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Following an outbreak of Cronobacter sakazakii infection in infant formula, the US Food and Drug Administration commissioned a series of reports and then undertook a major reorganization of its food program. This article describes the changes that went into effect on 1 October 2024, why those changes are likely to improve the new Human Foods Program, and additional work that must be undertaken to enhance the agency's impact upon public health. [ABSTRACT FROM AUTHOR]

This study addresses the critical need for innovation in the healthcare sector, particularly in Japan's functional food industry, amid rising chronic diseases and healthcare costs. It explores the complex relationship between regulatory design and corporate behaviour, focusing on how companies' compliance strategies influence their research and development (R&D) investments. A mixed-method approach was used, analysing data from 15 major dietary supplement companies and 74 products under Japan's Foods with Function Claims (FFCs) regulation. The study reveals a correlation between companies' engagement in the FFCs system and their preference for conducting in-house clinical trials, indicative of higher R&D investments (R = 0.66, p = 0.007), and that between the latter variable and average product sales, which is a measure of returns on regulatory compliance (R = 0.66, p = 0.008). Companies actively complying with FFCs regulations tend to conduct R&D and accumulate knowledge in-house, to innovate and differentiate their products, gaining competitive advantages. The study also highlights the role of a company's size, market presence, and industry origins in shaping regulatory strategies, with firms from other industries using FFCs regulations to explore new business opportunities. The research underscores the importance of flexible regulatory frameworks that encourage R&D investment, leading to innovation and competitive advantages in the healthcare sector. [ABSTRACT FROM AUTHOR]

Background: The Jun proto-oncogene (JUN), also referred to as C-JUN, is an integral component of the JNK signaling pathway, which is crucial for the formation and differentiation of spermatogonial stem cells (SSCs). Investigations into the transcriptional regulation of chicken JUN can offer a molecular foundation for elucidating its mechanistic role in SSCs. Methods: In this study, we successfully cloned a 2000 bp upstream sequence of the JUN transcription start site and constructed a series of pGL3 recombinant vectors containing JUN promoters of varying lengths. Results: We verified the promoter activity of the 2000 bp upstream sequence by assessing the fluorescence intensity of DF-1 and identified the promoter activities of different regions via dual-luciferase assays. The transcription of JUN and its promoter region spanning −700 to 0 bp was modulated by an activator of the JNK signaling pathway. Bioinformatics analysis revealed that this −700 to 0 bp region was highly conserved among avian species and predicted the presence of binding sites for Wilms tumor 1 (WT1) and CCAAT/enhancer binding protein alpha (CEBPA). The JNK signaling pathway activator was found to upregulate the expression of these transcription factors in DF-1 cells. Through the deletion of binding sites and the overexpression of WT1 and CEBPA, we demonstrated that WT1 inhibited the transcription of JUN, while CEBPA promoted it. Conclusions: In conclusion, the −700 to 0 bp region is the key region of the JUN promoter, with WT1 inhibiting JUN transcription. The results of the study not only provide ideas for exploring the regulatory mechanism of JUN in chicken SSCs, but also lay an important foundation for the study of avian SSCs. [ABSTRACT FROM AUTHOR]

Cys is one of the least abundant amino acids in proteins. However, it is often highly conserved and is usually found in important structural and functional regions of proteins. Its unique chemical properties allow it to undergo several post-translational modifications, many of which are mediated by reactive oxygen, nitrogen, sulfur, or carbonyl species. Thus, in addition to their role in catalysis, protein stability, and metal binding, Cys residues are crucial for the redox regulation of metabolism and signal transduction. In this review, we discuss Cys post-translational modifications (PTMs) and their role in plant metabolism and signal transduction. These modifications include the oxidation of the thiol group (S-sulfenylation, S-sulfinylation and S-sulfonylation), the formation of disulfide bridges, S-glutathionylation, persulfidation, S-cyanylation S-nitrosation, S-carbonylation, S-acylation, prenylation, CoAlation, and the formation of thiohemiacetal. For each of these PTMs, we discuss the origin of the modifier, the mechanisms involved in PTM, and their reversibility. Examples of the involvement of Cys PTMs in the modulation of protein structure, function, stability, and localization are presented to highlight their importance in the regulation of plant metabolic and signaling pathways. [ABSTRACT FROM AUTHOR]

Due to the fast-changing environments caused by artificial intelligence development, the socio-technical challenge in contemporary educational systems focuses on the need for more regulative measures guiding system stakeholders' behavior. In fulfilling the present legal gap, enacted soft law regulation has been laid out, and a detailed systematic literature review was conducted in the paper presented. The specific methodological approach was selected to deal with two crucial research tasks: to reveal and recommend fundamental governing mechanisms regarding the use and application of generative artificial intelligence; more precisely, large language models in educational systems. Three systematically guided layers of quantitative and qualitative content analysis of central policy, legislation, and regulatory mechanisms in governing AI in education were extracted from the 142 Scopus Database and Web of Science research papers analyzed and presented. These research findings benefit policymakers, regulatory and legislative bodies, and agencies in constructing governing frames for using and applying generative artificial intelligence in education. [ABSTRACT FROM AUTHOR]

With increasing interest in the emotional responses to music, some studies are specifically looking into music's regulatory function on emotion, known as "music emotion regulation (MER)". The purpose of this study was to examine the concepts on the regulatory impact of music on emotion using a scoping review procedure. Through an electronic database and manual searches based on the guidelines suggested by the JBI Manual for Evidence Synthesis, a total of 47 studies were identified and included for analysis. The results showed that there were some definitional challenges in each component of music emotion regulation. Most studies treated music as a single variable without exploring the regulatory mechanism of the intra-musical elements that constitute music. When examining the regulatory impact of music on emotion, emotion was inclusive of other terms ranging from feeling to mood. Most of the MER studies employed the terms used in the emotion regulation strategies; however, there were some regulatory processes that pertained solely to music's cathartic effect. Overall, the results showed that music emotion regulation (MER) was not clearly distinguished from music emotion (ME) studies. Future research should allocate more attention to the theoretical mechanism behind music's intrinsic regulatory effect in emotion regulation (MER) studies. [ABSTRACT FROM AUTHOR]

Simple Summary: Diapause is a state in which insects respond to environmental changes, leading to developmental stagnation, which is crucial in the life history of insects. miRNA regulates the expression of genes after transcription and participates in the regulation of important biological processes of insect growth and development. In this study, we screened differentially expressed miRNAs (DEMs) in non-diapause/diapause and diapause/non-diapause comparison groups of Ostrinia furnacalis and predicted their target genes. The expression patterns of key target genes Kr-h, JHE, JHEH, FOXO, Cry, and Per in diapause-related metabolic pathways at different stages of diapause were opposite to those of miRNAs, suggesting their regulatory roles in the diapause process. This study improves the scientific understanding of diapause in O. furnacalis; the learning can be applied to other insects. microRNAs (miRNAs) function as vital regulators of diapause in insects through their ability to post-transcriptionally suppress target gene expression. In this study, the miRNA of Ostrinia furnacalis, an economically important global crop pest species, was characterized. For the included analyses, 9 small RNA libraries were constructed using O. furnacalis larvae in different diapause states (non-diapause, ND; diapause, D; diapause-termination, DT). The results identified 583 total miRNAs, of which 256 had previously been identified, whereas 327 were novel. Furthermore, comparison analysis revealed that 119 and 27 miRNAs were differentially expressed in the D vs. ND and DT vs. D, respectively. Moreover, the expression patterns of their miRNAs were also analyzed. GO and KEGG analysis of the target genes of differentially expressed miRNAs highlighted the importance of these miRNAs as diapause regulators in O. furnacalis, especially through metabolic processes, endocrine processes, 20-hydroxyecdysone, and circadian clock signaling pathways. In summary, this study highlighted the involvement of specific miRNAs in the control of diapause in O. furnacalis. To the best of our knowledge, this is the first study to identify miRNA expression patterns in O. furnacalis, thereby providing reference and novel evidence enhancing our current understanding of how small RNAs influence insect diapause. [ABSTRACT FROM AUTHOR]

Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas (CRISPR-associated proteins) systems provide acquired heritable protection to bacteria and archaea against selfish DNA elements, such as viruses. These systems must be tightly regulated because they can capture DNA fragments from foreign selfish elements, and also occasionally from self-chromosomes, resulting in autoimmunity. Most known species from the halophilic archaeal genus Haloferax contain type I-B CRISPR-Cas systems, and the strongest hotspot for self-spacer acquisition by H. mediterranei was a locus that contained a putative transposable element, as well as the gene HFX_2341, which was a very frequent target for self-targeting spacers. To test whether this gene is CRISPR-associated, we investigated it using bioinformatics, deletion, over-expression, and comparative transcriptomics. We show that HFX_2341 is a global transcriptional regulator that can repress diverse genes, since its deletion results in significantly higher expression of multiple genes, especially those involved in nutrient transport. When over-expressed, HFX_2341 strongly repressed the transcript production of all cas genes tested, both those involved in spacer acquisition (cas1, 2 and 4) and those required for destroying selfish genetic elements (cas3 and 5–8). Considering that HFX_2341 is highly conserved in haloarchaea, with homologs that are present in species that do not encode the CRISPR-Cas system, we conclude that it is a global regulator that is also involved in cas gene regulation, either directly or indirectly. [ABSTRACT FROM AUTHOR]

This research paper presents a comprehensive analysis of pesticide use in global and Indian agriculture, focusing on the mounting food security challenges due to population growth and the increased demand for food and fiber crops. While pesticides are crucial in mitigating losses due to pests, diseases, and weeds, increasing apprehension regarding their adverse effects on human and environment health necessitates a critical examination of their usage patterns. Despite India's relatively low per-hectare pesticide usage of 0.4 kg compared to China's 1.83 kg, issues with pesticide residue contamination in the food chain require urgent attention. Additionally, significant regional disparities in pesticide application highlight the need for more uniform and sustainable agricultural practices. Therefore, this study examines the evolving trends in global and Indian pesticide application, providing a comprehensive analysis of the shifting dynamics across various Indian states and crop varieties. Furthermore, it analyzes various pesticide categories and their respective market shares, providing insights into production and export patterns. Our research also explores regulatory frameworks aimed at optimizing pesticide use while minimizing detrimental effects on human health and the environment. [ABSTRACT FROM AUTHOR]

WRKY transcription factors (TFs) can participate in plant biological stress responses and play important roles. SlWRKY80 was found to be differentially expressed in the Mi-1- and Mi-3-resistant tomato lines by RNA-seq and may serve as a key node for disease resistance regulation. This study used RNAi to determine whether SlWRKY80 silencing could influence the sensitivity of 'M82' (mi-1/mi-1)-susceptible lines to M. incognita. Further overexpression of this gene revealed a significant increase in tomato disease resistance, ranging from highly susceptible to susceptible, combined with the identification of growth (plant height, stem diameter, and leaf area) and physiological (soluble sugars and proteins; root activity) indicators, clarifying the role of SlWRKY80 as a positive regulatory factor in tomato defense against M. incognita. Based on this phenomenon, a preliminary exploration of its metabolic signals revealed that SlWRKY80 stimulates different degrees of signaling, such as salicylic acid (SA), jasmonic acid (JA), and ethylene (ETH), and may synergistically regulate reactive oxygen species (ROS) accumulation and scavenging enzyme activity, hindering the formation of feeding sites and ultimately leading to the reduction of root gall growth. To our knowledge, SlWRKY80 has an extremely high utilization value for improving tomato resistance to root-knot nematodes and breeding. [ABSTRACT FROM AUTHOR]

The rapid development of the Internet of Vehicles using centralized systems faces significant challenges, including reliability and security vulnerabilities and high latency. This paper introduces a blockchain-enabled authentication and communication network for scalable IoV to enhance security, reduce latency, and relieve the dependency on centralized infrastructures. The network applies blockchain-enabled domain name services and mutual authentication for fault tolerance consensus, such as PBFT and RAFT, featuring a primary layer of road side units and edge servers for inter-vehicle communication and a sub-layer within each vehicle for intra-vehicle communication. The study evaluates various scenarios and assesses roadside unit availability based on random distribution along vehicle routes. This paper also discusses the legal issues involved in the proposed model, highlighting that the IoV system should be governed by a contract-based decentralized IoV system comprising both smart contracts and traditional contracts. This model offers a novel approach to developing a decentralized, secure, efficient, and ethical IoV ecosystem, advancing autonomous and reliable vehicular networks. [ABSTRACT FROM AUTHOR]

Nuclear hormone receptors (NHRs) are a family of ligand-regulated transcription factors that control key aspects of development and physiology. The regulation of NHRs by ligands derived from metabolism or diet makes them excellent pharmacological targets, and the mechanistic understanding of how NHRs interact with their ligands to regulate downstream gene networks, along with the identification of ligands for orphan NHRs, could enable innovative approaches for cellular engineering, disease modeling and regenerative medicine. We review recent discoveries in the identification of physiologic ligands for NHRs. We propose new models of ligand-receptor co-evolution, the emergence of hormonal function and models of regulation of NHR specificity and activity via one-ligand and two-ligand models as well as feedback loops. Lastly, we discuss limitations on the processes for the identification of physiologic NHR ligands and emerging new methodologies that could be used to identify the natural ligands for the remaining 17 orphan NHRs in the human genome. [ABSTRACT FROM AUTHOR]

The aim of our study was to determine whether granzyme B-expressing regulatory B cells (GZMB+ B cells) are enriched in the blood of transplant patients with renal graft tolerance. To achieve this goal, we analysed two single-cell RNA sequencing (scRNAseq) datasets: (1) peripheral blood mononuclear cells (PBMCs), including GZMB+ B cells from renal transplant patients, i.e., patients with stable graft function on conventional immunosuppressive treatment (STA, n = 3), drug-free tolerant patients (TOL, n = 3), and patients with antibody-mediated rejection (ABMR, n = 3), and (2) ex-vivo-induced GZMB+ B cells from these groups. In the patient PBMCs, we first showed that natural GZMB+ B cells were enriched in genes specific to Natural Killer (NK) cells (such as NKG7 and KLRD1) and regulatory B cells (such as GZMB, IL10, and CCL4). We performed a pseudotemporal trajectory analysis of natural GZMB+ B cells and showed that they were highly differentiated B cells with a trajectory that is very different from that of conventional memory B cells and linked to the transcription factor KLF13. By specifically analysing GZMB+ natural B cells in TOLs, we found that these cells had a very specific transcriptomic profile associated with a reduction in the expression of HLA molecules, apoptosis, and the inflammatory response (in general) in the blood and that this signature was conserved after ex vivo induction, with the induction of genes associated with migration processes, such as CCR7, CCL3, or CCL4. An analysis of receptor/ligand interactions between these GZMB+/− natural B cells and all of the immune cells present in PBMCs also demonstrated that GZMB+ B cells were the B cells that carried the most ligands and had the most interactions with other immune cells, particularly in tolerant patients. Finally, we showed that these GZMB+ B cells were able to infiltrate the graft under inflammatory conditions, thus suggesting that they can act in locations where immune events occur. [ABSTRACT FROM AUTHOR]

