Search Results (8,169)

Background/Objectives: Senecio scandens Buch.-Ham. is a flavonoid-rich traditional medicinal plant with established immunomodulatory properties. However, the mechanisms underlying the immunoregulatory and intestinal protective effects of its flavonoid extract (Senecio scandens flavonoids—SSF) remain unclear. This study characterized SSF’s bioactive components and evaluated its efficacy against cyclophosphamide (CTX)-induced immunosuppression and intestinal injury. Methods: The constituents of SSF were identified using UHPLC/Q-Orbitrap/HRMS. Mice with CTX-induced immunosuppression were treated with SSF (80, 160, 320 mg/kg) for seven days. Immune parameters (organ indices, lymphocyte proliferation, cytokine, and immunoglobulin levels) and gut barrier integrity markers (ZO-1, Occludin, Claudin-1 protein expression; sIgA secretion; microbiota composition) were assessed. Network pharmacology combined with functional assays elucidated the underlying regulatory mechanisms. Results: Twenty flavonoids were identified in SSF, with six prototype compounds detectable in the blood. The SSF treatment significantly ameliorated CTX-induced weight loss and atrophy of the thymus and spleen. It enhanced splenic T- and B-lymphocyte proliferation by 43.6% and 29.7%, respectively; normalized the CD4⁺/CD8⁺ ratio (1.57-fold increase); and elevated levels of IL-2, IL-6, IL-10, TNF-α, IFN-γ, IgM, and IgG. Moreover, SSF reinforced the intestinal barrier by upregulating tight junction protein expression and sIgA levels while modulating the gut microbiota, enriching beneficial taxa (e.g., the Lachnospiraceae_NK4A136_group, Akkermansia) and suppressing pathogenic Alistipes. Mechanistically, SSF activated the TLR/MyD88/NF-κB pathway, with isoquercitrin identified as a pivotal bioactive constituent. Conclusions: SSF effectively mitigates CTX-induced immunosuppression and intestinal damage. These findings highlight SSF’s potential as a dual-functional natural agent for immunomodulation and intestinal protection. Subsequent research should validate isoquercitrin’s molecular targets and assess SSF’s clinical efficacy. Full article

As an efficient clean energy technology, water electrolysis for hydrogen production has its efficiency limited by the sluggish oxygen evolution reaction (OER) kinetics, which drives the demand for the development of high-performance anode OER catalysts. This work constructs bimetallic (Al, Mn) co-doped nanoporous spinel CoFe₂O₄ (np-CFO) with a tunable structure and composition as an OER catalyst through a simple two-step dealloying strategy. The as-formed np-CFO (Al and Mn) features a hierarchical flaky configuration; that is, there are a large number of fine nanosheets attached to the surface of a regular micron-sized flake, which not only increases the number of active sites but also enhances mass transport efficiency. Consequently, the optimized catalyst exhibits a low OER overpotential of only 320 mV at a current density of 10 mA cm⁻², a minimal Tafel slope of 45.09 mV dec⁻¹, and exceptional durability. Even under industrial conditions (6 M KOH, 60 °C), it only needs 1.83 V to achieve a current density of 500 mA cm⁻² and can maintain good stability for approximately 100 h at this high current density. Theoretical simulations indicate that Al and Mn co-doping could indeed optimize the electronic structure of CFO and thus decrease the energy barrier of OER to 1.35 eV. This work offers a practical approach towards synthesizing efficient and stable OER catalysts. Full article

Introduction: Despite clinical evidence for efficacy, there has been minimal uptake of transcranial direct current stimulation (tDCS) for musculoskeletal conditions. Thus, our objective was to explore the perceptions and experiences of people living with lower-limb musculoskeletal injury as well as healthy physically active populations and relate this to the usage of tDCS and key aspects of tDCS design that would improve the capacity for implementation. Methods: We conducted a qualitative descriptive study of 16 participants (44% women) using semi-structured focus groups to identify the descriptions and experiences of people living with lower-limb musculoskeletal injury and healthy physically active populations. A thematic template was used to create a coding structure. Codes were then grouped, and key themes were derived from the data. Results: Four primary themes were identified from focus groups. These were (i) the impact of musculoskeletal injuries on health and quality of life, (ii) performance and injury recovery as facilitators to using tDCS, (iii) barriers and facilitators to tCDS application and (iv) design and aesthetic factors for a tDCS device. Discussion: Our qualitative descriptive study identified four themes relevant to the successful implementation of tDCS into rehabilitative and performance practice. To increase the likelihood of successful tDCS implementation, these barriers should be addressed and facilitators promoted. This should include innovative approaches to device application and structure that allow for a stylish, user-friendly design. Full article

