Search Results (37,756)

Inflammatory bowel disease (IBD) is a chronic, heterogeneous condition characterized by recurrent intestinal inflammation and sustained mucosal barrier damage, profoundly impairing patients’ quality of life and imposing a considerable socioeconomic burden. Current therapeutic options are often constrained by low oral bioavailability, pronounced systemic toxicity, and inadequate tissue specificity, limiting their ability to achieve precise and durable efficacy. In recent years, membrane vesicle-based drug delivery systems (MV-DDSs) have shown considerable promise for precision IBD therapy owing to their excellent biocompatibility, mucosal barrier-penetrating capacity, and low immunogenicity. Building upon a systematic discussion of the roles of MV-DDSs in suppressing inflammatory signaling, modulating oxidative stress, preserving barrier integrity, reshaping the gut microbiota, and regulating programmed cell death, this review further compares the differences in key molecular targets and functional outcomes among vesicles of diverse origins and carrying distinct therapeutic payloads. These insights provide a comprehensive strategic reference and theoretical foundation for the rational design, mechanistic optimization, and clinical translation of MV-DDSs in IBD therapy. Full article

Streak cameras, essential for ultrahigh temporal resolution diagnostics in laser-driven inertial confinement fusion, underpin the streak tube imaging LiDAR (STIL) system—a flash LiDAR technology offering high spatiotemporal resolution, precise ranging, enhanced sensitivity, and wide field of view. This study establishes a theoretical model of the STIL system, with numerical simulations predicting limits of temporal and spatial resolutions of ~6 ps and 22.8 lp/mm, respectively. Dynamic simulations of laser backscatter signals from targets at varying depths demonstrate an optimal distance reconstruction accuracy of 98%. An experimental STIL platform was developed, with the key parameters calibrated as follows: scanning speed (16.78 ps/pixel), temporal resolution (14.47 ps), and central cathode spatial resolution (20 lp/mm). The system achieved target imaging through streak camera detection of azimuth-resolved intensity profiles, generating raw streak images. Feature extraction and neural network-based three-dimensional (3D) reconstruction algorithms enabled target reconstruction from the time-of-flight data of short laser pulses, achieving a minimum distance reconstruction error of 3.57%. Experimental results validate the capability of the system to detect fast, low-intensity optical signals while acquiring target range information, ultimately achieving high-frame-rate, high-resolution 3D imaging. These advancements position STIL technology as a promising solution for applications that require micron-scale depth discrimination under dynamic conditions. Full article

The European Green Deal (EGD) aims at driving the green transition in the EU and positions cities as pivotal actors in achieving climate neutrality and environment protection. Despite ambitious policy commitments, significant implementation gaps persist at the local level impeding urban green transitions. This study assesses barriers to the EGD urban implementation by integrating several methods (scoping literature review, expert consultations, and computational network analysis) to identify structural conditions hampering change. Barriers are clustered into five domains and reviewed by experts to distill eight structural conditions perpetuating the status quo of urban development, hindering transformative change. The findings illustrate how the emerged structural conditions, ranked by their in-degree centrality, regard insufficient policy implementation; upgrade of consolidated built environments’ layout; short-term mindset; lack of knowledge and data sharing among stakeholders; silos in policymaking and development processes; competition among stakeholders over space use; limited social acceptance; and limited financial resources. Conversely, high-out-degree barriers—such as limited technical expertise in urban departments and GDP-oriented paradigms—emerge as system triggers where targeted interventions could catalyze change. This research provides actionable insights for policymakers by identifying leverage points which could promote urban green transitions and enhance the EGD local implementation for accelerating urban green transitions. Full article

In this paper, we report how digital resources support engineering students in the early stages of mathematical modelling within a Challenge-Based Education (CBE) course. The study was conducted in a second-year engineering course involving mathematics, physics, and ethics. Through a case study of two student teams, we analyze how a digital curriculum resource—specifically, a dashboard designed for feedback and progress monitoring—helped students identify, define, and begin modelling a real-world problem related to crowd flow on train platforms. Using the instrumental approach, we examined the dual processes of instrumentation (integration of resources) and instrumentalization (adaptation and repurposing of tools). Results show that the Dashboard played a central role in fostering self-regulated learning, interdisciplinary collaboration, and the iterative refinement of guiding questions. Students used data analysis, simulations, and modelling techniques to build and validate mathematical representations in answer to the guiding questions. Our findings contribute to ongoing discussions on how mathematics education in engineering can be enhanced through activity-based learning and targeted use of digital tools. We argue that digital feedback systems like dashboards can bridge the gap between abstract mathematical content and its meaningful application in engineering contexts, thus fostering engagement, autonomy, and authentic learning. Full article

