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SUMMARY Nourishing the embryo with endosperm and enclosing both embryo and endosperm in the seed coat are two important evolutionary innovations. Seed coat is conventionally viewed as a protective layer that functions after the seed has matured. Here, we challenge this notion by showing that a subregion of the seed coat, termed the chalazal seed coat (CZSC), is geared to gate seed nutrition loading in developing seeds. The CZSC develops the coordinative system comprising the apoplastic isolation, mediated by the restricted suberization, and the active transport, mediated by the specific expression of a variety of transporters, at as early as the globular embryo stage in both Arabidopsis and soybean seeds. This coordinated system in the CZSC disrupts the vascular continuum to the maternal tissues and forces the nutrient transport into selective and active absorption. We further reveal that the precision of the spatiotemporal suberin deposition and transporter expression is controlled by the regulatory hierarchy of SHR‐MYBs cascades. Our results provide a mechanistic insight into the assimilate accumulation in dicot seeds. [ABSTRACT FROM AUTHOR]

Background: Urban neighborhood environments play an important role in facilitating or hindering residents to engage in active mobility and social participation. However, while there is much quantitative research, in-depth knowledge that contextualizes residents' subjective perceptions of barriers and facilitators of active mobility and social participation is still insufficient. Therefore, a qualitative approach was used to collect subjectively perceived barriers and facilitators of active mobility and social participation of residents from different neighborhoods with objectively determined high vs. low walkability. Furthermore, to better understand (non) concordance of objective environmental characterizations and actual levels of behavior, low and high walkability neighborhood-specific barriers, proposed improvements, and particularities that determine (non) engagement in active mobility and social participation were explored. Methods: Three focus groups (N = 6, N = 6, and N = 5) with 17 participants (7 women, 10 men) aged 21–64 (mean age 43.4 ± 14,6 years) were conducted utilizing a pre-structured interview guideline. Participants lived in 11 different neighborhoods with either high or low objectively determined walkability. The focus groups were transcribed verbatim, followed by a thematic analysis of the content with deductive and inductive code categories, utilizing the MAXQDA software. Results: Notable was the consensus of many perceived barriers and facilitators of active mobility and social participation along with their assignability to the same context (points-of-interest, infrastructure; safety, communication, community; topography, physical compositions, weather, aesthetics; personal / individual attitudes, influences, evaluations). Another main finding was that high and low walkability neighborhood-specific particularities were revealed that are in contrast to some objective characterizations of walkability: For example, too high density can inhibit active mobility, and too many options can inhibit social participation. Conclusions: The consensus of many barriers and facilitators of active mobility and social participation suggests that valuable synergies could be created by coordinating interventions aiming to promote both active mobility and social participation in urban neighborhoods. Also, considering subjective perceptions of residents helps to identify neighborhood-specific factors that determine (non) engagement in active mobility and social participation. The findings can help city planners and public health officials improve the promotion of active mobility and social participation in the creation of health-enhancing urban neighborhoods. [ABSTRACT FROM AUTHOR]

Environmental factors have been identified as having a direct relationship with physical activity (PA) and sedentary behavior. The main aim of this study was to investigate the relationship between microscale built-environment attributes and the levels of PA and sedentary behavior in young people. This study included 465 adolescents (55% girls) between 14 and 18 years from Valencia, Spain. Accelerometers and self-reported questionnaires were used to measure PA, including active commuting, and sedentary behavior, and the MAPS (Microscale Audit of Pedestrian Streetscapes)-Global tool was used for microscale variables. Mixed-effects regression models were used for data analysis. Higher levels of moderate-to-vigorous activity were identified when more positive elements were found in the street characteristics. Greater active commuting in the neighborhood had a positive relationship not only with more positive elements of land use and destinations but also with the overall score of the MAPS-Global tool. The sedentary levels were higher when higher levels of negative aesthetics and social characteristics were identified, and the participants were less sedentary when more bike facilities were observed. The main results of this study provide us with evidence of the relationship between the microscale variables of the built environment and both PA and sedentary behavior. [ABSTRACT FROM AUTHOR]

Abstract Background Urban neighborhood environments play an important role in facilitating or hindering residents to engage in active mobility and social participation. However, while there is much quantitative research, in-depth knowledge that contextualizes residents’ subjective perceptions of barriers and facilitators of active mobility and social participation is still insufficient. Therefore, a qualitative approach was used to collect subjectively perceived barriers and facilitators of active mobility and social participation of residents from different neighborhoods with objectively determined high vs. low walkability. Furthermore, to better understand (non) concordance of objective environmental characterizations and actual levels of behavior, low and high walkability neighborhood-specific barriers, proposed improvements, and particularities that determine (non) engagement in active mobility and social participation were explored. Methods Three focus groups (N = 6, N = 6, and N = 5) with 17 participants (7 women, 10 men) aged 21–64 (mean age 43.4 ± 14,6 years) were conducted utilizing a pre-structured interview guideline. Participants lived in 11 different neighborhoods with either high or low objectively determined walkability. The focus groups were transcribed verbatim, followed by a thematic analysis of the content with deductive and inductive code categories, utilizing the MAXQDA software. Results Notable was the consensus of many perceived barriers and facilitators of active mobility and social participation along with their assignability to the same context (points-of-interest, infrastructure; safety, communication, community; topography, physical compositions, weather, aesthetics; personal / individual attitudes, influences, evaluations). Another main finding was that high and low walkability neighborhood-specific particularities were revealed that are in contrast to some objective characterizations of walkability: For example, too high density can inhibit active mobility, and too many options can inhibit social participation. Conclusions The consensus of many barriers and facilitators of active mobility and social participation suggests that valuable synergies could be created by coordinating interventions aiming to promote both active mobility and social participation in urban neighborhoods. Also, considering subjective perceptions of residents helps to identify neighborhood-specific factors that determine (non) engagement in active mobility and social participation. The findings can help city planners and public health officials improve the promotion of active mobility and social participation in the creation of health-enhancing urban neighborhoods.

The study aims to develop an analytical framework for assessing cycling infrastructure from adolescents' safety perspectives, facilitating the prioritisation of areas based on effectiveness and existing conditions. Through an online survey (n = 323), we explored the perceived safety of Australian adolescents with different types of cycling lanes. The majority of survey participants prefer physically separated or protected cycleways. However, only 8.8% of the adolescent population in Greater Sydney has continuous cycleways to their catchment high-schools through these types of cycleways. Our study found a larger number of adolescents (28.1%) have access to nearby parks via safe cycleways. Although this difference appears to be due to the greater number of parks available, it could potentially contribute to significantly higher rates of recreational cycling participation in Sydney. This study also introduces an evaluation metric that combines the composite cycleway connectivity index, adolescent population density, and home-to-school distances to assist high-level selection and prioritisation of future infrastructure projects aimed at promoting active school travel. • A framework to assess cycling infrastructure from adolescents' safety perspective, aiding investment prioritisation. • Most adolescents prefer separate or protected cycleways, but limited access exists in Greater Sydney, Australia. • An evaluation metric for assessing adolescent cycling infrastructure was introduced at the school catchment area level. [ABSTRACT FROM AUTHOR]

