bluuebunny/crossref_metadata_2025 huggingface dataset:
Review—Recent Advances in Graphene-Based Field-Effect-Transistor Biosensors: A Review on Biosensor Designing Strategy
Authors: Wang Shuo , Qi Xin , Hao Danni , Moro Ramiro , Ma Yanqing , Ma Lei
Published: January 2022

Biosensors for quick diagnosis and in situ monitoring are increasingly needed in health care. Field-effect transistor (FET) based biosensors have attracted much attention due to their high sensitivity and compatibility with point-of-care applications. As the most important 2D material, graphene has been investigated intensively as a channel material for transistor-based sensors due to its easily enhanced selectivity by rather simple functionalization. However, in order to realize its practical applications, challenges still remain, such as device stability and reproducibility. Here, we review recent progress in the general design strategy of high-performance graphene field-effect transistor (GFET) biosensors with emphasis on the device physics, defects, Debye screening, and functionalization. Finally, both current applications and perspectives on future development are given.
Estimating in vivo potassium distribution and fluxes with stable potassium isotopes
Authors: Youn Jang H. , Oh Young Taek , Gili Stefania , McDonough Alicia A. , Higgins John
Published: January 2022

Extracellular potassium (K+) homeostasis is achieved by a concerted effort of multiple organs and tissues. A limitation in studies of K+ homeostasis is inadequate techniques to quantify K+ fluxes into and out of organs and tissues in vivo. The goal of the present study was to test the feasibility of a novel approach to estimate K+ distribution and fluxes in vivo using stable K+ isotopes. 41K was infused as KCl into rats consuming control or K+-deficient chow ( n = 4 each), 41K-to-39K ratios in plasma and red blood cells (RBCs) were measured by inductively coupled plasma mass spectrometry, and results were subjected to compartmental modeling. The plasma 41K/39K increased during 41K infusion and decreased upon infusion cessation, without altering plasma total K+ concentration ([K+], i.e., 41K + 39K). The time course of changes was analyzed with a two-compartmental model of K+ distribution and elimination. Model parameters, representing transport into and out of the intracellular pool and renal excretion, were identified in each rat, accurately predicting decreased renal K+ excretion in rats fed K+-deficient vs. control diet ( P < 0.05). To estimate rate constants of K+ transport into and out of RBCs, 41K/39K were subjected to a simple model, indicating no effects of the K+-deficient diet. The findings support the feasibility of the novel stable isotope approach to quantify K+ fluxes in vivo and sets a foundation for experimental protocols using more complex models to identify heterogeneous intracellular K+ pools and to answer questions pertaining to K+ homeostatic mechanisms in vivo.
A simple method to generate human airway epithelial organoids with externally orientated apical membranes
Authors: Boecking Carolin A. , Walentek Peter , Zlock Lorna T. , Sun Dingyuan I. , Wolters Paul J. , Ishikawa Hiroaki , Jin Byung-Ju , Haggie Peter M. , Marshall Wallace F. , Verkman Alan S. , Finkbeiner Walter E.
Published: January 2022

Organoids, which are self-organizing three-dimensional cultures, provide models that replicate specific cellular components of native tissues or facets of organ complexity. We describe a simple method to generate organoid cultures using isolated human tracheobronchial epithelial cells grown in mixed matrix components and supplemented at day 14 with the Wnt pathway agonist R-spondin 2 (RSPO2) and the bone morphogenic protein antagonist Noggin. In contrast to previous reports, our method produces differentiated tracheobronchospheres with externally orientated apical membranes without pretreatments, providing an epithelial model to study cilia formation and function, disease pathogenesis, and interaction of pathogens with the respiratory mucosa. Starting from 3 × 105 cells, organoid yield at day 28 was 1,720 ± 302. Immunocytochemistry confirmed the cellular localization of airway epithelial markers, including CFTR, Na+/K+ ATPase, acetylated-α-tubulin, E-cadherin, and ZO-1. Compared to native tissues, expression of genes related to bronchial differentiation and ion transport were similar in organoid and air-liquid interface (ALI) cultures. In matched primary cultures, mean organoid cilia length was 6.1 ± 0.2 µm, similar to that of 5.7 ± 0.1 µm in ALI cultures, and ciliary beating was vigorous and coordinated with frequencies of 7.7 ± 0.3 Hz in organoid cultures and 5.3 ± 0.8 Hz in ALI cultures. Functional measurement of osmotically induced volume changes in organoids showed low water permeability. The generation of numerous single testable units from minimal starting material complements prior techniques. This culture system may be useful for studying airway biology and pathophysiology, aiding diagnosis of ciliopathies, and potentially for high-throughput drug screening.
Effects of chronic intermittent hypoxia on left cardiac function in young and aged mice
Authors: Wei Qin , Xu Xuan , Chen Long , Wang Tao , Xie Liang , Yu Fu-Chao , Song Si-Fan , Sheng Zhi-Qiang , Tong Jia-Yi
Published: January 2022

