Involvement of M2 macrophages polarization in PM2.5-induced COPD by upregulating MMP12 via IL4/STAT6 pathway.

Biomass-related airborne fine particulate matter (PM2.5) is an important risk factor for chronic obstructive pulmonary disease (COPD). Macrophage polarization has been reported to be involved in PM2.5-induced COPD, but the dynamic characteristics and underlying mechanism of this process remain unclear. Our study established a PM2.5-induced COPD mouse model and revealed that M2 macrophages predominantly presented after 4 and 6 months of PM2.5 exposure, during which a notable increase in MMP12 was observed. Single cell analysis of lung tissues from COPD patients and mice further revealed that M2 macrophages were the dominant macrophage subpopulation in COPD, with MMP12 being involved as a hub gene. In vitro experiments further demonstrated that PM2.5 induced M2 polarization and increased MMP12 expression. Moreover, we found that PM2.5 increased IL-4 expression, STAT6 phosphorylation and nuclear translocation. Nuclear pSTAT6 then bound to the MMP12 promoter region. Furthermore, the inhibition of STAT6 phosphorylation effectively abrogated the PM2.5-induced increase in MMP12. Using a coculture system, we observed a significantly reduced level of E-cadherin in alveolar epithelial cells cocultured with PM2.5-exposed macrophages, while the decrease in E-cadherin was reversed by the addition of an MMP12 inhibitor to the co-culture system. Taken together, these findings indicated that PM2.5 induced M2 macrophage polarization and MMP12 upregulation via the IL-4/STAT6 pathway, which resulted in alveolar epithelial barrier dysfunction and excessive extracellular matrix (ECM) degradation, and ultimately led to COPD progression. These findings may help to elucidate the role of macrophages in COPD, and suggest promising directions for potential therapeutic strategies.

Characteristics of inflammatory phenotypes in patients with chronic obstructive pulmonary disease: a cross-sectional study.

BACKGROUND: The relationship between airway inflammation in chronic obstructive pulmonary disease (COPD) and clinical characteristics remains unclear. This study aimed to investigate the airway inflammatory phenotypes in COPD and their association with clinical characteristics. METHODS: 895 patients with COPD were recruited from Guangdong Province, China in this study. Each patient underwent questionnaire interviews, spirometry testing, CT scans and induced sputum examination. Classification of airway inflammation phenotypes was based on sputum inflammatory cell counts. Covariance analysis was applied to assess associations with airway inflammation phenotypes. RESULTS: In this study, we found that neutrophilic phenotype (NP, 58.0%) was the most common airway inflammation phenotype in patients with COPD, followed by mixed granulocytic phenotype (MGP, 32.6%), eosinophilic phenotype (EP, 5.4%) and paucigranulocytic phenotype (PP, 4.0%). Compared with NP patients, those with MGP exhibited more frequent chronic respiratory symptoms, and a higher proportion of individuals classified under Global Initiative for Chronic Obstructive Lung Disease stages 3 and 4. After adjusting for confounding factors, MGP patients had lower lung function, and more severe emphysema and air trapping. On the contrary, patients with PP had the best pulmonary function and less emphysema and air trapping. CONCLUSIONS: NP was the most common airway inflammation phenotype in patients with COPD. Patients with MGP had more respiratory symptoms, greater loss of lung function, and more severe emphysema and gas trapping compared with those with NP. Meanwhile, PP may be a phenotype of mild damage to lung structure in patients with COPD.

Stability of SARS-CoV-2 in cold-chain transportation environments and the efficacy of disinfection measures.

