bluuebunny/crossref_metadata_2025 huggingface dataset:
An Updated Overview of the Role of CYP450 during Xenobiotic Metabolization in Regulating the Acute Myeloid Leukemia Microenvironment
Authors: Sandoval Cristian , Calle Yolanda , Godoy Karina , Farías Jorge
Published: March 2023

Oxidative stress is associated with several acute and chronic disorders, including hematological malignancies such as acute myeloid leukemia, the most prevalent acute leukemia in adults. Xenobiotics are usually harmless compounds that may be detrimental, such as pharmaceuticals, environmental pollutants, cosmetics, and even food additives. The storage of xenobiotics can serve as a defense mechanism or a means of bioaccumulation, leading to adverse effects. During the absorption, metabolism, and cellular excretion of xenobiotics, three steps may be distinguished: (i) inflow by transporter enzymes, (ii) phases I and II, and (iii) phase III. Phase I enzymes, such as those in the cytochrome P450 superfamily, catalyze the conversion of xenobiotics into more polar compounds, contributing to an elevated acute myeloid leukemia risk. Furthermore, genetic polymorphism influences the variability and susceptibility of related myeloid neoplasms, infant leukemias associated with mixed-lineage leukemia (MLL) gene rearrangements, and a subset of de novo acute myeloid leukemia. Recent research has shown a sustained interest in determining the regulators of cytochrome P450, family 2, subfamily E, member 1 (CYP2E1) expression and activity as an emerging field that requires further investigation in acute myeloid leukemia evolution. Therefore, this review suggests that CYP2E1 and its mutations can be a therapeutic or diagnostic target in acute myeloid leukemia.
Tissue Engineering Challenges for Cultivated Meat to Meet the Real Demand of a Global Market
Authors: Santos Andressa Cristina Antunes , Camarena Denisse Esther Mallaupoma , Roncoli Reigado Gustavo , Chambergo Felipe S. , Nunes Viviane Abreu , Trindade Marco Antonio , Stuchi Maria-Engler Silvya
Published: March 2023

Cultivated meat (CM) technology has the potential to disrupt the food industry—indeed, it is already an inevitable reality. This new technology is an alternative to solve the environmental, health and ethical issues associated with the demand for meat products. The global market longs for biotechnological improvements for the CM production chain. CM, also known as cultured, cell-based, lab-grown, in vitro or clean meat, is obtained through cellular agriculture, which is based on applying tissue engineering principles. In practice, it is first necessary to choose the best cell source and type, and then to furnish the necessary nutrients, growth factors and signalling molecules via cultivation media. This procedure occurs in a controlled environment that provides the surfaces necessary for anchor-dependent cells and offers microcarriers and scaffolds that favour the three-dimensional (3D) organisation of multiple cell types. In this review, we discuss relevant information to CM production, including the cultivation process, cell sources, medium requirements, the main obstacles to CM production (consumer acceptance, scalability, safety and reproducibility), the technological aspects of 3D models (biomaterials, microcarriers and scaffolds) and assembly methods (cell layering, spinning and 3D bioprinting). We also provide an outlook on the global CM market. Our review brings a broad overview of the CM field, providing an update for everyone interested in the topic, which is especially important because CM is a multidisciplinary technology.
ABCB1 and ABCC1 Function during TGF-β-Induced Epithelial-Mesenchymal Transition: Relationship between Multidrug Resistance and Tumor Progression
Authors: da Costa Kelli Monteiro , Freire-de-Lima Leonardo , da Fonseca Leonardo Marques , Previato José Osvaldo , Mendonça-Previato Lucia , Valente Raphael do Carmo
Published: March 2023

Multidrug resistance (MDR) and induction of metastasis are some of the puzzles encountered during cancer chemotherapy. The MDR phenotype is associated with overexpression of ABC transporters, involved in drug efflux. Metastasis originates from the epithelial-mesenchymal transition (EMT), in which cells acquire a migratory phenotype, invading new tissues. ABC transporters’ role during EMT is still elusive, though cells undergoing EMT exhibit enhanced ABCB1 expression. We demonstrated increased ABCB1 expression but no change in activity after TGF-β-induced EMT in A549 cells. Moreover, ABCB1 inhibition by verapamil increased snail and fibronectin expression, an event associated with upregulation of ABCB1, evidencing coincident cell signaling pathways leading to ABCB1 and EMT-related markers transcription, rather than a direct effect of transport. Additionally, for the first time, increased ABCC1 expression and activity was observed after EMT, and use of ABCC1 inhibitors partially inhibited EMT-marker snail, although increased ABCC1 function translated into collateral sensibility to daunorubicin. More investigations must be done to evaluate the real benefits that the gain of ABC transporters might have on the process of metastasis. Considering ABCC1 is involved in the stress response, affecting intracellular GSH content and drug detoxification, this transporter could be used as a therapeutic target in cancer cells undergoing EMT.
The MdmiR156n Regulates Drought Tolerance and Flavonoid Synthesis in Apple Calli and Arabidopsis
Authors: Chen Guo , Wang Yaping , Liu Xueli , Duan Siyue , Jiang Shenghui , Zhu Jun , Zhang Yugang , Hou Hongmin
Published: March 2023

