Search Results (9,639)

Osteoarthritis (OA) remains a major contributor to pain and disability; however, the current management is largely reactive, focusing on symptoms rather than preventing irreversible cartilage loss. This review first examines the mechanistic foundations for pharmacological chondroprotection—illustrating how conventional agents, such as glucosamine sulfate and chondroitin sulfate, can potentially restore extracellular matrix (ECM) components, may attenuate catabolic enzyme activity, and might enhance joint lubrication—and explores the delivery challenges posed by avascular cartilage and synovial diffusion barriers. Subsequently, a practical “What–How–When” framework is introduced to guide community pharmacists in risk screening, DMOAD selection, chronotherapeutic dosing, safety monitoring, and lifestyle integration, as exemplified by the CHONDROMOVING infographic brochure designed for diverse health literacy levels. Building on these strategies, the P4–4P Chondroprotection Framework is proposed, integrating predictive risk profiling (physicians), preventive pharmacokinetic and chronotherapy optimization (pharmacists), personalized biomechanical interventions (physiotherapists), and participatory self-management (patients) into a unified, feedback-driven OA care model. To translate this framework into routine practice, I recommend the development of DMOAD-specific clinical guidelines, incorporation of chondroprotective chronotherapy and interprofessional collaboration into health-professional curricula, and establishment of multidisciplinary OA management pathways—supported by appropriate reimbursement structures, to support preventive, team-based management, and prioritization of large-scale randomized trials and real-world evidence studies to validate the long-term structural, functional, and quality of life benefits of synchronized DMOAD and exercise-timed interventions. This comprehensive, precision-driven paradigm aims to shift OA care from reactive palliation to true disease modification, preserving cartilage integrity and improving the quality of life for millions worldwide. Full article

Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) is eroding therapeutic options for urinary tract infections. We isolated a multidrug-resistant strain from the urine of a chronically bacteriuric patient and confirmed its identity by Vitek-2 and MALDI-TOF MS. Initial disk-diffusion profiling against 48 antibiotics revealed susceptibility to only 5 agents. One month later, repeat testing showed that tetracycline alone remained active, highlighting the strain’s rapidly evolving resistome. Given the scarcity of drug options, we performed an “aromatogram” with seven pure essential oils, propolis, and two commercial phytotherapeutic blends. Biomicin Forte^® produced a 30 mm bactericidal halo, while thyme, tea tree, laurel, and palmarosa oils yielded clear inhibition zones of 11–22 mm. These in vitro data demonstrate that carefully selected plant-derived products can target CR-Kp where conventional antibiotics fail. Integrating aromatogram results into One Health’s stewardship plans may therefore help preserve last-line antibiotics and provide adjunctive options for persistent urinary infections. Full article

It is believed that caspases may play a significant role in the development of cancer, and the expression levels of genes encoding these proteins may influence the prognosis and clinical course of cancer. Taking into account the information presented, we examined the expression profiles of 11 genes from the caspase family in patients diagnosed with triple-negative breast cancer (TNBC). We qualified 29 patients with TNBC. A fragment of the tumor and a fragment of normal tissue surrounding the tumor were collected from each patient. Then, RNA was isolated, and the reverse transcription process was performed. The expression levels of caspase family genes were determined using the real-time PCR method. The obtained data were correlated with clinical data and compared with data from the Cancer Genome Atlas database using the Breast Cancer Gene Expression Miner v4.8 and Ualcan. Based on the results of the conducted research, it can be assumed that the levels of expression of caspase family genes may be correlated with the clinical course of cancer in patients with TNBC, and further research may indicate that profiling the expression levels of these genes may be used in selecting personalized treatment methods. Full article

