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本文阐述了临床上前庭康复的几个关键问题。根据前庭代偿的原理，前庭代偿存在窗口期或关键期；前庭康复的临床策略包括凝视稳定性训练、姿势稳定性训练和习服训练；前庭康复选择基于前庭疾病分类，即根据急性、发作性和慢性前庭综合征指导选择前庭康复策略；根据前庭代偿过程中，不同前庭功能检查结果与前庭康复之间的关系，通过前庭功能检查方法动态评价、观察前庭康复的进展，也是临床上前庭康复工作的迫切需要。.

Background The relationship between arrhythmia and coronary slow flow (CSF) is unclear. We aimed to explore the association between atrial fibrillation (AF) and CSF. Method In this cross-sectional study, we included 2,060 participants patients from PCI-registry (NCT 02498470) who underwent coronary angiography with clinical chest pain and without significant coronary stenosis. According to coronary blood flow rate measured by the thrombolysis in myocardial infarction frame count (TFC) method, CSF was defined as TFC>27. AF was identified by ECG performed during hospitalization. We used logistic regression to assess the association between AF and CSF. Results Among 2,060 participants, 132 participants were diagnosed with AF. CSF rates were higher in AF group than in the control group (22.0% vs 13.9%, P=0.011). Logistic regression showed that AF was independently associated with CSF after adjustment for traditional risk factors (OR=2.06; 95%, 1.28–3.34; P=0.003). Conclusion Our study demonstrated that AF was association with increased risk of CSF. Further studies are needed to confirm this finding and explore the potential mechanism. Funding Acknowledgement Type of funding sources: None.

Background The association between daily carbohydrate intake and right ventricular (RV) morphology has not been well studied. We aimed to figure out the relationship between daily carbohydrate intake and right ventricular structure and function in a large multiethnic population-based cohort. Methods The Multi-ethnic Study of Atherosclerosis (MESA) -Right Ventricle Study measured RV mass and volumes by cardiac MRI in participants aged 45 to 84 years without clinical cardiovascular disease (CVD) in the MESA study. Participants were divided into three groups based on average daily carbohydrate intake: low (≤45%), medium (45–55%), and high (≥55%). Results The study sample included 3,776 participants which were aged 61.5±10.1 years, 47.5% male, 40.0% white, 24.9% African American, 21.8% Hispanic, and 13.3% Chinese. Higher levels of daily carbohydrate intake were linearly associated with greater RV stroke volume (RVSV), and RV ejection fraction (RVEF) (P Conclusions Carbohydrate intake was independently associated with differences in RV morphology after adjustment for all covariates. This association may be explained by the decreased intake of specific nutrients from carbohydrates. Given the nature of the study, causality cannot be proven. Therefore, further studies are needed to extend these findings, which if confirmed, may suggest a need to rethink recommendations for carbohydrate intake in clinical practice, for optimal nutrient achievement, meals need to be well formulated. Funding Acknowledgement Type of funding sources: None.

Background Malnutrition is commonly prevalent in patients with heart failure (HF) and associated with poor prognosis. However, few studies have explored the association between malnutrition status and incident HF in community population. Method 379,759 participants (46.3% women) without HF at baseline from the UK Biobank were included. Nutritional status was evaluated using the Controlling Nutritional Status (CONUT) score, with higher scores reflecting worse nutritional status. Association between CONUT score and incident HF were investigated using Cox proportional hazard regression models, with adjustment for traditional risk factors. Results During a median follow-up of 8.1 years, 5,520 cases (1.5%) of HF occurred. The hazard ratio for incident HF with 1-point increase of CONUT scores was 1.16 (95% CI, 1.12–1.20, P Funding Acknowledgement Type of funding sources: None.

Background Little is known about whether the residential distance to coast is associated with incident myocardial infarction (MI), as well as which mechanisms may explain the association. We aim to explore this association using data from a prospective, population-based cohort with unprecedented sample size and broad geographical coverage. Methods 377,340 participants from the prospective, population-based UK Biobank cohort were included. Residential distance to the coast was defined as participant's residence location to coast. Results 4,059 MI occurred during median 8.0 years follow-up. Using group (64 km) were both associated with a higher risk of incident MI (HR 1.12, 95% CI 1.04–1.21 and HR 1.09, 95% CI 1.01–1.18, respectively). HR for offshore region (64 km) was larger in subgroup in urban area (HR 1.12, 95% CI 1.03–1.22, Pinteraction = 0.065) and in subgroup of high nitrogen dioxide air pollution (HR 1.29, 95% CI 1.11–1.50, Pinteraction = 0.021). Conclusions Our findings highlight the complex and diverse associations between residential distance to the coast and incident MI. Funding Acknowledgement Type of funding sources: None. Figure 1

