren Qingqing , Li Jingya
Published: June 2022

Data visualization is in a process of constant change, the edge is constantly expanding, and information can be conveyed with the help of graphic technology. This article aims to study the Hainan port logistics supply chain and its flexible operation mechanism of digital visualization remote control and hopes that through the blessing of remote control technology, the port’s ability to deal with the external environment will be improved. Based on the theory of logistics service availability of supply line flexibility, this paper constructs the evaluation of Hainan port logistics service supply chain flexibility; logistics flexibility refers to the ability of an enterprise to respond quickly and effectively to changes in customer demand for transportation, delivery, and services. Logistics flexibility includes four important elements: logistics supply flexibility, procurement flexibility, distribution flexibility, and demand management flexibility. Using the concept of two-level planning to build a port collection and distribution network optimization model in the supply chain environment and analyze related examples to find the best route for port transportation, the attributes related to port flexibility are selected from the perspectives of strategic flexibility, system flexibility, service provider flexibility, and organizational flexibility. The test outcomes of this document show the radiation capacity of Haikou port is relatively strong, the proportion of people who think it is excellent is 60%, and the proportion of people who think that the radiation ability of Haikou Port is good is 20%. Haikou Port has a good resource utilization capacity; 70% think its resource utilization rate is good, and 20% think its resource utilization is very good. Haikou Port’s response capability is relatively average compared to Kia’s capability, and even 10% of people think that Haikou Port’s response capability is very average, so Haikou Port needs to strengthen training for port response capabilities. According to the operating flexibility data, the informatization development of Haikou Port is showing a good level.
Machine Learning Algorithm for Soil Analysis and Classification of Micronutrients in IoT‐Enabled Automated Farms
Authors: Blesslin Sheeba T. , Anand L. D. Vijay , Manohar Gunaselvi , Selvan Saravana , Wilfred C. Bazil , Muthukumar K. , Padmavathy S. , Ramesh Kumar P. , Asfaw Belete Tessema
Published: June 2022

The available nutrient status of the mulberry gardens in the districts of Tamil Nadu is analyzed and evaluated to find the status. In this work, the soil is classified based on the test report to a number of features with fertility indices for boron (B), organic carbon (OC), potassium (K), phosphorus (P), and available boron (B), along with the parameter soil reaction (pH). A total of 10 steps are used for cross‐validation purposes wherein in every step, the data involves 10% for validation and the remaining for training data. A fast learning classification methodology known as extreme learning method (ELM) is trained using the data to identify the micronutrients present in the soil. Activation functions such as hard limit, triangular basis, hyperbolic tangent, sine‐squared, and Gaussian radial basis are used to optimize the methodology. Based on the analysis performed, the nutrients are classified and the optimal soil conditions are proposed for different regions that are analyzed. Based on the study conducted, it is found that the soils in Tamil Nadu have normal electrical conductivity and are red in colour. They are found to be rich in potassium (35% of the samples), nitrogen (80% of the samples), and sulphur (75% of the sample) and sufficient or poor in magnesium, boron, zinc, and copper.
Analysis of Biomechanical Parameters of Martial Arts Routine Athletes’ Jumping Difficulty Based on Image Recognition
Authors: Qiao Mengjie , Dong Shibiao
Published: June 2022

