Search Results (45)

Background/Objectives: The medical mushroom Ophiocordyceps sinensis (Caterpillar Fungus), known for its ability to enhance “vitality,” is one of the most popular medicines in Asian traditional medical systems. According to the Chinese Pharmacopeia, O. sinensis is standardized for its adenosine content, the precursor of ATP, which mediates numerous physiological and pathological processes in many diseases. The related fungus of order Hypocreales, Cordyceps militaris, and its major bioactive constituents, 3′-deoxyadenosine (cordycepin), also exhibit pleiotropic biological activities. This review aims to provide a rationale for the adaptogenic and resilience-supporting effects of these medicinal fungi and to align food and drug regulation in Western countries. Methods: In this narrative review, we integrated results from chemical, pharmacokinetic, network pharmacology, preclinical, and clinical studies of O. sinensis, C. militaris, and cordycepin using network pharmacology and bioinformatics tools. Results: Across studies, recurrent mechanistic hubs included PI3K–Akt, AMPK–mTOR, MAPK, NF-κB, apoptosis, and adaptive stress-response signaling pathways, linking immune regulation and metabolic homeostasis. Experimental studies confirmed modulation of cytokine production, kinase signaling, and mitochondrial regulators. Clinical meta-analyses demonstrate consistent adjunctive benefits in renal and pulmonary disorders, although heterogeneity in preparation and methodological limitations remains significant. The review reveals controversy regarding the bioavailability of cordycepin in vivo and its concentration in vitro studies, raising the hypothesis that cordycepin may act as a driver, triggering the organism’s adaptive stress response in stress-induced and aging-related diseases. Pharmacokinetic data indicate that systemic cordycepin concentrations after oral administration remain in the nanomolar range, suggesting that some predicted molecular interactions may occur indirectly or through systems-level mechanisms. The review, for the first time, suggests establishing a regulatory category for resilience-supporting physiological modulators to align food and drug regulation in the EU with contemporary systems biology, thereby complementing the work of EFSA, EMA, FDA, and Asian authorities. Conclusions:O. sinensis, C. militaris, and 3-deoxyadenosine share a common adaptogenic mechanism for maintaining homeostasis of cellular and integrated biological system functions. The systems-level network analysis and reductionistic molecular ligand preceptor pharmacology provide complementary approaches for understanding the multi-target bioactivity of these fungi. This review clarifies conceptual and regulatory barriers to recognizing resilience-supporting interventions and informs future regulatory innovation. Full article

Glioblastoma (GB) is one of the most aggressive brain tumours, with a high mortality rate. Tumour heterogeneity, GB’s invasive nature, the blood–brain barrier (BBB) and resistance development offer significant challenges in devising an effective strategy to manage GB. Clinicians rely on tumour resection, radiotherapy and temozolomide (TMZ) chemotherapy, but their efficacy is hindered due to poor BBB penetration. EGFR (epidermal growth factor receptor), NF-κB, angiogenic pathways, RAS/RAF/MAPK, PI3K/Akt/mTOR, etc., play an important role in GB progression. Development in nanotechnology, pharmaceutical science and genetic engineering enables the design of drug candidates with superior efficacy and safety profiles. This review delves into recent advancements in nanoparticles, hydrogels, extracellular vesicles, microneedles and other drug delivery platforms used in GB treatment. These novel drug delivery systems achieved superior BBB penetration, tumour targeting, and controlled release and better survival outcomes in preclinical setups. This review also discusses the major translational challenges, including those of large-scale production, tumour heterogeneity, off-target effects and M2 macrophage induction. Innovative strategies focusing on drug delivery as a biological decision-making process, integrating tumour stress responses into drug carrier and system-level design principles, are discussed, outlining future prospects. Full article

The rise of the circular economy and e-commerce has led to the emergence of e-commerce closed-loop supply chains (ECLSCs). In practice, investing in process innovation (PI) is key to improving profitability and competitiveness. However, manufacturers at the downstream of ECLSCs often face financial constraints and quality uncertainty of used products, while research on how to select financing strategies under these conditions remains limited. To explore the optimal financing scheme for the ECLSC, this study investigates two financing schemes: bank financing (BF) and FinTech platform financing (FPF), which offers a combination of debt financing (DF) and equity financing (EF). Some key findings are derived. For the ECLSC, the FPF scheme is more profitable when the unit manufacturing cost for new components exceeds the threshold or PI costs are relatively low. Additionally, the FPF performs better when the FPF interest rate is low and the DF ratio is high. The BF is more beneficial when consumer sensitivity to recycling prices or service is low. The FPF enables the ECLSC to achieve maximum profits and minimize environmental impact within a specific range. Furthermore, the financing models are extended to incorporate considerations of fairness, where the optimal financing scheme is primarily influenced by the manufacturing cost. Full article

