Regulatory Processes Research Articles

Comprehensive Predictions of Mef2-Mediated Chromatin Loops, Which May Inhibit Ubx Binding by Blocking Low-Affinity Binding Sites

Gene regulation depends on the interaction between chromatin-associated factors, such as transcription factors (TFs), which promote chromatin loops to ensure tight contact between enhancer and promoter regions. So far, positive interactions that lead to gene activation have been the main focus of research, but regulations related to blocking or inhibiting factor binding are also essential to maintaining a defined cellular status. To understand these interactions in greater detail, I investigated the possibility of the muscle differentiation factor Mef2 to prevent early Hox factor binding, leading to the proper timing of regulatory processes and the activation of differentiation events. My investigations relied on a collection of publicly available genome-wide binding data sets of Mef2 and Ubx (as the Hox factor), Capture-C interactions, and ATAC-seq analysis in Mef2 mutant cells. The analysis indicated that Mef2 can form possible chromatin loops to Ubx-bound regions. These regions contain low-affinity Ubx binding sites, and the chromatin architecture is independent of Mef2’s function. High levels of Ubx may disrupt the loops and allow specific Ubx bindings to regulate defined targets. In summary, my investigations highlight that the use of many publicly available data sets enables computational approaches to make robust predictions and, for the first time, suggest a molecular function of Mef2 as a preventer of Hox binding, indicating that it may act as a timer for muscle differentiation.

Regulation of energy metabolism by non-coding RNAs in livestock species: a review.

The optimisation of livestock production relies on efficient energy metabolism. This review focused on elaborate regulatory processes governed by non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). It explores the complex energy metabolism processes in livestock, elucidating the functions of ncRNAs in the expression of genes and pathways. miRNAs have been identified as significant regulators of glycolysis and glucose metabolism, whereas lncRNAs are known to affect adipogenesis and mitochondrial activity. Moreover, circRNAs have a substantial influence on the regulation of energy. In addition, this is not only enriching non-coding RNA-mediated energy control but also sheds light on possible applications. It is derived from its ability to condense complex molecular systems, thereby offering crucial insights to researchers. Through a comprehensive analysis of the intricate relationship between ncRNAs and energy metabolism, the information of this review provides a valuable framework for the implementation of focused interventions that hold the potential to significantly enhance the efficiency of livestock production.

Fantastic Reality and Playfulness as a Means for Adaptive Emotion Regulation

This study explores the interplay between Fantastic Reality Ability (FRA), assessed using the FRAME scale, and playfulness, measured with the OLIW-S, in relation to cognitive emotion regulation strategies among 298 Israeli adults. Participants completed self-report measures evaluating FRA, playfulness, and emotion regulation processes. Results revealed robust positive associations between FRA and various facets of playfulness, and specific connections to adaptive emotion regulation. Particularly, higher levels of FRA coping and lighthearted playfulness emerged as significant predictors of adaptive emotion regulation, while maladaptive regulation showed associations with lower FRA control and distinct playfulness facets. These findings highlight the potential of cultivating imaginative capabilities and embracing playful approaches to bolster emotional resilience and adaptive coping strategies during challenging circumstances and crises. Practical implications for interventions aimed at enhancing psychological well-being are discussed, emphasizing the integration of FRA and playfulness in developing effective coping strategies.

Preparation of liquid metal/thermoplastic polyurethane composites with enhanced thermal conductivity via rolling regulation

Abstract This work reports a method for preparing liquid metal/thermoplastic polyurethane (LM/TPU) elastic composite materials through melt blending, and enhancing the thermal conductivity of the composites using a rolling regulation process. Through observation of the microstructure of the composite material, it is found that the vane mixer can effectively disperse LM uniformly, which leads to a significant enhancement in thermal conductivity from 0.21 W m−1 K−1 of pure TPU to 2.12 W m−1 K−1 for composite with 50 vol % LM. After rolling regulation, SEM images reveal the formation of interconnected thermal conduction pathways within the composites. The thermal conductivity of the composite material with 30 vol % LM increases from 1.74 W m−1 K−1 to 2.50 W m−1 K−1, which is higher than the pre-regulation thermal conductivity of the composite with 50 vol % LM. Moreover, the thermal conductivity of the composite material with 50 vol % LM increases even further to 3.16 W m−1 K−1. The rheological behavior of the composite further substantiates the establishment of a network configuration after the rolling regulation that facilitates heat transfer. This implies that the melt blending-rolling regulation process can achieve the fabrication of composite materials with high thermal conductivity, offering a reliable strategy for industrial development of flexible thermal conductive materials.

