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There are no effective pharmacological treatments for sarcopenia. We aim to identify potential therapeutic targets for sarcopenia by integrating various publicly available datasets. We integrated druggable genome data, cis‐eQTL/cis‐pQTL from human blood and skeletal muscle tissue, and GWAS summary data of sarcopenia‐related traits to analyse the potential causal relationships between drug target genes and sarcopenia using the Mendelian Randomization (MR) method. Sensitivity analyses and Bayesian colocalization were employed to validate the causal relationships. We also assessed the side effects or additional indications of the identified drug targets using a phenome‐wide MR (Phe‐MR) approach and investigated actionable drugs for target genes using available databases. MR analysis identified 17 druggable genes with potential causation to sarcopenia in human blood or skeletal muscle tissue. Six of them (HP, HLA‐DRA, MAP 3K3, MFGE8, COL15A1, and AURKA) were further confirmed by Bayesian colocalization (PPH4 > 90%). The up‐regulation of HP[higher ALM (beta: 0.012, 95% CI: 0.007–0.018, P= 1.2*10−5) and higher grip strength (OR: 0.96, 95% CI: 0.94–0.98, P= 4.2*10−5)], MAP 3K3[higher ALM (beta: 0.24, 95% CI: 0.21–0.26, P= 1.8*10−94), higher grip strength (OR: 0.82, 95% CI: 0.75–0.90, P= 2.1*10−5), and faster walking pace (beta: 0.03, 95% CI: 0.02–0.05, P= 8.5*10−6)], and MFGE8[higher ALM (muscle eQTL, beta: 0.09, 95% CI: 0.06–0.11, P= 6.1*10−13; blood pQTL, beta: 0.05, 95% CI: 0.03–0.07, P= 3.8*10−09)], as well as the down‐regulation of HLA‐DRA[lower ALM (beta: ‐0.09, 95% CI: −0.11 to −0.08, P= 5.4*10−36) and lower grip strength (OR: 1.13, 95% CI: 1.07–1.20, P= 1.8*10−5)] and COL15A1[higher ALM (muscle eQTL, beta: ‐0.07, 95% CI: −0.10 to −0.04, P= 3.4*10−07; blood pQTL, beta: ‐0.05, 95% CI: −0.06 to −0.03, P= 1.6*10−07)], decreased the risk of sarcopenia. AURKAin blood (beta: ‐0.16, 95% CI: −0.22 to −0.09, P= 2.1*10−06) and skeletal muscle (beta: 0.03, 95% CI: 0.02 to 0.05, P= 5.3*10−05) tissues showed an inverse relationship with sarcopenia risk. The Phe‐MR indicated that the six potential therapeutic targets for sarcopenia had no significant adverse effects. Drug repurposing analysis supported zinc supplementation and collagenase clostridium histolyticummight be potential therapeutics for sarcopenia by activating HPand inhibiting COL15A1, respectively. Our research indicated MAP 3K3, MFGE8, COL15A1, HP, and HLA‐DRAmay serve as promising targets for sarcopenia, while the effectiveness of zinc supplementation and collagenase clostridium histolyticumfor sarcopenia requires further validation.

Pre-upsetting deformation is an effective way to optimize the microstructure of plastic forming components and achieve deep modification. In this paper, the pre-upsetting deformation of AZ31 Mg alloy billet was carried out before alternating forward extrusion, and the effect of pre-upsetting deformation temperature on the recrystallization behavior and texture evolution of AZ31 Mg alloy formed by alternating forward extrusion was analyzed. The results showed that the strains generated by the pre-upsetting deformation at different temperatures all leaded to a high dynamic recrystallization (DRX) driving force. This results in a high percentage of recrystallized grains in all pre-upsetting alternating forward extrusion (UAFE) formations. The highest percentage of recrystallized grains 94.5% was observed in U2AFE (pre-upsetting deformation at 623 K). The behavior of DRX has a significant impact on both the distribution and strength of texture. In the case of U2AFE, the maximum basal texture strength is 8.65. This is due to the maximum pole density of the deformed texture, which is composed of non-recrystallized grains and is as high as 9.25. In contrast, the maximum pole density of the recrystallized texture, which is composed of recrystallized grains, is only 8.09. Therefore, non-recrystallized grains play a crucial role in the formation of texture in UAFE. This study provides scientific guidance and technical support for the research of high-performance Mg alloy alternating forward extrusion molding technology.

