Crowd management attempts to guide pedestrian crowds effectively and efficiently. Static crowd-management measures, such as fences, are often used to guide the crowd. Another way to steer pedestrian walking behavior is through “nudging,” that is, gently coaxing people into the “preferred” direction, for instance, by lighting conditions. This paper examines the impact of light intensity (brightness) and color on pedestrian route-choice behavior using data from a VR experiment. The study develops two types of discrete-choice models—a panel mixed logit model and a latent class choice model—featuring the route-choice behavior of pedestrians under varying lighting conditions in a virtual maze in a controlled virtual reality experiment. We found that pedestrians avoided red and dark corridors and chose green and blue corridors. On average, the green light most effectively “pulled” people toward a specific route. In addition, this study uncovered three segments in the population: (1) light-sensitive individuals, (2) darkness-avoiding individuals, and (3) individuals with a severe right-handed bias. We found that the impact of color and brightness levels on route-choice behavior differed greatly across segments.

Silica-polyethylenimine (silica-PEI) and, more recently, silica-alkoxylated polyethylenimine (APEI) adsorbents are promising materials for CO2 capture due to their high adsorption capacity and selectivity. The ability to reuse silica supports recovered from spent adsorbents can enhance overall material efficiency and facilitate the development of regeneration strategies given our earlier work demonstrating that spent PEI generates pyrazines and other chemicals during pyrolysis. In this study, spent silica-APEI adsorbents were subjected to four different treatments to recover silica supports and to investigate how thermal regeneration influences pore structure and subsequent reimpregnation performance. Single-stage and two-stage pyrolysis at 500-600 °C resulted in moderate mesopore contraction (13%) and total pore volume reduction (10%) compared to the initial silica, largely independent of the specific pyrolysis route applied. The recovered silicas were successfully reimpregnated with fresh PEI, exhibiting an optimal loading of 45 wt %, slightly lower than that of the original silica (47 wt %). At optimal PEI loadings, the regenerated silica-PEI displayed an approximately 10% reduction in CO2 adsorption capacity relative to fresh silica-based adsorbents. These results demonstrate that silica supports largely retain functional compatibility with PEI after high-temperature pyrolysis, laying the foundation for further studies with multiple cycles to assess the overall cost and life cycle benefits.

Tobacco and cannabis co-use by route of administration in the United States, 2022/2023.

Peptide-based vaccines: insights in a relationship between the explored administration routes and delivery systems.

Toward mutational epidemiology: using mutational signatures of environmental exposures to assess cancer risk.

Protoberberine alkaloids are a characteristic group of natural products in Coptis plants known for their notable pharmacological activities. However, the structural similarity and the substrate promiscuity of their biosynthetic enzymes have left the precise synthetic pathways remain unclarified, posing challenges to regulate product formation. In this study, we identified CcOMT8, a key enzyme responsible for C2-methoxylation in the biosynthesis of epiberberine in C. chinensis, through methyl jasmonate elicitation analysis and comparative genomics-based microsynteny analysis. Functional characterisation demonstrated that CcOMT8 specifically catalyses 2-O-methylation of (S)-scoulerine, as verified by heterologous expression in both microbial and plant systems. Its lack of activity toward (S)-cheilanthifoline further confirmed the specific route for epiberberine biosynthesis. Structural investigations of CcOMT8 and its complexes revealed key aspects of substrate recognition and a catalytic mechanism mediated by the His253-Asp254-Glu312 triad. Comparative structural analysis with 9-O-methyltransferases indicated that hydrophilic residues and reduced steric hindrance in the substrate binding pocket govern the regioselectivity of CcOMT8. Using focused rational iterative site-specific mutagenesis (FRISM), we developed an optimised mutant, S109L/C250A/L300A, with 4.88-fold enhanced catalytic efficiency. This study elucidates the biosynthetic pathway of epiberberine in Coptis, clarifies the molecular basis of enzyme-directed metabolic flux, and provides efficient biocatalysts for the synthetic biosynthesis of protoberberine alkaloids.

