bluuebunny/crossref_metadata_2025 huggingface dataset:
Overcoming Methicillin-Resistance Staphylococcus aureus (MRSA) Using Antimicrobial Peptides-Silver Nanoparticles
Authors: Masimen Mohammad Asyraf Adhwa , Harun Noor Aniza , Maulidiani M. , Ismail Wan Iryani Wan
Published: July 2022

Antibiotics are regarded as a miracle in the medical field as it prevents disease caused by pathogenic bacteria. Since the discovery of penicillin, antibiotics have become the foundation for modern medical discoveries. However, bacteria soon became resistant to antibiotics, which puts a burden on the healthcare system. Methicillin-resistant Staphylococcus aureus (MRSA) has become one of the most prominent antibiotic-resistant bacteria in the world since 1961. MRSA primarily developed resistance to beta-lactamases antibiotics and can be easily spread in the healthcare system. Thus, alternatives to combat MRSA are urgently required. Antimicrobial peptides (AMPs), an innate host immune agent and silver nanoparticles (AgNPs), are gaining interest as alternative treatments against MRSA. Both agents have broad-spectrum properties which are suitable candidates for controlling MRSA. Although both agents can exhibit antimicrobial effects independently, the combination of both can be synergistic and complementary to each other to exhibit stronger antimicrobial activity. The combination of AMPs and AgNPs also reduces their own weaknesses as their own, which can be developed as a potential agent to combat antibiotic resistance especially towards MRSA. Thus, this review aims to discuss the potential of antimicrobial peptides and silver nanoparticles towards controlling MRSA pathogen growth.
Hyperferritinemia, Low Circulating Iron and Elevated Hepcidin May Negatively Impact Outcome in COVID-19 Patients: A Pilot Study
Authors: Szabo Robert , Petrisor Cristina , Bodolea Constantin , Simon Robert , Maries Ioana , Tranca Sebastian , Mocan Teodora
Published: July 2022

Inflammation in COVID-19 produces intracellular iron overload with low circulating iron available for metabolic processes. The accumulated intracellular iron generates reactive species of oxygen and results in ferroptosis, a non-programmed cell death. Since no organ is spared, iron dysmetabolism increases the mortality and morbidity. Hepcidin and the mediator interleukin 6 are believed to play a role in the process. Our aim is to evaluate the predictive values of serologic iron and inflammatory parameters in COVID-19 critically ill patients. Hence, 24 patients were included. Hepcidin and interleukin 6, along with routine blood parameters, were determined and outcomes, such as death, multiple organ damage (MOD), anemia, and need for transfusions, were assessed. The results of this pilot study indicate that iron metabolism parameters individually, as well as models consisting of multiple laboratory and clinical variables, may predict the outcomes. Further larger studies are needed to validate the results of this pilot stud. However, this paper identifies a new direction for research.
Comprehensive Expression Analyses of Plastidial Thioredoxins of Arabidopsis thaliana Indicate a Main Role of Thioredoxin m2 in Roots
Authors: Sahrawy Mariam , Fernández-Trijueque Juan , Vargas Paola , Serrato Antonio J.
Published: July 2022

Thioredoxins (TRXs) f and m are redox proteins that regulate key chloroplast processes. The existence of several isoforms of TRXs f and m indicates that these redox players have followed a specialization process throughout evolution. Current research efforts are focused on discerning the signalling role of the different TRX types and their isoforms in chloroplasts. Nonetheless, little is known about their function in non-photosynthetic plastids. For this purpose, we have carried out comprehensive expression analyses by using Arabidopsis thaliana TRXf (f1 and f2) and TRXm (m1, m2, m3 and m4) genes translationally fused to the green fluorescence protein (GFP). These analyses showed that TRX m has different localisation patterns inside chloroplasts, together with a putative dual subcellular localisation of TRX f1. Apart from mesophyll cells, these TRXs were also observed in reproductive organs, stomatal guard cells and roots. We also investigated whether photosynthesis, stomatal density and aperture or root structure were affected in the TRXs f and m loss-of-function Arabidopsis mutants. Remarkably, we immunodetected TRX m2 and the Calvin–Benson cycle fructose-1,6-bisphosphatase (cFBP1) in roots. After carrying out in vitro redox activation assays of cFBP1 by plastid TRXs, we propose that cFBP1 might be activated by TRX m2 in root plastids.
A Review of Properties of Nanocellulose, Its Synthesis, and Potential in Biomedical Applications
Authors: Randhawa Aayushi , Dutta Sayan Deb , Ganguly Keya , Patil Tejal V. , Patel Dinesh K. , Lim Ki-Taek
Published: July 2022

Cellulose is the most venerable and essential natural polymer on the planet and is drawing greater attention in the form of nanocellulose, considered an innovative and influential material in the biomedical field. Because of its exceptional physicochemical characteristics, biodegradability, biocompatibility, and high mechanical strength, nanocellulose attracts considerable scientific attention. Plants, algae, and microorganisms are some of the familiar sources of nanocellulose and are usually grouped as cellulose nanocrystal (CNC), cellulose nanofibril (CNF), and bacterial nanocellulose (BNC). The current review briefly highlights nanocellulose classification and its attractive properties. Further functionalization or chemical modifications enhance the effectiveness and biodegradability of nanocellulose. Nanocellulose-based composites, printing methods, and their potential applications in the biomedical field have also been introduced herein. Finally, the study is summarized with future prospects and challenges associated with the nanocellulose-based materials to promote studies resolving the current issues related to nanocellulose for tissue engineering applications.
A Multi-Objective Modified PSO for Inverse Kinematics of a 5-DOF Robotic Arm
Authors: Rokbani Nizar , Neji Bilel , Slim Mohamed , Mirjalili Seyedali , Ghandour Raymond
Published: July 2022