This review aims to provide a comprehensive overview of the botany, phytochemical composition, and dermatological effects of Cydonia oblonga (CO), with a particular focus on its therapeutic mechanisms across various skin conditions. Among the different parts of the plant, the fruit and peel are especially rich in bioactive compounds, primarily polyphenols such as phenolic acids, anthocyanins, and flavonoids, which are known for their potent antioxidant activity. These constituents contribute significantly to the fruit and peel’s health-promoting properties. To date, multiple extracts derived from various CO parts have been studied in both in vitro and in vivo models. Reported dermatological effects include antioxidant, antimicrobial, anti-inflammatory, anti-allergic, UV-protective, moisturizing, and anti-aging effects, as well as beneficial outcomes in conditions such as wound healing, erythema, and hyperpigmentation. As a result, formulations containing CO-derived compounds have been developed for use in both diseased and healthy skin care. However, only a limited number of these effects have been validated in human clinical studies. Given the promising results from preclinical research, future directions should prioritize in vivo investigations in human subjects to determine optimal concentrations and delivery systems for targeting specific skin disorders. Full article

Schwann cells (SCs) are the primary glial cells of the Peripheral Nervous System (PNS), which insulate and provide protection and nutrients to the axons. Technological and experimental advances in neuroscience, focusing on the biology of SCs, their interactions with other cells, and their role in the pathogenesis of various diseases, have paved the way for exploring new treatment strategies that aim to harness the direct protective or causative properties of SCs in neurological disorders. SCs express cytokines, chemokines, neurotrophic growth factors, matrix metalloproteinases, extracellular matrix proteins, and extracellular vesicles, which promote the inherent potential of the injured neurons to survive and accelerate axonal elongation. The ability of SCs to support the development and functioning of neurons is lost in certain hereditary, autoimmune, metabolic, traumatic, and toxic conditions, suggesting their role in specific neurological diseases. Thus, targeting, modifying, and replacing SC strategies, as well as utilizing SC-derived factors and exosomes, have been considered novel therapeutic opportunities for neuropathological conditions. Preclinical and clinical data have demonstrated that SCs and SC-derived factors can serve as viable cell therapy for reconstructing the local tissue microenvironment and promoting nerve anatomical and functional recovery in both peripheral and central nerve injury repair, as well as in peripheral neuropathies. However, despite the promising successes of genetic engineering of SCs, which are now in preclinical and clinical trials, improving tactics to obtain ‘repair’ SCs and their products from different sources is the key goal for future clinical success. Finally, further development of innovative therapeutic approaches to target and modify SC survival and function in vivo is also urgently needed. Full article

Background: Structurally active phospholipoproteomic formulations that lack pharmacodynamic targets or systemic absorption present unique challenges for validation. Designed for immune compatibility or structural modulation—rather than therapeutic effect—these platforms cannot be evaluated through conventional clinical or molecular frameworks. Methods: This study introduces a standardized, non-invasive ex vivo protocol using real-time kinetic imaging to document biological behavior under neutral conditions. Eight human tumor-derived adherent cell lines were selected for phenotypic stability and imaging compatibility. Phospholipoproteomic preparations were applied under harmonized conditions, and cellular responses were recorded continuously over 48 h. Results: Key parameters included signal continuity, morphological integrity, and inter-batch reproducibility. The system achieved high technical consistency without labeling, endpoint disruption, or destructive assays. Outputs included full kinetic curves and viability signals across multiple cell–fraction pairings. Conclusions: This method provides a regulatorily compatible foundation for functional documentation in non-pharmacodynamic programs where clinical trials are infeasible. It supports early-stage screening, batch comparability, and audit-ready records within SAP, CTD, or real-world evidence (RWE) ecosystems. By decoupling validation from systemic exposure, the protocol enables scalable, technically grounded decision-making for structurally defined immunobiological platforms. Full article

Paracetamol and nonsteroidal anti-inflammatory drugs are the most popular first-line analgesics, being freely available without any medical prescription. For this reason, it is difficult to estimate their actual consumption among the population. One tool for surveillance of pharmaceutical use is wastewater-based epidemiology, a useful approach for monitoring public health by analyzing specific biomarkers in wastewater. Background/Objectives: In this study, the consumption of paracetamol and four nonsteroidal anti-inflammatory drugs (ibuprofen, naproxen, ketoprofen, and diclofenac) was evaluated by analyzing their residues as specific biomarkers in wastewater and the fraction excreted as drug metabolites in urine. Methods: For this purpose, composite wastewater samples were collected from the influent of the wastewater treatment plant in Cluj-Napoca, Romania, in four sampling campaigns (September 2021, February 2022, February 2024, and October 2024), and the target biomarkers were analyzed by liquid chromatography–tandem mass spectrometry. Results: The results of consumption expressed in g/day/1000 inhabitants showed variations for the five studied pharmaceuticals in the following ranges: 6.65–185.57 for paracetamol, 0.32–2.44 for ibuprofen, 0.29–0.82 for naproxen, 0.21–2.65 for ketoprofen, and 0.23–1.11 for diclofenac, depending on the sampling period. This variation can be explained either by the different behaviors regarding the consumption of the pharmaceutical products studied by the population during the sampling periods or by an inappropriate estimate of the number of inhabitants connected to the sewage system. Conclusions: Future studies need to establish a more comprehensive model that considers many other variables that may influence the results obtained through WBE. Full article