This article documents and explores the history of the e-scooter ban in Toronto, Ontario, Canada as a pathway to examining broader issues concerning the eradication of accessibility barriers in public spaces for pedestrians with disabilities and respectful uses of consultation to develop disability-inclusive regulations. The use of e-scooters poses a particular dilemma to accessibility for persons with disabilities. On the one hand, the concept of disability contemplates attitudinal and environmental barriers, as noted, for example, in the Preamble of the United Nations (UN) Convention on the Rights of Persons with Disabilities (CRPD). Attitudinal and environmental barriers have traditionally stemmed from interests that are inherently opposed to the collective interests of disabled persons. Examples include attitudes that project stigma against persons with disabilities or a focus on seeking to preserve historical features of the built environment for their aesthetics, without consideration for their accessibility or functionality for disabled persons. They have also generally originated in periods of historical marginalization or exclusion of persons with disabilities. By contrast, e-scooter debates and connected debates regarding the regulation of micromobility vehicles, contain at least one dimension that could very well be shared with persons with disabilities—that is, the preservation of the environment. E-scooters are also a phenomenon of contemporary disability exclusion: policies concerning environmental sustainability, including those promoting e-scooters, are being developed contemporaneously with growing international and national legal recognition of disability rights. These factors render arguments over appropriate regulation of the use of public spaces more complex as, within those arguments, one sees two competing positive policy directions that need to be addressed: the rights of pedestrians with disabilities and environmental sustainability. This article concludes with theoretical and practical suggestions for strengthening regulatory policymaking to address these and other complex intersectional issues of accessibility policy design. [ABSTRACT FROM AUTHOR]

The microbiota plays a crucial role in maintaining the host's intestinal homeostasis, influencing numerous physiological functions. Various factors, including diet, stress, and antibiotic use, can lead to such imbalances. Probiotics have been shown to restore the microbiota, contributing to maintaining this balance. For instance, the weaning stage in piglets is crucial; this transition can cause unfavorable changes that may contribute to the onset of diarrhea. Probiotic supplementation has increased due to its benefits. However, its mechanism of action is still controversial; one involves the regulation of intestinal immunity. When recognized by immune system cells through membrane receptors, probiotics activate intracellular signaling pathways that lead to changes in gene expression, resulting in an anti-inflammatory response. This complex regulatory system involves transcriptional and post-transcriptional mechanisms, including the modulation of various molecules, emphasizing microRNAs. They have emerged as important regulators of innate and adaptive immune responses. Analyzing these mechanisms can enhance our understanding of probiotic–host microbiota interactions, providing insights into their molecular functions. This knowledge can be applied not only in the swine industry, but also in studying microbiota-related disorders. Moreover, these studies serve as animal models, helping to understand better conditions such as inflammatory bowel disease and other related disorders. [ABSTRACT FROM AUTHOR]

Financial technology (Fintech) has influenced business by helping create better services for consumers and businesses. Fintech, however, brings new challenges for regulators, who struggle to keep pace with the constant evolution of technology and the resulting disruption. The progress of technology and regulations in the Fintech industry has been uneven across developed and developing countries, resulting in numerous opportunities and challenges. Considerable progress has recently been made in the adoption of Fintech and the subsequent development and implementation of regulations in the US, the UK, and India. While the United States (US) and the United Kingdom (UK) are global leaders in Fintech innovation, India has shown fast-paced growth in adopting and utilizing Fintech services. This paper examines the growth and evolution of Fintech in the US, the UK, and India and also explores how the regulatory agencies across these countries have responded to the evolution of Fintech. This paper finds that economies should work towards improving digital infrastructure, financial inclusion, and financial literacy and enhance the collaboration among regulators, Fintech firms, and other stakeholders. [ABSTRACT FROM AUTHOR]

This review addresses the issue of replacing manufactured microplastics in seed coatings used in agriculture. Firstly, it focuses on the policy and regulatory actions taken on microplastics at a global level. There is no consensus within the scientific community on the definition of a microplastic and, more generally, on the classification of plastic debris. Nevertheless, several decision schemes have been proposed in an attempt to define the notion of microplastics. The different criteria relevant to this definition, such as the size, physical state, chemical structure, origin, and persistence of microplastics, are discussed, with a comparison being made between the REACH regulation and the scientific literature. Seed production and processing are also discussed, with the functions of seed coatings being explained in order to gain a better understanding of the properties to be considered in a substitution strategy for currently used microplastics. The main challenges are multiple; substitutes must provide the same performance as microplastics: (i) improving the adherence of the treatment to the seed, (ii) distributing the treatment more evenly over the seed, (iii) reducing the amount of dust-off when handling treated seed, and (iv) improving the seed flowability, which is particularly important during the sowing stage, all while preserving the physiological properties of the seed. Substitute polymers are proposed according to the desired performance and functional properties: two main chemical families of biopolymers were identified in the literature: polysaccharides and proteins. Among them, 13 and 6 polymers, respectively, complied with REACH regulation, demonstrating adhesion, dust reduction performances, and preservation of seed physiological quality in particular. This work aims to guide future studies on microplastic substitution in seed coatings, and to highlight research needs in this area. It is based on an analysis and discussion of the literature, identifying and listing potential substitutes. [ABSTRACT FROM AUTHOR]

Catastrophic cyber incidents—events of low probability but high impact, with the potential to incur billions of dollars in damages—are prompting insurers to elevate premiums, create higher barriers for potential buyers, and tighten policies with exclusions. While these responses of the insurance industry are important to prevent its insolvency during catastrophic incidents due to excessive claims, they lead to a notable gap in market protection. Using a content analysis of multistakeholder comments submitted in response to a Treasury Department Request for Information (RFI), this study seeks to define what constitutes a catastrophic cyber event, identify mitigation strategies, evaluate the current capacity of the cyber insurance sector to handle such incidents, and investigate the potential roles and support mechanisms that the government can provide to enhance the insurance sector's capacity to manage these extreme risks. This paper is one of the pioneering studies using data and a multistakeholder perspective to provide essential guidance for policymakers, regulators, the insurance industry, and the cybersecurity sector in formulating robust policies and strategies to address catastrophic cyber risks, ultimately enhancing national economic and technological resilience. [ABSTRACT FROM AUTHOR]

The key to promoting high-quality economic development (HQED) is to identify the influencing factors and the complex relationships among them. Under the guidance of China's new development concept, we systematically analyze the factors influencing the HQED based on the DPSIR (Driver-Pressure-State-Impact-Response) model. We also establish a system dynamics model and adopt Vensim PLE x64 software to simulate the impact of dynamic changes on HQED, which include innovation, coordination, green, openness, sharing systems, and their combinations. The results show that increasing green investment is the most effective, followed by enhancing regional coordination, enhancing foreign trade, and improving human capital. Among the studied factors, improving livelihood is the weakest. For multiple policy scenarios, the balanced scenario is the most efficient, followed by the environment-oriented, and the weakest is the openness-oriented scenario. Interestingly, combined policies are also more effective than single policies, which does not always apply. Furthermore, the effect of the policy combination is more obvious with the strengthening of the implementation intensity, which is important for policymakers. [ABSTRACT FROM AUTHOR]

