Search Results (1,153)

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

The Chinese red panda (Ailurus styani) is a rare and endangered animal in China; the increase in global temperature and the interference of human activities have caused irreversible effects on the suitable habitat of wild red pandas and threatened their survival. Therefore, it is necessary to carry out scientific research and protection for Chinese red pandas. In this study, the MaxEnt model was used to predict and analyze the suitable habitats of Chinese red pandas in the large and small Xiangling Mountains. The results showed that the main ecological factors affecting the suitable habitat distribution of Chinese red pandas in the Daxiangling Mountains are the average slope (45.6%, slope), the distance from the main road (24.2%, road), and the average temperature in the coldest quarter (11%, bio11). The main ecological factors affecting the suitable habitat distribution of Chinese red pandas in the Xiaoxiangling Mountains are bamboo distribution (67.4%, bamboo), annual temperature range (20.7%, bio7), and the average intensity of human activities (8.7%, Human Footprint). The predicted suitable habitat area of the Daxiangling Mountains is 123.835 km², and the predicted suitable habitat area of the Xiaoxiangling Mountains is 341.873 km². The predicted suitable habitat area of the Daxiangling Mountains accounts for 43.45% of the total mountain area, and the predicted suitable habitat area of the Xiaoxiangling Mountains accounts for 71.38%. The suitable habitat area of the Xiaoxiangling Mountains is nearly three times that of the Daxiangling Mountains, and the proportion of suitable habitat area of the Xiaoxiangling Mountains is much higher than that of the Daxiangling Mountains. The suitable habitat of Chinese red pandas in the Daxiangling Mountains is mainly distributed in the southeast, and the habitat is coherent but fragmented. The suitable habitat of Chinese red panda in Xiaoxiangling Mountains is mainly distributed in the east, and the habitat is more coherent. The results of this study can provide a scientific basis for the protection of the population and habitat of Chinese red pandas in Sichuan. Full article

Objectives: To investigate the efficacy and underlying mechanisms of IBCar’s biological activity in breast cancer models, both in cell culture and in mice, and to compare its effects on cancer versus normal cells. Methods: The cytotoxicity of IBCar was evaluated using the MTS assay to assess metabolic activity and the clonogenic assay to determine reproductive integrity. The impact of IBCar on microtubule integrity, mitochondrial function, and multiple signaling pathways was analyzed using Western blotting, microarray analysis, and live cell imaging. The therapeutic effectiveness of orally administered IBCar was assessed in a transgenic mouse model of Luminal B breast cancer and in mice implanted with subcutaneous triple-negative breast cancer xenografts. Results: IBCar demonstrated potent cytotoxicity across a diverse panel of breast cancer cell lines, including those with mutant or wild-type TP53, and cell lines with short and long doubling times. Comparative analysis revealed distinct responses between normal and cancer cells, including differences in IBCar’s effects on the mitochondrial membrane potential, endoplasmic reticulum stress and activation of cell death pathways. In breast cancer cells, IBCar was cytotoxic at nanomolar concentrations, caused irreversible microtubule depolymerization leading to sustained mitochondrial dysfunction, endoplasmic reticulum stress, and induced apoptosis. In normal cells, protective mechanisms included reversible microtubule depolymerization and activation of pro-survival signaling via the caspase-8 and riptosome pathways. The therapeutic potential of IBCar was confirmed in mouse models of Luminal B and triple negative BC, where it exhibited strong antitumor activity without detectable toxicity. Conclusions: These findings collectively support IBCar as a promising, effective, and safe therapeutic candidate for breast cancer treatment. Full article