Obstructive sleep apnea (OSA) is an independent risk factor for cardiovascular disease that is characterized by chronic intermittent hypoxia (CIH), and its impact is related to age. This study aims to assess the age-related impact of CIH on cardiac function and to further explore the mechanism. After 8 wk of severe CIH exposure, the hearts of young mice showed slight physiological hypertrophy, decreased diastolic function, and collagen I accumulation but no obvious change in contractile function. However, the contractile function of the hearts of aged mice was severely decreased. CIH exposure promoted the fragmentation of mitochondria in the hearts of aged mice and decreased the mitochondrial membrane potential of cardiomyocytes, but these effects were not observed in young mice exposed to the same conditions. CIH induced significant decreases in basal respiration, maximum respiration, and ATP production in cardiac mitochondria of aged mice compared with those of young mice. The assessment of mitochondrial-related proteins showed that young mouse hearts had upregulated adaptive nuclear respiratory factors (Nrf)1/2 sirtuin (SIRT)1/3 and transcription factor A (TFAM) expression that stabilized mitochondrial function in response to CIH exposure. Aged mouse hearts exhibited maladaptation to CIH exposure, and downregulation of SIRT1 and TFAM expression resulted in mitochondrial dysfunction.
Degenerative cervical myelopathy delays responses to lateral balance perturbations regardless of predictability
Authors: Boerger T. F. , McGinn L. , Wang M. C. , Schmit B. D. , Hyngstrom A. S.
Published: January 2022

Frontal plane reactive postural control is impaired in persons with degenerative cervical myelopathy because of delayed muscle responses. Additionally, postural control varies across stance width, predictability, and perturbation magnitude.
5G-EECC: Energy-Efficient Collaboration-Based Content Sharing Strategy in Device-to-Device Communication
Authors: Khan Nauman , Khan Imran Ali , Arshed Jawad Usman , Afzal Mehtab , Ahmed Muhammad Masroor , Arif Muhammad
Published: January 2022

In the past few years, mobile data traffic has seen exponential growth due to the emergence of smart applications. Although throughput enhancement techniques such as macro- and femtocells reduce cell size, they are relatively expensive to implement. Mobile device-to-device (D2D) communication has emerged as a solution to support the growing popularity of multimedia content for local service in next-generation 5G cellular networks. Content sharing is the prominent feature, which helps D2D communication in reducing offload traffic on the network, improving the energy efficiency of the device, and reducing backhaul connectivity costs. In traditional mapping approaches such as one to one or one to many, a massive amount of traffic is distributed among the devices resulting in high-energy consumption. In this paper, we propose a novel energy-efficient content sharing scheme called Energy-Efficient Collaboration-based Content (EECC) sharing strategy in D2D communication that shares content equally across devices based on their capacities and battery life under mobility. The proposed work includes cluster formation, cluster head selection, and helper node selection. In addition, we relied on a cooperative caching policy to ensure that content is distributed efficiently. The simulation results indicate a 12.05% reduction in energy compared to the state-of-the-art technique with a 2-gigabyte video file. To evaluate scalability, we increased the file size from 3 to 4 gigabytes, yet the performance in terms of energy consumption remained the same.
Research on the Evolution of High-Quality Development of China’s Provincial Foreign Trade
Authors: Wu Yanqiu , Zhang Shuxiao
Published: January 2022

The new development concept is the theoretical guidance and important foundation for high-quality foreign trade development in the new era. This paper develops an evaluation index system to measure the high-quality development level of foreign trade based on the meaning of high-quality development of foreign trade under the new concept of development. The dynamic changing trend of high-quality development of China's provincial foreign trade from 2013 to 2019 and the ranking change of the development index are examined in this paper using a time series factor model. Finally, China's provinces are categorized based on the quality of their foreign trade development. The findings show that, from 2013 to 2019, China's high-quality foreign trade development has been on the rise; the level of high-quality foreign trade development has been raised to varying degrees in the eastern, central, and western regions of China, but each region plays a different role. Compared to 2013, the truly “high-quality” areas of China’s provincial foreign trade development were always concentrated in the eastern region, which ranked high on the comprehensive evaluation index, while the “low-quality” areas were mainly concentrated in the central and western regions, which ranked low on the comprehensive evaluation index.
Investigation on the Horizontal Landing Velocity and Pitch Angle Impact on the Soft-Landing Dynamic Characteristics
Authors: Lin Qing , Ren Jie
Published: January 2022

The dynamic analysis of the soft landing of the lunar probe is very important to the design of the probe. The initial movement and attitude parameters of the probe during landing have a direct influence on the landing impact. In order to investigate the lunar probe soft-landing dynamic impact by different initial horizontal velocities, pitch angles, and inclinations of the lunar slope, an inertial force-based 7-DOF soft-landing dynamic model is applied under two conditions: the upward and downward slope landing surfaces. The impact on the dynamic characteristics of soft landing is analyzed in terms of body displacement, body overload, and the forces of the primary and secondary buffer struts due to the change of initial horizontal velocity and initial pitch angle of the probe. The result shows that, in 2-2 landing mode, the stress conditions on the primary and secondary struts are obviously impacted by initial horizontal velocity, and the initial pitch angle affects the body overload and the loading state of the secondary buffer strut. The body overload and landing impact could be significantly mitigated if the lunar probe’s horizontal landing speed is limited within 1 m/s, the pitch angle is limited within 12°, and the landing is along the uphill terrain with the inclination of the lunar slope less and equal to 9°. The analysis can directly determine the range of the horizontal speed and pitch attitude angle to ensure the safety of landing, and provide a reference for the reasonable control design of the lander’s horizontal speed and pitch attitude.
Study on Liquefaction Resistance of Pile Group by Shaking Table Test
Authors: Zhang Cong , Feng Zhongju , Guan Yunhui , Chen Huiyun , Wang Fuchun , Xu Boxi
Published: January 2022