The normative framework is one of the constitutive edges of state regulation of religion. It contributes to the configuration of different forms of relations between state and religions. This can be observed in at least three areas. First, in the way the state defines religion. Second, in the way it recognises and legislates its relationship with different religions. Finally, in the rules it establishes for confessional institutions and actors at different levels of social life (education, health, prisons, etc.). In this article, we propose to comparatively analyse the national legal systems that regulate religion in Italy and Argentina, with special emphasis on the equal or differentiated treatment of different religions. The policies of recognition and integration of religious minorities find in the normative framework an empowering or limiting factor, depending on the national context. Although both countries share a dominant Catholic matrix, their historical developments and legal formats present contrasts that project different scenarios of religious governance, which we will try to elucidate. [ABSTRACT FROM AUTHOR]

Phaseolotoxin is an antimetabolite toxin produced by diverse pathovars of Pseudomonas syringae which affects various plants, causing diseases of economic importance. Phaseolotoxin contributes to the systemic dissemination of the pathogen in the plant, therefore it is recognized as a major virulence factor. Genetic traits such as the Pht cluster, appear defining to the toxigenic strains phaseolotoxin producers. Extensive research has contributed to our knowledge concerning the regulation of phaseolotoxin revealing a complex regulatory network that involves processes at the transcriptional and posttranscriptional levels, in which specific and global regulators participate. Even more, significant advances in understanding how specific signals, including host metabolites, nutrient sources, and physical parameters such as the temperature, can affect phaseolotoxin production have been made. A general overview of the phaseolotoxin regulation, focusing on the chemical and physical cues, and regulatory pathways involved in the expression of this major virulence factor will be given in the present work. [ABSTRACT FROM AUTHOR]

This paper examines the regulatory impact on the European Banking Sector using advanced deep learning techniques to analyze the relationship between Sustainable Finance guidelines and the SX7P Index from January 2012 to December 2023. Utilizing Long Short-Term Memory Auto-encoder (LSTM-AE), Variational Autoencoder (VAE), and Convolutional Neural Network (CNN) for anomaly detection, the study compares anomalies and investigates their correlation with European Banking Authority (EBA) events and Sustainable Finance guidelines from January 2020 to December 2023. Through the analysis of 43 pertinent EBA documents, the research identifies patterns and variations in anomalies, assessing their association with regulatory changes. The results reveal significant anomalies aligning with regulatory events, indicating a potential causal relationship. Notably, the VAE methodology shows the strongest correlation between EBA Sustainable Finance events and anomalies. This research advances the understanding of deep learning applications in financial markets and offers valuable insights for policymakers and financial institutions regarding regulatory shifts in Sustainable Finance. [ABSTRACT FROM AUTHOR]

There is a growing interest in the use of pyrolysis plants for the conversion of solid waste into useful products (e.g., oil, gas, and char) and the analysis of air-polluting emissions associated with such a process is an emerging research field. This study applied a systematic mapping approach to collating, describing, and cataloging available evidence related to the type and level of air pollutants emitted from pyrolysis plants, the factors affecting emissions, and available mitigation strategies that can be adopted to reduce air pollution. The scientific literature indexed in Scopus and Google Scholar, as well as available industry reports, was interrogated to document the evidence. A database comprising 63 studies was synthesized and cataloged from which 25 air pollutants from pyrolysis plants were considered, including volatile organic compounds and persistent organic pollutants. Air pollutant levels varied depending on the scale of the pyrolysis plants, their operating conditions, and the feedstock used. Various technologies, such as wet scrubbers, electrostatic precipitators, and baghouse filters, are available and have been utilized to reduce emissions and comply with the existing EU regulations for waste incineration (2010/75/EU). The systematic mapping identified several knowledge gaps that need to be addressed to inform relevant environmental policymaking, technology development, and the adoption of best practices for the mitigation of emissions from pyrolysis plants. [ABSTRACT FROM AUTHOR]

The flavonoids in citrus fruits are crucial physiological regulators and natural bioactive products of high pharmaceutical value. Melatonin is a pleiotropic hormone that can regulate plant morphogenesis and stress resistance and alter the accumulation of flavonoids in these processes. However, the direct effect of melatonin on citrus flavonoids remains unclear. In this study, nontargeted metabolomics and transcriptomics were utilized to reveal how exogenous melatonin affects flavonoid biosynthesis in "Bingtangcheng" citrus fruits. The melatonin treatment at 0.1 mmol L−1 significantly increased the contents of seven polymethoxylated flavones (PMFs) and up-regulated a series of flavonoid pathway genes, including 4CL (4-coumaroyl CoA ligase), FNS (flavone synthase), and FHs (flavonoid hydroxylases). Meanwhile, CHS (chalcone synthase) was down-regulated, causing a decrease in the content of most flavonoid glycosides. Pearson correlation analysis obtained 21 transcription factors co-expressed with differentially accumulated flavonoids, among which the AP2/EREBP members were the most numerous. Additionally, circadian rhythm and photosynthesis pathways were enriched in the DEG (differentially expressed gene) analysis, suggesting that melatonin might also mediate changes in the flavonoid biosynthesis pathway by affecting the fruit's circadian rhythm. These results provide valuable information for further exploration of the molecular mechanisms through which melatonin regulates citrus fruit metabolism. [ABSTRACT FROM AUTHOR]

Understanding the oceanic carbon cycle, particularly in the Arctic regions, is crucial for addressing climate change. However, significant research gaps persist, especially regarding climate effects on the oceanic carbon cycle in these regions. This review systematically explores Arctic-related research, focusing on mechanisms, regulatory frameworks, and modelling approaches in the oceanic carbon cycle, carbon sink, climate change impact, and maritime shipping. The findings highlight the Arctic's limited observer presence and high operational costs, hindering the data availability and studies on carbon-cycle changes. This underscores the need to integrate real-time Arctic Ocean monitoring data. Carbon sink research urgently requires direct methods to measure anthropogenic carbon uptake and address uncertainties in air–ocean carbon fluxes due to sea ice melting. Unlike terrestrial carbon cycling research, carbon-cycle studies in the oceans, which are essential for absorbing anthropogenic emissions, receive insufficient attention, especially in the Arctic regions. Numerous policies often fall short in achieving effective mitigation, frequently depending on voluntary or market-based approaches. Analyzing carbon-cycle and sink models has uncovered limitations, primarily due to their global perspective, hampering in-depth assessments of climate change effects on the Arctic regions. To pave the way for future research, enhancing Arctic Ocean climate data availability is recommended, as well as fostering international cooperation in carbon-cycle research, enforcing carbon policies, and improving regional modelling in the Arctic Ocean. [ABSTRACT FROM AUTHOR]

Inflammasomes contribute to colorectal cancer signaling by primarily inducing inflammation in the surrounding tumor microenvironment. Its role in inflammation is receiving increasing attention, as inflammation has a protumor effect in addition to inducing tissue damage. The inflammasome's function is complex and controlled by several layers of regulation. Epigenetic processes impact the functioning or manifestation of genes that are involved in the control of inflammasomes or the subsequent signaling cascades. Researchers have intensively studied the significance of epigenetic mechanisms in regulation, as they encompass several potential therapeutic targets. The regulatory interactions between the inflammasome and autophagy are intricate, exhibiting both advantageous and harmful consequences. The regulatory aspects between the two entities also encompass several therapeutic targets. The relationship between the activation of the inflammasome, autophagy, and epigenetic alterations in CRC is complex and involves several interrelated pathways. This article provides a brief summary of the newest studies on how epigenetics and autophagy control the inflammasome, with a special focus on their role in colorectal cancer. Based on the latest findings, we also provide an overview of the latest therapeutic ideas for this complex network. [ABSTRACT FROM AUTHOR]

