NIR-II Absorbed Dithienopyrrole-Benzobisthiadiazole Based Nanosystems for Autophagy Inhibition and Calcium Overload Enhanced Photothermal Therapy.

Although the current cancer photothermal therapy (PTT) can produce a powerful therapeutic effect, tumor cells have been proved a protective mechanism through autophagy. In this study, a novel hybrid theranostic nanoparticle (CaCO3@CQ@pDB NPs, CCD NPs) is designed and prepared by integrating a second near-infrared (NIR-II) absorbed conjugated polymer DTP-BBT (pDB), CaCO3, and autophagy inhibitor (chloroquine, CQ) into one nanosystem. The conjugated polymer pDB with asymmetric donor-acceptor structure shows strong NIR-II absorbing capacity, of which the optical properties and photothermal generation mechanism of pDB are systematically analyzed via molecular theoretical calculation. Under NIR-II laser irradiation, pDB-mediated PTT can produce powerful killing ability to tumor cells. At the same time, heat stimulates a large amount of Ca2+ inflow, causing calcium overload induced mitochondrial damage and enhancing the apoptosis of tumor cells. Besides, the released CQ blocks the self-protection mechanism of tumor cells and greatly enhances the attack of PTT and calcium overload therapy. Both in vitro and in vivo experiments confirm that CCD NPs possess excellent NIR-II theranostic capacity, which provides a new nanoplatform for anti-tumor therapy and builds great potential for future clinical research.

In-depth analysis of ambient air pollution changes due to the COVID-19 pandemic in the Asian Monsoon region.

The COVID-19 pandemic has given a chance for researchers and policymakers all over the world to study the impact of lockdowns on air quality in each country. This review aims to investigate the impact of the restriction of activities during the lockdowns in the Asian Monsoon region on the main criteria air pollutants. The various types of lockdowns implemented in each country were based on the severity of the COVID-19 pandemic. The concentrations of major air pollutants, especially particulate matter (PM) and nitrogen dioxide (NO2), reduced significantly in all countries, especially in South Asia (India and Bangladesh), during periods of full lockdown. There were also indications of a significant reduction of sulfur dioxide (SO2) and carbon monoxide (CO). At the same time, there were indications of increasing trends in surface ozone (O3), presumably due to nonlinear chemistry associated with the reduction of oxides of nitrogens (NOX). The reduction in the concentration of air pollutants can also be seen in satellite images. The results of aerosol optical depth (AOD) values followed the PM concentrations in many cities. A significant reduction of NO2 was recorded by satellite images in almost all cities in the Asian Monsoon region. The major reductions in air pollutants were associated with reductions in mobility. Pakistan, Bangladesh, Myanmar, Vietnam, and Taiwan had comparatively positive gross domestic product growth indices in comparison to other Asian Monsoon nations during the COVID-19 pandemic. A positive outcome suggests that the economy of these nations, particularly in terms of industrial activity, persisted during the COVID-19 pandemic. Overall, the lockdowns implemented during COVID-19 suggest that air quality in the Asian Monsoon region can be improved by the reduction of emissions, especially those due to mobility as an indicator of traffic in major cities.

Refined Sea Salt Markers for Coastal Cities Facilitating Quantification of Aerosol Aging and PM2.5 Apportionment.

Sea salt (ss) aerosols in PM2.5 are often quantified through source apportionment by applying sodium (Na+) and chloride (Cl-) as the markers, but both markers can be substantially emitted from anthropogenic sources. In this study, we differentiate ss from nonss (nss) portions of Na+ and Cl- to better apportion PM2.5 in a coastal tropical urban environment. Size-resolved ionic profiles accounting for Cl- depletion of aged ss were applied to 162-day measurements during 2012 and 2018-2019. Results show that the nss (likely anthropogenic) portions, on average, account for 50-80% of total Na+ and Cl- in submicron aerosols (PM1). This corresponds to up to 2.5 µg/m3 of ss in submicron aerosols that can be ∼10 times overestimated if one attributes all Na+ and Cl- in PM1 to ss. Employing the newly speciated ss- and nss-portions of Na+ and Cl- to source apportionment of urban PM2.5 via positive matrix factorization uncovers a new source of transported anthropogenic emissions during the southwest monsoon, contributing to 12-15% of PM2.5. This increases anthropogenic PM2.5 by ≥19% and reduces ss-related PM2.5 by >30%. In addition to demonstrating Cl- depletion (aging) in submicron aerosols and quantifying ssNa+, nssNa+, ssCl-, as well as nssCl- therein, the refined PM2.5 apportionment resolves new insights on PM2.5 of anthropogenic origins in urban environments, useful to facilitate policy making.

