bluuebunny/crossref_metadata_2025 huggingface dataset:
The Importance of CXCL1 in the Physiological State and in Noncancer Diseases of the Oral Cavity and Abdominal Organs
Authors: Korbecki Jan , Szatkowska Iwona , Kupnicka Patrycja , Żwierełło Wojciech , Barczak Katarzyna , Poziomkowska-Gęsicka Iwona , Wójcik Jerzy , Chlubek Dariusz , Baranowska-Bosiacka Irena
Published: June 2022

CXCL1 is a CXC chemokine, CXCR2 ligand and chemotactic factor for neutrophils. In this paper, we present a review of the role of the chemokine CXCL1 in physiology and in selected major non-cancer diseases of the oral cavity and abdominal organs (gingiva, salivary glands, stomach, liver, pancreas, intestines, and kidneys). We focus on the importance of CXCL1 on implantation and placentation as well as on human pluripotent stem cells. We also show the significance of CXCL1 in selected diseases of the abdominal organs, including the gastrointestinal tract and oral cavity (periodontal diseases, periodontitis, Sjögren syndrome, Helicobacter pylori infection, diabetes, liver cirrhosis, alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), HBV and HCV infection, liver ischemia and reperfusion injury, inflammatory bowel disease (Crohn’s disease and ulcerative colitis), obesity and overweight, kidney transplantation and ischemic-reperfusion injury, endometriosis and adenomyosis).
Positive Correlation of the Gene Rearrangements and Evolutionary Rates in the Mitochondrial Genomes of Thrips (Insecta: Thysanoptera)
Authors: Liu Qiaoqiao , He Jia , Song Fan , Tian Li , Cai Wanzhi , Li Hu
Published: June 2022

Extensive gene rearrangement is characteristic in the mitogenomes of thrips (Thysanoptera), but the historical process giving rise to the contemporary gene rearrangement pattern remains unclear. To better understand the evolutionary processes of gene rearrangement in the mitogenomes of thrips, we sequenced the mitogenome of the banded thrip species Aeolothrips xinjiangensis. First, we found a novel mitochondrial gene order in this species. This mitogenome is 16,947 bp in length and encodes the typical 37 coding genes (13 protein-coding genes, 22 tRNA genes, and two rRNA genes) of insects. The gene arrangement was dramatically different from the putative ancestral mitogenome, with 26 genes being translocated, eight of which were inverted. Moreover, we found a novel, conserved gene block, trnC-trnY, which has not been previously reported in the mitogenomes of thrips. With this newly assembled mitogenome, we compared mitogenome sequences across Thysanoptera to assess the evolutionary processes giving rise to the current gene rearrangement pattern in thrips. Seven identical gene blocks were shared by two sequenced banded thrip mitogenomes, while the reversal of ND2 combined with TDRL events resulted in the different gene orders of these two species. In phylogenetic analysis, the monophyly of the suborders and families of Thysanoptera was well supported. Across the gene orders of 14 thrips, only two conserved gene blocks, ATP8-ATP6 and ND4-ND4L, could be found. Correlation analysis showed that the degree of gene rearrangement was positively correlated with the non-synonymous substitution rate in thrips. Our study suggests that the mitogenomes of thrips remain stable over long evolutionary timescales after massive rearrangement during early diversification.
Systematic Functional Annotation Workflow for Insects
Authors: Bono Hidemasa , Sakamoto Takuma , Kasukawa Takeya , Tabunoki Hiroko
Published: June 2022

Next-generation sequencing has revolutionized entomological study, rendering it possible to analyze the genomes and transcriptomes of non-model insects. However, use of this technology is often limited to obtaining the nucleotide sequences of target or related genes, with many of the acquired sequences remaining unused because other available sequences are not sufficiently annotated. To address this issue, we have developed a functional annotation workflow for transcriptome-sequenced insects to determine transcript descriptions, which represents a significant improvement over the previous method (functional annotation pipeline for insects). The developed workflow attempts to annotate not only the protein sequences obtained from transcriptome analysis but also the ncRNA sequences obtained simultaneously. In addition, the workflow integrates the expression-level information obtained from transcriptome sequencing for application as functional annotation information. Using the workflow, functional annotation was performed on the sequences obtained from transcriptome sequencing of the stick insect (Entoria okinawaensis) and silkworm (Bombyx mori), yielding richer functional annotation information than that obtained in our previous study. The improved workflow allows the more comprehensive exploitation of transcriptome data and is applicable to other insects because the workflow has been openly developed on GitHub.
Multi-Level Wavelet-Based Network Embedded with Edge Enhancement Information for Underwater Image Enhancement
Authors: Sun Kaichuan , Meng Fei , Tian Yubo
Published: June 2022

As an image processing method, underwater image enhancement (UIE) plays an important role in the field of underwater resource detection and engineering research. Currently, the convolutional neural network (CNN)- and Transformer-based methods are the mainstream methods for UIE. However, CNNs usually use pooling to expand the receptive field, which may lead to information loss that is not conducive to feature extraction and analysis. At the same time, edge blurring can easily occur in enhanced images obtained by the existing methods. To address this issue, this paper proposes a framework that combines CNN and Transformer, employs the wavelet transform and inverse wavelet transform for encoding and decoding, and progressively embeds the edge information on the raw image in the encoding process. Specifically, first, features of the raw image and its edge detection image are extracted step by step using the convolution module and the residual dense attention module, respectively, to obtain mixed feature maps of different resolutions. Next, the residual structure Swin Transformer group is used to extract global features. Then, the resulting feature map and the encoder’s hybrid feature map are used for high-resolution feature map reconstruction by the decoder. The experimental results show that the proposed method can achieve an excellent effect in edge information protection and visual reconstruction of images. In addition, the effectiveness of each component of the proposed model is verified by ablation experiments.
Analytical Penetration Solutions of Large-Diameter Open-Ended Piles Subjected to Hammering Loads
Authors: Qin Wei , Li Xue , Dai Guoliang , Hu Pan
Published: June 2022

