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Esophageal squamous cell carcinoma (ESCC) has a high incidence and low survival rate, necessitating the identification of novel specific biomarkers. Centromere-associated proteins (CENPs) have been reported to be biomarkers for many cancers, but their roles in ESCC have seldom been investigated. Here, the potential clinical roles of CENPs in ESCC patients were demonstrated by a systematic bioinformatics analysis. Most CENP-encoding genes were differentially expressed between tumor and normal tissues. CENPA, CENPE, CENPF, CENPI, CENPM, CENPN, CENPQ, and CENPR were upregulated universally in the three datasets. Survival analysis demonstrated that high expression of CENPE and CENPQ was positively correlated with the outcomes of ESCC patients. The CENPE-based forecast model was more accurate than the tumor-node-metastasis (TNM) staging-based model, which was classified as stage I/II vs. III/IV. More importantly, the forecast model based on the commonly upregulated CENPs exhibited a much higher area under the curve (AUC) value (0.855) than the currently known TTL, ZNF750, AC016205.1, and BOLA3 biomarkers. The nomogram model integrating the CENPs, TNM stage, and sex was highly accurate in the prognosis of ESCC patients ( AUC = 0.906 ). Besides, gene set enrichment analysis (GSEA) demonstrated that CENPE expression is significantly correlated with cell cycle, G2/M checkpoint, mitotic spindle, p53, etc. Finally, in validation experiments, we also found that CENPE and CENPQ were significantly overexpressed in esophageal cancer cells. Taken together, these results clearly suggest that CENPs are clinically promising diagnostic and prognostic biomarkers for ESCC patients.

Angiomotin-like 2 (AMOTL2) is a key modulator of signaling transduction and participates in the regulation of various cellular progresses under diverse physiological and pathological conditions. However, whether AMOTL2 participates in asthma pathogenesis has not been fully studied. In the present work, we studied the possible role and mechanism of AMOTL2 in regulating transforming growth factor-β1 (TGF-β1)-induced proliferation and extracellular matrix (ECM) deposition of airway smooth muscle (ASM) cells. Our results showed marked reductions in the abundance of AMOTL2 in TGF-β1-stimulated ASM cells. Cellular functional investigations confirmed that the up-regulation of AMOTL2 dramatically decreased the proliferation and ECM deposition induced by TGF-β1 in ASM cells. In contrast, the depletion of AMOTL2 exacerbated TGF-β1-induced ASM cell proliferation and ECM deposition. Further research revealed that the overexpression of AMOTL2 restrained the activation of Yes-associated protein 1 (YAP1) in TGF-β1-stimulated ASM cells. Moreover, the reactivation of YAP1 markedly reversed AMOTL2-mediated suppression of TGF-β1-induced ASM cell proliferation and ECM deposition. Together, these findings suggest that AMOTL2 restrains TGF-β1-induced proliferation and ECM deposition of ASM cells by down-regulating YAP1 activation.

A new polychiral bisabolane sesquiterpene, bisabolanoic acid A (1), was isolated from the mangrove-derived fungus Colletotrichum sp. SCSIO KcB3-2. Its planar structure was identified on the basis o...

Matrix metalloproteinases (MMPs) are involved in the cleavage of several components of the extracellular matrix and serve important roles in tumor growth, metastasis and invasion. Previous studies have focused on the expression of one or several MMPs in esophageal squamous cell carcinoma (ESCC); however, in the present study, the transcriptomics of all 23 MMPs were systematically investigated with a focus on the prognostic value of the combination of MMPs. In this study, 8 overlapping differentially expressed genes of the MMP family were identified based on data obtained from Gene Expression Omnibus and The Cancer Genome Atlas. The prognostic value of these MMPs were investigated; the receiver operating characteristic curves, survival curves and nomograms showed that the combination of 6 selected MMPs possessed a good predictive ability, which was more accurate than the prediction model based on Tumor-Node-Metastasis stage. Gene set enrichment analysis and gene co-expression analysis were performed to investigate the potential mechanism of action of MMPs in ESCC. The MMP family was associated with several signaling pathways, such as epithelial-mesenchymal transition (EMT), Notch, TGF-β, mTOR and P53. Cell Counting Kit-8, colony formation, wound healing assays and western blotting were used to determine the effect of BB-94, a pan-MMP inhibitor, on proliferation and migration of ESCC cells. BB-94 treatment decreased ESCC cell growth, migration and EMT. Therefore, MMPs may serve both as diagnostic and prognostic biomarkers of ESCC, and MMP inhibition may be a promising preventive and therapeutic strategy for patients with ESCC.

Gliomas are the most common primary intracranial tumors and closely related to circadian clock. Due to the high mortality and morbidity of gliomas, exploring novel diagnostic and early prognostic markers is necessary. Circadian clock genes (CCGs) play important roles in regulating the daily oscillation of biological processes and the development of tumor. Therefore, we explored the influences that the oscillations of circadian clock genes (CCGs) on diagnosis and prognosis of gliomas using bioinformatics. In this work, we systematically analyzed the rhythmic expression of CCGs in brain and found that some CCGs had strong rhythmic expression; the expression levels were significantly different between day and night. Four CCGs (ARNTL, NPAS2, CRY2, and DBP) with rhythmic expression were not only identified as differentially expressed genes but also had significant independent prognostic ability in the overall survival of glioma patients and were highly correlated with glioma prognosis in COX analysis. Besides, we found that CCG-based predictive model demonstrated higher predictive accuracy than that of the traditional grade-based model; this new prediction model can greatly improve the accuracy of glioma prognosis. Importantly, based on the four CCGs’ circadian oscillations, we revealed that patients sampled at night had higher predictive ability. This may help detect glioma as early as possible, leading to early cancer intervention. In addition, we explored the mechanism of CCGs affecting the prognosis of glioma. CCGs regulated the cell cycle, DNA damage, Wnt, mTOR, and MAPK signaling pathways. In addition, it also affects prognosis through gene coexpression and immune infiltration. Importantly, ARNTL can rhythmically modulated the cellular sensitivity to clinic drugs, temozolomide. The optimal point of temozolomide administration should be when ARNTL expression is highest, that is, the effect is better at night. In summary, our study provided a basis for optimizing clinical dosing regimens and chronotherapy for glioma. The four key CCGs can serve as potential diagnostic and prognostic biomarkers for glioma patients, and ARNTL also has obvious advantages in the direction of glioma chronotherapy.