This paper uses image segmentation technology to examine the biomechanical parameters of martial arts routine athletes’ whirlwind legs and backflips, two difficult jumping sports. The successful completion of the whirlwind leg, a typical martial arts jumping difficulty, during the buffer period of the take-off stage, the left knee angle flexion, the drop of the body’s center of gravity, and the drop of the horizontal speed of the center of gravity are all significantly correlated, so it is only necessary to grasp airborne altitude and speed from landing. The 720-degree cyclone foot has a flying height of 0.470.11 m, which is 4 cm higher than the 540-degree cyclone foot (0.430.11 m). The antigravity of the last foot is greater than about 1.3 kgf/kg of the left foot during the run-up stage, which allows for a higher rotational angular velocity and completion of the 720-degree difficulty of the whirlwind foot. As a result, it is crucial to pay attention to how you step with your right foot. In the backflip, the coordination of the two legs and the upper body is crucial. The right foot’s effective braking can help to increase the body’s rising angle. The trunk inclination angle in the flying stage is between 110° and 120°, the knee angle is between 60° and 70°, and the angle between the two legs is between 35° and 35°. When lifting off the ground and landing, the tibialis anterior muscle discharge is greater than the gastrocnemius muscle discharge, which helps to maintain the balance between the fulcrums. As a result, it is necessary to let the non-supporting leg fall first in order to achieve the goal of a smooth landing.
Solving the Problem of Time, Cost, and Quality Trade‐Off in Project Scheduling under Fuzzy Conditions Using Meta‐Heuristic Algorithms
Authors: Ghadir Hojjatullah , Shayannia Seyed Ahmad , Miandargh Mehdi Amir
Published: June 2022

Balancing the project’s time, cost, and quality involves deciding on different implementation methods for each project activity. Time and cost are minimized simultaneously, and the quality of the final product or service is maximized. Indeed, the use of search methods to determine the optimal execution methods of each activity requires the evaluation and review of various performance criteria such as time, cost, and especially the final quality of each activity. These performance measures, especially the quality of the different implementation methods, are reported and recorded in inaccurate, ambiguous, and vague numbers or concepts. In this research, new methods have been proposed to evaluate and investigate the trade‐off of time, cost, and quality of the project in conditions of uncertainty. This means that by fuzzy number theory, the specifications and conditions of a project are included in the problem of balancing time, cost, and quality. In fact, time, cost, and quality are considered triangular and trapezoidal fuzzy numbers. Also, the fuzzy multiattribute utility function approach (in which the concept of fuzzy computational operators is included) has been used to evaluate different combinations of execution methods of project activities. Since different quality combinations can be obtained with different combinations of parameters involved in the implementation of an algorithm, the Taguchi experimental design method has been used to adjust the parameters of the proposed algorithm. To solve the proposed model, particle mass optimization algorithms and artificial bee colonies have also been studied.
Application of a New Loss Function-Based Support Vector Machine Algorithm in Quality Control of Measurement Observation Data
Authors: Wu Youping , Tao Guoqiang
Published: June 2022

The loss function of the traditional support vector machine (SVM) method consists of hinge function and regularization, which is difficult to achieve the quality control of observation data. It requires a new loss function to measure the quality of the observed data. At this stage, researchers will use data cleaning or data preprocessing to process observational data. The data preprocessing method will normalize the data features, which will make the data process the same interval and a distribution. However, this method is also difficult to guarantee the accuracy of the data. This study uses the SVM method to study the integrity, unity, and accuracy of the observation data. This study also proposes a new loss function, which can obtain the uncertainty distribution of the observed data. The loss function of traditional SVM methods is that the uncertainty distribution of the data cannot be obtained. The results show that the SVM algorithm with the new loss function has better accuracy in processing the observed data. For the maximum prediction error of the observed data, the error with the new loss function is only 2.58%, which is reduced by 0.21% compared to the SVM method with the old loss function. However, the prediction error of the SVM algorithm with the old loss function is 2.78%, and the SVM algorithm with the new loss function has obvious prediction accuracy.
Insights into Nanopesticides for Ticks: The Superbugs of Livestock
Authors: Zaheer Tean , Ali Muhammad Muddassir , Abbas Rao Zahid , Atta Khazeena , Amjad Iqra , Suleman Anum , Khalid Zain , Aqib Amjad Islam
Published: June 2022

