bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of the effect of grouting parameters on pile-soil interaction of grouted piles
Authors: Shi Si-Si , Wan Zhi-Hui , Hu Tao , Qian Xiao-Nan , Duan Chang , Qi Kai
Published: December 2023

Reasonable control of grouting parameters was the key to improving the pile-soil interaction. However, quantitative analysis on the effect of grouting parameters on the pile-soil interaction was still lacking. This article developed an intelligent post-grouting system for precise control and quantitative analysis of grouting parameters. The conventional preparation method for shear tests were improved in this article. By changing the normal stress of the pile-soil interface during grouting, the test sample could simulate the grout distribution of the pile-soil interface at different depths. Through the improved experimental methods, a more accurate analysis of the mechanism for the pile-soil interaction was achieved. And the effectiveness of the intelligent post-grouting system was further verified by the case application. The results indicated that increasing the grout volume could improve the interface shear strength when the normal stress and grouting pressure were constant. This improvement effect caused by increasing grout volume decreased when the normal stress was high. Increasing the grouting pressure increased the interface shear strength when the normal stress and the grout volume remained constant. This improvement effect caused by increasing grouting pressure decreased when the grout volume was small. By appropriately controlling the two grouting parameters, the cohesion and the shear strength of the pile-soil interface were increased by 5.8–18.8 times and 1.16–2.91 times, respectively. The results indicated that the intelligent post-grouting system could accurately control the grouting parameters and effectively improve the pile-soil interaction of bored piles. The intelligent post-grouting system effectively reduced geotechnical engineering risks and improved the bearing capacity of pile.
Non-intrusive load identification method based on GAF and RAN networks
Authors: Jianyuan Wang , Yibo Sun
Published: December 2023

Non-intrusive load identification can improve the interaction efficiency between the power supply side and the user side of the grid. Applying this technology can alleviate the problem of energy shortage and is a key technique for achieving efficient management on the user side. In response to the cumbersome process of manually selecting load features and the low accuracy of identification in traditional machine learning algorithms for non-intrusive load identification, this paper proposes a method that transforms the one-dimensional reactive electric signal of the load into a two-dimensional image using Gram coding and utilizes the Residual Attention Network (RAN) for load classification and recognition. By transforming the one-dimensional electrical signal into a two-dimensional image as the input to the RAN network, this approach retains the original load information while providing richer information for the RAN network to extract load features. Furthermore, the RAN network effectively addresses the poor performance and gradient vanishing issues of deep learning networks through bottleneck residual blocks. Finally, experiments were conducted on a public dataset to verify the effectiveness of the proposed method.
A joint clearing model for the participation of renewable energy and energy storage in the frequency modulation ancillary service market considering performance differences
Authors: Wang Chang , Jiang Yu , Guo Hao , Bai Kun , Zhang Xiangyu , Wang Aoer
Published: December 2023

The increasing growth in installed capacity for renewable energy sources has progressively replaced traditional thermal power units as synchronous power contributors. This transition has led to a reduction in system inertia and resources for frequency regulation, creating a need for renewable energy and energy storage to participate in system frequency modulation. Empirical studies indicate that the current market mechanism for frequency modulation auxiliary services, which predominantly rely on thermal power, is suboptimal for leveraging the unique capabilities of diverse frequency modulation resources. This inadequacy hinders the power industry’s pursuit of the “dual carbon” goals—carbon neutrality and carbon peak. Hence, this paper proposes a joint clearing model for the involvement of renewable energy and energy storage in the frequency modulation auxiliary service market. It considers performance differences and employs the Analytic hierarchy process (AHP) to guide the optimization of the weights of frequency modulation performance indicators for various frequency modulation resources. This approach allows renewable energy, energy storage, and thermal power to maximize the benefits of their own differentiated advantages in various frequency modulation performance indicators. Consequently, this fosters an increased share of renewable energy within the system while ensuring frequency stability, thereby expediting the achievement of the power industry’s “dual carbon” goals. Finally, computational analyses substantiate that the proposed joint clearing model, accounting for performance differentials, can enhance the renewable energy share in the system and simultaneously reduce the societal costs associated with frequency modulation services.
Development of implicit and explicit attentional modulation of the processing of social cues conveyed by faces and bodies in children and adolescents
Authors: Oldrati Viola , Bardoni Alessandra , Poggi Geraldina , Urgesi Cosimo
Published: December 2023