This study aims to develop an optimal underwriting strategy for affordable (H1 and M1) and premium (L1 and M2) electric vehicles (EVs), balancing financial risk and sustainability commitments. The research is motivated by regulatory pressures, risk management needs, and sustainability goals, necessitating an adaptation of traditional underwriting models. The study employs a modified Delphi method with industry experts to identify key risk factors, including accident risk, repair costs, battery safety, driver behavior, and PCAF carbon impact. A sensitivity analysis was conducted to examine premium adjustments under different risk scenarios, categorizing EVs into four risk segments: Low-Risk, Low-Carbon (L1); Medium-Risk, Low-Carbon (M1); Medium-Risk, High-Carbon (M2); and High-Risk, High-Carbon (H1). Findings indicate that premium EVs (L1 and M2) exhibit lower volatility in underwriting costs, benefiting from advanced safety features, lower accident rates, and reduced carbon attribution penalties. Conversely, budget EVs (H1 and M1) experience higher premium fluctuations due to greater accident risks, costly repairs, and higher carbon costs under PCAF implementation. The worst-case scenario showed a 14.5% premium increase, while the best-case scenario led to a 10.5% premium reduction. The study recommends prioritizing premium EVs for insurance coverage due to their lower underwriting risks and carbon efficiency. For budget EVs, insurers should implement selective underwriting based on safety features, driver risk profiling, and energy efficiency. Additionally, incentive-based pricing such as telematics discounts, green repair incentives, and low-carbon charging rewards can mitigate financial risks and align with net-zero insurance commitments. This research provides a structured framework for insurers to optimize EV underwriting while ensuring long-term profitability and regulatory compliance. Full article

Background: Bimekizumab, secukinumab, and ixekizumab are IL-17-targeting biologics approved for the treatment of moderate-to-severe plaque psoriasis. While secukinumab and ixekizumab selectively inhibit IL-17A, bimekizumab targets both IL-17A and IL-17F, potentially providing greater anti-inflammatory efficacy. This study aimed to compare the real-world effectiveness, safety, and tolerability of these agents in a Polish dermatology center between 2019 and 2024. Methods: We conducted a retrospective analysis of 98 patients meeting at least one of the following criteria: PASI ≥ 10, BSA ≥ 10, DLQI ≥ 10, or involvement of special areas with inadequate response or contraindications to ≥2 systemic therapies. Patients with prior exposure only to IL-17 inhibitors were excluded. PASI, BSA, and DLQI scores were recorded at baseline, week 4, and week 12. Due to differences in dosing schedules, outcomes were aligned using standardized timepoints and exponential modeling of continuous response trajectories. Mixed-effects ANOVA was used to assess the influence of baseline factors (age, BMI, PsA status) on treatment outcomes. Adverse events were documented at each monthly follow-up visit. Results: Bimekizumab showed the greatest effect size for PASI reduction (Hedges’ g = 3.662), followed by secukinumab (2.813) and ixekizumab (1.986). Exponential modeling revealed a steeper response trajectory with bimekizumab (intercept = 0.289), suggesting a more rapid PASI improvement. The efficacy of bimekizumab was particularly notable in patients who were previously treated with IL-23 inhibitors. All three agents demonstrated favorable safety profiles, with no serious adverse events or discontinuations. The most frequent adverse events were mild and included upper respiratory tract infections and oral candidiasis. Conclusions: This real-world analysis confirmed that IL-17 inhibitors effectively improved PASI, BSA, and DLQI scores in moderate-to-severe psoriasis. Bimekizumab demonstrated the most rapid early improvements and a higher modeled likelihood of complete clearance, without significant differences at week 12. All agents were well tolerated, underscoring the need for further individualized, large-scale studies. Full article

In the context of the valorization of agri-food by-products, tomato (Solanum lycopersicum L.) seeds represent a protein-rich matrix containing potential bioactives. The aim of the present work is to develop a biochemical pipeline for (i) achieving high protein recovery from tomato seed, (ii) optimizing the hydrolysis with different proteases, and (iii) characterizing the resulting peptides. This approach was instrumental for obtaining and selecting the most promising peptide mixture to test for antifungal activity. To this purpose, proteins from an alkaline extraction were treated with bromelain, papain, and pancreatin, and the resulting hydrolysates were assessed for their protein/peptide profiles via SDS-PAGE, SEC-HPLC, and RP-HPLC. Bromelain hydrolysate was selected for antifungal tests due to its greater quantity of peptides, in a broader spectrum of molecular weights and polarity/hydrophobicity profiles, and higher DPPH radical scavenging activity, although all hydrolysates exhibited antioxidant properties. In vitro assays demonstrated that the bromelain-digested proteins inhibited the growth of Fusarium graminearum and F. oxysporum f.sp. lycopersici in a dose-dependent manner, with a greater effect at a concentration of 0.1 mg/mL. The findings highlight that the enzymatic hydrolysis of tomato seed protein represents a promising strategy for converting food by-products into bioactive agents with agronomic applications, supporting sustainable biotechnology and circular economy strategies. Full article

