Search Results (75,695)

Osteosarcoma (OS) is a highly aggressive bone cancer with limited therapeutic options. Carnosic acid (CA), a phenolic diterpene with well-established antioxidant properties, has shown anticancer activity, yet its mechanisms in OS remain unclear. In this study, we found that CA suppressed proliferation and induced apoptosis in human osteosarcoma cells in a dose-dependent manner. Mechanistically, CA activated the STING/IRF3 signaling pathway and enhanced nitric oxide (NO) production, factors closely linked to redox modulation and mitochondrial apoptotic signaling. Pharmacological inhibition or siRNA-mediated knockdown of STING, as well as blockade of NO synthesis, significantly reduced CA-induced apoptosis in vitro. In a xenograft mouse model, CA treatment suppressed tumor growth, and this effect was partially reversed by STING inhibition. These findings suggest that CA exerts antitumor effects in OS through modulation of innate immune and redox-related signaling pathways, supporting its potential as a therapeutic compound that links antioxidant and immunomodulatory actions. Full article

Nitrophenol (NP) and methylene blue (MB) are considered among the most hazardous organic contaminants frequently released from pharmaceutical, textile, and paper industries, posing significant risks to both human health and the environmentThe conventional treatment involves adsorption, oxidation, biological, filtration, and other photochemical degradation methods, which often suffer from low efficiency, limited reusability, and the production of secondary toxic by-products. In this context, the nanomaterials (NMs) mediated catalytic reduction of MB into leucomethylene blue and p-NP into p-aminophenol (p-AP) has emerged as a promising approach, due to its high efficiency and effectiveness. . This review emphasized on the green synthesis of nanomaterials(NMs) for catalytic applications, which align with the principles of the circular economy and the Sustainable Development Goals (SDGs). This thorough review systematically examines the mechanistic understanding of the reduction of both p-NP and MB viadifferent green synthesized NMs and evaluating their catalytic efficiencies. Furthermore, a detailed discussion of the reduction of pollutants (p-NP and MB) is provided, along with their mechanistic insights. In addition, this paper also provides a comparative table highlighting the effects of using different precursors, experimental conditions on the conversion catalytic efficiency and reusability potency. Thus, this work provides the insights into recent research on the catalytic reduction of p-NP and MB into valuable products , highlighting the significance of green synthesized nanocatalysts for effective wastewater treatment. Full article

Background/Objectives: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of various malignancies, but their use is frequently accompanied by immune-related adverse events, among which immune-mediated colitis (IMC) represents one of the most common and clinically significant gastrointestinal toxicities. IMC may lead to treatment interruption, increased morbidity, and compromised quality of life. This review aims to provide a comprehensive overview of the pathophysiology, risk factors, diagnosis, management, and emerging therapeutic strategies with particular emphasis on the role of the gut microbiota and fecal microbiota transplantation (FMT). Methods: This review integrates current international guidelines, meta-analyses, clinical trials, and recent translational studies addressing IMC. The available evidence on immunological mechanisms, predictive biomarkers, clinical presentation, diagnostic algorithms, and treatment options was critically synthesized to outline a structured and multidisciplinary management approach. Results: IMC is driven by dysregulated immune activation, cytokine release, and alterations in gut microbiota. Incidence and severity vary according to ICI class, combination regimens, tumor type, and patient-related factors. Diagnosis requires exclusion of infectious causes, laboratory assessment, and endoscopic and histologic evaluation with CTCAE-based severity grading. Corticosteroids remain the cornerstone of first-line therapy, while infliximab and vedolizumab are effective in steroid-refractory cases. Emerging therapies, including JAK inhibitors and FMT, have shown promising results in refractory disease. Conclusions: IMC is a complex and potentially severe complication of ICI therapy that necessitates early recognition, accurate grading, and individualized, multidisciplinary management. Severity-guided treatment, timely escalation to biologics, and careful balancing of immunosuppression with antitumor efficacy are essential for optimal outcomes. Future research should focus on biomarker validation, microbiome-targeted therapies, and prospective trials to refine therapeutic algorithms and define the optimal role and timing of FMT in clinical practice. Full article

