Wildfire smoke exposure during pregnancy and perinatal, obstetric, and early childhood health outcomes: A systematic review and meta-analysis.

BACKGROUND: Maternal exposure to air pollution during pregnancy is associated with adverse birth outcomes, although less is known for wildfire smoke. This systematic review evaluated the association between maternal exposure to wildfire smoke during pregnancy and the risk of perinatal, obstetric, and early childhood health outcomes. METHODS: We searched CINAHL Complete, Ovid/EMBASE, Ovid/MEDLINE, ProQuest, PubMed, Scopus, Web of Science, and Google Scholar to identify relevant epidemiological observational studies indexed through September 2023. The screening of titles, abstracts, and full-texts, data extraction, and risk of bias assessment was performed by pairs of independent reviewers. RESULTS: Our systematic search yielded 28,549 records. After duplicate removal, we screened 14,009 studies, identifying 31 for inclusion in the present review. Data extraction highlighted high methodological heterogeneity between studies, including a lack of geographic variation. Approximately 56.5% and 16% originated in the United States and Brazil, respectively, and fewer in other countries. Among the studies, wildfire smoke exposure during pregnancy was assessed using distance of residence from wildfire-affected areas (n = 15), measurement of air pollutant concentration during wildfires (n = 11), number of wildfire records (n = 3), aerosol index (n = 1), and geographic hot spots (n = 1). Pooled meta-analysis for birthweight and low birthweight were inconclusive, likely due to low number of methodologically homogenous studies. However, the reviewed studies provided suggestive evidence for an increased risk of birthweight reduction, low birthweight, preterm birth, and other adverse health outcomes. CONCLUSIONS: This review identified 31 studies evaluating the impacts of maternal wildfire smoke exposure on maternal, infant, and child health. Although we found suggestive evidence of harm from exposure to wildfire smoke during pregnancy, more methodologically homogenous studies are required to enable future meta-analysis with greater statistical power to more accurately evaluate the association between maternal wildfire smoke and adverse birth outcomes and other health outcomes.

A systematic review of animal feeding operations including concentrated animal feeding operations (CAFOs) for exposure, health outcomes, and environmental justice.

BACKGROUND: Despite growing literature on animal feeding operations (AFOs) including concentrated animal feeding operations (CAFOs), research on disproportionate exposure and associated health burden is relatively limited and shows inconclusive findings. OBJECTIVE: We systematically reviewed previous literature on AFOs/CAFOs, focusing on exposure assessment, associated health outcomes, and variables related to environmental justice (EJ) and potentially vulnerable populations. METHODS: We conducted a systematic search of databases (MEDLINE/PubMed and Web of Science) and performed citation screening. Screening of titles, abstracts, and full-text articles and data extraction were performed independently by pairs of reviewers. We summarized information for each study (i.e., study location, study period, study population, study type, study design, statistical methods, and adjusted variables (if health association was examined), and main findings), AFO/CAFO characteristics and exposure assessment (i.e., animal type, data source, measure of exposure, and exposure assessment), health outcomes or symptoms (if health association was examined), and information related to EJ and potentially vulnerable populations (in relation to exposure and/or health associations, vulnerable populations considered, related variables, and main findings in relation to EJ and vulnerable populations). RESULTS: After initial screening of 10,963 papers, we identified 76 eligible studies. This review found that a relatively small number of studies (20 studies) investigated EJ and vulnerability issues related to AFOs/CAFOs exposure and/or associated health outcomes (e.g., respiratory diseases/symptoms, infections). We found differences in findings across studies, populations, the metrics used for AFO/CAFO exposure assessment, and variables related to EJ and vulnerability. The most commonly used metric for AFO/CAFO exposure assessment was presence of or proximity to facilities or animals. The most investigated variables related to disparities were race/ethnicity and socioeconomic status. CONCLUSION: Findings from this review provide suggestive evidence that disparities exist with some subpopulations having higher exposure and/or health response in relation to AFO/CAFO exposure, although results varied across studies.

Unraveling near real-time spatial dynamics of population using geographical ensemble learning.