This study investigated the antiliquefaction property of the pile group. It is shown in the pore pressure ratio, pile acceleration, and bending moment response of saturated silt fine sand. The response law of pile acceleration and bending moment during liquefaction development is proved. The results show that liquefaction occurs in single piles, four piles, and six piles under the action of 0.35 g seismic wave. But the time of liquefaction is different. There is an obvious difference in the response of pile acceleration and bending moment during liquefaction. Liquefaction in the saturated silt fine sand develops from shallow to deep. The complete liquefaction of six piles takes the longest time, while the single pile takes the shortest time, and the average delay was 8.82 s. With the increase of the number of piles, there are some differences in pile acceleration, magnification factor, and pile bending moment, which are mainly reflected in time. The peak acceleration appearance of six piles was 3.08 s later than that of the single pile on average. The maximum bending moment appearance of six piles was 1.96 s later than that of the single pile on average. The acceleration and bending moment of the pile begins to attenuate when the pore pressure ratio increases. It shows that the saturated silt fine sand has softening and damping effect before liquefaction. In summary, the antiliquefaction performance of the pile group is better than that of a single pile. In the seismic design of pile foundation in liquefied soil, the antiliquefaction performance of the pile group is better.
A Fuzzy Qualitative Simulation Study of College Student’s Mental Health Status
Authors: Deng Xiying
Published: January 2022

The fuzzy qualitative approach used in this paper provides an in‐depth study and analysis of the simulation of the mental health state of college students, which is continued from another perspective using structural equation modeling, in which sufficient conditions for the equation to satisfy local asymptotic stability, instability, and global attraction at the zero equilibrium point and sufficient conditions for the existence and instability of nonzero equilibrium points are discussed, respectively. In addition, the paper proves the boundedness of the solutions of the equation by mathematical induction and obtains sufficient conditions to ensure that the solutions are bounded. The intrinsic causes of college students’ psychological problems lie in the lack of social support in the family and outside the family and the influence of the overall social environment on college students. Finally, this paper puts forward some suggestions and countermeasures based on this research finding from three levels: family, school, and society, giving full play to the role of family support; schools should expand the main body of support, enrich the form of support, and provide comprehensive and multifaceted social support for college students. Finally, the simulation of the equation is carried out to verify the correctness of its conclusion. The rate of mental subhealth is 1.605 times that of college students admitted to ideal universities, which is consistent with our actual situation. At the level of condition guarantee, the hardware facilities, management system, and professional team of mental health education for college students are evaluated; from the specific content, the teaching work, educational activities, psychological counseling, and crisis intervention of mental health education for college students are evaluated; from the perspective of effect, the degree of goal achievement, social adaptation, and result satisfaction of the effect of mental health education for college students are evaluated. The final part analyzes and elaborates on the construction of evaluation indexes of mental health education for college students, the design of weight of guiding indexes, and the content and optimization path of the evaluation test. The results of the study show that personal ability and external pressure are important factors influencing college students’ mental health, and the influence of external pressure is greater. Logistic regression and structural equation modeling methods complement each other, and the findings of structural equation modeling are more comprehensive and integrated, while logistic regression illustrates the degree of each influencing factor.
Pore Changes in Purple Mudstone Based on the Analysis of Dry-Wet Cycles Using Nuclear Magnetic Resonance
Authors: Dang Chen , Sui Zhili , Yang Xiuyuan , Ge Zhenlong
Published: January 2022

The study on the change of rock pore structure during the weathering of purple mudstone is of guiding significance to the stability of the bank slope of the three gorges reservoir. In this paper, the pore changes in the wet and dry circulation of purple mudstone in the three gorges reservoir area are studied by means of nuclear magnetic resonance (NMR). The results show that the simulated weathering of wet and dry circulation has a great influence on the purple mudstone. With an increase in the number of dry-wet cycles, the purple mudstone pore volume ratio significantly changed. Originally, it consisted of a small pore structure with a single pore diameter of 0.01–0.1 µm and changed to a variety of pore structures with various pore diameters of 0.001–100 µm. With the increase in the number of dry-wet cycles, the micropores (0.001–0.1 µm) were transformed into macropores (0.1–1 µm). The area of the second peak of the three samples (large pores 0.1–1 µm) increased from 0.9413, 0.9974, and 0.6779 to 0.9871, 1.1498, and 0.9901, respectively.
Proliferation of Cyber Situational Awareness: Today’s Truly Pervasive Drive of Cybersecurity
Authors: Nazir Hafiz Muhammad Jamsheed , Han Weihong
Published: January 2022

Situation awareness (SA) issues necessitate a comprehension of present activities, the ability to forecast, what will happen next, and strategies to assess the threat or impact of current internet activities and projections. These SA procedures are universal, domain-independent and can be used to detect cyber intrusions. This study introduces cyber situation awareness (CSA), its origin, conception, aim, and characteristics based on an analysis of function shortages and development requirements. Furthermore, we discussed the CSA research framework and examined the research history, which is the essential aspect, and assessed the present issues of the research as well. The assessment approaches were divided into three methods: mathematics model, knowledge reasoning, and pattern recognition. The study then goes into detail regarding the core idea, assessment procedure, strengths, and weaknesses of novel approaches, and then, it addresses CSA from three perspectives: model, knowledge representation, and assessment methods. Many common approaches are contrasted, and current CSA application research in the realms of security, transmission, survivability, and system evaluation is discussed. Finally, this study summarized the findings of the present from technical and application systems, outlined CSA’s future development directions, and provided adversary activities and information that can be used to improve an organization’s SA operations.
Study on Restraining Cavitation of Axial Piston Pump Based on Structure of Cylinder Block and Valve Plate Triangular Throttling Groove
Authors: Zegang Sun , Yundong Li , Ning Liang , Hongmin Zhong
Published: January 2022