China boasts abundant geoheritage, including numerous paleontological geosites; however, many of these geosites are currently at high risk of degradation and face considerable challenges in protection and management. Using Liaoning Province as a case study, this study employs Geographic Information Systems (GIS) and spatial analysis to conduct the systematic data mining of provincial paleontological geosites. We quantitatively examine their spatiotemporal distribution patterns, identify key natural and socio-economic factors influencing their spatial occurrence, and pinpoint areas at high risk of degradation. Results reveal that the distribution of paleontological geosites across prefectural-city, regional, and geological time scales is highly uneven, leading to significant disparities in scientific research, resource allocation, and geotourism development. Significant spatial correlations are observed between the locations of these geosites and natural parameters as well as socio-economic indicators, providing a theoretical foundation for designing targeted conservation measures and precise management strategies. Based on these findings, the study proposes a multi-scale geoheritage conservation framework for Liaoning, which systematically addresses protection strategies across three distinct dimensions: at the prefectural-level city scale, through precise basic management, systematic investigation, and differentiated protection measures; at the regional scale, by enhancing collaborative mechanisms and establishing an integrated conservation network; and at the geological time scale, by deepening value recognition and promoting forward-looking conservation initiatives. This study not only offers tailored recommendations for conserving paleontological heritage in Liaoning, but also presents a transferable research model for other regions rich in paleontological resources worldwide, thereby bridging the gap between geoheritage conservation needs and practical solutions. Full article

Background: This paper provides the first national analysis of antimicrobial use (AMU) of oral and parenteral dosages in Bangladesh, as well as biannual trends for the years from 2019 to 2023. It also analyzes the effect of the COVID-19 pandemic on AMU. Methods: AMU was analyzed in accordance with the WHO Anatomical Therapeutic Chemical classification and defined daily doses per 1000 inhabitants per day methodology. Data on antimicrobial medicine dispatched from manufacturers’ central warehouse was collected and categorized based on the WHO’s Access, Watch, and Reserve (AWaRe) classification. Findings: This AMU surveillance demonstrates an increase in the use of antimicrobial medicines from 2021 to 2022, and in 2023, it decreased, with our national AMU surveillance data indicating that cefixime and azithromycin were the most consumed antibiotics during this period. Most antibiotics used in Bangladesh are broad-spectrum ‘Watch’-category antibiotics. Among oral antibiotics, 50 to 67% are from the ‘Watch’-category. When considering only parenteral antibiotics, 70 to 91 % fall under the ‘Watch’-category. Third-generation cephalosporin consumption has been found to be higher than second- and first-generation cephalosporins. The oral antimicrobials are more commonly used than parenteral ones. AMU notably increased during the COVID-19 pandemic, especially in the case of systemic antibacterial use. Conclusions: To achieve the global target of 70% use of Access category antibiotics by 2030, the use of Watch-group antibiotics, like cefixime, azithromycin, ciprofloxacin, levofloxacin, and ceftibuten, needs to be reduced through investing in and strengthening stewardship programs and eliminating self-medication in Bangladesh. The findings of this study provide useful information to policymakers to tackle AMR in Bangladesh. Full article

Understanding the spatiotemporal dynamics of water quality parameters and microbial communities in drinking water distribution systems (DWDS) and their interrelationships is critical for ensuring the safety of tap water supply. This study investigated the diurnal, monthly, and annual variation patterns of water quality and the stage-specific succession behaviors of microbial communities in a DWDS located in southeastern China. Results indicated that hydraulic shear stress during peak usage periods drove biofilm detachment and particle resuspension. This process led to significant diurnal fluctuations in total cell counts (TCC) and metal ions, with coefficients of variation ranging from 0.44 to 1.89. Monthly analyses revealed the synergistic risks of disinfection by-products (e.g., 24.5 μg/L of trichloromethane) under conditions of low chlorine residual (<0.2 mg/L) and high organic loading. Annual trends suggested seasonal coupling: winter pH reductions correlated with organic acid accumulation, while summer microbial blooms associated with chlorine decay and temperature increase. Nonlinear interactions indicated weakened metal–organic complexation but enhanced turbidity–sulfate adsorption, suggesting altered contaminant mobility in pipe scales. Microbial analysis demonstrated persistent dominance of oligotrophic Phreatobacter and prevalence of Pseudomonas in biofilms, highlighting hydrodynamic conditions, nutrient availability, and disinfection pressure as key drivers of community succession. These findings reveal DWDS complexity and inform targeted operational and microbial risk control strategies. Full article

