bluuebunny/crossref_metadata_2025 huggingface dataset:
A Simple and Portable Personal Glucose Meter Method Combined with Molecular Docking for Screening of Lipase Inhibitors
Authors: Zhang Hao , Yang Feng-Qing , Gao Jian-Li
Published: September 2022

With the increase of obesity incidence, the development of antiobesity drugs has aroused extensive interest. In this study, a simple and portable personal glucose meter (PGM) method based on the lipase-mediated reaction combined with molecular docking was developed for the screening of lipase inhibitors. Lipase can catalyse the hydrolysis of 4-acetamidophenyl acetate to form acetaminophen, which can directly trigger the reduction of K3[Fe(CN)6] to K4[Fe(CN)6] in the glucose test strips and generate an electrical signal that can be detected by the PGM. When lipase inhibitors exist, the yield of acetaminophen will be reduced and results in a corresponding decrease of the PGM signal. Therefore, the activity of lipase can be measured by the PGM. After optimization of the experimental conditions, the inhibitory activity of fourteen small-molecule compounds and fifteen natural product extracts on lipase were evaluated by the developed PGM method. The results indicate that tannic acid, (-)-epigallocatechin gallate, (-)-epigallocatechin, (-)-epicatechin gallate, and epicatechin have good inhibitory effect on lipase (% of inhibition higher than 40.0%). Besides, the natural product extracts of Galla Chinensis, lemon, and Rhei Radix et Rhizoma have a good inhibitory effect on lipase with % of inhibition of (97.5 ± 0.6)%, (88.1 ± 0.7)%, and (79.1 ± 1.6)%, respectively. Finally, the binding sites and modes of six small-molecule compounds on lipase were investigated by the molecular docking study. The results show that the developed PGM method is an effective approach for the discovery of potential lipase inhibitors.
New Method for High Water Pressure Tunnel Design Based on Machine Learning for Smart Grid Energy Management and Groundwater Environmental Balance
Authors: You Xiaoming , Yan Gongxing , Yang Zhengqiang
Published: September 2022

In recent years, underwater shield tunnels are being developed according to large-scale sections. The problems of large buried depth and high water pressure have posed major challenges to the safety of segmented structures. The load-bearing capacity and damage of segmented structures under high water pressure features have always attracted attention. Based on a machine learning approach to smart grid energy management, this paper proposes a design method for high voltage tunnels in a balanced groundwater environment and tests the capacity of the high voltage tunnels. Based on the high water pressure failure test phenomenon of the large-section shield tunnel of the GIL project, this paper analyzes the failure characteristics and laws of the segment structure under high water pressure conditions. On this basis, an evaluation index for the load-bearing performance of the segment structure is proposed, and control suggestions are given based on the research results. According to the fault characteristics and the section structure law, the section performance evaluation index is proposed, and the control parameter recommendations are given based on the test results. Valuable discoveries and breakthroughs have been made in the failure of the prototype segment structure and the difference in the mechanical properties of the segment structure in the form of the high water pressure tunnel assembly. The research results show that under the condition of staggered assembly of high-voltage tunnels, the maximum dislocation amount of the high-voltage tunnel structure during instability failure is 10 mm, and the bolt strength is improved. The more important aspect is the existence of concave and tenon between the rings. In structure, the maximum stress of the bolts between the rings is only 38.6% of the yield stress at the time of instability failure. This indicates that the distributed concave-convex tenon between the segments not only can control the dislocation of the segments but also can ensure that the longitudinal bolts are well protected. It is safe to ensure the pressure resistance of the high water pressure tunnel.
Multifactor Authentication for Smart Emergency Medical Response Transporters
Authors: Alghamdi Turki , Gebali Fayez , Salem Fares
Published: September 2022

Securing telehealth IoT infrastructure is essential to provide high-level medical care and prevent cyberattacks. A vulnerable stage in IoT telehealth is while the patient is being transported to a healthcare facility, the transporter could be an ambulance or an air ambulance. In this paper, we propose a multifactor authentication scheme to secure the system when the patient is in transit to the healthcare facility. We apply this scheme to an ambulance, using physical unclonable functions (PUFs) embedded in the ambulance to facilitate authentication and secure key exchange. We validated the security of the proposed scheme using formal and informal security analysis. The analysis supports our claim that the proposed scheme protects against many types of attacks.
Rough Approximation Spaces via Maximal Union Neighborhoods and Ideals with a Medical Application
Authors: Hosny Mona , Al-shami Tareq M. , Mhemdi Abdelwaheb
Published: September 2022

One of the most popular and important tools to deal with imperfect knowledge is the rough set theory. It starts from dividing the universe to obtain blocks utilizing an equivalence relation. To make it more flexibility and expand its scope of applications, many generalized rough set models have been proposed and studied. To contribute to this area, we introduce new generalized rough set models inspired by “maximal union neighborhoods and ideals.” These models are created with the aim to help decision‐makers to analysis and evaluate the given data more accurately by decreasing the ambiguity regions. We confirm this aim by illustrating that the current models improve the approximations operators (lower and upper) and accuracy measures more than some existing method approaches. We point out that almost all major properties with respect to rough set model can be kept using the current models. One of the interesting obtained characterizations of the current models is preserving the monotonic property, which enables us to evaluate the vagueness in the data and enhance the confidence in the outcomes. Moreover, we compare the current approximation spaces with the help of concrete examples. Finally, we show the performance of the current models to discuss the information system of dengue fever disease and eliminate the ambiguity of the medical diagnosis, which produces an accurate decision.
Application Research of Ceramic Exhibits and VR User Experience Based on Deep Learning Method Based on Nonlinear Random Matrix Combined with Internet of Things Technology and Visualization System
Authors: Bai Yue
Published: September 2022