Background/Objectives: Physical activity is a cornerstone of diabetes mellitus (DM) management and is strongly recommended in the American Diabetes Association (ADA)’s guidelines. This study aims to investigate the self-reported physical activity levels of individuals with DM in Germany, as well as the barriers and facilitators they encounter. Methods: Individuals with type 1 DM (T1DM) and type 2 DM (T2DM) were asked to fill out an online questionnaire that was partly based on the International Physical Activity Questionnaire (IPAQ). Results: The questionnaire was completed by 338 persons with either T1DM (57.1%) or T2DM (42.9%) (females: 56.2%, males: 42.0%, gender diverse persons: 1.8%) of all age groups (at least 18 years). In total, 80.5% of respondents were aware of the current physical activity recommendations. Among the respondents, 58% reported meeting the recommendations for endurance-type physical activity, while only 30.5% reported meeting those for strength training. The three most frequently cited barriers to physical activity were lack of time, lack of motivation and current state of health. Supporting factors included coverage of costs, availability of exercise programs in close proximity to the patient’s home and target group specific exercise programs. Conclusions: The results imply that many individuals with DM in Germany do not meet ADA’s physical activity recommendations, especially considering that self-reports often overestimate actual behavior. In particular, the actual number of individuals who regularly engage in strength training may be too low. There is a clear need to better communicate the benefits of different forms of physical training and to provide physical activity programs aligned with patients’ individual needs. Full article

Fine particulate matter (PM_2.5) exposure has been linked to increased lung damage due to compromised vascular barrier function, while 3-deoxysappanchalcone (3-DSC), a chalcone derived from Caesalpinia sappan, is known for its pharmacological benefits such as anti-cancer, anti-inflammatory, and antioxidant effects; however, its potential role in mitigating PM_2.5-induced pulmonary damage remains unexplored. To confirm the inhibitory effects of 3-DSC on PM_2.5-induced pulmonary injury, this research focused on evaluating how 3-DSC influences PM_2.5-induced disruption of the barrier of the endothelial cells (ECs) in the lungs and the resulting pulmonary inflammation. Permeability, leukocyte migration, proinflammatory protein activation, reactive oxygen species (ROS) generation, and histology were assessed in PM_2.5-treated ECs and mice. This study demonstrated that 3-DSC effectively neutralized the reactive oxygen species (ROS) generated by PM_2.5 exposure in the lung endothelial cells, suppressing ROS-triggered p38 MAPK activation while enhancing Akt signaling pathways critical to preserving vascular barrier function. In animal models, 3-DSC administration markedly decreased vascular permeability, attenuated the influx of immune cells into the lung tissue, and lowered inflammatory mediators like cytokines in the airways of PM_2.5-exposed mice. These data suggest that 3-DSC might exert protective effects on PM_2.5-induced inflammatory lung injury and vascular hyperpermeability. Full article

Background: Ulcerative colitis (UC), characterized by chronic intestinal inflammation, epithelial barrier dysfunction, and immune imbalance demands novel ameliorative strategies beyond conventional approaches. Methods: In this study, the probiotic properties of Lactobacillus paracasei L21 (L. paracasei L21) and its ability to ameliorate colitis were evaluated using an in vitro lipopolysaccharide (LPS)-induced intestinal crypt epithelial cell (IEC-6) model and an in vivo dextran sulfate sodium (DSS)-induced UC mouse model. Results: In vitro, L. paracasei L21 decreased levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-8) while increasing anti-inflammatory IL-10 levels (p < 0.05) in LPS-induced IEC-6 cells, significantly enhancing the expression of tight junction proteins (ZO-1, occludin, claudin-1), thereby restoring the intestinal barrier. In vivo, both viable L. paracasei L21 and its heat-inactivated postbiotic (H-L21) mitigated weight loss, colon shortening, and disease activity indices, concurrently reducing serum LPS and proinflammatory mediators. Interventions inhibited NF-κB signaling while activating HIF1α/AhR pathways, increasing IL-22 and mucin MUC2 to restore goblet cell populations. Gut microbiota analysis showed that both interventions increased the abundance of beneficial gut bacteria (Lactobacillus, Dubococcus, and Akkermansia) and improved faecal propanoic acid and butyric acid levels. H-L21 uniquely exerted an anti-inflammatory effect, marked by the regulation of Dubosiella, while L. paracasei L21 marked by the Akkermansia. Conclusions: These results highlight the potential of L. paracasei L21 as a candidate for the development of both probiotic and postbiotic formulations. It is expected to provide a theoretical basis for the management of UC and to drive the development of the next generation of UC therapies. Full article