Erratum: Circular RNA Hsa_circRNA_101996 promotes the development of Gastric Cancer via Upregulating Matrix Metalloproteinases-2/Matrix Metalloproteinases-9 through MicroRNA-143/Ten-eleven translocation-2 Pathway: Erratum.

[This corrects the article DOI: 10.7150/jca.62121.].

A chimp algorithm based on the foraging strategy of manta rays and its application.

To address the issue of poor performance in the chimp optimization (ChOA) algorithm, a new algorithm called the manta ray-based chimpa optimization algorithm (MChOA) was developed. Introducing the Latin hypercube method to construct the initial population so that the individuals of the initial population are evenly distributed in the solution space, increasing the diversity of the initial population. Introducing nonlinear convergence factors based on positive cut functions to changing the convergence of algorithms, the early survey capabilities and later development capabilities of the algorithm are balanced. The manta ray foraging strategy is introduced at the position update to make up for the defect that the algorithm is prone to local optimization, which effectively improves the optimization performance of the algorithm. To evaluate the performance of the proposed algorithm, 27 well-known test reference functions were selected for experimentation, which showed significant advantages compared to other algorithms. Finally, in order to further verify the algorithm's applicability in actual production processes, it was applied to solve scheduling problems in three flexible workshop scenarios and an aviation engine job shop scheduling in an enterprise. This confirmed its efficacy in addressing complex real-world problems.

A cleaved METTL3 potentiates the METTL3-WTAP interaction and breast cancer progression.

N6-methyladenosine (m6A) methylation of RNA by the methyltransferase complex (MTC), with core components including METTL3-METTL14 heterodimers and Wilms' tumor 1-associated protein (WTAP), contributes to breast tumorigenesis, but the underlying regulatory mechanisms remain elusive. Here, we identify a novel cleaved form METTL3a (residues 239-580 of METTL3). We find that METTL3a is required for the METTL3-WTAP interaction, RNA m6A deposition, as well as cancer cell proliferation. Mechanistically, we find that METTL3a is essential for the METTL3-METTL3 interaction, which is a prerequisite step for recruitment of WTAP in MTC. Analysis of m6A sequencing data shows that depletion of METTL3a globally disrupts m6A deposition, and METTL3a mediates mammalian target of rapamycin (mTOR) activation via m6A-mediated suppression of TMEM127 expression. Moreover, we find that METTL3 cleavage is mediated by proteasome in an mTOR-dependent manner, revealing positive regulatory feedback between METTL3a and mTOR signaling. Our findings reveal METTL3a as an important component of MTC, and suggest the METTL3a-mTOR axis as a potential therapeutic target for breast cancer.

Beating thermal noise in a dynamic signal measurement by a nanofabricated cavity optomechanical sensor.

Thermal fluctuations often impose both fundamental and practical measurement limits on high-performance sensors, motivating the development of techniques that bypass the limitations imposed by thermal noise outside cryogenic environments. Here, we theoretically propose and experimentally demonstrate a measurement method that reduces the effective transducer temperature and improves the measurement precision of a dynamic impulse response signal. Thermal noise-limited, integrated cavity optomechanical atomic force microscopy probes are used in a photothermal-induced resonance measurement to demonstrate an effective temperature reduction by a factor of ≈25, i.e., from room temperature down as low as ≈12 K, without cryogens. The method improves the experimental measurement precision and throughput by >2×, approaching the theoretical limit of ≈3.5× improvement for our experimental conditions. The general applicability of this method to dynamic measurements leveraging thermal noise-limited harmonic transducers will have a broad impact across a variety of measurement platforms and scientific fields.

AHNAK2 is a biomarker and a potential therapeutic target of adenocarcinomas.