With the continuous development of the Internet of Things technology, the development of its technology has attracted more and more attention. Without the support of new technologies, China’s traditional civilization can continue and develop. Therefore, the pottery display in the virtual museum is discussed to strengthen the supporting role of the contemporary art museum. Based on the application of Internet of Things technology in virtual museums and based on its artistic expression in virtual museums, it integrates interactive experience with digital media art forms to lay a solid foundation for it. Through a virtual exhibition example of “Tang Dynasty Three-color Porcelain” to test the operability of its artistic expression, the interactive design of interactive experience is realized by using the methods of graphics, patterns, colors, and light. Through the actual operation and summary of its implementation, give optimal feedback to it so as to guide its specific application in the virtual museum, so as to promote its popularization and promotion in reality, thereby promoting its innovation and diversified development.
DA-ActNN-YOLOV5: Hybrid YOLO v5 Model with Data Augmentation and Activation of Compression Mechanism for Potato Disease Identification
Authors: Dai Guowei , Hu Lin , Fan Jingchao
Published: September 2022

To solve the problems of weak generalization of potato early and late blight recognition models in real complex scenarios, susceptibility to interference from crop varieties, colour characteristics, leaf spot shapes, disease cycles and environmental factors, and strong dependence on storage and computational resources, an improved YOLO v5 model (DA-ActNN-YOLOV5) is proposed to study potato diseases of different cycles in multiple regional scenarios. Thirteen data augmentation techniques were used to expand the data to improve model generalization and prevent overfitting; potato leaves were extracted by YOLO v5 image segmentation and labelled with LabelMe for building data samples; the component modules of the YOLO v5 network were replaced using model compression technology (ActNN) for potato disease detection when the device is low on memory. Based on this, the features extracted from all network layers are visualized, and the extraction of features from each network layer can be distinguished, from which an understanding of the feature learning behavior of the deep model can be obtained. The results show that in the scenario of multiple complex factors interacting, the identification accuracy of early and late potato blight in this study reached 99.81%. The introduced data augmentation technique improved the average accuracy by 9.22%. Compared with the uncompressed YOLO v5 model, the integrated ActNN runs more efficiently, the accuracy loss due to compressed parameters is less than 0.65%, and the time consumption does not exceed 30 min, which saves a lot of computational cost and time. In summary, this research method can accurately identify potato early and late blight in various scenarios.
Research on the Safety Thickness of Tunnel Outburst Prevention in Water-Rich Fault Fracture Zone Based on Janssen’s Theory
Authors: Zhong Zuliang , Li Yapeng , Zhou Xiaohan
Published: September 2022

In the construction of tunnel in water-rich fault fracture zone, when the thickness of outburst prevention is insufficient, it is very easy to cause water and mud inrush engineering accident. Therefore, it is very necessary to study the safety thickness of outburst prevention for this type of tunnel. In this paper, the expression of in situ stress in water-rich fault fracture zone is derived based on Janssen’s theory. Two mechanical models of outburst prevention rock mass are established, and according to the shear balance theory, the calculation formula for the safe thickness of outburst prevention is determined and the parameter sensitivity analysis is carried out. Finally, it is verified by engineering examples and numerical simulation. The results show that: (1) the calculation formula of outburst prevention thickness proposed in this paper is more perfect and shows good prediction effect for deep- and shallow-buried tunnels; (2) the greater the angle

α

between tunnel axis and fault zone and the dip

θ

of fault fracture zone, the smaller the critical safety thickness of outburst prevention and the safer it is for tunnel construction; (3) when the fault fracture zone inclines inward relative to the tunnel face, the gravity of the rock mass in the fault zone will lead to an increase in the safety thickness of outburst prevention, and reinforcement measures should be taken during actual construction.
Dapagliflozin Inhibits Ventricular Remodeling in Heart Failure Rats by Activating Autophagy through AMPK/mTOR Pathway
Authors: Ma Honghong , Ma Yanmei
Published: September 2022