Colorectal liver metastasis (CRLM) poses a significant challenge in oncology due to its high incidence and poor prognosis in unresectable cases. Current treatments, including surgical resection, systemic chemotherapy, and liver-directed therapies, often fail to effectively target hypoxic tumor regions, which are inherently more resistant to these interventions. This review examines the potential of a novel therapeutic strategy combining irreversible electroporation (IRE) ablation and Clostridium novyi-nontoxic (C. novyi-NT) bacterial therapy. IRE is a non-thermal tumor ablation technique that uses high-voltage electric pulses to create permanent nanopores in cell membranes, leading to cell death while preserving surrounding structures, and is often associated with temporary tumor hypoxia due to disrupted perfusion. C. novyi-NT is an attenuated, anaerobic bacterium engineered to selectively germinate and proliferate in hypoxic tumor regions, resulting in localized tumor cell lysis while sparing healthy, oxygenated tissue. The synergy between IRE-induced hypoxia and hypoxia-sensitive C. novyi-NT may enhance tumor destruction and stimulate systemic antitumor immunity. Furthermore, the integration of advanced imaging and artificial intelligence can support precise treatment planning and real-time monitoring. This integrated approach holds promise for improving outcomes in patients with CRLM, though further preclinical and clinical validation is needed. Full article

Despite advances in surgery, chemotherapy, and radiation treatments for pancreatic ductal adenocarcinoma (PDAC), 5-year survival rates remain at nearly 11%. Cholangiocarcinoma, while not as severe, also possesses similar survival rates. Fewer than 20% of patients are surgical candidates at time of diagnosis; therefore, it is imperative that alternative therapies are effective for non-surgical patients. There are several thermal ablative techniques, including radiofrequency ablation (RFA), high-intensity focused ultrasound (HIFU), microwave ablation (MWA), alcohol ablation, stereotactic body radiotherapy (SBRT), cryoablation, irreversible electroporation (IRE), biliary intraluminal brachytherapy, and biliary photodynamic therapy (PDT). Emerging literature in animal models and human patients has demonstrated that endoscopic ultrasound (EUS)-guided RFA (EUS-RFA) prevents tumor progression through coagulative necrosis, protein denaturation, and activation of anticancer immunity in local and distant tumor tissue (abscopal effect). RFA treatment has been shown to not only reduce tumor-associated immunosuppressive cells but also increase functional T cells in distant tumor cells not treated with RFA. The remarkable ability to reduce tumor progression and promote tumor microenvironment (TME) remodeling makes RFA a very promising non-surgical therapy technique that has the potential to reduce mortality in this patient population. EUS-RFA offers superior precision and safety compared to other ablation techniques for pancreatic and biliary cancers, due to real-time imaging capabilities and minimally invasive nature. Future research should focus on optimizing RFA protocols, exploring combination therapies with chemotherapy or immunotherapy, and expanding its use in patients with metastatic disease. This review article will explore the current data and underlying pathophysiology of EUS-RFA while also highlighting the role of ablative therapies as a whole in immune activation response. Full article

This work proposes a hybrid model that combines the Galam model of opinion dynamics with the Bass diffusion model used in technology adoption on Barabasi–Albert complex networks. The main idea is to advance a version of the Bass model that can suitably describe an opinion formation context while introducing irreversible transitions from group B (opponents) to group A (supporters). Moreover, we extend the model to take into account the presence of a charismatic competitor, which fosters conversion back to the old technology. The approach is different from the introduction of a mean field due to the interactions driven by the network structure. Additionally, we introduce the Kolmogorov–Sinai entropy to quantify the system’s unpredictability and information loss over time. The results show an increase in the regularity of the trajectories as the preferential attachment parameter increases. Full article

Fast charging accelerates lithium-ion battery operation but increases the risk of lithium (Li) plating—a process that undermines efficiency, longevity, and safety. Here, we introduce a predictive modeling framework that captures the onset and severity of Li plating under practical fast-charging conditions. By integrating an empirically parameterized SOC threshold model with time-dependent kinetic simulations and Arrhenius based thermal analysis, we delineate operating regimes prone to irreversible Li accumulation. The framework distinguishes reversible and irreversible plating fractions, quantifies energy losses, and identifies a critical activation energy (0.25 eV) associated with surface-limited deposition. Visualizations in the form of severity maps and voltage-zone risk classifications enable direct application to battery management systems. This approach bridges electrochemical degradation modeling with real-time charge protocol design, offering a practical tool for safe, high-performance battery operation. Full article

