Advancing Open Science

It is a common phenomenon that the stairs of modern historical brick–timber buildings cannot meet existing fire protection specifications, something which has become a difficulty in their renovation. In response, this study proposes two different renovation strategies for the Hui-shaped Chinese Baroque brick–timber building in Harbin and constructs multiple fire scenarios. Using a coupled PyroSim–Pathfinder (version 2023.2.0816) simulation approach, a finite element model of the building under fire and a corresponding evacuation model are established. The aim is to investigate how variations in stair width, number, position, and overall building scale under the two renovation strategies influence evacuation movement time and the number of evacuation failures, and to compare the effectiveness of common fire protection measures. The results show that, for the same stair configuration and building mass, the fire development patterns of the two renovation strategies are similar. Increasing the stair width from the original 0.9 m to 1.1 m produces no significant improvement in evacuation performance. When the number of indoor existing stairways increases from one to two, the proportion of occupants evacuated safely rises from 68% to 91%. External corridor staircases provide the best evacuation performance, and a single such stair can satisfy the safe evacuation of all occupants. When the same additional floor area is provided, increasing the number of storeys extends the evacuation movement time by approximately twice that caused by increasing the building footprint. Automatic sprinkler systems and mechanical smoke exhaust systems exhibit more pronounced fire protection effects.

Introduction: Patients with extremely elevated IL-6 levels remain poorly characterized, and no specific plasma concentration has been established to reliably predict mortality or guide immunomodulatory interventions. We hypothesized that extreme hypercytokinemia is associated with increased mortality in sepsis. The primary objective was to identify, in patients with hyperinflammatory endotype, an IL-6 threshold associated with a significantly elevated risk of death. Methods: We conducted a retrospective, single-center observational study based on a historical cohort of adult patients with consecutive activation of the in-hospital sepsis code, a prospective and standardized institutional care pathway, at Vall d’Hebron University Hospital between July 2018 and December 2024. Patients fulfilling Sepsis-2 diagnostic criteria and criteria for severe sepsis or septic shock were eligible. Plasma interleukin-6 (IL-6) levels were routinely determined in all patients. The analysis included patients with complete clinical and laboratory data available in the study database. To identify the IL-6 threshold associated with critical risk of death, a cumulative conditional relative frequency analysis was performed. A quantile-based analysis was conducted using predefined intervals of 1000 pg/mL and 15,000 pg/mL. A multivariable logistic regression analysis was conducted to identify clinical and laboratory parameters independently associated with IL-6 > 15,000 pg/mL and outcome. Results are presented as odds ratios (ORs). Survival differences were assessed using Kaplan–Meier analysis. Results: Overall mortality was 31% in the 1669 patients analyzed. Median IL-6 concentration was 772 pg/mL (IQR: 164–8750 pg/mL) with significantly higher levels in non-survivors (2137 pg/mL, IQR: 267–34,758). A critical IL-6 cutoff of 14,930 pg/mL was identified, which was rounded to 15,000 pg/mL for clinical applicability. IL-6 > 15,000 pg/mL was associated with increased mortality (OR 2.22, 95% CI: 1.12–5.36). Kaplan–Meier analysis revealed significantly reduced survival in patients above this IL-6 threshold (p < 0.0001). Conclusions: In this cohort of patients with severe sepsis or septic shock, plasma IL-6 levels > 15,000 pg/mL defined a critical threshold beyond which mortality risk exceeded survival probability. Critical hypercytokinemia may serve as a clinically relevant biomarker to identify patients with sepsis and multiorgan dysfunction who could benefit from precision immunomodulatory therapies.

Synucleinopathies, including Parkinson’s disease (PD), are neurodegenerative disorders characterized by aberrant aggregation of α-synuclein (α-syn), a presynaptic protein with an intrinsic disorder nature. The transition of soluble monomers into oligomeric and fibrillar species represents a key molecular event driving neuronal dysfunction and neurodegeneration. Emerging evidence suggests that nutraceuticals, bioactive compounds derived from dietary sources, can modulate α-syn aggregation at multiple conformational stages. Polyphenols, alkaloids, ginsenosides, and food-derived peptides interfere with α-syn structure and assembly, suppressing the formation of toxic oligomer species and promoting the clearance of misfolded assemblies. Despite this potential, clinical translational of nutraceuticals is currently limited by poor systemic bioavailability and restricted central nervous system penetration due to blood–brain barrier constraints, which have largely confined research to preclinical studies. In this context, this review summarizes current knowledge of nutraceutical interventions targeting the conformational landscape of α-syn and highlighting both direct and indirect molecular mechanisms with involved in aggregation-prone species. Furthermore, we critically examine key challenges related to bioavailability and clinical translation, focusing on advanced delivery systems and precision-based approaches to enhance neuroprotective efficacy and support the potential of nutraceuticals as novel or adjunctive therapeutic strategies for PD.