Background: Low temperature is conducive to the survival of COVID-19. Some studies suggest that cold-chain environment may prolong the survival of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and increase the risk of transmission. However, the effect of cold-chain environmental factors and packaging materials on SARS-CoV-2 stability remains unclear. Methods: This study aimed to reveal cold-chain environmental factors that preserve the stability of SARS-CoV-2 and further explore effective disinfection measures for SARS-CoV-2 in the cold-chain environment. The decay rate of SARS-CoV-2 pseudovirus in the cold-chain environment, on various types of packaging material surfaces, i.e., polyethylene plastic, stainless steel, Teflon and cardboard, and in frozen seawater was investigated. The influence of visible light (wavelength 450 nm-780 nm) and airflow on the stability of SARS-CoV-2 pseudovirus at -18°C was subsequently assessed. Results: Experimental data show that SARS-CoV-2 pseudovirus decayed more rapidly on porous cardboard surfaces than on nonporous surfaces, including polyethylene (PE) plastic, stainless steel, and Teflon. Compared with that at 25°C, the decay rate of SARS-CoV-2 pseudovirus was significantly lower at low temperatures. Seawater preserved viral stability both at -18°C and with repeated freeze-thaw cycles compared with that in deionized water. Visible light from light-emitting diode (LED) illumination and airflow at -18°C reduced SARS-CoV-2 pseudovirus stability. Conclusion: Our studies indicate that temperature and seawater in the cold chain are risk factors for SARS-CoV-2 transmission, and LED visible light irradiation and increased airflow may be used as disinfection measures for SARS-CoV-2 in the cold-chain environment.

Administration of recombinant human thrombopoietin is associated with alleviated thrombocytopenia in adult intensive care unit patients with pneumonia: A single-center retrospective study.

Background: Recombinant human thrombopoietin (rhTPO) is reported to stimulate platelet production and increase peripheral platelet counts; it is primarily used to manage chemotherapy-induced thrombocytopenia and idiopathic thrombocytopenic purpura. However, the effect of rhTPO in patients with pneumonia and thrombocytopenia remains uncertain. Objective: To assess the association of rhTPO and platelet counts in ICU patients with pneumonia and thrombocytopenia. Materials and Methods: A retrospective cohort study was performed in the ICU department, Nanfang Hospital, Southern Medical University, Guangzhou, China. From January 2016 to April 2021, patients with pneumonia and thrombocytopenia were allocated to two groups-the rhTPO and no-rhTPO groups-according to whether they received rhTPO treatment or not during their ICU stay. Demographical and clinical data were collected and analyzed using statistical software; p < 0.05 was considered statistically significant. Results: Out of 327 patients, 149 were in the rhTPO group and 178 were in the no-rhTPO group. Within the first 7 days, platelet counts increased more for patients in the rhTPO group compared with those in the no-rhTPO group (99.21 ± 102.613 vs. 2.08 ± 43.877, p = 0.000). The clinical recovery rate of platelets increased within 7 days (65.8 vs. 18.5%, p = 0.000) and, after 7 days of enrollment, hemorrhagic scores decreased more apparently in the rhTPO group (2.81 ± 2.856 vs. 1.16 ± 2.123, p = 0.000). Further, bleeding events ceased in 66.7% of the patients in the rhTPO group compared with 37.3% of the patients in the no-rhTPO group (p = 0.000). Less red-blood-cells transfusions were needed in the rhTPO group (3.639 ± 4.630 vs. 5.818 ± 6.858, p = 0.009). Furthermore, through logistic regression, rhTPO administration was found to be an independent indicator that affected the platelet recovery rate within 7 days. Conclusion: This study finds that rhTPO administration is associated with increased platelet counts, alleviated bleeding, and reduced blood transfusion. For patients with pneumonia and thrombocytopenia, rhTPO may be an effective therapeutic drug; however, more RCT trails are needed to confirm our observation.

Effects of Different Concentrations of BSA on In Vitro Corrosion Behavior of Pure Zinc in Artificial Plasma.

When medical metallic materials are implanted in the body and come into contact with the body fluid environment, proteins will be rapidly adsorbed on the surface and affect the corrosion process of the material. Currently, there is no uniform understanding of the effect of protein adsorption on the corrosion behavior of materials due to the limitations of the nature of metal materials, protein concentrations, and different media environments. The effect of various bovine serum albumin (BSA) concentrations in artificial plasma (AP) on the corrosion behavior of pure Zn during 14 days of immersion was investigated in this research. The corrosion rate of pure Zn was slowed down by the addition of BSA, and the decelerating effect of lower protein concentration on the corrosion rate of Zn was more significant in the initial stage of immersion. With prolonging the immersion time, the corrosion rate of pure Zn in different media slowed down and stabilized, and the corrosion rates of pure Zn showed a decreasing trend with an increase of BSA concentration. Furthermore, the Langmuir adsorption isotherm model was utilized to study the relationship between the BSA concentration and corrosion behavior of pure Zn and to analyze the role of proteins in the degradation mechanism of pure Zn. This work could be useful for further exploration of potential clinical applications of zinc alloys.