Raising the rotational speed is an effective way to improve the power density of axial piston pump, but high rotational speed tends to cause plunger cavity and valve plate throttling groove cavitation. The cavitation of axial piston pump must reduce its volumetric efficiency and cause vibration and noise. In order to reduce the cavitation of axial piston pump and improve the performance of axial piston pump, the optimization of anticavitation structure parameters of cylinder block and valve plate throttling groove is studied in this paper. Firstly, according to the condition of no cavitation in the piston cavity fluid, the mathematical model of the ratio of plunger cavity diameter to axial piston pump cylinder block kidney hole hydraulic diameter is established. It is found that when the ratio is small, the cavitation degree of the piston cavity is weakened. Secondly, this paper analyzes and studies the influence of the valve plate triangular throttling groove structure parameters on the cavitation flow of the triangular throttling groove. It is found that reducing the structural parameters γ or θ can reduce the cavitation intensity of the triangular throttling groove fluid. Finally, combined with the analysis result of the ratio of piston cavity between the piston cavity diameter and the cylinder block kidney hole hydraulic diameter and the research results of the anticavitation of the valve plate triangular throttling groove, the optimized structure of anticavitation of the axial piston pump is proposed, and the simulation results show that the improved axial piston pump has better anticavitation performance.
Canonical Wnt Signaling in the Pathology of Iron Overload-Induced Oxidative Stress and Age-Related Diseases
Authors: Armstrong Austin , Mandala Ashok , Malhotra Milan , Gnana-Prakasam Jaya P.
Published: January 2022

Iron accumulates in the vital organs with aging. This is associated with oxidative stress, inflammation, and mitochondrial dysfunction leading to age-related disorders. Abnormal iron levels are linked to neurodegenerative diseases, liver injury, cancer, and ocular diseases. Canonical Wnt signaling is an evolutionarily conserved signaling pathway that regulates many cellular functions including cell proliferation, apoptosis, cell migration, and stem cell renewal. Recent evidences indicate that iron regulates Wnt signaling, and iron chelators like deferoxamine and deferasirox can inhibit Wnt signaling and cell growth. Canonical Wnt signaling is implicated in the pathogenesis of many diseases, and there are significant efforts ongoing to develop innovative therapies targeting the aberrant Wnt signaling. This review examines how intracellular iron accumulation regulates Wnt signaling in various tissues and their potential contribution in the progression of age-related diseases.
New Insights into Cartilage Tissue Engineering: Improvement of Tissue‐Scaffold Integration to Enhance Cartilage Regeneration
Authors: Jelodari Sahar , Ebrahimi Sadrabadi Amin , Zarei Fatemeh , Jahangir Shahrbanoo , Azami Mahmoud , Sheykhhasan Mohsen , Hosseini Samaneh
Published: January 2022

Distinctive characteristics of articular cartilage such as avascularity and low chondrocyte conversion rate present numerous challenges for orthopedists. Tissue engineering is a novel approach that ameliorates the regeneration process by exploiting the potential of cells, biodegradable materials, and growth factors. However, problems exist with the use of tissue‐engineered construct, the most important of which is scaffold‐cartilage integration. Recently, many attempts have been made to address this challenge via manipulation of cellular, material, and biomolecular composition of engineered tissue. Hence, in this review, we highlight strategies that facilitate cartilage‐scaffold integration. Recent advances in where efficient integration between a scaffold and native cartilage could be achieved are emphasized, in addition to the positive aspects and remaining problems that will drive future research.
Research on the Privacy Security of Face Recognition Technology
Authors: Pang Luning
Published: January 2022

To solve the problem that privacy data are easy to leak in the application of face recognition technology in apps, a method which is based on differential privacy for privacy security protection is proposed. Firstly, Bayesian GAN is conducted to obtain the training data with the same distribution as the privacy data, and the algorithm of differential privacy is conducted to train the training data to obtain these labels with privacy protection. Then, based on the proposed lightface lightweight face recognition model, the tag with noise is generated, and the gradient descent is conducted on the recovered face feature vector from the attack. Finally, through the analysis of privacy loss, an accurate privacy protection boundary is provided. From the results of experiments, it could be known that the proposed privacy security protection method can effectively protect the parameter information of the face recognition model under the face recognition technology and reduce the recognition accuracy of the image recovered by the attacker. Compared with the privacy protection methods such as DPSGD and PATE, it has strong privacy protection ability and can be applied to the privacy protection of practical APP.
Remote Sensing Image Recognition Based on LOG-T-SSA-LSSVM and AE-ELM Network
Authors: Sun Chang-Jian , Gao Fang
Published: January 2022

