Failure properties of roadway with extra-thick coal seams and its control techniques.

The dense conventional combined support hardly controls the overall subsidence of the roadway roof in extra-thick coal seam and affects the excavation efficiency, leading to the technical problem of mining proportion imbalance in the mine. In this study, the typical mining roadway with extra-thick coal seams in the Yanzhou mining area was taken as the engineering background, the roof stress distribution of the development face during the extra-thick coal seam mining was simulated, the deformation and failure characteristics of the roof at different layers under different thicknesses of the top coal were analyzed, and the progressive fragmentation and discontinuous deformation and failure mechanism of the top coal were revealed. Furthermore, the reinforced support technique of the thick anchorage and high preload in roof was put forward，and the reinforced technique was successful applied in the typical roadway in of Baodian Coal Mine, the experimental results showed that the fracture damage of the top coal in the mining roadway was effectively controlled, the deformation of the surrounding rock under the proposed support scheme was reduced by 40 %-50 % and the excavation speed was increased by 33 %.

Experimental study on the influence of water-rock interaction on the time-varying characteristics of coal rock mass.

In order to study the influence of water-rock interaction on the mass time-varying characteristics of coal rocks, coal was selected as the research object and subjected to chemical immersion tests with different pH aqueous solutions for 12 days. By experiment, the time-varying patterns of mass change fraction in coal samples, pH value in solution, and ions concentration of calcium and magnesium were obtained. Based on the gray correlation theory, the correlation degree between the mass change fraction and four influencing factors was analyzed. The gray prediction models for the mass time-varying characteristics of coal rocks have been established. The research shows that: (1) the influence ways and degree of different pH aqueous solutions on the mass changes of coal rocks are different, (2) during the process of water-rock interaction, the change law of pH value, ions concentration of calcium and magnesium in solution are obvious, (3) the multiple regression models can be used to predict the mass change of coal rocks accurately under water-rock interaction.

Long non-coding RNA FENDRR suppresses cancer-associated fibroblasts and serves as a prognostic indicator in colorectal cancer.

Genetically abnormal fibroblasts are notably more prevalent in colorectal cancer (CRC) than in adjacent normal tissue, emphasizing their significance in driving the heterogeneity of the tumor microenvironment. Functioning as a significant regulatory gene in the context of fibrosis, FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR) has exhibited abnormal expression in colorectal cancer and interstitial localization in our experiments. However, current research on the role of FENDRR in cancer has focused solely on its impact on cancer cells. Its crucial role in the tumor stroma is yet to be explored. The goal of this study was to understand the relationship between atypical FENDRR expression, its distinct localization, and genetically abnormal fibroblasts in CRC. We aimed to establish the function of FENDRR within the stromal compartment of patients through bioinformatics. Our study confirmed that FENDRR suppresses cancer-associated fibroblasts by inhibiting their activation and collagen generation in CRC. Furthermore, our findings suggest that low FENDRR expression indicates a poor prognosis. Therefore, we propose that FENDRR is a promising therapeutic target for future studies in CRC.

Oridonin alleviates the inhibitory effect of lipopolysaccharide on the proliferation and osteogenic potential of periodontal ligament stem cells by inhibiting endoplasmic reticulum stress and NF-κB/NLRP3 inflammasome signaling.

BACKGROUND: The aim of this study was to investigate the protective effect and mechanism of oridonin in an in vitro lipopolysaccharide (LPS)-induced human periodontal ligament stem cells (hPDLSCs) model of periodontitis. METHODS: Primary hPDLSCs were isolated and cultured, and then the expression of surface antigens CD146, STRO-1 and CD45 of hPDLSCs was detected by flow cytometry. The mRNA expression level of Runx2, OPN, Col-1, GRP78, CHOP, ATF4 and ATF6 in the cells was tested by qRT-PCR. MTT was taken to determine the cytotoxicity of oridonin at different concentrations (0-4 µM) on hPDLSCs. Besides, ALP staining, alizarin red staining and Oil Red O staining were utilized to assess the osteogenic differentiation (ALP concentration, mineralized calcium nodule formation) and adipogenic differentiation abilities of the cells. The proinflammatory factors level in the cells was measured by ELISA. The protein expression level of NF-κB/NLRP3 pathway-related proteins and endoplasmic reticulum (ER) stress-related markers in the cells were detected by Western blot. RESULTS: hPDLSCs with positive CD146 and STRO-1 expression and negative CD45 expression were successfully isolated in this study. 0.1-2 µM of oridonin had no significant cytotoxicity on the growth of hPDLSCs, while 2 µM of oridonin could not only greatly reduce the inhibitory effect of LPS on the proliferation and osteogenic differentiation of hPDLSCs cells, but also inhibit LPS-induced inflammation and ER stress in hPDLSCs cells. Moreover, further mechanism research showed that 2 µM of oridonin suppressed NF-κB/NLRP3 signaling pathway activity in LPS-induced hPDLSCs cells. CONCLUSIONS: Oridonin promotes proliferation and osteogenic differentiation of LPS-induced hPDLSCs in an inflammatory environment, possibly by inhibiting ER stress and NF-κB/NLRP3 pathway. Oridonin may have a potential role in the repair and regeneration of hPDLSCs.