In this paper, a new modified particle swarm optimization, m-PSO, is proposed, in which the novelty consists of proposing a fitness-based particle swarm optimization algorithm, PSO, which adapts the particles’ behavior rather than the PSO parameters and where particles evolve differently considering their level of optimality. A multi-objective optimization, MO, approach is then built based on m-PSO. In the proposed method, particles with fitness better than the mean local best are only updated toward the global best, while others keep moving in a classical manner. The proposed m-PSO and its multi-objective version MO-m-PSO are then employed to solve the inverse kinematics of a 5-DOF robotic arm which is 3D-printed for educational use. In the MO-m-PSO approach of inverse kinematics, the arm IK problem is formulated as a multi-objective problem searching for an appropriate solution that takes into consideration the end-effector position and orientation with a Pareto front strategy. The IK problem is addressed as the optimization of the end-effector position and orientation based on the forward kinematics model of the systems which is built using the Denavit–Hartenberg approach. Such an approach allows to avoid classical inverse kinematics solvers challenges such as singularities, which may simply harm the existence of an inverse expression. Experimental investigations included the capacity of the proposal to handle random single points in the workspace and also a circular path planning with a specific orientation. The comparative analysis showed that the mono-objective m-PSO is better than the classical PSO, the CSA, and SSA. The multi-objective variants returned accurate results, fair and better solutions compared to multi-objective variants of MO-PSO, MO-JAYA algorithm, and MO-CSA. Even if the proposed method were applied to solve the inverse kinematics of and educational robotics arms for a single point as well as for a geometric shape, it may be transposed to solve related industrial robotized arms withthe only condition of having their forward kinematics model.
Optical Property Measurement and Temperature Monitoring in High-Intensity Focused Ultrasound Therapy by Diffuse Optical Tomography: A Correlation Study
Authors: Yang Hao , Aleman Sean , Jiang Huabei
Published: July 2022

In this article, we propose a new approach utilizing diffuse optical tomography (DOT) to monitoring the changes in tissues’ optical properties and temperature in high-intensity focused ultrasound (HIFU) therapy. By correlating the tissue reduced scattering coefficient (μs’) reconstructed by DOT and the temperature measured by a thermocouple, the quantitative relationship between μs’ and temperature in HIFU treatment was explored. The experiments were conducted using porcine and chicken breast muscle tissues during HIFU; the temperature of each tissue sample was recorded using a thermocouple. To incorporate the temperature dependency of tissue optical properties, both polynomial and exponential models were utilized to fit the experimental data. The results show that the change of μs’ during HIFU treatment could be detected in real-time using DOT and that this change of μs’ is quantitatively correlated with tissue temperature. Furthermore, while the tissue-type-dependent relationship between μs’ and temperature is non-linear in nature, it is stable and repeatable. Therefore, our approach has the potential to be used to predict temperature of tissue during HIFU treatment.
Adaptive Cruise Control in Electric Vehicles with Field-Oriented Control
Authors: Petri Ana-Maria , Petreuș Dorin Marius
Published: July 2022

An adaptive cruise control system is highly used in conventional internal combustion engine vehicles, but due to the electrification of the vehicles, the adaptive cruise control system must be placed in relation with the electric motor control block. This paper presents the relationship between an adaptive cruise control system and the motor control in the case of an electric vehicle. An indirect filed-oriented control of an induction machine is considered for the electric traction system. The adaptive cruise control block computes the required acceleration to ensure the velocity set by the driver based on the set velocity, the actual velocity of the vehicle, a safe distance, and the relative distance between the host car and a leading car. The proposed system was implemented in MATLAB/Simulink and, also, in a low-scale laboratory experimental setup. The correct operation of the system was tested using a speed profile, and both systems, simulated and experimental, have the expected response. The velocity, acceleration, rotor speed, torque response, and relative and safe distance are the responses presented to prove the efficiency of the proposed implementation.
Development of an Oxy-Fuel Combustion System in a Compression-Ignition Engine for Ultra-Low Emissions Powerplants Using CFD and Evolutionary Algorithms
Authors: Serrano José Ramón , Bracho Gabriela , Gomez-Soriano Josep , Fernandes Cássio
Published: July 2022