Aiming at the influence of different working conditions on recognition accuracy in remote sensing image recognition, this paper adopts hierarchical strategy to construct a network. Firstly, in order to establish the classification relationship between different samples, labeled samples are used for classification. A Logistic-T-distribution-Sparrow Search Algorithm-Least Squares Support Vector Machines (LOG-T-SSA-LSSVM) classification network is proposed. LOG-T-SSA algorithm is used to optimize parameters in LSSVM to establish a better network to achieve accurate classification between sample sets and then identify according to different categories. Through UCI dataset test, the accuracy of LOG-T-SSA-LSSVM network classification is significantly improved compared with that of contrast network. The autoencoder is integrated with Extreme Learning Machine, and the autoencoder is used to realize data compression. The advantages of Extreme Learning Machine (ELM) network, such as less training parameters, fast learning speed, and strong generalization ability, are fully utilized to realize efficient and supervised recognition. Experiments verify that the autoencoder-extreme learning machine (AE-ELM) network has a good recognition effect when the sigmoid activation function is selected and the number of hidden layer neurons are 2000. Finally, after image recognition under different working conditions, it is proved that the recognition accuracy of AE-ELM based on LOG-T-SSA-LSSVM classification is significantly improved compared with traditional ELM network and Particle Swarm Optimization-Extreme Learning Machine (PSO-ELM) network.
[Retracted] Medicolite‐Machine Learning‐Based Patient Care Model
Authors: Khan Rijwan , Srivastava Akhilesh Kumar , Gupta Mahima , Kumari Pallavi , Kumar Santosh
Published: January 2022

This paper discusses the machine learning effect on healthcare and the development of an application named “Medicolite” in which various modules have been developed for convenience with health‐related problems like issues with diet. It also provides online doctor appointments from home and medication through the phone. A healthcare system is “Smart” when it can decide on its own and can prescribe patients life‐saving drugs. Machine learning helps in capturing data that are large and contain sensitive information about the patients, so data security is one of the important aspects of this system. It is a health system that uses trending technologies and mobile internet to connect people and healthcare institutions to make them aware of their health condition by intelligently responding to their questions. It perceives information through machine learning and processes this information using cloud computing. With the new technologies, the system decreases the manual intervention in healthcare. Every single piece of information has been saved in the system and the user can access it any time. Furthermore, users can take appointments at any time without standing in a queue. In this paper, the authors proposed a CNN‐based classifier. This CNN‐based classifier is faster than SVM‐based classifier. When these two classifiers are compared based on training and testing sessions, it has been found that the CNN has taken less time (30 seconds) compared to SVM (58 seconds).
Urinary Exosomal Long Noncoding RNA TERC as a Noninvasive Diagnostic and Prognostic Biomarker for Bladder Urothelial Carcinoma
Authors: Chen Chen , Shang Anquan , Sun Zujun , Gao Yuting , Huang Jingjuan , Ping Yili , Chang Wenjing , Gu Chenzheng , Sun Junjun , Ji Ping , Yuan Yi , Lu Renquan , Li Dong
Published: January 2022

Purpose. Bladder cancer is one of the most common urological malignancies worldwide, and approximately 90% of bladder cancer cases are histologically typed as bladder urothelial carcinoma (BLCA). Exosomes are 30 to 200 nm extracellular vesicles that transport microRNAs, long noncoding RNAs (lncRNAs), mRNAs, circular RNAs, and proteins across tissues and through circulation. Urinary exosomes may contain genetic information from tumor cells. Herein, we explored the clinical significance of urinary exosomal lncRNA telomerase RNA component (TERC) levels to provide an urgently needed diagnostic and prognostic biomarker for BLCA. Materials and Methods. In this study, we used RNA-sequencing of samples from four BLCA patients and three healthy controls to identify that TERC was differentially expressed in urinary exosomes. We then used quantitative PCR in different types of clinical samples to validate the biomarker and analyzed results using receiver operating characteristic curves. Results. We found that TERC was significantly upregulated in urinary exosomes from BLCA patients compared with those from healthy controls (

P
<
0.0001

). Urinary exosomal TERC showed higher sensitivity (78.65%) and accuracy (77.78%) than existing indicators including nuclear matrix protein-22 and urine cytometry. Using the cut-off value 4.302, the area under the curve for urinary exosomal TERC was 0.836 (95% confidence interval: 0.768–0.891,

P
<
0.0001

). Furthermore, this noninvasive assay could distinguish low-grade and high-grade tumors (

P
=
0.0153

). Conclusions. TERC is enriched in urinary exosomes from BLCA patients. Urinary exosomal TERC could become a diagnostic and prognostic biomarker for BLCA that allows clinicians to realize noninvasive detection of BLCA.
Antizyme Inhibitor 1 Regulates Matrikine Expression and Enhances the Metastatic Potential of Aggressive Primary Prostate Cancer
Authors: Van den Broeck Thomas , Moris Lisa , Gevaert Thomas , Davicioni Elai , Boeckx Bram , Lambrechts Diether , Helsen Christine , Handle Florian , Ghesquière Bart , Soenen Stefaan , Smeets Elien , Eerlings Roy , El Kharraz Sarah , Devlies Wout , Karnes R. Jeffrey , Lotan Tamara , Van Poppel Hendrik , Joniau Steven , Claessens Frank
Published: January 2022

Molecular drivers of metastasis in patients with high-risk localized prostate cancer are poorly understood. Therefore, we aim to study molecular drivers of metastatic progression in patients with high-risk prostate cancer. A retrospective matched case-control study of two clinico-pathologically identical groups of patients with high-risk prostate cancer was undertaken. One group developed metastatic recurrence (n = 19) while the other did not (n = 25). The primary index tumor was identified by a uro-pathologist, followed by DNA and RNA extraction for somatic copy-number aberration (SCNA) analysis and whole-transcriptome gene expression analysis. In vitro and in vivo studies included cell line manipulation and xenograft models.

