Search Results (9,118)

Background: Anti-programmed death 1 receptor (PD-1) therapy is a promising treatment strategy for patients with unresectable advanced or recurrent gastric/gastroesophageal junction (G/GEJ) cancer. However, its response rate and survival benefits are still limited; an immunological analysis of the residual tumor after anti-PD-1 therapy would be important. Methods: We evaluated the clinical efficacy of tumor resection (TR) after chemotherapy or anti-PD-1 therapy in patients with unresectable advanced or recurrent G/GEJ cancer and analyzed the immune status of tumor microenvironment (TME) by immunohistochemistry using their surgically resected specimens. Results: Patients treated with TR after anti-PD-1 therapy had significantly longer survival compared to those treated with chemotherapy and anti-PD-1 therapy alone. Expression of human leukocyte antigen (HLA) class I and major histocompatibility complex (MHC) class II on tumor cells was markedly downregulated after anti-PD-1 therapy compared to chemotherapy. Furthermore, the downregulation of HLA class I may be associated with the activation of transforming growth factor-β signaling pathway in the TME. Conclusions: Immune escape from cytotoxic T lymphocytes may be induced in the TME in patients with unresectable advanced or recurrent G/GEJ cancer after anti-PD-1 therapy due to the downregulation of HLA class I and MHC class II expression on tumor cells. TR may be a promising treatment strategy for these patients when TR is feasible after anti-PD-1 therapy. Full article

Rabies remains a significant global public health concern, causing an estimated 59,000–69,000 human fatalities annually. Despite being entirely preventable through vaccination, rabies continues to impose substantial economic burdens worldwide. This study presents a scoping review of the economic research on rabies to determine overlaps and gaps in knowledge and inform future research strategies. We selected 150 studies (1973–2024) to analyze. The review categorizes the literature based on geographic distribution, species focus, and type of study. Findings indicate that economic studies are disproportionately concentrated in developed countries, such as the United States and parts of Europe, where rabies risk is low, while high-risk regions, particularly in Africa and Asia, remain underrepresented. Most studies focus on dog-mediated rabies, reflecting its dominant role in human transmission, while fewer studies assess the economic impacts of wildlife and livestock-mediated rabies. Case studies and modeling approaches dominate the literature, whereas cost–benefit and cost–effectiveness analyses—critical for informing resource allocation—are limited. The review highlights the need for more economic evaluations in rabies-endemic regions, expanded research on non-dog reservoirs, and broader use of economic methods. Addressing these gaps will be crucial for optimizing rabies control and supporting global initiatives to eliminate dog-mediated rabies by 2030. Full article

The modern livestock industry incorporates widely used antibiotic growth promoters into animal feed at sub-therapeutic levels to enhance growth performance and feed efficiency. However, this practice contributes to the emergence of antibiotic-resistant pathogens in livestock, which may be transmitted to humans through the food chain, thereby diminishing the efficacy of antibiotics in treating bacterial infections. Current research explores the potential of essential oils from derived medicinal plants as alternative phytobiotics. This review examines modern encapsulation strategies that incorporate essential oils into natural-origin matrices to improve their stability and control their release both in vitro and in vivo. We discuss a range of encapsulation approaches utilizing polysaccharides, gums, proteins, and lipid-based carriers. This review highlights the increasing demand for antibiotic alternatives in animal nutrition driven by regulatory restrictions, and the potential benefits of essential oils in enhancing feed palatability and stabilizing the intestinal microbiome in monogastric animals and ruminants. Additionally, we address the economic viability and encapsulation efficiency of different matrix formulations. Full article

This paper examines the effect of digital innovation on cost stickiness in manufacturing firms, focusing on the underlying mechanisms and contextual factors. Using data from Chinese A-share listed manufacturing firms from 2012 to 2023, we find that, first, for each one-unit increase in the level of digital technology, the cost stickiness index of enterprises decreases by an average of 0.4315 units, primarily through digital process innovation and digital business model innovation, whereas digital product innovation does not exhibit a statistically significant impact. Second, manufacturing servitization and the optimization of human capital structure are identified as key mediating mechanisms. Digital innovation promotes servitization by transitioning firms from product-centric to service-oriented business models, thereby reducing fixed costs and improving resource flexibility. It also optimizes human capital by increasing the proportion of high-skilled employees and reducing labor adjustment costs. Third, the effect of digital innovation on cost stickiness is found to be heterogeneous. Firms with high financing constraints benefit more from the cost-reducing effects of digital innovation due to improved resource allocation efficiency. Additionally, mid-tenure executives are more effective in leveraging digital innovation to mitigate cost stickiness, as they balance short-term performance pressures with long-term strategic investments. These findings contribute to the understanding of how digital transformation reshapes cost behavior in manufacturing and provide insights for policymakers and firms seeking to achieve sustainable development through digital innovation. Full article