Background Currently, coronary artery disease (CAD) is a main cause of mortality worldwide. Exposing the unknown pathogenic mechanism and exploring potential therapeutic targets of CAD is a critical issue in current CAD research. We aimed to identify potential therapeutic target for CAD using 2-sample Mendelian randomization (MR) approach among differential expression proteins between CAD and control group. Methods Serum samples from 16 first-onset CAD patients diagnosed by coronary angiography and 10 non-CAD controls were collected and detected using protein array. We identified differentially expressed proteins based on “DEseq2” R package and found the core module using MCODE plugin in Cytoscape. Proteins in core modules were used as candidate protein for causal inference. Genetic instrument variables (IV) of candidate proteins were extracted from Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-RS). Two-sample MR was performed to detect the causal association between the candidate proteins and CAD. For the identified protein causally associated with CAD, sensitivity analyses were used to confirm the finding, including using other MR approach, using more stringent instrument variables, and external cohorts for verification. Network MR was performed to explore whether metabolic risk factors for CAD mediated the risk of identified proteins, including indices of lipid metabolism, glucose metabolism, obesity and blood pressure. Mediation analysis was used to measure the effect of mediation. Results A total of 81 differentially expressed protein were found in CAD group compare to control group, among which 3 core functional modules were found. In five candidate proteins with available instrumental variables, only GP73 was causally associated with CAD risk. Per 1 SD increment in genetically determined GP73 level was associated with 12% increased CAD risk (odds ratio: 1.12; 95% confidence interval: 1.06–1.18, FDR Conclusion Based on protein array and bioinformatics analysis, this study screened out 3 modules that play core functions in the differential expressed proteins. Among the 19 proteins in the core module, there was a causal relationship between circulating GP73 levels and incident CAD, and the causal effect is mainly mediated by lipid metabolism. The results suggest that GP73 can not only be used as a novel biomarker of CAD, but also may provide a new potential therapeutic target for the management of CAD. Funding Acknowledgement Type of funding sources: None. Figure 1

Colorectal cancer (CRC) is the fourth leading cause of death worldwide and there is a need for more specific therapeutic targets and biomarkers for the disease. Transforming growth factor β1-induced transcript 1 (TGFΒ1I1) was reported to be downregulated in CRC tissues; however, the precise roles of TGFΒ1I1 in CRC remain unclear.The expression of TGFΒ1I1 in CRC cell lines and tissues was assessed by quantitative Polymerase Chain Reaction (qPCR). TGFΒ1I1 was overexpressed in SW620 and RKO cells. Cell viability was analyzed by a CCK-8 assay. The proportion of apoptotic cells was analyzed by flow cytometry. The EdU cell proliferation assay of SW620 and RKO cells after transfection was performed via flow cytometry. The migration potency of SW620 and RKO cells was analyzed using a cell migration assay. A wound healing assay was performed to assess the migration potency of SW620 and RKO cells. The invasion potency of SW620 and RKO cells after TGFΒ1I1 overexpression was analyzed. The protein levels of VEGF, TGF-β, MMP9, p-Smad2/3, N-cadherin, and E-cadherin were analyzed by Western blot.Decreased expression of TGFΒ1I1 was found in CRC tissues and cell lines. Overexpression of TGFΒ1I1 inhibited the proliferation and induced the apoptosis of CRC cells. The overexpression of TGFΒ1I1 inhibited the migration and invasion of CRC cells. We also found that the overexpression of TGFΒ1I1 in CRC cells inhibited the TGF-β pathway and epithelial-mesenchymal transition (EMT) progress.TGFΒ1I1 suppressed cell migration and invasion in CRC by inhibiting the TGF-β pathway and EMT progress.