Livestock is an integral part of agriculture countries where ticks play significant role as potent pests causing considerable losses to economy and health. Drug resistance has made these pests supersede conventional therapies and control programs Nanotechnology here comes as an advancing and significant candidate alternatively able to reverse drug resistance. Nanoparticles, hence, against ticks may better be considered as nanopesticides that act in ways other than conventional drug efficacies. The methods of nanoparticles production include green synthesis, chemical synthesis, and arthropod-based synthesis. Pros and cons of these nanopesticides are by no means neglectable. Studies are fewer than needed to comprehensively discuss nanopesticides. Current review thus systematically covers aspects of ticks as livestock pests, their drug resistance, advent of nanotechnology against pests, their production methodologies, mechanisms of actions of ticks, and current limitations. This review opens several avenues for further research on nanoparticles as nanopesticides against ticks.
A Wushu Referee’s Decision Support System Using Error Recognition Theory
Authors: Lu Jin , Xie Ming
Published: June 2022

To realize the recognition and scoring of Wushu Athletes’ wrong actions by electronic referees, reduce the difficulty of referees’ recognition, help reduce man-made errors and influence in the process of competition judgment, and make the referee work fairer and more scientific, therefore, this paper aims to make an in-depth study on the Wushu referee decision support system based on the theory and method of error recognition. Firstly, this paper discusses the overall architecture of the Wushu decision support system, analyzes the functions and database design of each system in the system, constructs a digital and information-based Wushu referee decision support system, and uses the error matrix logic equation to solve the recognition state and goal. The Nrej3d technology is introduced for collecting the characteristics of martial arts wrong actions, and matching recognition is completed by using the sports space, to complete the research on the decision support system of martial arts referees based on the theory and method of wrong recognition. The simulation results show that the method proposed in this paper is superior to other methods in the recognition accuracy and effective measurement of martial arts wrong movements and has a certain application value.
VGG-UNet/VGG-SegNet Supported Automatic Segmentation of Endoplasmic Reticulum Network in Fluorescence Microscopy Images
Authors: Daniel Jesline , Rose J. T. Anita , Vinnarasi F. Sangeetha Francelin , Rajinikanth Venkatesan
Published: June 2022

This research work aims to implement an automated segmentation process to extract the endoplasmic reticulum (ER) network in fluorescence microscopy images (FMI) using pretrained convolutional neural network (CNN). The threshold level of the raw FMT is complex, and extraction of the ER network is a challenging task. Hence, an image conversion procedure is initially employed to reduce its complexity. This work employed the pretrained CNN schemes, such as VGG-UNet and VGG-SegNet, to mine the ER network from the chosen FMI test images. The proposed ER segmentation pipeline consists of the following phases; (i) clinical image collection, 16-bit to 8-bit conversion and resizing; (ii) implementation of pretrained VGG-UNet and VGG-SegNet; (iii) extraction of the binary form of ER network; (iv) comparing the mined ER with ground-truth; and (v) computation of image measures and validation. The considered FMI dataset consists of 223 test images, and image augmentation is then implemented to increase these images. The result of this scheme is then confirmed against other CNN methods, such as U-Net, SegNet, and Res-UNet. The experimental outcome confirms a segmentation accuracy of >98% with VGG-UNet and VGG-SegNet. The results of this research authenticate that the proposed pipeline can be considered to examine the clinical-grade FMI.
Analysis of Gender on Editorial Boards of Sport Sciences Journals
Authors: Pastor-Cisneros Raquel , Castro Inmaculada Torres , Adsuar-Sala Jose Carmelo , Bautista-Bárcena Lucía
Published: June 2022

This study analyses gender distribution on editorial boards of journals in the Sport Sciences category included in Journal Citation Reports (JCR). As far as we know, this study provides the first measure of gender distribution on editorial boards in Sport Sciences. A database consisting of 4,596 editors of journals in the Sport Sciences category was collected. The gender of these editors is inferred based on their first name using the package Gender data included in the statistical software R. This article found that 23% of the 4,596 editor ships are held by women. This proportion decreases to 10% if we focus on the most important editor of the journal, the so-called Editor in Chief (EiC). However, having a woman EiC is positively correlated with the presence of women on editorial boards. No significant correlation between the impact factor of the journal and the proportion of women editors on its editorial board was found. In addition, most women holding the position of EiC of journals in the first and second quartiles share this position with men.
Mechanism of Huangqi Sanxian Decoction Inhibiting Osteoclast Differentiation Based on Network Pharmacology
Authors: Shi Jian-Xin , Cai Xiao-Qun , Zhao Ze-Hao , Deng Yu , Zhou Zhi-Kun
Published: June 2022