This study aims to investigate the impact of strategic drivers, specifically IT & Business Strategy Alignment (IT-BSA), Transglobal Leadership (TL), and Product Innovation (PI), on the adoption of Green Supply Chain Management (GSCM) and its subsequent effect on Sustainable Performance (SP). A key objective is to examine the moderating role of Risk Management (RM) in the relationship between these drivers and GSCM. This research employs a quantitative methodology, utilizing survey data collected from 216 middle and top Indonesian oil and gas managers. The hypothesized relationships were tested using Partial Least Squares Structural Equation Modeling (PLS-SEM). The findings reveal that IT-BSA, TL, and PI are significant positive GSCM antecedents. Furthermore, GSCM has a strong, positive impact on SP. The results confirm that RM significantly and positively moderates the influence of all three strategic drivers on GSCM adoption. These findings provide a clear managerial roadmap, highlighting that an active risk management framework is critical for translating internal capabilities into effective sustainability practices, thereby enhancing a firm’s competitive advantage and long-term performance. Full article

The accurate analysis of the sealing performance of underground lined cavern hydrogen storage is critical for enhancing the stability and economic viability of storage facilities. This study conducts an innovative investigation into hydrogen leakage behavior by developing a multiphysical coupled model for a composite system of support structures and surrounding rock in the operation process. By integrating Fick’s first law with the steady-state gas permeation equation, the gas leakage rates of stainless steel and polymer sealing layers are quantified, respectively. The Arrhenius equation is employed to characterize the effects of temperature on hydrogen permeability and the evolution of gas permeability. Thermalmechanical coupled effects across different materials within the storage system are further considered to accurately capture the hydrogen leakage process. The reliability of the established model is validated against analytical solutions and operational data from a real underground compressed air storage facility. The applicability of four materials—stainless steel, epoxy resin (EP), ethylene–vinyl alcohol copolymer (EVOH), and polyimide (PI)—as sealing layers in underground hydrogen storage caverns is evaluated, and the influences of four operational parameters (initial temperature, initial pressure, hydrogen injection temperature, and injection–production rate) on sealing layer performance are also systematically investigated. The results indicate that all four materials satisfy the required sealing performance standards, with stainless steel and EP demonstrating superior sealing performance. The initial temperature of the storage and the injection temperature of hydrogen significantly affect the circumferential stress in the sealing layer—a 10 K increase in initial temperature leads to an 11% rise in circumferential stress, while a 10 K increase in injection temperature results in a 10% increase. In addition, the initial storage pressure and the hydrogen injection rate exhibit a considerable influence on airtightness—a 1 MPa increase in initial pressure raises the leakage rate by 11%, and a 20 kg/s increase in injection rate leads to a 12% increase in leakage. This study provides a theoretical foundation for sealing material selection and parameter optimization in practical engineering applications of underground lined caverns for hydrogen storage. Full article

In recent years, with the development of electronic products toward high frequency and high speed, Printed Circuit Board (PCB) routing technology has been continuously evolving to meet the requirements of complex signal transmission. Meanwhile, the increase in circuit frequency and device density has led to a sharp deterioration of simultaneous switching noise (SSN), which has escalated from a minor interference to a core bottleneck. SSN not only impairs signal integrity and increases bit error rate, but also interferes with circuit operation, causes device failure, and even leads to system collapse, becoming a “fatal obstacle” to the performance and reliability of high-frequency products. The SSN problem has become increasingly severe due to the rise in circuit operating frequency and device density, posing a key challenge in high-speed circuit design. To address the challenge of suppressing SSN at the PCB board level in high-speed digital circuits, this paper proposes a collaborative optimization scheme integrating simulation analysis and the Seagull Optimization Algorithm (SOA). In this study, a multi-physical field coupling model of SSN is established to reveal that SSN essentially arises from the electromagnetic interaction between the parasitic inductance of the power distribution network (PDN) and high-speed transient current. Based on the research on frequency-domain impedance analysis, time-domain response prediction, and decoupling capacitor suppression mechanism, the limitations of traditional capacitor placement in suppressing GHz-level high-frequency noise are overcome. This method enables precise power integrity (PI) design via simulation analysis frequency-domain parameter extraction and power–ground noise simulation quantify PDN impedance characteristics and the coprocessor switching current spectrum; resonance analysis locates key frequency points and establishes an SSN–planar resonance correlation model to guide decoupling design; finally, noise coupling analysis optimizes signal–power plane spacing, markedly reducing mutual inductance coupling. On this basis, the SOA is innovatively introduced to construct a multi-objective optimization model, with capacitor frequency, capacitance value, and package size as variables. A spiral search algorithm is used to balance noise-suppression performance and cost constraints. Simulation results show that this scheme can reduce the SSN amplitude by 37.5%, effectively suppressing the signal integrity degradation caused by SSN and providing a feasible solution for SSN suppression. Full article

