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Metastasis is responsible for the rapid recurrence and poor survival of malignancies. Epithelial–mesenchymal transition (EMT) has a critical role in metastasis. Increasing evidence indicates that EMT can be regulated by microRNAs (miRNAs). miR-148a is a liver-abundant miRNA. However, the role of miR-148a in the development of liver cancer remains largely unknown. In this study, we found that, compared with normal livers, miR-148a was significantly decreased in hepatocellular carcinoma (HCC) tissues, especially in those with the portal vein tumor thrombus. An in vitro transwell assay and an in vivo orthotopic liver xenograft model showed that the restoration of miR-148a expression significantly repressed the migration and pulmonary metastasis of hepatoma cells. Linear regression analysis revealed a positive correlation between the expression of miR-148a and the mRNA level of E-cadherin gene in human HCC tissues. Both gain- and loss-of-function studies disclosed that miR-148a promoted the expression of epithelial marker (E-cadherin) and reduced the levels of mesenchymal markers (N-cadherin, fibronectin or vimentin) in hepatoma cells. These data suggest that miR-148a may suppress EMT and cancer metastasis. Further mechanistic investigations showed that miR-148a directly inhibited Met expression by binding to its 3′-UTR. Moreover, the reintroduction of miR-148a attenuated the downstream signaling of Met, like activated phosphorylation of AKT-Ser473 and inhibitory phosphorylation of GSK-3β-Ser9, and consequently reduced the nuclear accumulation of Snail, a transcription factor that promotes EMT. Taken together, miR-148a may negatively regulate Met/Snail signaling and therefore inhibit the EMT and metastasis of hepatoma cells. These findings highlight the significance of miR-148a downregulation in tumor progression and implicate miR-148a as an attractive candidate for cancer therapy.

The microRNA miR-125b is multi-faceted, with the ability to function as a tumor suppressor or an oncogene, depending on the cellular context. To date, the pro-apoptotic role of miR-125b and its underlying mechanisms are unexplored. In this study, both gain- and loss-of-function experiments revealed that miR-125b expression not only induced spontaneous apoptosis in various cell lines derived from the liver, lung and colorectal cancers, but also sensitized cancer cells to diverse apoptotic stimuli, including nutrient starvation and chemotherapeutic treatment. Furthermore, downregulation of miR-125b was a frequent event in hepatocellular carcinoma (HCC) tissues, and the miR-125b level was positively associated with the rate of apoptosis in HCC tissues. Subsequent investigations identified Mcl-1, Bcl-w and interleukin (IL)-6R as direct targets of miR-125b. Restoration of miR-125b expression not only diminished the expression of Mcl-1 and Bcl-w directly but also indirectly reduced the Mcl-1 and Bcl-xL levels by attenuating IL-6/signal transducer and activator of transcription 3 signaling. Consistent with these findings, introduction of miR-125b reduced the mitochondrial membrane potential and promoted the cleavage of pro-caspase-3. These data indicate that miR-125b may promote apoptosis by suppressing the anti-apoptotic molecules of the Bcl-2 family and miR-125b downregulation may facilitate tumor development by conferring upon cells the capability to survive under conditions of nutrient deprivation and chemotherapeutic treatment. Our findings highlight the importance of miR-125b in the regulation of apoptosis and suggest miR-125b as an attractive target for anti-cancer therapy.

Invasion and metastasis are the major features of malignant tumors that are responsible for 90% of cancer-related deaths. Recently, microRNAs have been discovered to have a role in suppressing tumor metastasis. This study's aim was to clarify the roles of miR-145 in gastric carcinomas and its underlying molecular mechanism in regulating tumor metastasis. Here, we demonstrate a stepwise downregulation of miR-145 level in nontumorous gastric mucosa, primary gastric cancers and their secondary metastases. In vitro analysis of miR-145's ectopic expression and loss-of-function suggests that it suppresses gastric cancer cell migration and invasion. In vivo spontaneous metastasis and experimental metastasis assay further confirm its function in suppressing the invasion-metastasis cascade, including impairing local invasion and inhibiting hematogenous metastasis in gastric cancers. Furthermore, we identified a novel mechanism of miR-145 to suppress metastasis. N-cadherin (CDH2) was proved to be a direct target of miR-145, using luciferase assay and western blot. Re-expressing N-cadherin in miR-145-transfected cells reverses their migration and invasion defects. Although not a direct target of miR-145, matrix metallopeptidase 9 (MMP9), but not MMP2, was also significantly decreased in miR-145-expressing cells. We suggest that miR-145 suppresses tumor metastasis by inhibiting N-cadherin protein translation, and then indirectly downregulates its downstream effector MMP9.