This study uses an optimization approach for developing a combustion system in a compression–ignition engine that is able to operate under oxy-fuel conditions, and produces mainly CO2 and H2O as exhaust gases. This is achieved because the combustion concept uses pure oxygen as an oxidizer, instead of air, avoiding the presence of nitrogen. The O2 for the combustion system can be obtained by using a mixed ionic–electronic conducting membrane (MIEC), which separates the oxygen from the air onboard. The optimization method employed maximizes the energy conversion of the system, reducing pollutant emissions (CxHy, particulate matter, and carbon monoxides) to levels near zero. The methodology follows a novel approach that couples computational fluid dynamics (CFD) and particle swarm optimization (PSO) algorithms to optimize the complete combustion system in terms of engine performance and pollutant generation. The study involves the evaluation of several inputs that govern the combustion system design in order to fulfill the thermo-mechanical constraints. The parameters analyzed are the piston bowl geometry, fuel injector characteristics, air motion, and engine settings variables. Results evince the relevance of the optimization procedure, achieving very low levels of gaseous pollutants (CxHy and CO) in the optimum configuration. The emissions of CO were reduced by more than 10% while maintaining the maximum in-cylinder pressure within the limit imposed for the engine. However, indicated efficiency levels are compromised if they are compared with an equivalent condition operating under conventional diesel combustion.
Study on Accuracy of CFD Simulations of Wind Environment around High-Rise Buildings: A Comparative Study of k-ε Turbulence Models Based on Polyhedral Meshes and Wind Tunnel Experiments
Authors: Xiong Minghui , Chen Bing , Zhang Hua , Qian Yao
Published: July 2022

It is important to create a comfortable wind environment around high-rise buildings for outdoor activities. To predict the wind environment, Computational Fluid Dynamics (CFD) has been widely used by designers and engineers. However, the simulation results of different CFD turbulence models might significantly vary. This paper researched the wind environment around a typical high-rise building and verified the accuracy of the CFD simulations based on polyhedral meshes. The differences between the simulation results of the k-ε turbulence models and those of the wind tunnel experiments were compared from the perspectives of wind speed and turbulence energy. The results show that the modified k-ε models could still not perfectly match the wind tunnel experiment results. Specifically, in the low-wind-speed areas, the simulation results of the Realizable Two-Layer K-Epsilon (RTLKE) model were the closest to the experimental results of the wind tunnels, while in the high-wind-speed areas the simulation results of the Standard Two-Layer K-Epsilon (STLKE) model were the closest to the experimental results of the wind tunnels. Therefore, it is recommended that these two k-ε turbulence models are applied under different conditions—the RTLKE model should be used to simulate low-wind areas around high-rise buildings (e.g., defining the size of the static-wind area around high-rise buildings, predicting the diffusion time of pollutants around high-rise buildings, etc.); STLKE should be used to simulate high-wind-speed areas around high-rise buildings (e.g., the high speed wind area around high-rise buildings during a typhoon, the maximum wind speed area around high-rise buildings, etc.). It is expected that findings from this research study supplement some existing high-rise building design guidance.
A Numerical Study on the Crack Propagation of Homogenized Micro-Crack Crushing for Concrete Pavement
Authors: Li Wenjie , Guo Ying , Liang Bin , Yue Jinchao
Published: July 2022

Homogenized micro-crack crushing is a new method of concrete pavement rehabilitation that makes full use of the bearing capacity of the original concrete pavement, whereby the treated pavement can be directly overlaid with hot mixed asphalt concrete. In order to solve the problem of longitudinal crack extension of a cracked core in the weak position of local pavement, the crack propagation mode of concrete slabs under low-velocity impact from different numbers and distributions of impact heads was studied using numerical simulation. Moreover, field tests were also carried out to determine the optimal layout of drop hammer impact heads, and the numerical simulation results were compared with the experimental data. The results show that, when a concrete slab is impacted by a single impact head, the bottom of the slab first cracks and then the crack develops upward until the main crack runs through the concrete slab. However, when the concrete slab is impacted by multiple-impact heads, including three or four impact heads, the concrete slab forms a triangular or quadrilateral fracture core, respectively. The numerical simulation results are in good agreement with the laboratory experiments. Through the optimized arrangement of the hammer’s impact heads, the problem of longitudinal crack extension of a cracked core can be effectively solved, and the probability of reflection cracks can be reduced.
Evaluation of Adhesion Characteristics According to Chemical Deterioration Conditions and Recycled Material Content of Butyl Rubber Compound Waterproof Sheet
Authors: Sung Ju-Hyun , Kim Dong-Bum , Choi Su-Young , Park Jin-Sang , Jiang Bo , Oh Sang-Keun
Published: July 2022

This study sought to investigate the adhesion strength reduction of reclaimed butyl rubber self-adhesive waterproofing sheets after exposure to a chemical erosion environment. Ranges from 0 to 45% mixture ratio (with changing intervals of 5% ratio) of reclaimed butyl rubber replaced the new rubber content of commercial butyl rubber self-adhesive waterproofing sheets for testing, based on the optimal results for the reclaimed butyl rubber content in order to ensure performance that meets the standard criteria. The research results confirmed that performance degradation was relatively greater when exposed to an acidic environment that was responsible for chemical deterioration. It was also confirmed that, given the deterioration environment described above, the reclaimed butyl rubber content should be limited to 44% so as to ensure an adhesion performance similar to that of the untreated test sample (reclaimed butyl rubber content of 67%). Based on the above results, it was suggested that the optimal mixing range of reclaimed butyl rubber should be up to 44% of the total rubber content, considering performance degradation after field application in the production of self-adhesive waterproofing sheets.
Intelligent Construction and Management of Landscapes through Building Information Modeling and Mixed Reality
Authors: Zhao Xuefeng , Li Mengxuan , Sun Zhe , Zhao Yue , Gai Yihao , Wang Jingjing , Huang Chun , Yu Lei , Wang Sicong , Zhang Meng , Huang Lingli
Published: July 2022