Background: As populations age and digitalization accelerates globally, understanding whether digital inclusion can enhance the economic well-being of older adults is critical for achieving sustainable development. However, empirical evidence on the mechanisms linking digital life to sustainable income among older populations remains limited. Design: This study utilizes data from the 2023 Chinese General Social Survey (CGSS), comprising 3127 respondents aged 55 and older. We employ ordinary least squares (OLS) regression with city fixed effects, instrumental variable estimation, and mediation analysis to examine the impact of digital life on income and its underlying mechanisms, with a focus on sustainability outcomes. Results: Digital life significantly enhances income levels among older adults, a finding robust to endogeneity and sensitivity checks. Heterogeneity analysis shows stronger effects for rural seniors, those in western regions, and older women. Mediation analysis reveals that digital engagement boosts income through four pathways—employment, material capital, social capital, and human capital—each contributing to the economic sustainability of aging populations. Conclusions: Digital inclusion serves as a mechanism to transform seniors’ dormant assets into productive capital, thereby promoting sustainable income and contributing to the Sustainable Development Goals (SDGs), particularly SDG 8 (Decent Work and Economic Growth) and SDG 10 (Reduced Inequalities). Policies should prioritize targeted digital literacy training, age-friendly platform design, and integration with social protection systems to foster inclusive and sustainable aging societies. Full article

This study examines how zoning regimes mediate the capitalization of officially assessed land values into housing prices in a high-density metropolitan housing market. Using transaction-level housing data from New Taipei City, Taiwan, we estimate a hedonic pricing model combined with a boundary-based spatial comparison that restricts observations to properties located near zoning borders. The results indicate that official land values are significantly associated with housing prices but are only partially capitalized, with an estimated elasticity of approximately β ≈ 0.37 in the baseline specification. Interaction models further reveal that capitalization elasticities vary systematically across zoning regimes, suggesting that planning regulations influence how administratively determined land values are translated into market prices. These heterogeneous capitalization patterns remain stable across alternative boundary bandwidths and model specifications. The findings highlight the institutional role of zoning systems in shaping the relationship between administratively assessed land values and housing market outcomes. More broadly, the study contributes to the literature on housing market regulation by demonstrating how land-use institutions mediate price formation processes in densely developed urban environments. Full article

Background/Objectives: Lung cancer remains a major global health burden, largely driven by cigarette use. Although electronic cigarettes (e-cigarettes) are viewed as safer alternatives due to their reduced chemical load, growing evidence shows their vapor can disrupt cellular transcriptomes, including long noncoding RNAs (lncRNAs). In this study, we examined the regulation and function of vape-associated lncRNA transcript 1 (VALT1), a novel transcript upregulated in the oral transcriptomes of e-cigarette users and similarly elevated in non-small-cell lung cancer (NSCLC) tumors. Methods: Publicly available RNA-seq datasets were analyzed, and VALT1 was identified as an e-cigarette-responsive lncRNA. Its dose-dependent induction by e-cigarette smoke extract (eCSE) and cytoplasmic localization were confirmed via RT-qPCR. Its effects on cancer-associated phenotypes including proliferation, ROS detoxification, resistance to apoptosis, migration, cytoskeletal disorganization, and nuclear remodeling were assessed through overexpression and siRNA-mediated knockdown in A549 and BEAS-2B cells. Results: Acute eCSE exposure induced a biphasic, dose-dependent increase in VALT1 expression, accompanied by enhanced proliferation, ROS detoxification, apoptosis resistance, migration, cytoskeletal disorganization, and nuclear remodeling in A549 cells. VALT1 overexpression reproduced these phenotypes in both cell lines without eCSE treatment, whereas knockdown attenuated them. VALT1 promoted survival under cytotoxic stress in A549 but not BEAS-2B cells. Conclusions: These findings support an active role for VALT1 as an e-cigarette vapor-upregulated transcript that contributes to its phenotypic readout and enhances cellular survival under extracellular chemical stress—thereby aggravating tumorigenic phenotypes even in the absence of mutations that contribute to malignant transformation. Full article

Deaf and Hard-of-Hearing (DHH) students face persistent barriers in geometry education due to instructional approaches that inadequately support visual communication and embodied learning. This study examined DHH students’ experiences with GeoMETriA, a metaverse-based geometry learning platform integrating sign language instruction, three-dimensional visualization, and avatar-mediated interaction. Guided by the Cognitive Affective Model of Immersive Learning (CAMIL), a multi-phase qualitative design was employed, including pre-workshop interviews with four special education teachers and post-workshop focus group discussions with seven DHH secondary students following a four-session learning workshop. The findings indicate that gamified activities and peer collaboration enhanced interest and sustained engagement, while avatar customization supported embodiment and a sense of presence. Students described progression from initial uncertainty to greater confidence through practice and scaffolded support. However, cognitive and usability challenges emerged, particularly concerning sign language video pacing, navigation complexity, and limited instructional scaffolding. The study contributes theoretically by extending CAMIL-informed interpretations to sign-supported metaverse learning, empirically by documenting how engagement, embodiment, and self-efficacy develop during immersive geometry learning, and practically by offering design implications including adjustable sign language delivery, structured scaffolding, and culturally responsive avatar options. These findings suggest that metaverse-based platforms hold promise for supporting DHH learners when accessibility and learner-centered principles are embedded as foundational design considerations. Full article

