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Background Exostosin-1 (EXT1) is associated with the spread and metastasis of cancer cells. In this study, we investigate the prognostic value and immunological relevance of EXT1 in various cancers.Methods The expression profiles and clinical data of 33 different cancers were collected. The differences of EXT1 expression between tumor and normal tissues were analyzed using a t-test and paired t-test. Univariate Cox regression analysis was performed, and survival curves were plotted to evaluate the prognostic value of EXT1. The molecular mechanisms of EXT1 were determined, and a drug sensitivity analysis was conducted. Finally, the expression and function of EXT1 was verified in endocervical adenocarcinoma (CESC) cells.Results The Cancer Genome Atlas and Genotype-Tissue Expression databases showed that EXT1 expression was higher in CESC, cholangiocarcinoma, head and neck squamous cell carcinoma, esophageal carcinoma, kidney renal papillary cell carcinoma, liver hepatocellular carcinoma, lung squamous cell carcinoma, and stomach adenocarcinoma specimens than in normal specimens. Additionally, EXT1 expression correlated with survival time, including overall survival, disease-specific survival, disease-free interval, and progression-free interval, in multiple cancers. Functional enrichment analysis revealed that EXT1 is associated with immunity-, tumorigenesis-, and development-related pathways. Immunocorrelation analysis showed that EXT1 is related to the immune response, tumor microenvironment, and immunotherapeutic response in various cancers. Drug sensitivity analysis revealed that 152 drugs exhibited remarkably different sensitivities between the high- and low-EXT1 expression groups. Cell experiments showed that EXT1 expression was related to the proliferation, migration, and invasion of CESC tumor cells.Conclusion EXT1 is a potential target gene for immune infiltration and has prognostic value in multiple cancers; thus, it may provide new insights into cancer treatment.

The cooperation of Fe and Ce on V2O5–WO3/TiO2 improves the K and Pb resistance by promoting the redox and NOx adsorption ability.

Aim Imbalance of M1/M2 macrophages phenotype activation is a key point in diabetic kidney disease (DKD). Macrophages mainly exhibit M1 phenotype, which contributes to the inflammation and fibrosis in DKD. Studies indicate that autophagy plays an important role in M1/M2 activation. However, the mechanism of autophagy regulating macrophage M1/M2 phenotype in DKD is unknown. Thus, the aim of this study is to explore whether high glucose induced macrophage switch to M1 phenotype via down-regulating STAT-3-mediated autophagy. Methods DKD model rats were established in vivo by intraperitoneal injection of streptozocin (STZ). Rats were sacrificed at 18 weeks for histological and molecular analysis. RAW264.7 cells were cultured in vitro with 30mM glucose in the presence or absence of a STAT-3 activator (Colivelin) and an autophagy activator (Rapamycin). Meanwhile, M1 and M2 macrophage activation models were established as a control group. Immunofluorescence and Western Blot were used to detect the expression of autophagy-related proteins (LC3, Beclin-1), M1 markers (iNOS, TNF-α), and M2 markers (MR, Arg-1). Results In DKD, macrophages exhibited an M1 phenotype and showed less autophagy. Under high glucose conditions, RAW264.7 macrophages switched to the M1 phenotype. Autophagy was downregulated in high glucose induced M1 macrophages. Both the STAT-3 activator and the autophagy activator promoted the transition of glucose-induced M1 macrophages to M2 macrophages. Meanwhile, STAT-3 activation increased the expression of autophagy makers (LC3 and Beclin-1). However, autophagy activator had no effect on STAT-3 phosphorylation. Conclusion High glucose promotes macrophage switching to M1 phenotype via down-regulating STAT-3-mediated autophagy.