Osteoclasts (OCs) have been the unique cell type exhibiting the bone-resorption activity in body. It is important to identify drugs to resist osteoclastogenesis to manage the bone-loss disorders. Huangqi Sanxian decoction (HQSXD) is utilized for the treatment of postmenopausal osteoporosis (PMOP) for a long history in East Asia. This work aimed to examine HQSXD’s activity in OC differentiation. Based on staining with tartrate-resistant acid phosphatase (TRAP), it was found that HQSXD suppressed OC generation under the induction of RANKL produced in the bone marrow-derived monocytes/macrophages (BMMs), with no cytotoxic effect. Later analysis like molecular exploration and network pharmacology (NP) suggested the role of HQSXD in suppressing genes associated with osteoclastogenesis via PI3K/Akt-mediated mechanism dose-dependently. This work might illustrate the molecular pharmacological mechanism involved in HQSXD’s effect on treating OC-associated disorders. Moreover, NP was found to modernize traditional Chinese medicine (TCM) research.
Contribution of Illicit Drug Use to Pharmaceutical Load in the Environment: A Focus on Sub‐Saharan Africa
Authors: Ripanda Asha S , Rwiza Mwemezi J. , Nyanza Elias Charles , Machunda Revocatus L. , Vuai Said Hamadi
Published: June 2022

Illicit drug abuse and addiction are universal issues requiring international cooperation and interdisciplinary and multisectoral solutions. These addictive substances are utilized for recreational purposes worldwide, including in sub‐Saharan Africa. On the other hand, conventional wastewater treatment facilities such as waste stabilization ponds lack the design to remove the most recent classes of pollutants such as illicit drug abuse. As a result, effluents from these treatment schemes contaminate the entire ecosystem. Public health officials are concerned about detecting these pollutants at alarming levels in some countries, with potential undesirable effects on aquatic species and increased health hazards through exposure to contaminated waters or recycling treated or untreated effluents in agriculture. Contaminants including illicit substances enter the environment by human excreta following illegal intake, spills, or through direct dumping, such as from clandestine laboratories, when their manufacturer does not follow accepted production processes. These substances, like other pharmaceuticals, have biological activity and range from pseudopersistent to highly persistent compounds; hence, they persist in the environment while causing harm to the ecosystem. The presence of powerful pharmacological agents such as cocaine, morphine, and amphetamine in water as complex combinations can impair aquatic organisms and human health. These compounds can harm human beings and ecosystem health apart from their low environmental levels. Therefore, this article examines the presence and levels of illicit substances in ecological compartments such as wastewater, surface and ground waters in sub‐Saharan Africa, and their latent impact on the ecosystem. The information on the occurrences of illicit drugs and their metabolic products in the sub‐Saharan Africa environment and their contribution to pharmaceutical load is missing. In this case, it is important to research further the presence, levels, distribution, and environmental risks of exposure to human beings and the entire ecosystem.
Research on Landscape Ecology of Planning and Management of Ecotourism Area Considering Scientific Calculation Method
Authors: Fan Zhijun , Xu Songjun
Published: June 2022