The impact of extended decision times in planning and regulatory processes for energy infrastructure

Effective planning and regulatory processes ensure orderly energy systems. Often, decisions are not made within mandated timeframes and discrete approval processes are infrequent. A given delay may be compounded where multiple approval processes exist in sequence. These factors can negatively affect system costs and, ultimately, consumer welfare. We show that delays have meaningful impacts on electricity prices, system emissions, infrastructure investment and system operating costs. Our numerical simulation of data from Ireland shows that wholesale electricity prices are up to 10% higher and CO2 emissions up to 4% higher, attributable to delays associated with planning and regulatory approvals.

Upskilling the cell therapy manufacturing workforce: design, implementation, and evaluation of a massive open online course.

Cell therapies have gained prominence as a promising therapeutic modality for treating a range of diseases. Despite the recent clinical successes of cell therapy products, very few formal training programs exist for cell therapy manufacturing. To meet the demand for a well-trained workforce, we assembled a team of university researchers and industry professionals to develop an online course on the principles and practice of cell therapy manufacturing. The course covers the basic cell and systems physiology underlying cell therapy products, in addition to explaining end-to-end manufacturing from cell acquisition through to patient treatment, industrialization, and regulatory processes. As of September 2023, >10,000 learners have enrolled in the course, and >90% of respondents to the course exit survey indicated that they were "very likely" or "likely" to recommend the course to a peer. In this article, we discuss our experience in the collaborative design and implementation of the online course as well as lessons learned from quantitative and qualitative student feedback. We believe that this course can serve as a model for how academia and industry can collaborate to create innovative, scalable training programs to meet the demands of the modern biotechnology workforce.NEW & NOTEWORTHY We assembled a team of university researchers and industry professionals to develop an online course on the principles and practice of cell therapy manufacturing. We believe that this course can serve as a model for how academia and industry can collaborate to create innovative, scalable training programs to meet the demands of the modern biotechnology workforce.

Mannose: A Promising Player in Clinical and Biomedical Applications.

Mannose, an isomer of glucose, exhibits a distinct molecular structure with the same formula but a different atom arrangement, contributing to its specific biological functions. Widely distributed in body fluids and tissues, particularly in the nervous system, skin, testes, and retinas, mannose plays a crucial role as a direct precursor for glycoprotein synthesis. Glycoproteins, essential for immune regulation and glycosylation processes, underscore the significance of mannose in these physiological activities. The clinical and biomedical applications of mannose are diverse, encompassing its anti-inflammatory properties, potential to inhibit bacterial infections, role in metabolism regulation, and suggested involvement in alleviating diabetes and obesity. Additionally, mannose shows promise in antitumor effects, immune modulation, and the construction of drug carriers, indicating a broad spectrum of therapeutic potential. The article aims to present a comprehensive review of mannose, focusing on its molecular structure, metabolic pathways, and clinical and biomedical applications, and also to emphasize its status as a promising therapeutic agent.

TaFAR9 and TaFAR10 synergistically regulate fertility conversion of photo-thermo-sensitive genic male sterility lines in wheat by modulating ROS homeostasis