Nanozymes are commonly used in the construction of immunosensors, yet they are generally susceptible to pH condition, which greatly hindered their practical use. To break the limitation of pH conditions, polyethyleneimine-coated Prussian blue nanocubes (PBNCs@PEI) were synthesized as the pH-switchable nanozyme, which can show peroxidase-like and catalase-like activity in acidic and alkaline condition, respectively. Besides, the modification of PEI can largely improve the catalytic activity of PBNCs. Herein, the pH-switchable catalytic property of PBNCs@PEI was used to construct the dual-mode immunosensor for the detection of illegal additive, rosiglitazone. In acidic condition, PBNCs@PEI showed excellent peroxidase-like activity, which can trigger the colorimetric reaction of Au nanostars with TMB

Accumulation of amyloid-β (Aβ) in the brain is a central component of pathology in Alzheimer’s disease. A growing volume of evidence demonstrates close associations between periodontal pathogens including Porphyromonas gingivalis (P. gingivalis) and Treponema denticola (T. denticola) and AD. However, the effect and mechanisms of T. denticola on accumulation of Aβ remain to be unclear. In this study, we demonstrated that T. denticola was able to enter the brain and act directly on nerve cells resulting in intra- and extracellular Aβ1–40 and Aβ1–42 accumulation in the hippocampus of C57BL/6 mice by selectively activating both β-secretase and γ-secretase. Furthermore, both KMI1303, an inhibitor of β-secretase, as well as DAPT, an inhibitor of γ- secretase, were found to be able to inhibit the effect of T. denticola on Aβ accumulation in N2a neuronal cells. Overall, it is concluded that T. denticola increases the expression of Aβ1–42 and Aβ1–40 by its regulation on beta-site amyloid precursor protein cleaving enzyme-1 and presenilin 1.

Calciphylaxis, a rare disease mainly seen in patients with chronic kidney disease, is characterised by ischaemic skin damages and excruciating pain. Calciphylaxis has poor prognosis which often results in amputation and high mortality. Although guidelines for the management of calciphylaxis are not available, sodium thiosulfate has showed efficacy in many clinical reports. We report the case of a 64-year-old advanced calciphylaxis male patient who had two amputations due to intolerable pain manifested as deteriorating ulcer. After he was treated with intravenous sodium thiosulfate (STS), his pain was significantly relieved with a healing trend of the big wound. One more amputation for the remission of intractable pain was avoided. The treatment experience indicates that sodium thiosulfate is of great value in quick pain relief and reducing suffering of calciphylaxis patients. Keywords: Calciphylaxis, Calcific uremic arteriolopathy, Painful skin ulcer, Maintenance haemodialysis, Continuous....

Ovarian cancer is the deadliest among all the gynecologic malignancies, and it is also a kind of highly metastatic disease. Transforming growth factor-β1 (TGF-β1) is a dominant driver of epithelial-mesenchymal transformation (EMT) and promotes the metastasis of tumor cells and therapy resistance. Tumor necrosis factor-α-induced protein 8 (TNFAIP8)-like 2 (TIPE2) is a negative regulator of innate and adaptive immunity. It also involves the occurrence and development of different tumors. However, the roles of TIPE2 in ovarian cancer and whether TIPE2 reverses TGF-β1-induced EMT in ovarian cancer cells remain unclear. The present study demonstrated that TIPE2 protein was significantly down-regulated in ovarian cancer tissues and related to tumor pathological types, patients’age, tumor differentiation degree, and FIGO stage of tumor. TIPE2 inhibited the metastasis and EMT of ovarian cancer cells by combining with Smad2 in vitro and intraperitoneal metastasis model and reversed TGF-β1-induced migration, invasion of ovarian cancer cells by targeting the Smad2-EMT signaling pathway. Moreover, we found that TIPE2 decreased the expression of TGF-β1 and TGF-β1 down-regulated the levels of TIPE2 in ovarian cancer cells. There is a negative relationship between TIPE2 and TGF-β1. In summary, our results suggest TIPE2 plays an important inhibitory role in the metastasis of ovarian cancer by affecting TGF-β1/Smad2/EMT signal pathway and acts as a potential target in the diagnosis and treatment of ovarian cancer.