Since the late Qing, Christianity helped reconfigure China’s modern intellectual landscape not simply by importing “Western knowledge” but by constructing the epistemic frameworks through which knowledge was named, classified, and circulated. This article examines how the Christian idea of “homemaking” was scientized through translation and became jiazheng (家政, Home Economics) in Republican China, emerging as a new discipline within women’s education. It centers on Laura Marsden White (1867–1937), an American Protestant missionary and pioneer of women’s education who founded China’s first Christian women’s monthly, Nüduo (The Woman’s Messenger, 1912–1951) and initiated its jiazheng column as an institutional infrastructure for domestic science knowledge. Foregrounding White as a missionary–translator and translingual mediator, this study argues that her work participated in the construction of modern home economics rather than merely transmitting a ready-made field. Strategically aligning her translation with Confucian gendered ethics, White rendered home economics intelligible as jiazheng while simultaneously reorganizing household practices into a systematic, science-based curriculum. By circulating scientific knowledge, standardized curricular categories, and credentialed forms of expertise, White recast women’s domestic responsibilities as socially recognized knowledge and employable labor. Her translation offered Chinese women a historically specific route into schooling, writing, and public service, allowing them to negotiate the traditional gender divide without abandoning the culturally legible language of the family. Translation thus serves as both a medium of Protestant moral pedagogy and an engine of disciplinary formation and gendered social change.

The combined impacts of urban pluvial flooding and traffic congestion can severely delay emergency response. However, existing studies often focus on isolated scenarios, failing to systematically quantify the reduction in overall service capability and specific route disruptions to critical functional nodes under compound hazards. To address this problem, this study proposes a three-tier analytical framework to systematically evaluate the resilience of emergency services under compound hazards. The framework first utilizes spatial network analysis to simulate the overall spatial evolution of service capabilities for Emergency Medical Service (EMS) and Fire and Rescue Service (FRS) across various return periods and traffic conditions. It then delves into the emergency response coverage for vulnerable population places. Finally, the fastest-route analysis is employed to identify variations in rescue routing. The study reveals several critical insights. (1) As rainfall intensity and traffic congestion intensify, the coverage areas of EMS and FRS exhibit significant contraction and boundary erosion. Notably, the service areas of FRS show a distinct fragmentation pattern. (2) The protection levels for vulnerable population places (e.g., kindergartens, primary and secondary schools, and nursing homes) show a pronounced stepwise decline. Under extreme rainfall and the heaviest congestion, the 5 min coverage for these sites drops from 89.9% to 23.6% for EMS, and from 72.4% to only 15.1% for FRS, revealing a severe risk exposure for vulnerable groups. (3) Road inundation leads to a substantial extension of rescue routes and even results in the complete isolation of 141 primary and secondary schools. Overall, the framework provides actionable decision support to enhance urban emergency response under compound hazards.

Abstract A welding process inevitably influences the base material in the heat-affected zone (HAZ) of the weld seam, which can critically alter the mechanical properties of high-strength low-alloyed (HSLA) steels. To account for this, weldability is commonly assessed using the carbon equivalent (CE), neglecting essential factors such as microalloying concepts and specific manufacturing routes. Since strengthening mechanisms respond differently to welding thermal cycles, CE alone offers limited reliability for evaluating the weldability of HSLA steels. To address this, thermophysical simulations using a TA Instruments DIL 805 dilatometer were carried out on quenched and tempered and thermomechanical-controlled processed steels with yield strength levels of ~ 700 MPa. Time–temperature cycles based on gas metal arc welding were applied using peak temperatures of 1,200 °C, 1,000 °C, 800 °C, and 600 °C and cooling times t 8/5 of 5–25 s. To evaluate the changes in material properties, tensile testing, hardness measurements, and microscopic analyses were conducted. The results demonstrate significant manufacturing-related differences of mechanical and microstructural properties, with strength reductions of up to 40% and hardness increases of up to 51%. Therefore, a new evaluation approach was discussed for HSLA steels, which incorporates specific manufacturing routes to enable a more reliable assessment of weldability.