Landslides are among the most hazardous natural phenomena affecting Greater Abidjan, causing significant economic and social damage. Strategic planning supported by geographic information systems (GIS) can help mitigate potential losses and enhance disaster resilience. This study evaluates landslide susceptibility using logistic regression and frequency ratio models. The analysis is based on a dataset comprising 54 mapped landslide scarps collected from June 2015 to July 2023, along with 16 thematic predictor variables, including altitude, slope, aspect, profile curvature, plan curvature, drainage area, distance to the drainage network, normalized difference vegetation index (NDVI), and an urban-related layer. A high-resolution (5-m) digital elevation model (DEM), derived from multiple data sources, supports the spatial analysis. The landslide inventory was randomly divided into two subsets: 80% for model calibration and 20% for validation. After optimization and statistical testing, the selected thematic layers were integrated to produce a susceptibility map. The results indicate that 6.3% (0.7 km²) of the study area is classified as very highly susceptible. The proportion of the sample (61.2%) in this class had a frequency ratio estimated to be 20.2. Among the predictive indicators, altitude, slope, SE, S, NW, and NDVI were found to have a positive impact on landslide occurrence. Model performance was assessed using the area under the receiver operating characteristic curve (AUC), demonstrating strong predictive capability. These findings can support informed land-use planning and risk reduction strategies in urban areas. Furthermore, the prediction model should be communicated to and understood by local authorities to facilitate disaster management. The cost function was adopted as a novel approach to delineate hazardous zones. Considering the landslide inventory period, the increasing hazard due to climate change, and the intensification of human activities, a reasoned choice of sample size was made. This informed decision enabled the production of an updated prediction map. Optimal thresholds were then derived to classify areas into high- and low-susceptibility categories. The prediction map will be useful to planners in helping them make decisions and implement protective measures. Full article

Identifying habitat characteristics is essential for conserving critically endangered species. When quantifying species habitat characteristics, ignoring data types may lead to misunderstandings about species’ specific habitat requirements. This study focused on the critically endangered Chinese pangolin in Guangdong Province, China, and divided the study area into 600 m × 600 m grids based on its average home range. The burrow number within each grid was obtained through line transect surveys, with burrow numbers/line transect lengths used as direct indicators of habitat utilization intensity. The relationships with sixteen environmental variables, which could be divided into three categories, including topographic, human disturbance and land cover composition, were quantified using the GAM method. We also converted continuous data into binary data (0, 1), constructed GAMs and compared them with habitat utilization intensity models. Our results indicate that the habitat utilization intensity model identified profile curvature and slope as primary factors, showing a nonlinear response to profile curvature (Edf = 5.610, p = 0.014) and a positive relationship with slope (Edf = 1.000, p = 0.006). The presence–absence model emphasized distance to water (Edf = 1.000, p = 0.014), slope (Edf = 1.709, p = 0.043) and aspect (Edf = 2.000, p = 0.026). The intensity model explained significantly more deviance, captured complex nonlinear relationships and supported higher model complexity without overfitting. This study demonstrates that habitat utilization intensity data provides a more ecologically informative basis for in situ conservation (e.g., identifying core habitats), and the process from habitat selection to habitat utilization should be integrated to reveal species’ habitat characteristics. Full article

Plant genetics and chemotaxonomic analysis are considered key parameters in understanding evolution, plant diversity and adaptation. Korean Peninsula has a unique biogeographical landscape that supports various aromatic plant species, each with considerable ecological, ethnobotanical, and pharmacological significance. This review aims to provide a comprehensive overview of the chemotaxonomic traits, biological activities, phylogenetic relationships and potential applications of Korean aromatic plants, highlighting their significance in more accurate identification. Chemotaxonomic investigations employing techniques such as gas chromatography mass spectrometry, high-performance liquid chromatography, and nuclear magnetic resonance spectroscopy have enabled the identification of essential oils and specialized metabolites that serve as valuable taxonomic and diagnostic markers. These chemical traits play essential roles in species delimitation and in clarifying interspecific variation. The biological activities of selected taxa are reviewed, with emphasis on antimicrobial, antioxidant, anti-inflammatory, and cytotoxic effects, supported by bioassay-guided fractionation and compound isolation. In parallel, recent advances in phylogenetic reconstruction employing DNA barcoding, internal transcribed spacer regions, and chloroplast genes such as rbcL and matK are examined for their role in clarifying taxonomic uncertainties and inferring evolutionary lineages. Overall, the search period was from year 2001 to 2025 and total of 268 records were included in the study. By integrating phytochemical profiling, pharmacological evidence, and molecular systematics, this review highlights the multifaceted significance of Korean endemic aromatic plants. The conclusion highlights the importance of multidisciplinary approaches including metabolomics and phylogenomics in advancing our understanding of species diversity, evolutionary adaptation, and potential applications. Future research directions are proposed to support conservation efforts. Full article