As a widely used pesticide, abamectin could be a threat to nontarget organisms. In this study, the toxic mechanism of abamectin on osmoregulation in Procambarus clarkii was explored for the first time. The results of this study showed that with increasing abamectin concentration, the membrane structures of gill filaments were damaged, with changes in ATPase activities, transporter contents, biogenic amine contents, and gene expression levels. The results of this study indicated that at 0.2 mg/L abamectin, ion diffusion could maintain osmoregulation. At 0.4 mg/L abamectin, passive transport was inhibited due to damage to the membrane structures of gill filaments, and active transport needed to be enhanced for osmoregulation. At 0.6 mg/L abamectin, the membrane structures of gill filaments were seriously damaged, and the expression level of osmoregulation-related genes decreased, but the organisms were still mobilizing various transporters, ATPases, and biogenic amines to address abamectin stress. This study provided a theoretical basis for further study of the effects of contaminations in aquatic environment on the health of crustaceans. [ABSTRACT FROM AUTHOR]

Background: Little is known about the association between active commuting (i.e., walking or cycling to school) with lifestyle parameters and mental health in youths. The objective of the present study was to investigate the association between mental health problems and symptoms of depression, anxiety, and stress with lifestyle (i.e., food habits, screen time, physical activity, and sleep quality), active commuting, and gender. Methods: A total of 511 children and adolescents (boys, n = 249; girls, n = 262) aged 10 to 17 years participated in the study. Lifestyle parameters and mental health were evaluated using the Depression Anxiety and Stress Scale (DASS-21). Results: Girls reported higher levels of anxiety (p = 0.001), depression (p = 0.001), and stress (p = 0.001). Mental health problems showed a positive association with gender (girls, β = 3.06, p < 0.001) and a negative association with food habits (β = −0.65, p = 0.019). Anxiety was positively associated with gender (β = 7.88, p < 0.001) and negatively associated with food habits (β = −0.23, p = 0.019). Gender (girls) and food habits were also associated with symptoms of depression (β = 2.29, p < 0.001 and β = −0.27, p = 0.005, respectively). Finally, active commuting was inversely associated with stress (β = −1.24, p = 0.008), and stress was positively linked to gender (β = 2.53, p < 0.001). Conclusions: Active commuting, lifestyle parameters, and gender were associated with mental health in children and adolescents. Moreover, girls reported higher levels of anxiety, symptoms of depression, and stress. [ABSTRACT FROM AUTHOR]

The United Nations, through its 2030 Agenda and Sustainable Development Goals, advocates for the establishment of conducive environments for physical activity, following the ecological model. In line with this initiative, active transportation emerges as an accessible, cost-effective, and sustainable approach to augmenting daily physical activity levels. This study protocol endeavors to assess the impact of an active transportation education program rooted in the ecological model on the physical and mental well-being of high school students. Drawing upon scientific insights, we hypothesize that a 16-week active transportation intervention will lead to a 3% reduction in average body fat percentage and a noteworthy enhancement in executive function (including inhibition, cognitive flexibility, and working memory), physical fitness (comprising cardiorespiratory fitness and muscle strength), and mental health (encompassing mood disorders and cognitive functioning). If this intervention proves effective, it could offer a viable solution for the school community, especially in reducing congestion within the school environment. The study protocol aims to evaluate the impact of an active transportation educational program based on the ecological model on the physical and mental well-being of high school students. Three high schools located in the urban area of Talca, Chile, will be randomly selected (one public, one privately subsidized, and one private non-subsidized). Each high school will be randomly assigned an experimental group (n = 30) and a control group (n = 30; without intervention). The experimental groups will receive an active transportation educational intervention during their physical education classes for four months (60 to 90 min sessions, once a week), while the control group will receive no intervention. The primary outcome will provide information on body composition and executive function. Secondary outcomes will include objective physical activity level, physical fitness, mental well-being, academic achievement, health-related quality of life, perception of environmental urban features, physical activity barriers, and adherence to active transportation. It is expected that the results of the MOV-ES Project will transcend the physical health of schoolchildren and will have an impact on the school community, especially by decongesting the school environment. [ABSTRACT FROM AUTHOR]

Background: The placenta exerts a crucial role in fetus growth and development during gestation, protecting the fetus from maternal drugs and chemical exposure. However, diverse drugs and chemicals (xenobiotics) can penetrate the maternal placental barrier, leading to deleterious, adverse effects concerning fetus health. Moreover, placental enzymes can metabolize drugs and chemicals into more toxic compounds for the fetus. Thus, evaluating the molecular mechanisms through which drugs and chemicals transfer and undergo metabolism across the placental barrier is of vital importance. In this aspect, this comprehensive literature review aims to provide a holistic approach by critically summarizing and scrutinizing the potential molecular processes and mechanisms governing drugs and chemical transfer and metabolism across the placental barrier, which may lead to fetotoxicity effects, as well as analyzing the currently available experimental methodologies used to assess xenobiotics placental transfer and metabolism. Methods: A comprehensive and in-depth literature review was conducted in the most accurate scientific databases such as PubMed, Scopus, and Web of Science by using relevant and effective keywords related to xenobiotic placental transfer and metabolism, retrieving 8830 published articles until 5 February 2024. After applying several strict exclusion and inclusion criteria, a final number of 148 relevant published articles were included. Results: During pregnancy, several drugs and chemicals can be transferred from the mother to the fetus across the placental barrier by either passive diffusion or through placental transporters, resulting in fetus exposure and potential fetotoxicity effects. Some drugs and chemicals also appear to be metabolized across the placental barrier, leading to more toxic products for both the mother and the fetus. At present, there is increasing research development of diverse experimental methodologies to determine the potential molecular processes and mechanisms of drug and chemical placental transfer and metabolism. All the currently available methodologies have specific strengths and limitations, highlighting the strong demand to utilize an efficient combination of them to obtain reliable evidence concerning drug and chemical transfer and metabolism across the placental barrier. To derive the most consistent and safe evidence, in vitro studies, ex vivo perfusion methods, and in vivo animal and human studies can be applied together with the final aim to minimize potential fetotoxicity effects. Conclusions: Research is being increasingly carried out to obtain an accurate and safe evaluation of drug and chemical transport and metabolism across the placental barrier, applying a combination of advanced techniques to avoid potential fetotoxic effects. The improvement of the currently available techniques and the development of novel experimental protocols and methodologies are of major importance to protect both the mother and the fetus from xenobiotic exposure, as well as to minimize potential fetotoxicity effects. [ABSTRACT FROM AUTHOR]

We analyze the impacts of several improvements to urban transport and find that the bus can be made much more attractive by the simultaneous provision of dedicated lanes and higher service frequencies. At the same time, fare reforms, including free public transport, have limited impacts and do not seem to play an important role in reducing the use of the private car. In addition, our analysis considers active modes, bicycles in particular, and shows how they substitute for, or complement, public transport. We find that substitution prevails when public transport is rather accessible by walking (small spacing between the stations), but complementarity arises when the number of stations is small (large spacing between the stations). Our analysis is based on a micro-simulation approach, allowing us to develop a realistic and flexible framework where features like traffic lights, location of the stations, and road crossings for pedestrians are explicitly described.