This study proposes an exploratory framework for identifying stress locations during travel with low-speed mobility devices (LMDs), such as electric wheelchairs. In this framework, stress factors perceived during LMD travel were identified through a post-ride questionnaire, and the travel route was divided into 100 m segments to enable location-specific stress evaluation. The identified factors were quantified using environmental data to construct an environment-based stress estimation index. Based on these quantified factors, a Composite Stress Score (CSS) was calculated to estimate stress levels along the route. Experiments with healthy adult participants were conducted to examine the feasibility of the proposed method. The results identified poor road surface conditions and vibrations, encounters with other road users, and narrow sidewalks as key stress factors during LMD travel. To examine whether the proposed method captures stress-related responses, correlations between CSS-based stress estimates and heart rate variability (HRV) indices were analyzed. The results showed that CSS calculated from poor road surface/vibrations, encounters with other road users, and narrow sidewalks exhibited moderate negative correlations with SDNN, suggesting that higher CSS values may correspond to increased physiological stress responses. These findings provide preliminary support for the exploratory feasibility of estimating potential stress locations during LMD travel using environmental data. However, the generalizability of the results is limited due to the specific experimental route and the use of healthy adult participants.

Introduction: Human crowd crushes are catastrophic events where dense gatherings can lead to severe injuries and fatalities. Understanding crowd behavior and biomechanics is crucial for developing effective prevention strategies, such as eliminating bottlenecks and ensuring ingress and egress. Given the infeasibility of real-world trials, simulations are useful to examine crowd disasters. This study reports the results of a simulation that analyzes human behavior and injury patterns during a crowd crush by incorporating variable crowd densities and trajectories using ragdoll physics principles. Methods: This simulation was developed with ragdoll physics using the Unity Simulation Engine (Unity Technologies, 2023, San Francisco, USA). A custom-built virtual environment modeled a crowd crush incident and included three groups, each consisting of 500 individuals, converging from the left, right, and perpendicularly in a “T” junction. Pedestrians walking at speeds averaging 1 meter per second were randomly assigned. A series of 30 simulation trials was run with 1,500 pedestrians per trial. The number of injuries and fatalities was recorded. Results: A crowd simulator was successfully generated, allowing users to create groups with specific sizes, routes, and speeds, with visualization of humanoid subjects. The mean number of injuries was 191.6 (±18.75 SD), with a median of 191.5 injuries per trial and an interquartile range (IQR) of 182 to 206.5 injuries. For fatalities, the mean was 63.1 (±8.56 SD), with a median of 62 fatalities per trial and an IQR of 55.25 to 68.75 fatalities. Conclusion: The ragdoll physics simulation provides valuable insights into biomechanics, injuries, and fatalities associated with human crowd crushes. This tool has the potential to help improve crowd management protocols. Future research will focus on refining the model and its application in real-time crowd monitoring systems.

Spinal cord injury (SCI) is a highly disabling disorder of the central nervous system for which no curative therapy is currently available. In recent years, extracellular vesicles - particularly exosomes - have been investigated as cell-free therapeutic approaches in experimental models, owing to their low immunogenicity, favorable biocompatibility and capacity to traverse the blood-spinal cord barrier under specific conditions or delivery routes. This Review summarizes the therapeutic activities and mechanisms of exosomes from diverse sources - including mesenchymal stem cells, immune cells and neural cells - in SCI repair. Reported mechanisms include modulation of the inflammatory microenvironment; inhibition of apoptosis and pyroptosis; mitigation of ferroptosis; promotion of angiogenesis and axonal regeneration; and restriction of glial scar formation. We also discuss advances aimed at enhancing exosome efficacy through cell preconditioning, engineering strategies and integration with biomaterials. Although exosome-based approaches are promising, challenges remain in standardization, targeted delivery and long-term safety. Future work should elucidate the underlying mechanisms and advance clinical translation to robustly evaluate the therapeutic potential of exosomes for SCI repair.

