Search Results (6,182)

Interleukin-6 (IL-6) is a central mediator of systemic inflammation and is markedly elevated in critical illnesses, including sepsis, acute respiratory distress syndrome, and hyperinflammatory syndromes. Patient responses to immunomodulatory therapies vary, highlighting the need to better understand IL-6 regulation and its clinical implications. We retrospectively analyzed consecutive patients admitted to a medical intensive care unit in a quaternary academic center with a comprehensive cancer program, extracting clinical and laboratory data, including inflammatory markers and plasma IL-6 levels. Plasma IL-6 concentrations were measured using an electrochemiluminescence immunoassay. Survival analyses, multivariable adaptive Lasso regression, Bayesian logistic regression, and latent class analysis were performed to define determinants of IL-6 regulation, mortality, and inflammatory phenotypes. IL-6 levels were substantially elevated in sepsis (median 1150 pg/mL) and neutropenia (median 7866 pg/mL), with extreme concentrations exceeding 20,000 pg/mL when both were present. Although IL-6 across its full range was not independently predictive of intensive care unit mortality, dichotomized thresholds (≥200 pg/mL) correlated with lower survival. Advanced modeling defined a hyperinflammatory phenotype characterized by IL-6 ≥ 100 pg/mL and predicted mortality >40%, showing mortality of 58%, alongside distinct latent subgroups with heterogeneous inflammatory activity and outcomes. These results emphasize the prominent role of sepsis and neutropenia in driving IL-6 elevations and reveal inflammatory phenotypes with potential for risk stratification and targeted anti-cytokine therapy in critical illness. Full article

Food spoilage and contamination remain pressing global challenges, undermining food security and safety while driving economic losses. Conventional preservation strategies, including thermal treatments, refrigeration, and synthetic additives, often compromise nutritional quality and raise sustainability concerns, thereby necessitating natural, effective alternatives. Curcumin, a polyphenolic compound derived from Curcuma longa, has demonstrated broad-spectrum antimicrobial, antioxidant, and anti-inflammatory activities, making it a promising candidate for food preservation. However, its poor solubility, instability, and low bioavailability limit direct applications in food systems. Advances in nanotechnology have enabled the development of nanoformulated curcumin, enhancing solubility, stability, controlled release, and functional efficacy. This review examines the antimicrobial mechanisms of curcumin and its nanoformulations, including membrane disruption, oxidative stress via reactive oxygen species, quorum sensing inhibition, and biofilm suppression. Applications in active and smart packaging are highlighted, where curcumin nanoformulation not only extends shelf life but also enables freshness monitoring through pH-responsive color changes. Evidence across meats, seafood, fruits, dairy, and beverages shows improved microbial safety, oxidative stability, and sensory quality. Multifunctional systems, such as hybrid composites and stimuli-responsive carriers, represent next-generation tools for sustainable packaging. However, challenges remain with scale-up, migration safety, cytotoxicity, and potential promotion of antimicrobial resistance gene (ARG) transfer. Future research should focus on safety validation, advanced nanocarriers, ARG-aware strategies, and regulatory frameworks. Overall, nanoformulated curcumin offers a natural, versatile, and eco-friendly approach to food preservation that aligns with clean-label consumer demand. Full article

The sultanate of Oman has joined other nations in promoting sustainability, guided by Oman Vision 2040 and the Oman National Spatial Strategy. Oman now focuses on developing more human-centered cities, enhancing community well-being, boosting the local economy, and increasing investments. This study addresses a research gap by examining the social and economic impact of the sustainable neighborhood “Al-Mouj” on the nearby urban area “Al-Mawaleh North” to maximize sustainability benefits. It analyzes how a sustainable neighborhood influences the economy, society, quality of life, and overall well-being. The study also identifies key factors driving the growth of sustainable practices in society and the economy. It has four main objectives in terms of answering the research question, primarily through surveys of community members and business owners, and by analyzing land use development around Al-Mouj. Data collection methods include literature review, case study, questionnaires, and interviews. Data analysis employs spatial, statistical, and thematic techniques. Responses from 515 participants are examined to ensure reliable results. Ethnographic methods are used to gain insights from open-ended questionnaire responses and interviews. The results confirm that Al-Mouj’s mixed-use development and sustainability features positively influence mental and physical health and stimulate economic activity within the local community. This study provides decision-makers and urban planners valuable insights into sustainable neighborhoods’ social and economic impacts when developed as open communities. It highlights the challenges of following international NSAT standards, which do not fully address local concerns. Full article