Dynamic gridded population data are crucial in fields such as disaster reduction, public health, urban planning, and global change studies. Despite the use of multi-source geospatial data and advanced machine learning models, current frameworks for population spatialization often struggle with spatial non-stationarity, temporal generalizability, and fine temporal resolution. To address these issues, we introduce a framework for dynamic gridded population mapping using open-source geospatial data and machine learning. The framework consists of (i) delineation of human footprint zones, (ii) construction of muliti-scale population prediction models using automated machine learning (AutoML) framework and geographical ensemble learning strategy, and (iii) hierarchical population spatial disaggregation with pycnophylactic constraint-based corrections. Employing this framework, we generated hourly time-series gridded population maps for China in 2016 with a 1-km spatial resolution. The average accuracy evaluated by root mean square deviation (RMSD) is 325, surpassing datasets like LandScan, WorldPop, GPW, and GHSL. The generated seamless maps reveal the temporal dynamic of population distribution at fine spatial scales from hourly to monthly. This framework demonstrates the potential of integrating spatial statistics, machine learning, and geospatial big data in enhancing our understanding of spatio-temporal heterogeneity in population distribution, which is essential for urban planning, environmental management, and public health.

Comparative analysis of surgical and oncologic outcomes of robotic, laparoscopic and open radical nephrectomy with venous thrombectomy: a propensity-matched cohort study.

OBJECTIVE: To provide insight into the surgical and oncological outcomes of robotic, laparoscopic and open radical nephrectomy with venous thrombectomy (RALRN-VT, LRN-VT, ORN-VT) in patients with renal tumor and venous thrombus. MATERIALS AND METHODS: A propensity-matched retrospective cohort study containing 324 patients with renal tumor and venous thrombus from January 2014 to August 2021 was analyzed. We compared surgical outcomes and we used the Kalan-Meier method to assess the overall survival (OS), tumor-specific survival (TSS), metastasis-free survival (MFS) and local recurrence-free survival (LRFS). The Pearson chi-square test and Fisher exact test, Wilcoxon rank sum test, Cox proportional hazards regression model and log-rank test were used. RESULTS: After matching, baseline characteristics were comparable in the RALRN-VT, LRN-VT and ORN-VT group. The RALRN-VT group had the least operative time (median 134 min vs 289 min vs 330 min, P < 0.001), the least blood loss (median 250 ml vs 500 ml vs 1000 ml, P < 0.001) and the fewest packed red blood cells transfusion (median 400 ml vs 800 ml vs 1200 ml, P < 0.001). The ORN-VT group had the highest complication rate (18.2 vs 22.7 vs 43.2%, P = 0.005), the highest Clavien grade (P = 0.001) and the longest postoperative hospital stay (median 7d vs 8d vs 10d, P < 0.001). No significant difference in OS, TSS and MFS between the minimally invasive procedures (MIP, including RALRN-VT and LRN-VT) group and ORN-VT group was found. The hazard ratio of LRFS for the MIP group was 0.20 (95% CI 0.06-0.70, P = 0.01) compared with ORN-VT group. CONCLUSIONS: RALRN-VT can result in the best surgical outcomes compared with LRN-VT and ORN-VT. The MIP group had a better LRFS compared with ORN-VT group.

Global COVID-19 pandemic demands joint interventions for the suppression of future waves.

Emerging evidence suggests a resurgence of COVID-19 in the coming years. It is thus critical to optimize emergency response planning from a broad, integrated perspective. We developed a mathematical model incorporating climate-driven variation in community transmissions and movement-modulated spatial diffusions of COVID-19 into various intervention scenarios. We find that an intensive 8-wk intervention targeting the reduction of local transmissibility and international travel is efficient and effective. Practically, we suggest a tiered implementation of this strategy where interventions are first implemented at locations in what we call the Global Intervention Hub, followed by timely interventions in secondary high-risk locations. We argue that thinking globally, categorizing locations in a hub-and-spoke intervention network, and acting locally, applying interventions at high-risk areas, is a functional strategy to avert the tremendous burden that would otherwise be placed on public health and society.

Neighborhood built environments and cognition in later life.

Objectives: Maintaining good cognition is crucial in later life. However, most existing research has focused on individual factors impacting cognition, and few studies have investigated the association between neighborhood built environment and older adults' cognition. This study examined the association between neighborhood built environment and cognition among community-dwelling older adults and identified variations in this association between different age groups in the older population.Methods: Data were derived from a cross-sectional survey of 1873 people aged 65 years and above in Hong Kong. We merged individual data from the survey with neighborhood built environment data based on community auditing and geographical information system. After controlling for individual covariates, we used multivariable linear regression to examine the association between neighborhood built environment and cognition.Results: Residents aged 80 and younger in neighborhoods with a higher land-use mix and more public transport terminals exhibited better cognition. Only the number of community centers in a neighborhood was positively associated with cognition for people older than 80.Conclusion: The built environment creates diverse impacts on different age groups among older adults. Our findings provide useful information for urban planners and policymakers for planning community facilities and built environments that consider the needs of different age groups within the older population.