With the continuous development of social economy, ecotourism has also been greatly developed, and the ecological environment has been paid more and more attention by people. As a part of ecotourism, the planning and management of ecotourism areas has gradually become one of the focuses of research. In particular, the concept of “harmonious coexistence between man and nature” has gradually gained popularity. So how to protect the environment and promote the upgrading of ecotourism and landscape management in the development process is extremely important. This paper introduces the scientific calculation method and based on the scientific calculation method, first of all, it analyzes the relationship between landscape management and ecotourism, and combines the landscape elements such as scenic spots and corridors to build a corresponding network structure to support the planning practice of ecotourism areas, to maintain ecologically sustainable planning and development. Landscape ecology and tourism area management are important explorations in promoting ecotourism. The simulation experiment results show that the scientific calculation method is effective, which can provide support for the planning and management of ecotourism areas, and provide exploration for the construction of a harmonious environment between man and Earth.
Telomerase inhibition by retinoids precedes cytodifferentiation of leukemia cells and may contribute to terminal differentiation
Authors: Liu Liang , Berletch Joel B. , Green Jessica G. , Pate Mitchell S. , Andrews Lucy G. , Tollefsbol Trygve O.
Published: June 2022

Human promyelocytic leukemia HL60 cells display high telomerase activity, a phenotype related to their immortal status. All-trans retinoic acid (ATRA) is a clinically effective cytodifferentiating agent. To understand the mechanism underlying ATRA-induced cytodifferentiation, we did a kinetic analysis of the role of ATRA in inhibiting telomerase in HL60 cells. Our studies indicate that telomerase inhibition by ATRA occurred relatively early after treatment of HL60 cells due to a rapid decrease in hTERT gene expression. More importantly, however, we found through monitoring the expression of CD11b, a marker for granulocytic differentiation of HL60 cells, that down-regulation of telomerase preceded the differentiation of HL60 cells. These observations suggest that the hTERT gene may be a primary target of ATRA regulation of cellular differentiation and the antileukemia activity of ATRA may be mediated by its ability to induce the differentiation of the promyelocytic leukemia cells through down-regulation of the hTERT gene.
Retinoid X receptor-γ and peroxisome proliferator-activated receptor-γ expression predicts thyroid carcinoma cell response to retinoid and thiazolidinedione treatment
Authors: Klopper Joshua P. , Hays William R. , Sharma Vibha , Baumbusch Margaret A. , Hershman Jerome M. , Haugen Bryan R.
Published: June 2022

Poorly differentiated, metastatic thyroid cancer is difficult to treat. These tumors often do not concentrate radioactive iodine and may require chemotherapy, which is suboptimal and toxic. Nuclear hormone receptors peroxisome proliferator-activated receptor γ (PPARγ) and retinoid X receptor (RXR) are variably expressed in thyroid carcinoma cell lines. Expression of these receptors may predict thyroid cancer cell response to treatment with rexinoids and thiazolidinediones. We studied three thyroid carcinoma cell lines: BHP 5-16 (PPARγ−/RXRγ+), BHP 2-7 (PPARγ±/RXRγ−), and DRO-90 (RXRγ+/PPARγ+). BHP 5-16 (RXRγ+) cells treated with rexinoid had decreased proliferation to 69 ± 6% growth compared with vehicle. BHP 2-7 (PPARγ+) cells treated with thiazolidinedione had no decrease in cellular proliferation. DRO-90 (RXRγ+ and PPARγ+) cells had 36 ± 10%, 15 ± 3%, and 13 ± 4% growth when treated with rexinoid, thiazolidinedione, or a combination, respectively. We next investigated the role of apoptosis in the ligand-responsive BHP 5-16 and DRO-90 cells. BHP 5-16 cells underwent no significant apoptosis with rexinoid (1 μmol/L). DRO-90 cells, however, had 3.6 ± 1.3% apoptotic cells with vehicle, 13 ± 3.5% with rexinoid (1 μmol/L), 18 ± 4% with thiazolidinedione (1 μmol/L), and 28 ± 6% with combination treatment (1 μmol/L), suggesting that apoptosis plays a major role in this anaplastic cell line and that the effects of the two ligands are additive. We conclude that receptor expression is necessary for inhibition of thyroid carcinoma growth with ligand treatment but may not be sufficient for response. Additionally, expression of both RXRγ and PPARγ may be necessary for maximal growth inhibition by ligands and may be required for the increased apoptosis.
Disulfiram inhibits activating transcription factor/cyclic AMP-responsive element binding protein and human melanoma growth in a metal-dependent manner in vitro, in mice and in a patient with metastatic disease
Authors: Brar Sukhdev S. , Grigg Claude , Wilson Kimberly S. , Holder Walter D. , Dreau Didier , Austin Catherine , Foster Mareva , Ghio Andrew J. , Whorton A. Richard , Stowell Grayson W. , Whittall Linda B. , Whittle Robert R. , White David P. , Kennedy Thomas P.
Published: June 2022

