Search Results (7,803)

Background/Objectives: Proteolysis Targeting Chimeras (PROTACs) are heterobifunctional small molecules that induce ubiquitin–proteasome–mediated degradation of target proteins and have matured from proof-of-concept chemistry to a clinically validated therapeutic modality, with the first Phase 3 readout reported in 2025. A systematic bibliometric analysis covering this pivotal-trial era, however, has been lacking. This study aimed to map the historical trajectory, current research front, and emerging frontiers of PROTAC research. Methods: We analyzed 2630 PROTAC-related publications indexed in the Web of Science Core Collection (WoSCC) from 2001 to 2025 using a combined toolkit of CiteSpace, HistCite, the Alluvial Generator, and R (ggplot2), covering co-occurrence networks, burst detection, keyword clustering, citation historiography, alluvial flow analysis, and reference co-citation timeline visualization. Results: China and the USA led global output, and the Chinese Academy of Sciences, China Pharmaceutical University, and Harvard University were the most productive institutions; the Journal of Medicinal Chemistry was the leading publishing venue, and Alessio Ciulli, Jian Jin, and Craig M. Crews anchored the author network. Keyword burst analysis showed that early research centred on E3 ubiquitin ligase recruitment and small-molecule PROTAC design, whereas the current hotspots, resolved through keyword clustering and co-citation timelines, included structural basis and ternary complex design, EGFR-directed degradation, oral bioavailability optimization, applications in multiple myeloma and Alzheimer’s disease, tumour-targeted delivery, and computational/AI-driven design. Conclusions: This study extends the bibliometric record of PROTACs across 2001–2025 and identifies oral bioavailability, E3 ligase repertoire expansion, and CNS-penetrant degrader design as the emerging frontiers likely to shape the next phase of the field. Full article

Maize seed quality and kernel morphological traits are important determinants of grain utilization and are influenced by both genetic factors and growing-season conditions. This study evaluated the stability of seed quality and kernel morphological traits in two commercial maize hybrids (Costanza and LG 3535) across four growing seasons, three row spacing systems, and two plant density levels. Seed quality traits (protein, fat, ash, starch, crude fiber, and moisture content) and kernel morphological traits (length, width, and thickness) were evaluated using univariate and multivariate statistical analyses. Significant effects of hybrid, growing season, row spacing, and their interactions were detected for most evaluated traits. Growing-season variability influenced seed composition and kernel morphology, while row spacing and plant density further contributed to trait expression. Costanza exhibited greater stability for most traits, particularly starch content and kernel morphology, whereas LG 3535 showed more variable responses across growing seasons and row spacing combinations. Correlation and multivariate analyses revealed strong associations among starch content, kernel width, and kernel thickness, whereas protein, ash, and crude fiber were less closely associated with kernel size traits. These findings demonstrate the importance of hybrid × growing-season interactions in shaping maize kernel characteristics and highlight the value of multi-environment evaluation for identifying hybrids with stable kernel quality traits under Mediterranean production conditions. Full article

We construct Wick products by creation and annihilation operators on Guichardet–Fock spaces $\mathcal{F}$ and obtain commutation relations and s—adapted characters about the Wick products. Meanwhile, we introduce a concept of singular Bogoliubov transformation on Guichardet–Fock space, and prove that the Wick product under the singular Bogoliubov transformation still satisfies the commutative relationships. Full article