Disparities in the functional classification of secretory genes among aphid taxa may be attributed to variations in coding sequences and gene expression profiles. However, the driving factors that regulate sequence evolution remain unclear. This study aimed to investigate the differences in coding sequences and expression patterns of secretory genes between the rose grain aphid (Metopolophium dirhodum) and the pea aphid (Acrythosiphon pisum), with a particular focus on their roles in evolutionary adaptations and functional diversity. The study involved the rearing of aphids, RNA extraction, de novo transcriptome assembly, functional annotation, secretory protein prediction, and comparative analysis of coding sequences and expression patterns across various functional categories using bioinformatics tools. The results revealed that metabolic genes exhibited greater coding sequence divergence, indicating the influence of positive selection. Moreover, significant expression divergence was noted among functional categories, particularly in metabolic and genetic information processing genes, which exhibited higher variability. This study enhances our understanding of the molecular mechanisms that contribute to phenotypic and genetic diversity among aphid species. This study elucidates the relationship between variations in coding sequences and differences in gene expression among functional categories, thereby establishing a foundation for future studies on gene evolution in response to environmental pressures. Full article

Background: Lung cancer remains the leading cause of cancer-related mortality worldwide. Advances in screening, diagnosis, and management have transformed clinical practice, particularly with the integration of immunotherapy and target therapies. Methods: A systematic literature search was carried out for the period between October 2016 to September 2024. Phase II and III randomized trials evaluating ICI monotherapy, ICI–chemotherapy combinations, and dual ICI regimens in patients with advanced NSCLC were included. Outcomes of interest included overall survival (OS), progression-free survival (PFS), and treatment-related adverse events (AEs). Results: PD-1-targeted therapies demonstrated superior OS compared to PD-L1-based regimens, with cemiplimab monotherapyranking highest for OS benefit (posterior probability: 90%), followed by sintilimab plus platinum-based chemotherapy (PBC) and pemetrexed—PBC. PFS atezolizumab plus bevacizumab and PBC, and camrelizumab plus PBC were the most effective regimens. ICI–chemotherapy combinations achieved higher ORRs but were associated with greater toxicity. The most favorable safety profiles were observed with cemiplimab, nivolumab, and avelumab monotherapy, while atezolizumab plus PBC and sugemalimab plus PBC carried the highest toxicity burdens. Conclusions: In PD-L1-unselected advanced NSCLC, PD-1 blockade—particularly cemiplimab monotherapy—and rationally designed ICI–chemotherapy combinations represent the most efficacious treatment strategies. Balancing efficacy with safety remains critical, especially in the absence of predictive biomarkers. These findings support a patient-tailored approach to immunotherapy and highlight the need for further biomarker-driven and real-world investigations to optimize treatment selection. Full article

Background: Colorectal cancer (CRC) is a prevalent gastrointestinal malignancy, ranking third in incidence and second in cancer-related mortality. Despite therapeutic advances, challenges such as chemotherapy toxicity and drug resistance persist. Thus, there is an urgent need for novel CRC treatments. However, developing new drugs is time-consuming and resource-intensive. As a more efficient approach, drug repurposing offers a promising alternative for discovering new therapies. Methods: In this study, we screened 1068 small molecular compounds from an FDA-approved drug library in CRC cells. Menadione was selected for further study based on its activity profile. Mechanistic analysis included a cell death pathway PCR array, differential gene expression, enrichment, and network analysis. Gene expressions were validated by RT-qPCR. Results: We identified menadione as a potent anti-tumor drug. Menadione induced three programmed cell death (PCD) signaling pathways: necroptosis, apoptosis, and autophagy. Furthermore, we found that the anti-tumor effect induced by menadione in CRC cells was mediated through a key gene: MAPK8. Conclusions: By employing methods of cell biology, molecular biology, and bioinformatics, we conclude that menadione can induce multiple forms of PCD in CRC cells by activating MAPK8, providing a foundation for repurposing the “new use” of the “old drug” menadione in CRC treatment. Full article