Driven by stringent emission regulations, advanced combustion modes utilizing turbulent jet ignition technology are pivotal for enhancing the performance of marine low-speed natural gas dual-fuel engines. This review focuses on three novel combustion modes, yielding key conclusions: (1) Compared to the conventional DJCDC mode, the TJCDC mode exhibits a significantly higher swirl ratio and turbulence kinetic energy in the main chamber during initial combustion. This promotes natural gas jet development and combustion acceleration, leading to shorter ignition delay, reduced combustion duration, and a combustion center (CA50) positioned closer to the Top Dead Center (TDC), alongside higher peak cylinder pressure and a faster early heat release rate. Energetically, while TJCDC incurs higher heat transfer losses, it benefits from lower exhaust energy and irreversible exergy loss, indicating greater potential for useful work extraction, albeit with slightly higher indicated specific NOx emissions. (2) In the high-compression ratio TJCPC mode, the Liquid Pressurized Natural Gas (LPNG) injection parameters critically impact performance. Delaying the start of injection (SOI) or extending the injection duration degrades premixing uniformity and increases unburned methane (CH₄) slip, with the duration effects showing a load dependency. Optimizing both the injection timing and duration is, therefore, essential for emission control. (3) Increasing the excess air ratio delays the combustion phasing in TJCPC (longer ignition delay, extended combustion duration, and retarded CA50). However, this shift positions the heat release more optimally relative to the TDC, resulting in significantly improved indicated thermal efficiency. This work provides a theoretical foundation for optimizing high-efficiency, low-emission combustion strategies in marine dual-fuel engines. Full article

This article examines the seismic assessment and strengthening of a traditional load-bearing masonry structure subjected to strong motion data, with particular emphasis on the effects of soil–structure interaction (SSI). The case study is the Archaeological Museum of Lemnos (AML)—a three-storey building with a composite load-bearing system of timber-framed stone masonry. Over time, the structure has undergone irreversible modifications, primarily involving reinforced concrete (RC) interventions. The building’s seismic performance was evaluated using two finite element models developed in the SAP2000 software (v. 25.3.00). The first model simulates the original structure, strengthened by grout injections, while the second represents the current condition of the structural system following RC additions. Soil–structure interaction was also investigated, given that the local soil is classified as Category D according to Eurocode 8 (EC8). Each model was analyzed under two different support conditions: fixed-base and SSI-inclusive. A suite of appropriate accelerograms was applied to both models, in compliance with Eurocode 8 using the SeismoMatch software, and linear time-history analyses were conducted. The results underscore the significant impact of SSI on the increase of peak tensile stress and interstorey drift ratios (IDRs), and highlight the influence of different strengthening techniques on the seismic response of historic load-bearing masonry structures. Full article

Background: Protein carbonylation is an irreversible post-translational modification that is considered indicative of oxidative damage. Objective: The purpose of the study was to examine by an immunohistochemical method for the first time the extent and localization of protein carbonylation in biopsies of gingiva from periodontitis patients with or without diabetes mellitus (DM). Methods: These were processed for immunohistochemical staining of the carbonylated proteins, using the ENVISIOM FLEX Mini Kit, high pH, and anti-dinitrophenyl (DNP) antibody, a marker of oxidative damage to a given protein. The extent of protein carbonylation was semi-quantitatively estimated and evaluated by calculation of the Allred score (percentage of stained cells × intensity of staining). Results: The biopsies from periodontitis patients with diabetes mellitus (DM) exhibited higher staining scores as per the percentage of positively stained cells than the biopsies from patients with only periodontitis (means of 49.2 and 16.7, respectively), the difference being statistically significant (p = 0.036). The same trend was observed in the case of the combination of the above with the intensity of staining (score parameter) as well (means of 59.6 and 20.8, p = 0.036, respectively). Conclusions: An immunohistochemical method with the novelty of utilization for the first time of the anti-dinitrophenyl (DNP) antibody in gingival tissues was introduced and showed efficacy in detecting protein carbonylation indicative of oxidative stress and its impact in the pathogenesis of these two prevalent diseases of periodontitis and diabetes mellitus. Full article