Costs/benefits research to support active transport/electric micromobility investments are needed for optimal investment of public funds. This systematic review provides an evidence base of the economic effects of active transport and electric micromobility modes. Previous reviews including non-health benefits of active transport have been limited to Europe. Twenty-three studies from both the academic and grey literature were included in the review. Values for walking ranged from USD −0.25 ∼ 4.25/km, values for cycling ranged from USD −1.00 ∼ 1.95/km, and values for e-bike and e-scooter ranged from USD −0.44 ∼ 1.15/km. The largest benefit for active transport was due to health parameters. There were large variations in monetised benefits; some studies incorporated only certain types of benefits. Research gaps included inconsistent evidence for assumptions and a lack of data especially for electric micromobility modes. The quality of grey literature also varied.

G protein-coupled receptors (GPCRs) promote the expression of immediate early genes required for learning and memory. Here, we showed that β2-adrenergic receptor (β2AR) stimulation induced the nuclear export of phosphodiesterase 4D5 (PDE4D5), an enzyme that degrades the second messenger cAMP, to enable memory consolidation. We demonstrated that the endocytosis of β2AR phosphorylated by GPCR kinases (GRKs) mediated arrestin3-dependent nuclear export of PDE4D5, which was critical for promoting nuclear cAMP signaling and gene expression in hippocampal neurons for memory consolidation. Inhibition of the arrestin3-PDE4D5 association prevented β2AR-induced nuclear cAMP signaling without affecting receptor endocytosis. Direct PDE4 inhibition rescued β2AR-induced nuclear cAMP signaling and ameliorated memory deficits in mice expressing a form of the β2AR that could not be phosphorylated by GRKs. These data reveal how β2AR phosphorylated by endosomal GRK promotes the nuclear export of PDE4D5, leading to nuclear cAMP signaling, changes in gene expression, and memory consolidation. This study also highlights the translocation of PDEs as a mechanism to promote cAMP signaling in specific subcellular locations downstream of GPCR activation.

Abstract Background Physical inactivity is a global public health problem. A practical solution would be to build physical activity into the daily routine by using active modes of transport. Choice of transport mode can influence cancer risk through their effects on levels of physical activity, sedentary time, and environmental pollution. This review synthesizes existing evidence on the associations of specific transport modes with risks of site-specific cancers. Methods Relevant literature was searched in PubMed, Embase, and Scopus from 1914 to 17th February 2023. For cancer sites with effect measures available for a specific transport mode from two or more studies, random effects meta-analyses were performed to pool relative risks (RR) comparing the highest vs. lowest activity group as well as per 10 Metabolic Equivalent of Task (MET) hour increment in transport-related physical activity per week (∼150 min of walking or 90 min of cycling). Results 27 eligible studies (11 cohort, 15 case-control, and 1 case-cohort) were identified, which reported the associations of transport modes with 10 site-specific cancers. In the meta-analysis, 10 MET hour increment in transport-related physical activity per week was associated with a reduction in risk for endometrial cancer (RR: 0.91, 95% CI: 0.83–0.997), colorectal cancer (RR: 0.95, 95% CI: 0.91–0.99) and breast cancer (RR: 0.99, 95% CI: 0.89–0.996). The highest level of walking only or walking and cycling combined modes, compared to the lowest level, were significantly associated with a 12% and 30% reduced risk of breast and endometrial cancers respectively. Cycling, compared to motorized modes, was associated with a lower risk of overall cancer incidence and mortality. Conclusion Active transport appears to reduce cancer risk, but evidence for cancer sites other than colorectum, breast, and endometrium is currently limited.

Abstract Background Active School Travel (AST) initiatives align with the Ottawa Charter for Health Promotion, which calls for ‘creating supportive environments’ and ‘strengthening community action.’ However, their reliance on volunteers poses sustainability challenges. The main objectives of this study were to document the motivations, satisfaction, and experiences of volunteers involved in sustaining two AST initiatives in Ontario for an entire school year. Methods Two volunteer-led School Street initiatives in Kingston, Ontario successfully operated during pick-up and drop-off times of each school day. The first initiative operated for the entire 2021-2022 school year, and the second operated for the entire 2022-2023 school year. These initiatives were the first of their kind in the province of Ontario, Canada. Volunteers from both sites (n = 56) participated in online surveys and their motivations, satisfaction, and experiences of their role were compared using the 2-sided Fisher’s Exact Test. Results Over 80% of volunteers were highly motivated to promote safety and over 70% of volunteers were highly motivated to disrupt the status quo of unsupportive, car-centric urban environments by reimagining how streets can be used. By taking collective action to re-shape the environment around these public schools to support healthy, active living, our findings reveal that over 90% of volunteers were highly satisfied. Of the volunteers, 87% felt they contributed to child safety and 85% felt they had developed stronger community connections. They appreciated the short (i.e., 40 minute) time commitment of each shift, weekly email communications by the community organization leading the initiative, and the volunteer schedule. They also appreciated the positive social interactions during volunteer shifts, which they felt outweighed the minimal resistance they experienced. Conclusions This research demonstrates the importance of logistical, motivational, and social factors in recruiting and retaining volunteers for community-led School Streets. Our findings support appealing to prospective volunteers’ influence in achieving School Street objectives (e.g., improved safety) in recruitment efforts, as well as highlighting School Streets’ innovative approach. Communicating with volunteers throughout School Street planning and implementation processes and limiting traffic in the closed street zone (i.e., by excluding the school staff parking lot and private driveways from the scope) are additional recommendations based on the findings of this study.

Background: The Global Matrix 4.0 on physical activity (PA) for children and adolescents was developed to achieve a comprehensive understanding of the global variation in children's and adolescents' (5–17 y) PA, related measures, and key sources of influence. The objectives of this article were (1) to summarize the findings from the Global Matrix 4.0 Report Cards, (2) to compare indicators across countries, and (3) to explore trends related to the Human Development Index and geo-cultural regions. Methods: A total of 57 Report Card teams followed a harmonized process to grade the 10 common PA indicators. An online survey was conducted to collect Report Card Leaders' top 3 priorities for each PA indicator and their opinions on how the COVID-19 pandemic impacted child and adolescent PA indicators in their country. Results:Overall Physical Activity was the indicator with the lowest global average grade (D), while School and Community and Environment were the indicators with the highest global average grade (C+). An overview of the global situation in terms of surveillance and prevalence is provided for all 10 common PA indicators, followed by priorities and examples to support the development of strategies and policies internationally. Conclusions: The Global Matrix 4.0 represents the largest compilation of children's and adolescents' PA indicators to date. While variation in data sources informing the grades across countries was observed, this initiative highlighted low PA levels in children and adolescents globally. Measures to contain the COVID-19 pandemic, local/international conflicts, climate change, and economic change threaten to worsen this situation. [ABSTRACT FROM AUTHOR]

MDCK/Caco-2 assays serve as essential in vitro tools for evaluating membrane permeability and active transport, especially mediated by P-glycoprotein (P-gp). Despite their utility, challenges remain in quantifying active transport and using the efflux ratio (ER) to determine intrinsic values for active efflux. Such an intrinsic value for P-gp facilitated efflux necessitates knowing whether this transporter transports the neutral or ionic species of a compound. Utilising MDCK-MDR1 assays, we investigate a method for determining transporter substrate fraction preference by studying ER pH-dependence for basic, acidic and non-dissociating compounds. These results are compared with model fits based on various assumptions of transporter species preference. As an unexpected consequence of these assays, we also give evidence for an additional influx transporter at the basolateral membrane, and further extend our model to incorporate this transport. The combined influences of paracellular transport, the previously unaccounted for basolateral influx transporter, as well as potential pH effects on the transporter impedes the extraction of intrinsic values for active transport from the ER. Furthermore, we determined that using inhibitor affects the measurement of paracellular transport. While clear indications of transporter species preference remain elusive, this study enhances understanding of the MDCK system.