Model experiment research on HPTL anchoring technology for coal-rock composite roof in deep roadway.

Since the western region of China, which is typical of extraordinary resource endowments, has gradually emerged as the major mining zone in China, the mining of thick coal seams and roadways with coal-rock composite roof have become more and more common in this region. However, it is extremely difficult to realize safe and effective maintenance and control of such roadways due to the differences in natural endowments of coal-rock masses. With the roadway with coal-rock composite roof of Hulusu Coal Mine in western China as the engineering background, experiment research on large-scale similarity model was conducted through comprehensive measures such as the pneumatic loading system, the surrounding rock stress monitoring system, the roadway deformation monitoring system, the bolt load monitoring system, and the displacement field monitoring system in this paper. According to the results of the experiment, the control effects of the three support systems on the roadway with coal-rock composite roof were significantly different. When the single support of short anchor bolts was applied, the comparatively low initial anchor-hold failed to constrain the initial micro deformation of the roof. Consequently, wide-range fractures of the roof were triggered at a loading pressure of 0.8 MPa. In the meanwhile, the deep surrounding rocks witnessed a downward inflection point in stress, accompanied by the possibility of the collapse of the thin-layer anchorage zone at any time. As for the support combining both short anchor bolts and long anchor cables, though a reinforced effect on the bolt anchorage zone could be achieved with the help of the cables, the active reinforcement capacity of the bolt was limited. The bolt anchorage zone was the first to be damaged at a loading pressure of 0.9 MPa, which would subsequently affect the effective bearing capacity of the deep surrounding rocks. In the application of the single support of high-strength long anchor bolts, the long bolts with high pre-tightening force were able to lock multiple groups of coal-rock strata to form a thick-layer anchorage bearing structure capable of withstanding a load as high as 1.0 MPa. The crash and collapse of the coal wall eventually caused the subsidence of the roof. Based on the intense dynamic load experiment and the feedbacks of engineering application outcomes in the field, it was concluded that the high-pretension thick-layer (HPTL) anchoring technology can effectively constrain the deformation of roadways with coal-rock composite roof with favorable application outcomes.

Correlations between gastrointestinal and oral microbiota in children with cerebral palsy and epilepsy.

We here studied the correlation between gut and oral microbiota in children with cerebral palsy and Epilepsy (CPE). We enrolled 27 children with this condition from the social welfare center of Longgang District, collected their oral plaque and stool samples, and analyzed their gut microbiota (GM) and oral microbiota (OM) through 16S rRNA gene sequencing. Taxonomical annotation revealed that the levels of Firmicutes and Bacteroides in the oral cavity were significantly lower in CPE children than in healthy children, whereas the abundance of Actinomycetes increased significantly in CPE children. In addition, Prevotella, Fusobacterium, and Neisseria were the top three abundant genera, representing 15.49%, 9.34%, and 7.68% of the OM and suggesting potential correlations with caries, periodontitis, and malnutrition. For the GM, Bifidobacterium, Bacteroides, and Prevotella were the top three abundant genera in CPE children and probably contributed to the development of chronic inflammation and malnutrition. Furthermore, the OM and GM correlated with each other closely, and the bacterial components of these microbiota in CPE children were remarkably different from those in healthy children, such as Bifidobacterium, Fusobacterium, Bacteroides, and Neisseria. Conclusively, dysbiotic OM can translocate to the intestinal tract and induce GM dysbiosis, suggesting the consistency between OM and GM variations. Altered oral and gut microbial structures have potential impacts on the occurrence of clinical diseases such as periodontitis, caries, and malnutrition.

NAD+ Anabolism Disturbance Causes Glomerular Mesangial Cell Injury in Diabetic Nephropathy.