Electric vehicle (EV) transport by ship is expanding beyond industrial logistics centred on automobile production, trade, and pure car and truck carriers (PCTCs) into daily transportation for island tourism, commuting, and essential mobility. According to Korea Maritime Transportation Safety Authority (KOMSA) vessel status data as of March 2026, 104 of 146 domestic passenger ships were car-ferry passenger ships, accounting for 71.2% of the fleet and operating on 75 of 99 designated routes nationwide. Korea Shipping Association (KSA) operational records show that the EV transport rate on these routes increased from 0.76% in 2024 to 1.21% in 2025, with some routes exceeding 2.0–4.7%. Unlike enclosed multi-deck PCTC vehicle spaces, Korean coastal car-ferry passenger ships generally have single-tier open vehicle decks and bow ramp gates. Crosswinds on open decks may reduce smoke detector activation probability by 60–75%. Although Article 97 of the Standard for Ship Fire-Fighting Appliance newly requires dedicated EV fire-fighting equipment for car-ferry ships, it remains primarily equipment-prescriptive and does not yet provide open-deck-specific performance requirements for wind-resistant detection, fixed EV-zone cooling, EV-designated stowage arrangements, or passenger–operator safety management obligations. This study applies the five-step International Maritime Organization (IMO) Formal Safety Assessment (FSA) procedure to support improvements to EV fire-fighting equipment standards for coastal car-ferry passenger ships. Hazard identification (HAZID) was conducted with a 15-member advisory panel, and probability elicitation was performed through a Delphi survey with 10 core experts, showing strong consensus (Kendall’s W = 0.74, p < 0.01). Fault tree analysis (FTA) and event tree analysis (ETA) probabilities were derived from the Delphi results and the international literature. H-07, representing wind-induced smoke dilution, was identified as the dominant single-point vulnerability within the detection-failure branch. Monte Carlo-based FTA–ETA analysis (n = 10,000) estimated annual fire frequencies of 5.9 × 10⁻², 1.8 × 10⁻¹, and 2.9 × 10⁻¹ yr⁻¹ at EV loading ratios of 10%, 30%, and 50%, respectively, with 2.47 expected fatalities per fire. Risk entered the IMO ALARP band above a 30% EV loading ratio and exceeded the maximum tolerable crew risk above 50%. The combined application of risk control options (RCOs) 2, 3, and 4 reduced annual expected fatalities by 85.6%. Based on these results, six RCOs and institutional recommendations are proposed, including strengthened safety management obligations for passenger ship operators. Full article

Recently, the Quality by Design (QbD) principle has been implemented in the pharmaceutical industry to enhance product and process understanding through a science- and risk-based approach. This study aimed to apply QbD principles to the formulation development of felodipine push–pull osmotic pump (PPOP) capsules. The quality target product profile (QTPP) and critical quality attributes (CQAs) were established. A Box–Behnken experimental design was employed to optimize the formulation variables, including the amounts of Polyox WSR N80, Polyox WSR Coagulant, and sodium chloride, selected based on the initial risk assessment. Four responses were monitored: lag time, release rate and R² based on zero-order release kinetics, and drug release at 24 h. Results indicated that the optimal formulation consisted of 125 mg Polyox WSR N80, 26 mg Polyox WSR Coagulant, and 30 mg sodium chloride. This formulation met the predefined criteria for lag time (≤6 h) and release kinetics (R² ≥ 0.95), while drug release at 24 h remained below the target value (≥80%). Because most fitted response surface models were not statistically significant, the generated regression equations and response surfaces were interpreted qualitatively to identify formulation trends rather than as predictive models. Experimental verification showed reasonable consistency in overall response trends, although substantial deviations between predicted and observed values were observed for some responses, particularly drug release at 24 h. Therefore, the present work should be considered a formulation-development and QbD feasibility study rather than a definitive optimization study. These findings demonstrate that the QbD-based approach enabled systematic, multivariate optimization and design space establishment, providing a more structured framework for formulation refinement compared with prior exploratory development and supporting controlled drug release characteristics of felodipine PPOP capsules. Full article

Digital twin (DT) technology has expanded far beyond its industrial origins, increasingly finding application across environmental and territorial domains. This review provides a structured mapping of DT deployments at environmental and territorial scales over the period 2020–2025, examining 117 peer-reviewed publications (109 applied studies and 8 review articles) through a structured 16-parameter classification framework. The review traces three major conceptual shifts in the DT paradigm: from industrial assets to living entities, from discrete systems to Earth-scale representations, and from closed deterministic models to ecological and systemic frameworks, as reflected in the emergence of ecological digital twins (EcoDTs), environmental digital twins (EDTs), and territorial digital twin (TDT) definitions. The results reveal a clear growth trajectory in DT applications across themes, with urban systems as the most consolidated application domain, and progressive diversification into marine, coastal, forestry, river/lake, and Earth system applications from 2022 onward. Institutional actors dominate production in this space, aligned with European flagship initiatives such as Destination Earth (DestinE) and the European Digital Twin of the Ocean (EDITO). The findings position and expand the notion of territorial digital twins as an evolving paradigm, underscoring both the momentum generated by EU digital and environmental policy and the need for integrated tools to answer and respond to key environmental challenges. Full article