The integrative CNA and gene expression analyses identified an increase in Antizyme Inhibitor 1 (AZIN1) gene expression within a focal amplification of 8q22.3, which was associated with metastatic recurrence of patients with high-risk prostate cancer in four independent cohorts. The effects of AZIN1 knockdown were evaluated, due to its therapeutic potential. AZIN1 knockdown effected proliferation and metastatic potential of prostate cancer cells and xenograft models. RNA sequencing after AZIN1 knockdown in prostate cancer cells revealed upregulation of genes coding for collagen subunits. The observed effect on cell migration after AZIN1 knockdown was mimicked when exposing prostate cancer cells to bio-active molecules deriving from COL4A1 and COL4A2. Our integrated CNA and gene expression analysis of primary high-risk prostate cancer identified the AZIN1 gene as a novel driver of metastatic progression, by altering collagen subunit expression. Future research should further investigate its therapeutic potential in preventing metastatic recurrence.

Implications:

AZIN1 was identified as driver of metastatic progression in high-risk prostate cancer through matrikine regulation.
HIPK2 Cooperates with KRAS Signaling and Associates with Colorectal Cancer Progression
Authors: Di Segni Micol , Virdia Ilaria , Verdina Alessandra , Amoreo Carla Azzurra , Baldari Silvia , Toietta Gabriele , Diodoro Maria Grazia , Mottolese Marcella , Sperduti Isabella , Moretti Fabiola , Buglioni Simonetta , Soddu Silvia , Di Rocco Giuliana
Published: January 2022

Homeodomain-interacting protein kinase 2 (HIPK2) is an evolutionary conserved kinase that has gained attention as a fine tuner of multiple signaling pathways, among which those commonly altered in colorectal cancer. The aim of this study was to evaluate the relationship of HIPK2 expression with progression markers and mutational pattern and gain insights into the contribution of HIPK2 activity in colorectal cancer. We evaluated a retrospective cohort of colorectal cancer samples by IHC for HIPK2 expression and by next-generation sequencing (NGS) for the detection of mutations of cancer associated genes. We show that the percentage of HIPK2-positive cells increases with tumor progression, significantly correlates with tumor–node–metastasis (TNM) staging and associates with a worse outcome. In addition, we observed that high HIPK2 expression significantly associates with KRAS mutations but not with other cancer-related genes. Functional characterization of the link between HIPK2 and KRAS show that activation of the RAS pathway either due to KRAS mutation or via upstream receptor stimulation, increases HIPK2 expression at the protein level. Of note, HIPK2 physically participates in the active RAS complex while HIPK2 depletion impairs ERK phosphorylation and the growth of tumors derived from KRAS mutated colorectal cancer cells. Overall, this study identifies HIPK2 as a prognostic biomarker candidate in patients with colorectal cancer and underscores a previously unknown functional link between HIPK2 and the KRAS signaling pathway.

Implications:

Our data indicate HIPK2 as a new player in the complex picture of the KRAS signaling network, providing rationales for future clinical studies and new treatment strategies for KRAS mutated colorectal cancer.
Inactivation of p21-Activated Kinase 2 (Pak2) Inhibits the Development of Nf2-Deficient Tumors by Restricting Downstream Hedgehog and Wnt Signaling
Authors: Sementino Eleonora , Kadariya Yuwaraj , Cheung Mitchell , Menges Craig W. , Tan Yinfei , Kukuyan Anna-Mariya , Shrestha Ujjawal , Karchugina Sofiia , Cai Kathy Q. , Peri Suraj , Duncan James S. , Chernoff Jonathan , Testa Joseph R.
Published: January 2022

Because loss of the NF2 tumor suppressor gene results in p21-activated kinase (Pak) activation, PAK inhibitors hold promise for the treatment of NF2-deficient tumors. To test this possibility, we asked if loss of Pak2, a highly expressed group I PAK member, affects the development of malignant mesothelioma in Nf2;Cdkn2a-deficient (NC) mice and the growth properties of NC mesothelioma cells in culture. In vivo, deletion of Pak2 resulted in a markedly decreased incidence and delayed onset of both pleural and peritoneal malignant mesotheliomas in NC mice. In vitro, Pak2 deletion decreased malignant mesothelioma cell viability, migration, clonogenicity, and spheroid formation. RNA-sequencing analysis demonstrated downregulated expression of Hedgehog and Wnt pathway genes in NC;Pak2−/− mesothelioma cells versus NC;Pak2+/+ mesothelioma cells. Targeting of the Hedgehog signaling component Gli1 or its target gene Myc inhibited cell viability and spheroid formation in NC;P+/+ mesothelioma cells. Kinome profiling uncovered kinase changes indicative of EMT in NC;Pak2−/− mesothelioma cells, suggesting that Pak2-deficient malignant mesotheliomas can adapt by reprogramming their kinome in the absence of Pak activity. The identification of such compensatory pathways offers opportunities for rational combination therapies to circumvent resistance to anti-PAK drugs.

