Search Results (1,182)

Background/Objectives: Affecting close to one-third of the global population, metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent chronic liver disorder linked to metabolic risk factors such as obesity and insulin resistance. Liver fibrosis is a key determinant of prognosis, and its progression increases the risk of liver-related and overall mortality. This exploratory research evaluated the potential impact of a 3-month intervention involving dietary counseling and liraglutide therapy on liver fibrosis and related metabolic markers in patients with MASLD and obesity without diabetes. Methods: In this prospective, single-arm exploratory intervention, 28 adult patients with MASLD and obesity received structured dietary counseling and daily subcutaneous liraglutide for 12 weeks. Liver fibrosis was assessed using non-invasive indices (FIB-4, APRI, BARD, ELF) and transient elastography performed with the FibroScan^® device (Echosens, Paris, France). Results: After 3 months, a significant reduction in liver stiffness (−7.14%, p < 0.05) and ELF score (from 6.71 to 6.63; −1.2%, p < 0.05) was observed. APRI (p = 0.06) and FIB-4 (p = 0.09) showed trends toward improvement, while the BARD score and AST/ALT ratio remained unchanged. Conclusions: Short-term liraglutide therapy combined with lifestyle modification may improve early-stage liver fibrosis in patients with MASLD and obesity, as indicated by reductions in liver stiffness and ELF score. These preliminary findings highlight the potential of advanced non-invasive fibrosis markers in monitoring treatment response. However, as an exploratory study, results should be interpreted with caution, and larger, long-term trials are needed to confirm these observations and evaluate efficacy in patients with more advanced fibrosis stages. Full article

Operations management personnel emphasize the maintenance of workforce empowerment on the shop floor. This is made possible by implementing effective operations and human resource management practices. However, organizations are adept at controlling the workforce empowerment domain within operational scenarios. In the current industry revolution scenario, industry personnel often face failure due to a laggard mindset in the face of industry revolutions. There are higher possibilities of failure because of standardized operations controlling the shop floor. Organizations utilize well-established human resource concepts, including McClelland’s acquired needs theory, Herzberg’s two-factor theory, and Maslow’s hierarchy of needs, in order to enhance the workforce’s performance on the shop floor. Current SME individuals require fast-paced approaches for tracking the performance and idleness of a workforce in order to control them more efficiently in both flexible and transformational stages. The present study focuses on investigating the parameters and factors that contribute to workforce empowerment in an industrial revolution scenario. The present research is used to develop a framework utilizing operations and human resource management approaches in order to identify and address the issues responsible for deteriorating workforce contributions. The framework includes HRM and operations management practices, including Herzberg’s two-factor theory, Maslow’s theory, and lean and smart approaches. The developed framework contains four phases for achieving desired outcomes on the shop floor. The developed framework is validated by implementing it in a real-life electric vehicle manufacturing organization, where the human resources and operations team were exhausted and looking to resolve employee-related issues instantly and establish a sustainable work environment. The current industry is transforming from Industry 3.0 to Industry 4.0, and seeks future-ready innovations in operations, control, and monitoring of shop floor setups. The operations management and human resource management practices teams reviewed the results over the next three months after the implementation of the developed framework. The results revealed an improvement in workforce empowerment within the existing work environment, as evidenced by reductions in the number of absentees, resignations, transfer requests, and medical issues, by 30.35%, 94.44%, 95.65%, and 93.33%, respectively. A few studies have been conducted on workforce empowerment by controlling shop floor scenarios through modifications in operations and human resource management strategies. The results of this study can be used to fulfil manufacturers’ needs within confined constraints and provide guidelines for efficiently controlling workforce performance on the shop floor. Constraints refer to barriers that have been decided, including production time, working time, asset availability, resource availability, and organizational policy. The study proposes a decision-making plan for enhancing shop floor performance by providing suitable guidelines and an action plan, taking into account both workforce and operational performance. Full article