Predictors of High Sputum Eosinophils in Chronic Obstructive Pulmonary Disease.

Background: Eosinophils are involved in the development of chronic obstructive pulmonary disease (COPD) and inhaled corticosteroid responsiveness. We evaluated clinical predictors of high sputum eosinophil levels in a COPD cohort in China. Methods: We conducted an observational, prospective, population-based, cross-sectional study. Participants were tested for COPD and underwent spirometry, computed tomography scans, and a blood test. Participants also produced induced sputum and responded to an information-gathering questionnaire. High sputum eosinophils were defined as ≥3.0%. Multivariate logistic regression was used to identify predictors of high sputum eosinophil levels. Results: We recruited 895 patients with complete and quality control data. The median percentage of sputum eosinophil abundance was 2.00% (interquartile range: 0.75-5.00) and the prevalence of COPD with high sputum eosinophils was 38.0%. Covariance analysis indicated that the high sputum eosinophil group had lower lung function, more severe emphysema, and air trapping. Multivariate logistic regression indicated that high blood eosinophil levels, severe respiratory symptoms, being a former smoker, and a family history of respiratory diseases were associated with high sputum eosinophil levels. Conclusion: High blood eosinophil levels, severe respiratory symptoms, being a former smoker, and a family history of respiratory diseases may be predictors of high sputum eosinophil levels in Chinese COPD patients. High sputum eosinophils were associated with lower lung function, more emphysema, and gas trapping.

Wood smoke particulate matter (WSPM2.5) induces pyroptosis through both Caspase-1/IL-1ß/IL-18 and ATP/P2Y-dependent mechanisms in human bronchial epithelial cells.

Emerging evidences have linked the air pollution particulate matters, especially the fine particulate matter PM2.5, to the disease development of chronic obstructive pulmonary disease (COPD). Our previous studies reported that biofuel PM2.5 can induce devastated damage of human bronchial epithelial cells, this study aims to further investigate the underlying molecular mechanisms how biofuel PM2.5 induces bronchial epithelial cell death and dysfunction. In this study, biofuel PM2.5 extracted from wood smoke (WSPM2.5) was used according to our previous publication. A 16-HBE cell line was used as the cell model. Results showed that: Firstly, WSPM2.5 induced significant pyroptosis in 16-HBE cells, reflected by the typical changes including elevated release of lactate dehydrogenase release (LDH) and activated activity and expression of Caspase-1/IL-1ß/IL-18 signaling pathway. Then, specific inhibitors for both Caspases (Z-VAD-FMK) and Caspase-1 (VX-765), as well as specific siRNA knockdown of IL-1ß all effectively attenuated the WSPM2.5-induced upregulation of downstream inflammatory cytokines and chemokines (IL-6, IL-8, CXCL-1, CXCL-2, etc), respectively. Notably, WSPM2.5 caused a novel increase of intracellular-to-extracellular ATP secretion, which could also contribute to the WSPM2.5-induced pyroptosis and inflammation by activating the Caspase-1/IL-1ß/IL-18 signaling pathway through possible autocrine and/or paracrine mechanisms. Antagonism of ATP (Apyrase) or specific siRNA knockdown against ATP receptors (P2Y2 and P2Y7) both significantly inhibited the WSPM2.5-induced pyroptosis and inflammation. These results add up to the current knowledge and bring up novel insights that WSPM2.5 could induce significant pyroptosis and inflammation of human bronchial epithelial cells, through both a classic NLRP3/Caspase-1/IL-1ß-dependent and a novel ATP/P2Y-dependent mechanisms.

Thermal property and failure behavior of LaSmZrO thermal barrier coatings by EB-PVD.