Background: Physical inactivity is a global public health problem. A practical solution would be to build physical activity into the daily routine by using active modes of transport. Choice of transport mode can influence cancer risk through their effects on levels of physical activity, sedentary time, and environmental pollution. This review synthesizes existing evidence on the associations of specific transport modes with risks of site-specific cancers. Methods: Relevant literature was searched in PubMed, Embase, and Scopus from 1914 to 17th February 2023. For cancer sites with effect measures available for a specific transport mode from two or more studies, random effects meta-analyses were performed to pool relative risks (RR) comparing the highest vs. lowest activity group as well as per 10 Metabolic Equivalent of Task (MET) hour increment in transport-related physical activity per week (∼150 min of walking or 90 min of cycling). Results: 27 eligible studies (11 cohort, 15 case-control, and 1 case-cohort) were identified, which reported the associations of transport modes with 10 site-specific cancers. In the meta-analysis, 10 MET hour increment in transport-related physical activity per week was associated with a reduction in risk for endometrial cancer (RR: 0.91, 95% CI: 0.83–0.997), colorectal cancer (RR: 0.95, 95% CI: 0.91–0.99) and breast cancer (RR: 0.99, 95% CI: 0.89–0.996). The highest level of walking only or walking and cycling combined modes, compared to the lowest level, were significantly associated with a 12% and 30% reduced risk of breast and endometrial cancers respectively. Cycling, compared to motorized modes, was associated with a lower risk of overall cancer incidence and mortality. Conclusion: Active transport appears to reduce cancer risk, but evidence for cancer sites other than colorectum, breast, and endometrium is currently limited. [ABSTRACT FROM AUTHOR]

Background: Active School Travel (AST) initiatives align with the Ottawa Charter for Health Promotion, which calls for 'creating supportive environments' and 'strengthening community action.' However, their reliance on volunteers poses sustainability challenges. The main objectives of this study were to document the motivations, satisfaction, and experiences of volunteers involved in sustaining two AST initiatives in Ontario for an entire school year. Methods: Two volunteer-led School Street initiatives in Kingston, Ontario successfully operated during pick-up and drop-off times of each school day. The first initiative operated for the entire 2021-2022 school year, and the second operated for the entire 2022-2023 school year. These initiatives were the first of their kind in the province of Ontario, Canada. Volunteers from both sites (n = 56) participated in online surveys and their motivations, satisfaction, and experiences of their role were compared using the 2-sided Fisher's Exact Test. Results: Over 80% of volunteers were highly motivated to promote safety and over 70% of volunteers were highly motivated to disrupt the status quo of unsupportive, car-centric urban environments by reimagining how streets can be used. By taking collective action to re-shape the environment around these public schools to support healthy, active living, our findings reveal that over 90% of volunteers were highly satisfied. Of the volunteers, 87% felt they contributed to child safety and 85% felt they had developed stronger community connections. They appreciated the short (i.e., 40 minute) time commitment of each shift, weekly email communications by the community organization leading the initiative, and the volunteer schedule. They also appreciated the positive social interactions during volunteer shifts, which they felt outweighed the minimal resistance they experienced. Conclusions: This research demonstrates the importance of logistical, motivational, and social factors in recruiting and retaining volunteers for community-led School Streets. Our findings support appealing to prospective volunteers' influence in achieving School Street objectives (e.g., improved safety) in recruitment efforts, as well as highlighting School Streets' innovative approach. Communicating with volunteers throughout School Street planning and implementation processes and limiting traffic in the closed street zone (i.e., by excluding the school staff parking lot and private driveways from the scope) are additional recommendations based on the findings of this study. [ABSTRACT FROM AUTHOR]

Governments will have a key role in establishing the policy environment needed to optimise the social outcomes associated with the evolution of autonomous vehicles (AVs). However, little is known about the extent to which the general public would support the diverse range of policies that could be implemented across human transport and product delivery AV applications. To address this deficit, the aim of the present study was to explore public support for a range of human transport and product delivery AV policies. In total, 1078 adult Australians completed an online survey that assessed transport-related attitudes and behaviours, including support for 11 AV policies pertaining to human transport and product delivery AV applications. Results suggest policies that ensure walking and cycling paths are prioritised for active transport (supported by 65%), limit the numbers of personal flying passenger AVs in the airspace (62%) and delivery bots on streets (64%), and ensure that those with mobility limitations have priority access to autonomous product deliveries (60%) are likely to be acceptable to the general community. To a somewhat lesser extent, limiting the operating hours for AV delivery services (51%) and banning the advertising of unhealthy foods and beverages on the surface areas of delivery AVs (50%) are also likely to be broadly accepted. • Autonomous vehicles will provide driverless transport for humans and products. • Government policy will assist in optimising benefits and minimising disbenefits. • Australians support policies that facilitate active transport and reduce congestion. • Policies that increase costs and ban autonomous alcohol delivery had lower support. [ABSTRACT FROM AUTHOR]

In CNS drug discovery, the estimation of brain exposure to lead compounds is critical for their optimization. Compounds need to cross the blood–brain barrier (BBB) to reach the pharmacological targets in the CNS. The BBB is a complex system involving passive and active mechanisms of transport and efflux transporters such as P-glycoproteins (P-gp) and breast cancer resistance protein (BCRP), which play an essential role in CNS penetration of small molecules. Several in vivo, in vitro, and in silico methods are available to estimate human brain penetration. Preclinical species are used as in vivo models to understand unbound brain exposure by deriving the Kp,uu parameter and the brain/plasma ratio of exposure corrected with the plasma and brain free fraction. The MDCK-mdr1 (Madin Darby canine kidney cells transfected with the MDR1 gene encoding for the human P-gp) assay is the commonly used in vitro assay to estimate compound permeability and human efflux. The in silico methods to predict brain exposure, such as CNS MPO, CNS BBB scores, and various machine learning models, help save costs and speed up compound discovery and optimization at all stages. These methods enable the screening of virtual compounds, building of a CNS penetrable compounds library, and optimization of lead molecules for CNS penetration. Therefore, it is crucial to understand the reliability and ability of these methods to predict CNS penetration. We review the in silico, in vitro, and in vivo data and their correlation with each other, as well as assess published experimental and computational approaches to predict the BBB penetrability of compounds. [ABSTRACT FROM AUTHOR]

The aim of this study was to understand how policy actions implemented by city governments to improve infrastructure within the built environment can in turn influence healthy behaviors and population health. The authors investigated the associations between policy actions implemented by city governments to improve biking infrastructure and multiple health outcomes including leisure-time physical inactivity, obesity and coronary heart disease (CHD). In addition, this study tested if bike use for commuting and leisure-time physical activity were mediators between policy actions to improve biking infrastructure and health outcomes, and whether the health effects of bike infrastructure were different in cities of different population density. We merged local sustainability survey data with city-level chronic disease measures for the largest cities in the U.S. (n = 457). Results from regressions using Ordinary Least Squares estimation and mediation tests showed policies implemented to improve biking infrastructure were associated with lower prevalence of leisure-time physical inactivity, obesity and CHD. These relationships were most notable in medium-density cities (1,500–3,000/sq. mi). Moreover, leisure-time physical activity and active commuting mediated the relationship between bike infrastructure improvement policies and health outcomes. This study demonstrated the value of a policy-based intervention in enhancing population health. [ABSTRACT FROM AUTHOR]

