Polystyrene sulfonate resin as an ophthalmic carrier for enhanced bioavailability of ligustrazine phosphate controlled release system.

Topical ocular sustained-release drug delivery systems represent an effective strategy for the treatment of ocular diseases, for which a suitable carrier has yet to be sufficiently developed. Herein, an eye-compatible sodium polystyrene sulfonate resin (SPSR) was synthesized with a uniform particle size of about 3 µm. Ligustrazine phosphate (LP) was adsorbed to SPSR by cation exchange to form LP@SPSR. LP@SPSR suspension eye drops were further developed using the combination of Carbopol 934P and xanthan gum as suspending agents. The LP@SPSR suspension showed a sustained release in vitro, which was consistent with the observed porcine corneal penetration ex vivo. Pharmacokinetics in tear fluid of rabits indicated that LP@SPSR suspension led to prolonged ocular retention of LP and a 2-fold improved the area under the drug concentration-time curve (AUC0-t). Pharmacokinetics in the aqueous humor of rabbits showed 2.8-fold enhancement in the AUC0-t compared to LP solution. The LP@SPSR suspension exhibited no cytotoxicity to human corneal epithelial cells, nor irritation was observed in rabbit eyes. Thus, the LP@SPSR suspension has been validated as a safe and sustained release system leading to enhanced ophthalmic bioavailability for treating ocular diseases.

Urban heatwave, green spaces, and mental health: A review based on environmental health risk assessment framework.

Utilizing the framework of environmental health risk assessment and healing, the article reviews the effectiveness and potential of green space systems in mitigating the impact of high temperatures, promoting mental health, and improving the risk characteristics of high-temperature heat waves. We utilized CiteSpace software to conduct a time-zone analysis of the relationship between heatwaves, green spaces, and health using clustered data from 2001 to 2023. This study evaluates the role of green space systems in mitigating high temperatures and enhancing mental health within the environmental health risk assessment framework. Using CiteSpace software, we analyzed literature from 2001 to 2023, focusing on the interactions among heatwaves, green spaces, and health. Our results indicate that most existing research concentrates on hazard identification, with insufficient exploration of the dose-response relationships between green spaces and temperature reduction. Quantitative studies on green space design and spatial optimization are scarce, and guidance on effective configurations remains limited. Additionally, the health impacts of heatwaves vary by region, with a noticeable imbalance in research focus; Asia and Africa, in particular, are underrepresented in studies addressing heatwave effects. We conclude that effective mitigation strategies require: (1) a comprehensive environmental health risk assessment framework that integrates advanced methods like big data analysis and geospatial simulations to improve green space planning and design; (2) further theoretical exploration into the mechanisms by which green spaces regulate temperature and mental health, including detailed analysis of spatiotemporal patterns and the functional optimization of green space structures; and (3) the development of robust parameterized design guidance based on specific therapeutic dosages (green space stimulus) to optimize configurations and enhance the effectiveness of green spaces in mitigating adverse mental health impacts from deteriorating thermal environments. Future research should prioritize underrepresented regions, focusing on exposure levels, dose-response relationships, and high-temperature warning systems while fostering multidisciplinary collaboration to develop effective urban planning and climate adaptation strategies.

Lutein Loaded in ß-Cyclodextrin Metal-Organic Frameworks for Stability and Solubility Enhancements.