This study investigated the air pollution characteristics of synoptic-scale circulation in the Beijing megacity, and provided quantitative evaluation of the impacts of circulation patterns on air quality during the 2008 Beijing Summer Olympics. Nine weather circulation types (CTs) were objectively identified over the North China region during 2000–2009, using obliquely rotated T-mode principal component analysis (PCA). The resulting CTs were examined in relation to the local meteorology, regional transport pathways, and air quality parameters, respectively. The FLEXPART-WRF model was used to calculate 48-h backward plume trajectories for each CT. Each CT was characterized with distinct local meteorology and air mass origin. CT 1 (high pressure to the west with a strong pressure gradient) was characterized by a northwestern air mass origin, with the smallest local and southeasterly air mass sources, and CT 6 (high pressure to the northwest) had air mass sources mostly from the north and east. On the contrary, CTs 5, 8, and 9 (weak pressure field, high pressure to the east, and low pressure to the northwest, respectively) were characterized by southern and southeastern trajectories, which indicated a greater influence of high pollutant emission sources. In turn, poor air quality in Beijing (high loadings of PM10, BC, SO2, NO2, NOx, O3, AOD, and low visibility) was associated with these CTs. Good air quality in Beijing was associated with CTs 1 and 6. The average visibilities (with ±1σ) in Beijing for CTs 1 and 6 during 2000–2009 were 18.5 ± 8.3 km and 14.3 ± 8.5 km, respectively. In contrast, low visibility values of 6.0 ± 3.5 km, 6.6 ± 3.7 km, and 6.7 ± 3.6 km were found in CTs 5, 8, and 9, respectively. The mean concentrations of PM10 for CTs 1, 6, 5, 8, and 9 during 2005–2009 were 90.3 ± 76.3 μg m−3, 111.7 ± 89.6 μg m−3, 173.4 ± 105.8 μg m−3, 158.4 ± 90.0 μg m−3, and 151.2 ± 93.1 μg m−3, respectively. Analysis of the relationship between circulation pattern and air quality during the emission control period suggests that CTs are the primary drivers of day-to-day variations in pollutant concentrations over Beijing and its vicinity. During the Olympics period, the frequency of CT 6 was twice that of the mean in August from 2000 to 2009. This CT had northerly transport pathways and favorable meteorological conditions (e.g. frequent precipitation) for clean air during the Olympics. Assuming that relationships between CTs and air quality parameters in the same season are fixed in different years, the relative contributions of synoptic circulation to decreases in PM10, BC, SO2, NO2, NOx, CO, and horizontal light extinction during the Olympics were estimated as 19 ± 14%, 18 ± 13%, 41 ± 36%, 12 ± 7%, 10 ± 5%, 19 ± 11%, and 54 ± 25%, respectively.

Background Pregnant women experience physical, physiological, and mental changes. Health-related quality of life (HRQoL) is a relevant indicator of psychological and physical behaviours, changing over the course of pregnancy. This study aims to assess HRQoL of pregnant women during different stages of pregnancy. Methods This cross-sectional study was performed using the The EuroQoL Group’s five-dimension five-level questionnaire (EQ-5D-5L) to assess the HRQoL of pregnant women, and demographic data were collected. This study was conducted in a regional university hospital in Guangzhou, China. Results A total of 908 pregnant women were included in this study. Pregnant women in the early 2 nd trimester had the highest HRQoL. The HRQoL of pregnant women rose from the 1st trimester to the early 2nd trimester, and dropped to the bottom at the late 3rd trimester due to some physical and mental changes. Reports of pain/discomfort problem were the most common (46.0%) while self-care were the least concern. More than 10% of pregnant women in the 1st trimester had health-related problems in at least one dimension of whole five dimensions. In the whole sample, the EuroQoL Group’s visual analog scale (EQ-VAS) was 87.86 ± 9.16. Across the gestational stages, the HRQoL remained stable during the pregnancy but the highest value was observed in the 1st trimester (89.65 ± 10.13) while the lowest was in the late 3rd trimester (87.28 ± 9.13). Conclusions During pregnancy, HRQoL were associated with gestational trimesters in a certain degree. HRQoL was the highest in the early 2nd trimester and then decreased to the lowest in the late 3rd trimester due to a series of physical and psychological changes. Therefore, obstetric doctors and medical institutions should give more attention and care to pregnant women in the late 3rd trimester.

Pharmacogenetic/pharmacogenomic (PGx) approaches to psychopharmacology aim to identify clinically meaningful predictors of drug efficacy and/or side-effect burden. To date, however, PGx studies in psychiatry have not yielded compelling results, and clinical utilization of PGx testing in psychiatry is extremely limited. In this review, the authors provide a brief overview on the status of PGx studies in psychiatry, review the commercialization process for PGx tests and then discuss methodological considerations that may enhance the potential for clinically applicable PGx tests in psychiatry. The authors focus on design considerations that include increased ascertainment of subjects in the earliest phases of illness, discuss the advantages of drug-induced adverse events as phenotypes for examination and emphasize the importance of maximizing adherence to treatment in pharmacogenetic studies. Finally, the authors discuss unique aspects of pharmacogenetic studies that may distinguish them from studies of other complex traits. Taken together, these data provide insights into the design and methodological considerations that may enhance the potential for clinical utility of PGx studies.