Drought is the major abiotic stress that limits apple productivity and quality. To date, many important and divergent regulatory functions of miR156/SBP genes in plant growth and development have been well understood. However, little is known about the role of apple miR156 in response to abiotic stress. To better understand the functions of MdmiR156 in abiotic stress tolerance, we constructed the overexpression (OE) and short tandem target mimic (STTM) vector of MdmiR156n and performed its functional analysis through the characterization of transgenic apple calli and Arabidopsis thaliana plants. In this study, MdmiR156n overexpression significantly increased the length of primary roots and the number of lateral roots in transgenic Arabidopsis plants under drought stress. In addition, MdmiR156n transgenic Arabidopsis and apple calli had a lower electrolyte leakage rate and less cell membrane damage than WT and STTM156 after drought stress. Further studies showed that MdmiR156n overexpression promoted the accumulation of flavonoids and scavenging of reactive oxygen species (ROS) under drought conditions in transgenic apple calli and A. thaliana plants. Taken together, overexpression MdmiR156n enhances drought tolerance by regulating flavonoid synthesis and ROS signaling cascades in apple calli and A. thaliana.
Understanding Lamotrigine’s Role in the CNS and Possible Future Evolution
Authors: Costa Bárbara , Vale Nuno
Published: March 2023

The anti-epileptic drug lamotrigine (LTG) has been widely used to treat various neurological disorders, including epilepsy and bipolar disorder. However, its precise mechanism of action in the central nervous system (CNS) still needs to be determined. Recent studies have highlighted the involvement of LTG in modulating the activity of voltage-gated ion channels, particularly those related to the inhibition of neuronal excitability. Additionally, LTG has been found to have neuroprotective effects, potentially through the inhibition of glutamate release and the enhancement of GABAergic neurotransmission. LTG’s unique mechanism of action compared to other anti-epileptic drugs has led to the investigation of its use in treating other CNS disorders, such as neuropathic pain, PTSD, and major depressive disorder. Furthermore, the drug has been combined with other anti-epileptic drugs and mood stabilizers, which may enhance its therapeutic effects. In conclusion, LTG’s potential to modulate multiple neurotransmitters and ion channels in the CNS makes it a promising drug for treating various neurological disorders. As our understanding of its mechanism of action in the CNS continues to evolve, the potential for the drug to be used in new indications will also be explored.
Single-Cell Sequencing-Based Validation of T Cell-Associated Diagnostic Model Genes and Drug Response in Crohn’s Disease
Authors: Dai Zhujiang , Zhang Jie , Xu Weimin , Du Peng , Wang Zhongchuan , Liu Yun
Published: March 2023

Crohn’s disease is a highly heterogeneous autoimmune disease with a unique inflammatory phenotype of T cells at the lesion site. We aim to further explore the diagnosis of Crohn’s disease and drug prediction of T cell marker gene expression. We obtained single-cell expression profile data from 22 CDs or normal samples and performed cell annotation and cellular communication analysis. Through the intersection of T cell marker genes, differential genes, and WGCNA results, we identified T cell-specific key genes and their immune landscapes and potential pathogenesis, and validated them across multiple datasets and patient tissue samples. We also explored the differentiation characteristics of genes by pseudo-temporal analysis and assessed their diagnostic performance and drug sensitivity by molecular docking. Finally, we extended this study to the prognosis of IBD-associated colon cancer. TNF-centered 5-gene diagnostic model not only has excellent diagnostic efficacy, but is also closely associated with KRAS, P53, and IL6/JAK/STAT3 pathways and physiological processes, such as EMT, coagulation, and apoptosis. In addition, this diagnostic model may have potential synergistic immunotherapeutic effects, with positive correlations with immune checkpoints such as CTLA4, CD86, PDCD1LG2, and CD40. Molecular docking demonstrated that BIRC3 and ANXA1 have strong binding properties to Azathioprine and Glucoocorticoid. Furthermore, the 5-gene model may suggest antagonism to IFX and prognosis for colon cancer associated with inflammatory bowel disease. Single-cell sequencing targeting T cell-related features in patients with Crohn’s disease may aid in new diagnostic decisions, as well as the initial exploration of high-potential therapies.
Interaction Analysis of lncRNA and mRNA Based on the Full-Length Transcriptome of the Nymph-to-Adult Developmental Transition of Sogatella furcifera
Authors: Jia Zeyan , Yang Xibin , Yang Hong , Dai Renhuai , Zeng Qinghui , Jin Daochao
Published: March 2023

Little is known on how long noncoding RNAs (lncRNAs) and mRNAs cooperatively participate in regulating the nymph-to-adult development transition of Sogatella furcifera. Herein, lncRNA and mRNA libraries were constructed in three different developmental stages of S. furcifera, namely, prior to (PE), during (DE), and after (AE) ecdysis. Overall, 4649 lncRNAs were identified and divided into intergenic (53.90%), intronic (1.33%), sense (8.99%), antisense (21.75%), and bidirectional (3.94%) lncRNAs. Moreover, 795 differentially expressed lncRNAs were identified. Specifically, upon comparing PE and DE, 2719 target mRNAs were predicted for 574 lncRNAs. Upon comparing PE and AE, 2816 target mRNAs were predicted for 627 lncRNAs. Finally, upon comparing DE and AE, 51 target mRNAs were predicted for 35 lncRNAs. Kyoto Encyclopedia of Genes and Genome functional enrichment analysis revealed that the target genes of 795 lncRNAs were enriched in metabolic pathways, amino sugar and nucleotide sugar metabolism, and fatty acid metabolism. Subsequently, interaction analysis indicated that MSTRG.16086.1, MSTRG.16087.1, and MSTRG.2447.1 were functionally associated with cuticle protein and chitin biosynthesis. Finally, 11 differentially expressed lncRNAs were significantly enriched in 3rd and 4th instar nymphs. Our findings suggest that lncRNAs play a critical regulatory role during the molting of S. furcifera.
Can Alterations in Cerebrovascular CO2 Reactivity Be Identified Using Transfer Function Analysis without the Requirement for Carbon Dioxide Inhalation?
Authors: Ogoh Shigehiko , Watanabe Hironori , Saito Shotaro , Fisher James P. , Iwamoto Erika
Published: March 2023