Programmed cell death 4 (PDCD4) is regarded as an important tumor suppressor that is lowly expressed or deleted in numerous human types of cancer, including ovarian and endometrial cancer. Tripartite motif‑containing 27 (TRIM27) is closely related to the occurrence and development of tumors and is highly expressed in numerous types of cancer such as ovarian and endometrial cancer. PDCD4 can be degraded through ubiquitination, while TRIM27 has the E3 ubiquitin ligase activity. However, whether TRIM27 may regulate the expression of PDCD4 by ubiquitination effect remains unclear. In the present study, the expression of PDCD4 and TRIM27 in different ovarian and endometrial cancer cell lines was detected by reverse transcription‑quantitative PCR (RT‑qPCR), western blotting and immunocytochemistry. The impact of TRIM27 overexpression and knockdown on PDCD4 expression and the effective mechanism of TRIM27 regulating PDCD4 expression were also investigated

BACKGROUND AND AIMS Warfarin is a common anticoagulant drug. How to effectively reduce vascular calcification induced by warfarin while ensuring its anticoagulant effect is an urgent problem to be solved. Previous studies have found that warfarin enhances the expression and activity of transglutaminase 2 (TG2) in vascular smooth muscle cells (VSMCs), which mediates communication between cells and extracellular matrix (ECM). Matrix vesicles (MVs) are the center of hydroxyapatite crystal precipitation, which is released to ECM and interacts with ECM protein to initiate mineralization and form calcification core. This study observed the role of the warfarin-TG2-MVs axis in vascular calcification by culturing VSMCs in vitro. METHOD VSMCs were cultured in normal or osteogenic medium (OM) and stimulated with 10 μm warfarin for 3–14 days. The expressions of SM22α, Runx2, ALP, OPN and OPG were detected by RT-PCR and western blot. Alizarin red and von Kossa staining were performed to evaluate calcification, and calcium content was determined. Meanwhile, the expression and activity of TG2 were detected. Differential centrifugation was used to extract MVs and evaluate their release. Type I collagen was coated in the culture dish to determine the calcification of MV-collagen. RESULTS Warfarin stimulation promoted transdifferentiation of VSMCs, and the expression of osteogenic factors Runx2, ALPL and OPN were increased, while the expression of SM22α and calcification inhibitor OPG were decreased. When using OM, the above trend was more obvious. Alizarin red and von Kossa staining were performed when the cells were cultured for 14 days. The results of calcium staining in the warfarin intervention group were all positive. Warfarin promoted the expression and activity of TG2, and it gradually increased with the extension of the intervention time. The same number of cells were cultured for 7 days under different stimuli, and the medium was changed every other day. Then, the supernatant was collected for differential centrifugation. The amount of MVs produced by the warfarin and OM groups was significantly higher than that of other groups, and the ability to mineralize of MVs in type I collagen was increased. CONCLUSION Warfarin increased the expression and activity of TG2, promoted the release of MVs from VSMCs, and further cross-linked ECM to aggravate vascular calcification.

Calciphylaxis, also known as calcific uremic arteriolopathy (CUA), is typically characterized by subcutaneous tissue calcification and excruciatingly painful cutaneous lesions with high mortality. It is critical for dermatologists to make early diagnosis and appropriate management, yet currently only 56% of calciphylaxis cases are correctly diagnosed by conventional histological stain1. Specially, the identification of subtle calcium deposits of subcutaneous can be challenging but is believed crucial for early diagnosis of calciphylaxis2. More sensitive calcification staining is in high demand. In this study, Fluo-3 AM was found to be a rapid, sensitive and reliable fluorescent probe for the detection of calcium deposits and could be a promising diagnostic tool for calciphylaxis.