Vibrio fluvialis is an emerging foodborne pathogenic bacterium that can cause severe cholera-like diarrhea and various extraintestinal infections, posing challenges to public health and food safety worldwide. The arginine deiminase (ADI) pathway plays an important role in bacterial environmental adaptation and pathogenicity. However, the biological functions and regulatory mechanisms of the pathway in V. fluvialis remain unclear. In this study, we demonstrate that L-arginine upregulates the expression of the ADI gene cluster and promotes the growth of V. fluvialis. The ADI gene cluster, which we proved to be comprised of two operons, arcD and arcACB, significantly enhances the survival of V. fluvialis in acidic environments both in vitro (in culture medium and in macrophage) and in vivo (in mice). The mRNA level and reporter gene fusion analyses revealed that ArgR, a transcriptional factor, is necessary for the activation of both arcD and arcACB transcriptions. Bioinformatic analysis predicted the existence of multiple potential ArgR binding sites at the arcD and arcACB promoter regions that were further confirmed by electrophoretic mobility shift assay, DNase I footprinting, or point mutation analyses. Together, our study provides insights into the important role of the ArgR-ADI pathway in the survival of V. fluvialis under acidic conditions and the detailed molecular mechanism. These findings will deepen our understanding of how environmental changes and gene expression interact to facilitate bacterial adaptations and virulence. [ABSTRACT FROM AUTHOR]

This paper analyses sexual crimes within the Metaverse to develop an effective legal framework. The aim is to enhance safety in virtual realities, ensuring the Metaverse remains a secure, respectful, and liberating environment for all users. As the Metaverse continues to evolve, merging augmented physical reality with digital existence, it introduces new opportunities for socialisation, commerce, education, and entertainment. However, this digital realm also faces significant challenges, particularly the increase in sexual violence. This article evaluates the development of the Metaverse and its impact on sexual offences. It provides an overview of the Metaverse, followed by an in-depth exploration of the nature of sexual violence in this virtual space, its effects on victims, and the resulting legal and ethical issues. Additionally, this article examines the complexities of combating sexual violence within the Metaverse, reviewing the legal frameworks in various jurisdictions, including the United States, the European Union, the United Kingdom, and South Korea. These examinations reveal a range of legal viewpoints and possible solutions. This article outlines a proposed legal framework, highlighting key strategic areas for mitigating sexual violence in the Metaverse. The primary objective is to enrich the discourse on the Metaverse, pushing for strong, flexible, and holistic legal measures. Through this research, we aim to contribute to the creation of protective mechanisms against sexual violence in these emerging virtual landscapes. [ABSTRACT FROM AUTHOR]

Sigma factors are transcriptional regulators that are part of complex regulatory networks for major cellular processes, as well as for growth phase-dependent regulation and stress response. Actinoplanes sp. SE50/110 is the natural producer of acarbose, an α-glucosidase inhibitor that is used in diabetes type 2 treatment. Acarbose biosynthesis is dependent on growth, making sigma factor engineering a promising tool for metabolic engineering. ACSP50_0507 is a homolog of the developmental and osmotic-stress-regulating Streptomyces coelicolor σHSc. Therefore, the protein encoded by ACSP50_0507 was named σHAs. Here, an Actinoplanes sp. SE50/110 expression strain for the alternative sigma factor gene ACSP50_0507 (sigHAs) achieved a two-fold increased acarbose yield with acarbose production extending into the stationary growth phase. Transcriptome sequencing revealed upregulation of acarbose biosynthesis genes during growth and at the late stationary growth phase. Genes that are transcriptionally activated by σHAs frequently code for secreted or membrane-associated proteins. This is also mirrored by the severely affected cell morphology, with hyperbranching, deformed and compartmentalized hyphae. The dehydrated cell morphology and upregulation of further genes point to a putative involvement in osmotic stress response, similar to its S. coelicolor homolog. The DNA-binding motif of σHAs was determined based on transcriptome sequencing data and shows high motif similarity to that of its homolog. The motif was confirmed by in vitro binding of recombinantly expressed σHAs to the upstream sequence of a strongly upregulated gene. Autoregulation of σHAs was observed, and binding to its own gene promoter region was also confirmed. [ABSTRACT FROM AUTHOR]

Global support and standardization of regulation for biosimilars approval owes much of its legacy to the World Health Organization (WHO), since the first guidance by the organization on the matter was released in 2009. Since then, and with over a decade of research, the 2022 revision provides opportunities for time and financial savings to pharmaceutical manufacturers aiming to prove similarity of a potential biosimilar product to some reference product, particularly by clarifying that the use of a non-local reference product as a comparator in certain studies is permissible. This declaration has important implications, particularly in the emerging biological markets of the Middle East and North Africa region, where WHO guidelines have been integral to the regulatory framework of over a dozen countries for more than a decade. This article aims to review the impact of this revision on these countries and relevant policies on non-local comparator usage. Since 2022, this revision has been adopted only in Egypt. Many North African countries are yet to adopt a first draft of the formalized guidance. This analysis revealed that, although many of these countries reference the WHO guidelines, hesitation remains in terms of sourcing comparator products outside the US or European countries. This likely translates to slow regional development and cooperation of functioning, sustainable biosimilars markets. Future studies will be necessary to evaluate the continued development of guidance within these countries and changes in comparator sourcing norms as more time is allowed for their policies to mature and adapt to new standards. [ABSTRACT FROM AUTHOR]

Growing high-quality crystals with ideal properties is of great importance. The morphology of crystal is one key factor reflecting product quality, as it can affect the performance of products and downstream operations. In this work, the current state of crystal morphology modification is reviewed from different perspectives. First, the most widely used crystal growth models are discussed. Then, a variety of crystal morphology control methods, which include adjustment of crystallization operation parameters, addition of foreign molecules, change of different solvents, membrane assistance, the addition of external physical fields and the use of ball milling are summarized. As for applications, the control of crystal morphology has application potential in pharmaceutical and material fields, for example, energetic materials and semiconductor materials. Finally, the future development direction of crystal morphology regulation is discussed. [ABSTRACT FROM AUTHOR]

This article is devoted to the problem of signal decomposition into periodic and aperiodic components. According to the proposed approach, there is no need to evaluate the aperiodic component as a difference between the total signal of its periodic components. This research aims to create a general analytical approach that combines the Fourier and Maclaurin series methodologies into a single comprehensive series. As a result, analytical expressions for determining deposition coefficients were established for an aperiodic signal with a monoharmonic overlay. Recurrence relations were established to determine the coefficients of this series. These relations allow direct integrations of the obtained values of integrals to be avoided. The evaluated numerical values of the coefficients are also presented graphically and tabulated. It was proven that the values of these coefficients are universal numbers since they do not depend on the period/frequency of oscillations. The reliability of the proposed approach was confirmed by the fact that the evaluated coefficients are equal to the Fourier series coefficients in the case of a periodic signal. Also, for an aperiodic signal, these coefficients were reduced to the coefficients of the Maclaurin series. The usability of the proposed generalized analytical approach for signal decomposition is for control and monitoring systems of processes. [ABSTRACT FROM AUTHOR]

3D printing has been adopted into routine use for certain medical applications, but more widespread usage has been hindered by, among other things, unclear legislation. We performed an analysis, using legal doctrinal study and legal informatics, of relevant EU legislation and case law in four issues relevant to medical 3D printing (excluding bioprinting or pharmacoprinting): pre-market approval, post-market liability, intellectual property rights, and data protection. Several gaps and uncertainties in the current legislation and interpretations were identified. In particular, we regard the current EU regulatory framework to be quite limiting and inflexible, exemplifying a cautionary approach common in EU law. Though the need to establish high safety standards in order to protect patients as a disadvantaged population is understood, both legal uncertainties and overregulation are seen as harmful to innovation. Hence, more adaptive legislation is called for to ensure continuous innovation efforts and enhanced patient outcomes. [ABSTRACT FROM AUTHOR]