(1) Background: Swine hepatitis E (SHE) is an emerging zoonotic disease caused by the swine hepatitis E virus (SHEV). The open reading frame 3 (ORF3) protein is a recognized virulence factor of SHEV. Jaundice, the typical clinical sign of SHE, primarily results from disruptions in bile production, secretion, and excretion. However, the mechanism by which SHEV ORF3 influences bile metabolism remains unclear. (2) Methods: Building on our previous work involving adenovirus-mediated overexpression of genotype IV SHEV ORF3 in HepG2 cells and subsequent high-throughput lncRNA/transcriptome sequencing, this study performed KEGG enrichment analysis on differentially expressed lncRNAs. Candidate lncRNAs were validated via qRT-PCR. Cis-regulated target genes were predicted by integrating differentially expressed mRNA data. Furthermore, AlphaFold 3.0 was employed to analyze the molecular binding sites between lncRNA UBC (MSTRG.6881.4) and its target, UBC protein. (3) Results: We identified three lncRNAs associated with the bile secretion pathway (ko 04976) in HepG2 cells expressing genotype IV SHEV ORF3, which were further confirmed by qRT-PCR: lncRNA UBC (MSTRG.6881.4), lncRNA UBC (MSTRG.6881.9), and lncRNA UBC (MSTRG.6881.12). Bioinformatics prediction suggested six lncRNA-mRNA regulatory networks involved these lncRNAs and two downregulated UBC mRNA transcripts (ENST00000540700 and ENST00000536769). Molecular docking indicated that nucleotides 395U and 41C of lncRNA UBC (MSTRG.6881.4) could potentially bind to residues 82Lys, 88Thr, and 90Thr of the UBC protein, with predicted binding energies ranging from −4.73 to −0.75 kcal/mol. (4) Conclusions: The successful identification of bile secretion-related lncRNAs, coupled with the prediction of their regulatory networks and molecular interaction sites, has advanced our understanding of SHEV ORF3 function and the pathogenesis of SHEV infection. Full article

Purpose: Castration-resistant prostate cancer (CRPC) responds poorly to conventional chemotherapy. We evaluated a cell-based enzyme–prodrug therapy using adipose-derived stem cells (ADSCs) engineered to express cytosine deaminase (CD) or carboxylesterase 2 (CE2), paired with their respective prodrugs 5-fluorocytosine (5-FC) or irinotecan (CPT-11), to compare their antitumor efficacy. Materials and Methods: Human telomerase reverse transcriptase (hTERT)-immortalized ADSCs were transduced with CD or CE2, and transgene expression and stem cell phenotype were confirmed. CD expression was verified at the transcript level and by functional 5-FC-to-5-fluorouracil (5-FU) conversion, whereas CE2 expression was verified by transcript analysis and immunoblotting. Tumor tropism toward PC3 prostate cancer cells was tested using migration assays and analysis of chemoattractant ligand/receptor expression. Prodrug-induced self-killing and bystander tumor cell killing were assessed through viability assays and co-culture with PC3 cells. For the CE2/CPT-11 system, SN-38 was not directly quantified; functional activity was inferred from prodrug-dependent cytotoxicity and in vivo efficacy. In vivo efficacy was evaluated in nude mice with PC3 tumors treated systemically with engineered ADSCs plus prodrug. Results: CD- and CE2-expressing ADSCs were successfully established and retained mesenchymal stem cell (MSC) characteristics. Both cell types exhibited significant migration toward PC3 cells. The CE2/CPT-11 system produced stronger prodrug-mediated cytotoxicity than CD/5-FC, with CE2-modified ADSCs showing higher sensitivity to CPT-11 and inducing greater apoptosis in co-cultured PC3 cells. In vivo, both treatments suppressed tumor growth, but CE2/CPT-11 achieved greater inhibition (tumor volume ~26% of control vs. ~32% for CD/5-FC at day 14). No overt clinical toxicity was observed based on body weight and daily clinical monitoring; however, hematology/serum chemistry were not assessed. Conclusions: Engineered ADSCs home to CRPC tumors and enable local prodrug activation, producing significant antitumor effects. Within the constraints of our in vitro assays and subcutaneous xenograft model, CE2/CPT-11 demonstrated stronger efficacy outcomes than CD/5-FC. Mechanistic attribution to intratumoral SN-38 exposure should be confirmed by direct metabolite measurements in future studies. Full article