Epoxy adhesives derived from bisphenol A diglycidyl ether (BADGE) are widely utilized in segmental construction—particularly in precast concrete structures—and in building structural strengthening, owing to their outstanding adhesion properties and long-term durability. These materials constitute a significant class of polymeric adhesives in structural engineering applications. However, BADGE-based epoxy adhesives are susceptible to aging under service conditions, primarily due to environmental stressors such as thermal cycling, oxygen exposure, moisture ingress, ultraviolet radiation, and interaction with corrosive media. These aging processes lead to irreversible physicochemical changes, manifested as degradation of microstructure, mechanical properties, and dynamic mechanical properties to varying degrees, with performance deterioration becoming increasingly significant over time. Notably, for the mechanical properties of concern, the decline can exceed 40% in accelerated aging tests. A comprehensive understanding of the aging behavior of BADGE-based epoxy resin under realistic environmental conditions is essential for predicting long-term performance and ensuring structural safety. This paper provides a critical review of existing studies on the aging behavior of BADGE-based epoxy resins. This paper summarizes the findings of various aging tests involving different influencing factors, identifies the main degradation mechanisms, and evaluates current methods for predicting long-term durability (such as the Arrhenius method, Eyring model, etc.). Furthermore, this review provides recommendations for future research, including investigating multifactorial aging, conducting natural exposure tests, and establishing correlations between laboratory-based accelerated aging and field-exposed conditions. These recommendations aim to advance the understanding of long-term aging mechanisms and enhance the reliability of BADGE-based epoxy resins in structural applications. Full article

Glaucoma is a leading cause of irreversible blindness worldwide, yet early detection can prevent vision loss. This paper proposes a novel deep learning approach that combines two ophthalmic imaging modalities, fundus photographs and optical coherence tomography scans, as paired images from the same eye of each patient for automated glaucoma detection. We develop separate convolutional neural network models for fundus and optical coherence tomography images and a fusion model that integrates features from both modalities for each eye. The models are trained and evaluated on a private clinical dataset (Bangladesh Eye Hospital and Institute Ltd.) consisting of 216 healthy eye images (108 fundus, 108 optical coherence tomography) from 108 patients and 200 glaucomatous eye images (100 fundus, 100 optical coherence tomography) from 100 patients. Our methodology includes image preprocessing pipelines for each modality, custom convolutional neural network/ResNet-based architectures for single-modality analysis, and a two-branch fusion network combining fundus and optical coherence tomography feature representations. We report the performance (accuracy, sensitivity, specificity, and area under curve) of the fundus-only, optical coherence tomography-only, and fusion models. In addition to a fixed test set evaluation, we perform five-fold cross-validation, confirming the robustness and consistency of the fusion model across multiple data partitions. On our fixed test set, the fundus-only model achieves 86% accuracy (AUC 0.89) and the optical coherence tomography-only model, 84% accuracy (AUC 0.87). Our fused model reaches 92% accuracy (AUC 0.95), an absolute improvement of 6 percentage points and 8 percentage points over the fundus and OCT baselines, respectively. McNemar’s test on pooled five-fold validation predictions (b = 3, c = 18) yields ${\chi }^2=10.7$ (p = 0.001), and on optical coherence tomography-only vs. fused (b_o = 5, c_o = 20) ${\chi }_o^2=9.0$ (p = 0.003), confirming that the fusion gains are significant. Five-fold cross-validation further confirms these improvements (mean AUC $0.952\pm 0.011$. We also compare our results with the existing literature and discuss the clinical significance, limitations, and future work. To the best of our knowledge, this is the first time a novel deep learning model has been used on a fusion of paired fundus and optical coherence tomography images of the same patient for the detection of glaucoma. Full article