Objective. Heart failure (HF) is the end stage of heart disease caused by various factors which mainly involves ventricular remodeling (VR). In HF patients with reduced ejection fraction, dapagliflozin (DAPA) reduced the risk of worsening HF or cardiovascular death. Thus, we attempted to clarify the specific role of DAPA underlying HF progression. Methods. The HF rat model was established to mimic characteristics of HF in vivo. HE staining assessed histopathological changes in left ventricular myocardial tissue of rats in each group. ELISA measured plasma ANP and BNP levels of rats in each group. M-mode echocardiography detected cardiac function of rats in each group. TUNEL staining detected apoptosis of infarct margin cells in myocardial tissue of rats in each group. Western blot detected levels of apoptosis-related proteins, autophagy-related proteins, and AMPK/mTOR-related proteins in myocardial tissue of rats in each group. Immunohistochemical staining detected caspase-3 or LC3B level in myocardial tissue of rats in each group. The HF cellular model was established to mimic characteristics of HF in vitro. Flow cytometry detected H9C2 cell apoptosis under different conditions. Western blot detected levels of apoptosis-related proteins, autophagy-related proteins, and AMPK/mTOR-related proteins in H9C2 cells under different conditions. Immunofluorescence detected caspase-3 or LC3B level in H9C2 cells under different conditions. Results. DAPA attenuated left VR and improved cardiac function in HF rats. DAPA attenuated cardiomyocyte apoptosis in HF rats. DAPA facilitated cardiomyocyte autophagy in HF rats via the AMPK/mTOR pathway. DAPA repressed hypoxia-induced H9C2 cell apoptosis by facilitating autophagy. DAPA repressed hypoxia-induced H9C2 cell apoptosis via the AMPK/mTOR pathway. Conclusion. DAPA suppresses ventricular remodeling in HF through activating autophagy via AMPK/mTOR pathway, which provides a potential novel insight for seeking therapeutic plans of HF.
The Effects of Basic Psychological Needs, Task–Technology Fit, and Student Engagement on MOOC Learners’ Continuance Intention to Use
Authors: Shin Areum , Song Hae-Deok
Published: September 2022

Massive open online courses (MOOCs) continue to remain in the spotlight as a promising future education environment. However, more than 80% of learners stop learning before attending one-third of the course. Despite a continuous spread of MOOC and high dropout rate, little has examined the antecedent factors that influence student engagement in technology enhanced MOOC learning environment from the Job Demand-Resources (JD-R) model. The purpose of this study was to empirically identify the effects of individuals’ basic psychological needs and the task–technology fit on MOOC learners’ continuance intention to use, as well as the mediating effect of student engagement in MOOCs. Based on survey data from 201 Korean-MOOC learners, structural equation modeling was employed to assess the model. The findings are as follows: The basic psychological needs in MOOCs did not directly affect continuance intention to use, but did affect student engagement; the task–technology fit of MOOCs directly affected continuance intention to use and student engagement; and student engagement in MOOCs mediated between the basic psychological needs and task–technology fit, and continuance intention to use. It directly affected continuance intention to use. Implications were suggested for designing courses in MOOCs to increase student engagement for continuance intention to use.
Mendelian Susceptibility to Mycobacterial Diseases (MSMD) in a 13-Year-Old Ethiopian Girl with Autosomal Dominant Interferon Gamma Receptor 1(IFN-γ R1) Defect: A Clinical Diagnostic and Treatment Challenge
Authors: Gebeyehu Netsanet Azene , Deribessa Solomie Jebessa , Alexandra Freeman , Demissie Messay Tesfaye , Mihretu Gebre W , Gebremariam Aklilu Melaku , Engliz Dagmawit Mitiku , Kidane Tizita Yosef , Million Bekele Lidya , Weldetsadik Abate Yeshidinber
Published: September 2022

Background. Mendelian susceptibility to mycobacterial diseases (MSMD) is an inborn error of immunity categorized as defects in intrinsic and innate immunity. MSMD is characterized by vulnerability to less virulent mycobacteria, such as Bacillus Calmette-Guérin (BCG) vaccine strains, as well as environmental mycobacteria (EM). The definitive diagnosis is made by genetic analysis. Treatments constitute antimycobacterial, interferon-gamma, surgery, and hematopoietic stem cell transplantation (HSCT), which is the only known curative treatment. The mortality rate ranges from 40% to 80% depending on the severity of the mutation. Case. A 13-year-old female patient had multiple hospital visits since the age of 6 months. The most striking diagnosis was repeated mycobacterial infections. She had tuberculosis affecting lymph nodes, skin and soft tissue, bone and joints, the lungs, and epidural and paraspinal regions. She has taken all the childhood vaccines, including BCG. She has been treated four times with first-line and once with second-line antituberculosis drugs. Currently, she is on treatment for nontuberculous mycobacteria and is receiving interferon-gamma. Genetic studies showed autosomal dominant Mendelian susceptibility to mycobacterial disease due to IFNG-R1 defect. Conclusion. To the authors’ knowledge, this is the first case report of Mendelian susceptibility to mycobacterial diseases secondary to interferon gamma receptor 1(IFNG-R1) defect in Ethiopia. Although it has been immensely challenging, our multidisciplinary team has learned a lot from the clinical presentation, diagnosis, and management of this child.
Smart Sensor Network Optimization and Line Defect Identification Based on UAV Transmission Inspection under 5G Technology
Authors: Ni Juan , Zhan Tanbochi
Published: September 2022

Transmission line is a key link in the transmission line, as the main equipment in the grid are located in the field; in the long-term harsh environmental conditions, the line is very easy to appear broken strands, broken, and other defects, which need to be regularly monitored and maintained. The traditional manual line inspection operation is not only harsh, labor-intensive, inefficient, and low precision but also has a great impact on the personal safety of the operators due to the complicated operating conditions. This project mainly focuses on 5G, intelligent sensor network technology, and the application of UAVs in high-voltage line inspection, detection, and maintenance. The developed inspection UAVs can effectively improve the efficiency of line inspection and quickly discover fault points, which brings convenience to the construction of power systems. In the 5G environment, the use of UAV transmission inspection technology for line fault identification can overcome the shortcomings of manual faults, but also timely and comprehensive fault detection, and improve the effectiveness and standardization of monitoring work.
UAV Based on Communication Network to Obtain Oil Pipeline Data and 3D Modeling
Authors: Zheng Minggao , Liu Qihua
Published: September 2022