Background A combination of analgesic agents with different mechanisms can induce additive or synergistic analgesia. The N-type voltage-dependent calcium channel (N-VDCC) is a novel therapeutic target for pain control. In addition to providing effective pain relief when used alone, N-VDCC blockers produce synergistic analgesia when used in combination with opiates. However, the interaction between N-VDCC blockers and nonsteroidal anti-inflammatory drugs (NSAIDs) remains unclear. Methods Using isobolographic analysis and composite additive curve analysis, the antinociceptive interaction between ZC88, a selective N-VDCC blocker and ibuprofen, a classical NSAID, was investigated in two mouse models of visceral and somatic inflammatory pain. Results In the acetic acid writhing test, both ZC88 (10.5-42 mg/kg, intraperitoneally) and ibuprofen (50-200 mg/kg, orally) produced dose-dependent antinociception, with ED50 values of 27.2 and 100.5 mg/kg, respectively. ZC88 in combination with ibuprofen (ZC88 + ibuprofen) also induced significant antinociception, and isobolographic analysis revealed a synergistic interaction at 50% effect level. The experimental ED50 (ED50 mix ) of this combination (34.5 mg/kg) was significantly lower than the theoretical ED50 (ED50 add ; 63.8 mg/kg). Additionally, composite additive curve analysis displayed synergistic interaction at other effect levels. In the formalin test, ZC88 or ibuprofen alone significantly reduced late-phase rather than early-phase pain, with ED50 values of 31.3 and 123.9 mg/kg, respectively. Similarly, both isobolographic analysis and composite additive curve analysis revealed synergistic antinociception of ZC88 + ibuprofen (40.6 mg/kg of ED50 mix vs. 77.6 mg/kg of ED50 add ). Conclusion ZC88 in combination with ibuprofen produces synergistic antinociception in mouse models of somatic and visceral inflammatory pain. Significance Because ZC88 + ibuprofen achieves the same antinociceptive effect at lower doses, the use of this combination could result in fewer dose-related untoward effects. The potentiation of ZC88 on ibuprofen-induced antinociception indicates that N-VDCC blocker has potential benefit to treat severe inflammatory pain.

The cultivated peanut, A. hypogaea L., is an important oil and food crop globally.High-density genetic linkage mapping is a valuable and effective method for exploring complex quantitative traits. In this context, a recombinant inbred line (RIL) of 146 lines was developed by crossing Huayu28 and P76. We developed 433,679 high-quality SLAFs, of which 29,075 were polymorphic. 4,817 SLAFs were encoded and grouped into different segregation patterns. A high-resolution genetic map containing 2,334 markers (68 SSRs and 2,266 SNPs) on 20 linkage groups (LGs) spanning 2586.37 cM was constructed for peanut. The average distance between adjacent markers was 2.25 cM. Based on phenotyping in seven environments, QTLs for oleic acid (C18:1), linoleic acid (C18:2) and the ratio of oleic acid to linoleic acid (O/L) were identified and positioned on linkage groups A03, A04, A09, B09 and B10. Marker2575339 and Marker2379598 in B09 were associated with C18:1, C18:2 and O/L in seven environments, Marker4391589 and Marker4463600 in A09 were associated with C18:1, C18:2 and O/L in six environments. This map exhibits high resolution and accuracy, which will facilitate QTL discovery for essential agronomic traits in peanut.

Objective This study aimed to investigate the role of long non-coding RNA MEG3 (lncRNA MEG3) in osteosarcoma (OS) and further explore the underlying molecular mechanism. Materials and methods The expression profiles of MEG3 in OS cell lines and normal osteoblast cell line were detected by qRT-PCR. MEG3 was over-expressed in OS cell line by using LV-MEG3. MTT and colony-formation assays were applied for cell proliferation analysis. Cell migration assay was applied to investigate the cell migration ability. In addition, the expression levels of cell growth and metastasis related factors (Notch1, Hes1, TGF-β, N-cadheren and E-cadheren) were determined to illustrate the mechanisms. Results We found that compared with normal osteoblast hFOB1.19 cell line, MEG3 was significantly down-regulated in MG63 and U2OS cell lines, particularly in MG-63 cells. MEG3 was significantly up-regulated in MG63 cells by LV-MEG3. Cell proliferation and migration ability were obviously repressed by MEG3 over-expression. In addition, MEG3 over-expression markedly inhibited Notch1, Hes1,TGF-β and N-cadheren expression, and the expression level of E-cadheren was improved. Conclusions These results indicated that MEG3 could prevent cell growth and metastasis of OS by repressing Notch and TGF-β signaling pathway, thus providing a potential therapeutic target for OS treatment (Tab. 1, Fig. 4, Ref. 30).

Traditional Chinese medicine (TCM) prescriptions have been developed for thousands of years. Data forms are diverse, content is discrete and missing, and there are many uncertainties due to cultural and regional differences. Therefore, it has brought some difficulties to the mining of TCM prescriptions. Data based on the 3108 prescriptions for the treatment of typhoid fever, for example, is given priority to with data cleaning and data transformation of data preprocessing, prescriptions combined with multiple functions, expounds the unqualified prescriptions data cleansing, drug name normalization, dose for solving the problems of the unification, the data structured method, make the processed data can be effectively mining, It provides a strong support for exploring the compatibility law of prescription and the development of new drugs.

