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Understanding how the tumor microenvironment is shaped by various factors is important for the development of new therapeutic strategies. Tumor cells often undergo spontaneous apoptotic cell death in tumor microenvironment, these apoptotic cells are histologically co-localized with immunosuppressive macrophages. However, the mechanism by which tumor cell apoptosis modulates macrophage polarization is not fully understood. In this study, we aimed to explore the tumor promoting effects of apoptotic tumor cells and the signal pathways involved.Apoptotic cells and macrophages in tumors were detected by immunohistochemical staining. Morphological analysis was performed with Giemsa staining. Lipids generated from apoptotic cells were detected by liquid chromatography-mass spectrometry. Phosphatidylserine-containing liposomes were prepared to mimic apoptotic cells. The expression of protein was determined by real-time PCR, immunohistochemistry enzyme-linked immunosorbent assay and Western blotting. Mouse malignant ascites and subcutaneous tumor models were designed for in vivo analysis. Transgenic mice with specific genes knocked out and inhibitors specific to certain proteins were used for the mechanistic studies.The location and the number of apoptotic cells were correlated with that of macrophages in several types of carcinomas. Phosphatidylserine, a lipid molecule generated in apoptotic cells, induced polarization and accumulation of M2-like macrophages in vivo and in vitro. Moreover, sustained administration of phosphoserine promoted tumor growth in the malignant ascites and subcutaneous tumor models. Further analyses suggested that phosphoserine induced a M2-like phenotype in macrophages, which was related to the activation of phosphoserine receptors including T-cell immunoglobin mucin 4 (TIM4) and the FAK-SRC-STAT3 signaling pathway as well as elevated the expression of the histone demethylase Jumonji domain-containing protein 3 (JMJD3). Administration of specific inhibitors of these pathways could reduce tumor progression.This study suggest that apoptotic cell-generated phosphoserine might be a notable signal for immunosuppressive macrophages in tumors, and the related pathways might be potential therapeutic targets for cancer therapy.

Mei Liu,1,2 Rui-Bo Wang,1 Jian-Hong Xing,2 Ying-Xue Tang3 1Chinese Medicine College, Shandong University of Traditional Chinese Medicine, Jinan, 250355, Shandong, People’s Republic of China; 2Department of Obstetrics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, Shandong, People’s Republic of China; 3Postgraduate Department, Shandong University of Traditional Chinese Medicine, Jinan, 250355, ShandongCorrespondence: Ying-Xue TangPostgraduate Department, Shandong University of Traditional Chinese Medicine, Changqing Campus of Shandong University of Traditional Chinese Medicine, Jinan, 250355, Shandong, People’s Republic of ChinaTel +8653189628067Email doctortyx@163.comBackground: Preeclampsia (PE), a serious pregnancy disorder, is responsible for maternal and fetal mortality worldwide. At present, numerous candidate biomarkers have been studied to predict PE.Objective: To explore the role of Corin in PE risk prediction and then evaluate the predictive ability of soluble vascular endothelial growth factor receptor-1 (sFlt-1), placenta growth factor (PLGF), and sFlt-1/PLGF after the addition of Corin.Methods: A total of 135 pregnant women from Affiliated Hospital of Shandong University of Traditional Chinese Medicine participated in this study in their first trimester. A nested case–control study was conducted and all subjects were divided into PE groups (n=46) and controls (n=89). The levels of PLGF, sFlt-1, sFlt-1/PLGF ratio, and Corin of the two groups at 12– 16 weeks of gestation were measured and analyzed. Receiver operating characteristic (ROC) curve, net reclassification index (NRI) and integrated discrimination index (IDI) were calculated to evaluate the predictive ability of various biomarkers.Results: The concentrations of sFlt-1, sFlt-1/PLGF, and Corin in PE group were significantly higher than that in controls, while the concentration of PLGF in the PE group was lower. The area under curve (AUC) of sFlt-1, PLGF and sFlt-1/PLGF for predicting PE was 0.786, 0.719 and 0.866, respectively. Combined with Corin, the prediction ability of the above biomarkers could be improved to 0.876, 0.847, and 0.897, respectively. Corin in combination with sFlt-1/PLGF resulted in improvements with 12.6% being reclassified and a resulting NRI of 0.142 (0.020∼ 0.263) and IDI of 0.087 (0.037∼ 0.137).Conclusion: The addition of Corin to sFlt-1, PLGF and sFlt-1/PLGF can improve the ability of each marker to predict PE risk. Corin in combination with sFlt-1/PLGF can be used as ideal markers to identify the pregnant women who subsequently develop PE, which will help in risk stratification and better therapeutic management.Keywords: preeclampsia, Corin, soluble vascular endothelial growth factor receptor-1, placental growth factor, prediction

Background Preeclampsia (PE) is a severe hypertension-related disorder occurring during pregnancy that leads to significant mortality and morbidity in both the foetus and mother. Atractylenolide (ATL), a traditional Chinese natural agent isolated from the herb Atractylodes macrocephala, exhibits a series of pharmacological activities, including anti-oxidative stress and anti-inflammatory effects. Purpose The impacts of ATL on apoptosis and oxidative stress in HTR-8/SVneo cells during PE development was investigated. Study design We identified ATL by an overlap analysis of the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database using the keyword ‘gestational hypertension’ and Traditional Chinese Medicine (Batman-TCM) database using the keyword ‘Atractylodes macrocephala’. Methods Cell viability, proliferation, and migration were detected by CCK-8, EdU, and transwell assays. Flow cytometry and 2′,7′-dichlorodihydrofluorescein diacetate were used to assess apoptosis and reactive oxygen species (ROS) levels. Results EdU and CCK-8 assays demonstrated that ATL significantly enhanced the viability of HTR-8/SVneo cells. Transwell assays showed that ATL remarkably induced the migration of HTR-8/SVneo cells. Moreover, ROS production in HTR-8/SVneo cells was induced by H2O2, whilst ATL alleviated this H2O2-induced ROS production and apoptosis in cells. Conclusion ATL attenuated apoptosis and oxidative stress in HTR-8/SVneo cells in PE by activating the MAPK/ERK signalling pathway. ATL has potential to be utilized as a potential therapeutic candidate for PE.