Emotions and sex of other people shape the way we interact in social environments. The influence of these dimensions on cognitive processing is recognized as a highly conditional phenomenon. While much of researches on the topic focused on adults, less evidence is available for the pediatric population. This study aimed at examining the development of the modulation of attention control on emotion and sex processing using facial and body expressions in children and adolescents (8–16 years old). In Experiment 1a, participants performed a Flanker task (probing space-based attention) in which they had to indicate either the emotion (happy/fearful) or the sex of the target stimulus while ignoring the distracting stimuli at the side. We found evidence for intrusion of the sex, but not emotion, of the stimuli during both sex and emotion recognition tasks, thus both at an explicit (i.e., task relevant) and implicit (i.e., task irrelevant) level. A control experiment consisting of an emotional Flanker task confirmed that, in contrast with previous findings in adults, emotion did not modulate attention control in children and adolescents even when task relevant (Experiment 1b). In Experiment 2 participants performed a same-or-different judgment task (probing feature-based attention) in which they indicated whether the central stimulus matched the lateral ones for emotion or sex. Results showed that emotional features exerted an implicit influence during sex judgements; likewise, sex features intruded on the processing of both faces and bodies during emotion judgments. Finally, Experiment 3 explored the development of the explicit attention modulation exerted by the sex dimension on the processing of faces and bodies. To this aim, participants performed a Flanker task in which they were asked to recognize the sex of faces and bodies. The results indicated that, while younger participants showed a task-relevant influence of sexual features when processing faces, older participants showed such influence when processing bodies. These findings point to a greater attentional modulation exerted by sex, as compared to emotion, during social processing in children and adolescents and suggest a developmental trend of the saliency of facial and bodily cues for the perception of others’ sex.
Italian biodistricts and French territorial food projects: how science-policy-experience interplays shape the framings of transitions towards sustainable territorial food systems
Authors: Lamine Claire , Pugliese Patrizia , Barataud Fabienne , Berti Giaime , Rossi Adanella
Published: December 2023

The territorial scale is increasingly recognised as a relevant scale for analysing, conceiving and supporting the ecological transitions of agri-food systems. France and Italy have both been pioneer countries for the valorisation of territorially-based food identity and more recently experimented innovative forms of collective and public action to support transitions to sustainable territorial food systems. In Italy, the biodistrict frame has progressively been legitimised and recently adopted as a legal framework, while in France, despite many regional experiences focused on organic agriculture, the legal framework recently established with the territorial food system policy, officially driven by the agroecological transition paradigm, leaves a very variable place to organic agriculture and its principles, depending on local features and power configurations. Our objective in this paper is to understand these processes of institutionalisation. Based on a focused review of the French and Italian literature on this issue and on the analysis of the relative place of organics in policies, experiences and debates in France and Italy over the five last decades, we show that these processes of institutionalisation result from specific interplays between science, policy and experience, where the related actors take a different role, leading to different configurations and favouring different framings.
Systematic Review of Probiotics and Their Potential for Developing Functional Nondairy Foods
Authors: Aleman Ricardo S. , Yadav Ajitesh
Published: December 2023

The gastrointestinal tract is an environment that hosts various microorganisms, including pathogens. Generally, pathogenic bacteria enter the host body through food and the gastrointestinal tract. These pathogenic bacteria can colonize or infiltrate host cells and tissues, causing various infectious diseases. In recent years, the protective role of probiotic bacteria against gastrointestinal pathogens has been carefully investigated. Probiotics have been found to modulate intestinal microbial flora and play a significant role in the gastrointestinal tract’s function, especially by inhibiting the growth of pathogenic bacteria. However, the mechanism of action of probiotics has yet to be sufficiently proven and recognized. Several important mechanisms support the antagonistic effects of probiotics on various microorganisms, which is achieved, for example, through the production of different antimicrobial compounds, such as bacteriocins, various organic acids, antibiotics, antimicrobial proteins, and exopolysaccharides; mucosal barriers with mucosa and bacteria binding blockers; competition for nutrient uptake; and strengthening of the immune system. Accordingly, this review summarizes the recent studies that have examined the mechanism of action of probiotic bacteria and their beneficial effects in preventing pathogenic bacterial growth and improving gastrointestinal functions. Comprehending their mechanisms of action allows the selection of appropriate probiotic strains for specific applications in gastrointestinal dysfunction.
Photocatalytic Degradation of Vehicle Exhaust by Nano-TiO2 Cement Slurry: Experimental Factors and Field Application
Authors: Kuang Yachuan , Ding Fuzheng , Peng Zhiwei , Fan Fan , Zhang Zhaohuan , Ji Xiaoyong
Published: December 2023

Nano-TiO2 combined with cement slurry can be utilized to degrade nitrogen oxides (NOx) in vehicle exhaust, making it an excellent photocatalytic material for air purification. In practice, environmental factors can significantly affect the photocatalytic performance. In this study, a vehicle exhaust test system was developed, and the test methods and evaluation criteria for the degradation test are provided. This study investigated the photocatalytic degradation of NO2 using nano-TiO2 cement slurry through laboratory tests. The effects of temperature, relative humidity, ultraviolet (UV) radiation flux, cement slurry thickness, surface dust adherence, and the number of water rinsing cycles were examined. Additionally, nano-TiO2 cement slurries were applied to an expressway toll station. The results showed that the efficiency of photocatalytic degradation was significantly influenced by temperature and UV radiation flux, while the thickness of the cement slurry had minimal impact. The photocatalytic degradation efficiency was negatively correlated to the relative humidity, when the relative humidity of the cement slurry specimens was high. This is because the excess water (H2O) competes with NO2 for adsorption. The photocatalytic performance of the samples was significantly reduced by surface dust and rain erosion, as both led to a decrease in the amount of nano-TiO2 participating in the reaction. Furthermore, the photocatalytic material has wide-ranging potential applications. The findings of this study would support the promotion of environmentally friendly roads as a strategy to combat air pollution.
The Experiences of Older Adults with Dementia of “Balance Wise”—An Individual or Group-Delivered Exercise Programme: A Qualitative Study
Authors: Mesbah Normala , Perry Meredith , Hill Keith D. , Manlapaz Donald , Hale Leigh
Published: December 2023

