Identification of different isomer structures of atomic and molecular clusters has long been a challenging task in the field of cluster science. Here we present a three-dimensional (3D) assignment method, combining the energy (1D) and simulated (2D) spectra to assure the assignment of the global minimum structure. This method is more accurate and convenient than traditional methods, which only consider the total energy and first vertical detachment energies (VDEs) of anion clusters. There are two prerequisites when the 3D assignment method is ultilized. First, a reliable global minimum search algorithm is necessary to explore enough valleys on the potential energy surface. Second, trustworthy simulated spectra are necessary, that is to say, spectra that are in quantitative agreement. In this paper, we demonstrate the validity of the 3D assignment method using Au8M(-) (M=Si, Ge, Sn) systems. Results from this study indicate that the global minimum structures of Au8Ge(-) and Au8Sn(-) clusters are different from those described in previous studies.

Cognitive impairment, the leading cause of traumatic brain injury (TBI)-related disability, adversely affects the quality of life of TBI patients, and exacts a personal and economic cost that is difficult to quantify. The underlying pathophysiological mechanism is currently unknown, and an effective treatment of the disease has not yet been identified. This study aimed to advance our understanding of the mechanism of disease pathogenesis; thus, metabolomics based on gas chromatography/mass spectrometry (GC-MS), coupled with multivariate and univariate statistical methods were used to identify potential biomarkers and the associated metabolic pathways of post-TBI cognitive impairment. A biomarker panel consisting of nine serum metabolites (serine, pyroglutamic acid, phenylalanine, galactose, palmitic acid, arachidonic acid, linoleic acid, citric acid, and 2,3,4-trihydroxybutyrate) was identified to be able to discriminate between TBI patients with cognitive impairment, TBI patients without cognitive impairment and healthy controls. Furthermore, associations between these metabolite markers and the metabolism of amino acids, lipids and carbohydrates were identified. In conclusion, our study is the first to identify several serum metabolite markers and investigate the altered metabolic pathway that is associated with post-TBI cognitive impairment. These markers appear to be suitable for further investigation of the disease mechanisms of post-TBI cognitive impairment.

Enhanced recovery after surgery (ERAS) pathways are multimodal, evidence-based approaches to optimize patient outcome after surgery. However, the use of ERAS protocols to improve morbidity and recovery time without compromising safety following pancreaticoduodenectomy (PD) remains to be elucidated.We conducted a systemic review and meta-analysis to assess the safety and efficacy of ERAS protocols compared with conventional perioperative care (CPC) in patients following PD.PubMed, Medline, Embase, and Science Citation Index Expanded and Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library were searched between January 2000 and June 2015.The patients who underwent PD with ERAS protocols or CPC were eligible. The studies that compared postoperative length of hospital stay (PLOS), postoperative complications, or in-hospital costs in the 2 groups were included.A meta-analysis, meta-regression, sensitivity analysis, and subgroup analysis were performed to estimate the postoperative outcomes between the 2 groups and identified the potential confounders. We used the methodological index for nonrandomized studies checklist to assess methodological qualities. Weighted mean differences (WMD) or odds ratios (OR) were calculated with their corresponding 95% confidence intervals (CI). The publication bias tests were also performed through the funnel plots.In total, 14 nonrandomized comparative studies with 1409 ERAS cases and 1310 controls were analyzed. Implementation of an ERAS protocol significantly reduced PLOS (WMD: -4.17 days; 95%CI: -5.72 to -2.61), delayed gastric emptying (OR: 0.56; 95%CI: 0.44-0.71), overall morbidity (OR: 0.63; 95% CI: 0.54-0.74), and in-hospital costs compared to CPC (all P < 0.001). There were no statistically significant differences in other postoperative outcomes. Age, gender, and ERAS component implementation did not significantly contribute to heterogeneity for PLOS as shown by meta-regression analysis.Our study suggested that ERAS was as safe as CPC and improved recovery of patients undergoing PD, thus reducing in-hospital costs. General adoption of ERAS protocols during PD should be recommended.