Spatiotemporally continuous estimates of daily 1-km PM2.5 concentrations and their long-term exposure in China from 2000 to 2020.

Monitoring long-term variations in fine particulate matter (PM2.5) is essential for environmental management and epidemiological studies. While satellite-based statistical/machine-learning methods can be used for estimating high-resolution ground-level PM2.5 concentration data, their applications have been hindered by limited accuracy in daily estimates during years without PM2.5 measurements and massive missing values due to satellite retrieval data. To address these issues, we developed a new spatiotemporal high-resolution PM2.5 hindcast modeling framework to generate the full-coverage, daily, 1-km PM2.5 data for China for the period 2000-2020 with improved accuracy. Our modeling framework incorporated information on changes in observation variables between periods with and without monitoring data and filled gaps in PM2.5 estimates induced by satellite data using imputed high-resolution aerosol data. Compared to previous hindcast studies, our method achieved superior overall cross-validation (CV) R2 and root-mean-square error (RMSE) of 0.90 and 12.94 µg/m3 and significantly improved the model performance in years without PM2.5 measurements, raising the leave-one-year-out CV R2 [RMSE] to 0.83 [12.10 µg/m3] at a monthly scale (0.65 [23.29 µg/m3] at a daily scale). Our long-term PM2.5 estimates show a sharp decline in PM2.5 exposure in recent years, but the national exposure level in 2020 still exceeded the first annual interim target of the 2021 World Health Organization air quality guidelines. The proposed hindcast framework represents a new strategy to improve air quality hindcast modeling and can be applied to other regions with limited air quality monitoring periods. These high-quality estimates can support both long- and short-term scientific research and environmental management of PM2.5 in China.

Associations between metabolic syndrome and anthropogenic heat emissions in northeastern China.

BACKGROUND: Recent research attention has been paid to anthropogenic heat emissions (AE), temperature increase generated by human activity such as lighting, transportation, manufacturing, construction, and building climate controls. However, there is no epidemiological data available to investigate the association between anthropogenic heat emissions and metabolic syndrome (MetS), a cluster of conditions that increase risk of stroke, heart disease and diabetes. OBJECTIVE: To explore the relationships between AE and MetS in China. METHODS: We recruited 15,477 adults from the 33 Communities Chinese Health Study, a cross-sectional study in northeastern China. We retrieved anthropogenic heat flux by collecting socio-economic and energy consumption data as well as satellite-based nighttime light and Normalized Difference Vegetation Index datasets, including emissions from buildings, transportation, human metabolism, and industries. We also measured MetS components consisting of triglycerides, high density lipoprotein cholesterol, fasting glucose, systolic blood pressure, and diastolic blood pressure, and waist circumference. Restricted cubic spline models were applied to assess the associations between AE and MetS. RESULTS: The median flux of total AE was 30.98 W/m2 and industrial AE was the dominant contributor (87.64%). The adjusted odds ratio and 95% confidence interval (CI) of MetS for the 75th and 95th percentiles of the total AE against the threshold were 1.29 (95% CI: 1.21, 1.38) and 1.65 (95% CI: 1.47, 1.85). Greater AE was associated with higher odds of MetS in a dose-response pattern, and the lowest point of U-shape curve indicated the threshold effect. Participants who are young and middle-aged exhibited stronger associations between AE and MetS. CONCLUSIONS: Our novel findings reveal that AE are positively associated with MetS and that associations are modified by age. Further investigations into the mechanisms of the effects are needed.

Early-life exposure to submicron particulate air pollution in relation to asthma development in Chinese preschool children.