Frequent droughts in a warming climate tend to induce the degeneration of vegetation. Quantifying the response of vegetation to variations in drought events is therefore crucial for evaluating the potential impacts of climate change on ecosystems. In this study, the standardized precipitation index (SPI) was calculated using the precipitation data sourced from the China Meteorological Forcing Dataset (CMFD), and then the drought events in southern Tibet from 1982 to 2015 were identified based on the SPI index. The results showed that the frequency, severity, and intensity of drought events in southern Tibet decreased from 1982 to 2015, and the highest frequency of drought was found between 1993 and 2000. To evaluate the impact of drought events on vegetation, the vegetation characteristic indexes were developed based on the normalized difference vegetation index (NDVI) and the drought characteristics. The assessment of two drought events showed that the alpine grasslands and alpine meadows had high vegetation vulnerability (AI). The assessment of multiple drought events showed that responses of vegetation to drought were spatially heterogeneous, and the total explain rate of environmental factors to the variations in AI accounted for 40%. Among the many environmental factors investigated, the AI were higher at middle altitudes (2000–3000 m) than low altitudes (

The numerical simulation method was adopted to analyze the effect on boundary layer thickness reduction of various vortex generator parameters. Results show that vortex generators are capable of reducing boundary layer thickness for about 66 percent, and the influence on centerline Mach number distributions is neglectable. Practicable vortex generators for 2.4m transonic wind tunnel half-model test section side wall are founded. Research results can be used for further applications of vortex generator in wind tunnel tests.

For utilization of CO contained in tail gases of coal chemical industry, adsorption purification of HCN in closed carbide furnace tail gas was investigated on an activated carbon was modified with KOH (AC1) and the other activated carbon was modified with NaOH and sulfonated cobalt phthalocyanine (AC2). The experiment results show that two kinds of modified activated carbons are proved to be effective adsorbents for HCN removal, but the HCN adsorption capacity for AC2 is 1.47 times that for AC1. For AC2 adsorbent, the purification efficiency increased with the increase of oxygen content and adsorption temperature. The results show that, 1.5% for optimum oxygen content and 90°C for optimum adsorption temperature. The specific surface and the pore structure properties of AC2 adsorbent before and after HCN adsorption were tested by N2 adsorption experiments. The N2 adsorption tests show that, the predominant adsorption of HCN occurs in the micropores in radius 7.4～16.6 Å. Deactivated AC2 adsorbent could be restored to the original activated state, even after several regenerations.

A high-performance liquid chromatographic (HPLC) method was developed for simultaneous determination of chlorogenic acid, scutellarin, 3,5-dicaffeoylquinic acid, 4,5-dicaffeoylquinic acid in different parts of Erigerontis Herba.The four constituents were measured on an Agilent Zorbax SB-C18 column (4.6 mm x 450 mm, 5 microm) with a gradient elution of acetonitrile (A) -0.3% phosphoric acid solution (B) (0-10 min, 12%-15% A, 10-32 min, 15% A, 32-33 min, 15%-20% A, 33-50 min, 20%-22% A) at wavelength of 335 nm and 327 nm, and a flow rate of 1.0 mL x min(-1) and the column temperature was 30 degrees C.Linearity of each standard was established in the concentration range of 0.050 1-1.002 microg for chlorogenic acid, 0.165 9-3.318 microg for chlorogenic acid, 0.049 7-0.994 microg for 3,5-dicaffeoylquinic acid, 0.048 7-0.974 p.g for 4,5-dicaffeoylquinic acid respectively, with correlation coefficient r0.999 6. Average recoveries (n = 6) of 4 compounds were 98.53% with a RSD of 0.94%, 99.68% with a RSD of 0.49%, 98.78% with a RSD of 1.1%, 99.06% with a RSD of 0.81%, respectively.The developed method is simple, accurate, and precise, it can be used for the quantitative analysis of Erigeron breviscapus.

Benzo[a]pyrene (B[a]P), a ubiquitous environmental pollutant, is a potent procarcinogen and mutagen that can elicit tumors, leading to malignancy. Heat shock proteins (Hsp) have been shown to protect cells against damages caused by various stresses including exposure to numerous chemicals. Whether Hsps, or more specifically Hsp70, are involved in repair of B[a]P-induced DNA damage is currently unknown.We assessed the potential role of the inducible form of Hsp70 in B[a]P-induced DNA damage of human embryonic lung (HEL) cells using immunoblot and the comet assay (i.e., the single cell gel electrophoresis assay).Exposure to B[a]P induced a dose-dependent decrease in the level of Hsp70, but a dose-dependent +-increase in DNA damage both in untreated (control) HEL cells and in cells preconditioned by a heat treatment. Heat preconditioning prior to B[a]P exposure potentiated the effect of B[a]P at a low dose (10 micromol/L), but appeared to be protective at higher doses. There was a negative correlation between Hsp70 level and DNA damage in the non-preheated as well as in the preconditioned cells.These data suggest that exposure of HEL cells to B[a]P may induce a dose-dependent reduction in the levels of the inducible Hsp70. The detailed mechanisms for the reduction of Hsp70 levels by B[a]P and the role of Hsp70 in DNA damage under different concentrations of B[a]P remains to be determined.