The homeostasis of NAD+ anabolism is indispensable for maintaining the NAD+ pool. In mammals, the mainly synthetic pathway of NAD+ is the salvage synthesis, a reaction catalyzed by nicotinamide mononucleotide adenylyltransferase (NAMPT) and nicotinamide mononucleotide adenylyltransferase (NMNATs) successively, converting nicotinamide (NAM) to nicotinamide mononucleotide (NMN) and NMN to NAD+, respectively. However, the relationship between NAD+ anabolism disturbance and diabetic nephropathy (DN) remains elusive. Here our study found that the disruption of NAD+ anabolism homeostasis caused an elevation in both oxidative stress and fibronectin expression, along with a decrease in Sirt1 and an increase in both NF-κB P65 expression and acetylation, culminating in extracellular matrix deposition and globular fibrosis in DN. More importantly, through constitutively overexpressing NMNAT1 or NAMPT in human mesangial cells, we revealed NAD+ levels altered inversely with NMN levels in the context of DN and, further, their changes affect Sirt1/NF-κB P65, thus playing a crucial role in the pathogenesis of DN. Accordingly, FK866, a NAMPT inhibitor, and quercetin, a Sirt1 agonist, have favorable effects on the maintenance of NAD+ homeostasis and renal function in db/db mice. Collectively, our findings suggest that NMN accumulation may provide a causal link between NAD+ anabolism disturbance and diabetic nephropathy (DN) as well as a promising therapeutic target for DN treatment.

Role of RBM3 in the regulation of cell proliferation in hepatocellular carcinoma.

RNA binding motif protein 3 (RBM3) has been shown to be upregulated in several types of human tumors. Using tissue microarrays and immunohistochemistry, we showed here that both nuclear and cytoplasmic RBM3 expression levels were higher in hepatocellular carcinoma (HCC) tissues than in adjacent non-tumorous tissues. High nuclear RBM3 was found to be correlated with larger tumor size (P = 0.030), high serum AFP levels (P = 0.011), and advanced Edmonson grading (P = 0.006). Cytoplasmic RBM3 was associated with advanced Edmonson grading (P = 0.003). Kaplan-Meier survival analysis revealed that, although not statistically significant, there was a trend toward shortened overall survival in the subset of HCC patients with high RBM3 expression (both nuclear and cytoplasmic). In addition, we found that RBM3 could promote YAP1 expression in HCC cells. Moreover, we found that YAP1 played an essential part in RBM3-induced proliferation of HCC cells. Furthermore, we demonstrated that Verteporfin, a YAP1 inhibitor, could repress RBM3-induced proliferation of HCC cells. Our findings provide a new experimental basis for further understanding of the possible role of RBM3-YAP1 in the regulation of HCC proliferation.

HGF protected against diabetic nephropathy via autophagy-lysosome pathway in podocyte by modulating PI3K/Akt-GSK3ß-TFEB axis.

Podocyte loss is a detrimental feature and major cause of proteinuria in diabetic nephropathy (DN). Our previous study revealed that hepatocyte growth factor (HGF) prevented high glucose-induced podocyte injury via enhancing autophagy. In the current study, we aimed to assess the role of HGF on podocyte homeostasis in DN and clarify its mechanisms further. Diabetic mice treated with HGF had markedly reduced ratio of kidney weight to body weight, urinary albumin excretion, podocyte loss and matrix expansion compared with that in the non-treated counterpart. Simultaneously, HGF-treated diabetic mice exhibited increased autophagy activity as indicated by the decreased accumulation of sequestosome 1 (SQSTM1/ p62) and increased microtubule-associated proteins 1 light chains 3 (LC3) II/LC3I ratio. These beneficial effects of HGF were blocked by HGF/c-Met inhibitor Crizotinib or phosphatidylinositide 3-kinases (PI3K) inhibitor LY294002. Moreover, HGF treatment obviously prevented inactivation of the protein kinase B (Akt)-glycogen synthase kinase 3 beta (GSK3ß)-transcription factor EB (TFEB) axis in high glucose-stimulated podocytes, which was associated with improved lysosome function and autophagy. Accordingly, adenovirus vector encoding constitutively active GSK3ß (Ad-GSK3ß-S9A) offset whereas small interfering RNA against GSK3ß (GSK3ß siRNA) recapitulated salutary effects of HGF on lysosome number and autophagy in podocytes. These results suggested that HGF protected against diabetic nephropathy through restoring podocyte autophagy, which at least partially involved PI3K/Akt-GSK3ß-TFEB axis-mediated lysosomal function improvement.