BACKGROUND: Emerging research suggested an association of early-life particulate air pollution exposure with development of asthma in childhood. However, the potentially differential effects of submicron particulate matter (PM; PM with aerodynamic diameter ≤1 µm [PM1]) remain largely unknown. OBJECTIVE: This study primarily aimed to investigate associations of childhood asthma and wheezing with in utero and first-year exposures to size-specific particles. METHODS: We conducted a large cross-sectional survey among 5788 preschool children aged 3 to 5 years in central China. In utero and first-year exposures to ambient PM1, PM with aerodynamic diameter less than or equal to 2.5 µm, and PM with aerodynamic diameter less than or equal to 10 µm at 1 × 1-km resolution were assessed using machine learning-based spatiotemporal models. A time-to-event analysis was performed to examine associations between residential PM exposures and childhood onset of asthma and wheezing. RESULTS: Early-life size-specific PM exposures, particularly during pregnancy, were significantly associated with increased risk of asthma, whereas no evident PM-wheezing associations were observed. Each 10-µg/m3 increase in in utero and first-year PM1 exposure was accordingly associated with an asthma's hazard ratio in childhood of 1.618 (95% CI, 1.159-2.258; P = .005) and 1.543 (0.822-2.896; P = .177). Subgroup analyses suggest that short breast-feeding duration may aggravate PM-associated risk of childhood asthma. Each 10-µg/m3 increase in in utero exposure to PM1, for instance, was associated with a hazard ratio of 2.260 (1.393-3.666) among children with 0 to 5 months' breast-feeding and 1.156 (0.721-1.853) among those longer breast-fed. CONCLUSIONS: Our study added comparative evidence for increased risk of childhood asthma in relation to early-life PM exposures, highlighting stronger associations with ambient PM1 than with PM with aerodynamic diameter less than or equal to 2.5 µm and PM with aerodynamic diameter less than or equal to 10 µm.

Fractionated Irradiation of Right Thorax Induces Abscopal Damage on Bone Marrow Cells via TNF-α and SAA.

Radiation-induced abscopal effect (RIAE) outside of radiation field is becoming more attractive. However, the underlying mechanisms are still obscure. This work investigated the deleterious effect of thoracic irradiation (Th-IR) on distant bone marrow and associated signaling factors by irradiating the right thorax of mice with fractionated doses (8 Gy × 3). It was found that this localized Th-IR increased apoptosis of bone marrow cells and micronucleus formation of bone marrow polychromatic erythrocytes after irradiation. Tandem mass tagging (TMT) analysis and ELISA assay showed that the concentrations of TNF-α and serum amyloid A (SAA) in the mice were significantly increased after Th-IR. An immunohistochemistry assay revealed a robust increase in SAA expression in the liver rather than in the lungs after Th-IR. In vitro experiments demonstrated that TNF-α induced SAA expression in mouse hepatoma Hepa1-6 cells, and these two signaling factors induced DNA damage in bone marrow mesenchymal stem cells (BMSCs) by increasing reactive oxygen species (ROS). On the other hand, injection with TNF-α inhibitor before Th-IR reduced the secretion of SAA and attenuated the abscopal damage in bone marrow. ROS scavenger NAC could also mitigated Th-IR/SAA-induced bone marrow damage in mice. Our findings indicated that Th-IR triggered TNF-α release from lung, which further promoted SAA secretion from liver in a manner of cascade reaction. Consequently, these signaling factors resulted in induction of abscopal damage on bone marrow of mice.

TGF-ß mediates thoracic radiation-induced abscopal effects of testis injury in rat.

To investigate the thoracic irradiation induced abscopal effect on distal testes and the underlying inflammatory factors, the rats were irradiated on right thorax with fractionated doses. It was found the testes structures were damaged including disorder of spermatogenic cell arrangement and decrease of sperm number. Moreover, the expressions of caspase-3 and caspase-8 in testis tissue were enhanced, and the concentrations of TGF-ß and TNF-α in the rat serum were increased. When TM4 cells were treated with the conditioned medium (CS) collected from irradiated rat, the cellular ROS and apoptosis was significantly increased. When the CS was neutralized with anti-TGF-ß, its toxic effects were reduced. These results suggest that the thoracic irradiation-induced TGF-ß was involved in the above abscopal damage of testes, which reinforces the necessity of new prevention strategy development of radiotherapy in avoiding any abnormal genetic consequence.

Electric-field driven photoluminescence probe of photoelectric conversion in InGaN-based photovoltaics.