Lutein (Lut) is a recognized nutritional supplement known for its antioxidative and anti-inflammatory properties, crucial in mitigating ocular disease. However, enhancements to Lut stability and solubility remain challenges to be addressed in the healthcare industry. Herein, we fabricated and evaluated a food-grade highly porous ß-cyclodextrin metal-organic framework (ß-CD-MOF) for its ability to encapsulate Lut. Lut stability considerably improved when loaded into ß-CD-MOF to form a Lut@ß-CD-MOF complex, which exhibited better stability than Lut loaded into the γ-cyclodextrin metal-organic framework (Lut@γ-CD-MOF), Lut@ß-CD, and commercial product (Blackmores™) at 40°C, 60°C, and 70°C, respectively. The solubility of Lut@ß-CD-MOF in water increased by 26.8-fold compared to raw Lut at 37°C. Lut@ß-CD-MOF exhibited greater hydrophilicity, as determined by measuring the water contact angle. Molecular docking and other characterizations of Fourier transform infrared spectroscopy and powder X-ray diffraction confirmed that Lut was successfully encapsulated in the chamber formed by the three cyclodextrins in ß-CD-MOF. Thermogravimetric analysis and Raman spectroscopy demonstrated that Lut distributed in the ß-CD-MOF cavity deeply improved Lut stability and solubility. In conclusion, our findings underscored the function of ß-CD-MOF in enhancing Lut stability and solubility for formulation applications.

Beyond 1D and oversimplified kinematics: A generic analytical framework for surrogate safety measures.

This paper presents a generic analytical framework tailored for surrogate safety measures (SSMs) that is versatile across various highway geometries, capable of encompassing vehicle dynamics of differing dimensionality and fidelity, and suitable for dynamic, real-world environments. The framework incorporates a generic vehicle movement model, accommodating a spectrum of scenarios with varying degrees of complexity and dimensionality, facilitating the estimation of future vehicle trajectory evolution. It establishes a generic mathematical criterion to denote potential collisions, characterized by the spatial overlap between a vehicle and any other entity. A collision risk is present if the collision criterion is met at any non-negative estimated future time point, with the minimum threshold representing the remaining time to collision. The framework's proficiency spans from conventional one-dimensional (1D) SSMs to extended multi-dimensional, high-fidelity SSMs. Its validity is corroborated through simulation experiments that assess the precision of the framework when linearization is performed on the vehicle movement model. The outcomes showcase remarkable accuracy in estimating vehicle trajectory evolution and the time remaining before potential collisions occur, comparing to high-accuracy numerical integration solutions. The necessity of higher-dimensional and higher-fidelity SSMs is highlighted through a comparison of conventional 1D SSMs and extended three-dimensional (3D) SSMs. The results showed that using 1D SSMs over 3D SSMs could be off by 300% for Time-to-Collision (TTC) values larger than 1.5 s and about 20% for TTC values below 1.5 s. In other words, conventional 1D SSMs can yield highly inaccurate and unreliable results when assessing collision proximity and substantially misjudge the count of conflicts with predefined threshold (e.g., below 1.5s). Furthermore, the framework's practical application is demonstrated through a case study that actively evaluates all potential conflicts, underscoring its effectiveness in dynamic, real-world traffic situations.

Enhanced ophthalmic bioavailability and stability of atropine sulfate via sustained release particles using polystyrene sulfonate resin.

Atropine sulfate (ATS) eye drops at low concentrations constitute a limited selection for myopia treatment, with challenges such as low ophthalmic bioavailability and inadequate stability. This study proposes a novel strategy by synthesizing ophthalmic sodium polystyrene sulfonate resin (SPSR) characterized by a spherical shape and uniform size for cationic exchange with ATS. The formulation of ATS@SPSR suspension eye drops incorporates xanthan gum and hydroxypropyl methylcellulose (HPMC) as suspending agents. In vitro studies demonstrated that ATS@SPSR suspension eye drops exhibited sustained release characteristics, and tropic acid, its degradation product, remained undetected for 30 days at 40 °C. The ATS levels in the tear fluids and aqueous humor of New Zealand rabbits indicated a significant increase in mean residence time (MRT) and area under the drug concentration-time curve (AUC0-12h) for ATS@SPSR suspension eye drops compared to conventional ATS eye drops. Moreover, safety assessment confirmed the non-irritating nature of ATS@SPSR suspension eye drops in rabbit eyes. In conclusion, the cation-responsive sustained-release ATS@SPSR suspension eye drops enhanced the bioavailability and stability of ATS, offering a promising avenue for myopia treatment.

Controlled release of vitamin A palmitate from crosslinked cyclodextrin organic framework for dry eye disease therapy.