Dendrobium nobile is an important orchid plant that has been used as a traditional herb for many years. For the further pharmaceutical development of this resource, a combined transcriptome and metabolome analysis was performed in different parts of D. nobile. First, saccharides, organic acids, amino acids and their derivatives, and alkaloids were the main substances identified in D. nobile. Amino acids and their derivatives and flavonoids accumulated strongly in flowers; saccharides and phenols accumulated strongly in flowers and fruits; alkaloids accumulated strongly in leaves and flowers; and a nucleotide and its derivatives and organic acids accumulated strongly in leaves, flowers, and fruits. Simultaneously, genes for lipid metabolism, terpenoid biosynthesis, and alkaloid biosynthesis were highly expressed in the flowers; genes for phenylpropanoids biosynthesis and flavonoid biosynthesis were highly expressed in the roots; and genes for other metabolisms were highly expressed in the leaves. Furthermore, different members of metabolic enzyme families like cytochrome P450 and 4-coumarate-coA ligase showed differential effects on tissue-specific metabolic accumulation. Members of transcription factor families like AP2-EREBP, bHLH, NAC, MADS, and MYB participated widely in differential accumulation. ATP-binding cassette transporters and some other transporters also showed positive effects on tissue-specific metabolic accumulation. These results systematically elucidated the molecular mechanism of differential accumulation in different parts of D. nobile and enriched the library of specialized metabolic products and promising candidate genes. [ABSTRACT FROM AUTHOR]

The additional sex combs-like (ASXL) family, a mammalian homolog of the additional sex combs (Asx) of Drosophila, has been implicated in transcriptional regulation via chromatin modifications. Abnormal expression of ASXL family genes leads to myelodysplastic syndromes and various types of leukemia. De novo mutation of these genes also causes developmental disorders. Genes in this family and their neighbor genes are evolutionary conserved in humans and mice. This review provides a comprehensive summary of epigenetic regulations associated with ASXL family genes. Their expression is commonly regulated by DNA methylation at CpG islands preceding transcription starting sites. Their proteins primarily engage in histone tail modifications through interactions with chromatin regulators (PRC2, TrxG, PR-DUB, SRC1, HP1α, and BET proteins) and with transcription factors, including nuclear hormone receptors (RAR, PPAR, ER, and LXR). Histone modifications associated with these factors include histone H3K9 acetylation and methylation, H3K4 methylation, H3K27 methylation, and H2AK119 deubiquitination. Recently, non-coding RNAs have been identified following mutations in the ASXL1 or ASXL3 gene, along with circular ASXLs and microRNAs that regulate ASXL1 expression. The diverse epigenetic regulations linked to ASXL family genes collectively contribute to tumor suppression and developmental processes. Our understanding of ASXL-regulated epigenetics may provide insights into the development of therapeutic epigenetic drugs. [ABSTRACT FROM AUTHOR]

In this narrative, comprehensive, and updated review of the literature, we summarize evidence about the effectiveness of interventions aimed at reducing emotion dysregulation and improving emotion regulation in children, adolescents, and adults. After introducing emotion dysregulation and emotion regulation from a theoretical standpoint, we discuss the factors commonly associated with emotion regulation, including neurobiological and neuropsychological mechanisms, and the role of childhood adverse experiences and psycho–social factors in the onset of emotion dysregulation. We then present evidence about pharmacological and non-pharmacological interventions aiming at improving emotion dysregulation and promoting emotion regulation across the lifespan. Although our review was not intended as a traditional systematic review, and the search was only restricted to systematic reviews and meta-analyses, we highlighted important implications and provided recommendations for clinical practice and future research in this field. [ABSTRACT FROM AUTHOR]

Organic anion transporter 3 (OAT3), expressed at the basolateral membrane of kidney proximal tubule cells, facilitates the elimination of numerous metabolites, environmental toxins, and clinically important drugs. An earlier investigation from our laboratory revealed that OAT3 expression and transport activity can be upregulated by SUMOylation, a post-translational modification that covalently conjugates SUMO molecules to substrate proteins. Topotecan is a semi-synthetic derivative of the herbal extract camptothecin, approved by the FDA to treat several types of cancer. Ginkgolic acid (GA) is one of the major components in the extract of Ginkgo biloba leaves that has long been used in food supplements for preventing dementia, high blood pressure, and supporting stroke recovery. Both topotecan and GA have been shown to affect protein SUMOylation. In the current study, we tested our hypothesis that topotecan and GA may regulate OAT3 SUMOylation, expression, and transport function. Our data show that the treatment of OAT3-expressing cells with topotecan or GA significantly decreases the SUMOylation of OAT3 by 50% and 75%, respectively. The same treatment also led to substantial reductions in OAT3 expression and the OAT3-mediated transport of estrone sulfate, a prototypical substrate. Such reductions in cell surface expression of OAT3 correlated well with an increased rate of OAT3 degradation. Mechanistically, we discovered that topotecan enhanced the association between OAT3 and the SUMO-specific protease SENP2, a deSUMOylation enzyme, which contributed to the significant decrease in OAT3 SUMOylation. In conclusion, this study unveiled a novel role of topotecan and GA in inhibiting OAT3 expression and transport activity and accelerating OAT3 degradation by suppressing OAT3 SUMOylation. During comorbidity therapies, the use of topotecan or Ginkgo biloba extract could potentially decrease the transport activity of OAT3 in the kidneys, which will in turn affect the therapeutic efficacy and toxicity of many other drugs that are substrates for the transporter. [ABSTRACT FROM AUTHOR]

Anthocyanins are water-soluble flavonoid pigments that play a crucial role in plant growth and metabolism. They serve as attractants for animals by providing plants with red, blue, and purple pigments, facilitating pollination and seed dispersal. The fruits of solanaceous plants, tomato (Solanum lycopersicum) and eggplant (Solanum melongena), primarily accumulate anthocyanins in the fruit peels, while the ripe fruits of Atropa belladonna (Ab) have a dark purple flesh due to anthocyanin accumulation. In this study, an R2R3-MYB transcription factor (TF), AbMYB1, was identified through association analysis of gene expression and anthocyanin accumulation in different tissues of A. belladonna. Its role in regulating anthocyanin biosynthesis was investigated through gene overexpression and RNA interference (RNAi). Overexpression of AbMYB1 significantly enhanced the expression of anthocyanin biosynthesis genes, such as AbF3H, AbF3′5′H, AbDFR, AbANS, and Ab3GT, leading to increased anthocyanin production. Conversely, RNAi-mediated suppression of AbMYB1 resulted in decreased expression of most anthocyanin biosynthesis genes, as well as reduced anthocyanin contents in A. belladonna. Overall, AbMYB1 was identified as a fruit-expressed R2R3-MYB TF that positively regulated anthocyanin biosynthesis in A. belladonna. This study provides valuable insights into the regulation of anthocyanin biosynthesis in Solanaceae plants, laying the foundation for understanding anthocyanin accumulation especially in the whole fruits of solanaceous plants. [ABSTRACT FROM AUTHOR]