With the advancement of science and technology and the development of industry, the demand for oil is increasing, and the measurement of oil is becoming more and more reliable and accurate. The communication network refers to the physical connection of various isolated devices to realize the link of information exchange between people, people and computers, and computers and computers, so as to achieve the purpose of resource sharing and communication. Oil and natural gas pipelines are an important strategic resource and the economic lifeline of a country. China’s long-distance oil and natural gas pipelines have developed rapidly in recent years, and the Beijing-Shijiazhuang Pipeline, the “West-East Gas Pipeline,” and the western crude oil and refined oil pipeline projects have been completed. The UAV can produce geometric data with high precision and build its 3D model. Therefore, this study proposed a UAV based on the communication network to obtain oil pipeline data and 3D modeling. The study mainly talked about the energy consumption in the era of communication. The energy acquisition was analyzed, the pipeline transportation measures for petroleum energy under UAV technology were focused on, the three-dimensional modeling of its terrain capture was carried out, and then the experimental data were analyzed after the equipment was debugged in the experimental part. The final experimental results showed that, under different frequencies, the data collected by the host computer were compared with the field measurement data, and the errors of the water and oil phases were calculated. It can be clearly seen from the data that the error was less than 5%, which also proved that this method was feasible.
Self‐Delivering Supramolecular Nanofiber Based on Peptide‐Rhein Conjugate
Authors: Wang Jingjing , Rui Xue , Jin Zhetong , Leng Xuejiao , Chen Zhipeng
Published: September 2022

A peptide‐drug conjugate (PDC) is a single molecule formed by one or more drug molecules that are conjugated with functional short peptides. Some specially designed PDC can construct self‐delivering supramolecular nanomedicine and improve the therapeutic effect. The design and synthesis of novel PDCs with unique assembly behavior are important for the drug delivery system. Rhein is a natural product extracted from rhubarb and has extensive pharmacological properties. In the present work, we successfully synthesized a novel PDC (VKVK‐rhein) based on rhein through solid‐phase synthesis technology and conventional coupling chemical methods. The anthraquinone structure of rhein and the structure of the short peptide (VKVK, Val‐Lys‐Val‐Lys) provided VKVK‐rhein with special assembly properties. VKVK‐rhein can be assembled into supramolecular nanofibers in water. The equilibrium solubility, oil‐water distribution coefficient, zeta potential, and cell viability of VKVK‐rhein were systematically studied. Our work lays a foundation for further biological application of rhein‐based PDCs.
Urban Functional Area Recognition Based on Unbalanced Clustering
Authors: Wu Junjie , Zhang Jian , Zhang Huixia
Published: September 2022

Urban functional area recognition refers to refining the main functions of building coverage areas. At present, multisource data analysis is prone to data imbalance, and types with large data volume are more likely to affect data analysis results. Therefore, this study took the main urban area of Taiyuan as the research object and used the Synthetic Minority Oversampling Technology (SMOTE) method to reduce the impact of data imbalance. In this study, the SOMTE method was used to incrementally process the microblog check-in data in the main urban area of Taiyuan, which reduced the phenomenon of data imbalance and further improved the recognition accuracy. The Point of Interest (POI) data were clustered through K-nearest neighbor, and microblog check-in data were semantically analyzed by Linear Discriminant Analysis (LDA). Then, the eigenvalues of the two kinds of data results were obtained by frequency density analysis. Finally, feature fusion was carried out by means of weighted average. The fused data were divided into single and mixed functional areas according to the difference of frequency density, which was rendered and displayed on the ArcGIS platform, so as to realize the visual identification and division of urban functional areas, and the results were compared with Gaode Map. The experimental results showed that this method can effectively identify urban functional areas with a recognition accuracy of 85%, which provided reference value for the planning and research of urban functional areas in the future.
Design of Noise-Reducing Two-Stage Cage Control Valve and Its Fluid Characteristics and Cavitation Study
Authors: Yu Ruiming , Lu Xi
Published: September 2022

For all kinds of media noise, noise reduction valve cage cannot meet the equal percentage flow characteristics, and for manufacturing and processing and other technical problems, research and design of new noise reduction two-stage cage control valve are necessary. The valve adopts noise reduction valve cage and curve valve cage with noise reduction, forming a two-stage noise reduction, with uniform flow, diffusion, and noise reduction effect, to meet the regulating valve equal percentage flow characteristics. The spool is evenly stressed and not easy to loosen and fall off, and the small opening is not easy to vibrate and shake. The flow characteristics of the noise-reducing two-stage cage control valve are studied, and the fluid flow coefficients, flow characteristic curves, the relationship of flow coefficients with nominal diameter at the same stroke, and the relationship of flow coefficients with different nominal diameters at different strokes are analyzed. The relationship between nominal diameter constant opening and cavitation coefficient with inlet velocity, the relationship between inlet velocity and cavitation coefficient with nominal diameter at half opening, and the relationship between inlet velocity and cavitation coefficient with nominal diameter at full opening were studied, and the cavitation generation and its effect on noise were analyzed. The noise and cavitation test showed that noise is very small and cavitation is difficult to produce, all meeting the noise reduction requirements.
A Comparative Cyclic Voltametric Study on Rare Earth (Eu, Sm, Dy, and Tb) Ions Doped La10Si6O27 Nanophosphors for Sensor Application
Authors: Kumar A. Naveen , Jnaneshwara D.M. , Ravikumar C.R. , Murthy H.C. Ananda , Prashantha S.C. , Kumar M.R. Anil , Ajay K.M.
Published: September 2022