Background/Objectives: This study examines individual perceptions of national healthcare system efficiency before and after the COVID-19 pandemic across 18 countries grouped into three clusters (the Anglo-world, Europe, East Asia). This paper aims to identify the demographic, socioeconomic, health-related, and macroeconomic healthcare drivers of public assessments, and explain changes in attitudes between 2011–2013 and 2021–2023. Methods: Using individual-level data from the International Social Survey Programme (ISSP) for 2011–2013 and 2021–2023, logistic regression models of perceived healthcare inefficiency are estimated. In addition, the Oaxaca–Blinder decomposition model is adopted in order to decompose the assessment gap between the two periods. Models include a range of individual demographic and socioeconomic characteristics and national healthcare controls (healthcare expenditure, potential years of life lost). Results: Health-related factors, especially self-assessed health and trust in doctors, consistently emerge as predictors of more favourable evaluations across regions and periods. Higher national healthcare expenditure is associated with more positive public views and is the single largest contributor to the improved assessments in 2021–2023. Demographic and socioeconomic variables show smaller regionally and temporally heterogeneous effects. Decomposition indicates that both changes in observed characteristics (notably, expenditure and trust) and unobserved behavioural, cultural, or institutional shifts account for the gap in public healthcare assessments between the two time periods. Conclusions: Public assessments of healthcare systems are primarily shaped by individual health status, trust in providers, and national spending rather than differential demographic and socioeconomic traits. Therefore, policymakers should couple targeted investments in the healthcare sector in order to address adequately public healthcare needs, and strengthen doctor–patient relationships in order to sustain public support. Future research should focus on disentangling the cultural and behavioural pathways influencing healthcare attitudes. Full article

We study the relationship between the physical surface roughness of the glossy surfaces of dielectric objects and the roughness parameter in image rendering. The former refers to a measure of the microscopic surface structure of a real object’s surface. The latter is a model parameter used to produce the realistic appearance of objects. The target dielectric objects to analyze the surface roughness are handcrafted lacquer plates with controlled surface glossiness, as well as several plastics and lacquer products from everyday life. We first define the physical surface roughness as the standard deviation of the surface normal, and provide the computational procedure. We use a laser scanning system to obtain the precise surface height information at tiny flat areas of a surface. Next, a method is developed for estimating the surface roughness parameter based on images taken of the surface with a camera. With a simple setup for observing a glossy flat surface, we estimate the roughness parameter by fitting the Beckmann function to the image intensity distribution in the observed HDR image using the least squares method. A linear relationship is then found between the measurement-based surface roughness and image-based surface roughness. We present applications to glossy objects with curved surfaces. Full article

The etiology and pathophysiology of allergic diseases remain incompletely understood. Current immunological paradigms, while insightful, often fall short in fully elucidating the mechanisms underlying allergic and autoimmune disorders. Under the protein–homeostasis–system (PHS) hypothesis, allergic diseases have etiological substances, and immune reactions against them are responsible for clinical manifestations of allergic diseases. The etiological substances are mainly external in origin and very small with each biochemical property and react to target cells in various organ tissues. Eosinophils, mast cells, and immunoglobulin Es as major immune effectors in allergic diseases control toxic substances according to the chemical or biochemical properties of these substances. Mast cells in the central nervous system may be associated with allergic episodes through connection to peripheral mast cells, and this connection is proposed as the mast cell-associated network. The toxic and/or bioactive proteins/peptides and other non-protein substances, which are derived from injured cells caused by allergic reactions, induce activation of adaptive and innate immune components for controlling the substances. New insights into the etiology and pathophysiology of allergic diseases are introduced with the PHS hypothesis. Full article

In the context of China’s ‘dual carbon’ strategy, sustainable port–city integration has become critical for regional transformation. Based on the green development perspective, this study constructed a “port–industry–city” (PIC) coordinated development indicator system, conceptualizing ports, industries, and cities as distinct but interrelated subsystems. An improved coupling coordination degree model and an obstacle degree model were employed to analyze the coordinated development between Shanghai Port and its associated industries and urban areas during the green transformation process from 2014 to 2023. Three key findings were found: (1) The comprehensive development index of Shanghai Port exhibited a W-shaped fluctuation followed by rapid growth, while the overall PIC system showed a continuous upward trajectory, with the overall development level steadily rising. (2) During Shanghai Port’s green transformation process, the coordination level of the PIC system improved from moderate imbalance to intermediate coordination, though the overall level still requires improvement. (3) Port green transformation, infrastructure, and urban ecology represent primary obstacles requiring targeted, sustainable interventions. This study enriches the research on port–industry–city coordination and provides both theoretical support and a policy foundation for promoting regional sustainable development led by green port initiatives. Full article