Search Results (2,798)

Background and Clinical Significance: The oocyte zona pellucida (ZP) is an extracellular glycoprotein matrix with essential roles in oogenesis, fertilization, and early embryonic development. Abnormal ZP morphology is associated with female infertility and adverse outcomes after assisted reproductive technology (ART), but its molecular basis remains incompletely understood. Case Presentation: We present three patients with female infertility, abnormal oocyte ZP morphology, and adverse embryological outcomes, including fertilization failure and early developmental arrest. Whole-genome sequencing identified an extremely rare heterozygous missense variant in the ZP4 gene (rs1254095560) in one patient, resulting in the p.Leu342Pro substitution at a conserved amino acid position within the functionally important ZP-C subdomain of the protein. In silico modeling showed that the p.Leu342Pro substitution may alter the spatial folding of the ZP4 protein. Conclusions: These results and the known role of ZP4 in the organization of the zona pellucida allow this variant to be considered a candidate genetic factor potentially associated with disruption of the zona pellucida structure. The absence of comparable, apparently pathogenic coding variants in ZP genes in two other patients with a similar zona pellucida phenotype suggests genetic heterogeneity of this phenotype. Full article

Group III-nitride semiconductors (GaN, AlN, InN) serve as foundational materials for modern optoelectronics, high-frequency microelectronics, and next-generation energy harvesting devices. However, traditional high-temperature epitaxy (>700 °C) introduces severe thermal stress, high dislocation densities, and fundamental incompatibility with flexible substrates or CMOS back-end-of-line (BEOL) processes. Plasma-enhanced atomic layer deposition (PEALD) provides a disruptive, ultra-low thermal budget (<300 °C) pathway for atomic-scale precision growth and conformal coating. This review systematically summarizes recent frontiers in PEALD-synthesized Group III-nitrides and 2D/3D polar heterostructures. First, we dissect the microscopic nucleation kinetics, surface bond reconstruction, and impurity suppression mechanisms across diverse substrates, including Si, sapphire, quartz, metals, and flexible polymers. Next, we highlight 2D template-assisted van der Waals epitaxy on graphene and MoS2, and elucidate polarization-driven dipole interactions and band alignment engineering at 2D/3D polar interfaces (e.g., α-In₂Se₃, Janus MoSSe). Furthermore, we comprehensively discuss innovative applications in advanced photovoltaics (as electron transport and passivation layers in perovskite and quantum dot-sensitized solar cells), silicon-based microcavity lasers, high-electron-mobility transistors (HEMTs), and flexible multimodal sensors. Finally, key technological challenges—including the low-thermal-budget paradox, wafer-scale uniformity, and deposition throughput—are addressed alongside future perspectives in area-selective ALD and neuromorphic computing, presenting a cohesive blueprint from underlying physics to macroscopic system integration. Full article

Lymphoid malignancies comprise a diverse group of hematologic cancers characterized by extensive genetic, epigenetic, and microenvironmental heterogeneity. Despite substantial advances in targeted therapies and immunotherapeutic approaches, disease relapse and therapeutic resistance remain major clinical challenges. Increasing evidence suggests that malignant lymphoid cells are highly dependent on protein homeostasis (proteostasis) networks to cope with the elevated proteotoxic stress imposed by oncogenic signaling, rapid proliferation, immunoglobulin synthesis, and microenvironmental stressors. This dependence, often referred to as proteostasis addiction, represents a critical vulnerability that can be therapeutically exploited. Proteostasis is maintained through an integrated network that regulates protein synthesis, folding, quality control, and degradation. In lymphoid malignancies, dysregulation of these pathways drives adaptive responses involving molecular chaperones, the unfolded protein response (UPR), the ubiquitin–proteasome system (UPS), and autophagy–lysosome pathways. These mechanisms collectively enable tumor cells to survive conditions that would otherwise induce proteotoxic collapse and cell death. Notably, the clinical success of proteasome inhibitors in plasma cell neoplasms has provided proof of concept that targeting proteostasis can yield meaningful therapeutic benefit. In this review, we discuss the major sources of proteotoxic stress in lymphoid malignancies and summarize the molecular mechanisms that sustain proteostasis addiction. We further examine current and emerging therapeutic strategies aimed at disrupting proteostasis networks, including proteasome inhibitors, UPR-targeted agents, chaperone-directed therapies, and novel targeted protein degradation technologies. Finally, we highlight the contribution of proteostasis remodeling to therapeutic resistance and discuss future opportunities for biomarker development and precision medicine. A deeper understanding of proteostasis dependencies may facilitate the identification of novel therapeutic vulnerabilities and improve outcomes for patients with lymphoid malignancies. Full article