Evaluating resource and environmental carrying capacity (RECC) serves as a fundamental approach for assessing regional environmental baselines and is widely applied in territorial spatial planning. Focusing on Daye City—a characteristic resource-exhausted city in Hubei Province—this study developed a comprehensive RECC evaluation system. By integrating the obstacle degree model, hotspot analysis, and Geodetector, we investigated the spatial differentiation mechanisms of RECC and the resulting production–living–ecological (PLE) spatial conflicts, ultimately proposing targeted optimization pathways. The core findings are as follows: (1) The RECC of Daye City exhibits pronounced spatial polarization and a distinct north–south gradient. (2) The spatial stress of industrial/mining land emerges as the primary obstacle (36.47%). Together with geological hazard risk and soil erosion sensitivity, it forms a core constraint chain. The highly significant hotspots of these factors strongly overlap in the north-central mining districts. (3) Geodetector analysis reveals robust bivariate and nonlinear enhancement effects among these core obstacle factors. This indicates that the cascading vicious cycle of mining disturbance, ecological degradation, and declining carrying capacity fundamentally underlies the constrained RECC in mining regions. (4) PLE spatial conflicts across the study area are dominated by production–ecological conflicts (47.73%), presenting a spatial pattern that heavily couples with the polarized obstacle zones. Based on these findings, this study proposes differentiated regulation strategies centered on mitigating mining-induced stress and interrupting the cascading transmission of disaster risks. These strategies aim to restructure and optimize the territorial spatial pattern, providing robust quantitative decision support for the sustainable transformation of similar resource-exhausted cities. Full article

Leftover spaces, often associated with neglected urban corners, bear physical and conceptual similarities to ignored parts of designed wholes. This study proposes an analytical approach to develop resilient intervention strategies by analyzing the production of leftover spaces through users’ emotional experiences. An experimental pilot study was conducted along Söğütlüçeşme Street in Kadıköy, Istanbul, where all corner points were typologically classified based on morphological characteristics. To measure the impact of these configurations on spatial emotional characters, a survey was implemented using Plutchik’s wheel of emotions. Following a quantitative analysis of emotion frequencies and intensities, findings were visualized via radar charts and spatialized using QGIS 3.40 to generate an emotional map. The resulting emotional maps were further used to identify spatial vulnerabilities and resilience priorities across the study area. By making the gaps between point-based emotional clusters continuous through the IDW interpolation method, the emotional topography of the study area was modeled, thereby presenting an analytical framework that identifies emotional thresholds, spatial vulnerabilities, and resilience priorities. Results indicate that as the physical boundaries of corner voids expand, influenced by angling and massing decisions, public diversity increases, creating a positive emotional atmosphere. Conversely, compressed voids demonstrate a higher potential for producing leftover spaces. This study reveals that mapping user emotions as a data layer is critical for constructing more inclusive and resilient urban environments. Full article

Grain moisture content is a key variable for safe storage, drying control, and quality management. Microwave sensing is attractive because water strongly modulates the complex relative permittivity (ε* = ε′ – jε″) of granular agricultural products, thereby shaping broadband scattering-parameter spectra. This study presents a meter-referenced feasibility evaluation of an interpretable S-parameter–permittivity–moisture chain using a vector network analyzer over 2–18 GHz. Wheat, maize, and mung bean were prepared at six moisture levels, and the moisture values were referenced to two commercial grain moisture meters (MC_ref) to represent rapid on-site benchmarking rather than absolute gravimetric moisture determination. Therefore, the reported errors should be interpreted as commercial-meter-referenced calibration indicators rather than absolute gravimetric moisture prediction accuracy. Two free-space configurations were compared on the same platform: a two-horn transmission setup under controlled packing and a metal-backed double-pass reflection setup intended to represent single-sided access under loose bulk packing. After SOLT calibration and empty-holder background normalization, ε′ and ε″ were retrieved via complex-domain nonlinear least-squares fitting of physics-based slab models to measured S21 spectra. The results show that moisture-dependent dielectric responses were grain- and configuration-dependent. In particular, ε″ generally provided a more robust moisture-sensitive feature in the free-space transmission configuration, whereas the optimal single-parameter predictor in the metal-backed configuration differed among grains. A mid-band frequency window of approximately 8–16 GHz provided more stable inversion by avoiding low-frequency coupling artefacts and high-frequency signal-to-noise degradation. The metal-backed configuration preserved moisture trends but yielded lower effective ε′ values, likely due to increased air fraction under loose packing. These results indicate that packing state, grain type, and frequency-window selection are critical factors for transferring microwave moisture calibration from laboratory measurements to practical grain-handling scenarios. Full article