Cardiac inflammation and hypertrophy develop as a pathologic response to an array of insults, such as myocardial infarctions, chronic systemic hypertension, and valvular defects. Due to the high prevalence of such conditions, there is an increasing need to prevent and halt cardiac hypertrophy. Because cardiac damage and subsequent remodeling can lead to arrhythmias, heart failure, and even sudden cardiac death, inhibition of cardiac hypertrophy is key to reducing cardiovascular-related mortality. The immune system is the driving force behind inflammatory reactions. All three pathways of complement system activation—classical, lectin, and alternative—are implicated in developing cardiac damage, inflammation, and hypertrophy due to infectious and non-infectious causes, autoimmune diseases, genetic polymorphisms, and forms of complement dysregulation. Of interest in this review is the role of the complement system, a collection of soluble and membrane-bound proteins that mediate inflammatory processes through interactions with signaling molecules and immune cells. This review comprehensively discusses the roles of these complement pathways in contagious, chronic inflammatory, genetic, and metabolic diseases. An overview of the completed and terminated clinical trials aimed at preventing cardiovascular mortality by targeting various aspects of the complement system and inflammatory reaction is included. Most current treatments for cardiac inflammation and remodeling primarily target the renin–angiotensin–aldosterone system (RAAS), which prevents further remodeling by reducing myocardial workload. However, moving forward, there may be a place for emerging anti-complement therapeutics, which impair the inflammatory response that generates hypertrophy itself. Full article

The escalating heatwave risks over the Tibetan Plateau (TP) highlight unresolved gaps in understanding multitype mechanisms and diurnal urban canopy heat island (UCHI) responses. Using Xining’s high-density observational network (2018–2023) and by employing comparative analysis (urban–rural, heatwave versus non-heatwave days) and composite analysis, we found: During the record-breaking July 2022 heatwave across the TP, Xining reached an extreme UCHI peak (z-score: 3.0). Critically asymmetric UCHI responses as daytime heatwaves amplify mean intensity by 0.35 °C via extreme value shifts, whereas nighttime events suppress it by 0.31 °C. Crucially, heatwaves induce negligible daytime UCHI modulation but drive comparable magnitude nighttime UCHI intensification (during daytime events) and reduction (during nighttime events), demonstrating type-dependent and diurnally asymmetric urban thermal sensitivities. Heatwaves driven by distinct synoptic patterns; daytime events are controlled by an anomaly anticyclone (cloudless, dry conditions), while nighttime events occur under plateau-north anticyclones (cloudy, humid conditions). These patterns fundamentally reshape heatwave–UCHI interactions through divergent mechanisms: Daytime/nighttime heatwaves amplify/suppress nocturnal UCHI through enhanced/reduced urban heat storage and accelerated/inhibited rural radiative cooling. Our case study demonstrates that although heatwaves generally amplify nocturnal UCHI, in dry regions, their synoptic drivers significantly modify this nighttime synergy. The nocturnal UCHI during heatwave is not only driven by humidity effects but also modulated by cloud cover-regulated rural radiative cooling and urban thermal storage. These findings establish a mechanistic framework for heatwaves–UCHI interactions and provide actionable insights for heat-resilient planning in high-altitude arid cities. Full article

To address the flood risks driven by climate change and urbanization, this study proposes the DRIRA model (Driving Force, Resistance, Influence, Recoverability, Adaptability). Distinct from BRIC (Baseline Resilience Indicators for Communities) and PEOPLES (Population, Environmental/Ecosystem, Organized Governmental Services, Physical Infrastructure, Lifestyle, Economic Development, Social–Cultural Capital), the model emphasizes dynamic interactions across the entire disaster lifecycle, introduces the “Influence” dimension, and integrates SNA (Social Network Analysis) with a modified gravity model to reveal cascading effects and resilience linkages among cities. Based on an empirical study of 30 cities in the Central Plains Urban Agglomeration, and using a combination of entropy weighting, a modified spatial gravity model, and social network analysis, the study finds that: (1) Urban flood resilience increased by 35.5% from 2012 to 2021, but spatial polarization intensified, with Zhengzhou emerging as the dominant core and peripheral cities falling behind; (2) Economic development, infrastructure investment, and intersectoral governance coordination are the primary factors driving resilience differentiation; (3) Intercity resilience connectivity has strengthened, yet administrative fragmentation continues to undermine collaborative effectiveness. In response, three strategic pathways are proposed: coordinated development of sponge and resilient infrastructure, activation of flood insurance market mechanisms, and intelligent cross-regional dispatch of emergency resources. These strategies offer a scientifically grounded framework for balancing physical flood defenses with institutional resilience in high-risk urban regions. Full article

