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Background: Myocardial infarction (MI) elicits cardiac fibroblast activation and extracellular matrix (ECM) deposition to maintain the structural integrity of the heart. Recent studies demonstrate that Fap (fibroblast activation protein)—a prolyl-specific serine protease—is an important marker of activated cardiac fibroblasts after MI. Methods: Left ventricle and plasma samples from patients and healthy donors were used to analyze the expression level of FAP and its prognostic value. Echocardiography and histological analysis of heart sections were used to analyze cardiac functions, scar formation, ECM deposition and angiogenesis after MI. RNA-Sequencing, biochemical analysis, cardiac fibroblasts (CFs) and endothelial cells co-culture were used to reveal the molecular and cellular mechanisms by which Fap regulates angiogenesis. Results: We found that Fap is upregulated in patient cardiac fibroblasts after cardiac injuries, while plasma Fap is downregulated and functions as a prognostic marker for cardiac repair. Genetic or pharmacological inhibition of Fap in mice significantly improved cardiac function after MI. Histological and transcriptomic analyses showed that Fap inhibition leads to increased angiogenesis in the peri-infarct zone, which promotes ECM deposition and alignment by cardiac fibroblasts and prevents their overactivation, thereby limiting scar expansion. Mechanistically, we found that BNP (brain natriuretic peptide) is a novel substrate of Fap that mediates postischemic angiogenesis. Fap degrades BNP to inhibit vascular endothelial cell migration and tube formation. Pharmacological inhibition of Fap in Nppb (encoding pre-proBNP) or Npr1 (encoding the BNP receptor)-deficient mice showed no cardioprotective effects, suggesting that BNP is a physiological substrate of Fap. Conclusions: This study identifies Fap as a negative regulator of cardiac repair and a potential drug target to treat MI. Inhibition of Fap stabilizes BNP to promote angiogenesis and cardiac repair.

Skeletal stem cells (SSCs) were originally discovered in the bone marrow stroma. They are capable of self-renewal and multilineage differentiation into osteoblasts, chondrocytes, adipocytes, and stromal cells. Importantly, these bone marrow SSCs localize in the perivascular region and highly express hematopoietic growth factors to create the hematopoietic stem cell (HSC) niche. Thus, bone marrow SSCs play pivotal roles in orchestrating osteogenesis and hematopoiesis. Besides the bone marrow, recent studies have uncovered diverse SSC populations in the growth plate, perichondrium, periosteum, and calvarial suture at different developmental stages, which exhibit distinct differentiation potential under homeostatic and stress conditions. Therefore, the current consensus is that a panel of region-specific SSCs collaborate to regulate skeletal development, maintenance, and regeneration. Here, we will summarize recent advances of SSCs in long bones and calvaria, with a special emphasis on the evolving concept and methodology in the field. We will also look into the future of this fascinating research area that may ultimately lead to effective treatment of skeletal disorders.

Insulin-like growth factor I (IGF-1) is a key regulator of tissue growth and development in response to growth hormone stimulation. In the skeletal system, IGF-1 derived from osteoblasts and chondrocytes are essential for normal bone development; however, whether bone marrow (BM)-resident cells provide distinct sources of IGF-1 in the adult skeleton remains elusive. Here, we show that BM stromal cells (BMSCs) and megakaryocytes/platelets (MKs/PLTs) express the highest levels of IGF-1 in adult long bones. Deletion of Igf1 from BMSCs by Lepr-Cre leads to decreased bone formation, impaired bone regeneration, and increased BM adipogenesis. Importantly, reduction of BMSC-derived IGF-1 contributes to fasting-induced marrow fat accumulation. In contrast, deletion of Igf1 from MKs/PLTs by Pf4-Cre leads to reduced bone formation and regeneration without affecting BM adipogenesis. To our surprise, MKs/PLTs are also an important source of systemic IGF-1. Platelet-rich plasma (PRP) from Pf4-Cre; Igf1 f/f mice showed compromised osteogenic potential both in vivo and in vitro, suggesting that MK/PLT-derived IGF-1 underlies the therapeutic effects of PRP. Taken together, this study identifies BMSCs and MKs/PLTs as two important sources of IGF-1 that coordinate to maintain and regenerate the adult skeleton, highlighting reciprocal regulation between the hematopoietic and skeletal systems.