Intelligent construction and management processes are essential to ensure the efficiency of planting and maintenance of landscapes in large-scale projects. Unfortunately, various challenges still exist for achieving such a vision. For instance, creating detailed models of various plants to precisely capture the spatiotemporal changes is challenging. Moreover, transmitting massive plant-related data in time for project coordination and remote maintenance is also difficult through traditional landscape management practices. Integrated use of building information modeling (BIM) and mixed reality (MR) techniques could help establish digital representations of various plants with semantic information. Such integration of BIM and MR offers instinctual interactions by blending the physical and digital worlds. This study proposed an intelligent construction and management framework through BIM and MR to (1) establish detailed models of various plants, (2) capture spatiotemporal changes of plants across four seasons for model updating, and (3) establish a real-time data transmission method for effective project coordination and remote maintenance of various plants. The authors used the Jinhu Park project in the Xiong’an New District of China as a case study to validate the proposed method. Results show that the proposed method could support the sustainable development of landscapes in real practice.
Integrated Autopilot Guidance Based on Zero-Effort-Miss Formulation for Tail-Controlled Missiles
Authors: Kim Hyeong-Geun , Shin Jongho
Published: July 2022

This paper presents a control structure integrating guidance and control loops for tail-controlled missile systems. Motivated by the fact that common tail-controlled missiles involve non-minimum phase dynamics, the proposed controller is designed to prevent the internal dynamics from diverging, as well as achieving homing against the intended target. To minimize the miss distance at the end of homing, we derive a formulation of a zero-effort-miss using engagement kinematics that contain the rotating dynamics of the missile, which is different from existing approaches. Subsequently, to nullify the zero-effort-miss, a nonlinear controller is designed based on the Lyapunov stability theory. Since the derived controller has a similar structure to the conventional three-loop topology that has been utilized for various tail-controlled flight systems, it is expected that the proposed method can be applied to the actual system from a practical point of view. Numerical simulation results also show that the proposed method achieves target interception while possessing stable internal dynamics.
A Method for Finding the Static Equilibrium of the Non-Steered Wheel Suspension Systems Used in Passenger Cars
Authors: Alexandru Cătălin
Published: July 2022

In this work, an analytical method for finding the equilibrium configuration of the suspension systems used for the non-steered (usually rear) wheels of the passenger car is proposed. This study is based on the static model, which takes into account the elastic elements of the suspension (springs, bushings, anti-roll bar, buffers). The external loading of the suspension system comes from the contact forces between the wheels and the ground, depending on the specific operating regime of the vehicle (static or dynamic, by case). An algorithm for analysis of the relative movements in the wheel guiding mechanisms was developed (and further integrated in the general method for finding the equilibrium position) with the purpose of establishing the deformations of the elastic elements. Finally, a computer program was conceived and tested on a particular application.
Countrywide Mapping of Plant Ecological Communities with 101 Legends including Land Cover Types for the First Time at 10 m Resolution through Convolutional Learning of Satellite Images
Authors: Sharma Ram C.
Published: July 2022

This paper presents next-generation mapping of plant ecological communities including land cover and agricultural types at 10 m spatial resolution countrywide. This research introduces modelling and mapping of land cover and ecological communities separately in small regions-of-interest (prefecture level), and later integrating the outputs into a large scale (country level) for dealing with regional distribution characteristics of plant ecological communities effectively. The Sentinel-2 satellite images were processed for cloud masking and half-monthly median composite images consisting of ten multi-spectral bands and seven spectral indexes were generated. The reliable ground truth data were prepared from extant multi-source survey databases through the procedure of stratified sampling, cross-checking, and noisy-labels pruning. Deep convolutional learning of the time-series of the satellite data was employed for prefecture-wise classification and mapping of 29–62 classes. The classification accuracy computed with the 10-fold cross-validation method varied from 71.1–87.5% in terms of F1-score and 70.9–87.4% in terms of Kappa coefficient across 48 prefectural regions. This research produced seamless maps of 101 ecological communities including land cover and agricultural types for the first time at a country scale with an average accuracy of 80.5% F1-score.
Applications of Stretching Technique and Time Window Effects on Ultrasonic Velocity Monitoring in Concrete
Authors: Zhong Bibo , Zhu Jinying
Published: July 2022

Coda wave interferometry (CWI) has been used to measure the relative wave-velocity change (dV/V) caused by small changes in materials. This study uses the stretching processing technique which has been used for CWI analysis to investigate velocity changes of direct longitudinal (P) wave, direct shear (S) wave, and coda wave in concrete by choosing different time windows of ultrasonic signals. It is found that the obtained wave-velocity change depends on the time window position, because the relative contribution of P wave and S wave is different in each signal window. This paper presents three experimental scenarios of velocity change in concrete: early-age hydration, temperature change, and uniaxial loading. In early-age concrete, the S wave has a larger relative velocity change than the P wave, which is consistent with the microstructure development due to the hydration process. Temperature change causes a larger dV/V on the P wave than on the S wave, and the difference between P and S wave-velocity changes may be used to determine nonlinear elastic constants of materials. In the uniaxial loading experiment, analysis of the direct P wave can distinguish the acoustoelastic effects in the stress direction and the non-stress direction, which may potentially be used for stress evaluation in prestressed structures. However, the coda wave does not show this directional property to stress due to multiple scattering in the medium.
Applicability of a CEEMD–ARIMA Combined Model for Drought Forecasting: A Case Study in the Ningxia Hui Autonomous Region
Authors: Xu Dehe , Ding Yan , Liu Hui , Zhang Qi , Zhang De
Published: July 2022

