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Technical job interviews have become a vulnerable environment for social engineering attacks, particularly when they involve direct interaction with malicious code. In this context, the present manuscript investigates an exploratory case study, aiming to provide an in-depth analysis of a single incident rather than seeking to generalize statistical evidence. The study examines a real-world covert attack conducted through a simulated interview, identifying the technical and psychological elements that contribute to its effectiveness, assessing the performance of artificial intelligence (AI) assistants in early detection and proposing mitigation strategies. To this end, a methodology was implemented that combines discursive reconstruction of the attack, code exploitation and forensic analysis. The experimental phase, primarily focused on evaluating 10 large language models (LLMs) against a fragment of obfuscated code, reveals that the malware initially evaded detection by 62 antivirus engines, while assistants such as GPT 5.1, Grok 4.1 and Claude Sonnet 4.5 successfully identified malicious patterns and suggested operational countermeasures. The discussion highlights how the apparent legitimacy of platforms like LinkedIn, Calendly and Bitbucket, along with time pressure and technical familiarity, act as catalysts for deception. Based on these findings, the study suggests that LLMs may play a role in the early detection of threats, offering a potentially valuable avenue to enhance security in technical recruitment processes by enabling the timely identification of malicious behavior. To the best of available knowledge, this represents the first academically documented case of its kind analyzed from an interdisciplinary perspective. Full article

(This article belongs to the Special Issue Emerging Research in Artificial Intelligence for Code Analysis and Security)

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21 pages, 1794 KB

Open AccessArticle

Assessing the Early Impact of InvestEU on Romanian SME Financial Performance

by Emanuel Ciobanu, Ana-Maria Torjescu, Ioana Polec and Carmen Păunescu

Sustainability 2026, 18(2), 982; https://doi.org/10.3390/su18020982 (registering DOI) - 18 Jan 2026

Abstract

This article examines how European funding enhances the financial performance of Romanian SMEs, a sector facing growing regulatory pressure, market volatility, and resource constraints. The study combines a thematic analysis of InvestEU indicators and national SME financing data (2021–2023) with a firm-level difference-in-differences model comparing InvestEU-funded SMEs to a matched control group over 2023–2024. The qualitative evidence shows that InvestEU operates at the EU level as a multidimensional policy instrument fostering competitiveness, social inclusion, and long-term economic and environmental development, while Romanian SMEs continue to rely predominantly on their own funds and national co-financing, a conservative pattern that ensures stability but limits access to external capital and transformative investments. Econometric results indicate that funded SMEs record, on average, higher turnover and net profit growth than comparable non-funded firms and confirm a strong positive association between firm size and financial performance; however, the interaction term capturing the specific InvestEU effect is positive but not statistically significant at the 95% confidence level. The findings suggest that InvestEU has the potential to act as a catalyst for structural change but also highlight the need for longer observation periods, larger samples, and more comprehensive development indicators to assess its medium-and long-term impact on SME competitiveness. Full article

(This article belongs to the Section Economic and Business Aspects of Sustainability)

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25 pages, 11245 KB

Open AccessArticle

Multi-Objective Optimization Design of a Metakaolin–Slag-Based Binary Solid Waste Geopolymer Mortar Mix Proportion Using Response Surface Methodology

by Ruize Yin, Lianyong Zhu, Dawei Cheng, Pengchang Liang and Renfei Gao

Buildings 2026, 16(2), 402; https://doi.org/10.3390/buildings16020402 (registering DOI) - 18 Jan 2026