Cellular senescence is considered a crucial process for tumour suppression, which can be facilitated by immune surveillance. However, when senescent cells persist in tissues, they can also trigger a plethora of tumour‐promoting effects. Here, we discuss the main hallmarks, mechanisms and roles of senescence in cancer and provide a comprehensive revision of the available tools for its detection., Senescence refers to a cellular state featuring a stable cell‐cycle arrest triggered in response to stress. This response also involves other distinct morphological and intracellular changes including alterations in gene expression and epigenetic modifications, elevated macromolecular damage, metabolism deregulation and a complex pro‐inflammatory secretory phenotype. The initial demonstration of oncogene‐induced senescence in vitro established senescence as an important tumour‐suppressive mechanism, in addition to apoptosis. Senescence not only halts the proliferation of premalignant cells but also facilitates the clearance of affected cells through immunosurveillance. Failure to clear senescent cells owing to deficient immunosurveillance may, however, lead to a state of chronic inflammation that nurtures a pro‐tumorigenic microenvironment favouring cancer initiation, migration and metastasis. In addition, senescence is a response to post‐therapy genotoxic stress. Therefore, tracking the emergence of senescent cells becomes pivotal to detect potential pro‐tumorigenic events. Current protocols for the in vivo detection of senescence require the analysis of fixed or deep‐frozen tissues, despite a significant clinical need for real‐time bioimaging methods. Accuracy and efficiency of senescence detection are further hampered by a lack of universal and more specific senescence biomarkers. Recently, in an attempt to overcome these hurdles, an assortment of detection tools has been developed. These strategies all have significant potential for clinical utilisation and include flow cytometry combined with histo‐ or cytochemical approaches, nanoparticle‐based targeted delivery of imaging contrast agents, OFF‐ON fluorescent senoprobes, positron emission tomography senoprobes and analysis of circulating SASP factors, extracellular vesicles and cell‐free nucleic acids isolated from plasma. Here, we highlight the occurrence of senescence in neoplasia and advanced tumours, assess the impact of senescence on tumorigenesis and discuss how the ongoing development of senescence detection tools might improve early detection of multiple cancers and response to therapy in the near future.

Nucleoside triphosphates and deoxynucleoside triphosphates are important biochemical molecules. In this study, recombinant Escherichia coli that could display nucleotide kinases (INP-N-NMKases) and acetate kinase (INP-N-ACKase) on the cell surface were constructed by fusing an enzyme (NMKase/ACKase) to the N-terminus of ice nucleation protein (INP-N). By using intact recombinant bacteria cells as a catalyst coupled with an ACKase-catalyzed adenosine-5'-triphosphate (ATP) regeneration system, nucleoside triphosphates (NTPs) and deoxynucleoside triphosphates (dNTPs) could be synthesized efficiently. In a reaction system with 5 mmol/l substrate, the conversion rates of cytidine-5'-triphosphate (CTP) and deoxycytidine-5'-triphosphate (dCTP) were 96% and 93%, respectively, the conversion rate of ATP and deoxyadenosine-5'-triphosphate (dATP) was 96%, the conversion rate of deoxythymidine-5'-triphosphate (dTTP) was 91%, and the conversion rate of uridine-5'-triphosphate (UTP) was 80%. There was no obvious degradation. At 37 °C, the stability of the surface-displayed fusion protein, especially in the presence of the substrate, was significantly improved. Each whole cell could be reused more than 8 times.

Context Whereas the serratus anterior (SA) and the upper trapezius (UT) work as a force couple for scapular motion, weakness of the SA and overactivation of the UT are often present in overhead athletes with shoulder dysfunction. Therefore, researchers addressing an intramuscular imbalance between the SA and UT have focused on finding exercises that target the weak SA and minimally activate the UT. Objective To compare the effectiveness of push-up plus (PUP) exercise variants based on the electromyographic (EMG) activity of the SA and UT. Data Sources A systematic search of PubMed and Scopus between January 1, 2000, and March 31, 2008. Study Selection Studies of PUP exercises that involved EMG analysis. Data Extraction We assessed study quality using the Critical Appraisal Skills Program. For the systematic analysis, the following data were extracted: (1) author, year, and study design; (2) participant characteristics; (3) type of PUP intervention; (4) EMG outcome measures; and (5) main results. For the meta-analysis, the EMG data of the SA and UT were calculated using the mean difference of EMG activity with a 95% confidence interval. Data Synthesis Based on 19 studies with 356 participants, different hand positions (the distance between the hands, shoulder-flexion angle, and elbow-flexion angle) and different lower extremity positions variably affected the activation of the SA and UT during the PUP exercise. Also, when participants performed the PUP on an unstable surface compared with a stable surface, UT activity increased 2.74% (95% confidence interval = 0.07%, 5.41%). Conclusions The standard PUP exercise elicited high EMG activity of the SA. Participants generated higher SA and lower UT EMG activity when they performed the PUP exercise on a stable surface in full elbow extension, with the hands placed shoulder-width apart, shoulder-flexion angles of 110° or 120°, and the ipsilateral lower extremity lifted.

