Search Results (510)

Background: High plasma levels of Galectin-3 (Gal-3) and uric acid (UA) are associated with a decline in renal function in different populations. However, this association has not yet been studied in patients with coronary artery disease (CAD). Methods: We included 556 patients with stable CAD. Plasma levels of Gal-3, UA, N-Terminal probrain natriuretic peptide (NT-proBNP), calcidiol, fibroblast growth factor 23, phosphate, parathormone, and klotho were assessed at baseline. The primary outcome was the percentage decrease in eGFR; the secondary outcomes were the absolute decrease in eGFR and achieving a reduction of ≥20% in this parameter. Results: Age was 63.1 ± 12.2 years, and 73.9% of patients were male. The median eGFR was 86.77 (72.27, 97.85) mL/min/1.73 m². After 3.47 (2.10–5.72) years of follow-up, eGFR declined by 3.62% [−2.07–13.82]. Baseline UA (0.012 [CI95% 0.003, 0.020]; p = 0.008), Gal-3 (0.0153 [CI95% 0.001, 0.029]; p = 0.037), and NT-proBNP (0.017 [CI95% 0.000–0.025]; p = 0.027) were independent positive predictors of the percentage decrease in eGFR, while calcidiol (−0.005 [CI95% −0.009, −0.002]; p = 0.005) was an inverse predictor of this outcome. Similarly, UA and Gal-3 were positive independent predictors of the absolute decline in eGFR (0.009 [0.003, 0.017]; p = 0.004 and 0.012 [0.001, 0.023]; p = 0.031, respectively), while calcidiol was inversely associated (−0.003 [−0.005]–[−0.001]; p = 0.020). Uric acid (1.237 [1.046–1.463]; p = 0.013) and NT-proBNP (1.000 [1.000–1.001]; p = 0.049) levels were positive independent predictors of a ≥20% decrease in eGFR. In patients with eGFR ≥ 60 mL/min/1.73 m², UA was the only biomarker independently associated with renal function decline. Conclusions: In patients with CAD and normal or mildly reduced renal function, UA and Gal-3 plasma levels are independent positive predictors of a future decrease in eGFR. These findings could lead to a change in the approach to patients with CAD in the future. Full article

As climate change intensified water scarcity in Southern Europe, tourism-dependent regions such as Portugal’s Algarve faced growing pressure to adapt their water management systems. This study investigated how hotel groups in the Algarve have adopted and communicated water reuse technologies—specifically desalination and greywater recycling—under environmental, institutional, and reputational constraints. A comparative qualitative case study was conducted involving three hotel groups—Vila Vita Parc, Pestana Group, and Vila Galé—selected through purposive sampling based on organizational capacity and technology adoption stage. The analysis was supported by a supplementary mini-case from Mallorca, Spain. Publicly accessible documents, including sustainability reports, media coverage, and policy frameworks, were thematically coded using organizational environmental behavior theory and the OECD Principles on Water Governance. The results demonstrated that (1) higher organizational capacity was associated with greater maturity in water reuse implementation; (2) communication transparency increased alongside technological advancement; and (3) early-stage adopters encountered stronger financial, regulatory, and operational barriers. These findings culminated in the development of the Maturity–Communication–Governance (MCG) Framework, which elucidates how internal resources, stakeholder signaling, and institutional alignment influence sustainable infrastructure uptake. This research offered policy recommendations to scale water reuse in tourism through financial incentives, regulatory simplification, and public–private partnerships. The study contributed to the literature on sustainable tourism and decentralized climate adaptation, aligning with UN Sustainable Development Goals 6.4, 12.6, and 13. Full article