In the context of global warming, the increasing frequency of drought events has caused negative impacts on agricultural productivity and societal activities. However, the drought occurrences have not been well predicted by any single model, and precipitation may show nonstationary behavior. In this study, 60 years of monthly precipitation data from 1960 to 2019 for the Ningxia Hui Autonomous Region were analyzed. The standard precipitation index (SPI) was used to classify drought events. This study combined the strengths of autoregressive integrated moving average (ARIMA) and complementary ensemble empirical mode decomposition (CEEMD) to predict drought. First, based on the precipitation dataset, the SPI at timescales of 1, 3, 6, 9, 12, and 24 months was calculated. Then, each of these SPI time series was predicted using the ARIMA model and the CEEMD–ARIMA combined model. Finally, the models′ performance was compared using statistical metrics, namely, root-mean-square error (RMSE), mean absolute error (MAE), Kling–Gupta efficiency (KGE), Willmott index (WI), and Nash–Sutcliffe efficiency (NSE). The results show that the following: (1) Compared with the ARIMA forecast value, the prediction results of the CEEMD–ARIMA model were in good agreement with the SPI values, indicating that the combined model outperformed the single model. (2) Two different models obtained the lowest accuracy for the SPI1 prediction and the highest accuracy for the SPI24 prediction. (3) The CEEMD–ARIMA model achieved higher prediction accuracy than the ARIMA model at each time scale. The most precise model during the test phase was the CEEMD–ARIMA model at SPI24 at Xiji Station, with error measures of MAE = 0.076, RMSE = 0.100, NSE = 0.994, KGE = 0.993, and WI = 0.999. Such findings will be essential for government to make decisions.
Classification and Estimation of Typhoon Intensity from Geostationary Meteorological Satellite Images Based on Deep Learning
Authors: Jiang Shuailong , Tao Lijun
Published: July 2022

In this paper, a novel typhoon intensity classification and estimation network (TICAENet) is constructed to recognize typhoon intensity. The TICAENet model is based on the LeNet-5 model, which uses weight sharing to reduce the number of training parameters, and the VGG16 model, which replaces a large convolution kernel with multiple small kernels to improve feature extraction. Satellite cloud images of typhoons over the Northwest Pacific Ocean and the South China Sea from 1995–2020 are taken as samples. The results show that the classification accuracy of this model is 10.57% higher than that of the LeNet-5 model; the classification accuracy of the TICAENet model is 97.12%, with a classification precision of 97.00% for tropical storms, severe tropical storms and super typhoons. The mean absolute error (MAE) and root mean square error (RMSE) of the samples estimation in 2019 are 4.78 m/s and 6.11 m/s, and the estimation accuracy are 18.98% and 20.65% higher than that of the statistical method, respectively. Additionally, the model takes less memory and runs faster due to the weight sharing and multiple small kernels. The results show that the proposed model performs better than other methods. In general, the proposed model can be used to accurately classify typhoon intensity and estimate the maximum wind speed by extracting features from geostationary meteorological satellite images.
Determinant Indicators for Assessing the Adaptive Capacity of Agricultural Producers to Climate Change
Authors: Maldonado-Méndez María de Lourdes , Romo-Lozano José Luis , Monterroso-Rivas Alejandro Ismael
Published: July 2022

Assessing adaptive capacity to climate change is a complex task since it is a multidimensional component. There has been considerable discrepancy between the dimensions or elements that compose it. This study aimed to analyze the relevant dimensions and indicators that allow estimation of the adaptive capacity to climate change and to propose a set of indicators that will enable their application to assessment at the level of agricultural producers. A systematic review of scientific literature on evaluating or measuring adaptive capacity to climate change was carried out. Subsequently, the indicators were analyzed and selected through a coincidence analysis and were calibrated through a multicriteria evaluation with relevant actors in the southern Mexico, state of Chiapas. In total, 329 indicators were identified and analyzed. As a result, 19 indicators were selected and then grouped into six dimensions: economic resources, human resources, infrastructure for production and marketing, institutionality, social capital, and natural resources. These represent the 14 specific dimensions with the greatest potential to contribute to the estimation of adaptive capacity to climate change. The dimensions and indicators can be applied to assess the adaptive capacity of farmers in Mexico at a national or regional scale and specifically by producer types.
Benchmarking the Accuracy of AlphaFold 2 in Loop Structure Prediction
Authors: Stevens Amy O. , He Yi
Published: July 2022