The present study aimed to examine the validity of a novel method to assess cerebrovascular carbon dioxide (CO2) reactivity (CVR) that does not require a CO2 inhalation challenge, e.g., for use in patients with respiratory disease or the elderly, etc. In twenty-one healthy participants, CVR responses to orthostatic stress (50° head-up tilt, HUT) were assessed using two methods: (1) the traditional CO2 inhalation method, and (2) transfer function analysis (TFA) between middle cerebral artery blood velocity (MCA V) and predicted arterial partial pressure of CO2 (PaCO2) during spontaneous respiration. During HUT, MCA V steady-state (i.e., magnitude) and MCA V onset (i.e., time constant) responses to CO2 inhalation were decreased (p < 0.001) and increased (p = 0.001), respectively, indicative of attenuated CVR. In contrast, TFA gain in the very low-frequency range (VLF, 0.005–0.024 Hz) was unchanged, while the TFA phase in the VLF approached zero during HUT (−0.38 ± 0.59 vs. 0.31 ± 0.78 radians, supine vs. HUT; p = 0.003), indicative of a shorter time (i.e., improved) response of CVR. These findings indicate that CVR metrics determined by TFA without a CO2 inhalation do not track HUT-evoked reductions in CVR identified using CO2 inhalation, suggesting that enhanced cerebral blood flow response to a change in CO2 using CO2 inhalation is necessary to assess CVR adequately.
Cross Sectional and Case-Control Study to Assess Time Trend, Gender Differences and Factors Associated with Physical Activity among Adults with Diabetes: Analysis of the European Health Interview Surveys for Spain (2014 & 2020)
Authors: Llamas-Saez Carlos , Saez-Vaquero Teresa , Jiménez-García Rodrigo , López-de-Andrés Ana , Carabantes-Alarcón David , Zamorano-León José J. , Cuadrado-Corrales Natividad , Pérez-Farinos Napoleón , Wärnberg Julia
Published: March 2023

(1) Background: We aim to assess the time trend from 2014 to 2020 in the prevalence of physical activity (PA), identify gender differences and sociodemographic and health-related factors associated with PA among people with diabetes, and compare PA between people with and without diabetes. (2) Methods: We conducted a cross-sectional and a case–control study using as data source the European Health Interview Surveys for Spain (EHISS) conducted in years 2014 and 2020. The presence of diabetes and PA were self-reported. Covariates included socio-demographic characteristics, health-related variables, and lifestyles. To compare people with and without diabetes, we matched individuals by age and sex. (3) Results: The number of participants aged ≥18 years with self-reported diabetes were 1852 and 1889 in the EHISS2014 and EHISS2020, respectively. The proportion of people with diabetes that had a medium or high frequency of PA improved from 48.3% in 2014 to 52.6% in 2020 (p = 0.009), with 68.5% in 2014 and 77.7% in 2020 being engaged in two or more days of PA (p < 0.001). Males with diabetes reported more PA than females with diabetes in both surveys. After matching by age and gender, participants with diabetes showed significantly lower engagement in PA than those without diabetes. Among adults with diabetes, multivariable logistic regression showed confirmation that PA improved significantly from 2014 to 2020 and that male sex, higher educational level, and better self-rated health were variables associated to more PA. However, self-reported comorbidities, smoking, or BMI > 30 were associated to less PA. (4) Conclusions: The time trend of PA among Spanish adults with diabetes is favorable but insufficient. The prevalence of PA in this diabetes population is low and does not reach the levels of the general population. Gender differences were found with significantly more PA among males with diabetes. Our result could help to improve the design and implementation of public health strategies to improve PA among people with diabetes.
Management of Statin Intolerant Patients in the Era of Novel Lipid Lowering Therapies: A Critical Approach in Clinical Practice
Authors: Bosco Giosiana , Di Giacomo Barbagallo Francesco , Spampinato Salvatore , Lanzafame Lorena , Di Pino Antonino , Piro Salvatore , Purrello Francesco , Scicali Roberto
Published: March 2023

Statins are the cornerstone of lipid-lowering therapies effective for cardiovascular risk reduction. Although they are generally well tolerated, statin intolerance (SI) is frequent in clinical practice, and it is usually related to the onset of muscle symptoms, which are defined under the acronym SAMS (Statin-Associated Muscle Side Effects). These side effects are responsible for statin treatment discontinuation that results in increased cardiovascular risk. The National Lipid Association (NLA) has recently provided an updated definition of statin intolerance, and a distinction between complete and partial statin intolerance has been reported. The evaluation of symptom severity and the presence of muscle damage biomarker alterations make it essential to adopt a patient-centered approach aimed at obtaining a personalized therapeutic strategy. Firstly, it could be useful to administer a different statin, reduce the dosage or adopt an alternate dosage regimen. However, some patients are unable to tolerate any statin at every dosage, or despite taking statins at the maximum tolerated dose, they fail to achieve the recommended LDL-C target, and thus it is necessary to introduce a non-statin hypolipidemic treatment. Ezetimibe, proprotein-convertase subtilisin/kexin type 9 (PCSK9) inhibitors such as monoclonal antibodies (alirocumab and evolocumab) or RNA messenger silencing (inclisiran), bempedoic acid or nutraceuticals are non-statin lipid-lowering therapies that could be used as an alternative or in addition to statins to achieve an early and sustained LDL-C reduction in clinical practice. In this review, we evaluated SI management focusing on non-statin lipid lowering therapies and their implications in lipid lowering approaches in clinical practice.
Clinical and Laboratory Characteristics of Anaemia in Hospitalized Patients with Inflammatory Bowel Disease
Authors: Woźniak Małgorzata , Borkowska Anna , Jastrzębska Marta , Sochal Marcin , Małecka-Wojciesko Ewa , Talar-Wojnarowska Renata
Published: March 2023