The thiocarbamate alcoholism drug disulfiram blocks the P-glycoprotein extrusion pump, inhibits the transcription factor nuclear factor-κB, sensitizes tumors to chemotherapy, reduces angiogenesis, and inhibits tumor growth in mice. Thiocarbamates react with critical thiols and also complex metal ions. Using melanoma as the paradigm, we tested whether disulfiram might inhibit growth by forming mixed disulfides with critical thiols in a mechanism facilitated by metal ions. Disulfiram given to melanoma cells in combination with Cu2+ or Zn2+ decreased expression of cyclin A and reduced proliferation in vitro at lower concentrations than disulfiram alone. In electrophoretic mobility shift assays, disulfiram decreased transcription factor binding to the cyclic AMP-responsive element in a manner potentiated by Cu2+ ions and by the presence of glutathione, suggesting that thiocarbamates might disrupt transcription factor binding by inducing S-glutathionylation of the transcription factor DNA binding region. Disulfiram inhibited growth and angiogenesis in melanomas transplanted in severe combined immunodeficient mice, and these effects were potentiated by Zn2+ supplementation. The combination of oral zinc gluconate and disulfiram at currently approved doses for alcoholism also induced >50% reduction in hepatic metastases and produced clinical remission in a patient with stage IV metastatic ocular melanoma, who has continued on oral zinc gluconate and disulfiram therapy for 53 continuous months with negligible side effects. These findings present a novel strategy for treating metastatic melanoma by employing an old drug toward a new therapeutic use.
Differential sensitivity of cancer cells to docosahexaenoic acid–induced cytotoxicity: The potential importance of down-regulation of superoxide dismutase 1 expression
Authors: Ding Wei-Qun , Vaught Joshua L. , Yamauchi Hanako , Lind Stuart E.
Published: June 2022

Docosahexaenoic acid (DHA, 22:6 n-3), a polyunsaturated fatty acid found in fish oil, exerts cytotoxic effects on cancer cells. Although DHA was toxic toward five human cancer cell lines (MCF-7, MDA-MB-231, SiHa, Raji, and DHL-4), the lines were not uniformly sensitive. DHL-4, a bcl-2 overexpressing lymphoid line, was the most sensitive (IC50, 5.2 μmol/L) and the cervical cancer cell line, SiHa, was the most resistant (IC50, >300 μmol/L). Lipid peroxidation has been cited by others as an important component of DHA toxicity, and we confirmed that vitamin E prevents the cytotoxic effects of DHA. Lipid peroxidation was greater following DHA treatment of the sensitive DHL-4 cells than in the resistant SiHa cells, as assessed by thiobarbituric acid reactive substance generation. DHL-4 cells treated with DHA for 20 hours showed a 3.5-fold increase in thiobarbituric acid reactive substances, whereas SiHa cells showed no increase. Reverse transcription-PCR analysis detected a down-regulation of the expression of the major antioxidant enzyme, superoxide dismutase (SOD) 1, in DHL-4 cells but not in SiHa cells after DHA treatment. Knockdown of SOD1 expression in SiHa cells with small interfering RNA significantly enhanced lipid peroxidation and cytotoxicity on exposure to DHA. These results show that DHL-4 cells are highly sensitive to the cytotoxic effect of DHA and that regulation of SOD1 expression may play an important role in determining the sensitivity of different tumor cells to the cytotoxic effects of DHA.
Brain tumor cell lines resistant to O6-benzylguanine/1,3-bis(2-chloroethyl)-1-nitrosourea chemotherapy have O6-alkylguanine-DNA alkyltransferase mutations
Authors: Bacolod Manny D. , Johnson Stewart P. , Pegg Anthony E. , Dolan M. Eileen , Moschel Robert C. , Bullock Nancy S. , Fang Qingming , Colvin O. Michael , Modrich Paul , Bigner Darell D. , Friedman Henry S.
Published: June 2022