This study investigates the propagation characteristics and field distribution of photonic crystals composed of epsilon-near-zero (ENZ) materials and metal cylinders. The research reveals that the cutoff frequency of the photonic crystal formed by combining metal cylinders with an ENZ background is independent of the volume fraction of the metal cylinders and exhibits a stop-band profile within the measured frequency range. This unique behavior is attributed to the scattering of long-wavelength light when the wavelength approaches the effective wavelength range of the ENZ material. Taking advantage of this feature, the study selectively filters specific wavelength ranges from the mid-frequency band by varying the ratio of cylinder radius to lattice constant (R/a). Decreasing the R/a ratio enables the design of waveguide devices that operate over a broader guided wavelength range within the intermediate-frequency band. The findings emphasize the importance of the interaction between light and ENZ materials in shaping the transmission characteristics of photonic crystal structures. Full article

In response to increasingly stringent emission regulations, low-carbon fuels have received significant attention as sustainable energy sources for internal combustion engines. This study investigates four representative low-carbon fuels, methane, methanol, hydrogen, and ammonia, by systematically summarizing their combustion characteristics and emission profiles, along with a review of existing after-treatment technologies tailored to each fuel type. For methane engines, unburned hydrocarbon (UHC) produced during low-temperature combustion exhibits poor oxidation reactivity, necessitating integration of oxidation strategies such as diesel oxidation catalyst (DOC), particulate oxidation catalyst (POC), ozone-assisted oxidation, and zoned catalyst coatings to improve purification efficiency. Methanol combustion under low-temperature conditions tends to produce formaldehyde and other UHCs. Due to the lack of dedicated after-treatment systems, pollutant control currently relies on general-purpose catalysts such as three-way catalyst (TWC), DOC, and POC. Although hydrogen combustion is carbon-free, its high combustion temperature often leads to elevated nitrogen oxide (NO_x) emissions, requiring a combination of optimized hydrogen supply strategies and selective catalytic reduction (SCR)-based denitrification systems. Similarly, while ammonia offers carbon-free combustion and benefits from easier storage and transportation, its practical application is hindered by several challenges, including low ignitability, high toxicity, and notable NO_x emissions compared to conventional fuels. Current exhaust treatment for ammonia-fueled engines primarily depends on SCR, selective catalytic reduction-coated diesel particulate filter (SDPF). Emerging NO_x purification technologies, such as integrated NO_x reduction via hydrogen or ammonia fuel utilization, still face challenges of stability and narrow effective temperatures. Full article

Background: Anti-synthetase Syndrome (ASyS) is an idiopathic inflammatory myopathy characterized by muscle weakness and inflammatory infiltrates in muscles. Sjogren’s disease (SD) is an autoimmune condition primarily affecting exocrine glands. Both these conditions may present lung involvement. We describe a female patient with anti-synthetase/SD overlap syndrome and review the literature to identify published cases describing this overlap, aiming to better define its clinical, radiological, and serological features. Methods: The case description was based on a retrospective collection of clinical, laboratory, and imaging data related to the patient’s diagnostic process and clinical course. Data were anonymized and handled in accordance with the competent territorial Ethics Committee. A literature review was performed using the MEDLINE and Scopus databases by combining the keywords “Anti-Synthetase syndrome”, “Sjögren disease”, “Sjögren syndrome”, “Myositis”, and “Interstitial lung disease” (ILD). Published cases were selected if they met the 2016 EULAR/ACR criteria for SD and at least one of the currently proposed classification criteria for ASyS. Results: The described case concerns a 68-year-old woman with rapidly progressive ILD. The diagnosis of anti-synthetase/SD overlap syndrome was based on clinical, serological (anti-Ro52 and anti-PL7 antibodies), histological, and radiological findings. Despite immunosuppressive and antifibrotic treatment, the clinical course worsened, leading to a poor outcome. In addition, six relevant cases were identified in the literature. Clinical presentations, autoantibody profiles, radiological findings, and outcomes were highly heterogeneous. Among the reported cases, no standardized treatment protocols were adopted, reflecting the lack of consensus in managing this rare condition. Conclusions: In anti-synthetase/SD overlap syndrome, ILD may follow a rapidly progressive course. Early recognition can be challenging, especially in the absence of muscular involvement. This case-based review highlights the need for more standardized approaches to the diagnosis and management of this rare and complex overlap syndrome. Full article