Abstract

This study focuses on the development of sustainable construction materials via geopolymers synthesized from metakaolin and slag, aiming to identify environmentally friendly alternatives for construction material systems. A metakaolin–slag geopolymer mortar (MK–slag) was prepared using metakaolin and slag as fully solid waste raw materials, with sodium silicate solution and sodium hydroxide acting as composite activators. Initially, single-factor experiments were conducted to determine the optimal ranges for metakaolin–slag content, water/binder ratio, and water glass modulus. Subsequently, response surface methodology was employed to develop regression equations that analyze the main and interaction effects of these variables on the 7-day and 28-day compressive strength and water absorption of the mortar. The optimal mix ratio was then identified. The microstructure and formation mechanisms of MK–slag mortar were studied using scanning electron microscopy (SEM), X-ray diffraction (XRD), and mercury intrusion porosimetry (MIP). The results indicate that all factors follow quadratic polynomial relationships with the response variables, showing a regression coefficient (R²) greater than 0.98, indicating an excellent model fit and prediction accuracy. According to model predictions, the optimal mix parameters under multi-objective optimization were found to be a metakaolin-to-slag ratio of 45%: 55%, a water/binder ratio of 0.45, and a water glass modulus of 1.3. After 28 days of curing, the primary hydration products were gel-like substances such as N-A-S-H and C-A-S-H. These gels interweave and overlap to form a high-density, structurally robust binary solid waste geopolymer mortar. This approach expands the application of solid waste materials, such as metakaolin and slag, while enhancing the recycling and utilization efficiency of these waste products. Full article

(This article belongs to the Section Building Materials, and Repair & Renovation)

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14 pages, 1049 KB

Open AccessArticle

Fracture Conductivity and Its Effects on Production Estimation in Shale

by Raymond Cozby, Ismaeel Ibrahim, Jin Xue, Nnaemeka Okeke, Syed Muhammad Abdullah Safdar, Haithem Trabelsi, Racha Trabelsi and Fathi Boukadi

Processes 2026, 14(2), 338; https://doi.org/10.3390/pr14020338 (registering DOI) - 18 Jan 2026

Abstract

This study investigates the impact of fracture conductivity on hydraulically fractured wells in the Eagle Ford Shale using commercial simulation software. Motivated by recent findings on conductivity degradation and the proven reliability of sensitivity analyses in shale reservoirs, a 17-stage horizontal well was modeled to evaluate productivity optimization. The methodology involved holding fracture fluid volume constant while analyzing conductivity variations across both single-fracture and full-well models. Production simulations were validated against real-time field data. Results indicate that the simulation models accurately represent the reservoir, with single-fracture scenarios yielding similar cumulative production and full-well models showing only minor deviations. Ultimately, the observed differences do not justify a significant deviation from current completion techniques under the modeling assumptions considered, as infinite-acting flow remains the dominant regime due to the reservoir’s low permeability. Full article

(This article belongs to the Special Issue Recent Developments in Low-Carbon and Efficient Extraction Technologies of Deep Unconventional Reservoirs)

57 pages, 958 KB

Open AccessReview

Oxidative Stress and SIRT1-Nrf2 Anti-Ferroptotic Pathways in Granulosa Cells: A Molecular Key to Follicular Atresia and Ovarian Aging

by Charalampos Voros, Fotios Chatzinikolaou, Georgios Papadimas, Spyridon Polykalas, Despoina Mavrogianni, Aristotelis-Marios Koulakmanidis, Diamantis Athanasiou, Vasiliki Kanaka, Kyriakos Bananis, Antonia Athanasiou, Aikaterini Athanasiou, Ioannis Papapanagiotou, Charalampos Tsimpoukelis, Athanasios Karpouzos, Maria Anastasia Daskalaki, Nikolaos Kanakas, Marianna Theodora, Nikolaos Thomakos, Panagiotis Antsaklis, Dimitrios Loutradis and Georgios Daskalakis Show full author list Hide full author list

Int. J. Mol. Sci. 2026, 27(2), 950; https://doi.org/10.3390/ijms27020950 (registering DOI) - 18 Jan 2026