This study examines the safety and cost-effectiveness of implementing shoulder rumble strips (SRS) and road lighting on Saudi Arabian freeways, providing insights into their roles in fostering sustainable transport systems. By leveraging the Highway Safety Manual (HSM) framework, this research develops localized Crash Modification Factors (CMFs) for these interventions, ensuring evidence-based and context-specific evaluations. Data were collected for two periods—pre-pandemic (2017–2019) and post-pandemic (2021–2022). For each period, we obtained traffic crash records from the Saudi Highway Patrol database, traffic volume data from the Ministry of Transport and Logistic Services’ automated count stations, and roadway characteristics and pavement-condition metrics from the National Road Safety Center. The findings reveal that SRS reduces fatal and injury run-off-road crashes by 52.7% (CMF = 0.473) with a benefit–cost ratio of 14.12, highlighting their high cost-effectiveness. Road lighting, focused on nighttime crash reduction, decreases such crashes by 24% (CMF = 0.760), with a benefit–cost ratio of 1.25, although the adoption of solar-powered lighting systems offers potential for greater sustainability gains and a higher benefit–cost ratio. These interventions align with global sustainability goals by enhancing road safety, reducing the socio-economic burden of crashes, and promoting the integration of green technologies. This study not only provides actionable insights for achieving KSA Vision 2030’s target of improved road safety but also demonstrates how engineering solutions can be harmonized with sustainability objectives to advance equitable, efficient, and environmentally responsible transportation systems. Full article

Chronic visceral pain, a significant contributor to morbidity in the United States, affects millions and results in substantial economic costs. Despite its impact, the mechanisms underlying disorders of gut–brain interaction (DGBIs), such as irritable bowel syndrome (IBS), remain poorly understood. Visceral hypersensitivity, a hallmark of chronic visceral pain, involves an enhanced pain response in internal organs to normal stimuli. Various factors like inflammation, intestinal hyperpermeability, and epigenetic modifications influence its presentation. Emerging evidence suggests that persistent colonic stimuli, disrupted gut barriers, and altered non-coding RNA (ncRNA) expression contribute to the pathophysiology of visceral pain. Additionally, cross-sensitization of afferent pathways shared by pelvic organs underpins the overlap of chronic pelvic pain disorders, such as interstitial cystitis and IBS. Central sensitization and viscerosomatic convergence further exacerbate pain, with evidence showing IBS patients exhibit hypersensitivity to both visceral and somatic stimuli. The molecular mechanisms of visceral pain involve critical mediators such as cytokines, prostaglandins, and neuropeptides, alongside ion channels like transient receptor potential vanilloid 1 (TRPV1) and acid-sensing ion channels (ASICs). These molecular insights indicate potential therapeutic targets and highlight the possible use of TRPV1 antagonists and ASIC inhibitors to mitigate visceral pain. This review explores the neurophysiological pathways of visceral pain, focusing on peripheral and central sensitization mechanisms, to advance the development of targeted treatments for chronic pain syndromes, particularly IBS and related disorders. Full article

Plants are constantly exposed to environmental stressors such as drought, salinity, and extreme temperatures, which threaten their growth and productivity. To counter these challenges, they employ complex molecular defense systems, including epigenetic modifications that regulate gene expression without altering the underlying DNA sequence. This review comprehensively examines the emerging roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) as central signaling molecules orchestrating epigenetic changes in response to abiotic stress. In addition, biotic factors such as pathogen infection and microbial interactions are considered for their ability to trigger ROS/RNS generation and epigenetic remodeling. It explores how ROS and RNS influence DNA methylation, histone modifications, and small RNA pathways, thereby modulating chromatin structure and stress-responsive gene expression. Mechanistic insights into redox-mediated regulation of DNA methyltransferases, histone acetyltransferases, and microRNA expression are discussed in the context of plant stress resilience. The review also highlights cutting-edge epigenomic technologies such as whole-genome bisulfite sequencing (WGBS), chromatin immunoprecipitation sequencing (ChIP-seq), and small RNA sequencing, which are enabling precise mapping of stress-induced epigenetic landscapes. By integrating redox biology with epigenetics, this work provides a novel framework for engineering climate-resilient crops through the targeted manipulation of stress-responsive epigenomic signatures. Full article