With aging, pressure ulcers become a common health problem causing significant morbidity and mortality for physically limited or bedridden elderly persons. Here, we present our strategy for such patients. Between August 2010 and March 2019, 117 patients were enrolled. Patient age, etiology, defect size and location, flap reconstruction, outcome, and follow-up period were reviewed. Of these patients, 64 were female and 53 were male, with an age range of 21 to 96 years (mean 75.6). The mean area of defect was 61.5 cm2. The most common etiology was dementia (33.3%), and ulcers were most frequently caused by sacral pressure (70.3%). The commonest surgical treatment was a V–Y advancement flap (50%). The complication rate was 27.5%, including dehiscence and late recurrence. Negative pressure wound therapy could be used if the initial defect was large. V–Y advancement flap is the most frequent surgical treatment for sacral pressure ulcers because it is simple and available for most types of defect. Primary closure may be considered as the simplest method if the defective area is

Accumulating evidence shows that sirtuin 7 (SIRT7), a key mediator of many cellular activities, plays an important role in the pathogenesis of various diseases; however, little is known about the role of SIRT7 in asthma, which is characterized by airway remodeling. This study investigated the potential role of SIRT7 in regulating the proliferation and migration of airway smooth muscle (ASM) cells, which are critical events during airway remodeling in asthmatic conditions. The results demonstrated that SIRT7 expression was significantly upregulated in ASM cells treated with transforming growth factor-beta 1 (TGF-β1). Knockdown of SIRT7 inhibited the proliferation, promoted the apoptosis, and suppressed the migration of TGF-β1-treated ASM cells, while overexpression of SIRT7 had the opposite effect. Moreover, knockdown of SIRT7 inhibited protein expression of the TGF-β receptor I (TβRI), whilst overexpression of SIRT7 promoted the expression of TβRI. Importantly, knockdown of TβRI partially reversed the stimulatory effect of SIRT7 overexpression on the TGF-β1-induced proliferation and migration of ASM cells. Taken together, these results demonstrate that SIRT7 is involved in regulating TGF-β1-induced ASM cell proliferation and migration by regulating the expression of TβRI, thus indicating an important role of SIRT7 during airway remodeling in asthma.

A diet high in sodium chloride (NaCl) can affect renal function damage and increase urinary calcium excretion, leading to bone loss. in renal tubules, Na-Cl co-transporter (NCC) and chloride channel 5 (CLC-5) are involved in regulating urinary calcium excretion. In addition, some cytokines, such as Bone morphogenetic protein 7 (BMP-7) and 1α-hydroxylase, are synthesized by renal tubules, which target on bone and play important roles on bone metabolism. However, the specific mechanisms between NaCl and these ion channels or cytokines still need investigations from many aspects. This study, in culture normal rat renal tubular epithelial NRK-52E cells, showed that high concentrations of NaCl significantly inhibited the cell viability and increased the cell apoptosis. High concentration of NaCl reduce bone mineral density (BMD), as demonstrated by the significantly increased mRNA and protein levels of NCC and osteopontin (OPN), but decreased the levels of CLC-5, BMP-7, and 1α-hydroxylase. In addition, we found that ovariectomized (OVX) rats on a high-salt diet for 12 weeks had altered levels of these indices in the renal cortices. Moreover, the BMD in fourth and fifth lumbar vertebra (LV4 and 5) and femurs were significantly decreased and bone microstructure was destroyed of these rats. We also demonstrated that high concentration of NaCl enhanced the inhibition of these cytokines which is beneficial to increase BMD, induced by modulating ion channels NCC and CLC-5. In conclusion, our results indicate that high concentration of NaCl reduce BMD by regulating ion channels NCC and CLC-5.

Icaritin (ICT), a hydrolytic product of icariin from the genus Epimedium, has many indicated pharmacological and biological activities. Several studies have shown that ICT has potential osteoprotective effects, including stimulation of osteoblast differentiation and inhibition of osteoclast differentiation. However, the molecular mechanism for this anabolic action of ICT remains largely unknown. Here, we found that ICT could enhance MC3T3-E1 subclone 14 preosteoblastic cell differentiation associated with increased mRNA levels and protein expression of the differentiation markers alkaline phosphatase (ALP), type 1 collagen (COL1), osteocalcin (OC), osteoponin (OPN) and runt-related transcription factor 2 (RUNX2), and improved mineralization, confirmed by bone nodule formation and collagen synthesis. To characterize the underlying mechanisms, we examined the effect of ICT on estrogen receptor (ER) and mitogen-activated protein kinase (MAPK) signaling. ICT treatment induced p38 kinase and extracellular signal-regulated kinase 1/2 (ERK1/2) activation, but it demonstrated at the same time point no effect on activation of c-Jun N-terminal kinase (JNK). ER antagonist ICI182780, p38 antagonist SB203580 and ERK1/2 antagonist PD98059 markedly inhibited the ICT-induced the mRNA expression of ALP, COL1, OC and OPN. ICI182780 attenuated the ICT-induced phosphorylation of p38 and ERK1/2. These observations indicate a potential mechanism of osteogenic effects of ICT involving the ERK1/2 and p38 pathway activation through the ER.