Abstract

The functional deterioration of granulosa cells (GCs), essential for follicular growth, steroidogenesis, and oocyte competence, indicates ovarian aging and reduced fertility. An expanding corpus of research indicates that oxidative stress is a primary molecular contributor to granulosa cell dysfunction, culminating in mitochondrial impairment, reduced metabolic support for oocytes, and the activation of regulated apoptotic pathways that end in follicular atresia. Ferroptosis, an emergent type of iron-dependent lipid peroxidation, has been identified as a crucial mechanism contributing to chemotherapy-induced ovarian insufficiency, polycystic ovary syndrome (PCOS), and granulosa cell death in aging ovaries, in addition to conventional apoptosis. The SIRT1-Nrf2 axis acts as a crucial anti-oxidative and anti-ferroptotic system that protects GC viability, maintains mitochondrial homeostasis, and upholds redox equilibrium. SIRT1 promotes mitochondrial biogenesis and metabolic resilience by deacetylating downstream proteins, including FOXO3 and PGC-1α. Nrf2 simultaneously controls the transcriptional activation of detoxifying and antioxidant enzymes, including HO-1, SOD2, NQO1, and GPX4, which are critical inhibitors of ferroptosis. Disruption of SIRT1-Nrf2 signalling accelerates GC senescence, follicular depletion, and reproductive aging. In contrast, pharmaceutical and nutraceutical therapies, including metformin, melatonin, resveratrol, and agents that increase NAD⁺ levels, may reverse ovarian deterioration and reactivate SIRT1-Nrf2 activity. This narrative review highlights innovative treatment prospects for ovarian aging, fertility preservation, and assisted reproduction by synthesising current evidence on ferroptotic pathways, SIRT1-Nrf2 interactions, and oxidative stress in granulosa cells. An understanding of these interrelated biological networks enables the development of tailored therapies that postpone ovarian ageing and enhance reproductive outcomes for women receiving fertility therapy. Full article

(This article belongs to the Special Issue Molecular Studies in Endocrinology and Reproductive Biology)

40 pages, 3199 KB

Open AccessArticle

Scalable Satellite-Assisted Adaptive Federated Learning for Robust Precision Farming

by Sai Puppala and Koushik Sinha

Agronomy 2026, 16(2), 229; https://doi.org/10.3390/agronomy16020229 (registering DOI) - 18 Jan 2026

Abstract

Dynamic network conditions in precision agriculture motivate a scalable, privacy preserving federated learning architecture that tightly integrates ground-based edge intelligence with a space-assisted hierarchical aggregation layer. In Phase 1, heterogeneous tractors act as intelligent farm nodes that train local models, form capability- and task-aware clusters, and employ Network Quality Index (NQI)-driven scheduling, similarity-based check pointing, and compressed transmissions to cope with highly variable 3G/4G/5G connectivity. In Phase 2, cluster drivers synchronize with Low Earth Orbit (LEO) and Geostationary Earth Orbit (GEO) satellites that perform regional and global aggregation using staleness- and fairness-aware weighting, while end-to-end Salsa20 + MAC encryption preserves the confidentiality and integrity of all model updates. Across two representative tasks—nutrient prediction and crop health assessment—our full hierarchical system matches or exceeds centralized performance (e.g., AUC 0.92 vs. 0.91 for crop health) while reducing uplink traffic by ∼90% relative to vanilla FedAvg and cutting the communication energy proxy by more than 4×. The proposed fairness-aware GEO aggregation substantially narrows regional performance gaps (standard deviation of AUC across regions reduced from 0.058 to 0.017) and delivers the largest gains in low-connectivity areas (AUC 0.74 → 0.88). These results demonstrate that coupling on-farm intelligence with multi-orbit federated aggregation enables near-centralized model quality, strong privacy guarantees, and communication efficiency suitable for large-scale, connectivity-challenged agricultural deployments. Full article

(This article belongs to the Collection AI, Sensors and Robotics for Smart Agriculture)

17 pages, 548 KB

Open AccessArticle

Videogame Programming & Education: Enhancing Programming Skills Through Unity Visual Scripting

by Álvaro Villagómez-Palacios, Claudia De la Fuente-Burdiles and Cristian Vidal-Silva

Computers 2026, 15(1), 68; https://doi.org/10.3390/computers15010068 (registering DOI) - 18 Jan 2026