Melanoma is a highly malignant neoplasm of the skin with early metastatic spread and increasing incidence worldwide. Although there are significant therapeutic advances in immunotherapy, especially with the checkpoint inhibitors targeting PD-1 and CTLA-4, challenges such as treatment-related toxicities, a heterogeneous response to therapy, and drug resistance continue to exist. There are unmet needs for novel therapeutic strategies and/or approaches to complement the existing treatment options. Potential targets for future melanoma treatment are the gap junction proteins, connexins, which show an altered pattern of regulation during melanoma progression. In this review, we highlight the regulation of gap junctions during melanoma progression and the characterization of gap junctions as tumor suppressors during early-stage tumor development and then the reversion to enhancers of tumor metastasis during late-stage melanoma progression. We provide a comprehensive overview of gap junctions in the skin and how the connexin proteins, which comprise gap junctions, are alternatively regulated in melanoma progression. Connexins are protein channels in the human body that consist of 21 isoforms. These isoforms form gap junctions that provide important intercellular signaling and permeability channels. Each connexin protein consists of four transmembrane domains and a C-terminal tail, which is an important part of its function and regulation. Permeants of gap junctions include signaling molecules such as cyclic AMP and inositol triphosphate which are linked to key cellular behaviors such as proliferation and migration, making them essential for several tumor-related processes. At least ten connexin isoforms are found in normal skin. Connexin 43 (Cx43) is classified as the most prevalent isoform while Connexin 26 (Cx26) has been reported to be more specialized with restricted expression patterns. Cx43 and Cx26 regulate the growth, differentiation, and repair of the epidermis after injury. Evidence suggests that connexins have a stage-related function in melanoma. Loss of connexin expression and gap junctional intercellular communication is linked to tumor suppression and loss of differentiation in early-stage melanoma, while re-expression or overexpression of specific connexins, notably Cx43, may promote metastasis through enhanced tumor–stromal interactions and increased motility in late-stage melanoma. Such opposing actions of connexins support their candidacy as biomarkers and therapeutic targets. Understanding the dual-stage related functions of connexins in melanoma development and progression may lead to less cytotoxic and more efficient future therapeutic approaches. Full article

This study explores how innovation, economic diversification, and digitalization are boosting Oman’s efforts toward building a smart economy within the context of Oman’s banking and financial regulatory sector, while considering the role of artificial intelligence and governmental support. Supported by the and the Resource-Based View and Innovation Diffusion Theory, this study views innovative and digital competences as key national resources that help governments and organizations to adapt to technological variation and reinforce economic pliability. By using a quantitative approach and convenient sampling, the data were collected through a closed-ended structured questionnaire from 296 individuals representing businesses across Oman and analyzed using SmartPLS 4.0. The results demonstrate that innovation, diversification, and digitalization have a positive and significant impact on governmental support, which eventually plays a mediating role in leading the implementation of a smart economy. Although artificial intelligence was expected to strengthen the effects of digitalization and innovation, the findings reveal that its moderating role is not yet significant, suggesting an early stage of AI diffusion within the banking sector. These results not only confirm Resource-Based View and Innovation Diffusion Theory in an emerging economy but also present practical understandings for business leaders and policymakers. Furthermore, these findings underscore the importance of institutional readiness and diffusion maturity in shaping the role of advanced technologies in smart economy development. This study also suggests that incorporating AI-driven innovation, digital capability development, and strong governance can support Oman to attain the Vision 2040 goals of endorsing diversification, inclusive economic growth, and sustainability in the digital era. Full article

Glaucoma is a multifaceted optic neuropathy, characterized by the progressive loss of retinal ganglion cells. This damage frequently continues even after intraocular pressure (IOP) has been effectively lowered. This resistance to conventional IOP-lowering therapy underscores the critical role of interacting IOP-independent mechanisms; specifically metabolic failure and systemic mitochondrial dysfunction have emerged as key parallel drivers. This review analyzes the paradigm shift from a pressure-centric model to a bioenergetic one, focusing on mitochondrial function, peripheral blood mononuclear cell (PBMC) biomarkers, and oxygen consumption dynamics. We synthesize evidence demonstrating that glaucoma patients exhibit a metabolic vulnerability, characterized by lower PBMC oxygen consumption rates and depleted systemic nicotinamide adenine dinucleotide levels relative to healthy individuals. Furthermore, compromised systemic respiratory performance correlates with more rapid worsening of visual fields and structural thinning, independent of IOP status. Moreover, we delineate the role of Complex I defects, SARM1-mediated axonal degeneration, and proteomic alterations, which indicate defective mitophagy. These findings establish systemic metabolic profiling as a valuable supplementary tool for assessing patient risk and support the clinical translation of neuroprotective therapies targeting mitochondrial bioenergetics, specifically nicotinamide, pyruvate, coenzyme Q₁₀, and metformin. Full article