The spatial distribution of electric field in photovoltaic multiple quantum wells (MQWs) is extremely important to dictate the mutual competition of photoelectric conversion and optical transition. Here, electric-field-driven photoluminescence (PL) in both steady-state and transient-state has been utilized to directly investigate the internal photoelectric conversion processes in InGaN-based MQW photovoltaic cell. As applying the reversed external electric field, the compensation of the quantum confined stark effect (QCSE) in InGaN QW is beneficial to help the photoabsorbed minor carriers drift out from the localized states, whereas extremely weakening the PL radiative recombination. A directly driven force by the reversed external electric field decreases the transit time of photocarriers drifting in InGaN QW. And hence, the overall dynamic PL decay including both the slow and fast processes gradually speeds up from 19.2 ns at the open-circuit condition to 3.9 ns at a negative bias of -3 V. In particular, the slow PL decay lifetime declines more quickly than that of the fast one. It is the delocalization of photocarriers by electric-field drift that helps to further enhance the high-efficiency photoelectric conversion except for the tunneling transport in InGaN-based MQW photovoltaics. Therefore, it can be concluded that the electric-field PL probe may provide a direct method for evaluating the photoelectric conversion in multilayer quantum structures and related multijunction photovoltaic cells.

AMPK-KLF2 signaling pathway mediates the proangiogenic effect of erythropoietin in endothelial colony-forming cells.

Endothelial colony-forming cells (ECFCs) were proved to take part in postnatal vasculogenesis and injury repair. The angiogenic properties of ECFCs could be influenced by various cytokines, chemokines, and growth factors. Erythropoietin (EPO) is a promising cytokine participating in angiogenesis. However, the mechanisms for EPO's proangiogenic effect still remain largely elusive. Here, we investigated the role of the AMP-activated protein kinase (AMPK)-Krüppel-like factor 2 (KLF2) signaling pathway in the proangiogenic effect of EPO in ECFCs. Human ECFCs were isolated from cord blood and cultured. EPO significantly enhanced the migration and tube formation capacities of ECFCs and markedly increased the expression of endothelial markers and vascular endothelial growth factor (VEGF). Further, EPO caused the phosphorylation of AMPK and endothelial nitric oxide synthase, a process in which KLF2 was also upregulated on both mRNA and protein levels. The upregulation of KLF2 was blocked by inhibiting AMPK with Compound C or Ad-AMPK-DN, a recombinant adenovirus that encoded a dominant-negative mutant of AMPK. Furthermore, knockdown of KLF2 showed no effect on AMPK but abolished the EPO-enhanced migration and tube formation capacities of ECFCs. Of note, knockdown of KLF2 also diminished the EPO-induced expression of endothelial markers and VEGF; overexpression of KLF2 promoted the expression of endothelial markers and VEGF and enhanced the migration and tube formation capacities of ECFCs. These data suggest that upregulation of KLF2 by AMPK plays an essential role in EPO-induced angiogenesis.

[Mechanisms of prostaglandin E2-induced bone marrow-derived progenitor cell differentiation].

OBJECTIVE: To identify the functions and mechanisms of prostaglandin E2 (PGE2)-induced bone marrow-derived progenitor cells (BMPCs) maturation and its involved angiogenesis. METHODS: BMPCs harvested by flushing through the femoral and tibial bones and cultured. This population of cells was identified by immunofluorescence staining. From which, 1 µmol/L PGE2 was taken, and quantitative-PCR (Q-PCR) and Western blot were used to detect the expressions of endothelial markers and Kruppel like factor 2 (KLF2) in BMPCs. In vitro tube formation assay was performed to demonstrate the capacity of angiogenesis. Furthermore, PGE2 and its receptors EP2 and EP4 agonists were used to elucidate the regulation of PGE2 to KLF2. RESULTS: C-kit, von Willebrand factor (vWF) and vascular endothelial cadherin expressed in BMPCs. Treatment with PGE2 (1 µmol/L) significantly increased the differentiation of BMPCs. The mRNA levels of endothelial markers platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) and endothelial nitric oxide synthase (eNOS), were significantly upregulated in about 2 folds by PGE2 detected with Q-PCR assay. Matrigel tube formation assay also demonstrated PGE2 enhanced the ability of angiogenesis in BMPCs. In addition, the expression of KLF2 increased in more than 2 folds with PGE2 treatment compared with the control. Such effect of PGE2 could be blocked by EP4 blocking peptide. CONCLUSION: Promoting the differentiation of BMPCs, PGE2 reinforced their angiogenesis by binding to the receptor of EP4 in a KLF2-dependent manner.