This paper proposes the penetration displacement solutions of large-diameter open-ended steel pipe piles (LOSPs) with the diameter exceeding 2 m subjected to hammering load. The ultimate forcing equilibrium relationships between LOSP and soil are analyzed, and the calculated formula for self-sinking depth is derived. Next, a partial differential equation of pile hammering by single blow in soft soil is developed based on wave equation incorporating the kinematic method. A dynamic coefficient of frictional resistance (DCFR) is implemented in the process of derivation, and then the displacement Fourier analytical expression of LOSP under hammering load is presented. The parameters sensitivity of the analytical solution is investigated, and the displacement curve is compared with the numerical result. The new method presented in this paper could be used to assess the penetration development of driven piles under impact loading to predict the punching through or hammer refusal during penetration.
Deep-Learning for the Diagnosis of Esophageal Cancers and Precursor Lesions in Endoscopic Images: A Model Establishment and Nationwide Multicenter Performance Verification Study
Authors: Gong Eun Jeong , Bang Chang Seok , Jung Kyoungwon , Kim Su Jin , Kim Jong Wook , Seo Seung In , Lee Uhmyung , Maeng You Bin , Lee Ye Ji , Lee Jae Ick , Baik Gwang Ho , Lee Jae Jun
Published: June 2022

Background: Suspicion of lesions and prediction of the histology of esophageal cancers or premalignant lesions in endoscopic images are not yet accurate. The local feature selection and optimization functions of the model enabled an accurate analysis of images in deep learning. Objectives: To establish a deep-learning model to diagnose esophageal cancers, precursor lesions, and non-neoplasms using endoscopic images. Additionally, a nationwide prospective multicenter performance verification was conducted to confirm the possibility of real-clinic application. Methods: A total of 5162 white-light endoscopic images were used for the training and internal test of the model classifying esophageal cancers, dysplasias, and non-neoplasms. A no-code deep-learning tool was used for the establishment of the deep-learning model. Prospective multicenter external tests using 836 novel images from five hospitals were conducted. The primary performance metric was the external-test accuracy. An attention map was generated and analyzed to gain the explainability. Results: The established model reached 95.6% (95% confidence interval: 94.2–97.0%) internal-test accuracy (precision: 78.0%, recall: 93.9%, F1 score: 85.2%). Regarding the external tests, the accuracy ranged from 90.0% to 95.8% (overall accuracy: 93.9%). There was no statistical difference in the number of correctly identified the region of interest for the external tests between the expert endoscopist and the established model using attention map analysis (P = 0.11). In terms of the dysplasia subgroup, the number of correctly identified regions of interest was higher in the deep-learning model than in the endoscopist group, although statistically insignificant (P = 0.48). Conclusions: We established a deep-learning model that accurately classifies esophageal cancers, precursor lesions, and non-neoplasms. This model confirmed the potential for generalizability through multicenter external tests and explainability through the attention map analysis.
Driving SMEs’ Performance in South Africa: Investigating the Role of Performance Appraisal Practices and Managerial Competencies
Authors: Mashavira Nhamo , Guvuriro Sevias , Chipunza Crispen
Published: June 2022

Managerial competencies and performance appraisal practices are often ignored when considering the performance of Small-to-Medium Enterprises (SMEs). Yet, these competencies and practices are fundamental for the survival of the SMEs. SMEs are critical for economic growth and job creation in many economies. The current study sought to establish whether managerial competencies and performance appraisal practices correlate with SMEs’ performance in South Africa. Firm performance was measured using two variables: innovation and return on investment (ROI). The study adopted a structural equation modelling analytical approach. Interpersonal competencies were found to be a significant factor of managerial competencies, but conceptual and political competencies were not. The study also found that managerial competencies, and not performance appraisal practices, significantly correlated with both innovation and ROI. The study recommends that performance appraisal practices be tailored to suit SMEs in the developing countries context.
Causal Effects of Financial Education Intervention Aimed at University Students on Financial Knowledge and Financial Self-Efficacy
Authors: Salas-Velasco Manuel
Published: June 2022

Based on a randomized controlled experiment among final-year undergraduate students, we provide an assessment of the treatment effects of financial education intervention focused on debt-financed graduate education decision-making. Specifically, this study finds positive treatment effects on both college seniors’ objective financial knowledge and subjective financial knowledge and self-confidence (i.e., perceived financial self-efficacy). Individual financial well-being is thought to be enhanced by improved financial knowledge test scores and perceived financial self-efficacy. In addition, we carry out a causal mediation analysis to investigate the extent to which objective financial knowledge plays a mediating role in the effect of financial education treatment on the intervention outcome (perceived financial self-efficacy). The mediation proportion, the proportion of treatment effect on outcome explained by the intermediate variable of financial knowledge, is around 21%, which is important. Thus, policies that aim to improve financial capabilities among college students through financial education programs should be aware that financial literacy is a significant antecedent of (a prerequisite for) financial self-efficacy.
Multi-Objective Welding-Parameter Optimization Using Overlaid Contour Plots and the Butterfly Optimization Algorithm
Authors: Waheed Rehan , Saeed Hasan Aftab , Ahmed Bilal Anjum
Published: June 2022