This study aimed to understand the experience of older adults with dementia towards, and the practicality of, the Balance Wise exercise programme. A qualitative study guided by the General Inductive Approach was employed. Ten people with dementia aged 71–87 years who completed the exercise programme and four care partners aged 69–76 years old (three of whom also participated in Balance Wise) were interviewed in dyads. The programme (individually or group delivered) was held once a week for 30 min for 10 weeks and included balance and strength exercises, cognitive training, and other enjoyable physical activities. Interviews were thematically analysed. Three overarching themes were identified (i) decision making, (ii) comprehension, and (iii) perceived benefits. Participants acknowledged their decision to participate was influenced by ‘awareness’ about their declining memory and their ‘health belief’ about the potential benefits of exercise. ‘Perceived benefits’ were influenced by the ‘support system’ and improvement in postural stability. ‘Comprehension’ was, however, an important cognitive ability to understand the purpose of the activities in the programme and facilitated motivation. This study highlighted an important message that such programmes should be developed from the end-user perspective, and this included that the programme be flexible and safely delivered, as well as be fun and pleasurable, thus promoting socialisation.
Ergodicity Breaking and Self-Destruction of Cancer Cells by Induced Genome Chaos
Authors: Shityakov Sergey , Kravtsov Viacheslav , Skorb Ekaterina V. , Nosonovsky Michael
Published: December 2023

During the progression of some cancer cells, the degree of genome instability may increase, leading to genome chaos in populations of malignant cells. While normally chaos is associated with ergodicity, i.e., the state when the time averages of relevant parameters are equal to their phase space averages, the situation with cancer propagation is more complex. Chromothripsis, a catastrophic massive genomic rearrangement, is observed in many types of cancer, leading to increased mutation rates. We present an entropic model of genome chaos and ergodicity and experimental evidence that increasing the degree of chaos beyond the non-ergodic threshold may lead to the self-destruction of some tumor cells. We study time and population averages of chromothripsis frequency in cloned rhabdomyosarcomas from rat stem cells. Clones with frequency above 10% result in cell apoptosis, possibly due to mutations in the BCL2 gene. Potentially, this can be used for suppressing cancer cells by shifting them into a non-ergodic proliferation regime.
Structure and Thermoelectric Characterization of p-Type SnTe Nanobulk Material Synthesized by Charge Compensation Chemical Reaction
Authors: Fujiwara Ryosuke , Ikeda Yuta , Kawaguchi Takuto , Takashima Yohei , Tsuruoka Takaaki , Akamatsu Kensuke
Published: December 2023

SnTe is the most widely studied p-type thermoelectric (TE) alternative to PbTe. In this study, we prepared a nanostructured SnTe bulk material via spark plasma sintering from a precursor synthesized by a chemical precipitation process without using organic molecules. The sintered sample comprised tiny grains (100–300 nm) with high-density grain boundaries. Eventually, because the material would contain no impurities acting as scattering nodes of charge carriers, the material exhibited a relatively high electrical conductivity of 7.07 × 105 Sm−1 at 310 K. The material demonstrated low lattice thermal conductivity (0.87 Wm−1K−1 at 764 K), which can be owing to the increasing phonon scattering at grain boundaries. The maximum ZT was 0.31 at 764 K in the measured temperature range. This study provides a method for the design of phase-pure and surfactant-free SnTe thermoelectric materials that exhibit low lattice thermal conductivity and high carrier mobility using a chemical synthetic approach.
Oxygen Carrier Circulation Rate for Novel Cold Flow Chemical Looping Reactors
Authors: Alain Amanda E. , Bond Nicole K. , Champagne Scott , Hughes Robin W. , Macchi Arturo
Published: December 2023

To achieve net-zero emissions by the year 2050, carbon capture, utilization, and storage technologies must be implemented to decarbonize sectors with hard-to-abate emissions. Pressurized chemical looping (PCL) with a novel reactor design called a plug flow with internal recirculation (PFIR) fluidized bed is proposed as an attractive carbon capture technology to decarbonize small- and medium-scale emitters. The objective of this work is to examine the solid circulation rate between redox reactors in a cold flow chemical looping facility using an energy balance approach. The effects of static bed height, weir opening height, purge configuration, and gas flow rate on solid circulation rate were investigated. It was determined that parameters that greatly affected the total gas momentum, such as the fluidization ratio or number of purge rows, tended to also have a large effect on solid circulation rate. Parameters that had a small effect on total gas momentum, such as bed height, did not have a measurable effect on solid circulation rate. It was noted that parameters that posed a restriction to solids flow, such as a vertical purge jet or the weir itself, decreased the solid circulation rate compared to similar tests without restrictions.
The Genomic Shock Hypothesis: Genetic and Epigenetic Alterations of Transposable Elements after Interspecific Hybridization in Plants
Authors: de Tomás Carlos , Vicient Carlos M.
Published: December 2023