Water extract of Gastrodia elata Blume (WGE) has great potential as an anti-depressant and could be developed as a functional food. This study aims to assess the safety of WGE using in vitro and in vivo genotoxicity assays and a 28-day oral toxicity study. Results from a bacterial reverse mutation assay (Ames test) using five Salmonella typhimurium strains (TA98, TA100, TA102, TA1535, and TA1537) with or without metabolic activation (S9 system) showed that WGE did not induce mutagenicity. Nor did it induce clastogenic effects in Chinese hamster ovary (CHO–K1) cells with or without S9 activation. Moreover, WGE did not affect the proportion of immature to total erythrocytes or the number of micronuclei in immature erythrocytes of ICR mice. Finally, a dose-dependent 28-day repeated dose toxicity assessment of WGE (2040, 4080, and 8065 mg/kg body weight, p.o.) in mice revealed no adverse effects on behavior, mortality, body weight, haematology, clinical biochemistry, or organ weight. No toxicopathologic lesions were detected following administration of high-dose WGE compared to controls. In conclusion, WGE has no significant mutagenic or toxic properties, and the no-observed-adverse-effect level (NOAEL) of WGE can be defined as at least 8065 mg/kg/day orally for 28 days for male and female mice.

Colorectal cancer (CRC) is a global disease with high incidence and mortality rate. Hsp90 inhibitors induce cell death in various cancers, including CRC. However, the underlying mechanisms need to be clarified further. In this study, Caco-2 cells were treated with 0.25 μM SNX-2112, an Hsp90 inhibitor, for 48 h; subsequently, whole-transcriptome sequencing was performed. At the mRNA level in SNX-2112-treated Caco-2 cells, 1588 genes were upregulated, and 433 genes were downregulated. Six genes were found to be associated with necroptosis and apoptosis, and these 6 upregulated genes were validated by RT-qPCR. Hundred and six miRNAs were upregulated, and 48 miRNAs were downregulated in SNX-2112-treated Caco-2 cells. Eleven downregulated miRNAs were found to interact with the 6 upregulated genes. Moreover, 676 circRNAs were upregulated, and 291 circRNAs were downregulated in SNX-2112-treated Caco-2 cells. Among them, 126 circRNAs were found to be the target of the 11 downregulated miRNAs. The circRNA-miRNA-mRNA regulatory network of Hsp90 inhibitor-induced cell death in colorectal cancer was constructed. This regulatory network extends the underlying mechanism of Hsp90 and improves our understanding of Hsp90 inhibitors as potential targeted therapeutic agents.

Hypoxia deprives cells of energy and induces severe physical damage in embryophytes. Under hypoxia, the equilibrium between ethylene and H2O2 affects the response of the transcription factor AtERF73/HRE1. To evaluate the role of AtERF73/HRE1 during hypoxia signaling, we used three independent AtERF73/HRE1 knockout lines to detect H2O2 accumulation. The results revealed that under hypoxia, H2O2 accumulation in the AtERF73/HRE1 knockout lines decreased, indicating that AtERF73/HRE1 uses a negative feedback regulation mechanism to influence the production of H2O2 induced through hypoxia signal transduction. Quantitative RT-PCR analyses showed that oxygen deficiency had different effects on the expression of the hypoxia-induced genes Rboh B, D, G, and I in the AtERF73/HRE1 knockout lines. In particular, Rboh B and D expression were increased, whereas Rboh G expression was decreased. The expression of Rboh I was increased at 1 h but decreased at 3 h during hypoxia treatment in the AtERF73/HRE1 knockout lines. Similarly, the transcript levels of antioxidant and hypoxia-induced/ethylene response genes in the AtERF73/HRE1 knockout lines were affected by hypoxic stress, indicating that AtERF73/HRE1 is essential to hypoxia signal transduction in embryophytes. Additionally, in histochemical analysis, AtERF73/HRE1 promoter-induced GUS expression was detected in various plant parts throughout the plant growth process (e.g., leaves, inflorescences, siliques), particularly in the edges of mature leaves and guard cells. Taken together, our results confirm that AtERF73/HRE1 plays a role in H2O2 production by affecting the hypoxia-induced expression of Rboh genes in hypoxia signal transduction.

Background Patterns of scapular dyskinesis have unique scapular kinematics and associated muscular activation. The characteristics of unique dyskinesis patterns may be associated with functional disability. Objectives To investigate whether the shoulder function level and primary dysfunction items were different in unique dyskinesis pattern. The factors associated with shoulder dysfunction in different dyskinesis patterns were identified. Design Cross-sectional study. Methods Fifty-one participants with unilateral shoulder pain were classified as having a single dyskinesis pattern (inferior angle prominence, pattern I; medial border prominence, pattern II) or a mixed dyskinesis pattern (patterns I + II). Clinical measurements with the Flexilevel Scale of Shoulder Function (FLEX-SF), shoulder range of motion and pectoralis minor index were recorded. These clinical measurements, 3-D scapular kinematics (electromagnetic-based motion analysis), and associated muscular activation (electromyography on the upper/middle/lower trapezius and serratus anterior muscles) during arm elevation were analyzed for associations with functional disability. Results We found FLEX-SF scores and primary dysfunction items were similar among the patterns of dyskinesis. In inferior angle prominence, increased shoulder function was associated with decreased upper trapezius activity (R 2 = 0.155, p = 0.035), which accounted for approximately 16% of the variance of FLEX-SF scores. In medial border prominence, increased shoulder function was associated with increased lower trapezius activity (R 2 = 0.131, p = 0.017), which accounted for approximately 13% of the variance of FLEX-SF scores. Conclusion Upper and lower trapezius activities are important to consider in the evaluation of patients with pattern I and II, respectively. No other factors were related to shoulder dysfunction due to insufficient challenge of arm elevation tasks.