Adenocarcinoma is the second largest histological type of cervical cancer, second only to cervical squamous cell carcinoma. At present, despite the clinical treatment strategies of cervical adenocarcinoma and cervical squamous cell carcinoma being similar, the outcome and prognosis of cervical adenocarcinoma are significantly poor. Therefore, it is urgent to find specific biomarker and therapeutic target for cervical adenocarcinoma. In this study, we aim to reveal and verify the potential biomarkers and therapeutic targets of cervical adenocarcinoma. Weighted correlation network analysis (WGCNA) reveals the differentially-expressed genes significantly related to the histological characteristics of the two cervical cancer subtypes. We select the genes with the top 20 significance for further investigation. Through microarray and immunohistochemical (IHC) analyses of a variety of tumor tissues, we find that among these 20 genes, AHNAK2 is highly expressed not only in cervical adenocarcinoma, but also in multiple of adenocarcinoma tissues, including esophagus, breast and colon, while not in normal gland tissues. In vitro, AHNAK2 knockdown significantly inhibits cell proliferation and migration of adenocarcinoma cell lines. In vivo, AHNAK2 knockdown significantly inhibits tumor progression and metastasis of various adenocarcinomas. RNA-sequencing and bioinformatics analyses suggest that the inhibitory effect of AHNAK2 knockdown on tumor progression is achieved by regulating DNA replication and upregulating Bim expression. Together, we demonstrate that AHNAK2 is a biomarker and a potential therapeutic target for adenocarcinomas.

Development and Evaluation of Statistical Models Based on Machine Learning Techniques for Estimating Particulate Matter (PM2.5 and PM10) Concentrations.

Despite extensive research on air pollution estimation/prediction, inter-country models for estimating air pollutant concentrations in Southeast Asia have not yet been fully developed and validated owing to the lack of air quality (AQ), emission inventory and meteorological data from different countries in the region. The purpose of this study is to develop and evaluate two machine learning (ML)-based models (i.e., analysis of covariance (ANCOVA) and random forest regression (RFR)) for estimating daily PM2.5 and PM10 concentrations in Brunei Darussalam. These models were first derived from past AQ and meteorological measurements in Singapore and then tested with AQ and meteorological data from Brunei Darussalam. The results show that the ANCOVA model (R2 = 0.94 and RMSE = 0.05 µg/m3 for PM2.5, and R2 = 0.72 and RMSE = 0.09 µg/m3 for PM10) could describe daily PM concentrations over 18 µg/m3 in Brunei Darussalam much better than the RFR model (R2 = 0.92 and RMSE = 0.04 µg/m3 for PM2.5, and R2 = 0.86 and RMSE = 0.08 µg/m3 for PM10). In conclusion, the derived models provide a satisfactory estimation of PM concentrations for both countries despite some limitations. This study shows the potential of the models for inter-country PM estimations in Southeast Asia.

High Throughput Nanoimaging of Thermal Conductivity and Interfacial Thermal Conductance.

Thermal properties of materials are often determined by measuring thermalization processes; however, such measurements at the nanoscale are challenging because they require high sensitivity concurrently with high temporal and spatial resolutions. Here, we develop an optomechanical cantilever probe and customize an atomic force microscope with low detection noise ≈1 fm/Hz1/2 over a wide (>100 MHz) bandwidth that measures thermalization dynamics with ≈10 ns temporal resolution, ≈35 nm spatial resolution, and high sensitivity. This setup enables fast nanoimaging of thermal conductivity (η) and interfacial thermal conductance (G) with measurement throughputs ≈6000× faster than conventional macroscale-resolution time-domain thermoreflectance acquiring the full sample thermalization. As a proof-of-principle demonstration, 100 × 100 pixel maps of η and G of a polymer particle are obtained in 200 s with a small relative uncertainty (<10%). This work paves the way to study fast thermal dynamics in materials and devices at the nanoscale.

Programmed Cell Death Ligand 1 Is Enriched in Mammary Stem Cells and Promotes Mammary Development and Regeneration.

Programmed cell death ligand 1 (PD-L1) is widely expressed in a variety of human tumors, and inhibition of the PD-L1/PD-1 pathway represents one of the most promising therapy for many types of cancer. However, the physiological function of PD-L1 in tissue development is still unclear, although PD-L1 mRNA is abundant in many tissues. To address this puzzle, we investigated the function of PD-L1 in mammary gland development. Interestingly, we found that PD-L1 is enriched in protein C receptor (Procr)-expressing mammary stem cells (MaSCs), and PD-L1-expressing mammary basal cells (PD-L1+ basal cells) exhibit robust mammary regeneration capacity in transplantation assay. The lineage tracing experiment showed that PD-L1+ cells can differentiate into all lineages of mammary epithelium cells, suggesting that PD-L1+ basal cells have the activities of MaSCs. Furthermore, PD-L1 deficiency significantly impairs mammary development and reduces mammary regeneration capacity of mammary basal cells, suggesting that PD-L1 is not only enriched in MaSCs but also improves activities of MaSCs. In summary, these results demonstrated that PD-L1 is enriched in MaSCs and promotes mammary gland development and regeneration. Mechanistically, our data indicated that PD-L1 expression is induced by continuous activation of Wnt/ß-catenin signaling. In conclusion, these results demonstrated that PD-L1 is a marker of MaSCs, and PD-L1 is essential for mammary development. Our study provides novel insight into the physiological functions of PD-L1 in tissue development.