Photo-thermo-sensitive genic male sterility (PTGMS), which exhibits varying fertility levels under different environmental conditions, is a crucial method for heterosis utilization in wheat. However, the mechanisms underlying fertility conversion remain unclear. In the study, three BS type PTGMS lines were analyzed to study fertility conversion characteristics. The results indicated that the fertility conversion occurred during meiosis and was accompanied by an increase in reactive oxygen species (ROS) under a sterile environment. TaFAR9 encoding a novel fatty acyl CoA reductase was identified using transcriptome sequencing. Expression analysis suggested that TaFAR9 was localized in the endoplasmic reticulum (ER), with high expression levels in anthers. Furthermore, the down-regulation of TaFAR9 expression displayed characteristics of male sterility, accompanied by the accumulation of ROS. Cytological analysis revealed abnormal development in the anther and pollen walls of TaFAR9-silenced lines. Additionally, TaFAR9 and TaFAR10 were confirmed to physically interact using molecular docking simulation, yeast two-hybrid, luciferase complementation, and bimolecular fluorescence complementation assays. The reduced expression of TaFAR10 also exhibited male sterility and ROS burst. Moreover, the co-silencing of TaFAR9 and TaFAR10 produced sterility phenotypes that were similar to those observed when silencing TaFAR9 or TaFAR10 individually. Transcriptome analysis suggested that the ROS burst in BSMV: TaFAR9/10 anthers can result in cellular metabolic disorders. These findings indicate that TaFAR9 and TaFAR10 may form heterodimers that synergistically regulate fertility conversion in PTGMS lines by modulating ROS metabolism. And this study offers a fresh insight into the regulatory processes involved in fertility conversion in PTGMS lines.

Rapid and high-throughput identification of thermal-responsive genes based on cDNA-library in Upland Cotton

Severe high temperature (HT) climate significantly impacts cotton quality and yield. Consequently, it is essential to mine thermal-responsive genes and explore the underlying mechanisms of HT response in cotton. In this study, we employed a high-throughput cDNA-library method in conjunction with the ALRS system to screen thermotolerant genes in Upland cotton. As a result, a total of 16,120, 13,216 and 172 effective survival genes were filtered after HT stress exposure (42 °C, 220 rpm) for 48 h, 60 h and 72 h, respectively. Functional annotation and enrichment analysis revealed that 170 common genes were involved in regulatory processes associated with HT stress, and the relevant transcriptome data indicated that the majority of these genes responded to temperature fluctuations. Twenty-one genes were randomly selected for verification, and it was found that these genes could enhance yeast resistance to HT stress. Additionally, we selected mutants of homologous Arabidopsis genes for four candidate genes to validate plant thermotolerance during flowering; the thermotolerances of SALK_201915 and SALK_120540.1 were significantly worse. The results demonstrate that numerous candidate genes identified from the cDNA-library contribute to the highly complex molecular network that governs the response and resistance to HT stress in Upland cotton. The high-throughput heat-screening method utilized in this study was optimized for mining thermotolerant genes including improvement in yeast library construction, screening system, gradient reverse pressure, and sequencing library construction. We hope that this new method can be applied in future studies on stress in cotton and other species.

The role of desired positive affect in depression in daily life

BackgroundEmotion goals (desired affect) have been theorized to play an essential role in a person's emotional experiences, guiding emotion regulation processes toward experiencing desired states. Hence, understanding whether and which emotion goals are associated with reduced negative states is crucial for individuals struggling to regulate these states, such as persons with depression. Using ecological momentary assessment (EMA), we examined the relationship between momentary desired positive affect and subsequent depressive affect in daily life, as well as future depressive symptoms, among individuals with depressive disorders. MethodsA total of 50 female participants with depression reported their momentary desire for high arousal positive (HAP), low arousal positive states (LAP), and depressive affect three times a day for seven days. In addition, participants reported depressive symptoms at both baseline and four weeks after. ResultsMomentary desired LAP moderated the relationship between prior and subsequent depressive affect: the more a person wanted to feel LAP at the prior time point, the weaker the relationship between prior and subsequent depressive affect. LimitationsThe relatively short interval between the EMA and the follow-up measurement of depressive symptoms may have influenced the results. ConclusionsResults elucidated the role of desired affect, particularly desired LAP, in depression in daily life.

Study of the mechanism of fibroblast-like synoviocytes-derived exosomes inducing macrophages M1 polarization and CD8+T cells immune regulation ferroptosis and autophagy in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects the joints. The pathogenesis of RA is complex, involving membrane lipid antioxidant systems, oxidative stress, and lipid peroxidation. In this study, it was found that cysteine dioxygenase 1 (CDO1) is significantly upregulated in RA fibroblast-like synoviocytes (RA-FLS) and that exosomes derived from these RA-FLS deliver CDO1 to promote M1 polarization of macrophages, thus facilitating RA progression. In the immune microenvironment, CD8+T cells play a role in immune regulation by producing cytokines such as interferon gamma (IFNγ) in various diseases. The results of this study suggested that in RA-FLS, CD8+T cells deliver IFNγ, which not only inhibits the viability of RA-FLS but also affects glutathione (GSH) through CDO1, regulating the GPX4 antioxidant signaling pathway to promote ferroptosis and autophagy in cells. It was also discovered that IFNγ enhances the expression of TRI69, ubiquitinates and degrades FSP1, thereby forming a cooperative regulation process of GPX4 and FSP1 in ferroptosis. These findings provide a new direction for the treatment of RA.