Triclabendazole (TCBZ) is the gold standard treatment for fascioliasis. However, reports on resistance are increasing, emphasizing the need for alternative therapy. Combining TCBZ with ivermectin (IVM) was found to be effective for treating animal fascioliasis. Building on this, we aimed to evaluate the efficacy of the TCBZ/IVM combination therapy for human fascioliasis. This study enrolled 136 patients with Fasciola from Upper Egypt, and they were divided into the first group (n = 65), who received TCBZ monotherapy, and the second group (n = 71), who received the TCBZ/IVM combination. Assessments were to evaluate treatment response based on clinical, eosinophilic, and radiological parameters. Chronic fasciolosis was diagnosed in 17 patients (12.5%). No differences were observed in age and sex. Significant improvements were noted in all parameters in both groups, with more pronounced effects observed in the second group. A significantly higher complete response, including clinical, eosinophilic, and radiological improvements, was reported in the combined therapy group, with 53.3% compared to 26.2% in the monotherapy group (p < 0.001). A high baseline eosinophilic count was significantly associated with response. The efficacy of the TCBZ/IVM combination for treating human fascioliasis suggested a possible boosting effect, which can benefit regions of TCBZ failure. Further large-scale randomized studies are warranted to confirm these findings. Full article

Triple-negative breast cancer (TNBC) is a highly aggressive and therapeutically challenging subtype of breast cancer due to its lack of estrogen receptors, progesterone receptors, and HER2 (Human epidermal growth factor receptor 2) expression, which severely limits available treatment options. Recently, Simvastatin—a widely used HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitor for hyperlipidemia—has garnered interest for its potential anticancer effects. This study investigates the therapeutic potential of Simvastatin in triple-negative breast cancer (TNBC). The results demonstrate that Simvastatin significantly inhibits the proliferation of TNBC cells, particularly MDA-MB-231, in a dose- and time-dependent manner. Mechanistically, Simvastatin primarily induces G1 phase cell cycle arrest to exert its antiproliferative effects, with no significant evidence of apoptosis or necrosis. These findings support the potential repositioning of Simvastatin as a therapeutic agent to suppress TNBC cell growth. Further analysis shows that Simvastatin downregulates cyclin-dependent kinase 4 (CDK4), a key regulator of the G1/S cell cycle transition and a known marker of poor prognosis in breast cancer. These findings highlight a novel, apoptosis-independent mechanism of Simvastatin’s anticancer action in TNBC. Importantly, given that many breast cancer patients also suffer from hyperlipidemia, Simvastatin offers dual therapeutic benefits—managing both lipid metabolism and tumor cell proliferation. Thus, Simvastatin holds promise as an adjunctive therapy in the treatment of TNBC and warrants further clinical investigation. Full article

An imbalance between the generation of reactive oxygen species (ROS) and antioxidant defenses is known as oxidative stress, and it is implicated in a number of diseases. The superoxide radical O^2– is produced by numerous biochemically relevant redox processes and is thought to play role in diseases and pathological processes, such as aging, cancer, membrane or DNA damage, etc.; SOD, or superoxide dismutase, is essential for reducing oxidative stress. As a result, the elimination of ROS by SOD may be a useful disease prevention tactic. There have been reports of protective effects against neurodegeneration, apoptosis, carcinogenesis, and radiation. Exogenous SODs’ low bioavailability has drawn criticism. However, this restriction might be removed, and interest in SOD’s medicinal qualities increased with advancements in its formulation. This review discusses the findings of human and animal studies that support the benefits of SOD enzyme regulation in reducing oxidative stress in various ways. Additionally, this review summarizes contemporary understandings of the biology of Cu/Zn superoxide dismutase 1 (SOD1) from SOD1 genetics and its therapeutic potential. Full article