La2Zr2O7 coatings are promising candidates to substitute YSZ coatings in advanced gas turbine engines. In this work, Sm-doped La2Zr2O7 coatings were deposited by physical vapor deposition. This work focuses on the crystal structure, thermal conductivity, thermal expansion coefficient, morphology, composition, and thermal durability of LaSmZrO coatings. The LaSmZrO ceramics exhibit low thermal conductivity (1.69 W/mK at 800°C) and high thermal expansion coefficient (9.72∗10-6 K-1 at 1500°C) compared with La2Zr2O7. The LaSmZrO/YSZ coatings with feathery microstructure show relatively good thermal durability (8183 cycles or 856 h) under high temperature. The broken regions are observed at the ceramic coating/bond coating interface. The failure behaviors are relevant with crack evolution and thermally grown oxide growth. This work might guide the investigation of advanced coatings under high temperature.

PM2.5 induces pulmonary microvascular injury in COPD via METTL16-mediated m6A modification.

Fine particulate matter (PM2.5) exposure is a significant cause of chronic obstructive pulmonary disease (COPD), but the detailed mechanisms involved in COPD remain unclear. In this study, we established PM2.5-induced COPD rat models and showed that PM2.5 induced pulmonary microvascular injury via accelerating vascular endothelial apoptosis, increasing vascular permeability, and reducing angiogenesis, thereby contributing to COPD development. Moreover, microvascular injury in COPD was validated by measurements of plasma endothelial microparticles (EMPs) and serum VEGF in COPD patients. We then performed m6A sequencing, which confirmed that altered N6-methyladenosine (m6A) modification was induced by PM2.5 exposure. The results of a series of experiments demonstrated that the expression of methyltransferase-like protein 16 (METTL16), an m6A regulator, was upregulated in PM2.5-induced COPD rats, while the expression of other regulators did not differ upon PM2.5-induction. To clarify the regulatory effect of METTL16-mediated m6A modification induced by PM2.5 on pulmonary microvascular injury, cell apoptosis, permeability, and tube formation, the m6A level in METTL16-knockdown pulmonary microvascular endothelial cells (PMVECs) was evaluated, and the target genes of METTL16 were identified from a set of the differentially expressed and m6A-methylated genes associated with vascular injury and containing predicted sites of METTL16 methylation. The results showed that Sulfatase 2 (Sulf2) and Cytohesin-1 (Cyth1) containing the predicted METTL16 methylation sites, exhibited higher m6A methylation and were downregulated after PM2.5 exposure. Further studies demonstrated that METTL16 may regulate Sulf2 expression via m6A modification and thereby contribute to PM2.5-induced microvascular injury. These findings not only provide a better understanding of the role played by m6A modification in PM2.5-induced microvascular injury, but also identify a new therapeutic target for COPD.

Impaired AT2 to AT1 cell transition in PM2.5-induced mouse model of chronic obstructive pulmonary disease.

BACKGROUND: Particular matter 2.5 (PM2.5) is one of the most important air pollutant, and it is positively associated with the development of chronic obstructive pulmonary disease (COPD). However, the precise underlying mechanisms through which PM2.5 promotes the development of COPD remains largely unknown. METHODS: Mouse alveolar destruction were determined by histological analysis of lung tissues and lung function test. Alveolar type II cells (AT2) to alveolar type I cells (AT1) transition in PM2.5-induced COPD mouse model was confirmed via immunofluorescence staining and qPCR analysis. The differentially expressed genes in PM2.5-induced COPD mouse model were identified by RNA-sequencing of alveolar epithelial organoids and generated by bioinformatics analysis. RESULTS: In this study, we found that 6 months exposure of PM2.5 induced a significantly decreased pulmonary compliance and resulted in pulmonary emphysema in mice. We showed that PM2.5 exposure significantly reduced the AT2 to AT1 cell transition in vitro and in vivo. In addition, we found a reduced expression of the intermediate AT2-AT1 cell process marker claudin 4 (CLDN4) at day 4 of differentiation in mouse alveolar organoids treated with PM2.5, suggesting that PM2.5 exposure inhibited AT2 cells from entering the transdifferentiation process. RNA-sequencing of mouse alveolar organoids showed that several key signaling pathways that involved in the AT2 to AT1 cell transition were significantly altered including the Wnt signaling, MAPK signaling and signaling pathways regulating pluripotency of stem cells following PM2.5 exposure. CONCLUSIONS: In summary, these data demonstrate a critical role of AT2 to AT1 cell transition in PM2.5-induced COPD mouse model and reveal the signaling pathways that potentially regulate AT2 to AT1 cell transition during this process. Our findings therefore advance the current knowledge of PM2.5-induced COPD and may lead to a novel therapeutic strategy to treat this disease.