Global supply chains face increasing disruptions from cyber threats, geopolitical instability, extreme weather events, and a range of economic, social, and environmental sustainability challenges. As these disruptions intensify, enhancing Supply Chain Resilience (SCR) has become a strategic priority. This study investigates how Distributed Ledger Technology (DLT) can contribute to SCR by mitigating vulnerabilities and strengthening key capabilities within global supply chains. A qualitative research approach is employed, utilizing expert evaluations to examine DLT’s impact on supply chain vulnerabilities and capabilities. Five workshops were conducted with 25 industry professionals from logistics, IT, procurement, and risk management. Experts examined how DLT could address disruptions stemming from supplier instability, poor traceability, and regulatory and environmental pressures, while highlighting its potential to drive ethical sourcing and environmentally responsible practices. The structured discussions were guided by theoretical frameworks and expert evaluations were synthesized into two analytical matrices illustrating DLT’s influence on SCR. The findings reveal that the contribution of DLT to SCR and sustainability is highly context-dependent, with its effectiveness hinging on how it is embedded within governance structures and aligned with the interplay of complementary technologies. Building on these insights, the study presents the DLT-LFL (Distributed Ledger Technology–Learning Feedback Loop) framework, which integrates sensing, decision-making, adaptation, and predictive learning from distributed operational data, allowing supply chains to better anticipate disruptions, adjust processes dynamically, and continuously strengthen resilience and sustainable practices. The study also develops a practical checklist to assess how effective DLT applications and their integration with predictive and AI-driven analytics reduce vulnerabilities, strengthen capabilities, mitigate risks, and support adaptive decision-making. Full article

The plasma membrane (PM) of eukaryotic cells plays a key role in the response to stress, acting as the first line of defense against environmental changes and protecting cells against intracellular perturbations. In this work, we explore how membrane-bound chaperones and membrane lipid domains work together to shape plasma membrane properties—a partnership we refer to as the “epichaperome–plasma membrane lipid axis.” This axis influences membrane fluidity, curvature, and domain organization, which in turn shapes the spatial and temporal modulation of signaling platforms and pathways essential for maintaining cellular integrity and homeostasis. Changes in PM fluidity can modulate the activity of ion channels, such as transient receptor potential (TRP) channels. These changes also affect processes such as endocytosis and mechanical signal transduction. The PM proteome undergoes rapid changes in response to membrane perturbations. Among these changes, the expression of heat shock proteins (HSPs) and their accumulation at the PM are essential mediators in regulating the physical state and functional properties of the membrane. Because of the pivotal role in stress adaptation, HSPs influence a wide range of cellular processes, which we grouped into three main categories: (i) mechanistic insights, differentiating in vitro (liposome, reconstituted membrane systems) and in vivo evidence for HSP-PM recruitment; (ii) functional outputs, spanning how ion channels are affected, changes in membrane fluidity, transcytosis, and the process of endocytosis and exosome release; and (iii) pathological effects, focusing on how rewired lipid–chaperone crosstalk in cancer drives resistance to drugs through altered membrane composition and signaling. Finally, we highlight Membrane Lipid Therapy (MLT) strategies, such as nanocarriers targeting specific PM compartments or small molecules that inhibit HSP recruitment, as promising approaches to modulate the functional stability of epichaperome assembly and membrane functionality, with profound implications for tumorigenesis. Full article

The increasing capabilities of Unmanned Aerial Vehicles (UAVs) or drones are opening up diverse business opportunities. Innovations in drones, U-space, and UTM systems are driving the rapid development of new air mobility applications, often outpacing current regulatory frameworks. These applications now span multiple sectors, from infrastructure monitoring to urban parcel delivery, resulting in a projected increase in drone traffic within shared airspace. This growth introduces significant safety concerns, particularly in managing the separation between drones and manned aircraft. Although various research efforts have addressed this deconfliction challenge, a critical need remains for improved automated solutions at both strategic and tactical levels. In response, our SESAR-funded initiative, AI4HyDrop, investigates the application of machine learning to develop an intelligent system for UAV deconfliction. As part of this effort, we conducted a comprehensive literature review to assess the application of Artificial Intelligence (AI) in this domain. The AI algorithms used in drone deconfliction can be categorized into three types: deep learning, reinforcement learning, and bio-inspired learning. The findings lay a foundation for identifying the key requirements of an AI-based deconfliction system for UAVs. Full article

