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.

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.

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.

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.

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.

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.

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.

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.

Research on Ecological Landscape Design and Healing Effect Based on 3D Roaming Technology.

Impacted by the COVID-19 epidemic, the human sub-health in national high-tech zones (hereinafter referred to as high-tech zones) has become more prominent. It is critical for the mental sub-health group in the high-tech zone to relieve the anxiety and tension caused by the pressure of life and work. This paper uses SketchUp virtual engine (Unity 2019) software, and 3D roaming technology to carry out the ecological landscape transformation design of the Baotzixi ecological corridor in the East Lake High-tech Zone, to construct a 3D roaming landscape scene and measure its therapeutic effect by inviting subjects to participate in an interactive experience experiment on the ErgoLAB platform. The results illustrate that: (1) the thermogram trend shows that the more attractive the 3D roaming landscape scene is, the stronger the subjects' interest is; (2) the participants have a positive emotional arousal state in the immersive experience of the 3D roaming landscape scene after the modification design; and (3) the mean skin conductance (SC) fluctuation variance of the subjects is 5.819%, indicating that the healing effect is significant in the state of positive emotional arousal. The research results show that there is a connection between the subjects and the 3D roaming landscape scene after the transformation design of "high interest, emotional arousal and significant healing".

Social media mining under the COVID-19 context: Progress, challenges, and opportunities.

Social media platforms allow users worldwide to create and share information, forging vast sensing networks that allow information on certain topics to be collected, stored, mined, and analyzed in a rapid manner. During the COVID-19 pandemic, extensive social media mining efforts have been undertaken to tackle COVID-19 challenges from various perspectives. This review summarizes the progress of social media data mining studies in the COVID-19 contexts and categorizes them into six major domains, including early warning and detection, human mobility monitoring, communication and information conveying, public attitudes and emotions, infodemic and misinformation, and hatred and violence. We further document essential features of publicly available COVID-19 related social media data archives that will benefit research communities in conducting replicable and reproducible studies. In addition, we discuss seven challenges in social media analytics associated with their potential impacts on derived COVID-19 findings, followed by our visions for the possible paths forward in regard to social media-based COVID-19 investigations. This review serves as a valuable reference that recaps social media mining efforts in COVID-19 related studies and provides future directions along which the information harnessed from social media can be used to address public health emergencies.

The association between tree canopy cover over streets and elderly pedestrian falls: A health disparity study in urban areas.

Older pedestrians are vulnerable to outdoor falling while walking on streets/sidewalks, but few studies have examined the role of the street environment and tree canopy cover over streets in relation to pedestrian falls among the elderly. We used spatial analysis to examine the association between tree canopy cover over streets and pedestrian falls reported to Emergency Medical Service (EMS) providers from March 2013 to February 2020 among adults aged 65 and older living in urban areas of Marin County, CA. Tree canopy cover over streets was measured using 1-m resolution of tree canopy within street polygons. After controlling for socioeconomic status and built environments, we found an inverse association between tree canopy cover over streets and elderly pedestrian fall rates at the census block level. Specifically, with a 10-percentage point increase in tree canopy cover over streets of a block, we expected to see about an 11.2% decrease in the elderly pedestrian fall rate. We found that the inverse relationship between tree canopy cover over streets and elderly pedestrian falls was only significant during the leaf-on season in the spring and summer. Finally, sub-analysis found that the relationship between tree canopy cover over streets and elderly pedestrian falls was stronger in low-income areas, compared to high-income areas. Planting street trees is a potential evidence-based intervention to prevent pedestrian falls. However, special attention must go beyond the quantity of tree canopy cover over streets to consider biophysical factors and social conditions.

VisualCommunity: a platform for archiving and studying communities.

VisualCommunity is a platform designed to support community or neighborhood scale research. The platform integrates mobile, AI, visualization techniques, along with tools to help domain researchers, practitioners, and students collecting and working with spatialized video and geo-narratives. These data, which provide granular spatialized imagery and associated context gained through expert commentary have previously provided value in understanding various community-scale challenges. This paper further enhances this work AI-based image processing and speech transcription tools available in VisualCommunity, allowing for the easy exploration of the acquired semantic and visual information about the area under investigation. In this paper we describe the specific advances through use case examples including COVID-19 related scenarios.