BACKGROUND Varicose veins are common clinical entities. Foam sclerotherapy is a minimally invasive and simple procedure; however, the side effects, efficacy, and stability of sclerosing foam are not ideal. OBJECTIVE To summarize the current studies on sclerosing foam stability and promote foam sclerotherapy development. MATERIALS AND METHODS We reviewed the literature before June 2018 and included only representatives studies on sclerosing foam stability. We summarized the foam half-life time (FHT) of polidocanol (POL) under 17 preparation conditions and the FHT of sodium tetradecyl sulfate under 21 preparation conditions. The preparation conditions included various combinations of temperature, liquid-gas ratio, preparation method, etc. RESULTS: The FHT of POL varied between 40 and 4,000 seconds under different conditions. The FHT of sodium tetradecyl sulfate varied from 25.7 to 390 seconds. The higher the drug concentration, the lower the temperature required to increase foam stability. The addition of surfactant greatly increased foam stability. For different gas compositions, the FHT sequence was as follows: CO2 < CO2 + O2 < O2 < air. CONCLUSION Foam stability can be improved by changing the preparation conditions; therefore, the role of surfactants and predictive methods for FHT are worth investigating further.

Objective: Macrophage infiltration in kidney is a major pathological feature of diabetic nephropathy (DN), which has been demonstrated associate with macrophages autophagy homeostasis. However, the relationships between autophagy and the infiltration response related of macrophages adhesion and migration are unknown. This study aims to investigate the impact of macrophages adhesion and migration by modulating autophagy. Methods: In vivo, rats were randomly distributed into control (NC) and DN groups. The pathological changes in renal tissue were assessed, and expression of CD68, LC3, P62 were analyzed. In vitro, RAW264.7 cells were divided into NC and high glucose (HG) groups. The capacity of macrophages adhesion migration and the expression of autophagy markers were observed with and without autophagy modulators (rapamycin, 3-methyladenine, chloroquine, and bafilomycin A1 for RAPA, 3-MA, CQ, BAFA). The macrophages autophagosome and the process of degradation and fusion of autophagosome-lysosome were observed by electron microscopy. Results: In vivo, renal injury is aggravated in diabetic rat compared with NC group. The autophagy level is inhibited in renal tissues of DN group with the increasing expression of CD68 and P62, while expression level of LC3 decreased (p

Study question To describe lipidomic characteristics of offspring born to polycystic ovary syndrome (PCOS-off) women and assess the associations of clinical phenotypes changes with differential lipids. Summary answer PCOS-off showed specific changes in lipidomics and some differential lipids (e.g., phosphatidylcholines, lysophosphatidylcholine and sphingomyelin) may be the potential markers of aberrant cardiometabolic health. What is known already Polycystic ovary syndrome (PCOS), the most prevalent endocrine disorder characterized by ovulatory dysfunction, hyperandrogenism and polycystic ovarian morphology, affects about 8–13% of women of fertile age. Aberrant metabolic pathophysiological changes and increased pregnancy complications associated with PCOS predispose PCOS patients to have suboptimal intrauterine environments and that may produce a detrimental impact on the cardiometabolic health of their children. Study design, size, duration A total of 141 blood plasma samples from 70 children born to PCOS women (43 girls, 27 boys) and 71 healthy control children (44 girls, 27 boys) were obtained for lipidomics. Participants/materials, setting, methods Blood samples were centrifuged at 2000 rpm, 4 °C for 20 min, and the upper plasma was collected and used for lipid extraction. Then the waters ACQUITY UPLC I-Class system and The Xevo G2-S Q-TOF with an electrospray ionization (ESI) source (Waters, Manchester, UK) was used for chromatographic analysis and mass spectrometry analysis separately. Main results and the role of chance In total, 44 metabolites were found to be significantly altered in PCOS-off, including 8 up-regulated and 36 down-regulated metabolites. After stratified by sex, 44 metabolites were found to express differently in girls born to PCOS women (PCOS-g). 13 metabolites were up-regulated, and 31 metabolites were down-regulated, most of which belong to glycerolipids species. While 46 metabolites were found to express differently in boys born to PCOS women (PCOS-b) with 9 increased metabolites and 35 decreased ones, most of which were glycerophospholipids metabolites. Additionally, significant associations between metabolites changes and weight Z-score as well as high density lipoprotein level were found in PCOS-off. In PCOS-g, triglyceride, low density lipoprotein and high density lipoprotein level were found to be correlated with some metabolites, whereas in PCOS-b, thyroid stimulating hormone and high density lipoprotein were correlated with some lipids. Limitations, reasons for caution Other species of metabolites except lipids are not included in this study. Besides, some potential confounding maternal factors, such as smoking, drinking, breastfeeding etc. were not included due to the lack of data. Wider implications of the findings: The results had broadened our understanding of PCOS-off’s cardiometabolic status and emphasized monitor and special management in this susceptible group of population. Trial registration number Not applicable