This paper explores the symmetry of integrated control technology to ensure the smooth operation of shearers, scraper conveyors and hydraulic supports in the context of integrated mechanized coal mining, so as to achieve the dual goals of improving coal mining efficiency and ensuring operation safety. Article paper addresses the critical research gap in system-level coordination for mechanized coal mining. While the shearer, scraper conveyor, and hydraulic support have been extensively studied individually, their integrated control under dynamic and complex geological conditions remains a challenge, often leading to production bottlenecks and safety risks. This study proposes a novel integrated control model to bridge this gap. The study formulates the research problem of achieving continuous and safe mining operations under complex geological conditions and employs modeling and simulation to validate the proposed control methodology. In the subsequent stages, a technological solution for the control of the coal mining process is investigated, and the effectiveness of the constructed model is thoroughly tested through simulation modeling methods. The study shows that through proportional–integral (PI) control, precise interaction between coal mining machines, scraper conveyors and hydraulic supports can be achieved, thereby ensuring the continuity and safety of coal mining operations and effectively preventing production interruptions and potential accidents. The research results are analyzed, and a forecast is made for the future trend of technology development, namely, the movement toward intelligence, automation and precision, so as to further promote technological innovation and industrial upgrading in the coal mining industry. Full article

Colorectal cancer (CRC) remains a major contributor to global cancer-related mortality, with rising incidence observed in several regions, including Saudi Arabia. This review compiles and critically analyzes recent preclinical research from Saudi-based institutions that investigates the anti-CRC potential of natural and synthetic compounds. Numerous natural products such as Nigella sativa, Moringa oleifera, Curcuma longa, and marine-derived metabolites have demonstrated cytotoxic effects through pathways involving apoptosis induction, reactive oxygen species (ROS) generation, and inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and cyclooxygenase-2 (COX-2). In parallel, synthetic and semi-synthetic agents, including C4–G4 (semi-synthetic hybrids designed from flavonoids and benzoxazole scaffolds that act as dual epidermal growth factor receptor (EGFR)/COX-2 inhibitors)), oxazole derivatives, and camptothecin-based nanocarriers, exhibit promising anti-tumor activity via molecular targeting of cyclin-dependent kinase 8 (CDK8), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), and β-catenin pathways. Selected in vivo studies primarily utilizing xenograft and chemically induced rodent models have shown reductions in tumor volume and modulation of apoptotic and inflammatory biomarkers. Additionally, green-synthesized metallic nanoparticles (NPs) and polyethylene glycol (PEG)-modified carriers have been investigated to improve bioavailability and tumor targeting of lead compounds. While these findings are encouraging, the majority remain in preclinical phases. Limitations such as poor solubility, lack of pharmacokinetic data, and absence of clinical trials impede translational progress. This review highlights the need for standardized evaluation protocols, mechanistic validation, and region-specific clinical studies to assess efficacy and safety. Given Saudi Arabia’s rich biodiversity and growing research capacity under national strategies like Vision 2030, the country is well-positioned to contribute meaningfully to CRC drug discovery. By integrating bioactive natural products, rationally designed synthetics, and advanced delivery platforms, a pipeline of innovative CRC therapeutics tailored to local and global contexts may be realized. Full article