Distortion and residual stress are two unwelcome byproducts of welding. The former diminishes the dimensional accuracy while the latter unfavorably affects the fatigue resistance of the components being joined. The present study is a multi-objective optimization aimed at minimizing both the welding-induced residual stress as well as distortion. Current, voltage, and welding speed were the welding parameters selected. It was observed that the parameters that minimize distortion were substantially different from those that minimized the residual stress. That is, enhancing dimensional accuracy by minimizing distortion results in an intensification of residual stresses. A compromise between the two objectives was therefore necessary. The contour plots produced from the response surfaces of the two objectives were overlaid to find a region with feasible parameters for both. This feasible region was used as the domain wherein to apply the novel butterfly optimization algorithm (BOA). This is the first instance of the application of the BOA to a multi-objective welding problem. Weld simulation and a confirmatory experiment based on the optimum weld parameters thus obtained corroborate the efficacy of the framework.
Analysis of Carbonation Behavior of Cracked Concrete
Authors: Guo Qun , Jiang Lexin , Wang Jianmin , Liu Junzhe
Published: June 2022

The crack and carbonation of concrete pose a great challenge to its durability. Therefore, this paper studies the effect of cracks on the carbonation depth of cement paste under different factors. The relationship between carbonation and cracks was determined, and the carbonation mechanism of cement paste with cracks was clarified. The results show that a small water–binder ratio can effectively inhibit the carbonation process. The bidirectional carbonation enlarged the carbonation area around the crack. Within 21 days of the carbonation, the carbonation depth increased with carbonation time, and the Ca(OH)2 on the surface of the specimen was sufficient, allowing for a convenient chemical reaction with CO2. The influence of crack width on the carbonation process at the crack was greater than the influence of the crack depth. Carbonation influenced the hydration of cement-based materials, altering the types and quantities of hydration products. In conclusion, accurately predicting the regularity of carbonation in cracked structures is critical for improving the durability of concrete.
Correlation between Microstructure and Mechanical Properties of Heat-Treated Novel Powder Metallurgy Superalloy
Authors: Ye Xianjue , Yang Biaobiao , Liu Jiantao , Li Yunping
Published: June 2022

In this work, the quantification of key microstructural features like γ′ size morphology distribution, grain size, and localized stress distribution, especially near a fracture, were coupled with mechanical properties under various temperatures in Ni-base powder metallurgy superalloys subjected to sub-solvus or super-solvus heat treatments. Compared to super-solvus heat-treated alloy, sub-solvus heat-treated superalloy with a finer grain size exhibited higher ductility/strength at 550 °C, whilst adverse trend was observed at higher temperatures (750 and 830 °C). Besides, for both alloys, the strength and ductility decreased with the decrease in strain rate, resulting from oxidation behavior. Larger grain size or less grain boundary density can facilitate the retardation of oxidation behavior and weaken the propensity of early failure at higher temperatures.
Research on Elastic–Plastic Contact Behavior of Hemisphere Flattened by a Rigid Flat
Authors: Zhang Wangyang , Chen Jian , Wang Chenglong , Liu Di , Zhu Linbo
Published: June 2022

The contact behavior of a hemisphere pressed by a rigid plane is of great significance to the study of friction, wear, and conduction between two rough surfaces. A flattening contact behavior of an elastic–perfectly plastic hemisphere pressed by a rigid flat is researched by using the finite element method in this paper. This behavior, influenced by different elastic moduli, Poisson’s ratios, and yield strengths, is compared and analyzed in a large range of interference values, which have not been considered by previous models. The boundaries of purely elastic, elastic–plastic, and fully plastic deformation regions are given according to the interference, maximum mean contact pressure, Poisson’s ratio, and elastic modulus to yield strength ratio. Then, a new elastic–plastic constitutive model is proposed to predict the contact area and load in the elastic–plastic range. Compared with previous models and experiments, the rationality of the present model is verified. The study can be applied directly to the contact between a single sphere and a plane. In addition, the sphere contact can also be used to simulate the contact of single asperity on rough surfaces, so the present proposed model can be used to further study the contact characteristics of rough surfaces.
The Measurement of Contact Angle, pH, and Conductivity of Artificial Saliva and Mouthwashes on Enamel, Glass-Ionomer, and Composite Dental Materials
Authors: Qureshi Saima , Milić Lazar , Petrović Bojan , Vejin Marija , Kojić Sanja , Jarić Stefan , Stojanović Goran
Published: June 2022

The aim of this study was to tackle the topic of appropriate recommendations for artificial-saliva and mouthwash usage. The contact angle, pH, and conductivity of two artificial saliva solutions, four mouthwashes, and their mixtures on enamel, glass-ionomer, and composite dental materials were measured. The measurements were conducted with a MATLAB algorithm to minimize human error. The obtained values for the contact angle were in the range from 7.98° to 52.6°, and they showed completely nonlinear and nonuniform behavior for all investigated liquids and on all investigated substrates. Results reveal statistically significant differences among all tested liquids on all investigated substrates (p < 0.05). pH values ranged from 1.54 to 7.01. A wide range of conductivity values were observed, from 1205µS/cm in the saliva-stimulating solution to 6679 mS/cm in the artificial saliva. Spearman’s test showed a moderate positive correlation between the pH and conductivity of the tested fluids (R = 0.7108). A comparison of the data obtained using Image J software and the MATLAB algorithm showed consistency, not exceeding 5% error. When an experiment uses human material and bioactive materials THAT are used in biomedicine as substrates, an additional definition of protocols is highly recommended for future research on this topic.
TR-Net: A Transformer-Based Neural Network for Point Cloud Processing
Authors: Liu Luyao , Chen Enqing , Ding Yingqiang
Published: June 2022