The rare earth (RE = Eu, Sm, Dy, and Tb) ions doped La10Si6O27 nanophosphor was synthesized by a simple solution combustion method. The prepared La10Si6O27:RE3+ nanophosphors (LNPs) were subjected to diverse technical tools for exploring their structural, optical, morphological, and electrochemical features. The structural analysis using powder X-ray diffraction (PXRD) patterns revealed the hexagonal oxy apatite phase for LNPs with a crystallite size in the range of 25–50 nm, and the equivalent was affirmed by image analysis via transmission electron microscopy (TEM). Utilizing DRS data, the bandgap energy (Eg) values were recorded for LNPs. Cyclic voltametric (CV), electrochemical impedance spectroscopy (EIS), and sensor studies were performed using a modified carbon paste electrode of LNPs. The modified LNP electrodes were found to be highly effective in sensing paracetamol in acidic medium with a quick response time of 3 secs for sensing the drugs at 1 mM concentration. All the RE ions Eu3+, Sm3+, Dy3+, and Tb3+ (5 mol%)-doped LNPs exhibited the most promising electrochemical sensing characteristics.
Application of Virtual Reality Technology and 3D Technology in Game Animation Production
Authors: Wang Zehao , Deng Ye , Chen Wenlong
Published: September 2022

With the increasing pressure of modern young people, they begin to look for various ways to relax. Among them, game animation makes them immersive and has a low experience cost, which is one of the best ways to relax. Therefore, animation games have been welcomed by more and more young people. However, virtual reality technology and 3D technology have played a huge role in the production of game animation. Therefore, this paper aimed to study how virtual reality technology and 3D technology were applied in game animation production and put forward their advantages. This paper also proposed a method based on virtual reality technology and 3D technology and analyzed the production of game animation. The experimental results of this paper showed that in the survey results of the popularity of the A game, only 56 experiencers thought its effect was good, accounting for 18%. There were 145 experiencers who disliked the A game because they thought the A game was very boring and the game scene was very simple. In the survey results of the popularity of the B game, 222 experiencers liked this game, accounting for 71.6%, and 43 experiencers did not like the B game because they thought the 3D effect of the B game would make them dizzy and uncomfortable. It can be seen that the integration of virtual reality technology and 3D technology into game animation production is more popular, so the research in this paper is meaningful.
[Retracted] Development of College Students’ Resilience Scale
Authors: Wu Yin
Published: September 2022

In order to explore the dimensions of college students’ resilience and compile a measuring tool for contemporary Chinese college students’ resilience, semistructured interviews are conducted with 20 college students who have experienced adversity, and the initial dimension of college students’ resilience is obtained. Based on the initial dimensions, the project is compiled to form the “College Students’ Resilience Scale,” which is tested for 1374 college students, and four dimensions of the scale are obtained through exploratory factor analysis. The college students’ resilience scale consists of 26 items with 4 dimensions, namely, “self‐efficacy and adaptability,” “positive cognition,” “negative emotion adjustment ability,” and “perceived use of social support.” The self‐made college students’ resilience scale has good reliability and validity and is an effective measuring tool for college students’ resilience.
Analysis of Specific Perfluorohexane Sulfonate Isomers by Liquid Chromatography-Tandem Mass Spectrometry: Method Development and Application in Source Apportionment
Authors: Yang Liping , Chen Xin , Zhu Lingyan , Wang Yixin , Shan Guoqiang
Published: September 2022

Characterization of perfluorohexane sulfonate (PFHxS) isomers, a chemical proposed for listing under the Stockholm Convention, is important to elucidate its environmental behaviors and sources. Optimized chromatographic separation coupled with monitoring of the characteristic fragments enabled the identification of four mono-substituted and two di-substituted branched PFHxS isomers. The transitions of molecular ions m/z 399 to the fragments m/z 80 (n-), m/z 169 (iso-), m/z 319 (1m-), m/z 80 (2m-), and m/z 180 (3m-) were selected for quantifying the mono-substituted isomers. Method accuracy of the established LC-MS/MS was verified by comparing the results of technical products with those determined by 19F-nuclear magnetic resonance (NMR). The developed method was then used to quantify the isomeric compositions of PFHxS in the perfluorooctane sulfonate (PFOS) industrial products which contained PFHxS as an impurity, as well as in several kinds of water samples, with the limits of detection for all isomers in the range of 4 to 30 pg/L. For the first time, a liquid chromatography-tandem mass spectrometry method was established to separate and quantify the PFHxS isomers. The isomeric profiling of water samples suggested that PFHxS in the waters was mainly due to the direct contamination of PFHxS rather than from PFOS contamination.
Targeting STAT5 Signaling Overcomes Resistance to IDH Inhibitors in Acute Myeloid Leukemia through Suppression of Stemness
Authors: Liu Alex C.H. , Cathelin Severine , Yang Yitong , Dai David L. , Ayyathan Dhanoop Manikoth , Hosseini Mohsen , Minden Mark D. , Tierens Anne , Chan Steven M.
Published: September 2022