Barrett esophagus (BE) is considered precursor condition of esophageal adenocarcinoma. Its incidence and prevalence are increasing in general population. Studies reported that metabolic syndrome (MS) or diabetes mellitus (DM) is related to increased risk of BE. Current study was to assess and better understand the relationship between MS /DM and BE.

In recent years, concerns about the adverse effects of hormone replacement therapy have increased interest in alternative therapies for the management of the symptoms of perimenopause. Here, we investigated the effects of moxibustion, a traditional Chinese practice that is involved in heated Artemisia vulgaris (mugwort) stimulation, on hormonal imbalance and ovarian granulosa cell (GC) apoptosis in a rat model of perimenopause. Our results showed that mild warm moxibustion (MWM) modulated the circulating levels of estradiol and follicle-stimulating hormone and their receptors and inhibited apoptosis in the ovaries of perimenopausal rats, similar to the effect of estrogen. Further investigation revealed that the effects of MWM on ovary tissues and cultured GCs were mediated by the modulation of the activity of Forkhead box protein O1 and involved the JAK2/STAT3 pathway. Our results provide information on the factors and pathways modulated by MWM and shed light on the mechanism underlying the beneficial effect of moxibustion on the symptoms of perimenopause.

The effect of mesenchymal stem cell (MSCs)-based therapy on treating acute myocardial infarction (MI) is limited due to poor engraftment and limited regenerative potential. Here we engineered MSCs with integrin-linked kinase (ILK), a pleiotropic protein critically regulating cell survival, proliferation, differentiation, and angiogenesis. We firstly combined ferumoxytol with poly-L-lysine (PLL), and found this combination promisingly enabled MRI visualization of MSCs in vitro and in vivo with good safety. We provided visually direct evidence that intracoronary ILK-MSCs had substantially enhanced homing capacity to infarct myocardium in porcine following cardiac catheterization induced MI. Intracoronary transplantation of allogeneic ILK-MSCs, but not vector-MSCs, significantly enhanced global left ventricular ejection fraction (LVEF) by 7.8% compared with baseline, by 10.3% compared with vehicles, and inhibited myocardial remodeling compared with vehicles at 15-day follow-up. Compared with vector-MSCs, ILK-MSCs significantly improved regional LV contractile function, reduced scar size, fibrosis, cell apoptosis, and increased regional myocardial perfusion and cell proliferation. This preclinical study indicates that ILK-engineered MSCs might promote the clinical translation of MSC-based therapy in post-MI patients, and provides evidence that ferumoxytol labeling of cells combined with PLL is feasible in in vivo cell tracking.

Tomato yellow leaf curl virus (TYLCV) is a member of the family Geminiviridae, genus Begomovirus. The virus is a widespread plant virus that causes important economic losses in tomatoes. Genetic engineering strategies have increasingly been adopted to improve the resistance of tomatoes to TYLCV.

Long non-coding RNAs (lncRNAs) have emerged recently as key regulators of tumor development and progression. Our previous study identified an NF-KappaB interacting lncRNA (NKILA) which was negatively correlated with breast cancer metastasis and patient prognosis. However, its clinical significance and potential role in Tongue squamous cell carcinoma (TSCC) remain unclear. Here we show that NKILA is down-regulated in TSCC cancer tissues than that in matched adjacent noncancerous tissues. And low NKILA expression in TSCC is significantly correlated with tumor metastasis and poor patient prognosis. In vitro, overexpression of NKILA decreases TSCC cells migration and invasion. Mechanistic study shows that NKILA inhibits the phosphorylation of IκBα and NF-κB activation as well as the induction of the epithelial-mesenchymal transition (EMT) process. Ectopic expression of NKILA in Tscca cells inhibits NF-κB activator TNF-α-promoted cell migration and invasion, while applying NF-κB inhibitor Bay-117082 or JSH-23 in NKILA silenced CAL27 cells reverses cell migration capacity to lower level. In vivo experimental metastasis model also demonstrates NKILA inhibits lung metastasis of NOD/SCID mice with TSCC tumors. These results suggested that NKILA is a vital determinant of TSCC migration and invasion and NF-κB signaling pathway mediates this effect. Given the above mentioned function of NKILA, it could act as a potential predictor for overall survival in patients with TSCC and a potential therapeutic target for TSCC intervention.