Point cloud is a versatile geometric representation that could be applied in computer vision tasks. On account of the disorder of point cloud, it is challenging to design a deep neural network used in point cloud analysis. Furthermore, most existing frameworks for point cloud processing either hardly consider the local neighboring information or ignore context-aware and spatially-aware features. To deal with the above problems, we propose a novel point cloud processing architecture named TR-Net, which is based on transformer. This architecture reformulates the point cloud processing task as a set-to-set translation problem. TR-Net directly operates on raw point clouds without any data transformation or annotation, which reduces the consumption of computing resources and memory usage. Firstly, a neighborhood embedding backbone is designed to effectively extract the local neighboring information from point cloud. Then, an attention-based sub-network is constructed to better learn a semantically abundant and discriminatory representation from embedded features. Finally, effective global features are yielded through feeding the features extracted by attention-based sub-network into a residual backbone. For different downstream tasks, we build different decoders. Extensive experiments on the public datasets illustrate that our approach outperforms other state-of-the-art methods. For example, our TR-Net performs 93.1% overall accuracy on the ModelNet40 dataset and the TR-Net archives a mIou of 85.3% on the ShapeNet dataset for part segmentation.
ISVD-Based Advanced Simultaneous Localization and Mapping (SLAM) Algorithm for Mobile Robots
Authors: Somlyai László , Vámossy Zoltán
Published: June 2022

In the case of simultaneous localization and mapping, route planning and navigation are based on data captured by multiple sensors, including built-in cameras. Nowadays, mobile devices frequently have more than one camera with overlapping fields of view, leading to solutions where depth information can also be gathered along with ordinary RGB color data. Using these RGB-D sensors, two- and three-dimensional point clouds can be recorded from the mobile devices, which provide additional information for localization and mapping. The method of matching point clouds during the movement of the device is essential: reducing noise while having an acceptable processing time is crucial for a real-life application. In this paper, we present a novel ISVD-based method for displacement estimation, using key points detected by SURF and ORB feature detectors. The ISVD algorithm is a fitting procedure based on SVD resolution, which removes outliers from the point clouds to be fitted in several steps. The developed method removes these outlying points in several steps, in each iteration examining the relative error of the point pairs and then progressively reducing the maximum error for the next matching step. An advantage over relevant methods is that this method always gives the same result, as no random steps are included.
A Hybrid Interpolating Meshless Method for 3D Advection–Diffusion Problems
Authors: Meng Zhijuan , Chi Xiaofei , Ma Lidong
Published: June 2022

A hybrid interpolating meshless (HIM) method is established for dealing with three-dimensional (3D) advection–diffusion equations. To improve computational efficiency, a 3D equation is changed into correlative two-dimensional (2D) equations. The improved interpolating moving least-squares (IIMLS) method is applied in 2D subdomains to obtain the required approximation function with interpolation property. The finite difference method (FDM) is utilized in time domain and the splitting direction. Setting diagonal elements to one in the coefficient matrix is chosen to directly impose Dirichlet boundary conditions. Using the HIM method, difficulties created by the singularity of the weight functions, such as truncation error and calculation inconvenience, are overcome. To prove the advantages of the new method, some advection–diffusion equations are selected and solved by HIM, dimension splitting element-free Galerkin (DSEFG), and improved element-free Galerkin (IEFG) methods. Comparing and analyzing the calculation results of the three methods, it can be shown that the HIM method effectively improves computation speed and precision. In addition, the effectiveness of the HIM method in the nonlinear problem is verified by solving a 3D Richards’ equation.
Data-Driven Coupling Coordination Development of Regional Innovation EROB Composite System: An Integrated Model Perspective
Authors: Yang Yaliu , Wang Yuan , Zhang Yingyan , Liu Conghu
Published: June 2022

To promote coupling coordination development for regional innovation environment-resource-output-benefit (EROB) composite systems, we propose a data-driven integrated model method for measurement, evaluation, and identification. First, we construct an evaluation indicator system of coupling coordination development of regional innovation EROB composite systems. Second, we apply the entropy method to measure indicator weights and comprehensive development indices of regional innovation composite systems. The coupling coordination degree model is used to calculate and evaluate four subsystems’ coupling coordination development levels. The obstacle degree model is used to identify the main obstacle factors affecting coupling coordination development. Finally, using panel data of the Yangtze River Delta region (three provinces and one city) between 2014–2019 as a case study, we test the integrated model method. The results show that the comprehensive development level of the regional innovation EROB composite system in the Yangtze River Delta region maintained a stable growth trend; the coupling coordination development level among four subsystems continuously improved, with the main obstacle being the innovation resource subsystem. Accordingly, targeted policy suggestions are put forward. This study not only provides theoretical and methodological support for evaluating and optimizing regional innovation composite systems but also provides decision-making support for sustainable and high-quality development of regional economies.
Nonparametric Sieve Maximum Likelihood Estimation of Semi-Competing Risks Data
Authors: Huang Xifen , Xu Jinfeng
Published: June 2022