Background: Cucurbitacin B (CuB) is a relatively unique and valuable component in plants of the Cucurbitaceae family due to its diverse and remarkable physiological activities, but its specific mechanisms in regulating tumor metabolism and immune response remain unclear. The hypoxic tumor microenvironment (TME) of pancreatic cancer induces metabolic reprogramming in cancer cells, causing them to rely on glycolysis for energy. LDHA, a key enzyme in glycolysis, can suppress glycolysis and tumor growth when inhibited. Objective: The objective of this study was to investigate the mechanism of CuB against pancreatic cancer and its effect on the immune system. Methods: In this study, cell migration/invasion assays, immunofluorescence, ELISA, Western blot, CETSA, flow cytometry, mouse models, and metabolomic and transcriptomic analyses were utilized to systematically elucidate the mechanism by which CuB inhibits pancreatic cancer and activates the immune system. Results: This study confirms that CuB inhibits pancreatic cancer by suppressing the PI3K/Akt/mTOR pathway and activating PINK1/Parkin to induce mitophagy, thereby inhibiting cell migration, invasion, and proliferation. It downregulates the expression of LDHA to block glycolysis, reduce lactate production and efflux, and improve the acidic TME. CuB also induces ICD to activate dendritic cells, promote CD8+ T-cell and M1 macrophage infiltration, and reduce the levels of regulatory T cells. Metabolomic and transcriptomic analyses validate CuB’s dual effects on metabolic reprogramming and immune activation. Conclusions: This study, for the first time, reveals that CuB induces mitophagy via the PI3K/Akt/mTOR and PINK1/Parkin pathways to selectively eliminate damaged mitochondria and suppress tumor energy metabolism. CuB inhibits pancreatic cancer through a triple mechanism—inducing mitophagy, inhibiting glycolysis, and activating immunity—which provides innovative insights for pancreatic cancer therapy. Full article

Cancer presents significant challenges owing to its complex molecular pathways and resistance to therapy. Natural metabolites have significant medicinal potential by regulating the sensing and signaling pathways associated with cancer development. Recognizing their interactions within the tumor microenvironment may unveil innovative techniques for inhibiting malignant activities and improve therapy success. This article highlights studies regarding ovarian cancer metabolism, signaling mechanisms, and therapeutic natural substances. This study summarizes clinical and experimental results to emphasise the synergistic effects of alkaloids, flavonoids, and terpenoids in improving therapeutic effectiveness and alleviating drug resistance. Bioactive compounds are essential in regulating ovarian cancer metabolism and signaling pathways, affecting glycolysis, lipid metabolism, and the survival of tumor cells. This review examines metabolic programming and essential pathways, including glycolysis, TCA cycle, lipid metabolism, PI3K/AKT/mTOR, AMPK, and MAPK, emphasizing their therapeutic significance. The integration of metabolic treatments with medicines based on natural compounds has significant potential for enhancing treatment effectiveness and mitigating therapeutic resistance. Ovarian cancer needs an integrated strategy that includes metabolic reprogramming, signaling modulation, and drugs derived from natural products. Natural chemicals provide intriguing approaches to address chemotherapy resistance and improve treatment efficacy. Further research is required to enhance these methodologies and evaluate their practical applicability for improved patient outcomes. Full article

This comprehensive review of the synergistic use of Quality by Design (QbD) and the Pi–Buckingham theorem explores an innovative approach to enhancing product development and process optimization within the pharmaceutical industry. QbD is a systematic, proactive methodology that integrates quality considerations throughout the product lifecycle to ensure that pharmaceutical products meet regulatory standards for safety and efficacy from the outset of development. The Pi–Buckingham theorem serves as a foundational principle in dimensional analysis, facilitating the simplification of complex models by transforming physical variables into dimensionless parameters. This synergy enables researchers to better understand and control the factors affecting critical quality attributes (CQAs), thereby improving manufacturing outcomes and minimizing variability. Full article

In today’s fast-changing business environment, artificial intelligence (AI) capability plays a critical role in fostering product innovation (PI). Resource-based theory (RBT) posits that resources and capabilities characterized as valuable, rare, inimitable, and non-substitutable can generate a sustained competitive advantage, providing an appropriate theoretical framework for this study. Using RBT this study examines how business intelligence transforming capability (BITC) mediates the relationship between AI capability and PI and how formal and informal knowledge governance mechanisms (FKGMs and IKGMs, respectively) moderate the effect of AI capability on BITC. Using partial least squares structural equation modeling on 516 Chinese manufacturing enterprises, we empirically test a mediated moderation model. The findings reveal that BITC significantly mediates the relationship between AI capability and PI. Both FKGMs and IKGMs strengthen the effect of AI capability on BITC (with IKGMs showing a stronger influence). This study theoretically contributes by identifying BITC’s mediating role, defining AI capability and BITC boundary conditions, revealing FKGMs’ and IKGMs’ asymmetries, and extending RBT. In terms of practical contributions, the findings emphasize the necessity of developing BITC and strategically applying both FKGMs and IKGMs to maximize AI capability-driven PI benefits. Full article