Implications:

We provide evidence supporting a role for PAK inhibitors in treating NF2-deficient tumors. NF2-deficient tumors lacking Pak2 eventually adapt by kinome reprogramming, presenting opportunities for combination therapies to bypass anti-PAK drug resistance.
Impacts of COVID-19 Lockdown on Food Ordering Patterns among Youths in China: The COVID-19 Impact on Lifestyle Change Survey
Authors: Yang Shujuan , Chen Hui , Wu Jialong , Guo Bing , Zhou Junmin , Yuan Changzheng , Jia Peng
Published: January 2022

Introduction: Limited studies have focused on how the COVID-19 outbreak and thereby lockdown had affected the youth’s food ordering patterns, which was associated with their dietary behaviors and could have longer term impacts on their later-life health status if the trend persists. This study aimed to evaluate changes in food ordering patterns among youths in China after the COVID-19 outbreak. Methods: The data were obtained from a national retrospective survey (COINLICS) conducted in early May 2020 via social media platforms in China among more than 10,000 youth participants at 3 educational levels. Participants reported their basic sociodemographic characteristics, weight status, and lifestyles including food ordering patterns. We described and compared their weight status and food ordering patterns before COVID-19 (January) and under lockdown (February). Results: We observed significant changes in youths’ weight status and food ordering patterns under lockdown. A significant increase was observed in the prevalence of overweight/obesity (13.5%–17.0%) and obesity (8.7–10.8%), which varied by sex and educational level. Overall, the average weekly frequency of food ordering among the Chinese students had declined, with the largest decrease seen among graduate students, followed by undergraduate and high/vocational school students. Regardless of types of food, the percentage of participating youths who started ordering under lockdown was all lower than that of youths who stopped ordering. Among those who had still ordered foods under lockdown, a larger percentage of female than male high/vocational school students ordered barbecue/grill and cakes/pastries; no significant differences were found across the educational levels. Conclusion: The participating youths’ food ordering patterns had significantly changed during the COVID-19 lockdown, with heterogeneities observed to different extents between sexes and across educational levels. Our findings would inform policy makers and health professionals of these changes in time, for better policy making and public health practice.
Endoscopic Nasobiliary Drainage Comparable with Endoscopic Biliary Stenting as a Preoperative Drainage Method for Malignant Hilar Biliary Obstruction: A Multicenter Retrospective Study
Authors: Sugiura Ryo , Kuwatani Masaki , Hayashi Tsuyoshi , Yoshida Makoto , Ihara Hideyuki , Yamato Hiroaki , Onodera Manabu , Katanuma Akio ,   Hokkaido Interventional EUS/ERCP study (HONEST) group
Published: January 2022

Introduction: Preoperative endoscopic biliary drainage (PEBD) for malignant hilar biliary obstruction (MHBO) is widely accepted. Recent PEBD consists of endoscopic nasobiliary drainage (ENBD), conventional endoscopic biliary stenting (CEBS) with plastic stents across the papilla, and endoscopic biliary inside stenting (EBIS) with plastic stents above the papilla, while ENBD is the primary procedure in Asian countries. Thus, we aimed to compare the efficacy of ENBD with those of CEBS and EBIS as a means of PEBD for MHBO. Methods: We retrospectively identified patients with MHBO who underwent upfront surgery between January 2011 and December 2018 in a multicenter setting. The outcome measures were cumulative dysfunction of PEBD, risk factors for PEBD dysfunction, and adverse events. Results: We analyzed a total of 219 patients, comprising 163 males (74.4%); mean age, 69.7 (±7.6) years; Bismuth-Corlette (BC) classification I, II, IIIa, IIIb, and IV in 68, 49, 43, 30, and 29 patients, respectively; and diagnosis of hilar cholangiocarcinoma and gallbladder cancer in 188 and 31 patients, respectively. PEBD procedures were performed in 160 patients with ENBD, 31 patients with CEBS, and 28 patients with EBIS. PEBD dysfunction occurred in 58 patients (26.5%), and the cumulative dysfunction rates were not significantly different among PEBD methods (p = 0.60). Multivariate analysis showed that BC-IV was significantly associated with the occurrence of PEBD dysfunction (hazard ratio = 2.10, p = 0.02). The adverse event rates were not significantly different among PEBD groups (p = 0.70). Conclusion: ENBD as a means of PEBD for MHBO is comparable with CEBS and EBIS in rates of dysfunction and adverse events.
Prueba nasofaríngea con resultado positivo tardío para COVID-19, un estudio de caso con correlación clínica y patológica
Authors: Zhang Lei , Vunnamadala Syam P. , Yagi Shigeo , Meraj Riffat , Carbone Michele
Published: January 2022