Jiangsu Province is an important economic province on the eastern coast of China, revealing the spatial–temporal characteristics, dynamic degree, and transition direction of land use/cover change, and its main driving factors are significant for the effective use of land resources and the promotion of regional human–land coordinated development. Based on land use data of Jiangsu Province from 2000 to 2020, this study investigates the spatiotemporal evolution characteristics of land use/cover using the dynamics model and the transfer matrix model, and examines the influence and interaction of the driving factors between human activities and the natural environment based on 10-factor data using Geodetector. The results showed that (1) In the past 20 years, the type of land use/cover in Jiangsu Province primarily comprises cropland, water, and impervious, with the land use/cover change mode mainly consisting of a dramatic change in cropland and impervious and relatively little change in forest, grassland, water, and barren. (2) From the perspective of the dynamic rate of land use/cover change, the single land use dynamic degree showed that impervious is the only land type whose dynamics have positively increased from 2000 to 2010 and 2010 to 2020, with values of 3.67% and 3.03%, respectively. According to the classification of comprehensive motivation, the comprehensive land use motivation in Jiangsu Province in each time period from 2000 to 2010 and 2010 to 2020 is 0.46% and 0.43%, respectively, which belongs to the extremely slow change type. (3) From the perspective of land use/cover transfer, Jiangsu Province is mainly characterized by a large area of cropland transfer (−7954.30 km²) and a large area of impervious transfer (8759.58 km²). The increase in impervious is mainly attributed to the transformation of cropland and water, accounting for 4066.07 km² and 513.73 km² from 2010 to 2020, which indicates that the non-agricultural phenomenon of cropland in Jiangsu Province, i.e., the process of transforming cropland into non-agricultural construction land, is significant. (4) From the perspective of driving factors, population density (q = 0.154) and night light brightness (q = 0.156) have always been important drivers of land use/cover change in Jiangsu Province. The interaction detection indicates that the land use/cover change is driven by both socio-economic factors and natural geographic factors. (5) In response to the dual pressures of climate change and rapid urbanization, coordinating the multiple objectives of socio-economic development, food security, and ecological protection is the fundamental path to achieving sustainable land use in Jiangsu Province and similar developed coastal areas. By revealing the characteristics and driving factors of land use/cover change in Jiangsu Province, this study provides qualitative and quantitative theoretical support for the coordinated decision-making of economic development and land use planning in Jiangsu Province, specifically contributing to sustainable land planning, climate adaptation policy-making, and the enhancement of community well-being through optimized land use. Full article

In the context of global industrial chain decarbonization, the perpetuation of corporate green innovation has emerged as a linchpin for sustaining a competitive advantage in the pursuit of environmental sustainability. Employing a panel data framework, this investigation analyzes A-share listed firms in China from 2011 to 2023. In terms of supply chain perspectives, this study utilizes fixed effects models, mediation analysis, and moderation analysis to empirically examine how downstream enterprises’ digital transformation affects the sustainability of upstream enterprises’ green innovation, while deconstructing the “capability–motivation” dual pathway underlying such sustainability. The key findings are as follows: (1) downstream digital transformation significantly strengthens upstream green innovation persistence through both capability reinforcement and motivation amplification, with a notably stronger impact on the latter; (2) mechanism tests show that capability improvement primarily arises from knowledge spillovers and enhanced supply–demand coordination efficiency, while motivation enhancement stems from intensified market competition and greater responsiveness to tax incentives; and (3) supply chain structural characteristics exert critical moderating effects. This research elucidates the operational logic and boundary conditions of supply chain digital coordination in driving green innovation persistence, contributing to theoretical frameworks while offering actionable insights for policymaking and corporate strategic optimization in sustainable supply chain management. Full article

Glucosylceramide (GlcCer), a central glycosphingolipid derived from ceramide, is increasingly recognized as a bioactive lipid that intersects with key metabolic, inflammatory, and oncogenic pathways. While its dysregulation has long been associated with lysosomal storage disorders such as Gaucher disease (GD), growing evidence implicates GlcCer in cancer initiation and progression, particularly within tumor-predisposing conditions. GlcCer modulates membrane microdomains, intracellular trafficking, and cell signaling, counteracting ceramide-induced apoptosis and promoting cellular survival. In cancer, aberrant upregulation of UDP-glucose ceramide glucosyltransferase (UGCG), the enzyme responsible for GlcCer synthesis, drives tumor growth, metastasis, and multidrug resistance through activation of pathways such as phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), mitogen-activated protein kinase (MAPK), canonical Wnt pathway (Wnt/β-catenin), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways. Specific GlcCer species (e.g., C16:0, C18:0, C24:1) display tissue-dependent functions, adding structural specificity to their oncogenic potential. Moreover, emerging links between GlcCer metabolism and chronic inflammation, oxidative stress, and altered glucose utilization highlight its role as a metabolic node bridging inherited metabolic disorders and malignancy. This review integrates recent advances in GlcCer biology, emphasizing its roles in tumor-predisposing diseases and exploring its potential as a biomarker and therapeutic target in oncology. Full article