Fiber Bragg Grating Monitoring of Full-bolt Axial Force of the Bolt in the Deep Strong Mining Roadway.

With the increase of mining depth and strength, the evolution of bolt axial force is increasingly becoming important for ensuring the reliability and safety of support. To improve the problem of the existing coal mine roadway pressure-monitoring method, whereby it is difficult to continuously monitor the axial force of the bolt over a long period of time, a full rod fiber bragg grating (FBG) force-measuring bolt and system were designed based on the principle of fiber grating sensing. It was found that a trapezoidal groove is a relatively better groove. The linearity between the center wavelength offset of the fiber grating and the axial force was more than 0.99, and the conversion formula between the axial force of the bolt rod and the wavelength change of the fiber grating were obtained. The real-time monitoring revealed that the axial force of the bolt obviously changed before and after compression. The axial force distribution curve can be divided into the stable zone, growth zone, and peak zone. The influence of the roadway abutment pressure was approximately 130 m ahead of the working face, and the peak area was within the 25-35 m range of the advance working face. The axial force of the bolt rod at the end of the anchorage linearly increased with the tail end of the bolt, the axial force of the free segment was the largest, and the overall stress was essentially the same. The application results demonstrate the feasibility and effectiveness of the FBG full-length force bolt.

Application of a Layered Muscle Flap Technique for the Reconstruction of the Cupid's Bow and Vermilion in the Repair of Secondary Cleft Lip Deformities.

In the repair of unilateral cleft lip, the Cupid's bow, and vermilion on the affected side are sometimes lowered excessively. Methods involving skin and mucosa flaps have been used to correct this issue, but they pose some risk of scarring. The authors here describe a layered muscle flap technique that was based on the anatomical research of nasal-labial muscles, especially the levator labii superioris alaeque nasi muscle. This technique can be used to suspend the Cupid's bow and vermilion in secondary unilateral cleft lip repair. Forty-five patients with secondary unilateral cleft lip with excessively lowered Cupid's bows and vermilion on the affected side were included in this study, which lasted 3 years. These patients were treated using the layered muscle flap surgical technique. The heights of specific bilateral landmarks were measured on patient photos and used to define the symmetry of bilateral Cupid's bow and vermilion. The comparison between post-operative and pre-operative symmetries was used to evaluate the post-operative results, and most of them were satisfactory. The results were also mostly well retained in follow-up investigations. This layered muscle flap technique could be effective in selected cases.

The molecular mechanism study of insulin on proliferation and differentiation of osteoblasts under high glucose conditions.

To explore the molecular mechanism of insulin on proliferation and differentiation of MC3T3-E1 cell under high glucose conditions. We first investigated the effect of different concentrations of insulin on the osteoblast cell proliferation and cell differentiation at various time points by MTT analysis, cell cycle analysis, and expression detection of differentiation genes. Then, we used 200 ng/mL of insulin to treat the osteoblast cell at different time points for identifying the common differentially expressed mRNAs among various time points by RNA sequencing. Thirdly, we performed the gene ontology (GO) and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) analysis to explore the biological function of these common differentially expressed mRNAs. The results showed that insulin promoted the cell proliferation and differentiation of osteoblast cell. In RNA sequencing, a total of 31 common differentially expressed mRNAs were identified between different time points. Mt1, Tmem135, Avp, and Dlg2 were found to be associated with the new bone formation. In addition, three important signalling pathways, namely, lysosome, glutamatergic synapse, and chemokine signalling pathways, were found in the KEGG enrichment analysis. Our work demonstrated that insulin could promote the osteoblast cell proliferation and cell differentiation, which may play a key role in bone formation. SIGNIFICANCE OF THE STUDY: Our result showed that insulin could promote the proliferation and differentiation of osteoblast at both cellular and molecular levels, which may promote the new bone formation in the osteoblasts.

Erratum: Zhao, Y.; Zhang, N.; Si, G.; Li, X. Study on the Optimal Groove Shape and Glue Material for Fiber Bragg Grating Measuring Bolts. Sensors 2018, 18, 1799.

The authors wish to correct the affiliation of co-author Guangyao Si, due to name changes of which he was unaware during his leave of absence [...].

Identification of Shared Genes Between Ischemic Stroke and Parkinson's Disease Using Genome-Wide Association Studies.