A new macrocyclic oxamido carboxylate metalloligand was designed and three heteronuclear coordination polymers of the metalloligand and metal nodes Cu2+, Zn2+ and Cd2+ were prepared. X-ray single crystal analyses (CIF files CCDC nos. 1025722–1025724 for I–III) revealed that multiple favourable features endowed the metalloligand with a strong power to force the metal nodes to generate 1D helical coordination polymers. Thermogravimetric analyses showed that the complexes with Cu2+ and Zn2+ nodes exhibited moderate thermal stability. The three complexes were also characterized by IR spectra and PXRD.

Objectives The aim of this study was to investigate the predictive factors for relapse of IgG4-related disease (IgG4-RD) and observe the long-term clinical outcomes in patients with IgG4-RD. Methods We included in the present analysis 122 patients who were newly diagnosed with IgG4-RD, treated with glucocorticoid (GC) monotherapy or GC and immunosuppressant combination therapy, and followed for at least 3 years. Clinical relapse, response and side effects were recorded. Results The cumulative relapse rates of patients in this study were 10.66%, 22.95% and 27.87% at 12, 24 and 36 months, respectively. Complete drug withdrawal was an independent risk factor for disease relapse. Higher serum IgG4 concentrations, involvement of more organs, higher IgG4 RI scores and elevation of eosinophils at baseline were closely associated with disease relapse. Re-elevation of serum IgG4 concentrations and low GC maintenance dosage during the follow-up period were significantly associated with clinical relapse. The GC dosage should be more than 6.25 mg day-1 as monotherapy during the maintenance stage; moreover, combining with immunosuppressants can reduce the GC dosage. Adding GC or immunosuppressants for patients with re-elevation of serum IgG4 levels could prevent later disease relapse. No serious complications were noted during long-term follow-up. Conclusions The combination of GC with immunosuppressants was more effective than GC monotherapy during the steroid tapering and maintenance stages. Higher serum IgG4 levels, involvement of more organs, higher IgG4 RI scores, history of allergy, eosinophil elevation at baseline, re-elevation of serum IgG4 levels and lower GC maintenance dosage at follow-up might be predictive of relapse.

In view of the problems of low efficiency, prone to misjudgment, and complicated identification levels in the current market, the use of manual judgment methods for the cause of tire damage. A method of tire damage image recognition based on convolutional neural network algorithm is proposed, and an intelligent tire damage image recognition system is designed. Through image processing, feature extraction, classification and identification of the input tire damage image, the computer can automatically output the cause of the damage. The experimental results show the feasibility of this method and also improve the shortcomings of traditional manual judgment of the cause of tire damage.

Diseases caused by Aeromonas veronii in freshwater fish have been widely reported, but other species such as aquatic mammals have probably been overlooked. Here, we identified one isolate of A. veronii from a Yangtze finless porpoise Neophocaena asiaeorientalis asiaeorientalis exhibiting disease and mortality, and subsequently confirmed its virulence in artificial infection of BALB/c mice. The bacterial isolate was identified as A. veronii based on physiological, biochemical, and phenotypic features, and homology of the 16S rRNA, cpn60, rpoB, dnaJ and gyrB genes. Our results expand the known host spectrum of A. veronii, which is of great importance for the etiology of porpoise, dolphin, and other cetacean diseases.

To explore the effect of STEEL on fracture healing and its underlying mechanism.A total of 31 patients with long bone fracture and who received reoperation because of bone nonunion, delayed union or healing disorder in the Wuxi Nine Hospital Affiliated to Soochow University from July 2016 to February 2018 were selected. The bone callus at the fracture site was collected from each patient during the reoperation. QRT-PCR (Quantitative Real-Time Polymerase Chain Reaction) was used to detect STEEL expression in the callus tissues of the treatment group (bone nonunion or delayed union) and the control group. In addition, we measured the number of blood vessels in the fracture tissues by immunohistochemistry. After the construction of tibial fracture model in mice, STEEL expression and the total number of blood vessels in the treatment group (sawing treatment) and the control group (sham operation) were detected, respectively. For in vitro experiments, CCK-8 (cell counting kit-8) assay was performed to detect cell proliferation after knockdown or overexpression of STEEL in the vascular endothelial cells. The binding condition of STEEL and its interacting proteins were detected by RIP (RNA binding protein immunoprecipitation), and the binding of PARP 1 [poly (ADP-ribose) polymerase 1] with gene promoter was observed by ChIP (chromatin immunoprecipitation assay). Western blot was used to detect the expression level of VEGF (vascular endothelial growth factor).STEEL expression and the vascular density in the callus tissues of the treatment group were significantly lower than those of the control group. Downregulated STEEL remarkably decreased the proliferation ability of HUVEC cells. Meanwhile, the vascular density was also significantly decreased in mice with a tibial fracture. Overexpressed STEEL obtained the opposite results. STEEL could interact with PARP 1 to regulate expressions of downstream genes. Moreover, STEEL could also promote angiogenesis by elevating VEGF expression.We showed that STEEL expression could partly represent the angiogenesis of fracture sites. Moreover, it promoted angiogenesis by elevating VEGF expression.