Micro-nanobubbles can spontaneously generate hydroxyl free radicals (OH). Urea is a cheap reductant and can react with NOx species, and their products are nontoxic and harmless N2, CO2 and H2O. In this study, a Wet Direct Recycling Micro-nanobubble Flue Gas Multi-pollutants Removal System (WDRMRS) was developed for the simultaneous removal of NO, SO2 and Hg0. In this system, a micro-nanobubble generator (MNBG) was used to produce a micro-nanobubble gas-liquid dispersion system (MNBGLS) through recycling the urea solution from the reactor and the simulated flue gas composed of N2, NO, SO2 and Hg0. The MNBGLS, which has a large gas-liquid dispersion interface, was recycled continuously from the MNBG to the reactor, thus achieving cyclic absorption of various pollutants. All of the investigated parameters, including the initial pH and temperature of the absorbent as well as the concentrations of urea, NO and SO2 had significant effects on the NO removal efficiency but did not significantly affect the SO2 removal efficiency, whereas only the initial solution pH and NO concentration affected the Hg0 removal efficiency. The analysis results of the reaction mechanism showed that ·OH played a critical role in the removal of various pollutants. After the treatment by this system, the main removal products were Hg0 sediment, SO42- and NH4+ which could be easily recycled. The use of this system (MNBGLS) for the simultaneous removal of NO, SO2 and Hg0 is a new technology application and research. Recycling process based on MNBGLS succeeded in simultaneously removing NO, SO2 and Hg0. The system (MNBGLS) can provide a reference for commercial applications. The removal products are relatively simple and beneficial to recycling, which can reduce the cost of waste gas treatment.

Background The assessment of retroperitoneal lymph node status in patients with locally advanced cervical cancer is still a problem. This study aimed to explore the choice of these assessment methods. Methods Laparoscopic retroperitoneal lymphadenectomy was performed in 96 patients with advanced cervical cancer. The positive rates of lymph node metastasis were analyzed. The values of computed tomography lymph node minimum axial diameter (MAD) and squamous cell carcinoma antigen (SCC-Ag), and their combination in predicting retroperitoneal lymph node metastasis were compared. High-risk factors for common iliac lymph node (CILN) and/or para-aortic lymph node (PALN) metastasis were analyzed. Results The lymph node metastasis rate was 62.50% and the CILN and/or PALN metastasis rate was 31.25%. Overall, 96 patients had 172 visible lymph nodes. The positive rate of lymph node metastasis was significantly higher in the MAD ≥1.0 cm group (83.33%) than in the 0.5 cm ≤ MAD Conclusion Patients with MAD ≥1.0 cm and SCC-Ag ≥ 5.2 ng/mL, as well as high risk factors for CILN and/or PALN metastasis, should undergo resection of enlarged lymph nodes below the common iliac gland and lymphadenectomy of CILN/PALN to reduce tumor burden and to clarify lymph node metastasis status for accurate guidance in follow-up treatment. Patients with MAD

Border area is not only an important gateway for inland opening-up, but also an important part of completing the building of a moderately prosperous society and optimizing national urban spatial pattern in China. Due to the location, natural resources endowment, and traffic accessibility, the urbanization speed is relatively slow in border areas. Therefore, it is a special area that needs to pay close attention to, especially under the background of the Belt and Road Initiative and China’s regional coordinated development program. Based on the county-level data from 2000 to 2015, this paper tries to analyze the spatio-temporal pattern of urbanization in 134 border counties, and applies geographical detector method to study the driving forces of urbanization in border areas. Conclusions are as follows: (1) From 2000 to 2015, urbanization rate in border areas has been lower than the national average, and the gap has been widening. Some border counties in southern Xinjiang, Tibet, northeast of Inner Mongolia, and Yunnan, are even facing the problem of population loss. (2) In the same period, urbanization rate in the northwestern and southwestern border is low, while their urbanization rate grows relatively faster comparing with other border counties; urbanization rate in Tibet border is the lowest and grows relatively slowly; urbanization rate in the northeastern and northern border is slightly higher, but it grows slowly or even stagnates. (3) Transportation and industry are the important driving forces of urbanization in border areas, while the driving forces of market is relatively weak. And there are obvious mutual reinforcements among the driving forces, while the effort and explanatory power of resource force increases obviously after interaction. (4) Urbanization rate in the northwestern and southwestern border areas grows relatively fast, with industrial force and transportation force, market force and administrative force as the main driving forces respectively. Tibet border area has the lowest urbanization rate and growth rate, as the driving force of urbanization with strong contribution has not yet formed in Tibet. In the northeastern and northern border areas, the contribution of transportation force to urbanization is greater than other forces, and its interaction with market and industry has obvious effects.