Light regulation is critical in fungal growth, development, morphogenesis, secondary metabolism, and the biological clock. The fungus Elsinoë arachidis is known to produce the mycotoxin Elsinochrome (ESC), a key factor contributing to its pathogenicity, under light conditions. Although previous studies have predominantly focused on the light-induced production of ESC and its biosynthetic pathways, the detailed mechanisms underlying this process remain largely unexplored. This study explores the influence of light on ESC production and gene expression in E. arachidis. Under white light exposure for 28 days, the ESC yield was observed to reach 33.22 nmol/plug. Through transcriptome analysis, 5925 genes were identified as differentially expressed between dark and white light conditions, highlighting the significant impact of light on gene expression. Bioinformatics identified specific light-regulated genes, including eight photoreceptor genes, five global regulatory factors, and a cluster of 12 genes directly involved in the ESC biosynthesis, with expression trends confirmed by RT-qPCR. In conclusion, the study reveals the substantial alteration in gene expression associated with ESC biosynthesis under white light and identifies potential candidates for in-depth functional analysis. These findings advance understanding of ESC biosynthesis regulation and suggest new strategies for fungal pathogenicity control. [ABSTRACT FROM AUTHOR]

mRNA-lipid nanoparticle (LNP) medicinal products can be considered a platform technology because the development process is similar for different diseases and conditions, with similar noncoding mRNA sequences and lipid nanoparticles and essentially unchanged manufacturing and analytical methods often utilised for different products. It is critical not to lose the momentum built using the platform approach during the development, regulatory approval and rollout of vaccines for SARS-CoV-2 and its variants. This review proposes a set of modifications to existing regulatory requirements for mRNA products, based on a platform perspective for quality, manufacturing, preclinical, and clinical data. For the first time, we address development and potential regulatory requirements when the mRNA sequences and LNP composition vary in different products as well. In addition, we propose considerations for self-amplifying mRNA, individualised oncology mRNA products, and mRNA therapeutics. Providing a predictable development pathway for academic and commercial groups so that they can know in detail what product characterisation and data are required to develop a dossier for regulatory submission has many potential benefits. These include: reduced development and regulatory costs; faster consumer/patient access and more agile development of products in the face of pandemics; and for rare diseases where alternatives may not exist or to increase survival and the quality of life in cancer patients. Therefore, achieving consensus around platform approaches is both urgent and important. This approach with mRNA can be a template for similar platform frameworks for other therapeutics and vaccines to enable more efficient development and regulatory review. [ABSTRACT FROM AUTHOR]

Cyanogenic glucosides are specialized metabolites produced by over 3000 species of higher plants from more than 130 families. The deployment of cyanogenic glucosides is influenced by biotic and abiotic factors in addition to being developmentally regulated, consistent with their roles in plant defense and stress mitigation. Despite their ubiquity, very little is known regarding the molecular mechanisms that regulate their biosynthesis. The biosynthetic pathway of dhurrin, the cyanogenic glucoside found in the important cereal crop sorghum (Sorghum bicolor (L.) Moench), was described over 20 years ago, and yet no direct regulator of the biosynthetic genes has been identified. To isolate regulatory proteins that bind to the promoter region of the key dhurrin biosynthetic gene of sorghum, SbCYP79A1, yeast one-hybrid screens were performed. A bait fragment containing 1204 base pairs of the SbCYP79A1 5′ regulatory region was cloned upstream of a reporter gene and introduced into Saccharomyces cerevisiae. Subsequently, the yeast was transformed with library cDNA representing RNA from two different sorghum developmental stages. From these screens, we identified SbGATA22, an LLM domain B-GATA transcription factor that binds to the putative GATA transcription factor binding motifs in the SbCYP79A1 promoter region. Transient assays in Nicotiana benthamiana show that SbGATA22 localizes to the nucleus. The expression of SbGATA22, in comparison with SbCYP79A1 expression and dhurrin concentration, was analyzed over 14 days of sorghum development and in response to nitrogen application, as these conditions are known to affect dhurrin levels. Collectively, these findings suggest that SbGATA22 may act as a negative regulator of SbCYP79A1 expression and provide a preliminary insight into the molecular regulation of dhurrin biosynthesis in sorghum. [ABSTRACT FROM AUTHOR]

The monoamine transporters, including the serotonin transporter (SERT), dopamine transporter (DAT), and norepinephrine transporter (NET), are the therapeutic targets for the treatment of many neuropsychiatric disorders. Despite significant progress in characterizing the structures and transport mechanisms of these transporters, the regulation of their transport functions through dimerization or oligomerization remains to be understood. In the present study, we identified a conserved intramolecular ion-pair at the third extracellular loop (EL3) connecting TM5 and TM6 that plays a critical but divergent role in the modulation of dimerization and transport functions among the monoamine transporters. The disruption of the ion-pair interactions by mutations induced a significant spontaneous cross-linking of a cysteine mutant of SERT and an increase in cell surface expression but with an impaired specific transport activity. On the other hand, similar mutations of the corresponding ion-pair residues in both DAT and NET resulted in an opposite effect on their oxidation-induced dimerization, cell surface expression, and transport function. Reversible biotinylation experiments indicated that the ion-pair mutations slowed down the internalization of SERT but stimulated the internalization of DAT. In addition, cysteine accessibility measurements for monitoring SERT conformational changes indicated that substitution of the ion-pair residues resulted in profound effects on the rate constants for cysteine modification in both the extracellular and cytoplasmatic substrate permeation pathways. Furthermore, molecular dynamics simulations showed that the ion-pair mutations increased the interfacial interactions in a SERT dimer but decreased it in a DAT dimer. Taken together, we propose that the transport function is modulated by the equilibrium between monomers and dimers on the cell surface, which is regulated by a potential compensatory mechanism but with different molecular solutions among the monoamine transporters. The present study provided new insights into the structural elements regulating the transport function of the monoamine transporters through their dimerization. [ABSTRACT FROM AUTHOR]

The high level of regulation of innovative drugs on the market, which is necessary to protect consumers, produces important effects on drug availability and innovation. In public healthcare systems, the need to curb prices comes from expenditure considerations. The aim of price regulation is to obtain a more equitable allocation of the value of an innovative drug between industries and patients (by reducing prices to make drugs more affordable), but it may also reduce access. (In the listing process, the industry may find it more convenient to limit commercialisation to profitable subgroups of patients.) Furthermore, with the advent of personalised medicine, there is another important dimension that has to be considered, namely, incentives to invest in drug personalisation. In this paper, we review and discuss the impact of different pricing rules on the expenditure and availability of new drugs. [ABSTRACT FROM AUTHOR]

Iron is an essential nutrient for growth among all branches of life, but while iron is among the most common elements, bioavailable iron is a relatively scarce nutrient. Since iron is fundamental for several biological processes, iron deficiency can be deleterious. On the other hand, excess iron may lead to cell and tissue damage. Consequently, iron balance is strictly regulated. As iron excretion is not physiologically controlled, systemic iron homeostasis is maintained at the level of absorption, which is mainly influenced by the amount of iron stores and the level of erythropoietic activity, the major iron consumer. Here, we outline recent advances that increased our understanding of the molecular aspects of iron absorption. Moreover, we examine the impact of these recent insights on dietary strategies for maintaining iron balance. [ABSTRACT FROM AUTHOR]