Down syndrome (DS), stemming from the triplication of human chromosome 21, results in intellectual disability, with early mid-life onset of Alzheimer’s disease (AD) pathology. Early interventions to reduce cognitive impairments and neuropathology are lacking. One modality, maternal choline supplementation (MCS), has shown beneficial effects on behavior and gene expression in neurodevelopmental and neurodegenerative disorders, including trisomic mice. Loss of basal forebrain cholinergic neurons (BFCNs) and other DS/AD relevant hallmarks were observed in a well-established trisomic model (Ts65Dn, Ts). MCS attenuates these endophenotypes with beneficial behavioral effects in trisomic offspring. We postulate MCS ameliorates dysregulated cellular mechanisms within vulnerable BFCNs, with attenuation driven by novel gene expression. Here, choline acetyltransferase immunohistochemical labeling identified BFCNs in the medial septal/ventral diagonal band nuclei of the basal forebrain in Ts and normal disomic (2N) offspring at ~11 months of age from dams exposed to MCS or normal choline during the perinatal period. BFCNs (~500 per mouse) were microisolated and processed for RNA-sequencing. Bioinformatic assessment elucidated differentially expressed genes (DEGs) and pathway alterations in the context of genotype (Ts, 2N) and maternal diet (MCS, normal choline). MCS attenuated select dysregulated DEGs and relevant pathways in aged BFCNs. Trisomic MCS-responsive improvements included pathways such as cognitive impairment and nicotinamide adenine dinucleotide signaling, among others, indicative of increased behavioral and bioenergetic fitness. Although MCS does not eliminate the DS/AD phenotype, early choline delivery provides long-lasting benefits to aged trisomic BFCNs, indicating that MCS prolongs neuronal health in the context of DS/AD. Full article

Background: Metastatic melanoma is a highly aggressive malignancy with poor prognoses and frequent resistance to conventional chemotherapy. Approximately 40% of melanoma cases carry the BRAF^V600E mutation, for which vemurafenib, a selective BRAF^V600E inhibitor, is approved. Despite initial clinical benefits, vemurafenib often leads to drug resistance and relapse, highlighting the need for improved therapeutic strategies. Objectives, methods: In this study, we designed, synthesized, and characterized five novel vemurafenib analogs—RF-86A, RF-87A, RF-94A, RF-94B, and RF-96B—with the aim of enhancing anti-proliferative and anti-metastatic effects against human melanoma cells. Results: All compounds induced apoptosis in BRAF^V600E-mutated A375 cells, with RF-86A displaying the lowest IC₅₀ value among the series, comparable to that of vemurafenib. Moreover, RF-86A exhibited the highest selectivity index, as determined using HEK293T cells as a non-tumorigenic control. Additionally, migration assays and gelatin zymography demonstrated that the analogs, unlike vemurafenib, significantly inhibited matrix metalloproteinases MMP-2 and MMP-9, key enzymes involved in tumor invasion and metastasis. Conclusions: These findings suggest that structural modifications to the vemurafenib scaffold may improve therapeutic efficacy and offer a promising strategy to overcome acquired resistance. Full article

This research aims to develop an educational board game, “Sustainable Home: Energy Challenge,” based on Monopoly by integrating sustainable development goals and renewable energy to use ChatGPT in human–computer collaboration. ChatGPT was used for game conceptualization, rule development, board creation, card design, and simulation in an iterative design. The developed board game demonstrated ChatGPT’s efficiency in educational game design and the benefits of human–computer collaboration. Game simulations validated the board game’s potential as a simulation tool to enhance diversity, cooperation, and strategic depth. The game effectively promoted SDG engagement and sustainable development education in gamified learning. Full article

With the global aging population on the rise, identifying environmental factors that modulate immunosenescence is critical for health interventions. While urban green spaces are known to confer health benefits, the long-term effects of forest exposure on immunosenescence remain unclear. This study investigated the differential impacts of urban forest versus urban environments on immunosenescence using a D-galactose-induced murine model. Mice were assigned to urban or forest environments for 8 weeks, with serum cytokines (IL-2, IL-6, TNF-α, IFN-γ), T-cell subsets, and organ indices analyzed. Forest environments exhibited significantly higher humidity and negative air ion concentrations alongside lower noise levels compared to urban settings. Aged forest-exposed mice showed attenuated immunosenescence markers, including significantly lower IL-6 levels (p < 0.01) and improved thymic indices, suggesting urban forest environments may mitigate immune decline. These findings highlight the potential of urban forests in promoting healthy aging, advocating for their integration into urban planning. Further human studies are warranted to translate these findings into public health strategies. Full article