The dominant discourse on tourism resilience has traditionally emphasized physical infrastructure, environmental management, and technological solutions as key mechanisms for adapting destinations to climate change and socio-economic disruptions. While these dimensions remain essential, growing evidence suggests that the long-term sustainability of tourism destinations, particularly in remote and vulnerable regions, depends equally on less visible but equally essential community capacities. This paper introduces the concept of human infrastructure as a complementary perspective for understanding resilience in tourism development. Human infrastructure encompasses social relationships, local leadership, collective efficacy, cultural identity, community participation, intergenerational knowledge transfer, and educational capacity, which enable communities to adapt, recover, and innovate under conditions of uncertainty. Drawing upon an integrative conceptual review of the literature on tourism studies, community psychology, rural development, resilience theory, and sustainable development, this conceptual paper proposes a human-centered framework explaining how communities themselves function as adaptive infrastructures. The article argues that resilient tourism destinations emerge not only from investments in roads, visitor centers, and digital technologies, but also from investments in social cohesion, local knowledge systems, community empowerment, and cultural continuity. The paper concludes by discussing policy implications for sustainable tourism planning and proposing future research directions for operationalizing and measuring human infrastructure in tourism contexts. Full article

Microbiota has emerged as a potential regulator of female reproductive health through immunological, metabolic, and endocrine networks. Growing evidence suggests that the composition and stability of the vaginal, uterine, and gut microbiota are associated with fertility outcomes. Disruptions in reproductive tract homeostasis have been linked to infertility, implantation failure, pregnancy loss, and diminished success in assisted reproductive technologies. Beyond local interactions, maternal gut microbiota may influence systemic immunity and metabolic pathways related to vaginal and endometrial microbiota. While these findings highlight the microbiome-based signatures’ potential as predictive and prognostic biomarkers, their clinical applicability remains unconfirmed. Evidence is limited by small cohort sizes, methodological and analytical heterogeneity, and lack of standardization, limiting clinical translation. This narrative review summarizes the current knowledge regarding the microbiome’s role in female reproductive health, highlighting its potential impact on pathophysiology, diagnostics, and therapeutic strategies. While this approach allows for a broad conceptual overview, we explicitly note that it is not systematic. As a result, this review is limited by the absence of a standardized search protocol, which may introduce selection bias. Finally, we review advances in microbial engineering and synthetic biology, highlighting engineered living biotherapeutics as promising strategies to improve microbiome-based reproductive medicine. Full article

Ultrasound technology has emerged as a promising non-thermal approach for modifying the structural and functional properties of food matrices. However, its impact on starch digestibility remains insufficiently understood, particularly in complex systems such as cereal, legume, and pseudocereal flours. This study evaluated the effect of power ultrasound on the functional properties and in vitro digestibility of durum wheat (DWF), chickpea (CF), and amaranth (AF) flours. Flours were treated using an ultrasonic probe (20 kHz, 60% amplitude) for 10 and 20 min while maintaining the sample temperature at 15 °C. Structural and functional properties were assessed, including color, morphology, water absorption, FT-IR spectra, pasting behavior, thermal properties, and starch fractions. Ultrasound induced structural modifications, including starch granule disruption and increased surface roughness. Lightness increased in DWF, CF, and AF, although the magnitude of the response differed among flour types. Water absorption improved in DWF but decreased in CF and AF. FT-IR spectra suggested molecular rearrangements, while viscoelastic and thermal analyses showed increased viscosity in DWF and CF and reduced viscosity in AF. Ultrasound also modified starch fractions and in vitro starch digestibility in a flour-dependent manner, reflecting the distinct structural responses of cereal, legume, and pseudocereal starches to acoustic cavitation. Overall, ultrasound modified the functionality of flour and starch digestibility in a matrix-dependent manner, supporting its potential as a clean-label technology for tailoring the functional properties of different flour matrices. Full article