Bimodal Photothermal-driven Self-sustained Oscillator Based on MXene Structure

Soft robots capable of autonomous, continuous, fast, and adjustable motion speeds under constant external stimuli have great potential in environmental, industrial, military, and medical fields. Aiming at the difficulties of existing self-oscillators, including small oscillation range, difficulty of achieving non-reciprocal motion, and the slow forward speed of the resulting self-sustained soft robots. In this paper, a sunlight-driven self-oscillator based on MXene is prepared. By employing a bimorph structure and thermal regulation process, the self-oscillator exhibits two distinct oscillation modes: 'elastic' and 'plastic' deformation. These modes can be modulated within the same film by varying the light power. A broader amplitude range (3.6-302.3°, 3.3 times that of the existing studies) is achieved by attaching a load to the film's end to enhance the inertial force of movement. Non-reciprocal motion in both modes and stable oscillations in sunlight are achieved. Finally, a light-driven sailboat model is developed. The sailboat can achieve autonomous light-forward motion with a speed of up to 12.8 body length per minute (2.1 times that of existing studies), with its propulsion mechanism further explained through numerical simulation results. This research provides new strategies for constructing fast and large-amplitude self-oscillators and demonstrates the potential for applications in speed-adjustable autonomous forward devices.

Controversies over second-home development in outdoor recreation landscapes: A Norwegian case

During recent decades, there has been a steady increase in the number of second homes in rural municipalities of Norway. While second-home owners, as part-time residents, significantly contribute economically and socially to their host communities, the development has sparked concerns about the appropriation of natural areas in forests and mountain landscapes, the creation of urbanised enclaves within these areas and the potential challenges to municipal planning capacities and policies due to pressure from landowners, private investors and developers.We highlight three interrelated issues, focusing on opinions and discourses manifest in controversies over second-home development in a popular mountain destination in the southeastern region of Norway. First, we explore to what extent conflicts of interest between various private and public stakeholders arise from irreconcilable ways of engaging with land properties of the landscapes. Second, we analyse the disagreements regarding the allocation of responsibilities between the private and public sectors, which often serve as the foundation for controversies. Third, we examine how these controversies shape stakeholders’ perceptions and expressions of sustainability issues, especially among those with conflicting interests. It is concluded that the development process, increasingly driven by neoliberal public planning and land-use regulations for second-home developments, clashes with the common perceptions of residents and long-time second-home owners, who view the landscape as a collection of indistinct land properties. Landowners, developers and municipalities fail to sufficiently consider this, exacerbating the existing deficiencies in planning and regulatory processes and intensifying the controversies.

Review of penetration and impact of utility solar installation in developing countries: policy and challenges

This review examines the penetration and impact of utility-scale solar installations in developing countries, focusing on the policy landscape and challenges associated with their adoption. Solar energy has emerged as a vital component of the global shift towards renewable energy, offering substantial potential for alleviating energy poverty and fostering sustainable development in regions with abundant solar resources. Despite these opportunities, the penetration of utility-scale solar in developing countries faces several barriers. These include financial constraints, inconsistent policy frameworks, technological challenges, and social acceptance issues. This review explores the current status of solar energy adoption, highlighting regional trends and key countries such as Kenya, India, and South Africa, which have made significant strides in solar deployment. It assesses the economic, social, and environmental impacts of utility solar projects, emphasizing their role in job creation, electrification, and climate change mitigation. However, challenges such as high initial costs, limited access to financing, weak grid infrastructure, and regulatory bottlenecks continue to impede broader adoption. Policy and regulatory support are critical to overcoming these challenges. This review outlines the national and international frameworks that influence solar energy penetration, as well as the incentives, subsidies, and financing mechanisms available. Recommendations include streamlining regulatory processes, improving access to finance through innovative models, and enhancing grid infrastructure. Finally, the review discusses future trends, including advancements in solar technology, energy storage, and smart grid integration, which could accelerate the growth of solar installations in developing countries. The findings underscore the need for comprehensive strategies that address policy, financial, and social challenges to fully realize the potential of solar energy in these regions.