Controlled release drug delivery systems of eye drops are a promising ophthalmic therapy with advantages of good patient compliance and low irritation. However, the lack of a suitable drug carrier for ophthalmic use limits the development of the aforementioned system. Herein, the crosslinked cyclodextrin organic framework (COF) with a cubic porous structure and a uniform particle size was synthesized and applied to solidify vitamin A palmitate (VAP) by using the solvent-free method. The VAP@COF suspension eye drops were formulated by screening co-solvents, suspending agents, and stabilizing agents to achieve a homogeneous state and improve stability. According to the in vitro release study, the VAP@COF suspension exhibited a controlled release of VAP within 12 h. Both the ex vivo corneal contact angle and in vivo fluorescence tracking indicated that the VAP@COF suspension prolonged the VAP residence time on the ocular surface. This suspension accelerated the recovery of the dry eye disease (DED) model in New Zealand rabbits. Furthermore, the suspension was non-cytotoxic to human corneal epithelial cells and non-irritation to rabbit eyes. In summary, the particulate COF is an eye-acceptable novel carrier that sustains release and prolongs the VAP residence time on the ocular surface for DED treatment.

Exploring the dual impact: Dissecting the impact of tourism agglomeration on low-carbon agriculture.

Despite extensive research on the relationship between tourism and agriculture, the specific impact of tourism on agriculture's low-carbon transition has not been thoroughly investigated. This study analyzes the effects of tourism agglomeration on agricultural carbon intensity across 30 Chinese provinces from 2001 to 2020. It is framed within the context of rural digitalization, with a particular emphasis on the integration of agro-tourism and the total factor productivity of agriculture. Utilizing spatial econometric models, we find that tourism agglomeration hinders the low-carbon transition in agriculture by influencing carbon intensity both directly and indirectly. At the national level, the impact of tourism agglomeration follows an inverted-U curve with respect to agro-tourism integration and carbon intensity. At the regional level, the effects vary, with weaker indirect influences in major grain-producing areas. Furthermore, rural digitalization appears to lessen the adverse impacts of tourism on carbon intensity. This study also identifies significant spatial spillover effects from tourism agglomeration. The findings suggest that provinces with high tourist influx should enhance investments in climate-smart agricultural practices and technologies to counteract these negative impacts. Moreover, integrated governance of tourism and agriculture is essential for achieving carbon neutrality in both sectors.

Hypoxia-inducible factor 1α inhibits heat stress-induced pig intestinal epithelial cell apoptosis through eif2α/ATF4/CHOP signaling.

Unstoppable global warming and increased frequency of extreme heat leads to human and animals easier to suffer from heat stress (HS), with gastrointestinal abnormalities as one of the initial clinical symptoms. HS induces intestinal mucosal damage owing to intestinal hypoxia and hyperthermia. Hypoxia-inducible factor 1α (HIF-1α) activates numerous genes to mediate cell hypoxic responses; however, its role in HS-treated intestinal mucosa is unknown. This work aimed to explore HIF-1α function and regulatory mechanisms in HS-treated pig intestines. We assigned 10 pigs to control and moderate HS groups. Physical signs, stress, and antioxidant levels were detected, and the intestines were harvested after 72 h of HS treatment to study histological changes and HIF-1α, heat shock protein 90 (HSP90), and prolyl-4-hydroxylase 2 (PHD-2) expression. In addition, porcine intestinal columnar epithelial cells (IPEC-J2) underwent HS treatment (42 °C, 5 % O2) to further explore the functions and regulatory mechanism of HIF-1α. The results of histological examination revealed HS caused intestinal villi damage and increased apoptotic epithelial cell; the expression of HIF-1α and HSP90 increased while PHD-2 showed and opposite trend. Transcriptome sequencing analysis revealed that HS activated HIF-1 signaling. To further explore the role of HIF-1α on HS induced IPEC-J2 apoptosis, the HIF-1α was interfered and overexpression respectively, and the result confirmed that HIF-1α could inhibited cell apoptosis under HS. Furthermore, HS-induced apoptosis depends on eukaryotic initiation factor 2 alpha (eif2α)/activating transcription factor 4 (ATF4)/CCAAT-enhancer-binding protein homologous protein (CHOP) pathway, and HIF-1α can inhibit this pathway to alleviate IPEC-J2 cell apoptosis. In conclusion, this study suggests that HS can promote intestinal epithelial cell apoptosis and cause pig intestinal mucosal barrier damage; the HIF-1α can alleviate cell apoptosis by inhibiting eif2α/ATF4/CHOP signaling. These results indicate that HIF-1α plays a protective role in HS, and offers a potential target for HS prevention and mitigation.