Solar activity can significantly influence the performance and reliability of both space-borne and ground-based technological systems on Earth. This phenomenon, known as space weather, can impact modern aviation operations through complex and highly interconnected mechanisms, presenting a challenging area of study. Until now, no systematic investigation has explored the influence of space weather on flight cancellations outside of specific polar routes. By analyzing ~ 5 million flight departure records from 5 hub airports in China between 2015 and 2019, a period spanning the declining phase and subsequent minimum of Solar Cycle 24, we provide the first evidence of a systematic increase in flight cancellations during space weather events. Our comparative analysis reveals that the average cancellation rate during space weather events, specifically Solar Flares, Interplanetary Coronal Mass Ejections, and Solar Proton Events, was 96.96% higher than during quiet periods. Counter-intuitively, Stream Interaction Regions showed no increase and even a slight decrease in cancellation rates. Additionally, investigations on geomagnetic-ionospheric disturbances reveal a quasi-linear relation between the rate of flight cancellations and the magnitude of perturbations. Such increased flight cancellations persist even when accounting for other factors, such as the seasonal effects. These findings imply that disruptions in communication and navigation systems during space weather events can significantly impact modern aviation operations, leading to more frequent flight cancellations. The superposed epoch analysis uncovers a well-defined temporal response curve of cancellation rates to independent space weather events. The correlations observed suggest that prolonged flight delays induced by space weather may be another important driver of the increased cancellation rates. This research expands the conventional understanding of space weather’s impact on aviation and it implies the importance of integrating space weather as a systematic factor in flight operations and planning, which may also help improve aviation efficiency and safety.

Patient-specific lattice implants (PSLIs) and modular porous scaffolds have emerged as promising solutions for treating diaphyseal segmental defects of the femur and tibia, particularly where conventional reconstruction methods fall short. This second part of our two-part review focuses on how current studies transform computed tomography (CT) and μCT datasets into architected lattice implants, as well as how these constructs are fabricated and numerically, mechanically, biologically, and clinically verified. We outline imaging pipelines, including Digital Imaging and Communications in Medicine (DICOM) acquisition, segmentation, contralateral mirroring, and Hounsfield Units (HU)-density-elasticity mapping, and show how these choices impact finite element (FE) models and print-ready geometries. Next, lattice design strategies and mixed-material concepts are compared and linked to specific additive manufacturing routes in metals, polymers, and bioceramics, such as laser powder bed fusion (LPBF), electron beam melting (EBM), fused deposition modeling (FDM), material jetting, and extrusion-based bioprinting. Methodological overviews of linear-elastic models and homogenized finite element (FE) models, along with bench-top mechanical tests, in vitro cell assays, in vivo animal studies, and early clinical series, are utilized to categorize the studies into four pathways: simulation (S), mechanical (E_mech), biological (E_bio), and validation (V). Based on the reviewed literature, we establish a general workflow for CT implants. We identify common gaps in the process, observe insufficient reporting of imaging and modeling details, note a lack of data on fatigue and remodeling, and recognize the limited size of clinical cohorts. Additionally, we provide practical recommendations for developing more standardized and scalable planning pipelines. Part 1 of this two-part review studied defect patterns, anatomical location, and fixation strategies for patient-specific lattice implants used in femoral and tibial segmental reconstruction, with emphasis on how defect morphology and subregional anatomy influence construct selection and mechanical behavior. It established a defect- and fixation-centered review that provides the clinical and anatomical context for the workflow and validation analysis presented in Part 2.

Pollinator decline is driven by multiple factors, with pesticides being among the most significant. Current regulatory risk assessments rely almost exclusively on Apis mellifera, which may not adequately represent stingless bees (tribe Meliponini), key pollinators in tropical and subtropical ecosystems. This study systematically reviews evidence on pesticide toxicity in stingless bees, comparing their sensitivity with that of A. mellifera and evaluating implications for environmental risk assessment. Following PRISMA guidelines, major academic databases were searched for studies published between 2014 and 2025. Data extraction included bee species, pesticide compounds, exposure routes, and Species Sensitivity Ratios (SSR), calculated to quantify relative sensitivity. A total of 27 studies were identified, encompassing 115 experiments and 24 stingless bee species. Stingless bees showed higher sensitivity in 72% of trials, with adverse effects occurring at lower concentrations than those affecting A. mellifera. Oral exposure was the most common route (61%), and insecticides dominated the dataset (98%). Based on evidence from the past decade, stingless bees are consistently more sensitive to pesticides than A. mellifera. Thus, the continued reliance on A. mellifera as the sole surrogate species may underestimate risks to tropical pollinators. Expanding ecotoxicological testing frameworks to include stingless bees and their specific exposure routes would enhance the ecological relevance of pesticide risk assessments, strengthen pollinator conservation strategies, and contribute to the protection of biodiversity and agricultural sustainability in regions where these bees are key pollinators.