Background: Fragile X Syndrome (FXS) is an X-linked neurodevelopmental disorder characterised by intellectual disability, developmental delays, anxiety, and social and behavioural challenges. Currently, no effective treatments exist to address the root cause of FXS. Mouse models are the most widely used for studying molecular pathogenesis and conducting preclinical treatment testing. However, therapeutic interventions that show promise in rodent models have yet to succeed in clinical trials. After evaluating the current models, we have developed an ovine model to address this clinical translation gap. We expect this model to more accurately reflect the human condition in brain size, structure, and neurodevelopmental trajectory. We aim to establish this model as a valuable preclinical platform for testing therapies for FXS. Methods: To generate the sheep model, we used CRISPR-Cas9 dual-guide editing to knock out the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene in ovine embryos. Results: Two founder animals were created, one ram (male) and one ewe (female), both of which carried FMR1 gene knockouts. The ewe carries inactivating mutations on both alleles, with the edits in both animals resulting in no detectable Fragile X Messenger Ribonucleoprotein (FMRP) as expected. Both founders have undergone molecular characterisation and basic health checks, with the female founder showing increased joint flexibility, a characteristic of FXS. The ram has been used for breeding, with the successful transmission of the edited allele to his offspring. Importantly, specific lamb cohorts for postnatal treatment testing can be produced efficiently utilising accelerated breeding methods and preimplantation selection.

Passive protection is widely assumed to preserve biodiversity and ecological integrity, yet the evidence for long-term vegetation stability in protected temperate forests remains inconclusive. We resurveyed two deciduous forests in SW Poland after 30 years of strict protection to assess temporal changes in their understory vegetation, functional structure, and habitat conditions. Using paired phytosociological relevés (n = 40), collected using the Braun-Blanquet method, we compared baseline (1989–1991) and recent (2022) data with respect to species frequency, Ellenberg indicator values, basic functional traits, and functional diversity. Species composition proved highly stable: only 10% of vascular plant species exhibited significant changes in frequency in particular layers, largely reflecting the vertical redistribution of woody species rather than species turnover. Habitat conditions showed no significant temporal changes. In contrast, the functional structure of the herb layer changed markedly, with significant increases in community-weighted means of seed mass, plant height, and specific leaf area, accompanied by a significant rise in functional diversity. These shifts were partly driven by the increasing abundance of woody species and some opportunistic and invasive species. Our results demonstrate that functional traits may reveal directional ecological changes in passively protected forests even when species composition and habitat indicators remain unchanged, highlighting the importance of trait-based approaches for long-term forest surveys.

Gears, as critical power-transmission components in most power equipment, have a particularly urgent need for in situ inspection systems. Traditional gear inspection methods rely on contact inspection instruments, which are not only time-consuming, but also potentially damage the gear surface due to contact. This study delves into the detection requirements in the gear manufacturing process and establishes a rapid, non-contact detection mechanism and model using a CHCS. This model employs a CHCS to achieve high-speed, non-contact measurement on various surfaces with extremely high accuracy, enabling real-time monitoring of production process details, thereby improving production efficiency and ensuring product quality. Through actual inspection and comparison with a standard involute spur gear tooth profile model, this study implements a complete inspection system in a prototype. The results of gear inspection using a CHCS with an accuracy of 1 μm showed that the interquartile range of qualified gears under test (GUTs) was within 2.5 μm, and the beard line value was within 10 μm. The experiment demonstrated a layout equipped with a CHCS where the rotating axis represents the hobbing machine spindle. This method can be completed without moving the gear, enabling subsequent finishing processes.

Offshore wind energy is emerging as a vital component of the global transition to renewable energy, leveraging consistent wind conditions and higher power density compared to onshore systems. Integrating variable offshore wind power with hydrogen production via electrolysis provides a strategic pathway to convert surplus electricity into a storable and transportable energy carrier, thereby mitigating grid congestion, curtailment, and variability challenges. This review systematically examines the integration of offshore wind farms and hydrogen production technologies. Key components of the review include a comparative analysis of electrolyzer technologies, their suitability for offshore deployment, and the implications for energy storage and transport. The analysis employs a multi-step framework: (1) extensive search of the literature in scientific databases, (2) qualitative and quantitative assessment of system performance, and (3) synthesis of findings to identify trends and research gaps, enabling a thorough examination of technical challenges in the marine environment, and economic and policy barriers. The review highlights recent advancements, technical challenges, and economic considerations related to deployment of offshore wind-to-hydrogen systems. This review provides a comprehensive understanding of the current state of offshore hydrogen production, identifies research gaps, and outlines policy recommendations to accelerate its deployment. Offshore wind-powered hydrogen emerges as a cornerstone of a resilient, low-carbon energy future. The systematic approach ensures actionable insights and robust conclusions, facilitating the alignment of technological advancements with global decarbonization goals.

The utilization of polymer-based additive manufacturing processes for the production of functional components, consumer goods, spare parts, etc., has increased thanks to recent technological advances. The Arburg Plastic Freeforming (APF) process is a promising AM technology, in which standard plastic granules are deployed, and droplets are discharged along a track instead of using continuously extruded straws, unlike other filament-based processes, to the benefit of various industries that require good mechanical properties while maintaining dimensional precision. Due to the round shape of the droplets and tracks, however, defects such as voids can occur between individual paths during processing, which affect, most notably, mechanical properties. The electrical/ferroelectric properties of conductive/electroactive polymers are also affected. This study focuses on determining the optimal form factor for processing a special grade polyvinylidene fluoride (PVDF) material whilst other parameters, along with the ones ascertained in previous work, are kept constant. Along with tensile tests, X-ray computed microtomography (µ-CT) and scanning electron microscopy (SEM) analyses are implemented, particularly to observe microstructural porosity. Electrical properties and possible piezoelectric behavior are investigated via an originally adapted analytical method. The results provide important insights into the APF process and printing high-performance plastics with individual features, expanding the potential for further applications.