Identifying the driving forces of cultivated land fragmentation in China.

Cultivated land fragmentation (CLF) has severely affected China's agricultural production efficiency, large-scale operations, agricultural modernization, and food security. Exploring the spatiotemporal evolution patterns and driving forces of CLF is crucial for agricultural modernization. However, the driving forces of CLF in different agricultural regions in China still need to be clarified. In this study, CLF was measured in 2000, 2010, and 2020 based on remote sensing data with landscape pattern metrics, and the driving forces of spatial differentiation were detected based on a geographical detector model. The overall cultivated land area has slightly declined during the study period while the CLF has intensified. CLF showed significant spatial autocorrelation, with CLF increased-cultivated land decreased (2000 to 2010) and CLF decreased-cultivated land decreased (2010 to 2020). The contribution rate of land use intensity on CLF was the highest among all agricultural regions, excluding the Qinghai Tibet Plateau. In contrast, the contribution rates of other factors significantly varied across agricultural regions. These findings provide scientific support in formulating policies to conserve cultivated land for sustainable use of agricultural resources and CLF management in China.

How do people perceive driving risks in small towns? A case study in Central Texas.

The number of studies investigating the relationship between perceived and objective traffic risk from drivers' perspective is limited. This study aims to investigate this dynamic within an understudied transportation environment - small towns in Texas, USA, defined as incorporated places with a population of less than 50,000. A web-based survey was distributed to six small towns in central Texas to ascertain perceptual traffic risk factors and personal characteristics. A participatory GIS exercise was also conducted to collect where high-risk locations were perceived and to correlate them to high crash zones. This study spatially examined the relations between perceived and observed risk locations and statistically identified a set of contributing factors which could make crash-intensive areas more perceivable by road users. The results indicated that road users' perceived risk locations are not always associated with high crash rates. The match rate between perceived and observed risk locations varied significantly across studied sites. We found that some personal and built environment factors significantly impacted people's sensitivity to perceiving crash-intensive locations. The binary logistic regression model was accurate (74.13%) in highlighting whether a perceived risk location matches observed risk locations. The results emphasize the importance of considering perceived and objective risk simultaneously to gain a better understanding of traffic risk mitigation, especially in underserved small towns.

Perspectives and mechanisms for targeting mitotic catastrophe in cancer treatment.

Mitotic catastrophe is distinct from other cell death modes due to unique nuclear alterations characterized as multi and/or micronucleation. Mitotic catastrophe is a common and virtually unavoidable consequence during cancer therapy. However, a comprehensive understanding of mitotic catastrophe remains lacking. Herein, we summarize the anticancer drugs that induce mitotic catastrophe, including microtubule-targeting agents, spindle assembly checkpoint kinase inhibitors, DNA damage agents and DNA damage response inhibitors. Based on the relationships between mitotic catastrophe and other cell death modes, we thoroughly evaluated the roles played by mitotic catastrophe in cancer treatment as well as its advantages and disadvantages. Some strategies for overcoming its shortcomings while fully utilizing its advantages are summarized and proposed in this review. We also review how mitotic catastrophe regulates cancer immunotherapy. These summarized findings suggest that the induction of mitotic catastrophe can serve as a promising new therapeutic approach for overcoming apoptosis resistance and strengthening cancer immunotherapy.