In biomedical studies involving time-to-event data, a subject may experience distinct types of events. We consider the problem of estimating the transition functions for a semi-competing risks model under illness-death model framework. We propose to estimate the intensity functions by maximizing a B-spline based sieve likelihood. The method yields smooth estimates without parametric assumptions. Our proposed approach facilitates easy computation of the covariance of the model parameters and yields direct interpretation. Compared with existing approaches, our proposed method requires neither the subjective specification of the frailty distribution nor the Markov or semi-Markov assumption which may be unmet in real applications. We establish the consistency, the convergence rate, and the asymptotic normality of the proposed estimators under some regularity conditions. We also provide simulation studies to assess the finite-sample performance of the proposed modeling and estimation strategy. A real data application is further used to illustrate the proposed methodology.
A Feasible Method to Control Left Ventricular Assist Devices for Heart Failure Patients: A Numerical Study
Authors: Bakouri Mohsen , Alassaf Ahmad , Alshareef Khaled , Smida Amor , AlMohimeed Ibrahim , Alqahtani Abdulrahman , Aboamer Mohamed Abdelkader , Alharbi Yousef
Published: June 2022

Installing and developing a sophisticated control system to optimize left ventricular assist device (LVAD) pump speed to meet changes in metabolic demand is essential for advancing LVAD technology. This paper aims to design and implement a physiological control method for LVAD pumps to provide optimal cardiac output. The method is designed to adjust the pump speed by regulating the pump flow based on a predefined set point (operating point). The Frank–Starling mechanism technique was adopted to control the set point within a safe operating zone (green square), and it mimics the physiological demand of the patient. This zone is predefined by preload control lines, which are known as preload lines. A proportional–integral (PI) controller was utilized to control the operating point within safe limits to prevent suction or overperfusion. In addition, a PI type 1 fuzzy logic controller was designed and implemented to drive the LVAD pump. To evaluate the design method, rest, moderate, and exercise scenarios of heart failure (HF) were simulated by varying the hemodynamic parameters in one cardiac cycle. This evaluation was conducted using a lumped parameter model of the cardiovascular system (CVS). The results demonstrated that the proposed control method efficiently drives an LVAD pump under accepted clinical conditions. In both scenarios, the left ventricle pressure recorded 112 mmHg for rest and 55 mmHg for exercise, and the systematic flow recorded 5.5 L/min for rest and 1.75 L/min for exercise.
Estimation of Reliability Indices for Alpha Power Exponential Distribution Based on Progressively Censored Competing Risks Data
Authors: Nassar Mazen , Alotaibi  Refah , Zhang  Chunfang
Published: June 2022

In reliability analysis and life testing studies, the experimenter is frequently interested in studying a specific risk factor in the presence of other factors. In this paper, the estimation of the unknown parameters, reliability and hazard functions of alpha power exponential distribution is considered based on progressively Type-II censored competing risks data. We assume that the latent cause of failures has independent alpha power exponential distributions with different scale and shape parameters. The maximum likelihood method is considered to estimate the model parameters as well as the reliability and hazard rate functions. The approximate and two parametric bootstrap confidence intervals of the different estimators are constructed. Moreover, the Bayesian estimation method of the unknown parameters, reliability and hazard rate functions are obtained based on the squared error loss function using independent gamma priors. To get the Bayesian estimates as well as the highest posterior credible intervals, the Markov Chain Monte Carlo procedure is implemented. A comprehensive simulation experiment is conducted to compare the performance of the proposed procedures. Finally, a real dataset for the relapse of multiple myeloma with transplant-related mortality is analyzed.
The Marine-Derived Macrolactone Mandelalide A Is an Indirect Activator of AMPK
Authors: Mattos Daphne , Wan Xuemei , Serrill Jeffrey , Nguyen Minh , Humphreys Ian , Viollet Benoit , Smith Amos , McPhail Kerry , Ishmael Jane
Published: June 2022

The mandelalides are complex macrolactone natural products with distinct macrocycle motifs and a bioactivity profile that is heavily influenced by compound glycosylation. Mandelalides A and B are direct inhibitors of mitochondrial ATP synthase (complex V) and therefore more toxic to mammalian cells with an oxidative metabolic phenotype. To provide further insight into the pharmacology of the mandelalides, we studied the AMP-activated protein kinase (AMPK) energy stress pathway and report that mandelalide A is an indirect activator of AMPK. Wild-type mouse embryonic fibroblasts (MEFs) and representative human non-small cell lung cancer (NSCLC) cells showed statistically significant increases in phospho-AMPK (Thr172) and phospho-ACC (Ser79) in response to mandelalide A. Mandelalide L, which also harbors an A-type macrocycle, induced similar increases in phospho-AMPK (Thr172) and phospho-ACC (Ser79) in U87-MG glioblastoma cells. In contrast, MEFs co-treated with an AMPK inhibitor (dorsomorphin), AMPKα-null MEFs, or NSCLC cells lacking liver kinase B1 (LKB1) lacked this activity. Mandelalide A was significantly more cytotoxic to AMPKα-null MEFs than wild-type cells, suggesting that AMPK activation serves as a protective response to mandelalide-induced depletion of cellular ATP. However, LKB1 status alone was not predictive of the antiproliferative effects of mandelalide A against NSCLC cells. When EGFR status was considered, erlotinib and mandelalide A showed strong cytotoxic synergy in combination against erlotinib-resistant 11-18 NSCLC cells but not against erlotinib-sensitive PC-9 cells. Finally, prolonged exposures rendered mandelalide A, a potent and efficacious cytotoxin, against a panel of human glioblastoma cell types regardless of the underlying metabolic phenotype of the cell. These results add biological relevance to the mandelalide series and provide the basis for their further pre-clinical evaluation as ATP synthase inhibitors and secondary activators of AMPK.
Amino Acid-Coupled Bromophenols and a Sulfated Dimethylsulfonium Lanosol from the Red Alga Vertebrata lanosa
Authors: Jacobtorweihen Joshua , Schmitt Marthe , Spiegler Verena
Published: June 2022