Background and Objectives: Diabetes is a global public health challenge, with increasing prevalence worldwide. The implementation of artificial intelligence (AI) in the management of this condition offers potential benefits in improving healthcare outcomes. This study primarily investigates the barriers and facilitators perceived by healthcare professionals in the adoption of AI. Secondarily, by analyzing both quantitative and qualitative data collected, it aims to support the potential development of AI-based programs for diabetes management, with particular focus on a possible bottom-up approach. Materials and Methods: A scoping review was conducted following PRISMA-ScR guidelines for reporting and registered in the Open Science Framework (OSF) database. The study selection process was conducted in two phases—title/abstract screening and full-text review—independently by three researchers, with a fourth resolving conflicts. Data were extracted and assessed using Joanna Briggs Institute (JBI) tools. The included studies were synthesized narratively, combining both quantitative and qualitative analyses to ensure methodological rigor and contextual depth. Results: The adoption of AI tools in diabetes management is influenced by several barriers, including perceived unsatisfactory clinical performance, high costs, issues related to data security and decision-making transparency, as well as limited training among healthcare workers. Key facilitators include improved clinical efficiency, ease of use, time-saving, and organizational support, which contribute to broader acceptance of the technology. Conclusions: The active and continuous involvement of healthcare workers represents a valuable opportunity to develop more effective, reliable, and well-integrated AI solutions in clinical practice. Our findings emphasize the importance of a bottom-up approach and highlight how adequate training and organizational support can help overcome existing barriers, promoting sustainable and equitable innovation aligned with public health priorities. Full article

In the preceding and early stages of cancer progression, local drug delivery to pre-cancerous and cancerous skin lesions may be applied as an alternative or supplementary therapy. At present, 5-Fluorouracil, imiquimod, and tirbanibulin creams and ointments have established their place in practice, while several other active pharmaceutical ingredients (APIs) (e.g., calcipotriol, tretinoin, diclofenac) have been repurposed, used off-label, or are currently being investigated in mono- or combined chemotherapies of skin cancers. Apart from them, dozens to hundreds of therapeutics of natural and synthetic origin are proven to possess anti-tumor activity against melanoma, squamous cell carcinoma (SCC), and other skin cancer types in in vitro studies. Their clinical introduction is most often limited by low skin permeability, challenged targeted drug delivery, insufficient chemical stability, non-selective cytotoxicity, or insufficient safety data. A variety of prodrug and nanotechnological approaches, including vesicular systems, micro- and nanoemulsions, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanoparticles, and others, offer versatile solutions for overcoming the biophysical barrier function of the skin and the undesirable physicochemical nature of some drug molecules. This review aims to present the most significant aspects and latest achievements on the subject. Full article

Gut microbiota-derived trimethylamine N-oxide (TMAO) has been implicated in both intestinal and renal diseases; however, its specific role in modulating gut–kidney interactions remains unclear. This study aimed to investigate the effects of TMAO on gut–kidney crosstalk using a mouse model of diarrhea. Mice were divided into four groups: normal, model, TMAO, and TMAO + model. The normal group received sterile water, while the other groups were administered adenine + Folium sennae, TMAO, or a combination of TMAO and adenine + Folium sennae. Samples were collected to assess morphological changes in the colon and kidney, evaluate the colonic mucosal barrier and renal function, and measure NLRP3 inflammasome activity and inflammatory cytokine levels in colonic and renal tissues. TMAO levels and the gut microbiota composition were analyzed using 16S rRNA sequencing. The model group exhibited altered stool morphology, which was further aggravated by TMAO intervention. Both the model and TMAO + model groups exhibited significant damage to intestinal and renal tissues, along with compromised intestinal mucosal barriers and impaired renal function compared to controls. Inflammatory markers were elevated in these groups, with the TMAO + model group showing the most pronounced increases. Correlation analysis indicated significant relationships among TMAO levels, inflammasome activation, and inflammatory cytokines. The genera Mucispirillum and Anaerotruncus negatively correlated with TMAO, whereas Parabacteroides and Parasutterella genera positively correlated with TMAO. In conclusion, TMAO plays a critical role in modulating gut–kidney crosstalk by promoting inflammation, disrupting mucosal and renal integrity, and altering the gut microbial ecosystem. Full article