Ischemic stroke (IS) and Parkinson's disease (PD) are two neurological diseases that often strike individuals of advanced age. Although thought of as a disease of old age, PD can occur in younger patients. In many of these cases, genetic mutations underlie the disease. As with PD, stroke can also have a genetic component. Although many of the risk factors for IS are considered to be modifiable, a significant portion is not, suggesting that some of stroke risk factors may have a genetic origin. Large-scale genome-wide association studies (GWAS) have identified several IS and PD gene variants recently. Converging epidemiologic and pathological evidence suggests that IS and PD may be linked. However, it is still unclear whether these two conditions share a common mechanism. Here, we sought to determine the genetic mechanism underlying the possible association between IS and PD. We conducted a multi-step systemic analysis comprising (1) identification of IS and PD variants validated by known GWAS, (2) two separate gene-based tests using Versatile Gene-based Association Study 2 (VEGAS2) and PLINK, (3) a transcriptome-wide association study (TWAS), and (4) analyses of gene expression using an online tool in Gene Expression Omnibus. Our investigation revealed that IS and PD have in common five shared genes: GPX7, LBH, ZCCHC10, DENND2A, and NUDT14, which pass gene-based tests. Functionally, these genes are expressed differentially in IS and PD patients compared to neurologically healthy control subjects. This genetic overlap may provide clues on how IS and PD are linked mechanistically. This new genetic insight into these two diseases may be very valuable for narrowing the focus of future studies on the genetic basis of IS and PD and for developing novel therapies.

Diagnostic errors in fatal medical malpractice cases in Shanghai, China: 1990-2015.

BACKGROUND: Medical disputes remain unabated in China. Previous studies have shown the changes of diagnostic discrepancy over time in developed countries, but diagnostic discrepancy remains understudied in China, especially in the setting of medical disputes. We sought to describe the year-based changes of diagnostic discrepancies in medical disputes, and to identify factors associated with classes of diagnostic discrepancy. METHODS: We conducted a retrospective cohort study of all medically disputed cases from 1990 through 2015 in Shanghai, China, with use of necropsy as the gold standard for diagnosis. Cases were grouped based on national legislative eras. Diagnostic discrepancy was classified as major errors (class I and II), minor errors (class III and IV), no discrepancy (class V) and undetermined (class VI) based on discrepancy severity. RESULTS: There were 482 medical disputes. Cases were predominantly males (male: female = 1.6:1) and concentrated in patients less than 10 years old or between 50 and 70 years. Major and minor discrepancy accounted for 51.7 and 34.8%, respectively. Fifty-five cases (11.2%) were non-discrepant (Class V). The dispute rate remained high before the first round of legislation (mean 0.31 per 1 million patients) but declined dramatically afterwards (R2 = - 0.82, p < 0.001 for time trends). Over the national legislative eras, the annual number of cases with diagnostic errors declined steadily. Incidence rates of discrepancy decreased significantly for class I (R2 = - 0.73, p = 0.024), II (R2 = - 0.48, p = 0.013), III (R2 = - 0.69, p < 0.0001), IV (R2 = - 0.69, p < 0.0001) and V discrepancy (R2 = - 0.58, p = 0.0018). Diseases from the respiratory system had significantly lower risks of any diagnostic errors (OR = 0.48, 95% 0.24-0.95, p = 0.036). A neoplasm carrier increased by 92% the risk of any diagnostic error (OR = 1.92; 95%CI 1.18-3.14; p = 0.009) and hypertension reduced by 78% the risk of minor errors (OR = 0.22, 95%CI 0.06-0.91, p = 0.036). Severity of discrepancy relieved over years and associated with ageing in patients with cardiovascular diseases (p = 0.01). CONCLUSIONS: The rate of fatal medical disputes and diagnostic discrepancy declined after stepwise legislations in China. Respiratory diseases, neoplasm carrier and hypertension could be independent predictors for assessing diagnostic errors.

Effects of MMP-1 1G/2G polymorphism on osteoarthritis: A meta-analysis study.