Anaemia is the most common extraintestinal manifestation of inflammatory bowel disease (IBD). Due to its multifactorial etiopathogenesis, the differential diagnosis and treatment of anaemia in IBD is a significant clinical problem. The main aim of our study was to assess the usefulness of laboratory parameters, including hepcidin, in differential diagnoses of anaemia in hospitalized IBD patients. This study also estimated the impact of anaemia on the length of hospitalization and its relationship with clinical data of analyzed patients. The study included 118 adult patients diagnosed with IBD—55 with ulcerative colitis (UC) and 63 with Crohn’s disease (CD). Anaemia was significantly more frequent in patients with CD—42 (66.7%)—compared to 31 (56.4%) patients with UC (p = 0.033). The prevalence of anaemia increased significantly with the severity of IBD and the extent of inflammatory changes in the endoscopic examination. Hospitalization time was significantly longer in patients with anaemia, especially in the group with UC. Ferritin concentrations < 30 ng/mL were found only in 15 (20.55%) IBD patients (9 with UC and 6 with CD), and ferritin < 100 ng/mL was observed in 22 (30.14%) patients, equally frequent with UC and CD (p > 0.05). Significantly higher concentrations of transferrin were observed in patients with anaemia in the course of UC compared to CD (2.58 ± 0.90 g/L vs. 2.15 ± 0.82 g/L; p = 0.037). On the other hand, saturation of transferrin < 16% was equally common in UC and CD patients. In our study, hepcidin levels in anaemic UC patients were significantly lower compared to UC without anaemia (p = 0.042), with no similar differences in CD independently of anaemia presence (p = 0.565). To conclude, we observed a high incidence of anaemia in patients with IBD and its significant impact on the length of hospitalization in UC. Routinely determined single laboratory parameters are not sufficient for the differential diagnosis of anaemia, and a complex laboratory assessment, including of hepcidin levels, is necessary for the full picture of anaemia in the course of IBD.
Towards Lower Carbon Emissions: A Distributed Energy Management Strategy-Based Multi-Objective Optimization for the Seaport Integrated Energy System
Authors: Zhang Yuxin , Xiao Yang , Shan Qihe , Li Tieshan
Published: March 2023

To decrease fuel-based energy consumption, it is important to investigate the optimal energy management problem for the seaport integrated energy system in a fully distributed manner. A multi-objective energy management model is constructed, considering energy consumption, greenhouse gas emission, and carbon trading, which satisfy the sustainable development of the international shipping industry advocated by the International Maritime Organization (IMO). The carbon exhaust of a seaport is restrained by integrated carbon capture/storage devices. A fully distributed energy management strategy with dynamic-weighted coefficients is proposed to acquire the optimal solutions for the seaport integrated energy system. Moreover, to decrease the communication resources, an event-triggered mechanism between energy bodies was designed against the bandwidth limitation of the seaport. Finally, a rigorous mathematical analysis based on the multi-agent theory and the case studies proves the effectiveness of the proposed method.
Behavioral, Neurochemical and Developmental Effects of Chronic Oral Methylphenidate: A Review
Authors: Senior Daniela , Ahmed Rania , Arnavut Eliz , Carvalho Alexandra , Lee Wen Xuan , Blum Kenneth , Komatsu David E. , Hadjiargyrou Michael , Badgaiyan Rajendra D. , Thanos Panayotis K.
Published: March 2023

The majority of animal studies on methylphenidate (MP) use intraperitoneal (IP) injections, subcutaneous (SC) injections, or the oral gavage route of administration. While all these methods allow for delivery of MP, it is the oral route that is clinically relevant. IP injections commonly deliver an immediate and maximum dose of MP due to their quick absorption. This quick-localized effect can give timely results but will only display a small window of the psychostimulant’s effects on the animal model. On the opposite side of the spectrum, a SC injection does not accurately represent the pathophysiology of an oral exposure because the metabolic rate of the drug would be much slower. The oral-gavage method, while providing an oral route, possesses some adverse effects such as potential animal injury and can be stressful to the animal compared to voluntary drinking. It is thus important to allow the animal to have free consumption of MP, and drinking it to more accurately mirror human treatment. The use of a two-bottle drinking method allows for this. Rodents typically have a faster metabolism than humans, which means this needs to be considered when administering MP orally while reaching target pharmacokinetic levels in plasma. With this oral two-bottle approach, the pathophysiological effects of MP on development, behavior, neurochemistry and brain function can be studied. The present review summarizes these effects of oral MP which have important implications in medicine.
Sentiment and Emotion on Twitter: The Case of the Global Consumer Electronics Industry
Authors: Pezoa-Fuentes Claudia , García-Rivera Danilo , Matamoros-Rojas Sebastián
Published: March 2023