Content-based image retrieval (CBIR) techniques have currently gained increasing popularity in the medical field because they can use numerous and valuable archived images to support clinical decisions. In this paper, we concentrate on developing a CBIR system for retrieving brain tumors in T1-weighted contrast-enhanced MRI images. Specifically, when the user roughly outlines the tumor region of a query image, brain tumor images in the database of the same pathological type are expected to be returned. We propose a novel feature extraction framework to improve the retrieval performance. The proposed framework consists of three steps. First, we augment the tumor region and use the augmented tumor region as the region of interest to incorporate informative contextual information. Second, the augmented tumor region is split into subregions by an adaptive spatial division method based on intensity orders; within each subregion, we extract raw image patches as local features. Third, we apply the Fisher kernel framework to aggregate the local features of each subregion into a respective single vector representation and concatenate these per-subregion vector representations to obtain an image-level signature. After feature extraction, a closed-form metric learning algorithm is applied to measure the similarity between the query image and database images. Extensive experiments are conducted on a large dataset of 3604 images with three types of brain tumors, namely, meningiomas, gliomas, and pituitary tumors. The mean average precision can reach 94.68%. Experimental results demonstrate the power of the proposed algorithm against some related state-of-the-art methods on the same dataset.

Acute lymphoblastic leukaemia (ALL) is the most prevalent childhood malignancy. Although most children with ALL are cured, there is still a group of patients for which therapy fails owing to severe toxicities and drug resistance. Ginsenoside Rh2 (GRh2), a major bioactive component isolated from Panax ginseng, has been shown to have a therapeutic effect on some tumors. However, the molecular mechanisms of cell death induced by 20(S)-GRh2 in ALL cells remains unclear. In this study, we showed that 20(S)-GRh2 inhibited the cell growth and induced mitochondria-dependent apoptosis and autophagy. But it has no cytotoxic effect on human normal blood cells. Furthermore, autophagy plays a protective role in 20(S)-GRh2-induced apoptosis in ALL cell lines and human primary ALL cells. We demonstrated that either genetic or pharmacologic inhibition of autophagy could be more effective in reducing viability and enhancing 20(S)-GRh2-induced toxicity than 20(S)-GRh2 treatment alone. In addition, inhibition of autophagy could aggravate mitochondrial ROS generation and mitochondrial damage, and then accelerate mitochondria-dependent apoptosis. Taken together, these results suggest that inhibition of autophagy can sensitize ALL cells towards 20(S)-GRh2. The appropriate inhibition of autophagy could provide a powerful strategy to increase the potency of 20(S)-GRh2 as a novel anticancer agent for ALL therapy.

While combined oral contraceptives (COCs) are commonly used to treat polycystic ovary syndrome (PCOS), comparative data regarding metabolic effects of different progestogens on this patient population are missing. This study aimed to compare the different effects of drospirenone (DRP)-containing COCs with cyproterone acetate (CPA)-containing COCs, combined with metformin and lifestyle modifications in women with PCOS and metabolic disorders.

Endogenous small (sm) RNAs (primarily si- and miRNAs) are important trans/cis-acting regulators involved in diverse cellular functions. In plants, the RNA-dependent RNA polymerases (RDRs) are essential for smRNA biogenesis. It has been established that RDR2 is involved in the 24 nt siRNA-dependent RNA-directed DNA methylation (RdDM) pathway. Recent studies have suggested that RDR1 is involved in a second RdDM pathway that relies mostly on 21 nt smRNAs and functions to silence a subset of genomic loci that are usually refractory to the normal RdDM pathway in Arabidopsis. Whether and to what extent the homologs of RDR1 may have similar functions in other plants remained unknown.