The inhibition of protein–protein interactions is a growing strategy in drug development. In addition to structured regions, many protein loop regions are involved in protein–protein interactions and thus have been identified as potential drug targets. To effectively target such regions, protein structure is critical. Loop structure prediction is a challenging subgroup in the field of protein structure prediction because of the reduced level of conservation in protein sequences compared to the secondary structure elements. AlphaFold 2 has been suggested to be one of the greatest achievements in the field of protein structure prediction. The AlphaFold 2 predicted protein structures near the X-ray resolution in the Critical Assessment of protein Structure Prediction (CASP 14) competition in 2020. The purpose of this work is to survey the performance of AlphaFold 2 in specifically predicting protein loop regions. We have constructed an independent dataset of 31,650 loop regions from 2613 proteins (deposited after the AlphaFold 2 was trained) with both experimentally determined structures and AlphaFold 2 predicted structures. With extensive evaluation using our dataset, the results indicate that AlphaFold 2 is a good predictor of the structure of loop regions, especially for short loop regions. Loops less than 10 residues in length have an average Root Mean Square Deviation (RMSD) of 0.33 Å and an average the Template Modeling score (TM-score) of 0.82. However, we see that as the number of residues in a given loop increases, the accuracy of AlphaFold 2’s prediction decreases. Loops more than 20 residues in length have an average RMSD of 2.04 Å and an average TM-score of 0.55. Such a correlation between accuracy and length of the loop is directly linked to the increase in flexibility. Moreover, AlphaFold 2 does slightly over-predict α-helices and β-strands in proteins.
Forced Overexpression of Signal Transducer and Activator of Transcription 3 (STAT3) Activates Yes-Associated Protein (YAP) Expression and Increases the Invasion and Proliferation Abilities of Small Cell Lung Cancer (SCLC) Cells
Authors: Hsu Ping-Chih , Li Jhy-Ming , Yang Cheng-Ta
Published: July 2022

Background: We sought to investigate the interaction between signal transducer and activator of transcription 3 (STAT3) and the Yes-associated protein (YAP) signaling pathway in human small cell lung cancer (SCLC) cells. Methods: The STAT3-overexpressing SCLC cell lines H146 and H446 were established by plasmid DNA transfection for in vitro and in vivo experiments. Results: Overexpression of STAT3 increased YAP protein expression in H146 and H446 cells. STAT3 overexpression significantly increased YAP mRNA expression and the mRNA expression of the YAP signaling downstream genes CTGF and CYR61 in H146 and H446 cells (p < 0.05). We showed that STAT3 overexpression promoted EMT (epithelial–mesenchymal transition) with increased matrix metalloproteinase (MMP)-2 and MMP9 expression. Transwell assays showed that STAT3 overexpression increased the invasion ability of H146 and H446 cells. In addition, STAT3-overexpressing H146 cells grew significantly more rapidly than control H146 cells in the xenograft mouse model (p < 0.05). Immunohistochemistry (IHC) staining and Western blotting (WB) showed that STAT3-overexpressing H146 tumors had increased p-STAT3 and YAP staining and protein expression compared with control tumors. Increased EMT was also observed in STAT3-overexpressed xenograft tumors. Conclusions: The results of our study suggest that the overexpression of STAT3 promotes SCLC EMT, invasion, and proliferation through the activation of the YAP signaling pathway.
Micro- and Nanosized Carriers for Nose-to-Brain Drug Delivery in Neurodegenerative Disorders
Authors: Boyuklieva Radka , Pilicheva Bissera
Published: July 2022

Neurodegenerative disorders (NDs) have become a serious health problem worldwide due to the rapid increase in the number of people that are affected and the constantly aging population. Among all NDs, Alzheimer’s and Parkinson’s disease are the most common, and many efforts have been made in the development of effective and reliable therapeutic strategies. The intranasal route of drug administration offers numerous advantages, such as bypassing the blood–brain barrier and providing a direct entrance to the brain through the olfactory and trigeminal neurons. The present review summarizes the available information on recent advances in micro- and nanoscale nose-to-brain drug-delivery systems as a novel strategy for the treatment of Alzheimer’s and Parkinson’s disease. Specifically, polymer- and lipid-base micro- and nanoparticles have been studied as a feasible approach to increase the brain bioavailability of certain drugs. Furthermore, nanocomposites are discussed as a suitable formulation for administration into the nasal cavity.
Identification of a Prognostic Microenvironment-Related Gene Signature in Glioblastoma Patients Treated with Carmustine Wafers
Authors: Manini Ivana , Dalla Emiliano , Vendramin Vera , Cesselli Daniela , Di Loreto Carla , Skrap Miran , Ius Tamara
Published: July 2022

Despite the state-of-the-art treatment, patients diagnosed with glioblastoma (GBM) have a median overall survival (OS) of 14 months. The insertion of carmustine wafers (CWs) into the resection cavity as adjuvant treatment represents a promising option, although its use has been limited due to contrasting clinical results. Our retrospective evaluation of CW efficacy showed a significant improvement in terms of OS in a subgroup of patients. Given the crucial role of the tumor microenvironment (TME) in GBM progression and response to therapy, we hypothesized that the TME of patients who benefited from CW could have different properties compared to that of patients who did not show any advantage. Using an in vitro model of the glioma microenvironment, represented by glioma-associated-stem cells (GASC), we performed a transcriptomic analysis of GASC isolated from tumors of patients responsive and not responsive to CW to identify differentially expressed genes. We found different transcriptomic profiles, and we identified four genes, specifically down-regulated in GASC isolated from long-term survivors, correlated with clinical data deposited in the TCGA–GBM dataset. Our results highlight that studying the in vitro properties of patient-specific glioma microenvironments can help to identify molecular determinants potentially prognostic for patients treated with CW.
Association between Preexisting Sleep Disorders and Oncologic Outcome in Patients with Oral Cavity Squamous Cell Carcinoma: A Nationwide Propensity Score—Matched Population-Based Cohort Study
Authors: Ou Shih-Hao , Chen Wan-Ming , Shia Ben-Chang , Wu Szu-Yuan , Lin Hsuan-Chih
Published: July 2022