Posterior parietal cortex maps progress along routes sharing the same meta-structure but opposite action series.

This study aimed to clarify the lymphatic network around the anorectum using cadavers and consider a treatment strategy for locally advanced lower rectal cancer (LARC). We performed microscopic observations of three female cadavers using India ink into the submucosa at the dentate line (DL) of the cadaver. We examined the clinical outcomes of 74 patients with LARC who underwent total mesorectal excision after preoperative treatment, classifying them as anterior (A), lateral (L), or posterior (P) based on the deepest part of the tumor. Two of the three anterior walls contained the Denonvilliers' fascia (DVF), and the DVF became indistinct at the height of DL, where India ink extended to the vagina via the perivascular space and was absorbed into the vaginal lymph vessels. One case did not have DVF, and lymph vessels in the rectum distributed in close proximity to vagina. On the lateral posterior wall, the ink spread extensively from DL and the front of the levator ani muscle, whereas on the posterior wall, lymph vessels containing absorbed ink were observed from the hiatal ligament to the front of the sacrum. In the survival analysis, the 3-year disease-free survival rates were 71.9%, 100%, and 69.7% for A, L, and P groups, respectively, with a higher recurrence rate in the anterior and posterior walls. Lymphatic network beyond fascia around anorectum was spread to a specific route by location. The anatomical diversity of this network was thought to be involved in the poor outcome for LARC.

ABSTRACT Protein aggregation drives proteinopathies ranging from ALS to systemic amyloidosis, yet the multiscale determinants bridging sequence, structure, and kinetics remain elusive. We present SKALE, an interpretable machine learning framework that integrates sequence motifs, AlphaFold‐derived structural descriptors, and experimental kinetics to decode aggregation mechanisms. SKALE identifies latent hotspots that evade conventional tools and matches high‐performing neural baselines while preserving computational efficiency. In ALS‐linked SOD1 G86R, the model isolates a risk region at residues 72–91 where preserved β‐sheet geometry coincides with weakened hydrogen bonding to drive nucleation. Similarly, analysis of TDP‐43 S332N reveals that a locally unwound helix increases surface exposure, a prediction validated by showing that targeted deletion of model‐identified regions significantly reduces cellular aggregation. The framework generalizes to Tau P301L and PRNP variants where it uncovers distal aggregation‐prone regions to discriminate pathogenic drivers from neutral mutations. Interpretability analysis further disentangles global from mutation‐local mechanisms to reveal that β‐sheet propensity acts as a shared determinant while hydrogen bond dynamics define specific routes to nucleation. These findings establish SKALE as a scalable, disease‐agnostic engine that combines high‐fidelity prediction with biophysical resolution to decode the molecular logic of misfolding and guide therapeutic design.

This study reviewed the use of hydrochars in the adsorption of methylene blue, a toxic dye, from aqueous phases. Journal articles published predominantly between 2020 and 2025 were assessed. The articles were mainly identified through keyword searches on ScienceDirect, Scopus and Web of Science. The studies reported a high efficacy of hydrochars against the dye. Organic wastes were primarily used as a feedstock in the hydrothermal carbonization processes, aligning to the waste to resource principle, an efficient and cost effective route of synthesis of adsorbents. The pseudo-first order, pseudo-second order and the Elovich model best described the kinetic data while the Freundlich, Sips and Langmuir isotherms best fitted the experimental data, with model predicted adsorption capacities in the range of 30-1060 mg g− 1. All the reviewed studies reported a spontaneous and feasible adsorption process (negative ΔG), while the entropy (ΔS) and enthalpy (ΔH) values varied with feedstock used, the specific modification routes and modification conditions. Several systems retained between 65 and 95% capacity over five cycles with eluents such as HCl, ethanol and methanol. The mechanism of adsorption was reported by most of the studies to be through electrostatic interactions, hydrogen bonding and π-π interactions.

The synergistic effects of kPa-scale elastic modulus and size of poly(N-isopropylacrylamide)/sodium alginate nanospheres on endocytosis.