Mutant isocitrate dehydrogenase 1 (IDH1) and IDH2 block the differentiation of acute myeloid leukemia (AML) cells through production of R-2-hydroxyglutarate (R-2-HG). IDH inhibitors can induce differentiation of AML cells by lowering R-2-HG but have limited clinical efficacy as single agents. Here, we performed a genome-wide CRISPR knockout screen in an Idh1-mutated hematopoietic progenitor cell line to identify genes that increased the differentiation response to ivosidenib, an IDH1 inhibitor. The screen identified C-type lectin member 5a (Clec5a), which encodes a spleen tyrosine kinase (SYK)-coupled surface receptor, as one of the top hits. Knockout of Clec5a and Syk rendered cells more sensitive to ivosidenib-induced differentiation through a reduction in STAT5-dependent expression of stemness-related genes, including genes in the homeobox (HOX) family. Importantly, direct inhibition of STAT5 activity was sufficient to increase the differentiation response to IDH inhibitors in primary human IDH1- and IDH2-mutated AML cells, including those harboring mutations in receptor tyrosine kinase (RTK) and MAPK genes that have been linked to drug resistance. In patient-derived xenograft models of IDH1-mutated AML, combination treatment with ivosidenib and the STAT5 inhibitor pimozide was superior to each agent alone in inducing differentiation in leukemic cells without compromising normal hematopoiesis. These findings demonstrate that STAT5 is a critical mediator of resistance to IDH inhibitors and provide the rationale for combining STAT5 and IDH inhibitors in the treatment of IDH-mutated AML.

Significance:

A CRISPR knockout screen identifies a mechanism of resistance to IDH inhibitors in AML involving activated STAT5 signaling, suggesting a potential strategy to improve the clinical efficacy of IDH inhibitors.
ATF6-Mediated Signaling Contributes to PARP Inhibitor Resistance in Ovarian Cancer
Authors: McMellen Alexandra , Yamamoto Tomomi M. , Qamar Lubna , Sanders Brooke E. , Nguyen Lily L. , Ortiz Chavez Daniela , Bapat Jaidev , Berning Amber , Post Miriam D. , Johnson Joshua , Behbakht Kian , Nurmemmedov Elmar , Chuong Edward B. , Bitler Benjamin G.
Published: September 2022

High-grade serous ovarian cancer (HGSOC) is the deadliest ovarian cancer histotype due in-part to the lack of therapeutic options for chemotherapy-resistant disease. PARP inhibitors (PARPi) represent a targeted treatment. However, PARPi resistance is becoming a significant clinical challenge. There is an urgent need to overcome resistance mechanisms to extend disease-free intervals. We established isogeneic PARPi-sensitive and -resistant HGSOC cell lines. In three PARPi-resistant models, there is a significant increase in AP-1 transcriptional activity and DNA repair capacity. Using RNA-sequencing and an shRNA screen, we identified activating transcription factor 6 (ATF6) as a mediator of AP-1 activity, DNA damage response, and PARPi resistance. In publicly available datasets, ATF6 expression is elevated in HGSOC and portends a poorer recurrence-free survival. In a cohort of primary HGSOC tumors, higher ATF6 expression significantly correlated to PARPi resistance. In PARPi-resistant cell lines and a PDX model, inhibition of a known ATF6 regulator, p38, attenuated AP-1 activity and RAD51 foci formation, enhanced DNA damage, significantly inhibited tumor burden, and reduced accumulation of nuclear ATF6.

Implications:

This study highlights that a novel p38-ATF6-mediated AP-1 signaling axis contributes to PARPi resistance and provides a clinical rationale for combining PARPi and AP-1 signaling inhibitors.
Loss of the Volume-regulated Anion Channel Components LRRC8A and LRRC8D Limits Platinum Drug Efficacy
Authors: Widmer Carmen A. , Klebic Ismar , Domanitskaya Natalya , Decollogny Morgane , Howald Denise , Siffert Myriam , Essers Paul , Nowicka Zuzanna , Stokar-Regenscheit Nadine , van de Ven Marieke , de Korte-Grimmerink Renske , Galván José A. , Pritchard Colin E.J. , Huijbers Ivo J. , Fendler Wojciech , Vens Conchita , Rottenberg Sven
Published: September 2022

In recent years, platinum (Pt) drugs have been found to be especially efficient to treat patients with cancers that lack a proper DNA damage response, for example, due to dysfunctional BRCA1. Despite this knowledge, we are still missing helpful markers to predict Pt response in the clinic. We have previously shown that volume-regulated anion channels, containing the subunits LRRC8A and LRRC8D, promote the uptake of cisplatin and carboplatin in BRCA1-proficient cell lines. Here, we show that the loss of LRRC8A or LRRC8D significantly reduces the uptake of cisplatin and carboplatin in BRCA1;p53-deficient mouse mammary tumor cells. This results in reduced DNA damage and in vivo drug resistance. In contrast to Lrrc8a, the deletion of the Lrrc8d gene does not affect the viability and fertility of mice. Interestingly, Lrrc8d−/− mice tolerate a 2-fold cisplatin MTD. This allowed us to establish a mouse model for intensified Pt-based chemotherapy, and we found that an increased cisplatin dose eradicates BRCA1;p53-deficient tumors, whereas eradication is not possible in wild-type mice. Moreover, we show that decreased expression of LRRC8A/D in patients with head and neck squamous cell carcinoma, who are treated with a Pt-based chemoradiotherapy, leads to decreased overall survival of the patients. In particular, high cumulative cisplatin dose treatments lost their efficacy in patients with a low LRRC8A/D expression in their cancers. Our data therefore suggest that LRRC8A and LRRC8D should be included in a prospective trial to predict the success of intensified cisplatin- or carboplatin-based chemotherapy.