Transposable elements (TEs) are major components of plant genomes with the ability to change their position in the genome or to create new copies of themselves in other positions in the genome. These can cause gene disruption and large-scale genomic alterations, including inversions, deletions, and duplications. Host organisms have evolved a set of mechanisms to suppress TE activity and counter the threat that they pose to genome integrity. These includes the epigenetic silencing of TEs mediated by a process of RNA-directed DNA methylation (RdDM). In most cases, the silencing machinery is very efficient for the vast majority of TEs. However, there are specific circumstances in which TEs can evade such silencing mechanisms, for example, a variety of biotic and abiotic stresses or in vitro culture. Hybridization is also proposed as an inductor of TE proliferation. In fact, the discoverer of the transposons, Barbara McClintock, first hypothesized that interspecific hybridization provides a “genomic shock” that inhibits the TE control mechanisms leading to the mobilization of TEs. However, the studies carried out on this topic have yielded diverse results, showing in some cases a total absence of mobilization or being limited to only some TE families. Here, we review the current knowledge about the impact of interspecific hybridization on TEs in plants and the possible implications of changes in the epigenetic mechanisms.
ICO vs. Equity Financing under Imperfect, Complex and Asymmetric Information
Authors: Miglo Anton
Published: December 2023

This paper offers a game-theoretic model of a firm that raises funds for financing an innovative business project and chooses between ICO (initial coin offering) and equity financing. The model is based on information problems associated with both ICO and equity financing well-documented in the literature. Several new features are introduced, for example, information complexity, which is analyzed along with a more traditional imperfect information and an asymmetric information approach. The model provides several implications that have not yet been tested. For example, we find that the message complexity can be beneficial for firms conducting ICOs. Also, high-quality projects can use ICO as a signal of quality. Thirdly, the average size of projects undertaking equity financing is larger than that of firms conducting ICO.
Aquaculture in Zambia: The Current Status, Challenges, Opportunities and Adaptable Lessons Learnt from China
Authors: Zhang Lin , Maulu Sahya , Hua Fenglei , Chama Majory K. H. , Xu Pao
Published: December 2023

As a land-locked country in Southern Africa, Zambia is rich in natural resources suitable for fish production. However, aquaculture is still in its infancy with enormous potential as most of Zambia’s fish now comes from capture fisheries. The aim of this study was to review the recent progress, status, challenges, and opportunities in Zambia’s aquaculture industry while drawing some lessons from China’s aquaculture experience, focusing on policy instruments, external support, quality seeds, and the investment environment for possible adaptation. To achieve this, we reviewed the existing literature about aquaculture in Zambia. This paper starts by reviewing the overall fishery sector’s developments based on the analysis of relevant statistics over decades before narrowing down to the aquaculture sub-sector. The review shows that aquaculture production has continued to expand significantly and will soon play a leading role in food and nutrition security in Zambia. However, the industry still faces major challenges relating to investments, science and technology, fish seed and feed, and an underdeveloped value chain besides the increasing demand for fish products. Nevertheless, great potential still exists to further develop the aquaculture sub-sector and meet the ever-growing demand for fish products caused mainly by the rapid population increase.
Comparison of Abundance and Structure of Larval Fish Assemblages between Autumn and Spring in the Waters Surrounding Taiwan Bank, Western North Pacific
Authors: Hsieh Hung-Yen , Lee Ming-An , Chiu Wei-Lun , Meng Pei-Jie
Published: December 2023

The fluctuations in both time and space of larval fish assemblages in relation to hydrographic characteristics in the waters surrounding Taiwan Bank were studied in October 2021 (autumn) and March 2022 (spring). Throughout the study period, we identified a total of 149 taxa of fish larvae, encompassing 96 genera and 71 families. Engraulis japonicus, Diaphus slender type, unidentified Gobiidae, Apogon sp., unidentified Clupeidae, and Benthosema pterotum were the six dominant taxa and together constituted 47.39% of the total catch. There were no notable temporal variations observed in the abundance of fish larvae, but the species number of fish larvae was greater in spring than in autumn. Significant variations in species composition were observed between the different cruises, and the cluster analysis unveiled a distinct temporal structure of the assemblages of fish larvae. The dynamics of the prevailing currents induced by seasonal monsoons contribute significantly to the transportation of fish larvae. The distribution of fish larvae showed a good association with hydrographic characteristics, where seawater temperature and salinity emerged as the primary explanatory factors influencing the composition of larval fish assemblages in the waters surrounding Taiwan Bank. While the increased influx of nutrients from upwelling ensures abundant food availability, the hydrographic conditions may not be suitable for every fish larva.
Well-Posedness of Backward Stochastic Differential Equations with Jumps and Irregular Coefficients
Authors: Eddahbi Mhamed
Published: December 2023