Sentiment analysis is a new tool on new social media platforms, locations very attractive to the global consumer industry to investigate, due to their relevance and increased consumption in a pandemic. This study aims to determine the predominant sentiment and emotions on Twitter through a sentiment analysis in the consumer electronics industry, according to the top 30 companies of the Consumer Electronic Show 2020, by analyzing 96,000 tweets with a total of 273,221 words. The methodology used is quantitative, of a descriptive type, that integrates the study of emotions and sentiment through a statistical analysis of the tweets with R. The main results identify that the predominant sentiment is of positive assessment and the emotions of anticipation and confidence were the most representative. The contribution of this research is to provide empirical evidence of the global consumer electronics industry for correct decision-making through a data language analysis procedure on Twitter.
Lanthanide and Ladder-Structured Polysilsesquioxane Composites for Transparent Color Conversion Layers
Authors: Han Jaehyun , Burak Darya , Poliukhova Valeriia , Lee Albert S. , Jang Hoseong , Hwang Seungsang , Baek Kyung-Youl , Han Joonsoo , Ju Byeong-Kwon , Cho So-Hye
Published: March 2023

Ladder-type polysilsesquioxanes (LPSQs) containing phenyl as a high refractive index unit and cyclic epoxy as a curable unit were found to be excellent candidates for a transparent color conversion layer for displays due to being miscible with organic solvents and amenable to transparent film formation. Therefore, the LPSQs were combined with luminescent lanthanide metals, europium Eu(III), and terbium Tb(III), to fabricate transparent films with various emission colors, including red, orange, yellow, and green. The high luminescence and transmittance properties of the LPSQs–lanthanide composite films after thermal curing were attributed to chelating properties of hydroxyl and polyether side chains of LPSQs to lanthanide ions, as well as a light sensitizing effect of phenyl side chains of the LPSQs. Furthermore, Fourier-transform infrared (FT-IR) and X-ray photoelectron spectroscopy and nanoindentation tests indicated that the addition of the nanoparticles to the LPSQs moderately enhanced the epoxy conversion rate and substantially improved the wear resistance, including hardness, adhesion, and insusceptibility to atmospheric corrosion in a saline environment. Thus, the achieved LPGSG–lanthanide hybrid organic–inorganic material could effectively serve as a color conversion layer for displays.
Reinforcement Learning-Based Lane Change Decision for CAVs in Mixed Traffic Flow under Low Visibility Conditions
Authors: Gong Bowen , Xu Zhipeng , Wei Ruixin , Wang Tao , Lin Ciyun , Gao Peng
Published: March 2023

As an important stage in the development of autonomous driving, mixed traffic conditions, consisting of connected autonomous vehicles (CAVs) and human-driven vehicles (HDVs), have attracted more and more attention. In fact, the randomness of human-driven vehicles (HDV) is the largest challenge for connected autonomous vehicles (CAV) to make reasonable decisions, especially in lane change scenarios. In this paper, we propose the problem of lane change decisions for CAV in low visibility and mixed traffic conditions for the first time. First, we consider the randomness of HDV in this environment and construct a finite state machine (FSM) model. Then, this study develops a partially observed Markov decision process (POMDP) for describing the problem of lane change. In addition, we use the modified deep deterministic policy gradient (DDPG) to solve the problem and get the optimal lane change decision in this environment. The reward designing takes the comfort, safety and efficiency of the vehicle into account, and the introduction of transfer learning accelerates the adaptation of CAV to the randomness of HDV. Finally, numerical experiments are conducted. The results show that, compared with the original DDPG, the modified DDPG has a faster convergence velocity. The strategy learned by the modified DDPG can complete the lane change in most of the scenarios. The comparison between the modified DDPG and the rule-based decisions indicates that the modified DDPG has a stronger adaptability to this special environment and can grasp more lane change opportunities.
Construction of Infinite Series Exact Solitary Wave Solution of the KPI Equation via an Auxiliary Equation Method
Authors: Pei Feiyun , Wu Guojiang , Guo Yong
Published: March 2023

The KPI equation is one of most well-known nonlinear evolution equations, which was first used to described two-dimensional shallow water wavs. Recently, it has found important applications in fluid mechanics, plasma ion acoustic waves, nonlinear optics, and other fields. In the process of studying these topics, it is very important to obtain the exact solutions of the KPI equation. In this paper, a general Riccati equation is treated as an auxiliary equation, which is solved to obtain many new types of solutions through several different function transformations. We solve the KPI equation using this general Riccati equation, and construct ten sets of the infinite series exact solitary wave solution of the KPI equation. The results show that this method is simple and effective for the construction of infinite series solutions of nonlinear evolution models.
Optimally Initialized Model Reference Adaptive Controller of Wearable Lower Limb Rehabilitation Exoskeleton
Authors: Amiri Mohammad Soleimani , Ramli Rizauddin , Barari Ahmad
Published: March 2023

A wearable lower-limb rehabilitation exoskeleton functions to fulfill the recovery process of limb functionality and assist physiotherapists. This paper presents an optimized adaptive control system for a wearable lower-limb rehabilitation exoskeleton. The tuning of the controller gains is defined as an optimization problem for a closed-loop control system of the wearable lower-limb rehabilitation robot by genetic algorithm and particle swarm optimization. We presented a novel initialized model reference adaptive controller (IMRAC) for real-time joint trajectory tracking, in which controller gains are adjusted by the gradient-based method. An experimental test of a 4-degree of freedom lower-limb rehabilitation exoskeleton was carried out to observe the closed-loop performance of IMRAC for bipedal human walking. The statistical comparison between IMRAC and MRAC shows an efficient performance and robustness of our proposed method for the joint trajectory tracking of the lower-limb rehabilitation exoskeleton in real time.
A New Approach for Solving Nonlinear Fractional Ordinary Differential Equations
Authors: Jassim Hassan Kamil , Abdulshareef Hussein Mohammed
Published: March 2023