Background and Aims Patients with chronic kidney disease (CKD) have a predisposition to develop vascular calcification due to dysregulated homeostatic mechanisms. Macrophages can promote vascular calcification by releasing diverse extracellular vehicles including the newly found migrasomes (M-mig). Our previous research had found that M-mig provide nucleating foci for calcific mineral formation and initiating bone mineralization process. However, the specific mechanism by which M-mig influence the formation of vascular calcification remains incompletely understood. Method To study calcifying M-mig, we exposed M-mig to high Ca/P (Ca/P=3 mmol/L calcium/2 mmol/L phosphate) and/or with LPS for 1, 3, 5,7 days. The expression of M-mig surface integrin α5β1 was determined by fluorescence staining. To block the M-mig-integrin α5β1 mediated calcification, we modulated the expression of integrin α5 using siRNAs to produce M-migintegrin α5- or using 20 nM ATN-161 (small peptide antagonist of integrin α5β1) or integrin α5 antibody under high Ca/P stimulation. The stray mice artery co-cultivate with M-mig integrin α5- under high level Ca/P. Then the calcifying M-mig were assessed by TEM, Fluo-3 staining and calcium content assay. Results We discovered that Ca/P-stimulated macrophages released M-mig capable of mineralization. Amorphous calcium phosphate mineral deposit the surface or internal of M-mig. The M-mig exhibited increased Ca/P mineral content, implying aggregate larger calcifying M-mig that develop over time. Significantly, following a 7 days incubation with high level Ca/P, fiber tube and vesicle structure of M-mig showed rupture or fragmentation and the expression of M-mig surface integrin α5β1 increased. Pre-treatment with integrin α5β1 antagonist or block by integrin α5 antibody significantly reduced the calcifying M-mig formation. Further investigation showed that M-mig induced stray mice artery microcalcification while M-migintegrin α5- exhibited a reduce microcalcification. Conclusion Our finding revealed an association between microcalcification and integrin α5β1 signalling in the fiber tube and vesicle structure of M-mig and provide a new insight into vascular calcification in CKD.

Introduction Calciphylaxis is a rare but potentially fatal disease commonly occurred in dialysis patients. Despite some previous studies on risk factors for calciphylaxis, there is still a lack of data from Chinese population. Methods The retrospective matched case–control study about calciphylaxis was performed in Zhongda Hospital affiliated to Southeast University. The case group involved 20 hemodialysis patients who were newly diagnosed with calciphylaxis from October 2017 to December 2018. The 40 noncalciphylaxis patients undergoing dialysis with the same age and duration of dialysis were randomly selected as controls. Results Most of calciphylaxis patients were male and elderly, while overweight people were more susceptible to the disease. Although incidence of secondary hyperparathyroidism was higher in calciphylaxis patients, the differences in duration of elevated serum intact parathyroid hormone (iPTH) and its highest value did not reach statistical significance compared with controls. No significant difference in warfarin therapy was discernible between two groups. The univariate regression analysis indicated that male, score of use of activated vitamin D and its analogues, corrected serum calcium level, serum phosphate, Ca × P product, iPTH, albumin, and alkaline phosphatase (ALP) level were significantly associated with calciphylaxis. Elevated levels of serum phosphate (OR 4.584, p = 0.027) and ALP (OR 1.179, p = 0.036), decreased level of serum albumin (OR 1.330, p = 0.013) were independent risk factors after multivariate analysis. Conclusion This is the first report of risk factors associated with calciphylaxis in China. Increased levels of serum phosphate and ALP, decreased level of serum albumin were vital high-risk factors for calciphylaxis in Chinese hemodialysis population.