Cadmium is an environmental metal pollutant that has been a focus of research in recent years, which is reported to cause bone disease; however, its skeletal toxicity and the mechanism involved are not yet fully known. Therefore, this study used MC3T3-E1 subclone 14 cells to determine the mechanism of cadmium toxicity on bone. Cadmium chloride (Cd) significantly reduced cell viability in a concentration-dependent manner. Exposure to Cd inhibited osteoblast-related proteins (Runx2, Col-1, STC2) and decreased alkaline phosphatase (ALP) activity. Cd caused Exportin-1 accumulation and induced DNA damage. Cd significantly down-regulated caspase 9 and induced cleaved-PARP, cleaved-caspase 3 protein level. Treatment with JNK inhibitor, SP600125, suppressed cadmium-induced elevation in the ratio of phosphorylation of JNK to JNK. Inhibition of caspase with pan-caspase inhibitor, Z-VAD-FMK, prevented MC3T3-E1 subclone 14 cells from cadmium-induced reduction of Runx2, STC2, caspase 9, and accumulation of cleaved PARP and cleaved caspase 3. Cd-induced cell survival enhanced by SP600125 but rescued by Z-VAD-FMK or KPT-335. These results suggest that cadmium cytotoxicity on bone involved exportin 1 accumulation, phosphorylation of JNK, induction of DNA damage and pro-apoptosis, which was induced by activation of caspase-dependent pathways.

A one-pot process of enzymatic synthesis of deoxythymidine-5'-triphosphate (5'-dTTP) employing whole cells of recombinant Escherichia coli coexpressing thymidylate kinase (TMKase) and acetate kinase (ACKase) was developed. Genes tmk and ack from E. coli were cloned and inserted into pET28a(+), and then transduced into E. coli BL21 (DE3) to form recombinant strain pTA in which TMKase and ACKase were simultaneously overexpressed. It was found that the relative residual specific activities of TMKase and ACKase, in pTA pretreated with 20 mM ethylene diamine tetraacetic acid (EDTA) at 25°C for 30 min, were 94% and 96%, respectively. The yield of 5'-dTTP reached above 94% from 5 mM deoxythymidine 5'-monophosphate (5'-dTMP) and 15 mM acetyl phosphate catalyzed with intact cells of pTA pretreated with EDTA. The process was so effective that only 0.125 mM adenosine-5'- triphosphate was sufficient to deliver the phosphate group from acetyl phosphate to dTMP and dTDP.

Dynamic Causal Modeling (DCM) has been extended for the analysis of electroencephalography (EEG) based on a specific biophysical and neurobiological generative model for EEG. Comparing to methods that summarize neural activities with linear relationships, the generative model enables DCM to better describe how signals are generated and better reveal the underlying mechanism of the activities occurring in human brains. Since DCM provides us with an approach to the effective connectivity between brain areas, with exponential ranking, the abnormality of the observed signals can be further located to a specific brain region. In this paper, a combination of DCM and exponential ranking is proposed as a new method aiming at searching for the abnormal brain regions which are associated with chronic tinnitus.

Seed size is variable within many plant species, and understanding the underlying genetic factors can provide insights into mechanisms of local environmental adaptation. Here we make use of the abundant genomic and germplasm resources available for rice (Oryza sativa) to perform a large-scale genome-wide association study (GWAS) of grain width. Grain width varies widely within the crop and is also known to show climate-associated variation across populations of its wild progenitor. Using a filtered dataset of >1.9 million genome-wide SNPs in a sample of 570 cultivated and wild rice accessions, we performed GWAS with two complementary models, GLM and MLM. The models yielded 10 and 33 significant associations, respectively, and jointly yielded seven candidate locus regions, two of which have been previously identified. Analyses of nucleotide diversity and haplotype distributions at these loci revealed signatures of selection and patterns consistent with adaptive introgression of grain width alleles across rice variety groups. The results provide a 50% increase in the total number of rice grain width loci mapped to date and support a polygenic model whereby grain width is shaped by gene-by-environment interactions. These loci can potentially serve as candidates for studies of adaptive seed size variation in wild grass species.

Monosodium methyl arsenate (MSMA), a common arsenical herbicide, is a major contributor of anthropogenic arsenic (As) to the environment. Uncertainty about controls on MSMA fate and the rates and products of MSMA species transformation limits effective MSMA regulation and management. The main objectives of this research were to quantify the kinetics and mechanistic drivers of MSMA species transformation and removal from solution by soil. Laboratory MSMA incubation studies with two soils and varying soil organic carbon (SOC) levels were conducted. Arsenic removal from solution was more extensive and faster in sandy clay loam incubations than sand incubations, but for both systems, As removal was biphasic, with initially fast removal governed by sorption, followed by slower As removal limited by species transformation. Dimethylarsinic acid was the dominant product of species transformation at first, but inorganic As(V) was the ultimate transformation product by experiment ends. SOC decreased As removal and enhanced As species transformation, and SOC content had linear relationships with As removal rates (R2 = 0.59-0.95) for each soil and reaction phase. These results reveal the importance of edaphic conditions on inorganic As production and overall mobility of As following MSMA use, and such information should be considered in MSMA management and regulatory decisions.