In this paper, we focus on investigating the well-posedness of backward stochastic differential equations with jumps (BSDEJs) driven by irregular coefficients. We establish new results regarding the existence and uniqueness of solutions for a specific class of singular BSDEJs. Unlike previous studies, our approach considers terminal data that are square-integrable, eliminating the need for them to be necessarily bounded. The generators in our study encompass a standard drift, a signed measure across the entire real line, and the local time of the unknown process. This broadens the scope to include BSDEJs with quadratic growth in the Brownian component and exponential growth concerning the jump noise. The key methodology involves establishing Krylov-type estimates for a subset of solutions to irregular BSDEJs and subsequently proving the Tanaka-Krylov formula. Additionally, we employ a space transformation technique to simplify the initial BSDEJs, leading to a standard form without singular terms. We also provide various examples and special cases, shedding light on BSDEJs with irregular drift coefficients and contributing to new findings in the field.
Gastrointestinal Manifestations Are Associated with Severe COVID-19 in Children
Authors: Akkoyun Esra Betul , Ashraf Bilal , Hanners Natasha , Kahn Jeffrey , Most Zachary
Published: December 2023

Purpose: Although less severe than in adults, children can experience a range of COVID-19 symptoms, from asymptomatic to life-threatening, including respiratory and gastrointestinal symptoms. Medical conditions may also increase the severity of the disease in infected children. Methods: This study was performed at a single center, comparing cases and controls, and involving 253 pediatric patients who had been diagnosed with COVID-19. Two different outcomes were assessed. The first categorized symptomatic individuals who were hospitalized with COVID-19 (hospital) from those who were not (nonhospital). The second categorized admitted individuals who spent at least one day in the intensive care unit (ICU) from those who did not require intensive care (floor). Results: Ninety individuals (36%) had at least one underlying medical condition, the most common being pulmonary disorders, such as asthma (12%), followed by neurodevelopmental disorders (8%), gastrointestinal disorders (6%), and seizure disorders (6%). The hospital group was more likely to have a comorbidity, such as obstructive sleep apnea (OSA), diabetes mellitus, seizure disorder, hypertension, sickle cell disease, neurodevelopmental disorder, and immunocompromising conditions, including cancer, bone marrow transplant, and other immunodeficiencies, compared to the non-hospital group. Abdominal pain was more common in the hospital group. Shortness of breath (SOB) and diarrhea were significantly more common in the ICU group than in the floor group. Conclusions: Early identification of pediatric patients with severe COVID-19 is important to improve outcomes. In our single-center case–control study, we found that the presence of gastrointestinal symptoms on presentation was more commonly associated with severe COVID-19 in children.
Demyelinating Polyradiculoneuropathy in Chronic Lymphocytic Leukemia: A Case Report on BTKis versus Venetoclax-Rituximab
Authors: Cellini Alessandro , Visentin Andrea , Salvalaggio Alessandro , Cacciavillani Mario , Ferrari Sergio , Briani Chiara
Published: December 2023

The dysregulation of the immune system in Chronic Lymphocytic Leukemia (CLL) often allows for the development of immune-mediated diseases. Among them, autoimmune cytopenias are the most common, but cases of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) have been reported. We herein report on a patient who developed a CIDP while undergoing ibrutinib treatment for CLL, prompting drug discontinuation. Steroid treatment and a rituximab course proved to be ineffective at obtaining long-term control of CIDP, but therapy with venetoclax and rituximab, which was started due to CLL progression, led to the progressive amelioration of the symptoms up to complete remission of the neurological disease.
NADPH Dynamics: Linking Insulin Resistance and β-Cells Ferroptosis in Diabetes Mellitus
Authors: Moon Dong-Oh
Published: December 2023

This review offers an in-depth exploration of Nicotinamide Adenine Dinucleotide Phosphate (NADPH) in metabolic health. It delves into how NADPH affects insulin secretion, influences insulin resistance, and plays a role in ferroptosis. NADPH, a critical cofactor in cellular antioxidant systems and lipid synthesis, plays a central role in maintaining metabolic homeostasis. In adipocytes and skeletal muscle, NADPH influences the pathophysiology of insulin resistance, a hallmark of metabolic disorders such as type 2 diabetes and obesity. The review explores the mechanisms by which NADPH contributes to or mitigates insulin resistance, including its role in lipid and reactive oxygen species (ROS) metabolism. Parallelly, the paper investigates the dual nature of NADPH in the context of pancreatic β-cell health, particularly in its relation to ferroptosis, an iron-dependent form of programmed cell death. While NADPH’s antioxidative properties are crucial for preventing oxidative damage in β-cells, its involvement in lipid metabolism can potentiate ferroptotic pathways under certain pathological conditions. This complex relationship underscores the delicate balance of NADPH homeostasis in pancreatic health and diabetes pathogenesis. By integrating findings from recent studies, this review aims to illuminate the nuanced roles of NADPH in different tissues and its potential as a therapeutic target. Understanding these dynamics offers vital insights into the development of more effective strategies for managing insulin resistance and preserving pancreatic β-cell function, thereby advancing the treatment of metabolic diseases.
BAY-3827 and SBI-0206965: Potent AMPK Inhibitors That Paradoxically Increase Thr172 Phosphorylation
Authors: Hawley Simon A. , Russell Fiona M. , Ross Fiona A. , Hardie D. Grahame
Published: December 2023