Increasing high-impact, low-probability (HILP) disruptions requires a paradigm shift in emergency power for critical infrastructure (CI), moving away from traditional cost-driven assessments toward physical resilience. Existing multi-criteria decision frameworks for microgrid technology selection typically treat survivability as one criterion among several, with economic performance retained as an equal or dominant factor. This study addresses this gap by inverting that hierarchy: it develops a resilience-oriented, two-stage screening framework that prequalifies energy technologies (including CHP and CCHP) for CI facing prolonged outages based exclusively on survivability criteria, deferring economic optimization to later design stages. The methodology prioritizes islanding readiness, black-start capability, fuel autonomy, multi-vectorr energy coverage, implementation feasibility, and operational safety. A hospital serves as the reference CI due to its rigorous demand for simultaneous electricity, heat, cooling, and process loads. The framework applies a Stage I Go/No-Go boundary filter followed by a Stage II weighted scoring matrix, evaluating a broad technology basket encompassing gas, biogas, and biomass CHP, CCHP with absorption cooling, hybrid CHP/BESSs, RESs + BESSs, and diesel generators. Rather than providing a definitive techno-economic ranking, this study contributes a transparent, replicable, front-end engineering tool that can be generalized to other critical infrastructure classes. The results define boundary conditions for prequalifying multi-vector energy architectures, establishing a foundation for future FEED-stage modeling and dynamic simulation of CI microgrids. Full article

This study examines behavior among mutual funds across five sectors, including energy, utilities, real estate, technology, and healthcare, over a 27-year period (1999–2025). For each year, using daily NAV returns, each fund is regressed against the S&P 500 to separate fund-specific performance from broader market movements. All the resulting residual vectors for each year and fund are clustered together. These annual cluster assignments are then linked across time to construct each fund’s trajectory, showing how its relative performance position shifts from year to year. These trajectories capture long-term behavioral divergence and provide a simple, intuitive visualization. To identify and characterize fund trajectory and distinctiveness, we apply methods based on residual magnitudes, quantile migration patterns, and Hamming distance measures of (cluster, time) fund trajectories. These trajectories reveal how certain funds consistently diverge from market behavior, thereby contributing to portfolio diversity in terms of trajectory separation. We introduce a portfolio Hamming diversification index that measures separation between trajectories. Using trajectories and Hamming distances, we examine how fund behavior changes during major market disruptions, including the dot-com crash (2001), the financial crisis (2009), and the COVID-19 pandemic (2020–2021), and identify sector-specific differences in how fund trajectories respond to these events. The proposed methodology is intended as an exploratory descriptive methodology for studying long-term behavioral trajectories rather than as a replacement for traditional asset-pricing or performance-evaluation models. Full article

Porcine somatic cell nuclear transfer (SCNT) demonstrates significant potential for application in biomedical research, agricultural breeding, and xenotransplantation. However, compared to in vivo fertilized embryos, SCNT embryos exhibit suboptimal developmental capacity, higher rates of abortion, and neonatal abnormalities, which collectively hinder the large-scale application of this technology. Such developmental anomalies arise from a complex interplay of interconnected factors, primarily incomplete epigenetic reprogramming (the core driver), telomere shortening, mitochondrial dysfunction, and technical manipulation-related damage—all of which disrupt the spatiotemporal regulation of gene expression and embryonic lineage commitment. This article provides a critical and integrated review of porcine SCNT research, establishing a coherent conceptual framework that links biological mechanisms, developmental defects, diagnostic tools, and improvement strategies. We emphasize mechanistic insights into key barriers, evaluate the efficacy and limitations of existing diagnostic and therapeutic approaches, and highlight pig-specific biological features that distinguish porcine SCNT from other mammalian models. This review aims to offer a novel perspective on unresolved questions in the field and provide a rigorous reference for in-depth studies on porcine SCNT embryo development. Full article