Sporadic Parkinson’s Disease (PD) affects 3% of people over 65 years of age. People are living longer, thanks in large part to improvements in global health technology and health access for non-neurological diseases. Consequently, neurological diseases of senescence, such as PD, are representing an ever-increasing share of global disease burden. There is an intensifying research focus on the processes that underlie these conditions in the hope that neurological decay may be arrested at the earliest time point. The concept of neuronal death linked to ageing- neural senescence- first emerged in the 1800s. By the late 20th century, it was recognized that neurodegeneration was common to all ageing human brains, but in most cases, this process did not lead to clinical disease during life. Conditions such as PD are the result of accelerated neurodegeneration in particular brain foci. In the case of PD, degeneration of the substantia nigra pars compacta (SNpc) is especially implicated. Why neural degeneration accelerates in these particular regions remains a point of contention, though current evidence implicates a complex interplay between a vast array of neuronal cell functions, bioenergetic failure, and a dysfunctional brain immunological response. Their complexity is a considerable barrier to disease modification trials, which seek to intercept these maladaptive cell processes. This paper reviews current evidence in the domain of neurodegeneration in Parkinson’s disease, focusing on alpha-synuclein accumulation and deposition and the role of oxidative stress and inflammation in progressive brain changes. Recent approaches to disease modification are discussed, including the prevention or reversal of alpha-synuclein accumulation and deposition, modification of oxidative stress, alteration of maladaptive innate immune processes and reactive cascades, and regeneration of lost neurons using stem cells and growth factors. The limitations of past research methodologies are interrogated, including the difficulty of recruiting patients in the clinically quiescent prodromal phase of sporadic Parkinson’s disease. Recommendations are provided for future studies seeking to identify novel therapeutics with disease-modifying properties. Full article

Autoimmune diseases such as systemic lupus erythematosus and Sjögren’s syndrome show pronounced sex disparities in prevalence, severity, and clinical outcomes, with females disproportionately affected. Emerging evidence highlights sex-based differences in immune and inflammatory responses as key contributors to this bias. Genetic factors—including sex chromosomes, skewed X chromosome inactivation, and sex-biased microRNAs—as well as sex hormones and pregnancy modulate gene expression and immune cell function in a sex-specific manner. Additionally, sex hormone-dependent epigenetic modifications influence the transcription of critical immune regulators. These genetic and hormonal factors collectively shape the activation, differentiation, and effector functions of diverse immune cell types. Environmental factors—including infections, gut microbiota, environmental chemicals and pollutants, and lifestyle behaviors such as diet, smoking, UV exposure, alcohol and caffeine intake, physical activity, and circadian rhythms—further modulate immune function and autoimmune disease pathogenesis in a sex-dependent manner. Together, these mechanisms contribute to the heightened risk and distinct clinical features of autoimmunity in females. A deeper understanding of sex-biased immune regulation will facilitate the identification of novel biomarkers, enable patient stratification, and inform the development of sex-specific diagnostic and therapeutic strategies for autoimmune diseases. Full article

Mandelic acid (MA), as an important chiral aromatic hydroxy acid, is widely used in medicine, the chemical industry, and agriculture. With the continuous growth of market demand, traditional chemical synthesis methods are increasingly inadequate to meet the requirements of green and sustainable development due to issues such as complex processes, poor stereoselectivity, numerous byproducts, and serious environmental pollution. MA synthesis strategies based on biocatalytic technology have become a research hotspot due to their high efficiency, environmental friendliness, and excellent stereoselectivity. Significant progress has been made in enzyme engineering modifications, metabolic pathway design, and process optimization. Importantly, biomechanical research provides a transformative perspective for this field. By analyzing the mechanical response characteristics of microbial cells in bioreactors, biomechanics facilitates the regulation of relevant environmental factors during the fermentation process, thereby improving synthesis efficiency. Molecular dynamics simulations are also employed to uncover stability differences in enzyme–substrate complexes, providing a structural mechanics basis for the rational design of highly catalytically active enzyme variants. These biomechanic-driven approaches lay the foundation for the future development of intelligent, responsive biosynthesis systems. The deep integration of biomechanics and synthetic biology is reshaping the process paradigm of green MA manufacturing. This review will provide a comprehensive summary of the applications of MA and recent advances in its biosynthesis, with a particular focus on the pivotal role of biomechanical characteristics. Full article