Significance:

We demonstrate that lack of expression of Lrrc8a or Lrrc8d significantly reduces the uptake and efficacy of cisplatin and carboplatin in Pt-sensitive BRCA1;p53-deficient tumors. Moreover, our work provides support to confirm the LRRC8A and LRRC8D gene expression in individual tumors prior to initiation of intensive Pt-based chemotherapy.
Circulatory cytokeratin 17, marginal zone B1 protein and leucine-rich α2-glycoprotein-1 as biomarkers for disease severity and fibrosis in systemic sclerosis patients
Authors: Bălănescu Anca , Băicuș Cristian , Bălănescu Eugenia , Bălănescu Paul
Published: September 2022

IntroductionSystemic sclerosis (Ssc) is a multiorgan debilitating autoimmune disease that associates the triad: vascular involvement, tissue fibrosis and profound immune response alterations. Numerous previous studies focused on identification of candidate proteomic Ssc biomarkers using mass-spectrometry techniques and a large number of candidate Ssc biomarkers emerged. These biomarkers must firstly be confirmed in independent patient groups. The aim of the present study was to investigate the association of cytokeratin 17 (CK17), marginal zone B1 protein (MZB1) and leucine-rich α2-glycoprotein-1 (LRG1) with clinical and biological Ssc characteristics.
Material and methodsSerum CK17, MZB1 and LRG1 were assessed in samples of the available Ssc biobank comprising of samples from 53 Ssc patients and 26 matched age and gender controls.
ResultsCirculatory CK17, LRG1 and MZB1 concentrations were increased in Ssc patients. Cytokeratin 17 is independently associated with Ssc disease activity. Patients with pulmonary fibrosis expressed higher LRG1 and MZB1 concentrations. Serum MZB1 concentrations were also associated with extensive skin fibrosis.
ConclusionsSerum CK17, MZB1 and LRG1 were confirmed biomarkers for Ssc. LRG1 seems a good biomarker for pulmonary fibrosis, while MZB1 is a good biomarker for extensive skin fibrosis. CK17 proved to be independently associated with Ssc disease severity, higher CK17 values being protective for a more active disease.
A Linguistic and Socio-affective Approach to Developing an Online Spanish Heritage Placement Exam
Authors: Durán Urrea Evelyn , Lado Beatriz
Published: September 2022

This article describes the development and validation of a placement exam designed to identify and place Spanish heritage language learners in the heritage language program at Lehman College, the City University of New York (CUNY), an urban institution located in Northeastern United States (Bronx, New York City). Building upon previous research (e.g., Fairclough et al., 2010; Potowski et al., 2012), we provide an overview of the process we followed, including selecting content, computerization of the exam, and reliability analysis. A combination of quantitative analyses and qualitative observations during the pilot phase allowed us to identify the linguistic areas that were better at discriminating among levels, and the socio-affective factors that had to be taken into account to understand learners’ needs. As we continue to improve subsequent versions of the exam, this approach will allow us to better place students while reassessing and redesigning the curriculum.
The Uyghurs
Authors: Khen Hilly Moodrick-Even
Published: September 2022

The concept of cultural genocide has been abrogated from the Convention on the Prevention and Punishment of the Crime of Genocide (1948). The article elaborates on the concept of cultural genocide, its development, and its exclusion from the Genocide Convention and claims for its reconsideration in the discourse on genocide. It uses the Uyghurs’ case study to exemplify how the prohibition on cultural genocide against ethnic groups can become a soft law norm through states’ practice and legal instruments of international law that support the concept of cultural genocide. The article concludes with the legal and political merits of the prohibition on cultural genocide as a soft law norm. It focuses on how this process can promote the fight against genocide—particularly in the case of powerful states in the international arena, such as China.
Indonesia and the Third Indochina War: The End of Containment
Authors: Fibiger Mattias
Published: September 2022

The Third Indochina War called forth dramatic changes in the international relations of Southeast Asia. Foremost among these changes was a shift in the geopolitical orientation of the Association of Southeast Asian Nations (asean). The organization’s founders established asean in 1967 to contain Chinese influence in Southeast Asia. But in the wake of the Vietnamese invasion of Cambodia in late 1978, asean forged a tacit alliance with the People’s Republic of China to pursue a campaign of rollback against Vietnam. This article argues that asean’s volte-face and China’s reentry into networks of regional diplomacy depended upon a shift in Indonesian threat perceptions. As political Islam displaced Chinese communism as the key threat fixating Indonesian policy, the Suharto regime abandoned its longstanding attempts to integrate Vietnam into the architecture of regional order and instead accommodated itself to a Thai-led effort to enlist China as a counterweight against Vietnam. The reorientation of Indonesian diplomacy reveals the dynamics of a phenomenon that anthropologist Heonik Kwon has called the “decomposition” of the Cold War – the geographically and temporally uneven erosion of the Cold War as a social reality and the gradual elaboration of a post-Cold War era.
First adult record, redescription and distribution of Stemonosudis elongata (Aulopiformes: Paralepididae)
Authors: HO HSUAN-CHING , HUANG CHIH-HSIUNG
Published: September 2022