Abstract

Videogames (VGs) are highly attractive for children and young people. Although videogames were once viewed mainly as sources of distraction and leisure, they are now widely recognised as powerful tools for competence development across diverse domains. Designing and implementing a videogame is even more appealing for children and novice students than merely playing it, but developing programming competencies using a text-based language often constitutes a significant barrier to entry. This article presents the implementation and evaluation of a videogame development experience with university students using the Unity engine and its Visual Scripting block-based tool. Students worked in teams and successfully completed videogame projects, demonstrating substantial gains in programming and game construction skills. The adopted methodology facilitated learning, collaboration, and engagement. Building on a quasi-experimental design that compared a prior unit based on C# and MonoGame with a subsequent unit based on Unity Visual Scripting, the study analyses differences in performance, development effort, and motivational indicators. The results show statistically significant improvements in grades, reduced development time for core mechanics, and higher self-reported confidence when Visual Scripting is employed. The evidence supports the view of Visual Scripting as an effective educational strategy to introduce programming concepts without the syntactic and semantic barriers of traditional text-based languages. The findings further suggest that Unity Visual Scripting can act as a didactic bridge towards advanced programming, and that its adoption in secondary and primary education is promising both for reinforcing traditional subjects (history, language, mathematics) and for fostering foundational programming and videogame development skills in an inclusive manner. Full article

(This article belongs to the Special Issue Advances in Game-Based Learning, Gamification in Education and Serious Games)

27 pages, 2844 KB

Open AccessArticle

Extracellular Vesicles from Probiotic and Beneficial Escherichia coli Strains Exert Multifaceted Protective Effects Against Rotavirus Infection in Intestinal Epithelial Cells

by Cecilia Cordero, Aitor Caballero-Román, Sergio Martínez-Ruiz, Yenifer Olivo-Martínez, Laura Baldoma and Josefa Badia

Pharmaceutics 2026, 18(1), 120; https://doi.org/10.3390/pharmaceutics18010120 (registering DOI) - 18 Jan 2026

Abstract

Background/Objectives: Rotavirus remains a major cause of severe acute gastroenteritis
in infants worldwide. The suboptimal efficacy of current vaccines underscores the need
for alternative microbiome-based interventions, including postbiotics. Extracellular
vesicles (EVs) from probiotic and commensal E. coli strains have been shown to mitigate
diarrhea and enhance immune responses in a suckling-rat model of rotavirus infection.
Here, we investigate the regulatory mechanisms activated by EVs in rotavirus-infected
enterocytes. Methods: Polarized Caco-2 monolayers were used as a model of mature
enterocytes. Cells were pre-incubated with EVs from the probiotic E. coli Nissle 1917 (EcN)
or the commensal EcoR12 strain before rotavirus infection. Intracellular Ca²⁺
concentration, ROS levels, and the expression of immune- and barrier-related genes and
proteins were assessed at multiple time points post-infection. Results: EVs from both
strains exerted broad protective effects against rotavirus-induced cellular dysregulation,
with several responses being strain-specific. EVs interfered with viral replication by
counteracting host cellular processes essential for rotavirus propagation. Specifically, EV
treatment significantly reduced rotavirus-induced intracellular Ca²⁺ mobilization, ROS
production, and COX-2 expression. In addition, both EV types reduced virus-induced
mucin secretion and preserved tight junction organization, thereby limiting viral access
to basolateral coreceptors. Additionally, EVs enhanced innate antiviral defenses via
distinct, strain-dependent pathways: EcN EVs amplified IL-8-mediated responses,
whereas EcoR12 EVs preserved the expression of interferon-related signaling genes.
Conclusions: EVs from EcN and EcoR12 act through multiple complementary
mechanisms to restrict rotavirus replication, spread, and immune evasion. These findings
support their potential as effective postbiotic candidates for preventing or treating
rotavirus infection. Full article

(This article belongs to the Special Issue Probiotics in Pharmaceutics: Exploring the Therapeutic Potential and Formulation Strategies)

22 pages, 1347 KB

Open AccessArticle

Multi-Source Data Fusion for Anime Pilgrimage Recommendation: Integrating Accessibility, Seasonality, and Popularity

by Yusong Zhou and Yuanyuan Wang

Electronics 2026, 15(2), 419; https://doi.org/10.3390/electronics15020419 (registering DOI) - 18 Jan 2026