Al-Mg alloy plates with 10mm thick were welded by multi-pass MIG welding with the self-made wire as filler material, and microstructure of the welded joint were examined by metallographic and electron backscatter diffraction (EBSD). The results indicate, because of the grain refining effect of Zr, the grains in welding joints fusion zone formed grain-refining layer tissue by competitive growth. In the juncture zone of two welding passes, because of the grain epitaxial growth mechanism, it formed obvious coarse grain zone, which became a weak link of welding joints. And the coarse grain zone exist faint texture, but to the whole, the welding zone did not exist obvious preferred orientation.

A process of glucose-6-phosphate (G-6-P) production coupled with an adenosine triphosphate (ATP) regeneration system was constructed that utilized acetyl phosphate (ACP) via acetate kinase (ACKase). The genes glk and ack from Escherichia coli K12 were amplified and cloned into pET-28a(+), then transformed into E. coli BL21 (DE3) and the recombinant strains were named pGLK and pACK respectively. Glucokinase (glkase) in pGLK and ACKase in pACK were both overexpressed in soluble form. G-6-P was efficiently produced from glucose and ACP using a very small amount of ATP. The conversion yield was greater than 97 % when the reaction solution containing 10 mM glucose, 20 mM ACP-Na₂, 0.5 mM ATP, 5 mM Mg²⁺, 50 mM potassium phosphate buffer (pH 7.0), 4.856 U glkase and 3.632 U ACKase were put into 37 °C water bath for 1 h.

nternet of Things is known to be the third wave of the world information industry following the computers and the Internet. In China, The development of things already elevated to the height of the national strategy. With the application of things more and more widely, security and privacy of The Internet of Things is increasingly a cause for concern. It has also become one of the decisive factors of sustainable development networking industry. Analysis focus on the perception layer of Things layers of security issues and the security policy. Analysis of the privacy issues involved in the Internet of Things applications to the response options. Efforts in the direction pointed out that for the security and privacy issues of Things. On study of the safety of the perception layer, one attack model of perception layer based on attack tree are put forward.

Wenchuan earthquake caused huge losses in rural areas. The subject briefly introduced the earthquake damage characteristics of masonry structures, analyzed the earthquake damage reasons. The main purpose is to propose some measures to improve the seismic capacity of rural buildings in Beijing area. Through two seismic fortification measures, can effectively enhance the integrity of the masonry structure, reduce the seismic response, effectively improve the seismic capacity of the structure.

In this paper, a novel fuzzy measure, high order lambda measure, was proposed, based on the Choquet integral with respect to this new measure, a novel composition forecasting model which composed the GM(1,1) forecasting model, the time series model and the exponential smoothing model was also proposed. For evaluating the efficiency of this improved composition forecasting model, an experiment with a real data by using the 5 fold cross validation mean square error was conducted. The performances of Choquet integral composition forecasting model with the P-measure, Lambda-measure, L-measure and high order lambda measure, respectively, a ridge regression composition forecasting model and a multiple linear regression composition forecasting model and the traditional linear weighted composition forecasting model were compared. The experimental results showed that the Choquet integral composition forecasting model with respect to the high order lambda measure has the best performance.

The aim of the study was to investigate the inhibitory effects of RNA interference on XIAP gene expression of human endometrial carcinoma RL95-2 cell and the cell apoptosis. Specific small interference RNA (siRNA) of XIAP was designed and composed. Transfection of siRNA was conducted in endometrial carcinoma cell line RL95-2. The XIAP gene mRNA was assessed by real-time PCR and the change of XIAP protein was assessed with Western Blotting. The cell proliferation and apoptosis was assessed by MTT and flow cytometry methods. After transfection of siRNA specifically targeting XIAP, the relative fold of mRNA transfection in the specific transfection group was (0.04 ± 0.06) and the relative protein expression was (0.590 ± 0.178), which was significantly decreased when compared with the control group (P

Objective of the study is to find the association between p21 rs1059234 polymorphisms and endometrial cancer in Han women from Northeast China. Genotyping of rs1059234 in the p21 gene was performed by sequencing and PCR-restriction fragment length polymorphism (PCR-RFLP) of peripheral blood samples in 263 endometrial cancer patients (case group) and 315 healthy subjects (control group). C allele frequency of rs1059234 was significantly increased in patients of the case group when compared with that in the control group (P = 0.039). The CC genotype frequency of rs1059234 was also significantly increased in patients of case group (0.335, vs. 0.219, P = 0.045). CC genotype increased the risk of endometrial cancer (OR = 1.589, 95%CI: 1.010-2.502). However, after corrected with regression analysis, the CC genotype did not increase the risk of endometrial cancer (OR = 1.623, 95% CI: 0.720-3.659, P = 0.243). Our study demonstrates that in Han women from Northeast China, there is no association between rs1059234 polymorphism of p21 gene and risk of endometrial cancer.

Background Knowledge of the kinematics and associated muscular activity in individuals with scapular dyskinesis may provide insight into the injury mechanism and inform the planning of treatment strategies. We investigated scapular kinematics and associated muscular activation during arm movements in individuals with scapular dyskinesis. Methods A visual-based palpation method was used to evaluate 82 participants with unilateral shoulder pain. Scapular movements during arm raising/lowering movements were classified as abnormal single pattern (inferior angle prominence, pattern I; medial border prominence, pattern II; excessive/inadequate scapular elevation or upward rotation, pattern III), abnormal mixed patterns, or normal pattern (pattern IV). Scapular kinematics and associated muscular activation were assessed with an electromagnetic motion-capturing system and surface electromyography. Results More scapular internal rotation was found in pattern II subjects (4°, P = .009) and mixed pattern I and II subjects (4°, P = .023) than in control subjects during arm lowering. Scapular posterior tipping (3°, P = .028) was less in pattern I subjects during arm lowering. Higher upper trapezius activity (14%, P = .01) was found in pattern II subjects during arm lowering. In addition, lower trapezius (5%, P = .025) and serratus anterior activity (10%, P = .004) were less in mixed pattern I and II subjects during arm lowering. Conclusions Specific alterations of scapular muscular activation and kinematics were found in different patterns of scapular dyskinesis. The findings also validated the use of a comprehensive classification test to assess scapular dyskinesis, especially in the lowering phase of arm elevation.