Antimicrobial resistance (AMR) is a growing global threat, exacerbated by the adaptive mechanisms of Gram-negative ESKAPE pathogens, which include biofilm formation and outer membrane vesicle (OMV) production. Biofilms create robust protective barriers that shield bacterial communities from immune responses and antibiotic treatments, while OMVs contribute to both defense and offense by carrying antibiotic-degrading enzymes and delivering virulence factors to host cells. These mechanisms not only enhance bacterial survival but also increase the virulence and persistence of infections, making them a significant concern in clinical settings. This review explores the molecular processes that drive biofilm and OMV formation, emphasizing their critical roles in the development of AMR. By understanding these mechanisms, new therapeutic strategies can be developed to disrupt these defenses, potentially improving the efficacy of existing antibiotics and slowing the spread of resistance. Additionally, the use of OMVs in vaccine development and drug delivery offers promising avenues for future research. Addressing these challenges requires a comprehensive approach, combining advanced research with innovative therapies to combat the escalating threat of AMR and improve patient outcomes. Full article

Rotavirus (RV) is one of the main etiologic agents associated with diarrheal diseases (DDs), being responsible for approximately 200 thousand deaths annually. Currently, there are still many aspects regarding the virus biology, cell cycle, and pathophysiology of RV that need further elucidation. Therefore, the present work aimed to investigate whether the triggering receptor expressed on myeloid cells 1 (TREM-1) might be associated with RV infection. This immune receptor has been observed as an amplifier of inflammatory responses in different infectious and non-infectious diseases, including inflammatory bowel disease and celiac disease. Initially, we searched for public transcriptomic data regarding RV infection and the expression of TREM-1 and its associated genes, which were significantly upregulated in infected mice and children. Then, we infected monocytes with the virus, with or without a TREM-1 inhibitor. The inhibition of the receptor’s activity resulted in a significant decrease in IL-1β production. We also observed a reduction in cytopathic effects when MA104 cells were treated with TREM-1 inhibitors and then infected with simian RV. To further elucidate the interactions between the virus and TREM-1, in silico tools were used to simulate interactions between the receptor and RV proteins. These simulations suggested the occurrence of interactions between TREM-1 and VP5*, a protein involved in viral attachment to target cells, and also between the receptor and NSP4, a viral enterotoxin with immunostimulant properties. Hence, our results indicate that TREM-1 is involved in RV infection, both as a mediator of inflammatory responses and as a player in the host–virus relationship. Full article

Background/Objectives: Autism is characterized by atypical sensory processing, which affects spatial and temporal perception. Here, we explore sensory processing in children with autism, focusing on visuospatial and temporal tasks across visual and auditory modalities. Methods: Ninety-two children aged 4 to 6 participated, divided into three groups: autism (n = 32), neurotypical chronological age-matched controls (n = 28), and neurotypical developmental age-matched controls (n = 32). The autism group consisted of high-functioning children (26 boys). The participants completed computer-based tasks requiring spatial and temporal processing. Response accuracy and reaction times were recorded. Results: The autism group demonstrated higher accuracy in temporal tasks (visual and auditory modalities) and comparable accuracy in visuospatial modality, but slower response times in all tasks compared to both neurotypical controls. These results suggest a strategy that prioritizes accuracy over speed, while preserving spatial and temporal processing in autism. Conclusions: These findings suggest that temporal processing, rather than the sensory modality, drives decision-making strategies in children with autism. Our findings highlight the need for interventions aligned with autistic children’s slower but accurate processing style to support social interaction and reduce stress. In a fast-paced digitalized world, autistic children might benefit from slower, balanced, and inclusive, evidence-based approaches that align with their cognitive rhythm and reduce overstimulation. By incorporating these unique strategies, targeted programs can enhance the quality of life and adaptive skills of children with autism, thereby fostering better integration into social and sensory-rich environments. Full article