Plant-derived vesicles offer several advantages, including high yield, low cost, ethical compatibility, safety, and potential health benefits. These advantages enable them to overcome technological limitations associated with vesicles of mammalian origin. Ginseng, a prominent example of a natural botanical plant, is known for its abundant bioactive components. Recent studies confirmed that ginseng-derived vesicles offer significant advantages in the treatment of human diseases. Therefore, this study reviews the extraction and purification processes of ginseng-derived vesicle-like nanoparticles (GDVLNs), their therapeutic potential, and the active ingredients in GDVLNs that may exert pharmacological activities. Furthermore, this study evaluates the research and applications of nanosized ginseng extracts, with a primary focus on ginsenosides. Full article

Microbes perform diverse and vital functions in animals, plants, and humans, and among them, plant-associated microbiomes, especially endophytes, have attracted growing scientific interest in recent years. Numerous plant species thriving in diverse environments have been shown to host endophytic microbes. While endophytic bacteria commonly colonize plant tissues such as stems, roots, and leaves, seed-associated endophytes generally exhibit lower diversity compared to those in other plant compartments. Nevertheless, seed-borne microbes are of particular importance, as they represent the initial microbial inoculum that influences a plant’s critical early developmental stages. The seed endophytic microbiome is of particular interest due to its potential for vertical transmission and its capacity to produce a broad array of phytohormones, enzymes, antimicrobial compounds, and other secondary metabolites. Collectively, these functions contribute to enhanced plant biomass and yield, especially under abiotic and biotic stress conditions. Despite their multifaceted roles, seed microbiomes remain underexplored in plant ecology, and their potential benefits are not yet fully understood. This review highlights recent advances in our understanding of the diversity, community composition, mechanisms of action, and agricultural significance of seed endophytic microbes. Furthermore, it synthesizes current insights into how seed endophytes promote plant health and productivity and proposes future research directions to fully harness their potential in sustainable agriculture. Full article

Insulin resistance (IR) plays a pivotal role in the pathogenesis of several dermatological diseases, including psoriasis, acne, acanthosis nigricans, and hidradenitis suppurativa (HS). These conditions are characterized by chronic inflammation, oxidative stress, and metabolic dysfunction, which are exacerbated by IR. This narrative review examines the emerging role of nutraceutical insulin-sensitizing agents (ISAs), including myo-inositol, alpha-lipoic acid, vitamin D, vitamin C, and folic acid, in managing IR-related dermatological disorders. A comprehensive literature search was conducted across Cochrane Library and MEDLINE (1965–May 2025), focusing on clinical trials involving nutraceutical ISAs in dermatological conditions associated with IR. Only human studies published in English were included. Evidence from randomized controlled trials (RCTs) and observational studies suggests that ISAs improve glycemic control, reduce oxidative stress, and modulate inflammatory pathways in IR-related dermatoses. Notably, myo-inositol combined with magnesium and folic acid has demonstrated significant reductions in acne severity, hirsutism, and quality-of-life impairments in women with polycystic ovary syndrome. Similar benefits have been observed in psoriasis and HS, though data remain limited. Nutraceutical ISAs offer a promising adjunctive approach for the management of IR-associated dermatological diseases, potentially addressing both metabolic dysfunction and skin inflammation. However, robust RCTs with long-term follow-up are needed to confirm these preliminary findings and to establish optimal treatment regimens. Full article

Macroalgae (seaweeds) produce unique bioactive metabolites that have enabled their survival for millions of years, offering significant potential for human benefits. In the Israeli Mediterranean Sea, no comprehensive systematic surveys of seaweeds have been published since the 1990s, and their chemical composition remains largely unexplored. This study presents an extensive survey of intertidal seaweed communities along the shallow Israeli coastline, documenting their spatial, temporal, and biochemical diversity. Of the 320 specimens collected, 55 seaweed species were identified: 29 red (Rhodophyta), 14 brown (Phaeophyceae), and 12 green (Chlorophyta). A significant shift in species abundance was documented, with a single dominant annual bloom occurring during spring, unlike previously reported biannual blooms. Chemical analysis of the dominant species revealed significant seasonal variations in compound levels, with higher protein content in winter and increased antioxidant capacity during spring. Phenolic and natural sunscreen compounds (mycosporine-like amino acids, MAAs) showed no general seasonal trend. These findings highlight the optimal environmental conditions for seaweed growth and underscore their potential for aquaculture and biotechnology. We hypothesize that the ecologically unique conditions of the Israeli Mediterranean Sea may foster resilient seaweed species enriched with distinctive chemical properties, suitable for nutritional, health, pharmaceutical, and nutraceutical applications, particularly as climate-adaptive bioresources. Full article