Travelling using sustainable modes, such as active transport and public transport, improves students' well-being and mental health, and bolsters sustainability. This study aims to investigate factors that encourage students to use sustainable modes which are public transport and active transport. The random parameters (mixed) logit was employed using the Victorian Integrated Survey of Travel and Activity (VISTA) data from Victoria, Australia to comprehensively explore trip attributes, socio-demographics, and built environment factors impacts on school travel mode choice. The inadequacy of model validation in previous research was addressed with the inclusion of the model accuracy test, which arguably is as equally important as behavioural inference. The result showed that travel distance and destination to primary school were the biggest contributors to mode choice probability, negatively affecting sustainable mode choice. The model produced an excellent overall accuracy (85.80%). This research elaborated on the inference of factors affecting mode choice and thus provided recommendations to help develop policies supporting sustainable transportation plans to improve students' well-being. [ABSTRACT FROM AUTHOR]

Large-scale active transport infrastructure is essential to connect walking and cycling networks severed by physical impediments (e.g. waterways and motorways). Yet, implementations in car-centric urban areas have experienced localised 'bikelash' and Not-in-my-backyard (NIMBY) resistance. Our mixed-method, cross-sectional study from the Gold Coast, Australia, identified positive sentiments towards green bridge implementations within the broader urban area. However, support for future bridge implementations decreased with proximity to respondents' homes. State and local governments planning new facilities must account for this geographical discounting effect, where residents want to reside near active transport infrastructure to derive benefit from them, but not too close. [ABSTRACT FROM AUTHOR]

For cities seeking to promote active transport, overcoming the institutional practices of car-centric planning and investment is critical to redistributing funds toward dedicated walking and cycling infrastructure. Slowly, urban policy and research are expanding traditional mobility-centric economic evaluations beyond major road and rail projects. This review paper of the academic literature employs a systematic quantitative literature review (SQLR) methodology and contributes an up-to-date examination of academic economic evaluations undertaken on large-scale active transport infrastructure implementations (i.e. capital costs greater than USD$3 million as of 2022). Seventeen (17) peer-reviewed academic papers were included in the final analysis. Cost-benefit analysis (CBA), followed by cost-effective analysis (CEA) and health impact assessment (HIA), were the most common pre-implementation (ex ante) and post-implementation (ex post) assessment methods. Between implementation-types, contexts, and methodologies, the parameters factored in econometric evaluations present a large degree of variance. Despite this, all studies demonstrated the positive return on investment in large-scale active transport infrastructure, where all CBAs produced benefit-cost ratios greater than the breakeven threshold (i.e. >1). Results show health parameters contribute the greatest benefit to positive evaluations, accounting for 77% of total benefits (and 67% in the CBA papers). However, evaluations inconsistently factor or omit long-term, intergenerational, and non-mobility benefits that highlight a partiality in their approach and can be co-opted to support predetermined outcomes. Further research must seek to establish if more expansive, sustainability-orientated methods are needed, or whether to adopt policy positions acknowledging the positive returns walking and cycling infrastructure deliver. [ABSTRACT FROM AUTHOR]

Significant challenges persist in enhancing the delivery efficiency of tumor nanomedicines, predominantly due to the difficulty of successfully surpassing pathophysiological barriers. Enhancing tumor penetration of nanomedicines in such conditions represents a pivotal goal in advancing anticancer nanotherapeutics. Transcytosis emerges as a promising solution in this context, addressing the limitations of passive drug delivery. By harnessing diverse stimuli to induce transcytosis, nanocarriers can achieve precise drug delivery and deep tumor penetration, resulting in high therapeutic efficacy and reduced systemic exposure to the therapeutic compound. This review briefly examines various stimuli‐responsive nanosystems and offers an overview and outlook on the development of stimuli‐responsive nanocarriers for transcytosis‐based cancer drug delivery, aiming to provide informative insights for the design of nanomedicines capable of deep tissue penetration and enhanced therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Background: Road traffic injury contributes substantially to morbidity and mortality. Canada stands out among developed countries in not conducting a national household travel survey, leading to a dearth of national transportation mode data and risk calculations that have appropriate denominators. Since traffic injuries are specific to the mode of travel used, these risk calculations should consider travel mode. Methods: Census data on mode of commute is one of the few sources of these data for persons aged 15 and over. This study leveraged a national data linkage cohort, the Canadian Census Health and Environment Cohorts, that connects census sociodemographic and commute mode data with records of deaths and hospitalizations, enabling assessment of road traffic injury associations by indicators of mode of travel (commuter mode). We examined longitudinal (1996-2019) bicyclist, pedestrian, and motor vehicle occupant injury and fatality risk in the Canadian Census Health and Environment Cohorts by commuter mode and sociodemographic characteristics using Cox proportional hazards models within the working adult population. Results: We estimated positive associations between commute mode and same mode injury and fatality, particularly for bicycle commuters (hazard ratios for bicycling injury was 9.1 and for bicycling fatality was 11). Low-income populations and Indigenous people had increased injury risk across all modes. Conclusions: This study shows inequities in transportation injury risk in Canada and underscores the importance of adjusting for mode of travel when examining differences between population groups. [ABSTRACT FROM AUTHOR]

The blood–brain barrier presents a key limitation to the administration of therapeutic molecules for the treatment of brain disease. While drugs administered orally or intravenously must cross this barrier to reach brain targets, the unique anatomical structure of the olfactory system provides a route to deliver drugs directly to the brain. Entering the brain via receptor, carrier, and adsorption‐mediated transcytosis in the nasal olfactory and trigeminal regions has the potential to increase drug delivery. In this review, we introduce the physiological and anatomical structures of the nasal cavity, and summarize the possible modes of transport and the relevant receptors and carriers in the nose‐to‐brain pathway. Additionally, we provide examples of nanotherapeutics developed for intranasal drug delivery to the brain. Further development of nanoparticles that can be applied to intranasal delivery systems promises to improve drug efficacy and reduce drug resistance and adverse effects by increasing molecular access to the brain. This article is categorized under:Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease [ABSTRACT FROM AUTHOR]

Promoting active travel is key to achieving the sustainable development goals of sustainable communities, climate action, and health and well-being. Walking and non-motorized vehicle use (e.g., cycling, longboarding) are influenced by the perceptions of the neighborhood environment. However, most evidence is limited to studies conducted in urban areas. This study aims to assess the relationship between perceived environment and walking as well as non-motorized vehicle use stratified across different levels of urbanicity in adolescents in Germany. Cross-sectional data of 3976 adolescents aged 11–17 (51% female) from the nationwide Motorik-Modul Longitudinal Study in Germany were used. Age, gender, socioeconomic status, neighborhood environment perceptions, duration of walking, and non-motorized vehicle use were assessed via questionnaire. Separate cumulative link mixed models were calculated to analyze the relationships between environment perceptions and walking as well as non-motorized vehicle use across rural areas, small towns, medium-sized towns, and cities. The presence of public sports facilities was related to both walking and non-motorized vehicle use across urbanicity levels. Relationships with other aspects of the perceived environment, such as traffic safety concerns and walking or cycling infrastructure, were more context-specific meaning that associations differed based on active travel mode and urbanicity level. Additionally, non-motorized vehicle use differed considerably across sample points. To conclude, when creating active and sustainable environments for active travel, it is crucial to target specific travel modes and take the urbanicity and regional context into account. [ABSTRACT FROM AUTHOR]