Aging is a multifaceted biological process characterized by a progressive decline in cellular function and physiological resilience, increasing the risk of multiple chronic conditions. Chronic lung diseases frequently manifest within the aging population and are closely intertwined with systemic dysfunctions across cardiovascular, musculoskeletal, and neurological systems. In this review, we explore the biological mechanisms linking aging, multiple chronic conditions patterns, and chronic lung disease, with a particular focus on inflammaging and cellular aging. We also highlight shared pathological pathways such as oxidative stress, mitochondrial dysfunction, and the dysregulation of repair processes that underlie both natural aging and the accelerated aging seen in chronic lung disease. Additionally, we discuss the systemic impact of multiple chronic conditions on patient outcomes, including increased frailty, diminished physical capacity, cognitive impairment, and elevated mortality risk. This review advocates for a comprehensive, patient-centered approach that combines early detection, personalized pharmacological therapies targeting inflammatory and senescent pathways, and non-pharmacological interventions such as pulmonary rehabilitation, exercise, and dietary optimization. Emerging therapeutics, including senolytics and anti-inflammatory agents, present promising avenues for mitigating age-related lung decline and managing multiple chronic conditions. Full article

The recent global coronavirus pandemic highlighted the ever-present threat of respiratory virus outbreaks and the consequent need for ongoing research into antiviral therapy. To this end, structural analogues of the guanidinium-based drug camostat mesylate have been synthesised to probe their potential inhibition of Transmembrane Serine Protease 2 (TMPRSS2), a human protease that is essential for infection by many respiratory viruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Our in vitro fluorescence-based protease assays and supporting computational docking studies suggest that C-terminal camostat analogues retain TMPRSS2 inhibition potencies (IC₅₀ = 1–3 nM, BE = −6.6 to −7.0 kcal/mol) that match or exceed that of the parent drug. Analogues 1c and 1d emerge as lead candidates in this regard, thereby validating the rationale behind C-terminal structural modifications and highlighting these derivatives as promising scaffolds for the future development of targeted antiviral therapeutics. Replacement of camostat’s ester functionality with peptide linkages largely preserves non-covalent binding but disrupts in vitro protease inhibition, findings consistent with the parent drug’s known role as an acylating suicide inhibitor. Docking studies confirm that the replacement of aromatic residues with flexible, equivalent-length alkyl chains is detrimental to drug binding. These function and binding data offer new directions for the synthesis of further analogues of camostat and of other guanidinium-based protease inhibitors that have yet to be refined via structure–activity relationship studies. Further investigation will support tailoring this class of drugs for repurposing in antiviral therapy. Full article

Wind erosion poses a major threat to ecosystem stability and land productivity in arid and semi-arid regions. Accurate identification of its spatiotemporal dynamics and underlying driving mechanisms is a critical prerequisite for effective risk forecasting and targeted erosion control. This study applied the Revised Wind Erosion Equation (RWEQ) model to assess the spatial distribution, interannual variation, and seasonal dynamics of the Soil Wind Erosion Modulus (SWEM) across Inner Mongolia from 1990 to 2022. The GeoDetector model was further employed to quantify dominant drivers, key interactions, and high-risk zones via factor, interaction, and risk detection. The results showed that the average SWEM across the study period was 35.65 t·ha⁻¹·yr⁻¹ and showed a decreasing trend over time. However, localised increases were observed in the Horqin and Hulun Buir sandy lands and central grasslands. Wind erosion was most intense in spring (17.64 t·ha⁻¹·yr⁻¹) and weakest in summer (5.57 t·ha⁻¹·yr⁻¹). Gale days, NDVI, precipitation, and wind speed were identified as dominant drivers. Interaction detection revealed non-linear synergies between gale days and temperature (q = 0.40) and wind speed and temperature (q = 0.36), alongside a two-factor interaction between NDVI and precipitation (q = 0.19). Risk detection indicated that areas with gale days > 58, wind speed > 3.01 m/s, NDVI < 0.2, precipitation of 30.17–135.59 mm, and temperatures of 3.01–4.23 °C are highly erosion-prone. Management should prioritise these sensitive and intensifying areas by implementing site-specific strategies to enhance ecosystem resilience. Full article