Contemporary logistics systems operate in increasingly volatile and uncertain environments, where disruptions and digital transformation jointly shape system performance and continuity. In this context, resilience has emerged as a critical capability; however, existing approaches often remain fragmented, representing resilience either as isolated capabilities or aggregated indicators, while lacking an integrated conceptual architecture for resilience assessment. This study introduces the House of Resilience (HoR) as a hierarchical conceptual architecture that represents resilience as an emergent multi-layer system property and operationalizes this concept through the Fuzzy House of Resilience Assessment Model (FHOR-RAM). The model applies fuzzy logic with linguistic variables, triangular fuzzy numbers, and a hierarchical Mamdani-type fuzzy inference system to capture uncertainty in expert assessments and aggregate resilience measures at both layer and system levels. The proposed framework is illustrated through a real-world procurement system case study conducted in a manufacturing company operating within a global supply network. The results indicate a moderate overall resilience level (R_HoR = 0.402), with the weakest performance observed in the structural (R₃ = 0.31), strategic (R₄ = 0.33), and technological and risk assessment (R₁ = 0.34) layers, while the operational and adaptive layer achieved a moderate resilience level (R₂ = 0.51). The diagnostic analysis identified supplier dependency, lead-time instability, limited resilience governance, and insufficient digital capabilities as the principal resilience bottlenecks. Scenario analysis demonstrated that improvements targeting individual resilience dimensions provide only limited system-level gains, while coordinated development across multiple resilience layers enables a transition toward higher resilience levels (R_HoR = 0.647). The findings confirm that resilience should be addressed as a multidimensional and multi-layer system property rather than as an isolated technological capability. The study demonstrates that fuzzy inference provides an effective operational mechanism for translating the House of Resilience conceptual architecture into an interpretable and decision-oriented resilience assessment framework under uncertainty. The study demonstrates that fuzzy inference provides an effective operational mechanism for translating the House of Resilience conceptual architecture into an interpretable and decision-oriented resilience assessment framework under uncertainty. The case study illustrates how the framework can support structured resilience diagnosis and identification of potential improvement priorities within a procurement system. However, broader empirical validation, including multi-company studies and integration with organizational data sources, remains necessary to further evaluate its transferability and practical deployment potential. Full article

Supply chains increasingly face complex disruptions and rapid technological change, making the relationship between digital transformation (DT) and supply chain resilience (SCR) an important issue in supply chain management. Yet existing evidence remains fragmented across forms of DT, dimensions of SCR, contextual conditions, and performance outcomes. This study conducts a systematic review and meta-analysis of 200 studies, including 124 examining the DT-SCR relationship and 104 examining the SCR–performance relationship. The results show that DT is positively associated with SCR, with stronger associations for digital capabilities than digital technologies and for reactive than proactive SCR. The DT-SCR association is also stronger among SMEs and mature firms, in manufacturing sectors and developing countries, and in contexts characterized by high power distance, low individualism, and stronger long-term orientation, while uncertainty avoidance shows no significant moderating effect. SCR is positively associated with firm performance, with stronger associations for operational and market performance than financial performance. By integrating evidence on the antecedents, boundary conditions, and performance consequences of SCR, this study provides a more differentiated and context-sensitive understanding of the role of DT in supply chain resilience. Full article

In China’s Erhai Lake basin, strict agricultural pollution control policies have reduced ecological degradation but severely disrupted smallholder livelihoods, creating an urgent need for institutional actors capable of mediating between state mandates and rural communities. This study examines Science and Technology Backyards (STBs), university-based knowledge intermediaries, as a distinctive governance mechanism embedded within China’s state-led environmental governance system. Drawing on 60 days of ethnographic fieldwork and 33 semi-structured interviews with 36 participants in Gusheng Village, Dali City, we develop a socio-technical institutional framework that conceptualizes STB effectiveness as depending on the joint operation of three dimensions: technological rationality, social embeddedness, and institutional access. Empirically, the findings show that STBs operate through three bridging mechanisms: technical correction, power adjustment, and market linkage. However, their influence is structurally uneven. Vertically, STB engagement is strong at the prefectural level but weakens sharply at township and village levels. Horizontally, technology diffusion concentrates in core villages and disproportionately benefits large-scale farmers over smallholders. Market linkage remains the weakest mechanism due to deep institutional deficits in cooperative development, supply chain infrastructure, and state–market coordination. These findings contribute to understanding how knowledge intermediaries produce uneven governance outcomes within hierarchical political systems. Full article