Background Gestational diabetes mellitus (GDM) is one of the most common complications during pregnancy, and it has both short- and long-term adverse effects on the health of mothers and fetuses. To investigate the effect of exercise during pregnancy on the occurrence of GDM among normal-weight pregnant women. Methods We searched for studies published between January 1994 and June 2017 that appeared in the Web of Science, Scopus, ClinicalTrials.gov or Cochrane library databases. Randomized controlled trials that investigated the preventive effect of exercise on GDM in normal-weight women were included. Interventions including any confounding factors (e.g., dietary) were excluded. We extracted maternal characteristics, the diagnostic criteria of GDM, and basic information for intervention and obstetric outcomes. The primary outcome was the occurrence of GDM, and the secondary outcomes included gestational weight gain, gestational age at birth, birth weight, and the odds of cesarean section. A meta-analysis was conducted based on calculations of pooled estimates using the random-effects model. Results Eight studies were included in this systematic review and meta-analysis. Exercise during pregnancy was shown to decrease the occurrence of GDM [RR = 0.58, 95% CI (0.37, 0.90), P  = 0.01 and RR = 0.60, 95% CI (0.36, 0.98), P  = 0.04 based on different diagnosis criteria, respectively] in normal-weight women. Regarding secondary outcomes, exercise during pregnancy can decrease gestational weight gain [MD = − 1.61, 95% CI (− 1.99, − 1.22), P <0.01], and  had no significant effects on gestational age at birth [MD = − 0.55, 95% CI (− 1.57, 0.47), P  = 0.29], birth weight [MD = − 18.70, 95% CI (− 52.49, 15.08), P  = 0.28], and the odds of caesarean section [RR = 0.88, 95% CI (0.72, 1.08), P  = 0.21], respectively. Conclusions Exercise during pregnancy can ostensibly decrease the occurrence of GDM without reducing gestational age at delivery and increasing the odds of cesarean section in normal-weight women.

The \"Blue Sky Project\" was proposed in 1998 to investigate by how much emissions should be reduced to increase blue sky frequency in Beijing, which hosted the Summer Olympics in 2008. This paper focuses on the temporal variation of visibility and its dependence on meteorological conditions and suspended particles at Beijing using the hourly observed visibility data at Beijing Capital International Airport (BCIA) from 1999 to 2007. It has been found that about 47.8% (24.2%) of the hours in Beijing are \"bad\" (\"good\") hours with visibility below 10 km (equal or higher than 20 km) between 1999 and 2007. Due to the high Relative Humidity (RH), summer is the season with the lowest mean visibility in a year. Although PM10 index was reported in a decreasing trend (Chan and Yao, 2008), the increase of RH has resulted in a decreasing trend of visibility over BCIA in the summer from 1999 to 2007. To ensure blue sky (\"good\" visibility) for Olympics 2008, daily mean PM10 index should have been reduced from 81 to 44. This requires that not only vehicle emissions, but also other emissions should be limited. Observations verify that blue-sky-hour rate increased significantly after mean PM10 index was reduced to 53 during Olympics 2008, however, the visibility of 2009 returned to the mean level from 1999 to 2007 during the period 8−24 August. RH (aerosol) contribute 24% (76%) of the improvement of visibility during August 2008.

Background Population growth, population ageing, and urbanisation are major global demographic trends that call for an examination of the impact of urban densification on older adults’ health-enhancing behaviours, such as walking. No studies have examined the pathways through which urban densification may affect older adults’ walking. This information is key to evidence-based, health-oriented urban and transport planning. This study aimed to identify neighbourhood environment characteristics potentially responsible for the effects of neighbourhood densification on older adults’ frequency and amount of transportation and recreation walking within and outside the neighbourhood. Methods The Active Lifestyle and the Environment in Chinese Seniors (ALECS) project collected self-reported data from 909 older adults (≥ 65 years) living in 128 physically and socially diverse neighbourhoods in Hong Kong (71% response rate). Walking was measured using the Neighbourhood Walking Questionnaire for Chinese Seniors. Objective residential density and other neighbourhood environmental attributes were assessed using Geographic Information Systems. Generalised additive mixed models examined the total effects of neighbourhood residential density on walking and the mediating role of other environmental attributes and car ownership. Results A complex network of potential pathways of positive and negative influences of neighbourhood residential density on different aspects of walking was revealed. While residential density was positively related to within-neighbourhood transportation and outside-neighbourhood recreation walking only, it exhibited positive and/or negative nonlinear indirect effects on all examined aspects of walking via recreation, public transport, food/retail and street intersection densities, and/or car ownership. Conclusions High-density environments appear to support within-neighbourhood walking by providing access to food and retail outlets via well-connected street networks and discouraging car ownership. However, extreme density may lead to reductions in walking. Public transport density accompanying high-density areas may facilitate outside-neighbourhood walking but deter within-neighbourhood walking. The development of activity-friendly communities for ageing populations need to consider these opposing influences.