Background: With advancements in Generative Artificial Intelligence, various industries have made substantial efforts to integrate this technology to enhance the efficiency and effectiveness of existing processes or identify potential weaknesses. Context, however, remains a crucial factor in leveraging intelligence, especially in high-stakes sectors such as healthcare, where contextual understanding can lead to life-changing outcomes. Objective: This research aims to develop a practical medical multi-agent system framework capable of automating appointment scheduling and triage classification, thus improving operational efficiency in healthcare settings. Methods: We present MedScrubCrew, a multi-agent framework integrating established technologies: Gale-Shapley stable matching algorithm for optimal patient-provider allocation, knowledge graphs for semantic compatibility profiling, and specialized large language model-based agents. The framework is designed to emulate the collaborative decision making processes typical of medical teams. Results: Our evaluation demonstrates that combining these components within a cohesive multi-agent architecture substantially enhances operational efficiency, task completeness, and contextual relevance in healthcare scheduling workflows. Conclusions:MedScrubCrew provides a practical, implementable blueprint for healthcare automation, addressing significant inefficiencies in real-world appointment scheduling and patient triage scenarios. Full article

The mycelia of Hericium erinaceus contain neuroprotective cyathane diterpenoids (e.g., erinacine A). There is evidence that cultivation of submerged mycelia with surfactants increases glucose uptake and biomass, but the impact on erinacine production is unknown. Here, we tested the impact of glucose and polysorbate 80 on the mycelial erinacine profiles of five Hericium strains cultivated under submergence, including those of Hericium erinaceus, Hericium americanum, and Hericium coralloides. Metabolite profiling confirmed that mycelial extracts contained 13% to 91% of the erinacines A, C and P in additive-free cultures of all strains, with the remainder secreted to the culture medium. Overall, erinacine P production was several orders of magnitude greater than that of the other erinacines, except for H. erinaceus (DAOMC 251029), where erinacine C was most evident. H. coralloides (DAOMC 251017) produced the greatest concentrations of erinacines A and P. For the most part mycelial erinacine concentrations were reduced in cultures co-supplemented with glucose and polysorbate 80. This treatment caused an 83–100% reduction in the concentrations of erinacines A, C, and P in the mycelial extracts of most strains. By contrast, there was evidence that glucose and polysorbate 80 had no effect on erinacine A production within mycelia of H. americanum, and erinacine P concentrations in H. erinaceus (DAOMC 251029) and H. americanum (DAOMC 251011). In most strains, the secretion of erinacines to the culture medium declined with glucose and polysorbate 80. Conversely, these additives increased the concentrations of erinacines C and P in the culture medium filtrate of H. americanum (DAOMC 21467) and yielded more secreted erinacine P in H. erinaceus (DAOMC 251029). The information provides feasible strategies to produce mycelia with unique erinacine profiles including those rich in erinacine P. Full article

Air-quality standards (AQS) are key regulatory tools to protect public health by setting pollutant thresholds. However, most are based on sea-level data. High-altitude (HA) environments differ in atmospheric conditions, influencing pollutant behavior and human vulnerability. These differences have prompted proposals for altitude-specific AQS adjustments. This systematic review identifies models and criteria supporting such adaptations and examines regulatory air-quality frameworks in countries with substantial populations living at very high altitudes (VHA). This review follows PRISMA-P guidelines, focusing on studies examining AQS adjustment approaches based on altitude. The Population/Concept/Context (PCC) framework was used to define search terms: population (AQS), concept (air pollutants), and context (altitude), with equivalents. The literature was retrieved from PubMed, Scopus, Web of Science, and Gale OneFile: Environmental Studies and Policy. A total of 2974 articles were identified, with 2093 remaining after duplicate removal. Following title and abstract screening, 2081 papers were excluded, leaving 12 for full-text evaluation. Ultimately, six studies met the eligibility criteria. Three studies focused on adjustment models based on atmospheric conditions, such as temperature and pressure changes, while the other three examined human physiological responses, particularly the increased inhaled air volume. China, Peru, and Bolivia have the largest populations living above 3500 m a.s.l., yet none of these countries have specific air-quality regulations tailored to HA conditions. The review underscores the necessity for tailored AQS in HA environments, highlighting specific criteria related to both atmospheric conditions and human physiological responses. Full article