Abstract

Anime pilgrimage refers to the act of fans visiting real-world locations featured in anime works, offering visual familiarity alongside cultural depth. However, existing studies on anime tourism provide limited computational support for selecting pilgrimage sites based on contextual and experiential factors. This study proposes an intelligent recommendation framework based on multi-source data fusion that integrates three key elements: transportation accessibility, seasonal alignment between the current environment and the anime’s depicted scene, and a Cross-Platform Popularity Index (CPPI) derived from major global platforms. We evaluate each pilgrimage location using route-based accessibility analysis, season-scene discrepancy scoring, and robustly normalized popularity metrics. These factors are combined into a weighted Multi-Criteria Decision Making (MCDM) model to generate context-aware recommendations. To rigorously validate the proposed approach, a user study was conducted using a ranking task involving popular destinations in Tokyo. Participants were presented with travel conditions, spatial relationships, and popularity scores and then asked to rank their preferences. We used standard ranking-based metrics to compare system-generated rankings with participant choices. Furthermore, we conducted an ablation study to quantify the individual contribution of accessibility, seasonality, and popularity. The results demonstrate strong alignment between the model and user preferences, confirming that incorporating these three dimensions significantly enhances the reliability and satisfaction of real-world anime pilgrimage planning. Full article

(This article belongs to the Special Issue Advances in Intelligent Data Analysis and Its Applications, 3rd Edition)

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19 pages, 6939 KB

Open AccessArticle

Identification of OCT Family Genes in Tomato (Solanum lycopersicum) and Function of SlOCT20 Under Cold Stress

by Rui Lv, Fulei Mo, Yuxin Liu, Huixin Zhang, Mingfang Feng, Peiwen Wang, Mozhen Cheng, Shusen Liu, Zhao Liu, Xiuling Chen and Aoxue Wang

Biology 2026, 15(2), 176; https://doi.org/10.3390/biology15020176 (registering DOI) - 18 Jan 2026

Abstract

Plant organic cation transporters (OCTs) are involved in a variety of beneficial biological processes, such as cadaverine transfer in plants and soil, and play an active role in the formation of plant stress resistance. In this study, 52 OCT family genes were identified in tomato, and comprehensive bioinformatics analyses of these numbers, such as promoter cis-acting elements, gene mapping and collinearity, protein characterization and phylogenetic analysis. By analyzing the expression of tomato OCT family genes under cold and salt stresses using transcriptome data and qRT-PCR experiments, a key gene regulating cold stress tolerance, SlOCT20, was identified. Subcellular localization experiments indicated that SlOCT20 was mainly localized in the cell membrane. When the SlOCT20 gene was silenced in tomato, the tolerance to cold stress was significantly reduced and oxidative stress was aggravated, indicating that this gene positively regulates the tolerance to cold stress in tomato. Full article

(This article belongs to the Special Issue Unraveling the Molecular Mechanisms of Development and Stress Tolerance in Vegetables)

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26 pages, 5780 KB

Open AccessArticle

Analysis of Post-Fire Regeneration Dynamics in Pine Plantations Under Naturalistic Management with In Situ Burnt Logs

by Valentina Lucia Astrid Laface, Giuseppe Bombino, Carmelo Maria Musarella, Andrea Rosario Proto and Giovanni Spampinato

Sustainability 2026, 18(2), 971; https://doi.org/10.3390/su18020971 (registering DOI) - 17 Jan 2026