High-resolution greenspace dynamic data cube from Sentinel-2 satellites over 1028 global major cities.

Greenspace, offering multifaceted ecological and socioeconomic benefits to the nature system and human society, is integral to the 11th Sustainable Development Goal pertaining to cities and communities. Spatially and temporally explicit information on greenspace is a premise to gauge the balance between its supply and demand. However, existing efforts on urban greenspace mapping primarily focus on specific time points or baseline years without well considering seasonal fluctuations, which obscures our knowledge of greenspace's spatiotemporal dynamics in urban settings. Here, we combined spectral unmixing approach, time-series phenology modeling, and Sentinel-2 satellite images with a 10-m resolution and nearly 5-day revisit cycle to generate a four-year (2019-2022) 10-m and 10-day resolution greenspace dynamic data cube over 1028 global major cities (with an urbanized area >100 km2). This data cube can effectively capture greenspace seasonal dynamics across greenspace types, cities, and climate zones. It also can reflect the spatiotemporal dynamics of the cooling effect of greenspace with Landsat land surface temperature data. The developed data cube provides informative data support to investigate the spatiotemporal interactions between greenspace and human society.

Ultrafast Antisolvent Growth of Single-Crystal CsPbBr3 Microcavity for Whispering-Gallery-Mode Lasing.

In recent years, all-inorganic cesium lead bromide (CsPbBr3) perovskites have garnered considerable attention for their prospective applications in green photonics and optoelectronic devices. However, the development of efficient and economical methods to obtain high-quality micron-sized single-crystalline CsPbBr3 microplatelets (MPs) has become a challenge. Here, we report the synthesis of CsPbBr3 MPs on Si/SiO2 substrate by optimizing the ultrafast antisolvent method (FAS). This technique is able to produce well-dispersed, uniformly sized, and morphologically regular tetragonal phase single crystals, which can give strong green emission at room temperature, with excellent stability and excitonic character. Moreover, the crystals demonstrated lasing with a whispering gallery mode with a low threshold. These results suggest that the single-crystalline CsPbBr3 MPs synthesized by this method are of high optical quality, holding vast potential for future applications in photonic devices.

CD44 Is Associated with Poor Prognosis of ccRCC and Facilitates ccRCC Cell Migration and Invasion through HAS1/MMP9.

BACKGROUND: In many solid tumors, CD44 has been identified as a cancer stem cell marker as well as an important molecular in cancer progression and metastasis, making it attractive for potential therapeutic applications. However, our knowledge of the biological function and mechanism of CD44 in clear cell renal cell carcinoma (ccRCC) is limited. METHODS: In this study, the expression, prognostic values and functional enrichment analysis of CD44 in ccRCC were analyzed using public databases. Quantitative real-time PCR (qRT-PCR), Western blotting, and immunohistochemical (IHC) assays were taken to detect CD44 expression in ccRCC tissues. The effects of CD44 on the proliferation, migration and invasion of ccRCC cells were investigated by gain-of-function and loss-of-function experiments. Subcutaneous models further confirmed the role of CD44 in tumor growth. The relationship between CD44, HAS1 and MMP9 was investigated to uncover the regulatory mechanism of CD44 in ccRCC. RESULTS: CD44 was significantly upregulated in ccRCC and associated with poor overall survival (OS). Based on the functional enrichment analysis and PPI network, we found that CD44 had associations with ECM interaction and focal adhesion pathway. Clinical ccRCC sample validation revealed that CD44 mRNA and protein expression were significantly increased in ccRCC tissues, and strong CD44 staining was observed in four metastatic ccRCC cases. In vitro experiments showed that CD44 overexpression promoted cell proliferation, migration and invasion. In vivo experiments also demonstrated that CD44 overexpression accelerated tumor formation in mice. Finally, we found that CD44 regulates the expression of HAS1 in ccRCC, which is essential for the secretion of MMP9 and cell migratory ability. CONCLUSION: The upregulation of CD44 mRNA and protein expressions in ccRCC is indicative of unfavorable clinical prognoses. The CD44/HAS1/MMP9 axis is believed to exert a significant influence on the regulation of ECM degradation and ccRCC metastasis.

Racial/Ethnic Inequity in Transit-Based Spatial Accessibility to COVID-19 Vaccination Sites.