Sustainable poverty reduction models for the coordinated development of the social economy and environment in China.

Sustainable development in impoverished areas is still a global challenge owing to trade-offs between development and conservation. There are large poverty-stricken areas (PSAs) in China, which overlap highly with ecologically sensitive areas. China has made great efforts to alleviate poverty over the years. The coordinated relationship between the social economy and the environment in PSAs, however, remains under-recognized. This study developed a county-level index system encompassing the socioeconomic and environmental sectors of China's PSAs. The integrated indexes of the two sectors were developed to reveal the spatial-temporal socioeconomic and environmental patterns and coupling coordination degree (CCD) levels were calculated to assess the coordinated relationships between them. The CCD indicated the increasingly coordinated development of socioeconomic and environmental conditions in China's PSAs from 2000 to 2020. Meanwhile, although the socioeconomic index achieved considerable growth with a growth rate of 58.4%, the environmental index was mildly improved with a growth rate of 19.6%, instead of a reduction. PSAs still have a large gap in socioeconomic development compared to non-poor areas; however, PSAs perform better in environmental index. Overall, the increased coordinated development between the social economy and the environment from 2000 to 2020 can be attributed to China's long-term, large-scale, and targeted interventions in poverty reduction and environmental conservation. Further, benefiting from the geodiversity of China, we identified four poverty reduction models which include advantageously, sustained, periodic, and limited effective models, on the basis of CCD change patterns. The four models can provide valuable experience for the rest of the world in tackling similar trade-offs of poverty reduction and environmental challenges.

Peptide MSI-1 inhibited MCR-1 and regulated outer membrane vesicles to combat immune evasion of Escherichia coli.

Polymyxin resistance is conferred by MCR-1 (mobile colistin resistance 1)-induced lipopolysaccharide (LPS) modification of G- bacteria. However, the peptide MSI-1 exerts potent antimicrobial activity against mcr-1-carrying bacteria. To further investigate the potential role of MCR-1 in improving bacterial virulence and facilitating immune evasion, and the immunomodulatory effect of peptide MSI-1, we first explored outer membrane vesicle (OMV) alterations of mcr-1-carrying bacteria in the presence and absence of sub-MIC MSI-1, and host immune activation during bacterial infection and OMV stimulation. Our results demonstrated that LPS remodelling induced by MCR-1 negatively affected OMV formation and protein cargo by E. coli. In addition, MCR-1 diminished LPS-stimulated pyroptosis but facilitated mitochondrial dysfunction, further aggravating apoptosis in macrophages induced by OMVs of E. coli. Similarly, TLR4-mediated NF-κB activation was markedly alleviated once LPS was modified by MCR-1. However, peptide MSI-1 at the sub-MIC level inhibited the expression of MCR-1, further partly rescuing OMV alteration and attenuation of immune responses in the presence of MCR-1 during both infection and OMV stimulation, which can be exploited for anti-infective therapy.

Social Drivers of Mental Health: A U.S. Study Using Machine Learning.

INTRODUCTION: Social drivers of mental health can be compared on an aggregated level. This study employed a machine learning approach to identify and rank social drivers of mental health across census tracts in the U.S. METHODS: Data for 38,379 census tracts in the U.S. were collected from multiple sources in 2021. Two measures of mental health problems-self-reported depression and self-assessed poor mental health-among adults and three domains of social drivers (behavioral, environmental, and social) were analyzed on the basis of the unit of census tracts using the Extreme Gradient Boosting machine learning approach in 2022. The leading social drivers were found in each domain in the main sample and in the subsamples divided on the basis of poverty and racial segregation. RESULTS: The three domains combined explained more than 90% of the variance of both mental illness indicators. Self-reported depression and self-assessed poor mental health differed in major social drivers. The two outcome indicators had one overlapping correlate from the behavioral domain: smoking. Other than smoking, climate zone and racial composition were the leading correlates from the environmental and social domains, respectively. Census tract characteristics moderated the impacts of social drivers on mental health problems; the major social drivers differed by census tract poverty and racial segregation. CONCLUSIONS: Population mental health is highly contextualized. Better interventions can be developed on the basis of census tract-level analyses of social drivers that characterize the upstream causes of mental health problems.