OBJECTIVE: The aim of this meta-analysis was to clarify the role of Matrix metalloproteinase 1 (MMP-1) -1607 1G/2G (rs1799750) polymorphism on the osteoarthritis (OA) risk. METHODS: Articles were selected by retrieving the Web of Science, Embase and Pubmed. The strength of the association between -1607 1G/2G polymorphism and OA risk was assessed by odds ratios (ORs) with the corresponding 95% confidence interval (CI) for each study. RESULTS: No significant association between -1607 1G/2G polymorphism and OA risk was found in all the models overall (2G2G vs 1G1G, OR (95%CI) = 0.69 (0.36-1.32), P = 0.54; 2G2G + 2G1G vs 1G1G, OR (95%CI) = 0.88 (0.47-1.63), P = 0.69; 2G2G vs 2G1G + 1G1G, OR (95%CI) = 1.30 (0.68-2.47), P = 0.41; 2 G vs 1G, OR (95%CI) = 0.90 (0.86-1.54), P = 0.66). By subgroup analysis, significant association was found in the "< 60 years" group (2G2G vs 1G1G, OR (95%CI) = 3.46 (2.13-5.62), P = 0.00; 2G2G + 2G1G vs 1G1G, OR (95%CI) = 0.49 (0.31-0.79), P = 0.00; 2G2G vs 2G1G + 1G1G, OR (95%CI) = 2.74 (1.80-4.16, P = 0.00; 2 G vs 1G, OR (95%CI) = 0.56 (0.35-0.89), P = 0.01). CONCLUSIONS: This meta-analysis showed that -1607 1G/2G polymorphism may increase the susceptibility to OA among the younger populations (<60 years). More studies with detailed information are needed to validate our conclusion. LEVEL OF EVIDENCE: Level I Diagnostic Study.

Study on the Preferred Application-Oriented Index for Mental Fatigue Detection.

Most of the research on mental fatigue evaluation has mainly concentrated on some indexes that require sophisticated and large instruments that make the detection of mental fatigue cumbersome, time-consuming, and difficult to apply on a large scale. A quick and sensitive mental fatigue detection index is necessary so that mentally fatigued workers can be alerted in time and take corresponding countermeasures. However, to date, no studies have compared the sensitivity of common objective evaluation indexes. To solve these problems, this study recruited 56 human subjects. These subjects were evaluated using six fatigue indexes: the Stanford sleepiness scale, digital span, digital decoding, short-term memory, critical flicker fusion frequency (CFF), and speed perception deviation. The results of the fatigue tests before and after mental fatigue were compared, and a one-way analysis of variance (ANOVA) was performed on the speed perception deviation. The results indicated the significance of this index. Considering individual differences, the relative fatigue index (RFI) was proposed to compare the sensitivity of the indexes. The results showed that when the self-rated fatigue grade changed from non-fatigue to mild fatigue, the ranges of RFI values for digital span, digital decoding, short-term memory, and CFF were 0.175⁻0.258, 0.194⁻0.316, 0.068⁻0.139, and 0.055⁻0.075, respectively. Correspondingly, when the self-rated fatigue grade changed to severe fatigue, the ranges of RFI values for the above indexes were 0.415⁻0.577, 0.482⁻0.669, 0.329⁻0.396, and 0.114⁻0.218, respectively. These results suggest that the sensitivity of the digital decoding, digital span, short-term memory, and CFF decreased sequentially when the self-evaluated fatigue grade changed from no fatigue to mild or severe fatigue. The RFI individuality of the speed perception deviation is highly variable and is not suitable as an evaluation index. In mental fatigue testing, digital decoding testing can provide faster, more convenient, and more accurate results.

SIRT1 promotes formation of breast cancer through modulating Akt activity.

The silent information regulation factor 1 (sirtuin Type 1, SIRT1), as a kind of NAD+ dependent class III histone deacetylation enzyme, has been found to be involved in tumor proliferation, invasion, and metastasis. The roles of SIRTl in breast cancer is multifaceted depending on its substrate from upstream or downstream signaling pathway. In this study, we sought to make clear the regulating effects of SIRT1 in breast cancer cells, and to explore the underlying mechanisms through which SIRT1 regulates breast cancer. First, our results showed that SIRT1 was significantly up-regulated in breast cancer tissues and cells, which correlated with histological grade, tumor size, as well as lymph node metastasis. Then we established SIRT1-overexpressed and SIRT1- knockdown breast cancer cell lines to investigate the functions of SIRT1 in regulating colony formation, cell proliferation, cell cycle, cell apoptosis and migration. We found that overexpression of SIRT1 significantly promoted breast cancer growth both in vitro and in vivo, whereas knockdown of SIRT1 inhibited these phenotypes. Furthermore, SIRT1 was found to interact with Akt directly, consequently promoting the activity of Akt in breast cancer cells in vitro and positively correlating with expression of Akt, P-Akt, in breast cancer tissues in vivo. Down regulation the activity of Akt partially weakened the proliferative effect mediated by SIRT1. Taken together, our results demonstrated SIRT1's tumor promotion function and potential mechanisms in breast cancer, thus providing valuable therapeutic targets for breast cancer.