Abstract

Wildfires represent one of the most destructive natural disturbances, yet they play a fundamental ecological role in the regeneration and evolution of forest ecosystems. In Mediterranean regions, fire acts as a selective factor shaping plant adaptive strategies and the structure of vegetation mosaics. This study analyzes post-fire regeneration dynamics in Pinus radiata and P. pinaster plantations located in Roccaforte del Greco (Metropolitan City of Reggio Calabria, southern Italy), severely affected by the 2021 wildfires. Phytosociological surveys were conducted along permanent transects using the Braun-Blanquet method and analyzed through diversity indices (Shannon, Evenness), Non-Metric Multidimensional Scaling (NMDS), Indicator Species Analysis (IndVal), and hierarchical clustering. The results reveal a clear floristic differentiation among management conditions, with higher species diversity and variability, and a predominance of pioneer therophytes and hemicryptophytes in burned areas. The in situ retention of burned logs enhances structural and microenvironmental heterogeneity, facilitating the establishment of native species and supporting post-fire functional recovery. Overall, this preliminary study, focusing on early successional dynamics, suggests that the in situ retention of burned logs may positively contribute to ecosystem resilience and biodiversity in post-fire Mediterranean pine forests, while also highlighting the need for long-term monitoring to confirm the persistence of these effects. Full article

(This article belongs to the Special Issue Sustainable Management: Plant, Biodiversity and Ecosystem)

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40 pages, 1078 KB

Open AccessReview

Therapeutic Potential of Bovine Colostrum- and Milk-Derived Exosomes in Cancer Prevention and Treatment: Mechanisms, Evidence, and Future Perspectives

by Yusuf Serhat Karakülah, Yalçın Mert Yalçıntaş, Mikhael Bechelany and Sercan Karav

Pharmaceuticals 2026, 19(1), 168; https://doi.org/10.3390/ph19010168 (registering DOI) - 17 Jan 2026

Abstract

Due to their therapeutic potential and effects on cells, exosomes derived from bovine colostrum (BCE) and milk (BME) are molecules that have been at the center of recent studies. Their properties include the ability to cross biological barriers, their natural biocompatibility, and their structure, which enable them to act as stable nanocarriers. Exosomes derived from milk and colostrum stand out in cancer prevention and treatment due to these properties. BMEs can be enriched with bioactive peptides, lipids, and nucleic acids. The targeted drug delivery capacity of BMEs can be made more efficient through these enrichment processes. For example, BME enriched with an iRGD peptide and developed using hypoxia-sensitive lipids selectively transported drugs and reduced the survival rate of triple-negative breast cancer (TNBC) cells. ARV-825-CME formulations increased antitumor activity in some cancer types. The anticancer effects of exosomes are supported by these examples. In addition to their anticancer activities, exosomes also exhibit effects that maintain immune balance. BME and BCE can regulate inflammatory responses with their miRNA and protein loads. These effects of BMEs have been demonstrated in studies on colon, breast, liver, and lung cancers. The findings support the safety and scalability of these effects. However, significant challenges remain in terms of their large-scale isolation, load heterogeneity, and regulatory standardization. Consequently, BMEs represent a new generation of biogenic nanoplatforms at the intersection of nutrition, immunology, and oncology, paving the way for innovative therapeutic approaches. Full article

(This article belongs to the Special Issue Natural Products for Anticancer, Anti-Inflammatory and Antimicrobial Therapies)

20 pages, 4386 KB

Open AccessArticle

Characteristics and Sources of Particulate Matter During a Period of Improving Air Quality in Urban Shanghai (2016–2020)

by Xinlei Wang, Zheng Xiao, Lian Duan and Guangli Xiu

Atmosphere 2026, 17(1), 99; https://doi.org/10.3390/atmos17010099 (registering DOI) - 17 Jan 2026

Abstract

Following the implementation of the Shanghai Clean Air Act, this study investigates the evolution of air pollution in central Shanghai (Putuo District) by analyzing continuous monitoring data (2016–2020) and chemical speciation of particulate matter (2017–2018). The results confirm a transition toward a “low exceedance rate and low background concentration” regime. However, short-term exceedance episodes persist, generally occurring in winter and spring, with significantly amplified diurnal variations on exceedance days. Distinct patterns emerged between PM fractions: PM₁₀ exceedances were characterized by a single morning peak linked to traffic-induced coarse particles, while PM₂.₅ exceedances showed synchronized diurnal peaks with NO₂, suggesting a stronger contribution from vehicle exhaust. Source apportionment revealed that mineral components (21.61%) and organic matter (OM, 21.02%) dominated in PM₁₀, implicating construction and road dust. In contrast, PM_2.5 was primarily composed of OM (26.73%) and secondary inorganic ions (dominated by nitrate), highlighting the greater importance of secondary formation. The findings underscore that sustained PM_2.5 mitigation requires targeted control of gasoline vehicle emissions and gaseous precursors. Full article