Recently, researchers have been interested in studying fractional differential equations and their solutions due to the wide range of their applications in many scientific fields. In this paper, a new approach called the Hussein–Jassim (HJ) method is presented for solving nonlinear fractional ordinary differential equations. The new method is based on a power series of fractional order. The proposed approach is employed to obtain an approximate solution for the fractional differential equations. The results of this study show that the solutions obtained from solving the fractional differential equations are highly consistent with those obtained by exact solutions.
Tetrodotoxin Decreases the Contractility of Mesenteric Arteries, Revealing the Contribution of Voltage-Gated Na+ Channels in Vascular Tone Regulation
Authors: Park Joohee , Proux Coralyne , Ehanno William , Réthoré Léa , Vessières Emilie , Bourreau Jennifer , Favre Julie , Kauffenstein Gilles , Mattei César , Tricoire-Leignel Hélène , Henrion Daniel , Legendre Claire , Legros Christian
Published: March 2023

Tetrodotoxin (TTX) poisoning through the consumption of contaminated fish leads to lethal symptoms, including severe hypotension. This TTX-induced hypotension is likely due to the downfall of peripheral arterial resistance through direct or indirect effects on adrenergic signaling. TTX is a high-affinity blocker of voltage-gated Na+ (NaV) channels. In arteries, NaV channels are expressed in sympathetic nerve endings, both in the intima and media. In this present work, we aimed to decipher the role of NaV channels in vascular tone using TTX. We first characterized the expression of NaV channels in the aorta, a model of conduction arteries, and in mesenteric arteries (MA), a model of resistance arteries, in C57Bl/6J mice, by Western blot, immunochemistry, and absolute RT-qPCR. Our data showed that these channels are expressed in both endothelium and media of aorta and MA, in which scn2a and scn1b were the most abundant transcripts, suggesting that murine vascular NaV channels consist of NaV1.2 channel subtype with NaVβ1 auxiliary subunit. Using myography, we showed that TTX (1 µM) induced complete vasorelaxation in MA in the presence of veratridine and cocktails of antagonists (prazosin and atropine with or without suramin) that suppressed the effects of neurotransmitter release. In addition, TTX (1 µM) strongly potentiated the flow-mediated dilation response of isolated MA. Altogether, our data showed that TTX blocks NaV channels in resistance arteries and consecutively decreases vascular tone. This could explain the drop in total peripheral resistance observed during mammal tetrodotoxications.
Physical Simulation Study on Flow Field Characteristics of Molten Steel in 70t Ladle Bottom Argon Blowing Process
Authors: Li Zhiwei , Ouyang Wei , Wang Zhongliang , Zheng Ruixuan , Bao Yanping , Gu Chao
Published: March 2023

In the LF refining process, argon blowing at the bottom of ladle can play an important role in unifying the composition and temperature of molten steel and removing inclusions. However, unreasonable bottom argon blowing process can also cause many problems. Slag entrapment and slag surface exposure may occur, affecting the steel quality. Since the working conditions of different enterprises are very different, corresponding optimization is required for specific parameters. There were some problems in 70t ladle of a steel plant, such as unclear control of bottom argon blowing system in different refining periods, unobvious floating removal effect of inclusions in ladle, high total oxygen content and large fluctuation, etc. In this study, a 1:3 physical model was established according to the similarity principle. Then, on this basis, the experimental schemes with different blowing hole positions and argon flow rates were designed for simulation experiments. By means of mixing time measurement, flow field display and oil film measurement, the optimal argon blowing position was double holes 6, 12 (2/3R), and the included angle between them was 135°. The optimal argon flow rate for wire feeding and soft blowing should be 7.6 L/min (corresponding to the actual production of 180 L/min) and 0.6 L/min (corresponding to the actual production of 15 L/min), respectively. According to this scheme, the industrial experiments showed that the contents of total oxygen and nitrogen in the whole process were reduced, the surface density of inclusions in billet was reduced by 11.81% on average, and calcium sulfide and various inclusions containing aluminum were reduced to varying degrees.
Dielectrophoresis-Based Selective Droplet Extraction Microfluidic Device for Single-Cell Analysis
Authors: Shijo Seito , Tanaka Daiki , Sekiguchi Tetsushi , Ishihara Jun-ichi , Takahashi Hiroki , Kobayashi Masashi , Shoji Shuichi
Published: March 2023

We developed a microfluidic device that enables selective droplet extraction from multiple droplet-trapping pockets based on dielectrophoresis. The device consists of a main microchannel, five droplet-trapping pockets with side channels, and drive electrode pairs appropriately located around the trapping pockets. Agarose droplets capable of encapsulating biological samples were successfully trapped in the trapping pockets due to the difference in flow resistance between the main and side channels. Target droplets were selectively extracted from the pockets by the dielectrophoretic force generated between the electrodes under an applied voltage of 500 V. During their extraction from the trapping pockets, the droplets and their contents were exposed to an electric field for 400–800 ms. To evaluate whether the applied voltage could potentially damage the biological samples, the growth rates of Escherichia coli cells in the droplets, with and without a voltage applied, were compared. No significant difference in the growth rate was observed. The developed device enables the screening of encapsulated single cells and the selective extraction of target droplets.
Plant Pathogenic Microorganisms: State-of-the-Art Research in Spain
Authors: Fiallo-Olivé Elvira , Palacio-Bielsa Ana , Sacristán Soledad
Published: March 2023