Vegetated coastal wetlands, especially mangroves, seagrass beds, and salt marshes, are biodiversity-rich ecosystems whose blue carbon outcomes depend on living communities, sediment dynamics, hydrological connectivity, and landscape context. Biodiversity conservation and blue carbon management are often assessed through separate scientific, monitoring, and policy frameworks. This review uses a staged literature search and thematic synthesis to examine biodiversity–blue carbon linkages across the three major vegetated coastal wetland types. It considers how taxonomic, genetic, functional, and habitat diversity influence productivity, sediment stabilization, trophic exchange, carbon stocks, carbon burial, and carbon retention. It also evaluates how climate change, habitat fragmentation, hydrological alteration, pollution, and anthropogenic disturbance weaken these linkages. The synthesis compares representative carbon-stock and burial-rate baselines, examines conservation and restoration synergies and trade-offs, and expands the discussion of seagrass regime shifts. Field surveys, remote sensing, unmanned aerial vehicles, environmental DNA, and AI-enabled data integration are placed within a tiered monitoring framework. The review further develops an operational decision pathway for biodiversity-centered blue carbon management. Persistent blue carbon benefits arise where conservation and restoration maintain native communities, hydrological exchange, sediment stability, habitat complexity, migration space, and long-term stewardship capacity. Full article

Salt stress represents one of the main challenges for global agricultural production, and digital phenotyping has emerged as a promising alternative for identifying popcorn genotypes tolerant to salt stress. This study evaluated the accumulation of plant pigments in response to salt stress in 49 popcorn genotypes (7 inbred lines and 42 F₁ hybrids). Seeds were subjected to two saline conditions: without salt stress (NS—0 mM NaCl) and salt stressed (SS—100 mM NaCl). The evaluation included physiological parameters, and morphological and colorimetric attributes based on the CIELab color space were analyzed using the GroundEye^® system. Additionally, the salt stress tolerance index (SSTI) was calculated for all assessed genotypes. The SSTI ranged from 0.55 to 0.83, with values closer to 1.0 indicating higher tolerance to the stressor. Among the evaluated genotypes, L472 and four of its hybrids stood out for their salinity tolerance, as they combined efficient maintenance of chlorophyll content with higher SSTI estimates. In contrast, L217 and two of its hybrids were identified as sensitive, exhibiting some of the lowest SSTI estimates and significant accumulation of anthocyanins, which, in this study, indicated a response mechanism to oxidative damage. Digital phenotyping associated with CIELab colorimetric analysis constitutes an objective tool for identifying tolerant genotypes, thereby accelerating breeding programs aimed at developing cultivars adapted to saline environments. Full article

Large-scale location-based virtual reality (LBE VR) has become an important form of immersive cultural tourism, but its role in supporting sustained value transformation remains insufficiently understood. In this study, “sustained value transformation” refers to the extension, reinterpretation, and circulation of cultural, educational, social, and engagement-related value across physical venues, embodied virtual narratives, and digital platforms. Rather than assessing economic performance, environmental impact, or long-term operational viability, this study focuses on the cultural and social circulation of experiential value. It examines how physical venues, embodied virtual narratives, and digital platforms jointly mediate visitor experience in LBE VR-based cultural tourism. It compares representative LBE VR projects in museums and heritage institutions, emerging public cultural spaces, and commercial venues in China. A total of 10,862 project-related textual items and 464 visual samples were collected from Xiaohongshu and Douyin and analyzed through comparative content and visual analyses. The findings show that visitor choices are shaped by both the spirit of place in physical venues and platform-visible experience labels. In museums and heritage institutions, institutional knowledge authority and embodied narrative depth help visitors recognize interactive educational value. In emerging public cultural spaces, the intertwining of historical narratives and commercial operations produces more ambiguous experience labels. In commercial venues, platform discussions focus more strongly on value-for-money judgment, sensory stimulation, product quality, and service experience. The study argues that sustained value transformation in LBE VR-based cultural tourism cannot rely solely on platform traffic. Instead, it depends on collaboration among cultural institutions, tourism enterprises, platform content creators, educational actors, and community stakeholders to preserve cultural distinctiveness, improve experience quality, and extend cultural and social value beyond the immediate on-site experience. Full article