AMP-activated protein kinase (AMPK) is the central component of a signalling pathway that senses energy stress and triggers a metabolic switch away from anabolic processes and towards catabolic processes. There has been a prolonged focus in the pharmaceutical industry on the development of AMPK-activating drugs for the treatment of metabolic disorders such as Type 2 diabetes and non-alcoholic fatty liver disease. However, recent findings suggest that AMPK inhibitors might be efficacious for treating certain cancers, especially lung adenocarcinomas, in which the PRKAA1 gene (encoding the α1 catalytic subunit isoform of AMPK) is often amplified. Here, we study two potent AMPK inhibitors, BAY-3827 and SBI-0206965. Despite not being closely related structurally, the treatment of cells with either drug unexpectedly caused increases in AMPK phosphorylation at the activating site, Thr172, even though the phosphorylation of several downstream targets in different subcellular compartments was completely inhibited. Surprisingly, the two inhibitors appear to promote Thr172 phosphorylation by different mechanisms: BAY-3827 primarily protects against Thr172 dephosphorylation, while SBI-0206965 also promotes phosphorylation by LKB1 at low concentrations, while increasing cellular AMP:ATP ratios at higher concentrations. Due to its greater potency and fewer off-target effects, BAY-3827 is now the inhibitor of choice for cell studies, although its low bioavailability may limit its use in vivo.
Melatonin as a Promising Anti-Inflammatory Agent in an In Vivo Animal Model of Sepsis-Induced Rat Liver Damage
Authors: Benedeto-Stojanov Daniela , Ničković Vanja P. , Petrović Gordana , Rancić Andrija , Grgov Ivan , Nikolić Gordana R. , Marčetić Zoran P. , Popović Milica R. , Lazarević Milan , Mitić Katarina V. , Sokolović Dušan
Published: December 2023

Melatonin (MLT), earlier described as an effective anti-inflammatory agent, could be a beneficial adjunctive drug for sepsis treatment. This study aimed to determine the effects of MLT application in lipopolysaccharide (LPS)-induced sepsis in Wistar rats by determining the levels of liver tissue pro-inflammatory cytokines (TNF-α, IL-6) and NF-κB as well as hematological parameters indicating the state of sepsis. Additionally, an immunohistological analysis of CD14 molecule expression was conducted. Our research demonstrated that treatment with MLT prevented an LPS-induced increase in pro-inflammatory cytokines TNF-α and IL-6 and NF-κB levels, and in the neutrophil to lymphocyte ratio (NLR). On the other hand, MLT prevented a decrease in the blood lymphocyte number induced by LPS administration. Also, treatment with MLT decreased the liver tissue expression of the CD14 molecule observed after sepsis induction. In summary, in rats with LPS-induced sepsis, MLT was shown to be a significant anti-inflammatory agent with the potential to change the liver’s immunological marker expression, thus ameliorating liver function.
The DNA Alkyltransferase Family of DNA Repair Proteins: Common Mechanisms, Diverse Functions
Authors: Tessmer Ingrid , Margison Geoffrey P.
Published: December 2023

DNA alkyltransferase and alkyltransferase-like family proteins are responsible for the repair of highly mutagenic and cytotoxic O6-alkylguanine and O4-alkylthymine bases in DNA. Their mechanism involves binding to the damaged DNA and flipping the base out of the DNA helix into the active site pocket in the protein. Alkyltransferases then directly and irreversibly transfer the alkyl group from the base to the active site cysteine residue. In contrast, alkyltransferase-like proteins recruit nucleotide excision repair components for O6-alkylguanine elimination. One or more of these proteins are found in all kingdoms of life, and where this has been determined, their overall DNA repair mechanism is strictly conserved between organisms. Nevertheless, between species, subtle as well as more extensive differences that affect target lesion preferences and/or introduce additional protein functions have evolved. Examining these differences and their functional consequences is intricately entwined with understanding the details of their DNA repair mechanism(s) and their biological roles. In this review, we will present and discuss various aspects of the current status of knowledge on this intriguing protein family.
Genome-Wide Analysis of MYB Genes in Primulina eburnea (Hance) and Identification of Members in Response to Drought Stress
Authors: Zhang Jie , Zhang Yi , Feng Chen
Published: December 2023

Due to periodic water deficiency in karst environments, Primulina eburnea experiences sporadic drought stress in its habitat. Despite being one of the largest gene families and functionally diverse in terms of plant growth and development, MYB transcription factors in P. eburnea have not been studied. Here, a total of 230 MYB genes were identified in P. eburnea, including 67 1R-MYB, 155 R2R3-MYB, six 3R-MYB, and two 4R-MYB genes. The R2R3-type PebMYB genes could be classified into 16 subgroups, while the remaining PebMYB genes (1R-MYB, 3R-MYB, and 4R-MYB genes) were divided into 10 subgroups. Notably, the results of the phylogenetic analysis were further supported by the motif and gene structure analysis, which showed that individuals in the same subgroup had comparable motif and structure organization. Additionally, gene duplication and synteny analyses were performed to better understand the evolution of PebMYB genes, and 291 pairs of segmental duplicated genes were found. Moreover, RNA-seq analysis revealed that the PebMYB genes could be divided into five groups based on their expression characteristics. Furthermore, 11 PebMYB genes that may be involved in drought stress response were identified through comparative analysis with Arabidopsis thaliana. Notably, seven of these genes (PebMYB3, PebMYB13, PebMYB17, PebMYB51, PebMYB142, PebMYB69, and PebMYB95) exhibited significant differences in expression between the control and drought stress treatments, suggesting that they may play important roles in drought stress response. These findings clarified the characteristics of the MYB gene family in P. eburnea, augmenting our comprehension of their potential roles in drought stress adaptation.
3-O-Methyltolcapone and Its Lipophilic Analogues Are Potent Inhibitors of Transthyretin Amyloidogenesis with High Permeability and Low Toxicity
Authors: Poonsiri Thanalai , Dell’Accantera Davide , Loconte Valentina , Casnati Alessandro , Cervoni Laura , Arcovito Alessandro , Benini Stefano , Ferrari Alberto , Cipolloni Marco , Cacioni Elisa , De Franco Francesca , Giacchè Nicola , Rinaldo Serena , Folli Claudia , Sansone Francesco , Berni Rodolfo , Cianci Michele
Published: December 2023