School trips affect different aspects, such as air pollution and urban traffic, and of personal wellbeing, such as students' physical and mental health. The increasing concern about environmental sustainability has prompted a reevaluation of daily activities, including school transportation. While different factors that affect students' school trips have been investigated in the literature, the effect of the built environment has been evaluated only sporadically in previous studies. To fulfil this knowledge gap, this study aims to investigate the effect of the built environment on students' school trips by adapting and extending the well-known Neighborhood Environment Walkability Scale (NEWS) questionnaire. The questionnaire survey was conducted with parents from 36 schools in Yazd, Iran, providing a sample of 1688 students aged 7–18 years. The items from the NEWS questionnaire were placed in nine factors by performing factor analysis. The Multinomial Logit Regression model was applied to check the predictive power of these nine factors. It was found that the variables of land use mix-diversity, land use mix-access, crime, age, gender, household income and car ownership had a significant effect on students' school trips. The more easily students have access to different places, the less they use public services and cars compared with the active travel mode. The use of public services and cars increases with the increase in crime rate along the route to school. The findings indicate that built environment features may impact students' shift from traditional transportation modes to active alternatives, such as walking and cycling, contributing to the attainment of broader sustainability objectives. [ABSTRACT FROM AUTHOR]

Background: The Ireland North and South Report Card on Physical Activity (PA) for Children and Adolescents aims to monitor progress in PA participation across a range of internationally established indicators. Methods: Data were collated for 11 indicators and graded following the harmonised Active Healthy Kids Global Alliance report card process. Six representative studies (sample size range n = 898 to n = 15,557) were primarily used in the grading, with many indicators supplemented with additional studies and reports. Data collected since the implementation of COVID-19 public health measures in March 2020 were excluded. Results: Grades were awarded as follows: ‘Overall physical activity’, C-; ‘Organised Sport and Physical Activity’, C; ‘Active Play’, INC; ‘Sedentary Behaviours’, C-; ‘Physical Fitness’, INC; ‘Family and Peers’, D+; ‘School’, C-; ‘Physical Education’, D; ‘Community and Environment’, B+ and ‘Government’, B. Separate grades were awarded for disability as follows; ‘Overall physical activity’, F; ‘Organised Sport and Physical Activity’, D; ‘Sedentary Behaviours’, C-; ‘Family and Peers’, C; ‘School’, C- and ‘Government’, B. ‘Active Play’, ‘Physical Fitness’, ‘Physical Education’ and ‘Community and Environment’ were all graded INC for disability. Since the last report card in 2016, four grades remained the same, three increased (‘Overall physical activity’, ‘School’ and ‘Physical Education’) and two (‘Family and Peers,’ and ‘Government’) were awarded grades for the first time. Conclusion: Grades specific to children and adolescents with disability were generally lower for each indicator. While small improvements have been shown across a few indicators, PA levels remain low across many indicators for children and adolescents.

The size of the nucleus scales robustly with cell size so that the nuclear-to-cell volume ratio (N/C ratio) is maintained during cell growth in many cell types. The mechanism responsible for this scaling remains mysterious. Previous studies have established that the N/C ratio is not determined by DNA amount but is instead influenced by factors such as nuclear envelope mechanics and nuclear transport. Here, we developed a quantitative model for nuclear size control based upon colloid osmotic pressure and tested key predictions in the fission yeast Schizosaccharomyces pombe. This model posits that the N/C ratio is determined by the numbers of macromolecules in the nucleoplasm and cytoplasm. Osmotic shift experiments showed that the fission yeast nucleus behaves as an ideal osmometer whose volume is primarily dictated by osmotic forces. Inhibition of nuclear export caused accumulation of macromolecules in the nucleoplasm, leading to nuclear swelling. We further demonstrated that the N/C ratio is maintained by a homeostasis mechanism based upon synthesis of macromolecules during growth. These studies demonstrate the functions of colloid osmotic pressure in intracellular organization and size control.

In recent years, many cities throughout the world are facing the impact of last-mile logistics and the resulting rise in urban traffic and pollution. Effects on the environment have been curbed by these dynamics. Urban traffic has a considerable impact in terms of noise emissions, road safety and air pollution: hence, both public and private parties should undertake innovative solutions for reducing the negative effects of last-mile logistics and improving their operational effectiveness. This study aims to provide a systematic literature review of studies having as their main topic environmentally sustainable last-mile logistics with the perspective of economic studies. The review of the literature reveals that the majority of recent studies have been based on engineering and urban planning approaches. Costs and benefits of last-mile logistics are approached with a public economics focus, gathering details from the different papers, starting with the business studies and then exploring the technology-oriented ones. This study aims to detect the different topics and policies discussed in the literature, and it suggests how to incorporate them in creating new measures and policies for last-mile logistics in the urban area, or for revamping current ones. [ABSTRACT FROM AUTHOR]

The current environmental crisis is mostly due to global warming. Promoting walking and cycling requires both the availability of green public areas (such as parks, green paths, and greenways) and a mentality that values such active modes of transportation. Significant health advantages from increased physical activity (PA) are associated with transportation options like walking and cycling (sometimes known as "active transportation," AT): the health and environmental advantages of encouraging workers to use bicycles for transportation been widely acknowledged. The authors of this research set out to fill this information gap by investigating the theoretically theorized links between green public space awareness and attitudes toward active mobility, adapting to a changing environment, and improving one's mental and physical health, with leisure and tourist activities serving as a moderator. The data was collected quantitatively using purposive sampling and then analyzed using PLS-SEM. We surveyed Korean walkers (n = 282) and bikers (n = 315) online between May 25 and June 17, 2021, and used a partial least squares structural equation modeling (PLS-SEM) analysis to test our hypothesis. As stated in the findings, being conscious of green public space when using active transportation significantly affects how clean the air feels. Active transportation was shown to have a significant effect on health, and climate change mitigation efforts were found to have a significant effect on health. Those who used active transportation for tourism had a stronger connection between green public space awareness and air quality, in addition to environmental sustainability and ethical conduct mitigation, than those who used active transport for recreation. Therefore, the model may aid in locating transport and health scenarios that benefit both sectors. [ABSTRACT FROM AUTHOR]

Intermediation and transformative capacity building are identified as important issues in sustainability transformations. Yet the connection of these two concepts has not been systematically analysed. This empirical, qualitative case study on active transport in Finland investigates intermediation in building local transformative capacity. The study shows that intermediaries are a heterogeneous group of actors that support transformative capacity building by facilitating the flows of knowledge, linking actors, forming ties across different scales, and supporting visioning and strategic planning. Intermediation manifests in five of the seven elements of local transformative capacity building. Our study, thus, contrasts with previous understanding wherein intermediation is considered only as a criterion for multiform governance. As intermediation is central in building transformative capacity, it should be better acknowledged, particularly by authorities and policymakers to secure legitimacy, operational capabilities, and funding for intermediaries. [ABSTRACT FROM AUTHOR]