Epithelial-mesenchymal transition (EMT) is the culprit of tumor invasion and metastasis. As a critical transcription factor that induces EMT, snail is of great importance in tumor progression, and knocking down its expression by small interfering RNA (siRNA) may inhibit tumor metastasis. Herein, we developed a core-shelled bioinspired low-density lipoprotein (bio-LDL) in which snail siRNA-loaded calcium phosphate nanoparticles were wrapped as the core and doxorubicin was embedded in the outer phospholipids modified with a synthetic peptide of apoB100 targeting LDL receptor-abundant tumor cells. Bio-LDL exhibited pH-responsive release, lysosomal escape ability, enhanced cytotoxicity and apoptotic induction. Bio-LDL could significantly inhibit the expression of snail and regulate EMT-related proteins to reduce tumor migration and invasion in vitro. Bio-LDL also displayed favorable tumor targeting and synergistic inhibition of tumor growth and metastasis in vivo. Therefore, the multifunctional bio-LDL will be a promising co-delivery vector and holds potential value for clinical translation.

Micro-nanobubbles can spontaneously generate hydroxyl free radicals (OH). Urea is a cheap reductant and can react with NO

Norgestrel (NGT) is a synthetic progestin used in human and veterinary medicine. Adult female mosquitofish were exposed to NGT for 42 d at 377 ng L−1. The fin morphology and the liver transcriptome were assessed. NGT exposure increased ray 4:6 length ratio. As compared to the control, NGT treatment affected the expression of 11,772 annotated transcripts in female mosquitofish. Specifically, we found 5780 were repressed while 5992 were significantly induced. Gene ontology (GO) analysis showed that 53 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways and 158 GO terms were significantly over expressed. Genes showing the largest magnitude of expression changes were related to fin development, androgen biosynthesis, and lipid and fatty acid metabolisms, suggesting the involvement of these biological processes in response to NGT exposure in G. affinis. This first comprehensive study on the transcriptomic alterations by NGT in G. affinis not only provides valuable information on the development of molecular markers but also opens new avenues for studies on the molecular mechanisms of effects of NGT in particular and possibly other progestins in G. affinis.

Micro-nanobubbles can spontaneously generate hydroxyl free radicals (*OH). Urea is a cheap reductant and can react with NOx species, and their products are nontoxic and harmless N2, CO2 and H2O. In this study, a Wet Direct Recycling Micro-nanobubble Flue Gas Multi-pollutants Removal System (WDRMRS) was developed for the simultaneous removal of NO, SO2 and Hg0. In this system, a micro-nanobubble generator (MNBG) was used to produce a micro-nanobubble gas-liquid dispersion system (MNBGLS) through recycling the urea solution from the reactor and the simulated flue gas composed of N2, NO, SO2 and Hg0. The MNBGLS, which has a large gas-liquid dispersion interface, was recycled continuously from the MNBG to the reactor, thus achieving cyclic absorption of various pollutants. All of the investigated parameters, including the initial pH and temperature of the absorbent as well as the concentrations of urea, NO and SO2 had significant effects on the NO removal efficiency but did not significantly affect the SO2 removal efficiency, whereas only the initial solution pH and NO concentration affected the Hg0 removal efficiency. The analysis results of the reaction mechanism showed that played a critical role in the removal of various pollutants. After the treatment by this system, the main removal products were HgO sediment, and which could be easily recycled.

// Jing Yang 1, 2 , Qiaoling Zhu 2 , Qiao Liu 2 , Yingxia Wang 2 , Weimin Xie 1 and Lili Hu 3 1 Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China 2 Department of Obstetrics and Gynecology, Maternal and Child Health Care Hospital of Hunan Province, Changsha, China 3 Department of Obstetrics and Gynecology, Jilin Central Hospital, Jilin, China Correspondence to: Weimin Xie, email: xwm315423@163.com Keywords: statin, endometrial cancer, cancer risk, meta-analysis Received: March 17, 2017 Accepted: May 04, 2017 Published: June 27, 2017 ABSTRACT Several studies have evaluated the association between statin use and endometrial cancer risk. We carried out a meta-analysis of randomized controlled trials (RCTs) and non-randomized studies to evaluate the effect of statins on endometrial cancer risk. A comprehensive search of electronic databases, conference abstracts and clinical trial registers was conducted for published and unpublished results. Studies that evaluated exposure to statins and endometrial cancer risk were considered. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using either a fixed-effects or a random-effects model. Two RCTs and eleven non-randomized studies (four cohort and seven case-control studies) involving 9,517 cases of endometrial cancer were included in the analysis. There was no evidence of an association between statin use and endometrial cancer risk either among RCTs (RR, 0.72; 95% CI, 0.19 to 2.67) or among non-randomized studies (RR, 0.94; 95% CI, 0.82 to 1.07). Combined analysis of all included studies also showed that statin use did not significantly affect endometrial cancer risk (RR, 0.94; 95% CI, 0.82 to 1.07). The sensitivity analysis confirmed the stability of our results. Our findings do not support a protective effect of statins against endometrial cancer at the population level.