Bipolar disorder (BD) is a multifactorial mental disease with a prevalence of 1–5% in adults, caused by complex interactions between genetic and environmental factors. Environmental factors contribute to gene expression alterations through epigenetic mechanisms without changing the underlying DNA sequences. Interactions between the gut microbiota (GM) and diverse external factors, such as nutritional composition, may induce epigenetic alterations and increase susceptibility to BD. While epigenetic mechanisms are involved in both the pathogenesis of BD and drug treatment responses, epigenetic marks could be employed as predictors and indicators of drug response. This review highlights recent studies on the potential role of epigenetic aberrations in the development and progression of BD. Next, we focus on drug response-related alterations in the epigenetic landscape, including DNA methylation, histone modifications, and non-coding RNAs. Afterward, we delve into the potential roles of GM-induced epigenetic changes in the pathogenesis of BD and GM-based therapeutic strategies aimed at improving BD outcomes through epigenetic modifications. We also discuss how BD drugs may exert beneficial effects through modulation of the GM and the epigenome. Finally, we consider future research strategies that could address existing challenges. Full article

Selective water withdrawals (SWWs) are frequently used to minimize the downstream effects of dams by blending water from different depths to achieve a desired temperature regime in the river. In 2010, an SWW was installed on the outlet structure of the primary hydropower reservoir on the Deschutes River (Oregon, USA) to increase spring temperatures by releasing a combination of surface water and bottom waters from a dam that formerly only had a hypolimnetic outlet. The objective of increasing spring river temperatures was to recreate pre-dam river temperatures and optimize conditions for the spawning and rearing of anadromous fish. The operation of the SWW achieved the target temperature regime, but the release of surface water from a hypereutrophic impoundment resulted in a number of unintended consequences. These changes included significant increases in river pH and dissolved oxygen saturation. Inorganic nitrogen releases decreased in spring but increased in summer. The release of surface water from the reservoir increased levels of plankton in the river resulting in changes to the macroinvertebrates such as increases in filter feeders and a greater percentage of taxa tolerant to reduced water quality. No significant increase in anadromous fish was observed. The presence of large irrigation diversions upstream of the reservoir was not accounted for in the temperature analysis that led to the construction of the SWW. This complicating factor would have reduced flow in the river leading to increased river temperatures at the hydropower site during the measurement period used to develop representations of historical temperature. The analysis supports the use of numerical models to assist in forecast changes associated with SWWs, but the results from this project illustrate the need for greater consideration of complex responses of aquatic communities caused by structural modifications to dams. Full article

Accurate detection of cotton pests and diseases is essential for agricultural productivity yet remains challenging due to complex field environments, the small size of pests and diseases, and significant occlusions. To address the challenges presented by these factors, a novel cotton disease and pest detection method is proposed. This method builds upon the YOLOv8 baseline model and incorporates a Multi-Scale Sliding Window Attention Module (MSFE) within the backbone architecture to enhance feature extraction capabilities specifically for small targets. Furthermore, a Depth-Separable Dilated Convolution Module (C2f-DWR) is designed to replace the existing C2f module in the neck of the network. By employing varying dilation rates, this modification effectively expands the receptive field and alleviates the loss of detailed information associated with the downsampling processes. In addition, a Multi-Head Attention Detection Head (MultiSEAMDetect) is introduced to supplant the original detection head. This new head utilizes diverse patch sizes alongside adaptive average pooling mechanisms, thereby enabling the model to adjust its responses in accordance with varying contextual scenarios, which significantly enhances its ability to manage occlusion during detection. For the purpose of experimental validation, a dedicated dataset for cotton disease and pest detection was developed. In this dataset, the improved model’s mAP50 and mAP50:95 increased from 73.4% and 46.2% to 77.2% and 48.6%, respectively, compared to the original YOLOv8 algorithm. Validation on two Kaggle datasets showed that mAP50 rose from 92.1% and 97.6% to 93.2% and 97.9%, respectively. Meanwhile, mAP50:95 improved from 86% and 92.5% to 87.1% and 93.5%. These findings provide compelling evidence of the superiority of the proposed algorithm. Compared to other advanced mainstream algorithms, it exhibits higher accuracy and recall, indicating that the improved algorithm performs better in the task of cotton pest and disease detection. Full article