This study was to investigate the effect of miR-200c on regulation of ovarian cancer cell metastasis potential and explore the underlying molecular events. qRT-PCR was used to analyze the level of miR-200c expression in 48 ovarian cancer and 30 normal ovarian tissue samples. pre-miR-200c was used to manipulate miR-200c expression in ovarian cancer cells for detection of changed phenotypes of tumor cells. Bioinformatics analysis was then used to predict target genes of miR-200c and GO and pathway analyses drew the miR-200c-related gene network. Luciferase reporter assay confirmed the target of miR-200c as ZEB2. Western blot was used to detect gene expressions in ovarian cancer cells. Level of miR-200c expression was much higher in ovarian cancer than in normal ovarian tissues, and miR-200c expression was inversely associated with advanced clinical stage and lymph node metastasis of ovarian cancer (p < 0.01). The database search predicted 186 miR-200c-targeting genes, and GO analysis showed that functions of these target genes were enriched in the protein binding and other biological processes. Furthermore, miR-200c expression inhibited ovarian cancer cell ES-2 migration and invasion capacity by suppression of ZEB2 expression (p < 0.01). Overexpression of miR-200c regulated E-cadherin and vimentin expression in ovarian cancer cells. This study demonstrated high miR-200c expression in ovarian cancer tissues and ZEB2 as a targeting gene of miR-200c, which mediated the effects of miR-200c on regulation of ovarian cancer cell migration and invasion capacity and epithelial-to-mesenchymal transition. Thus, targeting of miR-200c or ZEB2 may serve as a potential therapeutic strategy for control of ovarian cancer.

Previous study has revealed that tumor-associated macrophages (TAMs) correlate with response to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in advanced non-small cell lung cancer (NSCLC). In the present study, we further determined that M2-TAMs, but not M1-TAMs, are related to the treatment response to EGFR-TKIs in advanced NSCLC and may be an independent predictor of survival. Eighty-eight advanced lung adenocarcinoma patients treated with a second-line EGFR-TKI were involved in this study. M2-TAMs counts but not M1-TAMs were significantly higher in patients with progressive disease than in those without (P < 0.001). A trend also remained in patients with known EGFR status (n = 61) and those with mutant EGFR (n = 49). High M2-TAMs counts were shown to be significantly related to poor progression-free survival (PFS) and overall survival (OS) in all patients, or subsets of patients with known EGFR status or patients with EGFR mutation (all P < 0.05). Multivariate Cox analyses showed that high M2-TAMs counts and EGFR mutations were both independent factors associated with PFS and OS (P < 0.05). Overall, we revealed that M2- but not M1-TAMs are related to the response of EGFR-TKIs treatment irrespective of EGFR mutation and can independently predict survival in advanced lung adenocarcinoma treated with a second-line EGFR-TKI.

Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), is a major bacterial pathogen associated with nosocomial and community-acquired S. aureus infections all over the world. A rapid detection assay for staphylococcal gene of nuc and mecA is needed. In this study, a rapid identification assay based on the loop-mediated isothermal amplification (LAMP) method was established. PCR and LAMP assays were used to detect Staphylococcus aureus and other related species for nuc and mecA. With optimization of the primers and reaction temperature, the LAMP successfully amplified the genes under isothermal conditions at 62 °C within 60 min, of which the results were identical with those of the conventional PCR methods. The detection limits of the LAMP for nuc and mecA were 1.47 and 14.7 pg/μl DNA per tube, respectively, by naked eye inspections, while the detection limits of the PCR for nuc and mecA were 14.7 pg/μl and 147 pg/μl DNA, respectively. Finally, The LAMP method was then applied to clinical blood plaque samples. The LAMP and PCR demonstrated identical results for the plaque samples with the culture assay. Together, the LAMP offers an alternative detection assay for nuc and mecA with a great advantage of the sensitivity and rapidity.

Pethidine is an opioid that gains its popularity for the effective pain control through acting on the opioid-receptors. However, rapid pain relief sometimes brings about unfavourable side effects that largely limit its clinical utility. Common side effects include nausea, vomiting and hypotension. In patients with impaired renal and liver function, and those who need long-term pain control, pethidine may cause excitatory central nervous system (CNS) effects through its neurotoxic metabolite, norpethidine, resulting in irritability and seizure attack. On the contrary, though not clinically apparent, pethidine potentially causes inhibitory impacts on the CNS and impairs normal cerebellar and oculomotor function in the short term. In this case report, we highlight opioid's inhibitory side effects on the cerebellar structure that causes dysmetria, dysarthria, reduced smooth pursuit gain and decreased saccadic velocity.