Background/Objective: The most effective strategy for addressing users’ prosthetic needs is a comprehensive clinical assessment that provides a holistic understanding of the individual’s symptoms, health, function, and environmental barriers and facilitators. A standardized evaluation form would provide guidance for a structured approach to comprehensive clinical assessments of people with LLA. The objective of this study was to determine a list of relevant elements to be included in prosthetic evaluation for adults with lower limb amputation. Methods: Three independent focus group discussions were conducted with prosthetists (n = 15), prosthesis users (n = 11), and decision makers (n = 4) to identify all relevant elements that should be included in the clinical assessment of prosthetic services. The final content was then determined using the Delphi technique, with 35 panelists (18 prosthetists and decision makers, and 17 prosthesis users) voting in each round. Results: A total of 91 elements were identified through the focus group, of which 78 were included through the Delphi process. The identified elements are mostly related to the physical health of the prosthesis user (e.g., mobility, pain, and medical information), while others address personal or psychosocial aspects (e.g., activities of daily living, goals, and motivation) or technical aspects (prosthesis-related). Conclusions: Through a Delphi consensus, a list of relevant elements to be included in a prosthetic evaluation was generated. These results will inform the development of a standardized clinical prosthetic assessment form. This form has the potential to improve the quality of clinical evaluations, guide interventions, and enhance the well-being of prosthetic users. Full article

Schizophrenia is a challenging multifactorial neuropsychiatric disease that involves interactions between genetic susceptibility and environmental insults. Increasing evidence implicates viral infections as significant environmental contributors, particularly during sensitive neurodevelopmental periods. This review synthesises current findings on the viral hypothesis of schizophrenia, encompassing a wide array of neurotropic viruses, including influenza viruses, herpesviruses (HSV-1 and 2, CMV, VZV, EBV, HHV-6 and 8), hepatitis B and C viruses, HIV, HERVs, HTLV, Zika virus, BoDV, coronaviruses (including SARS-CoV-2), and others. These pathogens can contribute to schizophrenia through mechanisms such as direct microinvasion, persistent central nervous system infection, immune-mediated neuroinflammation, molecular mimicry, and the disturbance of the blood–brain barrier. Prenatal exposure to viral infections can trigger maternal immune activation, resulting in cytokine-mediated alterations in the neurological development of the foetus that persist into adulthood. Genetic studies highlight the role of immune-related loci, including major histocompatibility complex polymorphisms, in modulating susceptibility to infection and neurodevelopmental outcomes. Clinical data also support the “mild encephalitis” hypothesis, suggesting that a subset of schizophrenia cases involve low-grade chronic neuroinflammation. Although antipsychotics have some immunomodulatory effects, adjunctive anti-inflammatory therapies show promise, particularly in treatment-resistant cases. Despite compelling associations, pathogen-specific links remain inconsistent, emphasising the need for longitudinal studies and integrative approaches such as viromics to unravel causal relationships. This review supports a “multi-hit” model in which viral infections interfere with hereditary and immunological susceptibilities, enhancing schizophrenia risk. Elucidating these virus–immune–brain interactions may facilitate the discovery of biomarkers, targeted prevention, and novel therapeutic strategies for schizophrenia. Full article