Purpose: To investigate the effects of preexisting sleep disorders on the oncologic outcomes of patients receiving standard treatments for oral squamous cell carcinoma (OSCC). Methods: The patients recruited from the Taiwan Cancer Registry Database who had received surgery for stage I–IVB OSCC. The Cox proportional hazards model was used to analyze all-cause mortality, locoregional recurrence (LRR), and distant metastasis (DM). The patients were categorized into those with and without sleep disorders (Groups 1 and 2, respectively) through propensity score matching. Results: In the multivariate Cox regression analysis, the adjusted hazard ratios for all-cause mortality, LRR, and DM for Group 1 compared with Group 2 were 1.19 (95% confidence interval (CI): 1.04–1.36; p = 0.011), 1.47 (95% CI: 1.23–1.75; p < 0.001), and 1.15 (95% CI: 1.02–1.44; p = 0.025), respectively. Conclusion: OSCC patients with sleep disorders demonstrated poorer oncologic outcomes than did those without sleep disorders. Therefore, before OSCC surgery, patients with OSCC should be screened for preexisting sleep disorders because they may serve as predictors for survival in these patients. Future studies investigating the survival benefits of pharmacological and behavioral treatments for sleep problems in patients with OSCC are warranted.
Genetics in Familial Intrahepatic Cholestasis: Clinical Patterns and Development of Liver and Biliary Cancers: A Review of the Literature
Authors: Vitale Giovanni , Mattiaccio Alessandro , Conti Amalia , Turco Laura , Seri Marco , Piscaglia Fabio , Morelli Maria Cristina
Published: July 2022

The family of inherited intrahepatic cholestasis includes autosomal recessive cholestatic rare diseases of childhood involved in bile acids secretion or bile transport defects. Specific genetic pathways potentially cause many otherwise unexplained cholestasis or hepatobiliary tumours in a healthy liver. Lately, next-generation sequencing and whole-exome sequencing have improved the diagnostic procedures of familial intrahepatic cholestasis (FIC), as well as the discovery of several genes responsible for FIC. Moreover, mutations in these genes, even in the heterozygous status, may be responsible for cryptogenic cholestasis in both young and adults. Mutations in FIC genes can influence serum and hepatic levels of bile acids. Experimental studies on the NR1H4 gene have shown that high bile acids concentrations cause excessive production of inflammatory cytokines, resistance to apoptosis, and increased cell regeneration, all risk conditions for developing hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). NR1H4 gene encodes farnesoid X-activated receptor having a pivotal role in bile salts synthesis. Moreover, HCC and CCA can emerge in patients with several FIC genes such as ABCB11, ABCB4 and TJP2. Herein, we reviewed the available data on FIC-related hepatobiliary cancers, reporting on genetics to the pathophysiology, the risk factors and the clinical presentation.
Long-Term Clinical Outcomes and Safety Analysis of Superficial Esophageal Cancer Patients Treated with Definitive or Adjuvant Radiotherapy
Authors: Lyu Bo , Yin Yutian , Zhao Yilin , Yang Xu , Gong Jie , Zhang Mai , Chai Guangjin , Li Zhaohui , Shi Mei , Hui Zhouguang , Zhao Lina
Published: July 2022

(1) Background: The role of radiotherapy (RT) in superficial esophageal squamous cell cancer (ESCC) remains unclear. The objective of our study was to perform a detailed outcome and safety analysis of RT as a definitive or adjuvant treatment for T1N0M0 staged ESCC patients. (2) Methods: A total of 55 patients treated with endoscopic resection (ER) + RT/concurrent chemoradiotherapy (CCRT) or RT/CCRT from January 2011 to June 2021 were included in this study. Eighteen patients with risk factors received ER + RT/CCRT, and thirty-seven patients solely received RT/CCRT. Kaplan–Meier curves were used to calculate the clinical outcomes, and toxicities were scored. (3) Results: The median follow-up time was 51.9 months. The estimated 5-year local recurrence-free survival (LRFS) and overall survival (OS) were 88.9% and 94.4% in the ER + RT/CCRT group and 91.8% and 91.7% in the RT/CCRT group. The predominant failure pattern was in-field local failure (5.5%, 3/55), with one patient in the ER + RT/CCRT group and two patients in the RT/CCRT group. One patient (1.8%, 1/55) had lung metastasis in the RT/CCRT group. The most common toxicities were Grades 1–2 in all patients, including esophagitis (74.5%, 41/55), myelosuppression (49.1%, 27/55) and esophageal stricture after RT (27.3%, 15/55). Two patients (11.1%, 2/18) and four patients (10.8%, 4/37) had Grade 3 esophageal stricture after RT in the ER + RT/CCRT group and RT/CCRT group, respectively. No patients experienced a Grade 4 or higher toxicity, and there were no treatment-related deaths. (4) Conclusions: Definitive or adjuvant RT/CCRT is an effective treatment alternative for superficial ESCC patients with satisfactory clinical outcomes and acceptable toxicities.
The Role of Citrate Homeostasis in Merkel Cell Carcinoma Pathogenesis
Authors: Drexler Konstantin , Schwertner Barbara , Haerteis Silke , Aung Thiha , Berneburg Mark , Geissler Edward K. , Mycielska Maria E. , Haferkamp Sebastian
Published: July 2022