The original description of Macroparalepis elongatus Ege, 1933 (family Paralepididae) was based on a young specimen taken from Sri Lanka. No adult information is available since it was described. Six additional specimens, including three adults and three young specimens, were found in the museum collections. The adult morphology is described for the first time and its distribution range is now extended to South Pacific Ocean off New Caledonia and Australia, and the Western Indian Ocean off Madagascar. Detailed description and comparison of these specimens and the holotype, as well as a revised diagnosis for the species, are provided.
Redescription of Lophiodes lugubris (Alcock, 1894), with the largest record of Lophiodes triradiatus (Lloyd, 1909) from the South China Sea (Lophiiformes: Lophiidae)
Authors: HO HSUAN-CHING , LIN CHIEN-HSIANG
Published: September 2022

A rare lophiid anglerfish species, Lophiodes lugubris, is redescribed on the basis of two syntypes and non-types. It is unique in having only 4 dorsal-fin spines, among the congeners. Examination of specimens reveals this species is widespread in the Indian Ocean and a specimen newly collected from off Dongsha Island represents the first record of the South China Sea, as well as the Pacific Ocean. A largest record specimen of Lophiodes triradiatus known to date is also documented. Comments on the morphology of sagittal otoliths taken from Taiwanese lophiids are provided.
New records of spongicolid shrimps (Crustacea, Decapoda, Stenopodidea) from Taiwan
Authors: CHEN CHIEN-LIN , CHAN TIN-YAM
Published: September 2022

Spongicolid shrimps of the three genera, Engystenopus Alcock & Anderson, 1894, Spongicola De Haan, 1844 and Spongicoloides Hansen, 1908 are recorded from Taiwan for the first time. The newly recorded species are Engystenopus palmipes Alcock & Anderson, 1894, Spongicola andamanicus Alcock, 1901, S. goyi Saito & Komai, 2008, S. levigatus Hayashi & Ogawa, 1987 and Spongicoloides iheyaensis Saito, Tsuchida & Yamamoto, 2006. A total of six genera and nine species of stenopodidean shrimps are now known from Taiwan. A key to the Taiwanese species of stenopodideans is provided.
A new freshwater goby of Rhinogobius lingtongyanensis (Teleostei, Gobiidae) from the Dongshi river basin, Fujian Province, southeastern China
Authors: CHEN I-SHIUNG , WANG SHEN-CHIH , CHEN KWANG-YIAO , SHAO KWANG-TSAO
Published: September 2022

A new species of freshwater gobiid fish of genus Rhinogobius Gill, 1859, were collected from the upper tributary of Dongshi river basin of Janchou City in southern region of Fujian Province, China. Rhinogobius lingtongyanensis n. sp. can be well distinguished from other congeners by the following features: (1) fins: second dorsal fin rays I/8; anal fin rays I/7; pectoral fin rays modally 16; (2) squamation: longitudinal scale series 25-27 (modally 26); predorsal scales 3-6 (modally 5-6); (3) vertebral count 26; and (4) specific colouration in male: lateral body with 6-7 major patches of irregularly grayish to brownish black marks; cheek blackish brown with four oblique grayish black stripes; branchiostegal membrane grayish blue without any light spots; first dorsal fin broad grayish brown band in middle, outer margin pinkish orange; pectoral fin base with longitudinal deep brown bar in upper region; and caudal fin gray with four vertical rows of brown spots, its base with a short brownish black bar. It belongs to the non-diadromous, fluvial hill-stream species. A diagnostic key to all valid species from Fujian Province, China is also provided in this paper.
A new freshwater gobiid species of Rhinogobius Gill, 1859 (Teleostei: Gobiidae) from northern Taiwan
Authors: CHEN I-SHIUNG , WANG SHEN-CHIH , SHAO KWANG-TSAO
Published: September 2022

A new freshwater rhinogoby has been collected and surveyed from northern Taiwan. The new species, Rhinogobius yangminshanensis n. sp. with fluvial life history can be well distinguished from other congeners by the following combination of features: (1) fin rays: second dorsal fin rays I/9; anal fin rays I/8; pectoral fin rays modally 16; (2) squamation: longitudinal scale series 28–30 (modally 29); perdorsal scales 9–10 (modally 9); (4) vertebral count 27; (5) rear edge of mouth: merely extending to vertical of anterior margin of pupil in male and (6) specific colouration: lateral side with 6–7 longitudinal rows of bright orange to orange red spots in male which general size about 1/2 of pupil diameter. Cheek and opercle with 24–35 orange spots in male. Branchiostegal membrane with many minute orange spots in male. Caudal fin with distally orange zone in male with about 3 vertical rows of orange or orange red spots. First dorsal fin with broad orange band on distally 1/3 area. A middle black spot in abterior first dorsal fin. Pectoral fin with two rows red orange spots in male. The phylogenetic comparisons have revealed that the great mitogenetic differences of R. yangminshanensis with all other congeneric species and sister species would be R. rubromaculatus in Taiwan. A diagnostic key to all valid species of Rhinogobius from Taiwan is also provided.