Vertebrata lanosa is a red alga that can commonly be found along the shores of Europe and North America. Its composition of bromophenols has been studied intensely. The aim of the current study was therefore to further investigate the phytochemistry of this alga, focusing more on the polar components. In total, 23 substances were isolated, including lanosol-4,7-disulfate (4) and the new compounds 3,5-dibromotyrosine (12), 3-bromo-5-sulfodihydroxyphenylalanine (13), 3-bromo-6-lanosyl dihydroxyphenylalanine (14), 3-(6′-lanosyl lanosyl) tyrosine (15) and 5-sulfovertebratol (16). In addition, 4-sulfo-7-dimethylsulfonium lanosol (7) was identified. While, in general, the dimethylsulfonium moiety is widespread in algae, its appearance in bromophenol is unique. Moreover, the major glycerogalactolipids, including the new ((5Z,8Z,11Z,14Z,17Z)-eicosapentaenoic acid 3′-[(6′’-O-α-galactopyranosyl-β-D-galactopyranosyl)]-1-glycerol ester (23), and mycosporine-like amino acids, porphyra-334 (17), aplysiapalythine A (18) and palythine (19), were identified.
Characterization of Plocamium telfairiae Extract-Functionalized Au Nanostructures and Their Anti-Adipogenic Activity through PLD1
Authors: Park Sun Young , Kang Hye mi , Song Woo Chang , Oh Jin-Woo , Park Geuntae , Choi Young-Whan
Published: June 2022

Here, Au nanostructure (AuNS) biosynthesis was mediated through ethanolic extract of Plocamium telfairiae (PT) without the use of stabilizers or surfactants. PT-functionalized AuNSs (PT-AuNSs) were analyzed using ultraviolet–visible spectroscopy, dynamic light scattering, high-resolution transmission electron microscopy, energy-dispersive spectroscopy, and Fourier-transform infrared spectroscopy. Stable monodisperse PT-AuNSs were synthesized, with a mean size of 15.36 ± 0.10 nm and zeta potential of −35.85 ± 1.36 mV. Moreover, biosynthetic AuNPs with a face-centered structure of PT-AuNS exhibited crystalline characteristics. In addition, many functional groups playing important roles in the biological reduction of PT extracts were adsorbed on the surface of PT-AuNSs. Furthermore, the effects of PT-AuNSs on adipogenesis in immature adipocytes were investigated. PT-AuNSs reduced morphological changes, lowered triglyceride content, and increased lipid accumulation by approximately 78.6% in immature adipocytes compared with the values in mature adipocytes (MDI-induced). PT-AuNS suppressed lipid accumulation by downregulating the transcript and protein expression of C/EBPα, PPARγ, SREBP 1, FAS, and aP2. Finally, PT-AuNS induced the transcript and protein expression of UCP1, PRDM16, and PGC1a, thereby increasing mitochondrial biogenesis in mature adipocytes and effectively inducing brown adipogenesis. In this study, the biosynthesized PT-AuNS was used as a potential therapeutic candidate because it conferred a potent anti-lipogenic effect. As a result, it can be used in various scientific fields such as medicine and the environment.
In-Situ Sludge Reduction in Membrane-Controlled Anoxic-Oxic-Anoxic Bioreactor: Performance and Mechanism
Authors: Li Chengyue , Maqbool Tahir , Kang Hongyu , Zhang Zhenghua
Published: June 2022

Conventional and advanced biological wastewater treatment systems generate excess sludge, which causes socio-economic and environmental issues. This study investigated the performance of membrane-controlled anoxic-oxic-anoxic (AOA) bioreactors for in-situ sludge reduction compared to the conventional anoxic-oxic-oxic membrane bioreactor (MBRcontrol). The membrane units in the AOA bioreactors were operated as anoxic reactors at lower sludge recirculation rates to achieve hydrolysis of extracellular polymeric substances (EPS) and extensive endogenous respiration. Compared to MBRcontrol, the AOA bioreactors operated with 90%, and 80% recirculation rates reduced the sludge growth up to 19% and 30%, respectively. Protein-like components were enriched in AOA bioreactors while fulvic-like components were dominant in MBRcontrol. The growth of Dechloromonas and Zoogloea genra was promoted in AOA bioreactors and thus sludge reduction was facilitated. Metagenomics analysis uncovered that AOA bioreactors exhibited higher proportions of key genes encoding enzymes involved in the glycolysis and denitrification processes, which contributed to the utilization of carbon sources and nitrogen consumption and thus sludge reduction.
National Surveillance of Acute Flaccid Paralysis Cases in Senegal during 2017 Uncovers the Circulation of Enterovirus Species A, B and C
Authors: Ndiaye Ndack , Fall Amary , Kébé Ousmane , Kiory Davy , Dia Hamet , Fall Malick , Dia Ndongo , Sall Amadou Alpha , Faye Martin , Faye Ousmane
Published: June 2022