Implementation and Comparison of Coffee Bean Drying Temperature SettingsBased on Fuzzy Logic

This research examines the implementation and measurement of temperature in drying coffee beansusing a fuzzy logic approach. Two main methods, namely the Mamdani Method and the SugenoMethod, were applied and evaluated in this context. Data on temperature, humidity, and water contentof coffee beans are collected during the drying process for use in the implementation of both methods.Implementation is carried out using MATLAB software, with detailed steps for each method. TheMamdani method involves fuzzification processes, inference using fuzzy rules, and defuzzification toobtain concrete values for temperature settings. Meanwhile, the Sugeno Method also involvesfuzzification of input data, but uses a linear fuzzy model for inference, so it does not require adefuzzification stage. The results and discussion of this study highlight the performance differencesbetween the two methods. Evaluation is carried out based on temperature prediction accuracy andenergy efficiency. The Mamdani Method shows good accuracy in predicting temperature, while theSugeno Method highlights efficiency and efficiency in the temperature regulation process. Therefore,this study provides valuable insight into selecting a suitable method for temperature regulation ofcoffee bean dryers

MicroRNA Nobel Prize: Timely Recognition and High Anticipation of Future Products—A Prospective Analysis

MicroRNAs (miRNAs) maintain cellular homeostasis by blocking mRNAs by binding with them to fine-tune the expression of genes across numerous biological pathways. The 2024 Nobel Prize in Medicine and Physiology for discovering miRNAs was long overdue. We anticipate a deluge of research work involving miRNAs to repeat the history of prizes awarded for research on other RNAs. Although miRNA therapies are included for several complex diseases, the realization that miRNAs regulate genes and their roles in addressing therapies for hundreds of diseases are expected; but with advancement in drug discovery tools, we anticipate even faster entry of new drugs. To promote this, we provide details of the current science, logic, intellectual property, formulations, and regulatory process with anticipation that many more researchers will introduce novel therapies based on the discussion and advice provided in this paper.

Deciphering the Interlinked CXCR4-Mediated Feedback Loop Among Signaling Pathways in Diabetic Wound Healing

Abstract: Diabetic chronic wounds and amputations are very serious complications of diabetes mellitus (DM) that result from an integration factor, including oxygen deprivation, elevated reactive oxygen species (ROS), reduced angiogenesis, and microbial invasion. These causative factors lead to tenacious wounds in an inflammatory state, which eventually results in tissue aging and necrosis. Wound healing in DM potentially targets C-X-C chemokine receptor type 4 (CXCR4) regulates several signalling pathways. The CXCR4 signalling pathway integrated with phospholipase C (PLC)/protein kinase-C (PKC) Ca2+ pathways, stromal cell-derived factor-1 (SDF-1), and mitogen- activated protein kinases (MAPKs) pathway for enhancing cell chemotaxis, proliferation, and survival. The dysregulated CXCR4 pathway is connected with poor wound healing in DM patients. Therapeutic strategies targeting CXCR4-based molecules such as UCUF-728, UCUF-965, and AMD3100 have been shown to enhance diabetic wound healing by altering miRNA expression, promoting angiogenesis, and accelerating wound closure. This study indicates that CXCR4 participation in various signalling pathways makes it essential for Understanding the healing of diabetic wounds. Using specific compounds to target CXCR4 offers a potentially effective treatment strategy to improve wound healing in diabetes. Our understanding of CXCR4 signalling and its regulation processes will enable us to develop more potent wound care solutions for diabetic chronic wounds. This report concludes that CXCR4's potential therapeutic targeting shows improvements in diabetic wound repair. This review will demonstrate that CXCR4 plays a major role in wound healing through its various signalling pathways. Targeting CXCR4 with certain agonist molecules shows a therapeutic approach to potentially increasing wound healing in diabetes. By enhancing our understanding of the CXCR4 signalling mechanism in future studies, we can develop more potential treatments for chronic diabetic wounds.