CO₂ methanation with renewable hydrogen is a promising strategy for carbon valorization and synthetic natural gas (SNG) production. However, the molecular mechanisms behind catalyst-dependent adsorption and mass transport in zeolite-confined spaces are still not fully elucidated. Herein, we performed comparative molecular simulations on HZSM-5, Ni/ZSM-5 and Ru/ZSM-5 by combining density functional theory (DFT), grand canonical Monte Carlo (GCMC) and molecular dynamics (MD) methods, aiming to clarify the thermodynamic and mass transport mechanisms of reactant enrichment and product desorption in CO₂ methanation. The electronic structures of the three systems were systematically evaluated via Mulliken charge analysis, differential charge density mapping, and frontier molecular orbital calculations. We further quantified the adsorption thermodynamics and diffusion kinetics of reactants and products, focusing specifically on the effects of temperature and framework Si/Al ratio for Ni/ZSM-5. The results show that Ni doping greatly modulates the local electronic environment of the ZSM-5 framework, enhancing the adsorption of CO₂ (−121.9 kJ·mol⁻¹) and H₂ (−81.6 kJ·mol⁻¹) and weakening the adsorption of CH₄ and H₂O. A higher Si/Al ratio reduces CO₂ adsorption capacity, while elevated temperatures inhibit reactant adsorption and lower the diffusion selectivity of CH₄. This demonstrates that moderately low temperatures and moderate Si/Al ratios can optimize the adsorption and diffusion behaviors of reactants and products. This work provides molecular-level insights into the adsorption and diffusion behaviors of Ni/ZSM-5 and offers theoretical references for the rational development of high-performance CO₂ methanation catalysts. Full article

In this paper, L1 phonemic systems are discussed in the context of their impact on the pronunciation and perception of English diphthongs in PE, drawing on World Englishes and phonetic analysis. The study focuses on speakers whose native languages are Punjabi, Seraiki, Pashto, and Urdu, and examines how changes in local vowel inventories and glide processes influence diphthong production. The controlled production and perception tasks were done on eight English diphthongs by 40 adult speakers (10 speakers per L1 group). The formant trajectories (F1, F2), duration, and intensity were recorded by acoustic analyses, which are used to measure the variation that occurs as the articulatory glide occurs between vowel targets. Perception was measured using diphthong identification tasks to assess listeners’ sensitivity to dynamic spectral movement. The results indicate systematic L1-conditioned restructuring. Deviations were the most pronounced in diphthongs with significant vowel gliding, especially centering diphthongs, characterized by a decrease in spectral movement, a constriction in vowel space, and a general tendency toward monophthongization. Closing diphthongs were generally more stable in production; however, they still exhibited systematic L1-conditioned variation, particularly in glide magnitude, spectral direction, and temporal realization. These patterns of production were highly consistent with the results of perceptual production: the diphthongs with lesser acoustic movement were also found to be less accurately recognized, and diphthongs in their L1s and speakers of phonemically richer vowel systems had partial glide contrasts. The findings demonstrate that the variation in diphthongs in PE is systematic, reflecting predictable relationships between the L1 phonemic system, perceptual assimilation, and sociolinguistic experience. The findings highlight the pedagogical value of L1-sensitive pronunciation instruction and contribute to the phonetic description of Pakistani English as a systematic contact variety. Full article

Predicting thermal breakthrough and optimizing injection-production parameters are essential for sustainable geothermal development. Traditional hydrothermal coupled simulations in porous media entail substantial computational costs, which limits their use in dense multi-parameter screening. This study develops a physics-constrained surrogate workflow for the Qihe geothermal doublet system by using COMSOL to generate hydrothermal simulation data and a deep neural network (DNN) to emulate the simulator response within a predefined operating domain. The DNN was trained on physics-driven synthetic outputs rather than independent field observations, and a 2.0 °C decrease in production temperature was used as the thermal breakthrough criterion. Under scenario-wise validation, the surrogate model achieved a test-set R² of 0.9995 and an RMSE of 0.0351 °C, indicating accurate approximation of the deterministic simulator response within the bounded parameter space. The surrogate-based global scan identified a favorable operating region near a well spacing of 462 m, a reinjection temperature of 20 °C, and a reinjection rate of 150 m³/h. To evaluate whether this result was affected by sparse well-spacing sampling, additional COMSOL simulations were performed at 430, 440, 450, 460, 462, 470, 480, 490, and 500 m under the same reinjection temperature and rate. These simulator-based validation cases showed a continuous thermal response with increasing well spacing. The 2.0 °C thermal breakthrough time increased from 46 yr at 430 m to 61 yr at 500 m, while the 50-year cumulative heat extraction increased from 6594.2 to 6722.9 TJ. The 430 and 440 m cases experienced thermal breakthrough before the 50-year design life, whereas the 450 m case was close to the design boundary. The 460 and 462 m cases did not reach the 2.0 °C decline threshold within the 50-year design life and retained relatively high heat-extraction efficiency per unit well spacing. Therefore, the engineering recommendation is revised from a single precise optimum to a locally validated spacing interval of approximately 460–462 m under the present equivalent-porous-medium assumption. The proposed workflow does not replace hydrothermal simulation; instead, it provides a rapid screening tool that narrows the design space before targeted simulator verification and field calibration. Full article