Erratum for Exposure to Concentrated Ambient Fine Particulate Matter Induces Vascular Endothelial Dysfunction via miR-21.

[This corrects the article DOI: 10.7150/ijbs.19868.].

The influence of alternating cyclic dynamic loads with different low frequencies on the bio-corrosion behaviors of AZ31B magnesium alloy in vitro.

The real physiological environment of human body is complicated with different degrees and forms of dynamic loads applied to implanted medical devices due to the daily activities of the patients, which would have impacts on the degradation behaviors of magnesium alloy implants. In this work, the bio-corrosion behaviors of AZ31B magnesium alloy under alternating cyclic dynamic loads with different low frequencies (0.1-2.5 Hz) were specially investigated. It was found that the bio-degradation performances under external dynamic stressed conditions were much severer than those under unstressed conditions and static loads. The corrosion rates were generally accelerated as the rise of cyclic frequency. Hereby a numerical model for the degradation process of Mg alloy was established. The corrosion current density i corr of Mg alloy and the applied loading frequency f matches a linear relationship of ln i corr ∝ f, which is the result of interactions between the cyclic alternating load and corrosive environment. This work could provide a theoretical reference and an experimental basis for further researches on the biodegradation behaviors of biomedical materials under dynamic conditions.

Andrographolide Suppresses the Growth and Metastasis of Luminal-Like Breast Cancer by Inhibiting the NF-κB/miR-21-5p/PDCD4 Signaling Pathway.

Tumor growth and metastasis are responsible for breast cancer-related mortality. Andrographolide (Andro) is a traditional anti-inflammatory drug used in the clinic that inhibits NF-κB activation. Recently, Andro has been found in the treatment of various cancers. Andro inhibits breast cell proliferation and invasion and induces apoptosis via activating various signaling pathways. Therefore, the underlying mechanisms with regard to the antitumor effects of Andro still need to be further confirmed. Herein, a MMTV-PyMT spontaneous luminal-like breast cancer lung metastatic transgenic tumor model was employed to estimate the antitumor effects of Andro on breast cancer in vivo. Andro significantly inhibited tumor growth and metastasis in MMTV-PyMT mice and suppressed the cell proliferation, migration, and invasion of MCF-7 breast cancer cells in vitro. Meanwhile, Andro significantly inhibited the expression of NF-κB, and the downregulated NF-κB reduced miR-21-5p expression. In addition, miR-21-5p dramatically inhibited the target gene expression of programmed cell death protein 4 (PDCD4). In the current study, we demonstrated the potential anticancer effects of Andro on luminal-like breast cancer and indicated that Andro inhibits the expression of miR-21-5p and further promotes PDCD4 via NF-κB suppression. Therefore, Andro could be an antitumor agent for the treatment of luminal-like breast cancer in the clinic.

The long noncoding RNA HCG18 participates in PM2.5-mediated vascular endothelial barrier dysfunction.

Increased vascular endothelial permeability can disrupt vascular barrier function and further lead to multiple human diseases. Our previous reports indicated that particulate matter 2.5 (PM2.5) can enhance the permeability of vascular endothelial cells. However, the regulatory mechanism was not comprehensively demonstrated. Therefore, this work elucidated this mechanism by demonstrating that PM2.5 can increase the permeability of HUVECs by inhibiting the expression of Hickson compact group 18 (HCG18). Moreover, we demonstrated that lncRNA HCG18 functioned as a ceRNA for miR-21-5p and led to the derepression of its target SOX7, which could further transcriptionally activate the expression of VE-cadherin to regulate the permeability of HUVECs. In this study, we provide evidence that HCG18/miR-21-5p/SOX7/VE-cadherin signaling is involved in PM2.5-induced vascular endothelial barrier dysfunction.

Exosomes with low miR-34c-3p expression promote invasion and migration of non-small cell lung cancer by upregulating integrin α2ß1.