Polioviruses have been eliminated in many countries; however, the number of acute flaccid paralysis cases has not decreased. Non-polio enteroviruses are passively monitored as part of the polio surveillance program. Previous studies have shown that some enteroviruses do not grow in conventional cell lines used for the isolation of poliovirus according to the WHO guidelines. In order to evaluate the presence of enteroviruses, real-time RT-PCR was performed on Human Rhabdomyosarcoma (RD)-positive and RD-negative stool samples. A total of 310 stool samples, collected from children under the age of 15 years with acute flaccid paralysis in Senegal in 2017, were screened using cell culture and real-time RT-PCR methods. The selected isolates were further characterized using Sanger sequencing and a phylogenetic tree was inferred based on VP1 sequences. Out of the 310 stool samples tested, 89 were positive in real-time RT-PCR. A total of 40 partial VP1 sequences were obtained and the classification analysis showed that 3 (13%), 19 (82.6%), and 1 (4.4%) sequences from 23 RD-positive non-polio enterovirus isolates and 3 (17.6%), 7 (41.1%), and 7 (41.1%) sequences from 17 RD-negative stool samples belonged to the species EV-A, B, and C, respectively. Interestingly, the EV-B sequences from RD-negative stool samples were grouped into three separate phylogenetic clusters. Our data exhibited also a high prevalence of the EV-C species in RD-negative stool samples. An active country-wide surveillance program of non-polio enteroviruses based on direct RT-PCR coupled with sequencing could be important not only for the rapid identification of the involved emergence or re-emergence enteroviruses, but also for the assessment of AFP’s severity associated with non-polio enteroviruses detected in Senegal.
Current Treatments to Control African Trypanosomiasis and One Health Perspective
Authors: Venturelli Alberto , Tagliazucchi Lorenzo , Lima Clara , Venuti Federica , Malpezzi Giulia , Magoulas George E. , Santarem Nuno , Calogeropoulou Theodora , Cordeiro-da-Silva Anabela , Costi Maria Paola
Published: June 2022

Human African Trypanosomiasis (HAT, sleeping sickness) and Animal African Trypanosomiasis (AAT) are neglected tropical diseases generally caused by the same etiological agent, Trypanosoma brucei. Despite important advances in the reduction or disappearance of HAT cases, AAT represents a risky reservoir of the infections. There is a strong need to control AAT, as is claimed by the European Commission in a recent document on the reservation of antimicrobials for human use. Control of AAT is considered part of the One Health approach established by the FAO program against African Trypanosomiasis. Under the umbrella of the One Health concepts, in this work, by analyzing the pharmacological properties of the therapeutic options against Trypanosoma brucei spp., we underline the need for clearer and more defined guidelines in the employment of drugs designed for HAT and AAT. Essential requirements are addressed to meet the challenge of drug use and drug resistance development. This approach shall avoid inter-species cross-resistance phenomena and retain drugs therapeutic activity.
Two New Species of Filamentous Sulfur Bacteria of the Genus Thiothrix, Thiothrix winogradskyi sp. nov. and ‘Candidatus Thiothrix sulfatifontis’ sp. nov.
Authors: Ravin Nikolai , Rossetti Simona , Beletsky Alexey , Kadnikov Vitaly , Rudenko Tatyana , Smolyakov Dmitry , Moskvitina Marina , Gureeva Maria , Mardanov Andrey , Grabovich Margarita
Published: June 2022

The metagenome of foulings from sulfidic spring “Serovodorodny” (Tatarstan, Russia), where members of the genus Thiothrix was observed, was sequenced. Representatives of the phyla Gammaproteobacteria, Cyanobacteria and Campilobacteriota dominated in the microbial community. The complete genome of Thiothrix sp. KT was assembled from the metagenome. It displayed 93.93–99.72% 16S rRNA gene sequence identity to other Thiothrix species. The average nucleotide identity (ANI) и digital DNA-DNA hybridization (dDDH) showed that the genome designated KT represents a new species within the genus Thiothrix, ‘Candidatus Thiothrix sulfatifontis’ sp. nov. KT. The taxonomic status has been determined of the strain Thiothrix sp. CT3, isolated about 30 years ago and not assigned to any of Thiothrix species due to high 16S rRNA gene sequence identity with related species (i.e., 98.8–99.4%). The complete genome sequence of strain CT3 was determined. The ANI between CT3 and other Thiothrix species was below 82%, and the dDDH values were less than 40%, indicating that strain CT3 belongs to a novel species, Thiothrix winogradskyi sp. nov. A genome analysis showed that both strains are chemo-organoheterotrophs, chemolithotrophs (in the presence of hydrogen sulfide and thiosulfate) and chemoautotrophs. For the first time, representatives of Thiothrix showed anaerobic growth in the presence of thiosulfate.
Effects of Nano-Aerators on Microbial Communities and Functions in the Water, Sediment, and Shrimp Intestine in Litopenaeus vannamei Aquaculture Ponds
Authors: Xu Yingkai , Li Lisong , Lou Suo , Tian Jiashen , Sun Shuhao , Li Xiaodong , Li Yingdong
Published: June 2022