Lactate dehydrogenase C4 (LDH-C4) is considered to be a good target protein for the development of contraceptive drugs. To develop contraceptive rodenticide against pika (Ochotona curzoniae) LDH-C4, the pika LDH-C gene was cloned and expressed in Escherichia coli. The recombinant protein was purified and characterized. The cDNA of pika LDH-C gene was cloned by RACE method. The cDNA was 1498 bp in length containing an ORF of 996 bp which encoded a polypeptide of 332 amino acids. The ORF of pika LDH-C was introduced in E. coli and expressed with no fusion tags added. The recombinant LDH-C4 protein was purified by heating, affinity chromatography and ion-exchange chromatography. The recombinant pika LDH-C4 was a tetramer with a molecular weight of approximately 140 kDa, and it had temperature-dependent catalytic activity, as it was thermally stable up to 60 degrees C. The optimal pH values in the forward and backward reactions were around 7.48 and 10.28, respectively. The apparent Michaelis constants for pyruvate and lactate were 51.2 +/- 3.8 and 8568.8 +/- 409 microM respectively. The inhibition constant for oxalic acid was 11.8 +/- 3.5 mM. This study laid a solid foundation for contraceptive rodenticide development against pika LDH-C4.

The southern Chinese Osmunda ×mildei has been suggested to be an intersubgeneric hybrid, i.e., O. japonica (subgenus Osmunda) × O. angustifolia (subgenus Plenasium) or O. japonica × O. vachellii (subgenus Plenasium). These interpretations were based on morphological, cytological, and/or chloroplast DNA data, yet the parents of the hybrid remained unclear. Molecular phylogenetic relationships inferred here from chloroplast rbcL sequences and three nuclear DNA markers show that O. ×mildei is most likely a hybrid between the paternal O. japonica and the maternal O. vachellii.

The hot deformation behaviour and microstructural evolution of a near-α titanium alloy (Ti–5·6Al–4·8Sn–2Zr–1Mo–0·35Si–0·7Nd) containing 0·06%C or 0·3%C with bimodal or Widmanstatten starting microstructures were investigated using isothermal compression test at strain rates of 0·01–10 s−1 in the α+β or β regions. In the α+β region, both alloys exhibited continuous flow softening. The globularisation of transformed β structure or the recrystallisation of globular α phase took place, which was more remarkable in the 0·3%C alloy. In the β region, both alloys exhibited steady-state flow behaviour. Dynamic recrystallisation of the β phase occurred in the 0·06%C alloy, while was absent in the 0·3%C alloy. Due to the solution hardening of carbon atoms for the phases and the pinning effect of the carbides on grain boundary, the apparent activation energies of the 0·3%C alloy are higher than those of the 0·06%C alloy in the corresponding α+β or β phase regions.

In order to acidize whole horizontal well interval uniformly, temporary plugging technology was chosen as one of the most effective methods. Laboratory tests were also carried out to evaluate their diverting properties. The results show that clean self-diverting acid could increase its viscosity during reaction with carbonate, and which made it divert to other layers. And for fiber, it has good temporary plugging and degradable performance, which can meet the demand of uniform acidification and lower damage to oil reservoir. According to the analysis of fiber characteristic, some using principles were also given. This technology was applied on ten wells, and temporary plugging and diverting display could be clearly observed by observing pumping pressure change. Furthermore, final production rate after stimulated was increased obviously. All these results showed that this technology could get a better application effect in horizontal well acidification.