Deoxynucleoside-5′-monophosphates (5′-dNMPs) are the basic components of DNA and are widely used in medicine and as chemical and biochemical reagents. A large amount of effort has been expended to obtain 5′-dNMPs of high quality and at a low cost. However, these procedures are inefficient and inconvenient. In this study, deoxyadenosine-5′-monophosphate (5′-dAMP), 2,6-diaminopurine deoxynucleoside-5′-monophosphate (5′-dDAMP), and deoxycytidine-5′-monophosphate (5′-dCMP) were biosynthesized using recombinant N-deoxyribosyltransferase II (NDT-II), deoxycytidine kinase, and acetate kinase in a one-pot reaction system. The ndt-II gene from Lactobacillus delbrueckii, dck from Bacillus subtilus, and ack from Escherichia coli K12 were overexpressed in E. coli BL21 (DE3). Thymidine was used as the deoxyribose donor; GTP was used as the phosphate donor, and acetyl phosphate was used to regenerate GTP. Under optimized conditions, each 10 mM adenine, 10 mM 2,6-diaminopurine, or 10 mM cytosine were converted into 9.01 mM 5′-dAMP, 8.68 mM 5′-dDAMP, or 6.23 mM 5′-dCMP, respectively. The high yield indicated that this process of biosynthesis of 5′-dAMP, 5′-dDAMP, or 5′-dCMP was efficient and economical, and this one-pot system may also potentially be used for the preparation of other types of 5′-dNMPs.

Recombinant E. coli pDEOA was constructed and lactose can be used instead of IPTG to induce the expression of thymidine phosphorylase by pDEOA. The use of lactose at concentrations higher than 0.5 mmol/L had an induction effect similar to that of IPTG but resulted in a longer initial induction time and better cell growth. The thymidine phosphorylase induced by lactose was very stable at 50°C. Intact pDEOA cells induced by lactose can be used as a source of thymidine phosphorylase. Under standard reaction conditions, several deoxynucleosides were effectively produced from thymidine.

Nucleoside phosphorylase is an important enzyme involved in the biosynthesis of nucleosides. In this study, purine nucleoside phosphorylase and pyrimidine nucleoside phosphorylase were co-expressed in Escherichia coli and the intact cells were used as a catalyst for the biosynthesis of nucleosides. For protein induction, lactose was used in place of isopropyl β-D-1-thiogalactopyranoside (IPTG). When the concentration of lactose was above 0.5 mmol/L, the ability to induce protein expression was similar to that of IPTG. We determined that the reaction conditions of four bacterial strains co-expressing these genes (TUD, TAD, DUD, and DAD) were similar for the biosyntheses of 2,6-diaminopurine nucleoside and 2,6-diaminopurine deoxynucleoside. When the substrate concentration was 30 mmol/L and 0.5% of the recombinant bacterial cell volume was used as the catalyst (pH 7.5), a greater than 90% conversion yield was reached after a 2-h incubation at 50 °C. In addition, several other nucleosides and nucleoside derivatives were efficiently synthesized using bacterial strains co-expressing these recombinant enzymes.

The genes encoding purine nucleoside phosphorylase (PNPase), uridine phosphorylase (UPase), and thymidine phosphorylase (TPase) from Escherichia coli K12 were cloned respectively into expression vector pET-11a or pET-28a. The recombinant plasmids were transformed into the host strain E. coli BL21(DE3) to construct four co-expression recombinant strains. Two of them had double recombinant plasmids (DUD and DAD) and the other two had tandem recombinant plasmid (TDU and TDA) in them. Under the repression of antibiotic, recombinant plasmids stably existed in host strains. Enzymes were abundantly expressed after induction with IPTG and large amount of target proteins were expressed in soluble form analyzed with SDS-PAGE. Compared with the host strain, enzyme activity of the recombinant strains had been notably improved. In the transglycosylation reaction, yield of 2,6-diaminopurine-2’-deoxyriboside (DAPdR) from 2,6-diaminopurine (DAP) and thymidine reached 40.2% and 51.8% catalyzed by DAD and TDA respectively; yield of 2,6-diaminopurine riboside (DAPR) from DAP and uridine reached 88.2% and 58.0% catalyzed by TDU and DUD respectively.

University Science Associate, which has dual identity of both university and association for science and technology , is the main functional departments of Chinese universities to carry out the science popularization work.The paper systematic research University Science Associate using the popular science lectures, competition, and forming scientific camp to carry out the science popularization work of science by Case and inductive analysis method etc.In the study, we found University Science Associate had, such as the form of a single, talent training is not enough, the lack of innovation. On the basis, the paper ,trying to combine the new situation, should take its advantages in the aspects like intelligence, audience, site, organization etc. to carry out science popularization work innovatively via innovating concept, broadening thought, cultivating talents, innovating work mode and so on under new situation.

The full-length cDNAs of two novel T-superfamily conotoxins, Lp5.1 and Lp5.2, were cloned from a vermivorous cone snail Conus leopardus using 3'/5'-rapid amplification of cDNA ends. The cDNA of Lp5.1 encodes a precursor of 65 residues, including a 22-residue signal peptide, a 28-residue propeptide and a 15-residue mature peptide. Lp5.1 is processed at the common signal site-X-Arg- immediately before the mature peptide sequences. In the case of Lp5.2, the precursor includes a 25-residue signal peptide and a 43-residue sequence comprising the propeptide and mature peptide, which is probably cleaved to yield a 29-residue propeptide and a 14-residue mature toxin. Although these two conotoxins share a similar signal sequence and a conserved disulfide pattern with the known T-superfamily, the pro-region and mature peptides are of low identity, especially Lp5.2 with an identity as low as 10.7% compared with the reference Mr5.1a. The elucidated cDNAs of these two toxins will facilitate a better understanding of the species distribution, the sequence diversity of T-superfamily conotoxins, the special gene structure and the evolution of these peptides.