The chemokine (C-X-C motif) receptor 4 (CXCR4) is expressed on native cardiomyocytes and can modulate isolated cardiomyocyte contractility. This study examines the role of CXCR4 in cardiomyocyte response to ischaemia-reperfusion (I/R) injury. Isolated adult rat ventricular cardiomyocytes were subjected to hypoxia/reoxygenation (H/R) to simulate I/R injury. In response to H/R injury, the decrease in CXCR4 expression was associated with dysfunctional energy metabolism indicated by an increased adenosine diphosphate/adenosine triphosphate (ADP/ATP) ratio. CXCR4-overexpressing cardiomyocytes were used to determine whether such overexpression (OE) can prevent bio-energetic disruption-associated cell death. CXCR4 OE was performed with adenoviral infection with CXCR4 encoding-gene or non-translated nucleotide sequence (Control). The increased CXCR4 expression was observed in cardiomyocytes post CXCR4-adenovirus transduction and this OE significantly reduced the cardiomyocyte contractility under basal conditions. Although the same extent of H/R-provoked cytosolic calcium overload was measured, the hydrogen peroxide-induced decay of mitochondrial membrane potential was suppressed in CXCR4 OE group compared with control group, and the mitochondrial swelling was significantly attenuated in CXCR4 group, implicating that CXCR4 OE prevents permeability transition pore opening exposure to overload calcium. Interestingly, this CXCR4-induced mitochondrial protective effect is associated with the enhanced signal transducer and activator of transcription 3 (expression in mitochondria. Consequently, in the presence of H/R, mitochondrial dysfunction was mitigated and cardiomyocyte death was decreased to 65% in the CXCR4 OE group as compared with the control group. I/R injury leads to the reduction in CXCR4 in cardiomyocytes associated with the dysfunctional energy metabolism, and CXCR4 OE can alleviate mitochondrial dysfunction to improve cardiomyocyte survival.

Brain-derived neurotrophic factor (BDNF) is associated with coronary artery diseases. However, its role and mechanism in myocardial infarction (MI) is not fully understood.

Macrophage-derived lipoprotein lipase (LPL) has been shown uniformly to promote atherosclerotic lesion formation while the extent to which it affects plasma lipid and lipoprotein levels varies in wild-type and hypercholesterolemic mice. It is known that high levels of LPL in the bulk of adipose tissue and skeletal muscle would certainly mask the contribution of macrophage LPL to metabolism of plasma lipoprotein. Therefore, we chose LPL deficient (LPL⁻/⁻) mice with severe hypertriglyceridemia as an alternative model to assess the role of macrophage LPL in plasma lipoprotein metabolism via bone marrow transplant, through which LPL will be produced mainly by hematopoietic cell-derived macrophages.

Gene expression profiling is being widely applied in cancer research to identify biomarkers for clinical endpoint prediction. Since RNA-seq provides a powerful tool for transcriptome-based applications beyond the limitations of microarrays, we sought to systematically evaluate the performance of RNA-seq-based and microarray-based classifiers in this MAQC-III/SEQC study for clinical endpoint prediction using neuroblastoma as a model.

Previous studies have demonstrated that acupuncture is beneficial to patients with Crohn's disease (CD), but the mechanism underlying its therapeutic effects remains unclear. To identify the mechanism by which acupuncture treats CD, the balance between Th17 and Treg cells was assessed in CD patients. In this study, Ninety-two CD patients were randomly and equally assigned to a treatment group that were treated with herb-partitioned moxibustion and acupuncture or a control group with wheat bran-partitioned moxibustion and superficial acupuncture. The effect of these treatments on Th17 and Treg cells and their related molecular markers in the intestinal mucosa were detected before (week 0) and after (week 12) treatment. The results suggested that the ratio of Th17 and Treg cells was significantly decreased after treatment and that the levels of IL-17 and RORγt in the intestinal mucosa were obviously reduced, while the expression of FOXP3 was increased after treatment in both groups. In the treatment group, the expression of these molecules was more markedly regulated than the control group. In conclusion, moxibustion and acupuncture have been shown to regulate the ratio of Th17 and Treg cells in the intestinal mucosa of CD patients and restore the balance between these immune cell subsets.