Accumulation of amyloid-β (Aβ) in the brain is a central component of pathology in Alzheimer’s disease. A growing number of evidences demonstrate close associations between periodontal pathogens including Porphyromonas gingivalis (P. gingivalis) and Treponema denticola (T. denticola) and AD. However, the effect and mechanisms of T. denticola on accumulation of Aβ remain to be unclear. In this study, we demonstrated that T. denticola was able to enter brain and act directly on nerve cells resulting in intra and extracellular Aβ1−40 and Aβ1−42 accumulation in the hippocampus of C57BL/6 mice by selectively activating both β-secretase and γ-secretase. Furthermore, both KMI1303, an inhibitor of β- secretase, as well as DAPT, an inhibitor of γ- secretase were found to be able to inhibit the effect of T. denticola on Aβ accumulation in N2a neuronal cells. Overall, it is concluded that T. denticola increases the expression of Aβ1−42 and Aβ1−40 by its regulation on beta-site amyloid precursor protein cleaving enzyme-1 and Presenilin 1.

Accumulation of amyloid-β (Aβ) in the brain is a central component of pathology in Alzheimer's disease. A growing volume of evidence demonstrates close associations between periodontal pathogens including Porphyromonas gingivalis (P. gingivalis) and Treponema denticola (T. denticola) and AD. However, the effect and mechanisms of T. denticola on accumulation of Aβ remain to be unclear. In this study, we demonstrated that T. denticola was able to enter the brain and act directly on nerve cells resulting in intra- and extracellular Aβ

Background and Aims Calciphylaxis (CUA) is a rare but potentially fatal disease that is commonly occurred in dialysis patients. Since there is no data based on Chinese population, the study is aimed to investigate risk factors of CUA in Chinese hemodialysis patients. Method We retrospectively evaluated medical records of 20 hemodialysis patients who were newly diagnosed with CUA by skin biopsy admitted to Zhongda Hospital Southeast University from Oct.2017 to Dec.2018. Non-CUA dialysis patients with the same age and duration of dialysis were randomly selected as controls (Ratio=1:2). Results Most of CUA patients were male (80%) and elderly (55%), while 50% had a body mass index higher than 24. The mean time interval since start of dialysis to CUA diagnosis was 114.65±81.32 months, and the median time from appearance of skin lesion to diagnosis was 6 (2, 15) months. The incidence of hyperparathyroidism was higher in patients with CUA (80% vs 62.5%), but the differences of duration of elevated serum intact parathyroid hormone (iPTH) and its highest value were not significant compared with the controls. Warfarin therapy had no significant difference between two groups (15% vs 5%). Univariate logistic regression analysis indicated that male (OR 3.619, 95%CI 1.027-12.748), each 1 point increase in score of use of vitamin D and its analogues (OR 1.505, 1.029-2.201), each 1 mmol/L increase in corrected serum calcium level (OR 24.486, 1.570-381.873), each 1 mmol/L increase in serum phosphate level (OR 5.382, 1.767-16.389), each 1 pg/mL increase in iPTH level (OR 1.002, 1.000-1.003), each 1 g/L decline in serum albumin level (OR 1.181, 1.041-1.340), each 1 IU/L increase in serum alkaline phosphatase (ALP) level (OR 1.005, 1.000-1.009) and each 1 mg/L increase in hypersensitive c-reactive protein level (OR 1.029, 1.000-1.059) were significantly associated with CUA. Serum phosphate, albumin and ALP were still significant risk factors after multivariate analysis. Conclusion This is the first report of risk factors of CUA based on Chinese population. The results show that high levels of serum phosphate and ALP, low level of serum albumin are independent risk factors of CUA in Chinese hemodialysis patients. Unlike previous research from western countries, warfarin therapy didn’t show an increased risk in this study, propably because of the low exposure rate of it in China.