Transthyretin (TTR) is an amyloidogenic homotetramer involved in the transport of thyroxine in blood and cerebrospinal fluid. To date, more than 130 TTR point mutations are known to destabilise the TTR tetramer, leading to its extracellular pathological aggregation accumulating in several organs, such as heart, peripheral and autonomic nerves, and leptomeninges. Tolcapone is an FDA-approved drug for Parkinson’s disease that has been repurposed as a TTR stabiliser. We characterised 3-O-methyltolcapone and two newly synthesized lipophilic analogues, which are expected to be protected from the metabolic glucuronidation that is responsible for the lability of tolcapone in the organism. Immunoblotting assays indicated the high degree of TTR stabilisation, coupled with binding selectivity towards TTR in diluted plasma of 3-O-methyltolcapone and its lipophilic analogues. Furthermore, in vitro toxicity data showed their several-fold improved neuronal and hepatic safety compared to tolcapone. Calorimetric and structural data showed that both T4 binding sites of TTR are occupied by 3-O-methyltolcapone and its lipophilic analogs, consistent with an effective TTR tetramer stabilisation. Moreover, in vitro permeability studies showed that the three compounds can effectively cross the blood-brain barrier, which is a prerequisite for the inhibition of TTR amyloidogenesis in the cerebrospinal fluid. Our data demonstrate the relevance of 3-O-methyltolcapone and its lipophilic analogs as potent inhibitors of TTR amyloidogenesis.
Lipid Metabolism Regulators Are the Possible Determinant for Characteristics of Myopic Human Scleral Stroma Fibroblasts (HSSFs)
Authors: Ohguro Hiroshi , Umetsu Araya , Sato Tatsuya , Furuhashi Masato , Watanabe Megumi
Published: December 2023

The purpose of the current investigation was to elucidate what kinds of responsible mechanisms induce elongation of the sclera in myopic eyes. To do this, two-dimensional (2D) cultures of human scleral stromal fibroblasts (HSSFs) obtained from eyes with two different axial length (AL) groups, <26 mm (low AL group, n = 2) and >27 mm (high AL group, n = 3), were subjected to (1) measurements of Seahorse mitochondrial and glycolytic indices to evaluate biological aspects and (2) analysis by RNA sequencing. Extracellular flux analysis revealed that metabolic indices related to mitochondrial and glycolytic functions were higher in the low AL group than in the high AL group, suggesting that metabolic activities of HSSF cells are different depending the degree of AL. Based upon RNA sequencing of these low and high AL groups, the bioinformatic analyses using gene ontology (GO) enrichment analysis and ingenuity pathway analysis (IPA) of differentially expressed genes (DEGs) identified that sterol regulatory element-binding transcription factor 2 (SREBF2) is both a possible upstream regulator and a causal network regulator. Furthermore, SREBF1, insulin-induced gene 1 (INSIG1), and insulin-like growth factor 1 (IGF1) were detected as upstream regulators, and protein tyrosine phosphatase receptor type O (PTPRO) was detected as a causal network regulator. Since those possible regulators were all pivotally involved in lipid metabolisms including fatty acid (FA), triglyceride (TG) and cholesterol (Chol) biosynthesis, the findings reported here indicate that FA, TG and Chol biosynthesis regulation may be responsible mechanisms inducing AL elongation via HSSF.
Light-Chain Amyloidosis: The Great Impostor
Authors: Stefani Georgia , Kouvata Evangelia , Vassilopoulos George
Published: December 2023

Light-chain amyloidosis (AL) is a disease of protean manifestations due to a wide spectrum of organs that can be affected. The disorder is caused by the deposition of an extracellular amorphous material, the amyloid, which is produced by malignant plasma cells. The latter usually reside in the bone marrow; plasma cell infiltration is often low, in sharp contrast to what we observe in multiple myeloma. The disease may run below the physician’s radar for a while before clinical suspicion is raised and targeted tests are performed. In this short review, we try to answer most of the questions that a practicing physician may ask in a relative clinical setting. The text is formed as a series of reader-friendly questions that cover the subject of AL amyloidosis from history to current therapy.
Translocation of Adenosine A2B Receptor to Mitochondria Influences Cytochrome P450 2E1 Activity after Acetaminophen Overdose
Authors: Sanchez-Guerrero Giselle , Umbaugh David S. , Ramachandran Abhay A. , Artigues Antonio , Jaeschke Hartmut , Ramachandran Anup
Published: December 2023