With the ongoing spread of COVID-19, vaccination stands as an effective measure to control and mitigate the impact of the disease. However, due to the unequal distribution of COVID-19 vaccination sites, people can have different levels of spatial accessibility to COVID-19 vaccination. This study adopts an improved gravity-based model to measure the racial/ethnic inequity in transit-based spatial accessibility to COVID-19 vaccination sites in the Chicago Metropolitan Area. The results show that Black-majority and Hispanic-majority neighborhoods have significantly lower transit-based spatial accessibility to COVID-19 vaccination sites compared to White-majority neighborhoods. This research concludes that minority-dominated inner-city neighborhoods, despite better public transit coverage, are still disadvantaged in terms of transit-based spatial accessibility to COVID-19 vaccination sites. This is probably due to their higher population densities, which increase the competition for the limited supply of COVID-19 vaccination sites within each catchment area.

TPM2 attenuates progression of prostate cancer by blocking PDLIM7-mediated nuclear translocation of YAP1.

BACKGROUND: Prostate cancer (PCa) is a common malignant tumor of the genitourinary system. Clinical intervention in advanced PCa remains challenging. Tropomyosins 2 (TPM2) are actin-binding proteins and have been found as a biomarker candidate for certain cancers. However, no studies have explored the role of TPM2 in PCa and its regulatory mechanism. METHODS: TPM2 expression was assessed in Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) PCa patient dataset. The effect of TPM2 on PCa progression was assessed in vitro and in vivo by quantifying proliferation, migration, invasion and tumor growth assays, and the mechanism of TPM2 in PCa progression was gradually revealed by Western blotting, immunoprecipitation, and immunofluorescence staining arrays. RESULTS: TPM2 was found to be severely downregulated in tumor tissues of PCa patients compared with tumor-adjacent normal tissues. In vitro experiments revealed that TPM2 overexpression inhibited PCa cell proliferation, invasion and androgen-independent proliferation. Moreover, TPM2 overexpression inhibited the growth of subcutaneous xenograft tumors in vivo. Mechanistically, this effect was noted to be dependent on PDZ-binding motif of TPM2. TPM2 competed with YAP1 for binding to PDLIM7 through the PDZ-binding motif. The binding of TPM2 to PDLIM7 subsequently inhibited the nuclear transport function of PDLIM7 for YAP1. YAP1 sequestered in the cytoplasm phosphorylated at S127, resulting in its inactivation or degradation which in turn inhibited the expression of YAP1 downstream target genes. CONCLUSIONS: This study investigated the role of TPM2, PDLIM7, and YAP1 in PCa progression and castration resistance. TPM2 attenuates progression of PCa by blocking PDLIM7-mediated nuclear translocation of YAP1. Accordingly, targeting the expression or functional modulation of TPM2, PDLIM7, or YAP1 has the potential to be an effective therapeutic approach to reduce PCa proliferation and prevent the progression of castration-resistant prostate cancer (CRPC).

L1CAM deployed perivascular tumor niche promotes vessel wall invasion of tumor thrombus and metastasis of renal cell carcinoma.

The survival of tumor cells in the bloodstream, and vasculature adhesion at metastatic sites are crucial for tumor metastasis. Perivascular invasion aids tumor cell self-renewal, survival, and formation of metastases by facilitating readily available oxygen, nutrients, and endothelial-derived paracrine factors. Renal cell carcinoma (RCC) is among the most prevalent tumors of the urinary system, and the formation of venous tumor thrombus (VTT) is a characteristic feature of RCC. We observed high expression of L1CAM in the VTT with vessel wall invasion. L1CAM promotes the adhesion, migration, and invasion ability of RCC and enhances metastasis by interacting with ITGA5, which elicits activation of signaling downstream of integrin α5ß1. L1CAM promotes ADAM17 transcription to facilitate transmembrane ectodomain cleavage and release of soluble L1CAM. In response to soluble L1CAM, vascular endothelial cells release several cytokines and chemokines. Endothelial-derived CXCL5 and its receptor CXCR2 promote the migration and intravasation of RCC toward endothelial cells suggesting that crosstalk between endothelial cells and tumor cells has a direct guiding role in driving the metastatic spread of RCC. LICAM plays a crucial role in the invasive ability of RCC, and regulation of L1CAM expression may contribute therapeutically to preventing RCC progression.