Background/Objectives: Natural killer (NK) cells are essential mediators of innate immune defense and play a key role in tumor surveillance following liver transplantation (LT). Despite this, the prognostic relevance of pre-transplant NK cell activity in living donor LT (LDLT) has not been fully established. Methods: This retrospective analysis included 134 adult patients who underwent LDLT. NK cell activity was evaluated prior to transplantation using interferon-γ release assays and classified as low (<10 pg/mL) or high (≥10 pg/mL). Overall survival (OS) was assessed for all participants, whereas recurrence-free survival (RFS) was analyzed patients with HCC. Results: Patients classified as having high NK activity (≥10 pg/mL) experienced significantly better overall survival compared to those with low activity (log-rank p = 0.032). In the multivariate analysis, high NK activity showed a strong trend toward improved overall survival (HR, 0.52; 95% CI, 0.26–1.04; p = 0.063). Among recipients with HCC, high NK activity was associated with a markedly improved recurrence-free survival (log-rank p = 0.004). Multivariate Cox regression further established NK activity as an independent factor for tumor recurrence (HR, 0.27; 95% CI, 0.08–0.87; p = 0.028). Conclusions: Pre-transplant NK cell activity independently predicts both survival and recurrence following LDLT. Full article

Intimate partner violence (IPV) remains understudied in China despite its public health significance. Previous research lacks comprehensive analysis of how Chinese media frames this issue, creating a gap in understanding the sociocultural factors shaping public discourse. This study employs corpus-based framing analysis of 603 news articles (435,581 words) from major Chinese newspapers spanning 2012–2022, a period encompassing significant legal developments including the 2016 Domestic Violence Law. We analyze how IPV is framed through examination of keyword frequencies, collocation patterns, and concordance analysis. Our findings reveal that IPV is predominantly framed as matrimonial conflict and family dispute rather than criminal violence requiring state intervention. We argue that framing IPV as a ‘family issue’ operates as a spatial containment strategy, relocating violence to the domestic sphere while rerouting intervention into administrative/civil channels rather than criminal accountability spaces. Our findings reveal significant imbalances in stakeholder representation, with government and legal voices dominating the public discourse domain while community support organizations are marginalized. Source attribution patterns produce uneven zones of legitimacy, where state actors occupy authorized public space while survivors’ experiences remain confined to private, silenced domains. This research enhances the understanding of IPV media coverage in China while highlighting the need for more inclusive public discourse. Full article

Lung cancer progression is regulated by multiple factors, including ferroptosis and gut microbiota-mediated butyrate metabolism. This study investigates the anti-tumor effects of ginsenoside Rh4 on lung cancer cells via ferroptosis mechanisms in vitro and in vivo. In vitro, ginsenoside Rh4 inhibited the proliferation of Lewis lung carcinoma (LLC) and A549 cells and triggered ferroptosis, effects that were suppressed by the ferroptosis inhibitor Ferrostatin-1 (Fer-1). In vivo, tumor-bearing mouse models were established and treated with 100 mg/kg ginsenoside Rh4 for 21 days. Tumor growth, ferroptosis markers, gut microbiota, and butyrate were analyzed, with in vitro validation of butyrate’s pathway effects. Ginsenoside Rh4 induced ferroptosis in LLC cells both in vitro and in vivo, inhibiting tumor growth. It promoted ferroptosis by disrupting iron homeostasis through elevated Fe²⁺ and transferrin receptor (TFRC), and impaired antioxidant defense via depletion of glutathione (GSH) and reduction in ferritin heavy chain 1 (FTH1), solute carrier family 40 member 1 (SLC40A1), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4). Additionally, ginsenoside Rh4 enhanced lipid peroxidation, indicated by increased lipid peroxides (LPO) and malondialdehyde (MDA). In vivo, it suppressed the KEAP1/NRF2/HO-1 pathway, reducing antioxidant enzyme activity. Gut microbiota modulation and butyrate production further amplified ferroptosis by activating transcription factor 3 (ATF3)-mediated GPX4 suppression. Ginsenoside Rh4 induces ferroptosis by inhibiting the KEAP1/NRF2/HO-1 pathway and remodeling the gut microbiota to increase butyrate levels, which synergistically enhance tumor cell ferroptosis sensitivity through ATF3 activation and suppression of GPX4. Full article