Exosomes play critical roles in regulating various physiological and pathological processes, including immune stimulation, immune suppression, cardiovascular diseases, and cancers. Recent studies show that exosomes that transport specific microRNAs (miRNAs) are involved in tumor development. However, the molecular mechanism by which tumor invasion and migration are regulated by exosomes from non-small cell lung cancer (NSCLC) is not well understood. Here, we show that exosomes shuttling low levels of miR-34c-3p are involved in NSCLC progression. Our results showed that exosomes derived from NSCLC cells carrying low levels of miR-34c-3p could be transported into the cytoplasm of NSCLC cells and accelerate NSCLC invasion and migration by upregulating integrin α2ß1. A luciferase assay revealed that integrin α2ß1 was the direct target of miR-34c-3p, and overexpression of integrin α2ß1 could promote the invasion and migration of NSCLC cells. The analysis of exosomes derived from clinical serum samples indicated that the expression of miR-34c-3p was significantly downregulated in exosomes from NSCLC patients compared with that of normal controls. A549-derived exosomes promoted NSCLC cells lung metastases in vivo. Exosomes shuttling low levels of miR-34c-3p were associated with the progression of NSCLC in vitro and in vivo. Our data demonstrate that exosomes shuttling low levels of miR-34c-3p can accelerate the invasion and migration of NSCLC by upregulating integrin α2ß1. MiR-34c-3p can be a diagnostic and prognostic marker for NSCLC. High expression of integrin α2ß1 is positively related to the migration and metastasis of NSCLC cells.

Corrosion behavior and mechanical degradation of as-extruded Mg-Gd-Zn-Zr alloys for orthopedic application.

The microstructures, corrosion behavior, and mechanical degradation of the as-extruded Mg-6.0Gd-0.5Zn-0.4Zr (wt %, GZ60K) and Mg-6.0Gd-1.0Zn-0.4Zr (wt %, GZ61K) alloys were investigated. In both alloys, stacking faults and precipitates are formed in the recrystallized microstructures. The corrosion rate of GZ61K calculated by the hydrogen evolution in simulated body fluid is 0.34 ± 0.13 mm/year, which is lower than that of GZ60K (0.45 ± 0.09 mm/year); and the current density of GZ61K (5.23 ± 1.41 µA cm-2 ) is much lower than that of GZ60K (11.95 ± 3.37 µA cm-2 ). The corrosion results indicate GZ61K is more resistant to corrosion than GZ60K, but GZ60K presents more uniform corrosion mode as compared to GZ61K. After immersion in simulated body fluid for 7, 14, and 21 days, a slight decrease in the strength of both alloys is observed. The yield strength half-life is assessed for mechanical degradation and determined to be 125 and 85 days for GZ60K and GZ61K, respectively. The as-extruded GZ60K alloy with more uniform corrosion and longer mechanical integrity shows promising potential for orthopedic application.

[Inhibitory effect of andrographolide on angiogenesis induced by the supernatant from cultured tumor cells].

OBJECTIVE: To determine the effect of andrographolide (Andro) on angiogenesis of human umbilical vein endothelial cells (HUVECs).
 Methods: HUVECs were treated with different concentrations of Andro and the cell viability was detected with Cell Counting Kit-8 (CCK-8). HUVECs were treated with half lethal dose (IC50) of Andro. Matrigel was used to make capillary formation of HUVECs and the effect of Andro on capillary formation was evaluated by calculating the percentage of capillary formation. Moreover, the effects of Andro and the supernatant from cultured A549 tumor cells on capillary formation were evaluated by calculating the percentage of capillary formation. The effect of Andro on the expression of matrix metalloproteinase-9 (MMP-9) was determined with Western blot.
 Results: The cell viability of HUVECs decreased with the increase of Andro concentrations. IC50 was 20 µmol/L. The capillary formation of HUVECs was inhibited when treated with 20 µmol/L Andro for 24 hours. Moreover, Andro was able to antagonize the promotion of the capillary formation induced by the supernatant from cultured tumor cells. Andro could suppress the expression of MMP-9 and antagonize the capillary formation.
 Conclusion: Andro inhibits the capillary formation of HUVECs and can antagonize the promotion of angiogenesis induced by the supernatant from cultured tumor cells.