Circular RNA Hsa_circRNA_101996 promotes the development of Gastric Cancer via Upregulating Matrix Metalloproteinases-2/Matrix Metalloproteinases-9 through MicroRNA-143/Ten-eleven translocation-2 Pathway.

Background: The long-term survival rate of gastric cancer (GC) patients at advanced stages remains low worldwide. Circular RNAs (circRNAs) a newly studied type of non-coding RNA that play an important role in the pathogenesis and diagnosis of various diseases. In this research, we aimed to explore the functions of hsa_circRNA_101996 in GC cells and an animal model of GC. Methods: The expression of hsa_circRNA_101996, microRNA (miR)-143, and ten-eleven translocation (TET)-2 in GC tissues, the adjacent tissues, and cell lines were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Transwell assays were used to analyze the knockdown effects of hsa_circRNA_101996, miR-143, and overexpression of TET2 on cell proliferation, migration, and invasion abilities. Western blotting was used to analyze the expression of matrix metalloproteinases (MMP)2/MMP9. Binding interactions between, hsa_circRNA_101996 and miR-143 and between, miR-143 and TET2 were detected by Dual-luciferase reporter assays. Levels of protein expression were analyzed by Western blotting. Tumor models were established by subcutaneous injection of tumor cells in Bl6/Rag2/GammaC double knockout mice. Results: The result showed that hsa_circRNA_101996 expression was significantly upregulated in GC tissues compared to that in the adjacent tissues, and its level in cancer tissue was correlated with tumor size, lymphatic metastasis, and distant metastasis. Compared with the low hsa_circRNA_101996 expression group, the three-year survival rate of patients in the high hsa_circRNA_101996 expression group was significantly lower. The knockdown of hsa_circRNA_101996 dramatically suppressed the cell migration, invasion, and proliferation of GC cells by sponging to absorb miR-143 and elevated the expression of TET2. In vivo studies showed that the knockdown of hsa_circRNA_101996 delayed tumor growth. Furthermore, we revealed that TET2 regulates MMP2/MMP9 expression through the DNA demethylation pathway. Conclusion: Our findings indicate that hsa_circRNA_101996 promotes GC development by upregulating MMP2/MMP9 through miR-143/TET2 pathway, which may provide a novel target for GC.

Current status of premature mortality from four non-communicable diseases and progress towards the Sustainable Development Goal target 3.4: a population-based study in northeast China, 2004-2017.

BACKGROUND AND AIM: According to the United Nations' Sustainable Development Goal (SDG) target 3.4, premature mortality from four non-communicable diseases (cardiovascular diseases, cancer, chronic respiratory diseases, and diabetes mellitus, collectively referred to as NCD4) should achieve a minimum decline of 33% in 2030 relative to 2015. This remains a challenge for China. This study aimed to evaluate the current status and progress towards this target in Liaoning Province, one of the three provinces in northeast China. METHODS: We calculated the premature mortality rates (PMRs) per year and average annual percentage changes (AAPCs) from NCD4 using mortality data between 2004 and 2017. The trend was analyzed in the whole population, as well as in subpopulations of gender (male/female) and inhabiting area (urban/rural). PMRs from NCD4 for 2030 were projected by fitting a linear regression based on the current trend, which was identified by a Joinpoint model. FINDINGS: In the whole population, only chronic respiratory diseases showed a significant decline (AAPC: - 6.5%, p < 0.05), while only cancer showed a significant increase (AAPC: + 1.3%, p < 0.05); taken together, NCD4 showed a significant increase (AAPC: + 0.6%, p < 0.05). In the subpopulations, while males showed a significant increase in NCD4 (AAPC: + 1.5%, p < 0.05), cardiovascular diseases (AAPC: + 1.7%, p < 0.05), cancer (AAPC: + 1.8%, p < 0.05), and diabetes mellitus (AAPC: + 4.2%, p < 0.05), females showed a significant decline in NCD4 (AAPC: - 1.2%, p < 0.05), cardiovascular diseases (AAPC: - 1.8%, p < 0.05), diabetes mellitus (AAPC: - 2.1%, p < 0.05), but showed a mild increase in cancer (AAPC: + 0.5%, p > 0.05). A comparative analysis of the projected PMRs for 2030 with the 2015 levels revealed that only chronic respiratory diseases are expected to achieve the SDG target 3.4, apart from in the urban male subpopulation. CONCLUSION: Except for chronic respiratory diseases, NCD4 cannot be expected to achieve the SDG target 3.4 in the whole population of Liaoning Province. Under these circumstances, special attention should be paid to reducing the risks of cancer and providing preventative interventions for men.