Merkel cell carcinoma (MCC) is a rare but highly aggressive tumor of the skin with a poor prognosis. The factors driving this cancer must be better understood in order to discover novel targets for more effective therapies. In the search for targets, we followed our interest in citrate as a central and critical metabolite linked to fatty acid synthesis in cancer development. A key to citrate uptake in cancer cells is the high expression of the plasma membrane citrate transporter (pmCiC), which is upregulated in the different adenocarcinoma types tested so far. In this study, we show that the pmCiC is also highly expressed in Merkel cell carcinoma cell lines by western blot and human tissues by immunohistochemistry staining. In the presence of extracellular citrate, MCC cells show an increased proliferation rate in vitro; a specific pmCiC inhibitor (Na+-gluconate) blocks this citrate-induced proliferation. Furthermore, the 3D in vivo Chick Chorioallantoic Membrane (CAM) model showed that the application of Na+-gluconate also decreases Merkel cell carcinoma growth. Based on our results, we conclude that pmCiC and extracellular citrate uptake should be considered further as a potential novel target for the treatment of Merkel cell carcinoma.
ZEB2/TWIST1/PRMT5/NuRD Multicomplex Contributes to the Epigenetic Regulation of EMT and Metastasis in Colorectal Carcinoma
Authors: Zheng Yayuan , Dai Mingrui , Dong Yue , Yu Hanqiao , Liu Tianfu , Feng Xuejian , Yu Bin , Zhang Haihong , Wu Jiaxin , Kong Wei , Yu Xianghui , Wu Hui
Published: July 2022

(1) Background: The EMT plays a crucial role in tumor metastasis, which is the major cause for colorectal carcinoma-related mortality. However, the underlying regulators and mechanisms of EMT in CRC metastasis are still poorly understood; (2) Methods: The transcriptional regulators of EMT in CRC and their functions were examined using RT2212PCR, Western blotting, and luciferase reporter assay. The components of ZEB2/TWIST1 complex and their mutual interactions were identified via affinity purification, mass spectrometry, co-immunoprecipitation, and pull-down experiments. The functional mechanisms of ZEB2/TWIST1/PRMT5/NuRD axis were determined by chromatin immunoprecipitation and luciferase reporter assay. The contribution of ZEB2/TWIST1/PRMT5/NuRD complex in the CRC metastasis was investigated using wound healing, transwell assay, and in vivo xenograft mouse model; (3) Results: We found that ZEB2 and TWIST1 were both significantly upregulated in CRC tissues and EMT of CRC cells. ZEB2 could recruit TWIST1 to the E-cadherin promoter and synergistically repressed its transcription. In addition, ZEB2 physically interacted with TWIST1, PRMT5, and the nucleosome remodeling and deacetylase (NuRD) complex to form a novel repressive multicomplex, leading to epigenetic silencing of E-cadherin in CRC cells. Notably, the combined inhibition of ZEB2 and TWIST1 and epigenetic inhibition markedly reduced CRC metastasis in mice; (4) Conclusions: We revealed for the first time that ZEB2 could recruit TWIST1, PRMT5, and NuRD to form a repressive multicomplex and epigenetically suppresses the transcription of E-cadherin, thereby inducing the EMT process and metastasis in CRC. Our results also confirmed the therapeutic potential of epigenetic inhibitors in CRC.
Ras-Related Protein Rab-32 and Thrombospondin 1 Confer Resistance to the EGFR Tyrosine Kinase Inhibitor Osimertinib by Activating Focal Adhesion Kinase in Non-Small Cell Lung Cancer
Authors: Kosibaty Zeinab , Brustugun Odd Terje , Zwicky Eide Inger Johanne , Tsakonas Georgios , Grundberg Oscar , De Petris Luigi , McGowan Marc , Hydbring Per , Ekman Simon
Published: July 2022

Treatment with the tyrosine kinase inhibitor (TKI) osimertinib is the standard of care for non-small cell lung cancer (NSCLC) patients with activating mutations in the epidermal growth factor receptor (EGFR). Osimertinib is also used in T790M-positive NSCLC that may occur de novo or be acquired following first-line treatment with other EGFR TKIs (i.e., gefitinib, erlotinib, afatinib, or dacomitinib). However, patients treated with osimertinib have a high risk of developing resistance to the treatment. A substantial fraction of the mechanisms for resistance is unknown and may involve RNA and/or protein alterations. In this study, we investigated the full transcriptome of parental and osimertinib-resistant cell lines, revealing 131 differentially expressed genes. Knockdown screening of the genes upregulated in resistant cell lines uncovered eight genes to partly confer resistance to osimertinib. Among them, we detected the expression of Ras-related protein Rab-32 (RAB32) and thrombospondin 1 (THBS1) in plasmas sampled at baseline and at disease progression from EGFR-positive NSCLC patients treated with osimertinib. Both genes were upregulated in progression samples. Moreover, we found that knockdown of RAB32 and THBS1 reduced the expression of phosphorylated focal adhesion kinase (FAK). Combination of osimertinib with a FAK inhibitor resulted in synergistic toxicity in osimertinib-resistant cells, suggesting a potential therapeutic drug combination for overcoming resistance to osimertinib in NSCLC patients.