The efflux ratio (ER), determined by Caco-2/MDCK assays, is the standard in vitro metric to establish qualitatively whether a compound is a substrate of an efflux transporter. However, others have also enabled the utilisation of this metric quantitatively by deriving a relationship that expresses the ER as a function of the intrinsic membrane permeability of the membrane ( P 0 ) as well as the permeability of carrier-mediated efflux ( P p g p ). As of yet, P p g p cannot be measured directly from transport experiments or otherwise, but the ER relationship provides easy access to this value if P 0 is known. However, previous derivations of this relationship failed to consider the influence of additional transport resistances such as the aqueous boundary layers (ABLs) and the filter on which the monolayer is grown. Since single fluxes in either direction can be heavily affected by these experimental artefacts, it is crucial to consider the potential impact on the ER. We present a model that includes these factors and show both mathematically and experimentally that this simple ER relationship also holds for the more realistic scenario that does not neglect the ABLs/filter. Furthermore, we also show mathematically how paracellular transport affects the ER, and we experimentally confirm that paracellular dominance reduces the ER to unity and can mask potential efflux. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the association between travel mode choice and individual sociodemographic characteristics among urban city dwellers, as the selection of daily travel modes is influenced by several factors. The study collected 1,290 short daily trips data from 415 respondents living in Klang Valley using a random sampling technique. Logit regression models were utilized to identify the impact of sociodemographic traits on travel mode choices. Men, low education levels, students, and households without children and do not own private vehicles are more likely to choose active transportation. Besides, the study examines the potential for greenhouse gas (GHG) emission reduction. Based on Life Cycle Assessment (LCA), 142 kgCO2e or 108 kgCO2e/km of GHG were released by automobiles from the collected travel trip data. The result shows that active transport could potentially achieve 14.52% GHG emission reduction by stated preference and nearly 17% GHG emission reduction by criteria fulfillment. These findings could provide valuable information for developing practical planning policies aimed at reducing GHG emissions from the road transport sector. [ABSTRACT FROM AUTHOR]

The Ireland North and South Report Card on Physical Activity (PA) for Children and Adolescents aims to monitor progress in PA participation across a range of internationally established indicators. Data were collated for 11 indicators and graded following the harmonised Active Healthy Kids Global Alliance report card process. Six representative studies (sample size range n = 898 to n = 15,557) were primarily used in the grading, with many indicators supplemented with additional studies and reports. Data collected since the implementation of COVID-19 public health measures in March 2020 were excluded. Grades were awarded as follows: 'Overall physical activity', C-; 'Organised Sport and Physical Activity', C; 'Active Play', INC; 'Sedentary Behaviours', C-; 'Physical Fitness', INC; 'Family and Peers', D+; 'School', C-; 'Physical Education', D; 'Community and Environment', B+ and 'Government', B. Separate grades were awarded for disability as follows; 'Overall physical activity', F; 'Organised Sport and Physical Activity', D; 'Sedentary Behaviours', C-; 'Family and Peers', C; 'School', C- and 'Government', B. 'Active Play', 'Physical Fitness', 'Physical Education' and 'Community and Environment' were all graded INC for disability. Since the last report card in 2016, four grades remained the same, three increased ('Overall physical activity', 'School' and 'Physical Education') and two ('Family and Peers,' and 'Government') were awarded grades for the first time. Grades specific to children and adolescents with disability were generally lower for each indicator. While small improvements have been shown across a few indicators, PA levels remain low across many indicators for children and adolescents. [ABSTRACT FROM AUTHOR]

Internationally many adolescents do not meet the recommended level of regular physical activity. Although active transport to school (ATS) is promoted to increase physical activity in adolescents, relying solely on ATS is not feasible for those who live beyond walkable or cyclable distance to school. School choice education policies complicate the potential of ATS when adolescents do not enrol in the closest school. This research contributes to sparse New Zealand and growing international literature to examine parental perspectives on school choice, travel to school decisions and modes of travel to school in adolescents enrolled in the closest versus non-closest school. We analysed questionnaire responses from 352 parents in Dunedin, differentiating results for enrolment in the closest versus non-closest school. Overall, only 38.9% of adolescents enrolled in their closest school. The adolescents who enrolled in their closest school lived closer to school and more frequently used ATS compared to their peers who enrolled in a non-closest school (home-to-school distance (walkable (≤2.25 km)/cyclable (>2.25–4.0 km)/beyond cyclable (>4.0 km)): 47.4%/27.8%/24.8% versus 4.8%/20.3%/74.9%; p < 0.001; transport to school (active/motorised/mixed): 40.9%/56.9%/2.2% versus 9.3%/82.7%/7.9%; p < 0.001). Nearly three-quarters of school choice decisions were made by parents jointly with their adolescent. Parents whose adolescent enrolled in the closest school more frequently reported proximity to home, social connection and school's co-educational status (only for adolescents enrolled in co-educational school) as reasons for school choice compared to their counterparts. Mixed-mode initiatives may support adolescents to increase ATS when they attend a school beyond cyclable distance. [ABSTRACT FROM AUTHOR]

This paper is concerned with a distributed optimal control problem for a phase field model describing tumor growth with chemotaxis and active transport. First, comparing with the results in [H. Garcke, K.F. Lam, Well-posedness of a Cahn-Hilliard system modelling tumour growth with chemotaxis and active transport, European J. Appl. Math. 28 (2017), 284-316], we prove the existence of solutions for such a system with more general potential, the regularity of solutions and the continuous dependence of initial data as well as control variable with respect to a strong topology. It is worth pointing out that the potentials cover the case of classical quartic double-well potential, which is the standard approximation for the physical relevant logarithmic potential. Furthermore, the existence of an optimal control is proved by monotonicity arguments and compactness theorems. Beyond that, by overcoming some difficulties in mathematical analysis and calculation, especially in the proof of the Fréchet differentiability of the control-to-state operator, we derive the corresponding first-order necessary conditions of optimality in terms of the adjoint variables and the usual variational inequality. [ABSTRACT FROM AUTHOR]

Background: Active commuting to school may increase the total daily physical activity and achieve health benefits among preschool children. Rates of active commuting to school among Spanish children and adolescents have been widely analysed, while the rates of active commuting to school among Spanish preschool children are unknown. Aim: The main objective of this study was to examine the changes in the rates of active commuting to school in a sample of Spanish preschool children between 3 and 6 years old from 2013 to 2017. Methods: Data were found from five studies carried out across Spain. The study sample comprised 4787 preschool children (4.59 ± 0.77 years old; 51% males). The overall changes in active commuting to school were assessed using multilevel logistic regression analysis. Results: The rates of active commuting to school in Spanish preschool children are around 52%, and the active commuting to school rates have stayed stable throughout the period assessed (odds ratio from 0.40 to 0.58, all p > 0.05). Conclusion: In preschool children, the present study obtained a favourable result on active commuting to school, showing a pattern stability in the examined period similar to other ages. It will be of great importance to promote this behaviour to obtain high levels of active commuting to school. [ABSTRACT FROM AUTHOR]

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Significant challenges persist in enhancing the delivery efficiency of tumor nanomedicines, predominantly due to the difficulty of successfully surpassing pathophysiological barriers. Enhancing tumor penetration of nanomedicines in such conditions represents a pivotal goal in advancing anticancer nanotherapeutics. Transcytosis emerges as a promising solution in this context, addressing the limitations of passive drug delivery. By harnessing diverse stimuli to induce transcytosis, nanocarriers can achieve precise drug delivery and deep tumor penetration, resulting in high therapeutic efficacy and reduced systemic exposure to the therapeutic compound. This review briefly examines various stimuli‐responsive nanosystems and offers an overview and outlook on the development of stimuli‐responsive nanocarriers for transcytosis‐based cancer drug delivery, aiming to provide informative insights for the design of nanomedicines capable of deep tissue penetration and enhanced therapeutic efficacy.