Mammary Development and Breast Cancer: a Notch Perspective.

Mammary gland development primarily occurs postnatally, and this unique process is complex and regulated by systemic hormones and local growth factors. The mammary gland is also a highly dynamic organ that undergoes profound changes at puberty and during the reproductive cycle. These changes are driven by mammary stem cells (MaSCs). Breast cancer is one of the most common causes of cancer-related death in women. Cancer stem cells (CSCs) play prominent roles in tumor initiation, drug resistance, tumor recurrence, and metastasis. The highly conserved Notch signaling pathway functions as a key regulator of the niche mediating mammary organogenesis and breast neoplasia. In this review, we discuss mechanisms by which Notch contributes to breast carcinoma pathology and suggest potentials for therapeutic targeting of Notch in breast cancer. In summary, we provide a comprehensive overview of Notch functions in regulating MaSCs, mammary development, and breast cancer.

Baicalin Promotes Mammary Gland Development via Steroid-Like Activities.

Baicalin, the main flavonoid component extracted from Scutellaria roots, has a variety of biological activities and is therefore used in the treatment of many kinds of diseases. However, whether baicalin affects the normal development of tissues and organs is still unclear. Here, using a mouse mammary gland model, we investigated the effects of baicalin on the expansion of mammary stem cells (MaSCs) and mammary development, as well as breast cancer progression. Interestingly, we found that baicalin administration significantly accelerates duct elongation at puberty, and promotes alveolar development and facilitates milk secretion during pregnancy. Furthermore, self-renewal of MaSCs was significantly promoted in the presence of baicalin. Moreover, in a tumor xenograft model, baicalin promoted tumor growth of the MDA-MB-231 cell line, but suppressed tumor growth of the ZR-751 cell line. Mechanistically, baicalin can induce expression of the protein C receptor, while inhibiting the expression of the estrogen receptor. Transcriptome analysis revealed that baicalin is involved in signaling pathways related to mammary gland development, immune response, and cell cycle control. Taken together, our results from comprehensive investigation of the biological activity of baicalin provide a theoretical basis for its rational clinical application.

Liquid Phase Concentrated Growth Factor Improves Autologous Fat Graft Survival In Vivo in Nude Mice.

OBJECTIVE: The present study aimed to explore the efficacy and safety profile of liquid phase concentrated growth factor (LPCGF) in promoting autologous fat graft survival. METHODS: LPCGF/PRP was mixed with human fat tissues at different proportions and transplanted into nude mice. Three months after transplantation, the implanted fat tissues were retrieved for analysis. H&E staining was used to quantify the neovascularization. Immunohistochemical staining was applied to quantify the CD34-positive stem cells and the fluorescence intensity of VEGF and TGF-ß. RESULTS: Addition of LPCGF to autologous fat reduced the fat absorption by 5-15%, especially at the early stage, and no complications were observed. In addition, the effect was improved with increased CGF. Liquid phase concentrated growth factor improves autologous fat graft survival, and the most suitable ratio of LPCGF/fat is 1:8. CONCLUSION: LPCGF is rich in VEGF, TGF-ß and CD34-positive stem cells, which can improve the fat transplantation effect, but the specific influence of a single component requires future evaluation. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Peat-forest burning smoke in Maritime Continent: Impacts on receptor PM2.5 and implications at emission sources.