The adenosine A2B receptor (A2BAR) is a member of a family of G-protein coupled receptors (GPCRs), which has a low affinity for adenosine and is now implicated in several pathophysiological conditions. We have demonstrated the beneficial effects of A2BAR activation in enhancing recovery after acute liver injury induced by an acetaminophen (APAP) overdose. While receptor trafficking within the cell is recognized to play a role in GPCR signaling, its role in the mediation of A2BAR effects in the context of APAP-induced liver injury is not well understood. This was investigated here, where C57BL/6J mice were subjected to an APAP overdose (300 mg/kg), and the temporal course of A2BAR intracellular localization was examined. The impact of A2BAR activation or inhibition on trafficking was examined by utilizing the A2BAR agonist BAY 60-6583 or antagonist PSB 603. The modulation of A2BAR trafficking via APAP-induced cell signaling was explored by using 4-methylpyrazole (4MP), an inhibitor of Cyp2E1 and JNK activation. Our results indicate that APAP overdose induced the translocation of A2BAR to mitochondria, which was prevented via 4MP treatment. Furthermore, we demonstrated that A2BAR is localized on the mitochondrial outer membrane and interacts with progesterone receptor membrane component 1 (PGRMC1). While the activation of A2BAR enhanced mitochondrial localization, its inhibition decreased PGRMC1 mitochondria levels and blunted mitochondrial Cyp2E1 activity. Thus, our data reveal a hitherto unrecognized consequence of A2BAR trafficking to mitochondria and its interaction with PGRMC1, which regulates mitochondrial Cyp2E1 activity and modulates APAP-induced liver injury.
Damage-Accumulation-Induced Crack Propagation and Fatigue Life Analysis of a Porous LY12 Aluminum Alloy Plate
Authors: Lv Cheng , Wang Kejie , Zhao Xiang , Wang Fenghui
Published: December 2023

Rivets are usually used to connect the skin of an aircraft with joints such as frames and stringers, so the skin of the connection part is a porous structure. During the service of the aircraft, cracks appear in some difficult-to-detect parts of the skin porous structure, which causes great difficulties in the service life prediction and health monitoring of the aircraft. In this paper, a secondary development subroutine in PYTHON based on ABAQUS-XFEM is compiled to analyze the cracks that are difficult to monitor in the porous structure of aircraft skin joints. The program can automatically analyze the stress intensity factor of the crack tip with different lengths in the porous structure, and then the residual fatigue life can be deduced. For the sake of safety, the program adopts a more conservative algorithm. In comparison with the physical fatigue test results, the fatigue life of the simulation results is 16% smaller. This project provides a feasible simulation method for fatigue life prediction of porous structures. It lays a foundation for the subsequent establishment of digital twins for damage monitoring of aircraft porous structures.
Effect of Workpiece/Tool Heat Transfer and Friction Coefficients on Accuracy of Simulated Temperatures and Torques in a Friction Stir Welding Plunge
Authors: Goodson Matthew , Melander Ryan , Miles Michael P. , Munro Troy
Published: December 2023

Friction stir process models are typically validated by tuning heat transfer and friction coefficients until measured temperatures in either the tool or workpiece, but rarely in both, match simulated results. A three-dimensional finite element model for a tool plunge in an AA 6061-T6 is validated for temperature predictions in both the tool and workpiece using a friction coefficient that varies with time. Peak workpiece temperatures were within 1.5% of experimental temperatures and tool temperatures were off by 80 °C. The sensitivity of the predicted temperatures with respect to the workpiece/tool heat transfer coefficient was shown to be high for the tool and low for the workpiece, while the spindle torque was slightly underpredicted in the best case. These results show that workpiece/tool interface properties must be tuned by considering predictions on both sides of the heat generation interface in order to ensure a reliable process simulation.
Unknown Health States Recognition with Collective-Decision-Based Deep Learning Networks in Predictive Maintenance Applications
Authors: Lou Chuyue , Atoui Mohamed Amine
Published: December 2023

At present, decision-making solutions developed based on deep learning (DL) models have received extensive attention in predictive maintenance (PM) applications along with the rapid improvement of computing power. Relying on the superior properties of shared weights and spatial pooling, convolutional neural networks (CNNs) can learn effective representations of health states from industrial data. Many developed CNN-based schemes, such as advanced CNNs that introduce residual learning and multi-scale learning, have shown good performance in health states recognition tasks under the assumption that all the classes are known. However, these schemes have no ability to deal with new abnormal samples that belong to state classes not part of the training set. In this paper, a collective decision framework for different CNNs is proposed. It is based on a one-vs.-rest network (OVRN) to simultaneously achieve classification of known and unknown health states. OVRNs learn class-specific discriminative features and enhance the ability to reject new abnormal samples incorporated to different CNNs. According to the validation results on the public dataset of the Tennessee Eastman process (TEP), the proposed CNN-based decision schemes incorporating an OVRN have outstanding recognition ability for samples of unknown heath states while maintaining satisfactory accuracy on known states. The results show that the new DL framework outperforms state-of-the-art CNNs, and the one based on residual and multi-scale learning has the best overall performance.