UNLABELLED: The identification of molecules that can bind covalently to KRAS G12C and lock it in an inactive GDP-bound conformation has opened the door to targeting KRAS G12C selectively. These agents have shown promise in preclinical tumor models and clinical trials. FDA has recently granted approval to sotorasib for KRAS G12C mutated non-small cell lung cancer (NSCLC). However, patients receiving these agents as monotherapy generally develop drug resistance over time. This necessitates the development of multi-targeted approaches that can potentially sensitize tumors to KRAS inhibitors. We generated KRAS G12C inhibitor-resistant cell lines and observed that they exhibit sensitivity toward selinexor, a selective inhibitor of nuclear export protein exportin1 (XPO1), as a single agent. KRAS G12C inhibitors in combination with selinexor suppressed the proliferation of KRAS G12C mutant cancer cell lines in a synergistic manner. Moreover, combined treatment of selinexor with KRAS G12C inhibitors resulted in enhanced spheroid disintegration, reduction in the number and size of colonies formed by G12C mutant cancer cells. Mechanistically, the combination of selinexor with KRAS G12C inhibitors suppressed cell growth signaling and downregulated the expression of cell cycle markers, KRAS and NF-kB as well as increased nuclear accumulation of tumor suppressor protein Rb. In an in vivo KRAS G12C cell-derived xenograft model, oral administration of a combination of selinexor and sotorasib was demonstrated to reduce tumor burden and enhance survival. In conclusion, we have shown that the nuclear transport protein XPO1 inhibitor can enhance the anticancer activity of KRAS G12C inhibitors in preclinical cancer models. SIGNIFICANCE: In this study, combining nuclear transport inhibitor selinexor with KRAS G12C inhibitors has resulted in potent antitumor effects in preclinical cancer models. This can be an effective combination therapy for cancer patients that do not respond or develop resistance to KRAS G12C inhibitor treatment.

Abstract Introduction Physical activity (PA) is critical for disease prevention and maintaining functional ability with aging. Despite this, as many as 50% of older adults in populations worldwide are considered insufficiently active. There is a recognized need to mobilize policies targeted toward modifiable determinants of healthy aging like PA. This umbrella review aimed to summarize the evidence for determinants of PA in community-dwelling older adults. Methods A research librarian searched six databases. Systematic and scoping reviews were included if they investigated community-dwelling people with a mean age of 60 + years and examined a relationship between a determinant and any type of PA. Two independent reviewers screened and extracted data from all reviews. JBI methodology and Critical Appraisal Checklist for Systematic Reviews and Research Syntheses were followed and information on the quality of the evidence was extracted. Results From 17,277 records screened,11 reviews representing > 300 unique primary papers were ultimately included. Only 6% of studies included in all reviews had longitudinal designs. Included studies used a large variety of PA measures, with 76% using only self-report, 15% using only direct measures (e.g., accelerometry), 3% using both types, and 6% with no outcome measure reported. Only four reviews provided a definition of PA and there was substantial inconsistency in the way PA was categorised. Community level influences, which only included the physical environment, were the most commonly assessed (6/11) with more than 70% of the summarized relationships demonstrating null associations. Three out of four reviews reported a positive relationship between walkability and PA in general community-dwelling older adults. There was also evidence supporting relationships between presence of social support for PA, younger age, and men having higher PA from a single systematic review. None of the included reviews assessed the quality of evidence but over 60% performed a risk of bias assessment. Conclusions Walkability, age, gender, and social support for PA were the most supported PA determinants identified. Further research should focus on interpersonal and intrapersonal influences and incorporate direct measures of PA with clear operational definitions. There is a need for longitudinal study designs to further understand determinants of PA behaviour trajectories.

Abstract Background Active travel and school settings are considered ideal for promoting physical activity. However, previous research suggests limited effect of school-based interventions on overall physical activity levels among adolescents. The relationship between physical activity in different domains remains inconclusive. In this study, we examined the effects of adding two weekly hours of school-based physical activity on active travel rates. Method We analyzed data from 1370 pupils in the 9th-grade participating in the cluster RCT; the School In Motion (ScIM) project. Intervention schools (n = 19) implemented 120 min of class-scheduled physical activity and physical education, in addition to the normal 2 hours of weekly physical education in the control schools (n = 9), for 9 months. Active travel was defined as pupils who reported walking or cycling to school, while motorized travel was defined as pupils who commuted by bus or car, during the spring/summer half of the year (April–September), or autumn/winter (October–February). The participants were categorized based on their travel mode from pretest to posttest as; maintained active or motorized travel (“No change”), changing to active travel (motorized-active), or changing to motorized travel (active-motorized). Multilevel logistic regression was used to analyze the intervention effect on travel mode. Results During the intervention period, most participants maintained their travel habits. In total, 91% of pupils maintained their travel mode to school. Only 6% of pupils switched to motorized travel and 3% switched to active travel, with small variations according to season and trip direction. The intervention did not seem to influence the likelihood of changing travel mode. The odds ratios for changing travel habits in spring/summer season were from active to motorized travel 1.19 [95%CI: 0.53–2.15] and changing from motorized to active travel 1.18 [0.30–2.62], compared to the “No change” group. These findings were consistent to and from school, and for the autumn/winter season. Conclusion The extra school-based physical activity does not seem to affect rates of active travel among adolescents in the ScIM project. Trial registration Clinicaltrials.gov ID nr: NCT03817047. Registered 01/25/2019′ retrospectively registered’.

Background: Physiotherapists have a well-established focus on improving health at individual and group levels but have developed less competence to contribute at system levels to promote public health and sustainable societies. Promoting knowledge and implementation of active transport, which refers to different ways of moving from one place to another by actively using one's own body, appears a familiar arena to start getting involved in system levels and is considered an essential strategy for sustainable development. Purpose: To explore how well Tromsø is designed for active transport in the form of cycling, to gain a better understanding of (infra)structural factors that affect people's ability to use active means of transport and lay a foundation for proposals for improvement measures. The use of research approaches not common in physiotherapy gave us an additional angle to highlight opportunities for physiotherapy research that open in this field. Method: We adapted an urban design study method by starting from the Cycling Strategy for Tromsø and a combination of field observation and two different site analysis tools. Results and conclusion: Our assessment of two sections of the cycling network identified as "particularly well" and "particularly poorly" designed indicates that Tromsø is not sufficiently well designed for cycling to be perceived as a better year-round alternative to other means of transport and does not achieve its own ambitions for cycling in the city. Our research approach points to several exciting opportunities for future physiotherapy research and practice as we increase our engagement in public health and societal sustainability at system levels.