Crude oil is one of the most widely used energy sources and the most important commodities in the global economy. To illustrate the gap between crude oil trade and consumption, this study calculated the internal intensity of global crude oil tele-connection, compared the differences of topological structures, and tested the energy risks between the direct oil trade network and embodied oil transfer network. Based on the results, evident differences were identified between the direct trade network and embodied transfer network. The direct trade network had less relational links but a higher internal intensity level, while the embodied oil transfer network had more relational links but a lower internal intensity level. For the regional components, the crude-oil-rich and highly industrialized countries/regions occupied the core circle in the direct oil trade network, whereas the highly industrialized countries/regions occupied the core position in the embodied oil transfer network. When tested, node countries in the core circle of the trade network were less sensitive under deliberate attack, but the direct oil trade network was easier to collapse than the embodied transfer network. With the comparisons between direct trade and embodied transfers, this work provides a more systematic perspective on the tele-connected crude oil networks.

Wet desulfurization and denitrification technologies are one of the main research directions in the future air pollution control. Compared with the traditional macro-bubbles, the MNBs can spontaneously generate  · O H with high oxidizing ability, and also improve the gas solubility. Na2SO3 is a strong reducing agent and can react with NO, NO2, NO2– and NO3– to convert ionic N to non-toxic and harmless N2. In the study, based on the principle of wet desulfurization and denitrification, a new recycling oxidation–reduction process was firstly proposed for simultaneous removal of NO and SO2 by using the MNBGLS which was generated with a MNBG through recycling Na2SO3 aqueous solution at a given concentration from a column reactor and the simulated flue gas composed of NO, SO2, N2 and/or other gases such as O2 and CO2. The MNBGLS was recycled continuously from the MNBG to the reactor. The effects of various experimental parameters, such as operation time, initial pH and temperature of absorbent, Na2SO3 concentration, NO concentration, SO2 concentration, the presence of O2 and CO2, on the removal of NO and SO2, were investigated. All the investigated parameters affected the removal of NO, whereas only initial solution pH influenced the removal of SO2. This new process can not only achieve high NO and SO2 removal efficiencies but also treat NO2– and NO3– so as to reduce the cost of subsequent wastewater treatment. Moreover, the main removal product, SO42−, can be recycled. Thus it is an economical, environmentally friendly and efficient desulfurization and denitrification process.

This study sought to investigate any correlation between fat mass and obesity-associated gene (FTO) expression and the severity of type 2 diabetes mellitus (T2DM). In total 110 patients newly diagnosed with T2DM in the outpatient department of Yantai Yuhuangding Hospital between September 2016 and March 2017 were selected as study subjects and were divided into severe (58 cases) and mild groups (52 cases) according to T2DM severity. Patients in the severe group were followed up for 12 weeks. An additional 60 healthy individuals were selected to serve as the normal control group. Fasting plasma glucose (FPG), fasting insulin (FINs), fasting C-peptide (FCP), glycosylated hemoglobin (HbA1c) and homeostasis model assessment of insulin resistance (HOMA-IR) were examined for every patient in the study. Real-time polymerase chain reaction (RT-PCR) was used to detect FTO messenger ribonucleic acid (mRNA) expression levels in patient peripheral blood lymphocytes. Western blotting was used to detect serum FTO protein expression levels, upon which the correlation between FTO protein levels and all other indices were analyzed. Compared with the normal control group, both T2DM groups showed significantly increased waist circumferences, hip circumferences, body mass indexes (BMIs), blood glucose indexes (FPG, FCP, HbA1c, FINs, HOMA-IR) and FTO mRNA/protein levels (p