Measurement of contagion spatial spread probability in public places: A case study on COVID-19.

The scale and scope of the COVID-19 epidemic have highlighted the need for timely control of viral transmission. This paper proposed a new spatial probability model of epidemic infection using an improved Wasserstein distance algorithm and Monte Carlo simulation. This method identifies the public places in which COVID-19 spreads and grows easily. The Wasserstein Distance algorithm is used to calculate the distribution similarity between COVID-19 cases and the public places. Further, we used hypothesis tests and Monte Carlo simulation to estimate the spatial spread probability of COVID-19 in different public places. We used Snow's data to test the stability and accuracy of this measurement. This verification proved that our method is reliable and robust. We applied our method to the detailed geographic data of COVID-19 cases and public places in Wuhan. We found that, rather than financial service institutions and markets, public buildings such as restaurants and hospitals in Wuhan are 95 percent more likely to be the public places of COVID-19 spread.

Autophagy and cancer treatment: four functional forms of autophagy and their therapeutic applications.

Cancer is the leading cause of death worldwide. Drugs play a pivotal role in cancer treatment, but the complex biological processes of cancer cells seriously limit the efficacy of various anticancer drugs. Autophagy, a self-degradative system that maintains cellular homeostasis, universally operates under normal and stress conditions in cancer cells. The roles of autophagy in cancer treatment are still controversial because both stimulation and inhibition of autophagy have been reported to enhance the effects of anticancer drugs. Thus, the important question arises as to whether we should try to strengthen or suppress autophagy during cancer therapy. Currently, autophagy can be divided into four main forms according to its different functions during cancer treatment: cytoprotective (cell survival), cytotoxic (cell death), cytostatic (growth arrest), and nonprotective (no contribution to cell death or survival). In addition, various cell death modes, such as apoptosis, necrosis, ferroptosis, senescence, and mitotic catastrophe, all contribute to the anticancer effects of drugs. The interaction between autophagy and these cell death modes is complex and can lead to anticancer drugs having different or even completely opposite effects on treatment. Therefore, it is important to understand the underlying contexts in which autophagy inhibition or activation will be beneficial or detrimental. That is, appropriate therapeutic strategies should be adopted in light of the different functions of autophagy. This review provides an overview of recent insights into the evolving relationship between autophagy and cancer treatment.

Survivin suppression heightens BZML-induced mitotic catastrophe to overcome multidrug resistance by removing therapy-induced senescent A549/Taxol cells.

Mitotic catastrophe (MC) is a newly identified type of anticancer mechanism for multidrug resistance (MDR) prevention. However, the long cellular death process resulting from MC is not beneficial for anticancer treatment. BZML is a novel colchicine-binding site inhibitor which can overcome MDR by inducing MC; however, BZML-induced MC cells underwent a long cellular death process. Thus, to improve anticancer therapies based on drug-induced MC, BZML-induced MC was served as a model to further study the underlying molecular mechanisms in the process of MC. Here, BZML could induce p53-dependent senescence in A549/Taxol cells, a MDR cell line. This senescence was a secondary effect of MC in overcoming MDR. During MC, BZML-induced destruction of protein-degradation system contributed not only to an increase of p53 protein but also to the accumulation of survivin in nucleus of A549/Taxol cells. Importantly, the nuclear accumulation of survivin was not the inducer but the result of BZML-induced MC, and it promoted the survival of senescent cells. Moreover, it provided additional vulnerability and critical opportunities for sequentially applied therapies. Further, targeting survivin with YM155 accelerated the death of MC cells by timely eliminating therapy-induced senescent cells and strengthening the efficiency of BZML in overcoming MDR in A549/Taxol cells. Collectively, nuclear accumulation of survivin delayed cellular death during MC by promoting the survival of BZML-induced senescent A549/Taxol cells. Moreover, "one-two punch" approach to cancer treatment based on combination therapy with YM155 for survivin suppression might be a new strategy for potentiating MC to overcome MDR.