Antecedentes: Hay varias razones por las que las pruebas de PCR nasofaríngeas para la enfermedad por coronavirus 2019 (COVID-19) dan un resultado positivo tardío, no sólo en casos asintomáticos sino también en pacientes gravemente enfermos. Los atributos fisiopatológicos aún se desconocen. Exploramos esta posibilidad mediante el reporte de un caso. Presentación del caso: Un varón de 64 años con antecedentes de infección fúngica pulmonar, asma y enfermedad pulmonar obstructiva crónica (EPOC), diabetes y arteriopatía coronaria se presentó con dificultad respiratoria, fiebre e imágenes torácicas de opacidad esmerilada y engrosamiento intersticial reticular, altamente sospechoso de COVID-19. Sin embargo, las pruebas de hisopado nasofaríngeo fueron discordantemente negativas durante cuatro ocasiones en dos semanas, y los anticuerpos IgG para COVID-19 también fueron negativos. Sin embargo, el nivel de IgE en suero era elevado. No se identificaron otros patógenos. Sus síntomas se deterioraron a pesar del tratamiento con corticosteroides, antibióticos y broncodilatadores. Se realizaron un lavado broncoalveolar (LBA) y una biopsia en cuña a pulmón abierto para el diagnóstico de la etiología. Se demostró la presencia de neumonía organizativa fibrosante positiva para RNA viral COVID-19, y daños en las vías respiratorias caracterizados por un efecto citopático sospechoso de origen viral, inflamación mixta neutrofílica, linfoplasmática, histiocítica y eosinofílica, y fibrosis, además de los cambios esperados en el asma y la EPOC. Una semana después, las pruebas nasofaríngeas de COVID-19 repetidas en los días 40 y 49 resultaron positivas. Conclusión: Nuestro caso y la revisión de la literatura indican que el asma alérgica y el alto nivel de IgE asociado a ella, junto con la inhalación de corticosteroides, podrían contribuir a la positividad retardada del hisopado nasofaríngeo en las vías respiratorias superiores; la obstrucción crónica de las vías respiratorias relacionada con la EPOC y la adición de fibrosis provocaron dependencia del ventilador y un mal pronóstico en la neumonía por COVID-19, y deberían ser objeto de tratamiento junto con la terapia antiviral.
Mechanism of miRNA-141-3p in Calcium Oxalate-Induced Renal Tubular Epithelial Cell Injury via NLRP3-Mediated Pyroptosis
Authors: Gan Xiu-Guo , Wang Zhi-Hao , Xu Hai-Tao
Published: January 2022

Background/Aims: Renal calculi represent a prevalent disorder associated with mineral deposition in renal calyces and the pelvis. Aberrant microRNA (miRNA) expression is implicated in renal injury. This study investigated the mechanism of miR-141-3p in calcium oxalate (CaOx) crystal-induced renal tubular epithelial cell (RTEC) injury. Methods: Human RTECs HK-2 cells were treated with CaOx crystals to induce RTEC injury. Cell viability was evaluated using Cell Counting Kit-8 assay, and apoptosis was measured using flow cytometry. The contents of lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), interleukin (IL)-1β, and IL-18 were measured using enzyme-linked immunosorbent assay kits. The expressions of NLRP3, cleaved caspase-1, and GSDMD-N were detected using Western blot. miR-141-3p and NLRP3 expressions were determined using reverse transcription quantitative polymerase chain reaction. The binding of miR-141-3p and NLRP3 was validated using a dual-luciferase assay. The role of NLRP3 in the protection of miR-141-3p on RTEC injury was verified using functional rescue experiments. Results: CaOx crystals induced RTEC injury, manifested as attenuated cell viability, enhanced apoptosis, elevated intracellular LDH and MDA levels, and decreased SOD level. Pyroptosis of RTECs was enhanced by CaOx crystal induction, evidenced by elevated expressions of cleaved caspase-1, GSDMD-N, IL-1β, and IL-18. miR-141-3p expression was reduced in CaOx crystal-induced RTECs. miR-141-3p overexpression alleviated CaOx crystal-induced RTEC injury and suppressed pyroptosis of RTECs. miR-141-3p bound to NLRP3 and thereby repressed NLRP3 expression. NLRP3 overexpression reversed the protective effect of miR-141-3p overexpression on RTECs. Conclusion: miR-141-3p repressed NLRP3-mediated pyroptosis by suppressing NLRP3 expression, thus protecting CaOx crystal-induced RTEC injury.
Macrolichens of Mathikettan Shola National Park, Western Ghats: a preliminary investigation with some new records
Authors: Aswathi Anilkumar  , Stephen Sequeira  , Arun Christy  , S.M. Arsha
Published: January 2022

An extensive survey of lichens was conducted in different parts of Mathikettan Shola National Park, and analysed 55 macrolichen species under six families. Two species were found to be new to the Indian peninsula, and five species were new to the lichen flora of Kerala.
Comparison of bird diversity in protected and non-protected wetlands of western lowland of Nepal
Authors: Adhikari Jagan Nath , Khatiwada Janak Raj , Adhikari Dipendra , Sapkota Suman , Bhattarai Bishnu Prasad , Rijal Deepak , Sharma Lila Nath
Published: January 2022

Protected areas are considered important for biodiversity conservation, however, studies have shown that habitats outside protected areas can also support high diversity and are important for biodiversity conservation.  In this context, we compared the bird diversity between protected (Rani Taal in Shuklaphanta National Park) and non-protected (Sati Karnali Taal) wetlands in western Nepal. Bird surveys were conducted from February to August 2019, using open width point count method in 100 m intervals along transects.  A total of 122 species belonging to 18 orders and 44 families were recorded from the protected wetland, and 107 species belonging to 16 orders and 41 families from the non-protected wetland area. Insectivores had high abundance in both wetlands (43% and 47% in protected and non-protected wetlands, respectively). Forest-dependent birds were more abundant in protected wetland compared to non-protected wetland. Our study showed that both protected and non-protected wetlands along with agricultural landscapes, support a richness of birds. Hence priority should be given to both wetlands for the conservation of birds.