Background/Objectives: Heparosan is a component of the capsular polysaccharide in Escherichia coli K5 and Pasteurella multocida Type D. It shares a similar glycan structure with heparin and can be enzymatically modified to produce bioactive heparin. Methods: In this study, the probiotic strain E. coli Nissle 1917 (EcN), which naturally produces heparosan, was genetically engineered to utilize sucrose as a carbon source for growth while achieving high-yield heparosan biosynthesis. Results: By expressing the sucrose hydrolase genes sacA (from Bacillus subtilis) or spI (from Bifidobacterium adolescentis), EcN was enabled to utilize sucrose, achieving heparosan titers of 131 mg/L and 179 mg/L, respectively. Further metabolic engineering was performed to block the glycolytic and pentose phosphate pathways, thereby redirecting sucrose-derived glucose-6-phosphate and fructose-6-phosphate toward heparosan biosynthesis, while glycerol was supplemented as an auxiliary carbon source to support cell growth. Finally, the key biosynthesis genes galU, kfiD, and glmM were overexpressed, resulting in an engineered strain with a heparosan titer of 622 mg/L. Conclusions: This study represents the first successful engineering of EcN to utilize sucrose as the carbon source for growth, while achieving enhanced heparosan production through synergistic carbon source utilization. These findings establish a foundational strategy for employing this strain in the sucrose-based biosynthesis of other glycosaminoglycans. Full article

Aluminum (Al) is one of the most abundant metals on Earth and is well known as an environmental neurotoxic agent in the pathogenesis of Alzheimer’s disease. Aluminum toxicity is associated with oxidative stress, reduction of antioxidant enzymes, and disruption of the balance of cellular metals, such as iron (Fe), calcium (Ca), and copper (Cu), which causes structural and functional changes in the nervous tissue of the brain or peripheral nervous system. The intake of functional foods, rich in antioxidants, such as quercetin, may be beneficial in combating oxidative stress and neurodegenerative changes in the brain. The aim of this study was to provide deeper insight into the cellular and molecular neuroprotective effects of quercetin in regulating amyloid-beta (Aβ) accumulation, tau pathology, and neuroinflammation in the Al/D-galactose-induced rat model (Al/D-gal) of AD. The results showed that quercetin successfully modulated the impaired homeostatic and neuropathological consequences of aluminum chloride and D-galactose administration over 28 days: it directly protected neurons by regulating the level of oxidative stress and antioxidants, reduced Aβ aggregation by inhibiting the activity of acetylcholinesterase (AChE), increased the survival, growth, and differentiation of nerve cells by maintaining the level of brain-derived neurotrophic factor (BDNF), and regulated microglial immunoreactivity and neuroinflammation by reducing the level of proinflammatory cytokines. The multiple effects confirm that quercetin can be applied as an alternative non-pharmaceutical approach in reducing Al-induced neurotoxicity and maintaining adaptive homeostasis, which consequently affects the functioning of the central nervous system and the whole organism. Full article

The Global Navigation Satellite System (GNSS), Internet of Things (IoT) and cloud computing technologies enable high-precision positioning with flexible data communication, making real-time/near-real-time monitoring more economical and efficient. In this study, a multi-sensor GNSS-IoT system was developed for measuring precise water surface elevation (WSE). The system, which includes ultrasonic and accelerometer sensors, was deployed on a floating platform in Googong reservoir, Australia, over a four-month period in 2024. WSE data derived from the system were compared against independent reference measurements from the reservoir operator, achieving an accuracy of 7 mm for 6 h averaged solutions and 28 mm for epoch-by-epoch solutions. The results demonstrate the system’s potential for remote, autonomous WSE monitoring and its suitability for validating satellite Earth observation data, particularly from the Surface Water and Ocean Topography (SWOT) mission. Despite environmental challenges such as moderate gale conditions, the system maintained robust performance, with over 90% of solutions meeting quality assurance standards. This study highlights the advantages of combining the GNSS with IoT technologies and multiple sensors for cost-effective, long-term WSE monitoring in remote and dynamic environments. Future work will focus on optimizing accuracy and expanding applications to diverse aquatic settings. Full article