Pathogenic microorganisms, including fungi, oomycetes, bacteria, viruses, and viroids, constitute a serious threat to agriculture worldwide [...]
A Simple and Easily Implemented Method for the Regioselective Introduction of Deuterium into Azolo[1,5-a]pyrimidines Molecules
Authors: Danagulyan Gevorg G. , Panosyan Henrik A. , Gharibyan Vache K. , Hasratyan Ani H.
Published: March 2023

A method for the technically easy-to-implement synthesis of deuterium-labeled pyrazolo[1,5-a]pyrimidines and 1,2,4-triazolo[1,5-a]pyrimidines have been developed. The regioselectivity of such transformations has been shown. 1H NMR and mass spectrometric methods have proved the quantitative nature of such transformations and the kinetics of deuterium exchange has been studied. Spectrally, at different temperatures (+30 °C, −10 °C and −15 °C), the kinetics of the process was studied both in CD3OD and in deuterated alkali.
A Review on the Progress of Optoelectronic Devices Based on TiO2 Thin Films and Nanomaterials
Authors: Ge Shunhao , Sang Dandan , Zou Liangrui , Yao Yu , Zhou Chuandong , Fu Hailong , Xi Hongzhu , Fan Jianchao , Meng Lijian , Wang Cong
Published: March 2023

Titanium dioxide (TiO2) is a kind of wide-bandgap semiconductor. Nano-TiO2 devices exhibit size-dependent and novel photoelectric performance due to their quantum limiting effect, high absorption coefficient, high surface-volume ratio, adjustable band gap, etc. Due to their excellent electronic performance, abundant presence, and high cost performance, they are widely used in various application fields such as memory, sensors, and photodiodes. This article provides an overview of the most recent developments in the application of nanostructured TiO2-based optoelectronic devices. Various complex devices are considered, such as sensors, photodetectors, light-emitting diodes (LEDs), storage applications, and field-effect transistors (FETs). This review of recent discoveries in TiO2-based optoelectronic devices, along with summary reviews and predictions, has important implications for the development of transitional metal oxides in optoelectronic applications for researchers.
Inferior Nutritional Status Significantly Differentiates Dialysis Patients with Type 1 and Type 2 Diabetes
Authors: Grzywacz Anna , Lubas Arkadiusz , Niemczyk Stanisław
Published: March 2023

Diabetes mellitus is currently the leading cause of end-stage renal disease. Assessing nutritional status is an important component of care in this group. This prospective observational study aimed to assess the nutritional status of type 1 and type 2 diabetes patients on hemodialysis or peritoneal dialysis and its relationship with hospitalizations and all-cause death. Adult patients with end-stage renal disease, treated with dialysis, and suffering from type 1 or type 2 diabetes, being treated with insulin, were included in the study. Exclusion criteria comprised other types of diabetes, the patient’s refusal to participate in the study, and severe disorders impacting verbal-logical communication. The nutritional status based on the Nutritional Risk Index, the Geriatric Nutritional Risk Index, fat distribution measures, and the Charlson Comorbidity Index was estimated for 95 Caucasian dialysis patients with type 1 (n = 25) or type 2 (n = 70) diabetes. Patients with type 1 diabetes exhibited significantly inferior nutritional status and increased nutritional risk than those with type 2 diabetes. Lower values of nutritional indices significantly differentiated patients with type 1 from those with type 2 diabetes, with ≥84% sensitivity and specificity. Inferior nutritional status was related to all-cause hospitalizations, whereas higher comorbidity was associated with a greater likelihood of cardiovascular hospitalizations and all-cause death. The significant difference between patients with type 1 and type 2 diabetes being treated with dialysis indicates that these patients should not be considered as a homogeneous group, while also considering the greater age of patients with type 2 diabetes.
Combined Citrulline and Glutathione Supplementation Improves Endothelial Function and Blood Pressure Reactivity in Postmenopausal Women
Authors: Figueroa Arturo , Maharaj Arun , Kang Yejin , Dillon Katherine N. , Martinez Mauricio A. , Morita Masahiko , Nogimura Dai , Fischer Stephen M.
Published: March 2023

Postmenopausal women (PMW) may experience endothelial dysfunction associated with arginine (ARG) deficiency relative to asymmetric dimethylarginine (ADMA) caused by oxidative stress. Endothelial dysfunction contributes to increased blood pressure (BP) responsiveness to sympathoexcitation induced by the cold pressor test (CPT). We investigated the effects of citrulline alone (CIT) and combined with the antioxidant glutathione (CIT+GSH) on vascular function. Forty-four healthy PMW were randomized to CIT (6 g), CIT+GSH (2 g + 200 mg: Setria®) or placebo (PL) for 4 weeks. Brachial artery flow-mediated dilation (FMD), aortic stiffness (pulse wave velocity, PWV), brachial and aortic BP reactivity to CPT, and serum fasting blood glucose (FBG), ARG, and ARG/ADMA ratio were measured. Baseline FBG was higher in CIT+GSH vs. PL. FMD increased after CIT+GSH vs. PL (p < 0.05). CIT and CIT+GSH increased ARG/ADMA (p < 0.05), but did not affect aortic PWV. CIT+GSH attenuated the brachial and aortic systolic BP and mean arterial pressure (MAP) responses to CPT vs. PL and CIT (p < 0.05). The improvements in FMD were related to baseline FMD (r = −0.39, p < 0.05) and aortic MAP response to CPT (r = −0.33, p < 0.05). This study showed that CIT+GSH improved FMD and attenuated systolic BP and MAP reactivity in PMW. Although CIT increased ARG/ADMA, it did not improve FMD in healthy PMW.
First Case Reports of Nontuberculous Mycobacterial (NTM) Lung Disease in Ecuador: Important Lessons to Learn
Authors: Echeverria Gustavo , Rueda Veronica , Espinoza Wilson , Rosero Carlos , Zumárraga Martín J. , de Waard Jacobus H.
Published: March 2023