Nanobubble technology has promising development and application prospects in the fields of sewage treatment, soil and groundwater remediation, animal and plant growth, and biomedicine. However, few studies have investigated its effect on shrimp aquaculture. In this study, we investigated the effect of nano-aerators on microbial communities of the water, sediment, and shrimp gut in a Litopenaeus vannamei aquaculture pond using 16S rRNA high-throughput sequencing. The results indicated that the nano-aerator significantly increased the microbial community diversity and species abundance in the pond, and the microbial community diversity of the pond sediment increased under short-term aeration conditions. Compared to that with ordinary aerators, nano-aerators increased the proportion of beneficial bacteria, such as Exiguobacterium and Acinetobacter, in the water and sediment microbial communities. Moreover, the proportions of beneficial bacteria in the gut, including Rhodobacter, Oscillospira, and Faecalibacterium, were all increased by using the nano-aerator. Therefore, our findings suggest that nano-aerators could promote the activity of beneficial bacteria in aquaculture ecosystems, thereby regulating water quality, reducing disease incidence, and improving aquaculture efficiency and benefits. Our findings provide new insights into the effects of nano-aerators on microbes in crustacean culture ponds.
CO2-Degassing Carbonate Conduits in Early Pleistocene Marine Clayey Deposits in Southwestern Umbria (Central Italy)
Authors: Baldanza Angela , Bizzarri Roberto , Boschi Chiara , Famiani Federico , Frondini Francesco , Lezzerini Marco , Rowland Steven , Sutton Paul A.
Published: June 2022

Early Pleistocene marine deposits in southwestern Umbria (Orvieto–Allerona area, Italy) recently revealed the presence of more than forty carbonate conduits distributed over 2 km along the Paglia riverbed. In order to investigate their origins, analyses of their mineralogy, δ18O and δ13C stable isotopes, and organic geochemistry were conducted. All the carbonate conduits are made of euhedral microcrystals of dolomite with subordinate quartz, plagioclases, and micas. The stable carbon and oxygen isotope values of the bulk concretionary carbonates range from −0.57 to +4.79‰ (δ13C) and from +1.58 to +4.07‰ (δ18O), respectively. The lack of organic geochemical biomarkers of anaerobic methane oxidation (AOM) and the very low values of extractable organic matter suggest a non-biological origin for the dolomite precipitation. The latter is probably related to the rise of volcanic carbon dioxide due to the incipient Vulsini magmatism recorded in Early Pleistocene marine deposits all around the study site. The spatial distribution of the structures indicates that the upward migration of the CO2 was controlled by the fault system, while the vertical development of the conduits suggests that carbon dioxide degassing occurred, with multiple events. Carbon dioxide was probably stored in pockets within the clayey sediments until the pressure exceeded the eruptive threshold. These structures represent the first documentation of a volcanic carbon dioxide marine seepage event in the Umbria region.
Identification of a Hydrogen-Sulfide-Releasing Isochroman-4-One Hybrid as a Cardioprotective Candidate for the Treatment of Cardiac Hypertrophy
Authors: Wang Yu , Liu Yuechen , Wu Hongyu , Xu Shengtao , Ma Fenfen
Published: June 2022

Cardiac pathological hypertrophy is associated with undesirable epigenetic changes and causes maladaptive cardiac remodeling and heart failure, leading to high mortality rates. Specific drugs for the treatment of cardiac hypertrophy are still in urgent need. In the present study, a hydrogen-sulfide-releasing hybrid 13-E was designed and synthesized by appending p-hydroxythiobenzamide (TBZ), an H2S-releasing donor, to an analog of our previously discovered cardioprotective natural product XJP, 7,8-dihydroxy-3-methyl-isochromanone-4. This hybrid 13-E exhibited excellent H2S-generating ability and low cellular toxicity. The 13-E protected against cardiomyocyte hypertrophy In Vitro and reduced the induction of Anp and Bnp. More importantly, 13-E could reduce TAC-induced cardiac hypertrophy In Vivo, alleviate cardiac interstitial fibrosis and restore cardiac function. Unbiased transcriptomic analysis showed that 13-E regulated the AMPK signaling pathway and influenced fatty acid metabolic processes, which may be attributed to its cardioprotective activities.
Synthesis, Self-Assembly, and Cell Responses of Aromatic IKVAV Peptide Amphiphiles
Authors: Wu Fang-Yi , Lin Hsin-Chieh
Published: June 2022

Synthetic bioactive aromatic peptide amphiphiles have been recognized as key elements of emerging biomedical strategies due to their biocompatibility, design flexibility, and functionality. Inspired by natural proteins, we synthesized two supramolecular materials of phenyl-capped Ile-Lys-Val-Ala-Val (Ben-IKVAV) and perfluorophenyl-capped Ile-Lys-Val-Ala-Val (PFB-IKVAV). We employed UV-vis absorption, fluorescence, circular dichroism, and Fourier-transform infrared spectroscopy to examine the driving force in the self-assembly of the newly discovered materials. It was found that both compounds exhibited ordered π-π interactions and secondary structures, especially PFB-IKVAV. The cytotoxicity of human mesenchymal stem cells (hMSCs) and cell differentiation studies was also performed. In addition, the immunofluorescent staining for neuronal-specific markers of MAP2 was 4.6 times (neural induction medium in the presence of PFB-IKVAV) that of the neural induction medium (control) on day 7. From analyzing the expression of neuronal-specific markers in hMSCs, it can be concluded that PFB-IKVAV may be a potential supramolecular biomaterial for biomedical applications.