Cbf-14, a cationic peptide derived from cathelin-domain, exhibits anti-inflammation activity via inhibiting PI3K- Akt /ROS/ NF-κB signaling pathway.

Cbf-14 with the sequence RLLRKFFRKLKKSV, is an effective antimicrobial peptide derived from a cathelin-like domain. Previous reports have demonstrated that Cbf-14 not only exerts antimicrobial activity against penicillin-resistant bacteria but also alleviates bacterial-induced inflammation in E. coli BL21 (DE3)-NDM-1-infected mice. In this article, we demonstrated that Cbf-14 can effectively reduce RAW 264.7 intracellular infection caused by clinical strain E. coli and alleviate the inflammatory response of cells and improve cell survival after infection. Therefore, we established the LPS-stimulated RAW 264.7 cell inflammation model to uncover the molecular mechanisms of the peptide Cbf-14 in anti-inflammatory activity. The results reveal that Cbf-14 can decrease LPS-induced ROS secretion by blocking the membrane translocation of p47-phox subunits and suppressing p47-phox protein phosphorylation. Meanwhile, this peptide can down-regulate the over-expression of iNOS, and finally inhibit the NO excessive secretion from RAW 264.7 macrophages stimulated by LPS. Moreover, Cbf-14 also down-regulates the expression levels of p-IκB and p-p65 and inhibits the nuclear translocation of NF-κB through blocking MAPK- and/or PI3K-Akt signaling pathways. Overall, Cbf-14 exhibits anti-inflammatory activity through inhibiting NF-κB activity and ROS production via PI3K- Akt signaling pathway.

Developing Human-Centered Urban Digital Twins for Community Infrastructure Resilience: A Research Agenda.

Urban digital twins (UDTs) have been identified as a potential technology to achieve digital transformative positive urban change through landscape architecture and urban planning. However, how this new technology will influence community resilience and adaptation planning is currently unclear. This article: (1) offers a scoping review of existing studies constructing UDTs, (2) identifies challenges and opportunities of UDT technologies for community adaptation planning, and (3) develops a conceptual framework of UDTs for community infrastructure resilience. This article highlights the need for integrating multi-agent interactions, artificial intelligence, and coupled natural-physical-social systems into a human-centered UDTs framework to improve community infrastructure resilience.

Simulating the Spatial Impacts of a Coastal Barrier in Galveston Island, Texas: A Three-Dimensional Urban Modeling Approach.

Due to its vulnerability to hurricanes, Galveston Island, TX, USA, is exploring the implementation of a coastal surge barrier (also referred to as the "Ike Dike") for protection from severe flood events. This research evaluates the predicted effects that the coastal spine will have across four different storm scenarios, including a Hurricane Ike scenario and 10-year, 100-year, and 500-year storm events with and without a 2.4ft. sea level rise (SLR). To achieve this, we develop a 1:1 ratio, 3-dimensional urban model and ran real-time flood projections using ADCIRC model data with and without the coastal barrier in place. Findings show that inundated area and property damages due to flooding will both significantly decrease if the coastal spine is implemented, with a 36% decrease in the inundated area and $4 billion less in property damage across all storm scenarios, on average. When including SLR, the amount of protection of the Ike Dike diminishes due to flooding from the bay side of the island. While the Ike Dike does appear to offer substantial protection from flooding in the short term, integrating the coastal barrier with other non-structural mechanisms would facilitate more long-term protection when considering SLR.

Immersive Experience and Climate Change Monitoring in Digital Landscapes: Evidence from Somatosensory Sense and Comfort.