V. S. Naipaul’s 1975 novel Guerrillas is the earliest example of Caribbean fiction that purports to provide a realistic depiction of Trinidad’s brief but historically significant Black Power movement. Naipaul was an Indo-Trinidadian expatriate who immigrated to the U.K. in 1950 and remained there until his death in 2018. He was famously Anglophilic; and given his notorious insistence that culturally the West Indies are derivative, not creative, it is unsurprising that Naipaul depicts Black Power as an empty form that Trinidad and Great Britain import to their detriment from the U.S. In its fictionalization of the story of a real-life figure on the periphery of Black Power, Guerrillas presents Black Power’s presence in Trinidad and the UK as a failure and a sham. My article traces Naipaul’s transformation of what was originally a journalistic account into his novel Guerrillas in order to highlight the tendentiousness of his representation of Trinidadian Black Power. The plot of the novel repurposes the crux of Naipaul’s essay “The Killings in Trinidad” in which he reports how a Trinidadian Black Power poseur known as “Michael X” conspired in the January 1972 murder of a white woman named Gale Ann Benson. Crucial to Naipaul’s dismissal of Black Power as a derivative fiction, this article argues, is the fraudulent Michael X, himself a mimic man par excellence in his embodiment of Black Power as an empty and parodic form devoid of original content. I demonstrate how Naipaul’s marginalization of Caribbean Black Power depends on formal mimicry and on his selection of this marginal player/mimic man as representative of the movement in Trinidad. Full article

Prior research has reported an association between human papillomavirus (HPV) seropositivity and dementia or Alzheimer’s disease. This study aimed to cross-sectionally investigate the association between HPV seropositivity and cognitive function in older adults. The data used for this study were from the 2011–2014 National Health and Nutrition Examination Survey (NHANES) cycles. To account for the complex survey design and missing data, we applied survey-weighted regression models to each imputed dataset, using multiple imputation techniques. Across all cognitive test outcomes, no statistically significant association was observed between HPV status and cognitive performance after controlling for covariates. These findings suggest that there may not be a significant association between HPV infection and cognitive scores in this NHANES sample. Stakeholders, including policymakers and healthcare providers, should consider these findings in their professional decision-making. Future research should investigate the association between HPV seropositivity and cognition using other samples in order to further characterize the association between HPV and cognitive function in older adults. Full article

Lipoprotein (a) [Lp(a)] has been recognized as an independent, inherited, causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis, thus representing a major target of residual CV risk. Currently, no drug has been officially approved for lowering Lp(a) levels, and in clinical practice, Lp(a) is mainly used to (re)define CV risk, particularly in individuals at borderline CV risk and people with a family history of premature coronary heart disease, according to various guidelines. Specific Lp(a)-targeted antisense oligonucleotides (ASOs) and small interfering RNA (siRNA) agents have been developed to produce substantial Lp(a) reductions via the inhibition of apo(a) synthesis in the liver. These drugs are conjugated to N-acetylgalactosamine (GalNAc) to ensure their binding to asialoglycoproteins, which are specifically expressed on the surface of the hepatocytes. Such drugs include pelacarsen (an injectable ASO) and olpasiran, zerlasiran, and lepodisiran (injectable siRNA agents). Muvalaplin represents another therapeutic option to lower Lp(a) levels, since it is an oral selective small molecule inhibitor of Lp(a) formation, thus potentially exerting certain advantages in terms of its clinical use. The present narrative review summarizes the available clinical data on the efficacy and safety of these investigational Lp(a)-lowering therapies, as reported in phase 1 and 2 trials. The effects of these drugs on other [aside from Lp(a)] lipid parameters are also discussed. The phase 3 CV trial outcomes are ongoing for some of these agents (i.e., pelacarsen, olpasiran, and lepodisiran) and are briefly mentioned. Overall, there is an urgent need for evidence-based guidelines on Lp(a) reduction in daily clinical practice, following the results of the phase 3 CV trials, as well as for establishing the ideal Lp(a) quantification method (i.e., using an apo(a) isoform-independent assay with appropriate calibrators, reporting the Lp(a) level in molar units). Full article