In this article, an analytical solution to a hydraulic network with a wide range of pipe lengths (up to 10 km) is proposed. The Finite-Difference Time-Domain (FDTD) method was applied with the aim of creating a regulation model for controlling both the flow rate of water from one of the two sources and the discharge pressure in the system. The system inertia requires an understanding of boundary conditions in the operation of pipeline networks, which must be known in order to regulate the required parameters with only minor deviations. The proposed model was compared to experimental data, while the mean absolute deviations in the individual system branches ranged from 1 to 5.19%. The created regulation model was subsequently tested by applying linear, sine and stochastic changes in the output load, while the ability to control the discharge pressure and the selected water flow rate was analysed. The effect of coefficient ε, which multiplies the effect of the difference between the measured and the predicted value of the discharge pressure on the boundary conditions of the discharge pressure in the system, was analysed in this paper. With the use of the proposed unsteady simulation of the fluid flow in the hydraulic system arranged in parallel and in series, the maximum deviation of the regulated pressure was 1.2% and the maximum deviation of the regulated flow rate was 5.3%. [ABSTRACT FROM AUTHOR]

Shared kitchens, where users share kitchen space, are becoming popular worldwide due to the economic cost savings of startup businesses. This study conducted monitoring of microbial and chemical hazards from prepared foods and the environment of shared kitchen facilities, surveyed shared kitchen operators, and compared shared kitchen regulations between Korea and other countries. The monitoring results indicate that the hygiene status of the facilities and the microbial and chemical hazards in the prepared foods were all within the standard specifications, showing significantly lower levels compared to regular restaurants (p < 0.05). In particular, concurrent-use and time-division types of open shared kitchens showed significantly lower levels of both hazards than separated-individual kitchens. Survey results of hygiene inspection also confirmed better hygiene management in concurrent-use and time-division types of open shared kitchens in Korea. However, more frequent cleaning and disinfection, hygiene inspections, and training are high economic burdens in the operation of shared kitchens compared to regular restaurants. Moreover, mandatory insurance subscriptions, the operator’s responsibility in hygiene-related incidents, and high operational costs collectively challenge shared kitchens’ competitiveness in the food service market. Critical reassessments of regulations utilizing the benefits of shared kitchens are needed to promote a safe dining culture and the growth of shared kitchen startup businesses. [ABSTRACT FROM AUTHOR]

The low-carbon cooperation between providers and demanders is one of the ways to achieve sustainable development in cloud manufacturing, which has become an important issue. However, the effective ways for the cloud platform to encourage such cooperation are unclear. Considering the low-carbon strategies of the supply and demand sides and the regulation of the cloud platform, an evolutionary game model involving service providers, service demanders, and the cloud platform is established, and the tripartite evolutionary stability is discussed. Further, the impacts of important factors, such as regulatory costs, on the tripartite strategies are analyzed through numerical simulation. The results illustrate that the cloud platform reasonably optimizes the rewards and penalties for low-carbon cooperation to promote the enthusiastic participation of service providers and demanders. The cloud platform can set penalties (rewards) for providers based on their low-carbon costs and rewards (penalties). Additionally, the low-carbon costs of service providers and the additional costs of demanders negatively affect the low-carbon cooperation between providers and demanders. Meanwhile, the low-carbon costs and additional costs for the providers and demanders to engage in low-carbon cooperation are affected by the rewards and penalties of the cloud platform. The results could provide insights into the game decisions of the supply and demand sides and the cloud platform, facilitating sustainable supply chain advancement. [ABSTRACT FROM AUTHOR]

Cisplatin (CDDP) stands out as an effective chemotherapeutic agent; however, its application is linked to the development of significant adverse effects, notably nephro- and ototoxicity. The human organic cation transporter 2 (hOCT2), found in abundance in the basolateral membrane domain of renal proximal tubules and the Corti organ, plays a crucial role in the initiation of nephro- and ototoxicity associated with CDDP by facilitating its uptake in kidney and ear cells. Given its limited presence in cancer cells, hOCT2 emerges as a potential druggable target for mitigating unwanted toxicities associated with CDDP. Potential strategies for mitigating CDDP toxicities include competing with the uptake of CDDP by hOCT2 or inhibiting hOCT2 activity through rapid regulation mediated by specific signaling pathways. This study investigated the interaction between the already approved cationic drugs disopyramide, imipramine, and orphenadrine with hOCT2 that is stably expressed in human embryonic kidney cells. Regarding disopyramide, its influence on CDDP cellular transport by hOCT2 was further characterized through inductively coupled plasma isotope dilution mass spectrometry. Additionally, its potential protective effects against cellular toxicity induced by CDDP were assessed using a cytotoxicity test. Given that hOCT2 is typically expressed in the basolateral membrane of polarized cells, with specific regulatory mechanisms, this work studied the regulation of hOCT2 that is stably expressed in Madin–Darby Canine Kidney (MDCK) cells. These cells were cultured in a matrix to induce the formation of cysts, exposing hOCT2 in the basolateral plasma membrane domain, which was freely accessible to experimental solutions. The study specifically tested the regulation of ASP+ uptake by hOCT2 in MDCK cysts through the inhibition of casein kinase II (CKII), calmodulin, or p56lck tyrosine kinase. Furthermore, the impact of this manipulation on the cellular toxicity induced by CDDP was examined using a cytotoxicity test. All three drugs—disopyramide, imipramine, and orphenadrine—demonstrated inhibition of ASP+ uptake, with IC50 values in the micromolar (µM) range. Notably, disopyramide produced a significant reduction in the CDDP cellular toxicity and platinum cellular accumulation when co-incubated with CDDP. The activity of hOCT2 in MDCK cysts experienced a significant down-regulation under inhibition of CKII, calmodulin, or p56lck tyrosine kinase. Interestingly, only the inhibition of p56lck tyrosine kinase demonstrated the capability to protect the cells against CDDP toxicity. In conclusion, certain interventions targeting hOCT2 have demonstrated the ability to reduce CDDP cytotoxicity, at least in vitro. Further investigations in in vivo systems are warranted to ascertain their potential applicability as co-treatments for mitigating undesired toxicities associated with CDDP in patients. [ABSTRACT FROM AUTHOR]

This work presents the design and assessment of four control schemes for the monitoring and regulation of joint trajectories applied in the dynamic model of a SCORBOT-ER V plus robot, which includes the dynamics of the actuators, and the estimation of the friction forces present within the joints. The two classical control strategies calculated torque and PID, and the two advanced control strategies, fuzzy and predictive, are considered. In the latter case, a gravitational compensation stage is incorporated, as well as the inverse models of the motors and the transmissions of belt movement for each joint. Computational tests are performed by applying an external step-type disturbance to the third joint of the robot. Finally, an evaluation of the results obtained is presented through trajectory curves, joint errors, and the three performance indexes residual mean square, residual standard deviation, and index of agreement. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) of the temporomandibular joint (TMJ) occurs spontaneously in humans and various animal species, including horses. In humans, obtaining tissue samples is challenging and clinical symptoms appear late in the disease progression. Therefore, genetically modified, induced, and naturally occurring animal models play a crucial role in understanding the pathogenesis and evaluating potential therapeutic interventions for TMJ OA. Among the naturally occurring models, the equine TMJ OA model is characterized by slow, age-related progression, a wide range of clinical examinations, and imaging modalities that can be performed on horses, as well as easy tissue and synovial fluid collection. The morphological and functional similarities of TMJ structures in both species make the equine model of TMJ OA an excellent opportunity to track disease progression and response to treatment. However, much work remains to be carried out to determine the utility of human TMJ OA biomarkers in horses. Among the main TMJ OA biomarkers, IL-1, IL-6, TGF-β, TNF-α, and PGE2 have been recently investigated in the equine model. However, the majority of biomarkers for cartilage degradation, chondrocyte hypertrophy, angiogenesis, and TMJ overload—as well as any of the main signaling pathways—have not been studied so far. Therefore, it would be advisable to focus further research on equine specimens, considering both mediators and signaling. [ABSTRACT FROM AUTHOR]