Epigenetic modifications act as crucial regulators of gene activity and are influenced by both internal and external environmental factors, with diet being the most impactful external factor. On the other hand, cellular metabolism encompasses a complex network of biochemical reactions essential for maintaining cellular function, and it impacts every cellular process. Many metabolic cofactors are critical for the activity of chromatin-modifying enzymes, influencing methylation and the global acetylation status of the epigenome. For instance, dietary nutrients, particularly those involved in one-carbon metabolism (e.g., folate, vitamins B12 and B6, riboflavin, methionine, choline, and betaine), take part in the generation of S-adenosylmethionine (SAM), which represents the main methyl donor for DNA and histone methylation; α-ketoglutarate and ascorbic acid (vitamin C) act, respectively, as a co-substrate and cofactor for Ten-eleven Translocation (TET), which is responsible for DNA demethylation; and metabolites such as Acetyl-CoA directly impact histone acetylation, linking metabolism of the TCA cycle to epigenetic regulation. Further, bioactive compounds, such as polyphenols, modulate epigenetic patterns by affecting methylation processes or targeting epigenetic enzymes. Since diet and nutrition play a critical role in shaping epigenome functions and supporting human health, this review offers a comprehensive update on recent advancements in metabolism, epigenetics, and nutrition, providing insights into how nutrients contribute to metabolic balance, epigenome integrity maintenance and, consequently, disease prevention. Full article

Permeate Gap Membrane Distillation (PGMD) is an emerging desalination technology that offers a promising alternative for freshwater production, particularly in energy-efficient and sustainable applications. This review provides a comprehensive analysis of PGMD, covering its fundamental principles, heat and mass transfer mechanisms, and key challenges such as temperature and concentration polarization. Various optimisation strategies, including Response Surface Morphology (RSM), Differential Evolution techniques, and Computational Fluid Dynamics (CFD) modelling, are explored to enhance PGMD performance. The study further discusses the latest advancements in system design, highlighting optimal configurations and the integration of PGMD with renewable energy sources. Factors influencing PGMD performance, such as operational parameters (flow rates, temperature, and feed concentration) and physical parameters (gap width, membrane properties, and cooling plate conductivity), are systematically analysed. Additionally, the techno-economic feasibility of PGMD for large-scale freshwater production is evaluated, with a focus on cost reduction strategies, energy efficiency, and hybrid system innovations. Finally, this review outlines the current limitations and future research directions for PGMD, emphasising novel system modifications, improved heat recovery techniques, and potential industrial applications. By consolidating recent advancements and identifying key challenges, this paper aims to guide future research and facilitate the broader adoption of PGMD in sustainable desalination and water purification processes. Full article

Heart failure (HF) remains a leading cause of morbidity and mortality worldwide. Despite significant advances in pharmacological therapies, responses to treatment vary widely among patients. Growing evidence suggests that genetic factors play a crucial role in influencing individual responses to HF therapies. Genetic variations, including single-nucleotide polymorphisms (SNPs), gene expression profiles, and epigenetic modifications, have been shown to affect drug metabolism, receptor sensitivity, and the molecular pathways involved in HF progression. These genetic determinants may not only predict the efficacy of common therapeutic agents such as angiotensin-converting enzyme inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors, but also help identify patients at risk of adverse drug reactions. As personalized medicine continues to advance, a deeper understanding of the genetic basis of drug response in HF could enable more tailored treatment strategies, improving clinical outcomes and minimizing adverse effects. This review explores the current evidence on the genetic underpinnings of response to HF treatment and discusses its potential implications in clinical practice, highlighting current knowledge gaps. Full article

Intrinsically disordered regions (IDRs), defined as protein segments lacking stable tertiary structures, are ubiquitously present in the human proteome and enriched with disease-associated mutations. IDRs harbor molecular recognition features (MoRFs) and post-translational modification sites (e.g., phosphorylation), enabling dynamic intermolecular interactions through conformational plasticity. Furthermore, IDRs drive liquid–liquid phase separation (LLPS) of biomacromolecules via multivalent interactions such as electrostatic attraction and pi–pi interactions, generating biomolecular condensates that are essential throughout the cellular lifecycle. These condensates separate intracellular space, forming a physical barrier to avoid interference between other molecules, thereby improving reaction specificity and efficiency. As a dynamically equilibrated process, LLPS formation and maintenance are regulated by multiple factors, endowing the condensates with rapid responsiveness to environmental cues and functional versatility in modulating diverse signaling cascades. Consequently, disruption of LLPS homeostasis can derail its associated biological processes, ultimately contributing to disease pathogenesis. Moreover, precisely because liquid–liquid phase separation (LLPS) is co-regulated by multiple factors, it may provide novel insights into the pathogenic mechanisms of disorders such as autism spectrum disorder (ASD), which result from the cumulative effects of multiple etiological factors. Full article