Obstructive sleep apnoea (OSA) is a prevalent condition characterised by intermittent upper airway obstruction during sleep, resulting in recurrent hypoxia and sleep fragmentation. Emerging evidence highlights the significant impact of OSA on neuro-ophthalmological health, linking it to conditions such as glaucoma, optic neuropathy, papilledema, and visual field defects. These associations emphasise the importance of understanding the mechanisms connecting OSA to neuro-ophthalmological disorders to enhance early diagnosis and management. This review explores the pathophysiological pathways, including hypoxia-induced vascular dysregulation, oxidative stress, inflammation, and intracranial pressure fluctuations, that contribute to ocular and neurological impairments in OSA patients. Advanced diagnostic tools, such as optical coherence tomography and polysomnography, offer promising avenues for detecting subclinical neuro-ophthalmological changes, enabling timely intervention. Management strategies, primarily centred on continuous positive airway pressure therapy, have shown efficacy in mitigating OSA-related neuro-ophthalmological complications. However, surgical and pharmacological interventions and lifestyle modifications remain vital components of a multidisciplinary approach to care. Despite advancements, significant research gaps persist, particularly in understanding the long-term impact of OSA treatment on neuro-ophthalmological outcomes and identifying specific biomarkers for early detection. Future research should prioritise longitudinal studies, interdisciplinary collaborations, and personalised medicine approaches to address these challenges. Recognising and treating neuro-ophthalmological disorders in OSA patients is imperative for improving quality of life and preventing irreversible visual and neurological damage. Full article

Highly sensitive real-time detection of hydrogen sulfide (H₂S) is important for human health and environmental protection due to its highly toxic properties. The development of high-performance H₂S sensors remains challenging for poor selectivity, high limit detection and slow recovery from irreversible sulfidation. To solve these problems, we strategically prepared a layered structure of CuO-sensitized WO₃ flower-like hollow spheres with CuO as the sensitizing component. A 15 wt% CuO/WO₃ exhibits an ultra-high response (R_a/R_g = 571) to 10 ppm H₂S (131-times of pure WO₃), excellent selectivity (97-times higher than 100 ppm interference gas), and a low detection limit (100 ppb). Notably, its fast response (4 s) is accompanied by full recovery within 236 s. After 30 days of continuous testing, the response of 15 wt% CuO/WO₃ decreased slightly but maintained the initial response of 90.5%. The improved performance is attributed to (1) the p-n heterojunction formed between CuO and WO₃ optimizes the energy band structure and enriches the chemisorption sites for H₂S; (2) the reaction of H₂S with CuO generates highly conductive CuS, which significantly reduces the interfacial resistance; and (3) the hierarchical flowery hollow microsphere structure, heterojunction, and oxygen vacancy synergistically promote the desorption. This work provides a high-performance H₂S gas sensor that balances response, selectivity, and response/recovery kinetics. Full article

Dendrimers, 4-dimethylamino-1,8-naphthalimide (DAB) and its halogenated analog 3-bromo-4-dimethylamino-1,8-naphthalimide (DAB-Br), were evaluated on eukaryotic cells, human HFF-1 fibroblast cells, and five fungal species. Although both dendrimers have demonstrated antibacterial and antiviral potential, thus far, their effects on eukaryotic cells, particularly human and fungal cells, have not been investigated. For this purpose, their cytotoxicity, mechanisms of cellular entry, and antifungal activity were studied. Dynamic light scattering measurements revealed that both dendrimers exhibited positive surface charges (+28 to +35 mV), good colloidal stability, and nanoscale dimensions (117–234 nm), facilitating interactions with target cells. The MTT assay showed that DAB was more cytotoxic toward HFF-1 cells (IC₅₀ = 27 µg/mL) compared to DAB-Br (IC₅₀ = 68 µg/mL). In contrast, the resazurin-based antifungal assay demonstrated that DAB-Br had superior antifungal activity, achieving a lower minimum inhibitory concentration (0.148 µg/µL), compared to DAB (0.295 µg/µL). A trypan blue exclusion test revealed that both dendrimers entered cells through membrane permeabilization, either temporarily or permanently, depending on the concentration and exposure time. At concentrations above 30 µg/mL, irreversible permeabilization was observed within two hours of treatment, accompanied by a decrease in membrane lipid order, indicating altered membrane integrity and permeability. Conversely, at lower concentrations (7.5–15 µg/mL), dendrimers induced only temporary membrane permeabilization, with membranes remaining intact, suggesting a reversible interaction with the lipid bilayer. Conducting thorough and systematic research to fully explore their biological activities could provide valuable insight for future applications. Full article