(This article belongs to the Special Issue Advances in Air Pollution Control and Air Quality Improvement in Chinese Megacity Clusters: From Formation Mechanisms to Mitigation Strategies)

29 pages, 4487 KB

Open AccessProject Report

Designing for Health and Learning: Lessons Learned from a Case Study of the Evidence-Based Health Design Process for a Rooftop Garden at a Danish Social and Healthcare School

by Ulrika K. Stigsdotter and Lene Lottrup

Buildings 2026, 16(2), 393; https://doi.org/10.3390/buildings16020393 (registering DOI) - 17 Jan 2026

Abstract

This article presents a case study from a Social and Health Care School in Denmark, where a rooftop garden was designed to promote student health and support nature-based teaching across subject areas. A novel aspect of the project is the formal integration of the garden into teaching, implying that its long-term impact may extend beyond the students to the end-users they will later encounter in nursing homes and hospitals nationwide. This study applies the Evidence-Based Health Design in Landscape Architecture (EBHDL) process model, encompassing evidence collection, programming, and concept design, with the University of Copenhagen acting in a consultancy role. A co-design process with students and teachers was included as a novel source of case-specific evidence. Methodologically, this is a participatory practice-based case study focusing on the full design and construction processes, combining continuous documentation with reflective analysis of ‘process insights,’ generating lessons learned from the application of the EBHDL process model. This study identifies two categories of lessons learned. First, general insights emerged concerning governance, stakeholder roles, and the critical importance of site selection, procurement, and continuity of design responsibility. Second, specific insights were gained regarding the application of the EBHDL model, including its alignment with Danish and international standardised construction phases. These insights are particularly relevant for project managers in nature-based initiatives. The results also show how the EBHDL model aligns with Danish and international standardised construction phases, offering a bridge between health design methods and established building practice. The case focuses on the EBHDL process rather than verified outcomes and demonstrates how evidence-based and participatory approaches can help structure complex design processes, facilitate stakeholder engagement, and support decision-making in institutional projects. Full article

(This article belongs to the Special Issue Harmonizing Nature and Mind: Biophilic and Neuroarchitecture Synergies for Intelligent Buildings Enhancing Human Well-Being)

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26 pages, 997 KB

Open AccessArticle

MEP Pathway: First-Synthesized IspH-Directed Prodrugs with Potent Antimycobacterial Activity

by Alizée Allamand, Ludovik Noël-Duchesneau, Cédric Ettelbruck, Edgar De Luna, Didier Lièvremont and Catherine Grosdemange-Billiard

Microorganisms 2026, 14(1), 215; https://doi.org/10.3390/microorganisms14010215 (registering DOI) - 17 Jan 2026

Abstract

We report the first synthesis of IspH-directed prodrugs targeting the terminal enzyme of the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway, (E)-4-hydroxy-3-methylbut-2-enyl diphosphate reductase (IspH or LytB). A series of alkyne and pyridine monophosphate cycloSaligenyl (cycloSal) prodrugs were prepared to enhance membrane permeability by masking the phosphate group. The effects of electron-withdrawing (Cl, CF₃) and electron-donating (OCH₃, NH₂) substituents were examined, together with amino acid-functionalized and mutual prodrug analogs. Among the synthesized compounds, chlorine-substituted derivatives 5c and 6c displayed the strongest antimycobacterial activity against Mycobacterium smegmatis, surpassing isoniazid in agar diffusion assays. These results indicate that electron-withdrawing substituents accelerate prodrug hydrolysis and facilitate intracellular release of the active inhibitor. This work provides the first experimental evidence of an IspH-targeted prodrug approach, highlighting the cycloSal strategy as a valuable tool for delivering phosphorylated inhibitors and developing novel antimycobacterial agents acting through the MEP pathway. Full article

(This article belongs to the Section Antimicrobial Agents and Resistance)

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