Nontuberculous mycobacteria (NTM) lung infections are often misdiagnosed as tuberculosis, which can lead to ineffective antibiotic treatments. In this report, we present three cases of NTM lung infections in Ecuador that were initially diagnosed and treated as tuberculosis based on the results of sputum smear microscopy. The patients, all male, included two immunocompetent individuals and one HIV-positive subject. Unfortunately, sputum culture was not initiated until late in the course of the disease and the cause of the lung infection, Mycobacterium avium complex (MAC), was only identified after the patients had either passed away or were lost to follow-up. These cases are the first documented cases of NTM lung infections in the English medical literature from Ecuador. We emphasize the importance of accurate diagnosis of NTM infections by culture and identification to species level. Sputum smear staining alone cannot differentiate between mycobacterial species, which can lead to misidentification and ineffective treatments. Additionally, reporting NTM pulmonary disease as a notifiable disease to national TB control programs is recommended to obtain accurate prevalence data. These data are critical in determining the importance of this public health problem and the necessary actions needed to address it.
Structural Adaptation of the Single-Stranded DNA-Binding Protein C-Terminal to DNA Metabolizing Partners Guides Inhibitor Design
Authors: Tököli Attila , Bodnár Brigitta , Bogár Ferenc , Paragi Gábor , Hetényi Anasztázia , Bartus Éva , Wéber Edit , Hegedüs Zsófia , Szabó Zoltán , Kecskeméti Gábor , Szakonyi Gerda , Martinek Tamás A.
Published: March 2023

Single-stranded DNA-binding protein (SSB) is a bacterial interaction hub and an appealing target for antimicrobial therapy. Understanding the structural adaptation of the disordered SSB C-terminus (SSB-Ct) to DNA metabolizing enzymes (e.g., ExoI and RecO) is essential for designing high-affinity SSB mimetic inhibitors. Molecular dynamics simulations revealed the transient interactions of SSB-Ct with two hot spots on ExoI and RecO. The residual flexibility of the peptide–protein complexes allows adaptive molecular recognition. Scanning with non-canonical amino acids revealed that modifications at both termini of SSB-Ct could increase the affinity, supporting the two-hot-spot binding model. Combining unnatural amino acid substitutions on both segments of the peptide resulted in enthalpy-enhanced affinity, accompanied by enthalpy–entropy compensation, as determined by isothermal calorimetry. NMR data and molecular modeling confirmed the reduced flexibility of the improved affinity complexes. Our results highlight that the SSB-Ct mimetics bind to the DNA metabolizing targets through the hot spots, interacting with both of segments of the ligands.
An In Vitro Evaluation of the Potential Neuroprotective Effects of Intranasal Lipid Nanoparticles Containing Astaxanthin Obtained from Different Sources: Comparative Studies
Authors: Torres Joana , Pereira José Miguel , Marques-Oliveira Rita , Costa Inês , Gil-Martins Eva , Silva Renata , Remião Fernando , Peixoto Andreia Filipa , Sousa Lobo José Manuel , Silva Ana Catarina
Published: March 2023

The intranasal route has been suggested as a promising alternative to improve the direct transport of molecules to the brain, avoiding the need to cross the blood–brain barrier (BBB). In this area, the use of lipid nanoparticles, namely solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), has been highlighted as a promising strategy to improve the treatment of neurodegenerative diseases. In this work, formulations containing SLN and NLC that were loaded with astaxanthin that was obtained from different sources (astaxanthin extract (AE) from the algae Haematococcus pluvialis and pure astaxanthin (PA) from the fungi Blakeslea trispora) were prepared for nose-to-brain administration, and comparative in vitro experiments were performed to evaluate the biocompatibility of the formulations with nasal (RPMI 2650) and neuronal (SH-SY5Y) cells. Afterwards, the antioxidant activity of the formulations was evaluated for its potential neuroprotective effects, using different chemical aggressors. Finally, the cellular uptake of the astaxanthin was evaluated for the formulations that showed the greatest neuroprotection of the neuronal cells against chemical-induced damage. On the production day, all the formulations showed a particle size, a high encapsulation efficiency (EE), the presence of nanoparticles with a typical spherical shape, and a polydispersity index (PDI) and zeta potential (ZP) that are suitable for nose-to-brain administration. After three months of storage at room temperature, no significant changes were observed in the characterization parameters, predicting a good long-term stability. Furthermore, these formulations were shown to be safe with concentrations of up to 100 µg/mL in differentiated SH-SY5Y and RPMI 2650 cells. Regarding neuroprotection studies, the PA-loaded SLN and NLC formulations showed an ability to counteract some mechanisms of neurodegeneration, including oxidative stress. Moreover, when compared with the PA-loaded SLN, the PA-loaded NLC showed greater neuroprotective effects against the cytotoxicity induced by aggressors. In contrast, the AE-loaded SLN and NLC formulations showed no significant neuroprotective effects. Although further studies are needed to confirm these neuroprotective effects, the results of this study suggest that the intranasal administration of PA-loaded NLC may be a promising alternative to improve the treatment of neurodegenerative diseases.