Of 87 short-season soybean cultivars evaluated for reactions to three races (1, 3, and 5) of Phytophthora sojae Kaufmann and Gerdemann, 29 showed resistance to at least one of the three races. These resistant sources may be used for pyramiding Rps genes and deployment of P. sojae resistant soybean cultivars in Canada. Key words: Soybean, Glycine max, phytophthora root and stem rot, Phytophthora sojae

The aim of this study was to evaluate the anatomical and clinical relationship between lacunar infarction and the corticospinal tract (CST) in patients with acute lacunar infarction and predict clinical outcome. We examined 28 pyramidal tract stroke patients in the acute phase or early subacute phase (3 days) with a marked motor deficit. The anatomical location and the extent of CST involvement within the infarcts were visualized on three-dimensional colour-coded diffusion tensor tractography (DTT). With regard to the CST, all patients were divided into three clinical subgroups: Group 1 (intact type), Group 2 (partial involvement type) and Group 3 (whole involvement type). Subsequently, the severity of the motor deficit of each patient was determined according to the National Institutes of Health Stroke Scale (NIHSS) scores at the acute/early subacute phase (3 days after onset of symptoms), early chronic phase (8-14 days) and outcome (30-60 days). NIHSS scores of Group 1 (12/28) were significantly lower than those of Group 2 (9/28) at the acute phase or early subacute phase (U = -2.816, p0.01), and those of Group 2 were significantly lower than those of Group 3 (7/28) (U = -3.136, p0.01). At outcome,NIHSS scores of Group 1 were significantly lower than those of Group 2 (U = -2.846, p0.01), and scores of Group 2 were significantly lower than those of Group 3 (U = -3.130, p0.01). At the same time, the NIHSS scores of each group gradually decreased from acute phase to outcome, Neurological improvement was statistically different among the three topographical types of infarction (H = 26.15, p0.01; H = 11.03, p0.01; H = 10.05, p0.01). In conclusion, the three-dimensional colour-coded DTT allows in vivo differentiation of distinct CST stroke subtypes and may help in better establishing the prognosis for patients after CST stroke.

Lactate dehydrogenase C4 (LDH-C4) is considered to be a good target protein for the development of contraceptive drugs. To develop contraceptive rodenticide against pika (Ochotona curzoniae) LDH-C4, the pika LDH-C gene was cloned and expressed in Escherichia coli. The recombinant protein was purified and characterized. The cDNA of pika LDH-C gene was cloned by RACE method. The cDNA was 1498 bp in length containing an ORF of 996 bp which encoded a polypeptide of 332 amino acids. The ORF of pika LDH-C was introduced in E. coli and expressed with no fusion tags added. The recombinant LDH-C4 protein was purified by heating, affinity chromatography and ion-exchange chromatography. The recombinant pika LDH-C4 was a tetramer with a molecular weight of approximately 140 kDa, and it had temperature-dependent catalytic activity, as it was thermally stable up to 60 degrees C. The optimal pH values in the forward and backward reactions were around 7.48 and 10.28, respectively. The apparent Michaelis constants for pyruvate and lactate were 51.2 +/- 3.8 and 8568.8 +/- 409 microM respectively. The inhibition constant for oxalic acid was 11.8 +/- 3.5 mM. This study laid a solid foundation for contraceptive rodenticide development against pika LDH-C4.

The aim of this study was to identify the hub genes and dysregulated pathways of hepatocellular carcinoma (HCC) and explore the molecular mechanism of the biological process associated with HCC.Microarray data were got from NCBI Gene Expression Omnibus (GEO) database. The most significant top 100 up-regulated gene signatures and top 100 down-regulated gene signatures were identified by integrated analysis of the multiple microarray datasets using a novel model genome-wide relative significance (GWRS) and genome-wide global significance (GWGS). Gene Ontology (GO) enrichment analysis and pathway analysis of those genes were performed based on Gene Ontology website and Kyoto Encyclopedia of Genes and Genomes (KEGG). Protein-protein interaction (PPI) network was constructed using Cytoscape 2.1. In addition, we analysed the significantly dysregulated signaling pathways across the PPI network and KEGG pathway analysis.We screened 2920 up-regulated and 2231 down-regulated gene signatures across multiple studies by GWRS and GWGS. The top 100 up-regulated and top 100 down-regulated gene signatures were selected for further research. GO enrichment analysis showed that these genes significantly enriched in terms of mitosis (p = 5.83×10-20), nuclear division (p = 5.83×10-20) and M phase of mitotic cell cycle (p = 9.39×10-20). The most significant terms of KEGG pathway included cell cycle (p = 1.33×10-8), oocyte meiosis (p = 1.41×10-4), drug metabolism (p = 2.15×10-4) and p53 signaling pathway (p = 3.57×10-4). PPI network suggested that BIRC5, CDC20, CCNB1, BUB1B, MAD2L1 and CDK1 were important significant genes which were considered as hub genes. Across the PPI and pathway, cell cycle, oocyte meiosis and p53 signaling pathway were the significantly dysregulated pathways.Our study displayed robust gene signatures in HCC. It showed that the dysregulations of cell cycle, oocyte meiosis, p53 signaling pathway and progesterone-mediated oocyte maturation pathway were closely associated to the development and progression of HCC. Besides, genes BIRC5, CDC20, CCNB1, BUB1B, MAD2L1 and CDK1 as the hub genes might play important roles for diagnosing and therapy of HCC.