To evaluate the efficiency of innovation development in China’s high-tech manufacturing industry, this paper constructs a two-stage dynamic network cross-efficiency model. This model divides innovation activities into two stages: technology research and development and achievement transformation and introduces a 2-year lag period in the technology research and development stage and a 1-year lag period in the achievement transformation stage. It proposes the overall efficiency and efficiency models for each stage. The model was applied to 30 provinces in China, and the results showed that most provinces have achieved relatively ideal results in the overall efficiency and achievement transformation stage of high-tech manufacturing, while the efficiency in the technology research and development stage is generally lower than that in the achievement transformation stage. It is recommended that enterprises increase their R&D investments, break through technological barriers, and optimize the innovation chain. Full article

Urban transport is a key driver of greenhouse gas emissions in Europe, making its decarbonization essential to achieving EU climate neutrality targets. This study examines how European strategies, such as the Green Deal, the Sustainable and Smart Mobility Strategy, and the Fit for 55 package, are reflected in Romania’s transport policies, with a focus on implementation challenges and urban outcomes in Bucharest. By combining policy analysis, stakeholder mapping, and comparative mobility indicators, the paper critically assesses Bucharest’s current reliance on private vehicles, underperforming public transport satisfaction, and limited progress on active mobility. The study develops a context-sensitive reform framework for the Romanian capital, grounded in transferable lessons from Western and Central European cities. It emphasizes coordinated metropolitan governance, public trust-building, phased car-restraint measures, and investment alignment as key levers. Rather than merely cataloguing policy intentions, the paper offers practical recommendations informed by systemic governance barriers and public attitudes. The findings will contribute to academic debates on urban mobility transitions in post-socialist cities and provide actionable insights for policymakers seeking to operationalize EU decarbonization goals at the metropolitan scale. Full article

Carbon monoxide (CO) is a major toxic gas emitted from vehicle exhaust, industrial processes, and incomplete fuel combustion, posing serious environmental and health risks. Catalytic oxidation of CO into less harmful CO₂ is an effective strategy to reduce these emissions. In this study, we investigated the catalytic performance of platinum (Pt) single atoms doped on C₃N monolayers with various vacancy defects, including single carbon (C_V) and nitrogen (N_V) vacancies, using density functional theory (DFT) calculations. Our results demonstrate that Pt@N_V-C₃N exhibited the most favorable catalytic properties, with the highest O₂ adsorption energy (−3.07 eV). This performance significantly outperforms Pt atoms doped at other vacancies. It can be attributed to the strong binding between Pt and nitrogen vacancies, which contributes to its excellent resistance to Pt aggregation. CO oxidation on Pt@N_V-C₃N proceeds via the Eley–Rideal (ER2) mechanism with a low activation barrier of 0.41 eV for the rate-determining step, indicating high catalytic efficiency at low temperatures. These findings suggest that Pt@N_V-C₃N is a promising candidate for CO oxidation, contributing to developing cost-effective and environmentally sustainable catalysts. The strong binding of Pt atoms to the nitrogen vacancies prevents aggregation, ensuring the stability and durability of the catalyst. The kinetic modeling further revealed that the ER2 mechanism offers the highest reaction rate constants over a wide temperature range (273–700 K). The low activation energy barrier also facilitates CO oxidation at lower temperatures, addressing critical challenges in automotive and industrial pollution control. This study provides valuable theoretical insights for designing advanced single-atom catalysts for environmental remediation applications. Full article

Efflux is one of the key mechanisms used by Gram-negative bacteria to reduce internal antibiotic concentrations. These active transport systems recognize and expel a wide range of toxic molecules, including antibiotics, thereby contributing to reduced antibiotic susceptibility and allowing the bacteria to acquire additional resistance mechanisms. To date, unlike other resistance mechanisms such as enzymatic modification or target mutations/masking, efflux is challenging to detect and counteract in clinical settings, and no standardized methods are currently available to diagnose or inhibit this mechanism effectively. This review first outlines the structural and functional features of major efflux pumps in Gram-negative bacteria and their role in antibiotic resistance. It then explores various strategies used to curb their activity, with a particular focus on efflux pump inhibitors under development, detailing their structural classes, modes of action, and pharmacological potential. We discuss the main obstacles to their development, including the structural complexity and substrate promiscuity of efflux mechanisms, the limitations of current screening methods, pharmacokinetic and tissue distribution issues, and the risk of off-target toxicity. Overcoming these multifactorial barriers is essential to the rational development of less efflux-prone antibiotics or of efflux pump inhibitors. Full article