Hes1 is a transcription factor that influences cell proliferation and differentiation. However, the effect of Hes1 on invasiveness and the underlying mechanism remain unknown. In the current study, we found that Hes1 suppressed cell apoptosis, promoted cell growth, induced EMT phenotype and cytoskeleton reconstruction, and enhanced the metastatic potential of colon cancer cells in vitro and in vivo. Furthermore, we indicated that Bmi-1 mediated Hes1-induced cell proliferation and migration, downregulated PTEN and activated the Akt/GSK3β pathway, consequently induced EMT and cytoskeleton reconstruction, ultimately leading to enhanced invasiveness of cancer cells. In addition, we also found that both Hes1 and Bmi-1 could directly regulate PTEN by associating at the PTEN locus, and played important roles in regulating PTEN/Akt/GSK3β pathway. Our results provide functional and mechanistic links between Hes1 and Bmi-1/PTEN/Akt/GSK3β signaling in the development and progression of colon cancer.

In pregnancy, placenta can be exposed to glucocorticoids (GCs) via several ways, which may disturb placentation and adversely affect pregnancy. Preeclampsia (PE) is thought to be attributed, in part, to impaired trophoblast development. The purpose of the present study was to confirm that GC exposure in early placentation could lead to PE in rats, with the mechanisms involving dysregulated trophoblast development. In the study, pregnant rats were administered with 2.5mg/kg Dex subcutaneously once per day from gestational day 7 to 13. Maternal systolic blood pressure and urinary albumin were increased, while both fetus and placenta were restricted after GC exposure relative to the control group. GC exposure also contributed to placental abnormalities and renal impairment. Moreover, placental oxidative damage was increased along with placental hypoxia-inducible factor 1-alpha (HIF1A) overexpression after GC treatment. Mechanically, GC induced PE in rat partially through inhibiting trophoblast proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), which involved phospho-extracellular signal regulated kinase (p-ERK) downregulation. Furthermore, GC receptor was required for the inhibition of GC on trophoblast proliferation, migration, invasion and EMT in vitro. These findings suggest that GC exposure in early placentation could contribute to PE in pregnant rats, with the mechanisms involving inhibition of trophoblast proliferation, migration, invasion and EMT by GC.

Previous studies have indicated the association between C2 rs547154 polymorphism and polypoidal choroidal vasculopathy (PCV) risk, while the results are controversial and inconsistent. Herein, we perform a meta-analysis to gain a precise estimation of the association using 5 eligible studies involving 4076 subjects, of which 1220 were PCV cases, 1073 were age-related macular degeneration (AMD) cases and 1783 were controls. Allelic frequencies of C2 rs547154 polymorphism between PCV and AMD were also compared. Both crude and adjusted odds ratios (OR) with their 95% confidence interval (CI) were included to assess the strength of the association. The pooled OR in random-effect model for allele T versus G was 0.64 (95% CI, 0.52-0.80; p < 0.0001), for genotype TG versus GG was 0.65 (95% CI, 0.52-0.83; p, 0.0004), and for genotype TT + TG versus GG was 0.64 (95% CI, 0.51-0.80; p, 0.0002). No difference in allelic frequency was observed between PCV and AMD (OR, 0.86; 95% CI, 0.64-1.16; p, 0.32). Sensitivity analysis proved the robustness of our data. No significant ethnic divergence was suggested by subgroup analysis, and no publication bias was detected via Egger's test. In conclusion, our data indicate that C2 rs547154 polymorphism plays a protective role in the development of PCV.