2-Aminoethoxydiphenyl borate (2-APB) has been recently identified as a common agonist of TWIK-related K + channel (TREK)/TRAAK channels, a subfamily of two-pore domain K + (K2P) channels. TREK-2 displays much higher sensitivity to 2-APB compared with TREK-1, despite that these two channels share the highest homology among K2P members. However, the structural basis for their difference in response to 2-APB still remains unknown. Here we identified that the cytosolic C-terminus (Ct) domain plays a dominant role in controlling the stimulatory effects of 2-APB on TREK-2 channel. The distal Ct region negatively regulates the effect of 2-APB, while the proximal Ct is sufficient to evoke the full 2-APB activation of the channel. Further mapping within the proximal Ct revealed that His368 is required for 2-APB activation, and the cooperation of the other non-conserved residues is also necessary. We also identified a secondary active site for 2-APB, which is located at the bottom of the transmembrane segment M2. Finally, we demonstrated that key residues or domains required for 2-APB activation are not involved in the gating mechanism of the selectivity filter. In summary, we reveal a unique modulatory model of TREK-2-Ct that distinguishes it from TREK-1 in high sensitivity to 2-APB. The cooperation of the non-conserved residues within the proximal Ct of TREK-2 plays a dominant role in the 2-APB-induced channel opening, whereas the distal Ct negatively regulates the process.

Microstructural changes in Ti-5.6Al-4.8Sn-2.0Zr-1Mo-0.34Si-0.7Nd containing different amounts of carbon during solution treatment in the upper (α + β) field have been investigated. It was observed that the (α + β)/β transus temperature increases rapidly in the carbon range 0-0.32 wt-% and exhibits a maximum at a content of 0.32 wt-%, while the α/(α + β) transus temperature increases in a much less pronounced manner. For solution treatment in the high temperature (α + β) phase field, carbon addition in the range 0-0.23 wt-% retards the change in volume fraction of the primary α phase with temperature. This makes it easier to adjust the volume fraction of the primary α phase through control of heat treatment temperature. Regression equations to predict the variation of volume fraction of primary α phase were obtained by multiple regression analysis. The experimental results are discussed in terms of phase composition analysis and the Ti-8Al-C phase diagram.

The impedance as well as the resistance and reactance of the La0.75Sr0.25MnO3 manganite increase with increasing ac frequency due to the skin effect of the metal state below Curie temperature. The manganite La0.75Sr0.25MnO3 shows not only the colossal magnetoresistance effect but also the giant magnetoimpedance effect. For the giant magnetoimpedance, the magnetic field influences the impedance by affecting the penetration depth via the transverse permeability, whereas for the colossal magnetoresistance the magnetic field tends to align the local spins, leading to the decrease of the dc resistance via the interplay between a strong electron-phonon coupling and the double exchange effect of spin alignment on electron kinetic energy. (C) 2002 American Institute of Physics.

This work aims to detect the peritoneal fluid proteomic patterns in endometriosis patients, build diagnostic models, and evaluate its clinical significance.The authors used SELDI-TOF-MS protein chip array technology to detect biomarkers of peritoneal fluid in endometriosis patients. Fourteen endometriosis patients and 16 persons without endometriosis as control group were tested.Four potential biomarkers (4428m/z, 6891m/z, 13766m/z, and 6427m/z) were found.This method showed great potential in screening better biomarkers for endometriosis.

The single-dose pharmacokinetics of two gastric-retentive, extended-release tablet formulations of metformin hydrochloride in fed, healthy volunteers were compared with those of the currently marketed immediate-release metformin hydrochloride product. The plasma concentration-time profiles demonstrated extended-release characteristics from the gastric-retentive tablets. The mean bioavailability from each gastric-retentive tablet was approximately 115%, relative to the immediate-release (IR) product. Cmax values were lower and tmax values were greater for the gastric-retentive tablets compared with the IR product. In contrast to conventional extended-release metformin tablets reported in the literature, these gastric-retentive tablets showed extended-release plasma concentration profiles of metformin hydrochloride and increased bioavailability compared with the immediate-release tablet.