Dipalmitoylphosphatidic acid inhibits breast cancer growth by suppressing angiogenesis via inhibition of the CUX1/FGF1/HGF signalling pathway.

Tumour growth depends on a continual supply of the nutrients and oxygen, which are offered by tumour angiogenesis. Our previous study showed that dipalmitoylphosphatidic acid (DPPA), a bioactive phospholipid, inhibits the growth of triple-negative breast cancer cells. However, its direct effect on angiogenesis remains unknown. Our work showed that DPPA significantly suppressed vascular growth in the chick embryo chorioallantoic membrane (CAM) and yolk sac membrane (YSM) models. Meanwhile, tumour angiogenesis and tumour growth were inhibited by DPPA in the tumour tissues of an experimental breast cancer model, a subcutaneous xenograft mouse model and a genetically engineered spontaneous breast cancer mouse model (MMTV-PyMT). Furthermore, DPPA directly inhibited the proliferation, migration and tube formation of vascular endothelial cells. The anti-angiogenic effect of DPPA was regulated by the inhibition of Cut-like homeobox1 (CUX1), which transcriptionally inhibited fibroblast growth factor 1 (FGF1), leading to the downregulation of hepatocyte growth factor (HGF). This work first demonstrates that DPPA directly inhibits angiogenesis in cancer development. Our previous work along with this study suggest that DPPA functions as an anti-tumour therapeutic drug that inhibits angiogenesis.

Critical Care Resources in Guangdong Province of China: Three Surveys from 2005 to 2015.

OBJECTIVES: Data about the critical care resources in China remain scarce. The purpose of this study was to investigate the variation and distribution of critical care resources in Guangdong province from 2005 to 2015. DESIGN: Data in regard to critical care resources were collected through questionnaires and visits every 5 years from 2005. SETTING: All hospitals in Guangdong province were screened and hospitals that provide critical care services were enrolled. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: One hundred eleven, 158, and 284 hospitals that provide critical care services were enrolled in the three consecutive surveys respectively. The number of ICUs, ICU beds, intensivists, and nurses increased to 324, 3,956, 2,470, and 7,695, respectively, by 2015. Adjusted by population, the number of ICU beds per 100,000 (100,000) population increased by 147.7% from 2005 to 2015, and the number of intensivists and nurses per 100,000 population increased by 35.3% and 55.1% from 2011 to 2015. However, the numbers in the Pearl River Delta, a richer area, were higher than those in the non-Pearl River Delta area (ICU beds: 4.64 vs 2.58; intensivists: 2.90 vs 1.61; nurses: 9.30 vs 4.71 in 2015). In terms of staff training, only 17.85% of intensivists and 14.29% of nurses have completed a formal accredited critical care training program by 2015. CONCLUSIONS: Our study was the first one to investigate the trend and distribution of critical care resources in China. The quantity of ICU beds and staff has been increasing rapidly, but professional training for staff was inadequate. The distribution of critical care resources was unbalanced. Our study can be beneficial for healthcare policymaking and the allocation of critical care resources in Guangdong province and other provinces in China.

Exposure to Concentrated Ambient Fine Particulate Matter Induces Vascular Endothelial Dysfunction via miR-21.

Vascular endothelial permeability transition does not cause significant lesions, but enhanced permeability may contribute to the development of vascular and other diseases, including atherosclerosis, hypertension, heart failure and cancer. Therefore, elucidating the effect of Particulate Matter 2.5 (PM2.5) on vascular endothelial permeability could help prevent disease that might be caused by PM2.5. Our previous study and the present one revealed that PM2.5 significantly increased the permeability of vascular endothelial cells and disrupted the barrier function of the vascular endothelium in Sprague Dawley (SD) rats. We found that the effect occurred mainly through induction of signal transducer and activator of transcription 3 (STAT3) phosphorylation, further transcriptional regulation of microRNA21 (miR-21) and promotion of miR-21 expression. These changes post-transcriptionally repress tissue inhibitor of metalloproteinases 3 (TIMP3) and promote matrix metalloproteinases 9 (MMP9) expression. This work provides evidence that PM2.5 exerts direct inhibitory action on vascular endothelial barrier function and might give rise to a number of vascular diseases.