The chemotherapeutic activity of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU or carmustine) may be improved by the addition of O6-benzylguanine (O6-BG). The reaction of O6-BG with O6-alkylguanine-DNA alkyltransferase (AGT) prevents the repair of O6-chloroethyl lesions caused by BCNU. In clinics, the combination of O6-BG and BCNU is now being tested for the treatment of brain tumors. However, the effectiveness of this drug regimen may be limited by drug resistance acquired during treatment. To understand the possible mechanisms of resistance of brain tumor cells to the O6-BG/BCNU combination, we generated medulloblastoma cell lines (D283 MED, D341 MED, and Daoy) resistant to the combination of O6-BG and BCNU [O6-BG/BCNU resistant (OBR)]. DNA sequencing showed that all of the parent cell lines express wild-type AGTs, whereas every OBR cell line exhibited mutations that potentially affected the binding of O6-BG to the protein as evidenced previously by in vitro mutagenesis and structural studies of AGT. The D283 MED (OBR), Daoy (OBR), and D341 MED (OBR) cell lines expressed G156C, Y114F, and K165T AGT mutations, respectively. We reported previously that rhabdomyosarcoma TE-671 (OBR) also expresses a G156C mutation. These data suggest that the clonal selection of AGT mutants during treatment with O6-BG plus an alkylator may produce resistance to this intervention in clinical settings.
A G-quadruplex telomere targeting agent produces p16-associated senescence and chromosomal fusions in human prostate cancer cells
Authors: Incles Christopher M. , Schultes Christoph M. , Kempski Helena , Koehler Heike , Kelland Lloyd R. , Neidle Stephen
Published: June 2022

The trisubstituted acridine derivative BRACO-19 has been designed to interact with and stabilize the quadruplex DNA structures that can be formed by folding of the single-stranded repeats at the 3′ end of human telomeres. We suggest that the BRACO-19 complex inhibits the catalytic function of telomerase in human cancer cells and also destabilizes the telomerase-telomere capping complex so that cells enter senescence. Here, we present evidence showing that the inhibition of cell growth caused by BRACO-19 in DU145 prostate cancer cells occurs more rapidly than would be expected solely by the inhibition of the catalytic function of telomerase, and that senescence is accompanied by an initial up-regulation of the cyclin-dependent kinase inhibitor p21, with subsequent increases in p16INK4a expression. We also show that treatment with BRACO-19 causes extensive end-to-end chromosomal fusions, consistent with telomere uncapping.
Inhibition of angiogenesis by growth factor receptor bound protein 2-Src homology 2 domain bound antagonists
Authors: Soriano Jesus V. , Liu Ningfei , Gao Yang , Yao Zhu-Jun , Ishibashi Toshio , Underhill Charles , Burke Terrence R. , Bottaro Donald P.
Published: June 2022