The European Union operates in a highly fragmented international environment shaped by geopolitical rivalry, geoeconomic competition, technological disruption, and growing uncertainty regarding critical external dependencies. These developments have elevated economic security and resilience to the centre of European policymaking, challenging assumptions that traditionally linked economic openness with stability, prosperity, and sustainable development. The purpose of this article is to examine how geopolitical and geoeconomic fragmentation is reshaping the European Union’s approach to economic and technological resilience and to analyse the implications of this transformation for long-term competitiveness and sustainable development. Employing a qualitative research design based on policy analysis and systematic document analysis, supported by secondary statistical evidence from European and international institutional sources, the study investigates three interconnected dimensions of resilience: technological resilience, resource resilience, and competitiveness resilience. The findings indicate that the European Union is moving from an efficiency-oriented model of globalisation towards a resilience-oriented governance framework focused on managing sensitive dependencies in critical technologies, strategic resources, and supply chains. The analysis further demonstrates that resilience cannot be sustained through risk reduction measures alone. Its long-term effectiveness depends on productivity growth, innovation performance, technological capabilities, industrial strength, and investment capacity. The article concludes that competitiveness constitutes a foundational condition for durable resilience and that economic security increasingly functions as an enabling factor for sustainable development in a more contested global economic environment. Full article

Humanitarian supply chains often face sudden demand surges, disrupted transportation, limited inventory visibility, and fragmented coordination under disaster uncertainty. Digital twins can improve real-time visibility and adaptive resource allocation, but their effectiveness depends on stable collaboration among public, private, and platform actors. This study develops a digital twin-oriented tripartite evolutionary game and simulation framework involving the public sector, private logistics/material enterprises, and a digital twin platform provider. The model examines how digital twin-oriented governance, active resource and data sharing, and high-quality platform operation co-evolve under bounded rationality. Stability analysis identifies the conditions for convergence to the desired collaborative equilibrium. Numerical simulations, including global sensitivity analysis, stability-region analysis, scenario comparison, stochastic evolutionary dynamics, and Monte Carlo tests, show that enterprise sharing costs and platform operation costs are key barriers, whereas subsidies, platform payments, credible constraints, digital twin visibility, collaboration synergy, and disaster uncertainty promote collaboration. Scenario comparison further indicates that technology-only digital twin construction is insufficient, while adaptive incentive-compatible governance generates shorter convergence time and lower collaboration loss. The findings highlight digital twins as socio-technical coordination infrastructure requiring incentive-compatible governance in humanitarian supply chains. Full article

The integration of information technologies into operational technology (OT) environments that encompass industrial control systems (ICSs), Supervisory Control and Data Acquisition (SCADA) systems, and critical infrastructure such as water and wastewater management facilities has introduced significant cybersecurity vulnerabilities alongside urgent questions of ethics and accountability. The existing digital forensic ethics frameworks were developed for enterprise IT contexts and provide no specific governance for investigations conducted within safety-critical OT environments, where a forensic misstep can disrupt water delivery or disable safety controls. This paper employs a four-stage qualitative research design that consists of a systematic literature review, ethical framework analysis grounded in principlism cyberethics principles, forensic process mapping, and multi-case analysis of five documented real-world incidents to address this gap. The paper identifies and categorizes six primary ethical challenges that are unique to OT/ICS/SCADA digital forensics, maps each to the investigative phase at which it arises, proposes theWater ICS SCADA Ethical Digital Forensics (WISE-DF) framework as a six-phase principled investigation model with ethical safeguards embedded as mandatory procedural gates, and provides actionable recommendations for investigators, organizations, and policymakers. Validation employs three complementary approaches: standards-alignment against the National Institute of Standards and Technology (NIST) Special Publications (SP800-82r3) and Internal Report (IR 8428), the AmericasWater Infrastructure Act of 2018 (AWIA 2018), and the Environmental Protection Agency (EPA 2024); counter-argument testing of each recommendation; and Daubert-consistency evaluation assessing whether WISE-DF compliance produces forensic evidence that is capable of meeting U.S. federal admissibility requirements. Although the Daubert standard applies specifically to U.S. federal proceedings, the ethical framework and WISE-DF gates are designed to be generalizable across jurisdictions. Water and wastewater management serves as the primary illustrative case domain; the framework is designed to be generalizable across OT sectors. Full article