SS31 alleviates LPS-induced acute lung injury by inhibiting inflammatory responses through the S100A8/NLRP3/GSDMD signaling pathway

BackgroundAcute lung injury/acute respiratory distress syndrome (ALI/ARDS) is an acute, diffuse, inflammatory lung injury caused by various endogenous or exogenous factors. It is currently widely recognized that an excessive inflammatory response resulting from immune imbalance constitutes a crucial pathogenic mechanism in ALI/ARDS. SS31 is a novel mitochondria-targeted antioxidant peptide. This article validates the role of SS31 in lipopolysaccharide (LPS)-induced ALI.MethodsThe study applied transcriptome sequencing, immunofluorescence, PCR, immunofluorescence and other methods to explore the mechanism of SS31 in LPS induced ALI.ResultsTranscriptome sequencing results indicate that LPS-induced ALI is closely associated with immune regulatory processes, the Toll-like receptor pathway, and the NF-κB signaling pathway. The role of SS31 in acute lung injury is closely related to biological processes, such as immune regulation and cell death. This study demonstrated that SS31 can inhibit the expression of inflammatory factors IL-6, IL-1β, IL-18, and TNF-α, and reduce the expression of pyroptosis-related proteins NLRP3, and GSDMD-N. Further analysis revealed that S100A8 may be a key gene in the effect of SS31. LPS stimulation leads to increased expression of S100A8, while SS31 decreases its expression. Recombinant protein S100A8 can attenuate the inhibitory effect of SS31 on IL-1β, IL-18, NLRP3, and GSDMD-N.ConclusionsThe research results indicate that SS31 may inhibit the activation of the NLRP3 inflammasome and suppress inflammatory responses by regulating S100A8, thereby alleviating LPS-induced ALI in mice; this process may be related to pyroptosis.

Enhancing Emotion Regulation: A Review of tDCS Effects

Transcranial direct current stimulation (tDCS) has demonstrated increasing promise as a method of modifying brain activity and cognitive function. The objective of this comprehensive review of the literature is to evaluate the impact of tDCS on explicit and implicit emotion regulation strategies. An extensive review of the literature, conducted using keywords "tDCS," "emotion regulation," "implicit emotion regulation," and "explicit emotion regulation" in Google Scholar, PubMed, Scopus, and Web of Science databases, identified studies meeting the inclusion and exclusion criteria. Twenty studies overall, encompassing both implicit-automatic and explicit-controlled emotion regulation strategies, were found after an extensive review of the literature. There has been a lot of research conducted on explicit emotion regulation, however not as much on implicit emotion regulation. The review revealed that tDCS administration has demonstrated promising effects on enhancing emotion regulation performance across various tasks and neural targets. Nevertheless, inconsistencies in the literature highlight the necessity for further research to elucidate the precise mechanisms underlying tDCS-induced changes in emotion regulation, as well as to explore individual differences in treatment response. In conclusion, this review highlights the potential of tDCS as a valuable intervention for enhancing emotion regulation processes, with implications for both clinical practice and basic research in affective neuroscience.

Specific surface-modified iron oxide nanoparticles trigger complement-dependent innate and adaptive antileukaemia immunity

Considerable advances have been achieved in the application of nanomaterials for immunotherapies, yet the precise immune effects induced by protein corona remain elusive. Here, we explore the formation mechanism and immune regulation process of protein corona in acute myeloid leukaemia (AML) mouse models using commercialized iron oxide nanoparticles (IONPs), with different surface modifications, including an FDA-approved variant. Using macrophages depleted or Complement Component 3 (C3) knockout mice, we demonstrate that carboxymethyl dextran-coated IONP (IONP-COOH) reduces leukaemia burden. Mechanistically, IONP-COOH indirectly binds to C3b after activating the complement alternative pathway, subsequently enhancing phagocytosis of macrophages and activating adaptive immunity mediated by complement corona. While aminated dextran-coated IONPs directly absorb C3b and activate the lectin pathway, leading to immune cell exhaustion. Our findings suggest that IONP-COOH may serve as an immune activator for AML treatment, offering a promising approach to developing therapeutic nanomaterials by leveraging surface chemistry to enhance immunotherapy.