SHP2, a non-receptor protein tyrosine phosphatase, plays a pivotal role in regulating intracellular signaling pathways, particularly the RAS/MAPK and PI3K/AKT cascades, which are critical for cellular proliferation, differentiation, and survival. Aberrant SHP2 activity, often driven by gain-of-function mutations, is implicated in oncogenesis and drug resistance, making it an attractive therapeutic target. Traditional inhibitors targeting SHP2’s catalytic site face limitations such as poor selectivity and low bioavailability. Recent advancements in allosteric inhibitors, specifically targeting SHP2’s tunnel site, offer improved specificity and pharmacokinetics. Natural products, especially saponins with their unique structural diversity, have emerged as promising candidates for SHP2 inhibition. This review explores the structural and functional dynamics of SHP2, highlights the potential of saponin-based inhibitors, and discusses their mechanisms of action, including their interactions with key residues in the tunnel site. The therapeutic potential of saponins is further emphasized by their ability to overcome the limitations of catalytic inhibitors and their applicability in combination therapies. Future directions include structural optimization to improve pharmacokinetics and the development of innovative strategies such as PROTACs to enhance the clinical utility of saponin-based SHP2 inhibitors. Full article

With the rapid development of metaverse technology in the marketing field, it has become increasingly important to understand consumer purchase intentions for AI Brand Endorsers (AIBEs) within this digital environment. Based on cognitive–affective–behavioral (CAB) theory, this study constructs a new theoretical framework to explore the key factors influencing consumer purchase intentions for AIBE-recommended products in the context of the metaverse. We conducted an online survey with 302 Generation MZ consumers who have purchasing experience, employing Partial Least Squares Structural Equation Modeling (PLS-SEM) for in-depth data analysis and model evaluation. Additionally, we performed Multi-Group Analysis (MGA) to reveal differences among various occupations and generations. The findings indicate that attractiveness (ATT), anthropomorphism (ANT), and interactivity (INT) significantly influence hedonic motivation (HM) and social presence (SP). Furthermore, authenticity (AUT) positively affects both SP and trust in AIBEs (TAI). Consumer purchase intention (PI) is significantly impacted by SP but is not directly influenced by HM and TAI. Notably, technology readiness (optimism and innovativeness) positively and significantly influences consumer PI but does not alter the potential moderating effects of HM, SP, and TAI. This study not only broadens and deepens the application of CAB theory but also elucidates the potential development of AIBEs in future metaverse research, providing practical implications and guidance for marketers to enhance consumer purchase intentions and boost product sales. Full article

This narrative review presents the role of antioxidants in regulating the gut microbiota and the impact on the gut–brain axis, with a particular focus on neurodegenerative diseases, such as Alzheimer’s (AD) and Parkinson’s disease (PD). These diseases are characterised by cognitive decline, motor dysfunction, and neuroinflammation, all of which are significantly exacerbated by oxidative stress. This review elucidates the contribution of oxidative damage to disease progression and explores the potential of antioxidants to mitigate these pathological processes through modulation of the gut microbiota and associated pathways. Based on recent studies retrieved from reputable databases, including PubMed, Web of Science, and Scopus, this article outlines the mechanisms by which antioxidants influence gut health and exert neuroprotective effects. Specifically, it discusses how antioxidants, including polyphenols, vitamins, and flavonoids, contribute to the reduction in reactive oxygen species (ROS) production and neuroinflammation, thereby promoting neuronal survival and minimising oxidative damage in the brain. In addition, the article explores the role of antioxidants in modulating key molecular pathways involved in oxidative stress and neuroinflammation, such as the NF-κB, Nrf2, MAPK, and PI3K/AKT pathways, which regulate ROS generation, inflammatory cytokine expression, and antioxidant responses essential for maintaining cellular homeostasis in both the gut and the central nervous system. In addition, this review explores the complex relationship between gut-derived metabolites, oxidative stress, and neurodegenerative diseases, highlighting how dysbiosis—an imbalance in the gut microbiota—can exacerbate oxidative stress and contribute to neuroinflammation, thereby accelerating the progression of such diseases as AD and PD. The review also examines the role of short-chain fatty acids (SCFAs) produced by beneficial gut bacteria in modulating these pathways to attenuate neuroinflammation and oxidative damage. Furthermore, the article explores the therapeutic potential of microbiota-targeted interventions, including antioxidant delivery by probiotics and prebiotics, as innovative strategies to restore microbial homeostasis and support brain health. By synthesising current knowledge on the interplay between antioxidants, the gut–brain axis, and the molecular mechanisms underlying neurodegeneration, this review highlights the therapeutic promise of antioxidant-based interventions in mitigating oxidative stress and neurodegenerative disease progression. It also highlights the need for further research into antioxidant-rich dietary strategies and microbiota-focused therapies as promising avenues for the prevention and treatment of neurodegenerative diseases. Full article