Growth factor receptor bound protein 2 (Grb2) is an intracellular adaptor protein that participates in the signal transduction cascades of several angiogenic factors, including hepatocyte growth factor, basic fibroblast growth factor, and vascular endothelial growth factor. We described previously the potent blockade of hepatocyte growth factor–stimulated cell motility, matrix invasion, and epithelial tubulogenesis by synthetic Grb2-Src homology 2 (SH2) domain binding antagonists. Here, we show that these binding antagonists block basic morphogenetic events required for angiogenesis, including hepatocyte growth factor–, vascular endothelial growth factor–, and basic fibroblast growth factor–stimulated endothelial cell proliferation and migration, as well as phorbol 12-myristate 13-acetate–stimulated endothelial cell migration and matrix invasion. The Grb2-SH2 domain binding antagonists also impair angiogenesis in vitro, as shown by the inhibition of cord formation by macrovascular endothelial cells on Matrigel. We further show that a representative compound inhibits angiogenesis in vivo as measured using a chick chorioallantoic membrane assay. These results suggest that Grb2 is an important mediator of key proangiogenic events, with potential application to pathologic conditions where neovascularization contributes to disease progression. In particular, the well-characterized role of Grb2 in signaling cell cycle progression together with our present findings suggests that Grb2-SH2 domain binding antagonists have the potential to act as anticancer drugs that target both tumor and vascular cell compartments.
Cells resistant to HTI-286 do not overexpress P-glycoprotein but have reduced drug accumulation and a point mutation in α-tubulin
Authors: Loganzo Frank , Hari Malathi , Annable Tami , Tan Xingzhi , Morilla Daniel B. , Musto Sylvia , Zask Arie , Kaplan Joshua , Minnick Albert A. , May Michael K. , Ayral-Kaloustian Semiramis , Poruchynsky Marianne S. , Fojo Tito , Greenberger Lee M.
Published: June 2022

HTI-286, a synthetic analogue of hemiasterlin, depolymerizes microtubules and is proposed to bind at the Vinca peptide site in tubulin. It has excellent in vivo antitumor activity in human xenograft models, including tumors that express P-glycoprotein, and is in phase II clinical evaluation. To identify potential mechanisms of resistance induced by HTI-286, KB-3-1 epidermoid carcinoma cells were exposed to increasing drug concentrations. When maintained in 4.0 nmol/L HTI-286, cells had 12-fold resistance to HTI-286. Cross-resistance was observed to other Vinca peptide-binding agents, including hemiasterlin A, dolastatin-10, and vinblastine (7- to 28-fold), and DNA-damaging drugs, including Adriamycin and mitoxantrone (16- to 57-fold), but minimal resistance was seen to taxanes, epothilones, or colchicine (1- to 4-fold). Resistance to HTI-286 was retained when KB-HTI-resistant cells were grown in athymic mice. Accumulation of [3H]HTI-286 was lower in cells selected in intermediate (2.5 nmol/L) and high (4.0 nmol/L) concentrations of HTI-286 compared with parental cells, whereas accumulation of [14C]paclitaxel was unchanged. Sodium azide treatment partially reversed low HTI-286 accumulation, suggesting involvement of an ATP-dependent drug pump. KB-HTI-resistant cells did not overexpress P-glycoprotein, breast cancer resistance protein (BCRP/ABCG2/MXR), MRP1, or MRP3. No mutations were found in the major β-tubulin isoform. However, 4.0 nmol/L HTI-286-selected cells had a point mutation in α-tubulin that substitutes Ser for Ala12 near the nonexchangeable GTP-binding site of α-tubulin. KB-HTI-resistant cells removed from drug became less resistant to HTI-286, no longer had low HTI-286 accumulation, and retained the Ala12 mutation. These data suggest that HTI-286 resistance may be partially mediated by mutation of α-tubulin and by an ATP-binding cassette drug pump distinct from P-glycoprotein, ABCG2, MRP1, or MRP3.
Targeting ErbB receptor signaling: A pan-ErbB approach to cancer
Authors: Britten Carolyn D.
Published: June 2022

The ErbB receptors are localized to the cell membrane where they are activated by ligand to trigger a network of signaling pathways. In some cancer cells, dysregulation of ErbB-mediated signaling confers a growth advantage, resulting in cellular transformation and increased metastatic potential. Several agents that inhibit individual ErbB receptors have recently been approved for the treatment of human malignancies, validating ErbB receptors as therapeutic targets. One strategy to improve the efficacy of ErbB-targeted therapies is to inhibit multiple ErbB receptors, thereby interfering with the cooperation that exists between receptors. This minireview addresses the approaches being developed to concurrently inhibit multiple ErbB receptors.