In this study, the virtual engine software (Unity 2019, Unity Software Inc., San Francisco, California, the U.S.) was used to generate a digital landscape model, forming a virtual immersive environment. Through field investigation and emotional preference experiments, the ancient tree ecological area and the sunlight-exposed area were respectively monitored, and the somatosensory comfort evaluation model was established. The subjects showed the highest degree of interest in the ancient tree ecological area after landscape roaming experience, and the mean variance in SC fluctuation was 13.23% in experiments. The subjects were in a low arousal state and had a significant degree of interest in the digital landscape roaming scene, and there was a significant correlation between positive emotion, somatosensory comfort and the Rating of Perceived Exertion index; moreover, the somatosensory comfort of the ancient tree ecological area was higher than that of the sunlight-exposed area. Meanwhile, it was found that somatosensory comfort level can effectively distinguish the comfort level between the ancient tree ecological area and the sunlight-exposed area, which provides an important basis for monitoring extreme heat. This study concludes that, in terms of the goal of harmonious coexistence between human and nature, the evaluation model of somatosensory comfort can contribute to reducing people's adverse views on extreme weather conditions.

Investigation on the driver-victim pairs in pedestrian and bicyclist crashes by latent class clustering and random forest algorithm.

Pedestrians and bicyclists from marginalized and underserved populations experienced disproportionate fatalities and injury rates due to traffic crashes in the US. This disparity among road users of different races and the increasing trend of traffic risk for underserved racial groups called for an urgent agenda for transportation policy making and research to ensure equity in roadway safety. Pedestrian and bicyclist crashes involved drivers and pedestrians/bicyclists; the latter were usually victims. Traditional safety studies did not account for the interaction between the two parties and assumed that they were independent from each other. In this study we paired the driver and pedestrian/bicyclist involved in the same crash to understand the socioeconomic and demographic make-up of the two parties involved in crashes and assessed the geographic distribution of these crashes and crash-contributing factors. For this purpose, we applied thelatent class clustering analysis (LCA) to classify different crash types and analyze the patterns of the crashes based on the income and ethnicity of both drivers and victims involved in pedestrian and bicyclist crashes. We then used random forest algorithms and partial dependence plots (PDPs) to model and interpreted the contributing factors of the clusters in both pedestrian and bicyclist models. The clustering results showed a pattern of social segregation in pedestrian and bicyclist crashes that drivers and victims with similar socioeconomic characteristics tend to be involved in one crash. Pedestrian/bicyclist exposure, driver's age, victim's age, year of the car in use, annual average daily traffic (AADT), speed limit, roadbed width, and lane width were the most influential factors contributing to this pattern. Crashes that involved drivers and victims with lower income and non-white ethnicity tended to happen in the location with higher pedestrian/bicyclist exposure, higher speed limit, and wider road. The findings of this research can help to inform the decision-making process for improving safety to ensure equitable and sustainable safety for all road users and communities.

Revisiting the gravity laws of inter-city mobility in megacity regions.

Inter-city mobility is one of the most important issues in the UN Sustainable Development Goals, as it is essential to access the regional labour market, goods and services, and to constrain the spread of infectious diseases. Although the gravity model has been proved to be an effective model to describe mobility among settlements, knowledge is still insufficient in regions where dozens of megacities interact closely and over 100 million people reside. In addition, the existing knowledge is limited to overall population mobility, while the difference in inter-city travel with different purposes is unexplored on such a large geographic scale. We revisited the gravity laws of inter-city mobility using the 2.12 billion trip chains recorded by 40.48 million mobile phone users' trajectories in the Jing-Jin-Ji Region, which contains China's capital Beijing. Firstly, unlike previous studies, we found that non-commuting rather than commuting is the dominant type of inter-city mobility (89.3%). Non-commuting travellers have a travel distance 42.3% longer than commuting travellers. Secondly, we developed more accurate gravity models for the spatial distribution of inter-city commuting and non-commuting travel. We also found that inter-city mobility has a hierarchical structure, as the distribution of inter-city travel volume follows Zipf's law. In particular, the hierarchy of non-commuting travel volume among the cities is more in line with an ideal Zipf distribution than commuting travel. Our findings contribute to new knowledge on basic inter-city mobility laws, and they have significant applications for regional policies on human mobility.