Background and Aims Vascular calcification is an independent risk factor for all-cause mortality in patients with CKD. Macrophages play an important role in vascular calcification, which involve in the osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs). Recent research shows SGK1 is a highly attractive candidate for developing VSMCs calcification. Previous studies indicated that TGFβ1 induces vascular calcification by regulating osteo-/chondrogenic transdifferentiation of VSMCs. This study focus on the effects of macrophages-derived SGK1 on VSMCs transdifferentiation via regulating TGFβ1 expression. Method Before induced into M2 phenotype with IL-4, RAW 264.7 cells were treated with SGK1 inhibitor EMD638683 for 24 hours to reduce SGK1 expression. The above cells were grouped as: M0, M2, M2+EMD to explore the expression of SGK1 and TGFβ1 by using western blot, qRT-PCR and immunofluorescence staining, respectively. The culture medium (CM) of the above group macrophages was collected. Then mouse aortic smooth muscle cells (MAoSMCs ) were cultured in these supernatants with normal medium or osteogenic medium (OM) with or without TGFβ1 receptor inhibitor SB-431542 for 3 weeks to explore the transdifferentiation and calcification of MOVAS by using western blot, RT-qPCR, immunofluorescence staining, calcium quantification, Alizarin Red and Von Kossa Staining. Results As Alizarin Red and Von Kossa Staining shown, MAoSMCs contained more calcium deposits in the M2-CM group compared with either in the group of NC nor M0-CM. Consistent with the above results, We also found that M2-CM promoted MAoSMCs transdifferentiation, which was characterized by markedly increase of expression of osteo-/chondrogenic markers (Runx2, ALPL, FGF23) and decrease of the MAoSMCs marker (SM22α). Exploring the mechanism of the above phenomenon we found the expression of SGK1 and TGFβ1 were significantly increased in M2 group compared with M0 group. Interestingly, both SGK1 inhibitor EMD638683 which reduced TGFβ1 expression in M2 and TGFβ1 receptor inhibitor SB-431542 could partially blocked MAoSMCs osteo-/chondrogenic transdifferentiation and calcification. Furthermore, recombinant mouse TGFβ1 Protein increased calcium content in MAoSMCs by using calcium quantification, Alizarin Red and Von Kossa Staining and promoted MAoSMCs osteo-/chondrogenic transdifferentiation, which was characterized by markedly increase of expression of osteo-/chondrogenic markers (Runx2, ALPL, FGF23) and decrease of the MAoSMCs marker (SM22α). Conclusion Our findings shed light M2 macrophages promotes MAoSMCs osteo-/chondrogenic transdifferentiation and calcification by up-regulating TGFβ1 expression.

Whether and how context plays a role in metaphor processing remains a controversial issue. One major theory on metaphor comprehension, the graded salience hypothesis (GSH) model, emphasizes salience as the key factor determining the precedence of semantic access. Using event-related potential technique, the present study examined Chinese metaphors to investigate whether the salient meaning is always processed first regardless of context. The experiment employed a Prime-Target-Probe paradigm. Three-character Chinese verb–object metaphors were used as the Target proceeded by one of the three contexts (the Prime): (1) metaphorical context priming the Target’s metaphorical meaning, (2) literal context priming the Target’s literal meaning, and (3) irrelevant context as the control condition. The Target was then followed by the Probe, which was always related to the Target (except in the filler condition). Forty participants were asked to judge whether the Target and the following Probe were semantically related. The N400 elicited by the Target showed no contextual effect. The N400 amplitude elicited by the Probe was smaller in the metaphorical priming condition compared with the literal priming condition, while the N400 in the irrelevant control condition was between the other two conditions, demonstrating a clear context effect. In addition, an unexpected P240 component also showed the similar graded pattern. Our results mostly support the GSH model, indicating that the salient meaning invariantly gets activated first before the activation of the nonsalient meaning at the lexical access stage. However, context does play a role in a parallel way either facilitating or suppressing this interpretation in the latter meaning integration stage.