The manipulability of robot manipulators has been studied with respect to the ability to position the end-effector in its workspace. However, since manipulators have to manipulate objects with finite dimensions, the ability of a manipulator to position and orient an object is quite different from its end-effector manipulability. Object shape dependent kinematic manipulability measures are essential for the formulation of optimal path planning and trajectory synthesis algorithms used for moving objects in operations such as mating parts and for formulating related object shape optimization problems. The optimality criterion may be related to part positioning accuracy, mating accuracy, kinematics performance of the manipulator for applying force (torque) to the object at some stage of the assembly, or a number of other accuracy, force or control measures. In the present study, a class of shape dependent kinematics measures is developed for the object manipulability. The measures can be used to evaluate the manipulability of objects with various shapes, for path and trajectory synthesis, and for designing object shapes. No rigid body constraint is imposed and the object considered may be deforming, stretching or shrinking during its manipulation. A number of examples are presented.

We investigate the dynamics of an elastic medium described by a two-dimensional network of nodes of equal mass connected by springs whose force constants are equal inside the network and chosen at random at its surface. The system can be considered a billiard in the sense that the network is ordered all throughout its bulk. Being an eigenvalue problem its complexity is manifested in a frequency statistics which, in most of the spectrum, can be described by the Wigner-Dyson distribution. At low frequencies the dispersion relation is linear in the wave number and the network shows regular behavior (frequency statistics according to Poisson distribution). We study the dynamical behavior of this model by investigating how the system escapes from a normal mode of the ordered network, and calculate the Lyapunov exponent $\ensuremath{\lambda}$ in different frequency regions.

The recent liquidus-tracking method developed by Pegg et al. (2006a), as an alternative pathway to vitrification, achieved reasonable survival of post-thawing chondrocytes in situ. One of the main drawbacks of this method is the long duration of the cryoprotectant addition/removal process. This study was conducted to investigate the possibility of reducing the time by rationalizing the final dimethyl sulfoxide (Me2SO) concentration loaded in tissue before being plunged into liquid nitrogen. Using the differential scanning calorimetric technique, the critical cooling and warming rates for solutions of Me2SO in CPTes2 (a potassium-rich medium, modified slightly from Taylor's original formulation by Pegg et al.) were obtained. The critical cooling and warming rates for 47.5 percent (w/w) solution are2.5 degree C per min and10 degree C per min, respectively, which could be readily realized for 4 ml solution samples held in polypropylene cryovials as demonstrated by experiments. For articular cartilage, 47.5 percent (w/w) may be recommended as the final concentration of Me2SO loaded in the tissue, which will lead to a time cut of about one-third compared with the original protocol of Pegg et al. (2006a).

The magnetic domain and magnetic properties of heat resistant steels including 10CrMo910, P91 and 23CrMoNiWV88 are investigated in the present work. The magnetic properties characterized by magnetic hysteresis loop of the three materials under 500-600 are measured by vibrating sample magnetometer (VSM). The magnetic domain structure of as-received and crept specimens is observed by magnetic force microscope (MFM). The magnetic domain of ferrite phase change from initial stripe pattern to maze pattern during creep. The black and white fringes and stripe-like pattern have also been found in the P91 and 23CrMoNiWV88 specimens, respectively. The experimental results reveal that the magnetic domain structure is strongly influenced by microstructures with different distributions of the carbides. It is shown that the coercivity and remanence of each material although has a remarkable decrease at 500-600 especially for P91 almost 64% decrease, it’s still the sa me magnitude as the one at room temperature. All the short-term crept specimens with different creep damage have a linear increase in coercivity and remanence comparing to the as-received 10CrMo910 specimens. These results indicate that it should be possible to de velop an in-situ monitoring technology for creep damage based on magnetism measurement.

A linear stability analysis is used to investigate crack growth in two dimensional elastic media, and under mechanical or thermal stresses. Although in most cases a circular geometry is considered, the instability of a planar crack is also discussed. Several boundary conditions and size effects are considered. The results indicate that the tendency towards instabilities in mechanical breakdown is stronger than in the case of growth in fields governed by the Laplace equation (diffusion or electrostatic fields), in line with the smaller fractal dimensions obtained in the first case. Instabilities under thermal stresses are shown to depend on the actual thermal gradients. Finally, a model previously investigated numerically is used to show that plasticity decreases the strength of the instability. (c) 1995 The American Physical Society