This study characterizes the impacts of transported peat-forest (PF) burning smoke on an urban environment and evaluates associated source burning conditions based on carbon properties of PM2.5 at the receptor site. We developed and validated a three-step classification that enables systematic and more rapid identification of PF smoke impacts on a tropical urban environment with diverse emissions and complex atmospheric processes. This approach was used to characterize over 300 daily PM2.5 data collected during 2011-2013, 2015 and 2019 in Singapore. A levoglucosan concentration of ≥0.1 µg/m3 criterion indicates dominant impacts of transported PF smoke on urban fine aerosols. This approach can be used in other ambient environments for practical and location-dependent applications. Organic carbon (OC) concentrations (as OC indicator) can be an alternate to levoglucosan for assessing smoke impacts on urban environments. Applying the OC concentration indicator identifies smoke impacts on ∼80% of daily samples in 2019 and shows an accuracy of 51-86% for hourly evaluation. Following the systematic identification of urban PM2.5 predominantly affected by PF smoke in 2011-2013, 2015 and 2019, we assessed the concentration ratio of char-EC/soot-EC as an indicator of smoldering- or flaming-dominated burning emissions. When under the influence of transported PF smoke, the mean concentration ratio of char-EC to soot-EC in urban PM2.5 decreased by >70% from 8.2 in 2011 to 2.3 in 2015 but increased to 3.8 in 2019 (p < 0.05). The reversed trend with a 65% increase from 2015 to 2019 shows stronger smoldering relative to flaming, indicating a higher level of soil moisture at smoke origins, possibly associated with rewetting and revegetating peatlands since 2016.

Transcriptomic analysis identifies dysregulated genes and functional networks in human small airway epithelial cells exposed to ambient PM2.5.

Cellular models exhibiting human physiological features of pseudostratified columnar epithelia, provide a more realistic approach for elucidating detailed mechanisms underlying PM2.5-induced pulmonary toxicity. In this study, we characterized the barrier and mucociliary functions of differentiated human small airway epithelial cells (SAECs), cultured at the air-liquid interface (ALI). Due to the presence of mucociliary protection, particle internalization was reduced, with a concomitant decrease in cytotoxicity in differentiated S-ALI cells, as compared to conventional submerged SAEC cultures. After 24-hour exposure to PM2.5 surrogates, 117 up-regulated genes and 156 down-regulated genes were detected in S-ALI cells, through transcriptomic analysis using the Affymetrix Clariom™ S Human Array. Transcription-level changes in >60 signaling pathways, were revealed by functional annotation of the 273 differentially expressed genes, using the PANTHER Gene List Analysis. These pathways are involved in multiple cellular processes, that include inflammation and apoptosis. Exposure to urban PM2.5 led to complex responses in airway epithelia, including a net induction of downstream pro-inflammatory and pro-apoptotic responses. Collectively, this study highlights the importance of using the more advanced ALI model rather than the undifferentiated submerged model, to avoid over-assessment of inhaled particle toxicity in human. The results of our study also suggest that reduction of ambient PM2.5 concentrations would have a protective effect on respiratory health in humans.

Urban PM2.5 reduces angiogenic ability of endothelial cells in an alveolar-capillary co-culture lung model.

Adverse health effects arising from exposure to fine particulates have become a major concern. Angiogenesis is a vital physiological process for the growth and development of cells and structures in the human body, whereby excessive or insufficient vessel growth could contribute to pathogenesis of diseases. We therefore evaluated indirect effects of carbon black (CB) and inhalable airborne particles on the angiogenic ability of unexposed Human Umbilical Vein Endothelial Cells (HUVECs) by co-culturing HUVECs with pre-exposed Small Airway Epithelial Cells (SAECs). As endothelial cells are major components of blood vessels and potential targets of fine particles, we investigated if lung epithelial cells exposed to ambient PM2.5 surrogates could induce bystander effects on neighboring unexposed endothelial cells in an alveolar-capillary co-culture lung model. Epithelial exposure to CB at a non-toxic dose of 25 µg/mL reduced endothelial tube formation and cell adhesion in co-cultured HUVECs, and decreased expression of angiogenic genes in SAECs. Similarly, exposure of differentiated SAECs to PM2.5 surrogates reduced cell reproductive ability, adhesion and tube formation of neighboring HUVECs. This indicates epithelial exposure to CB and urban PM2.5 surrogates both compromised the angiogenic ability of endothelial cells through bystander effects, thereby potentially perturbing the ventilation-perfusion ratio and affecting lung function.