The optimal configuration of strength and ductility was the first choice in Mg-alloys plate forming. A rolling method with adding the hard plate and unique component structure design was proposed to achieve a symmetrical gradient structure from two upmost surfaces to the center of the AZ31 Mg-alloys plate during a single rolling pass. The microstructure evolution and mechanical properties of symmetrical gradient structure plates were studied. The results indicate that Mg-alloy plates' strength and tensile ductility reached 267 MPa and 26.1%, respectively. In the fine-grain region, the proportion of high-angle grain boundary was 56.4%, and the recrystallization structure was 57.3%. In the coarse-grain region, high-grain boundaries and recrystallization decreased to 42.9% and 42.1%, respectively. Both prismatic slip and pyramidal slip in the CG region were easier to initiate, which leads the interaction of multidirectional twins. The geometrically necessary dislocations mainly accumulate at the boundary of the different region. The fracture morphology showed a gradient distribution of dimples. The crack was deflected in the process of extension, which also leads high ductility of Mg-alloy. The design strategy provides a new idea for producing the high-performance plate with through-thickness symmetrical gradient structure.

BackgroundAlzheimer’s disease (AD) is the leading cause of dementia. Currently, there are no effective disease-modifying treatments for AD. Mendelian randomisation (MR) has been widely used to repurpose licensed drugs and discover novel therapeutic targets. Thus, we aimed to identify novel therapeutic targets for AD and analyse their pathophysiological mechanisms and potential side effects.MethodsA two-sample MR integrating the identified druggable genes was performed to estimate the causal effects of blood and brain druggable expression quantitative trait loci (eQTLs) on AD. A repeat study was conducted using different blood and brain eQTL data sources to validate the identified genes. Using AD markers with available genome-wide association studies data, we evaluated the causal relationship between established AD markers to explore possible mechanisms. Finally, the potential side effects of the druggable genes for AD treatment were assessed using a phenome-wide MR.ResultsOverall, 5883 unique druggable genes were aggregated; 33 unique potential druggable genes for AD were identified in at least one dataset (brain or blood), and 5 were validated in a different dataset. Among them, three prior druggable genes (epoxide hydrolase 2 (EPHX2), SERPINB1and SIGLEC11) reached significant levels in both blood and brain tissues. EPHX2 may mediate the pathogenesis of AD by affecting the entire hippocampal volume. Further phenome-wide MR analysis revealed no potential side effects of treatments targeting EPHX2, SERPINB1or SIGLEC11.ConclusionsThis study provides genetic evidence supporting the potential therapeutic benefits of targeting the three druggable genes for AD treatment, which will be useful for prioritising AD drug development.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ijpe.2009.06.043 Byline: Liang-Hsuan Chen, Fu-Sen Kang Keywords: Inventory; Imperfect items; Vendor-buyer; Delay in payment Abstract: Vendor-buyer models for trade credit issues in the existing literature always consider the items produced as perfect. However, a number of items in a lot may be of imperfect quality. This paper extends Chen and Kang's [2007. Integrated vendor-buyer cooperative models with variant permissible delay in payments. European Journal of Operational Research 183 (2), 658-673] study to develop integrated vendor-buyer models that consider a permissible delay in payment and imperfect quality to determine the optimal solutions of the buyer's order quantity and the frequency for each vendor's production run. To establish a cooperative relationship between the vendor and buyer for a win-win situation, a simple solution algorithm is presented to determine the cost saving of each side when the warranty cost per unit is increased. A numerical example is used to illustrate the results for the proposed models. Author Affiliation: Department of Industrial and Information Management, National Cheng Kung University, Tainan, Taiwan, ROC Article History: Received 29 May 2007; Accepted 30 June 2009

Our aim was to study the regulatory molecule networks involved in the epithelial-to-mesenchymal transition and thus promoting the early onset of metastasis in triple-negative breast cancer (TNBC). Forty pairs of human TNBC and their adjacent normal breast tissues were analyzed by real-time PCR and immunochemistry to demonstrate the correlation between the miR-205 expression and clinicopathological characteristics. In vitro, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay, cell migration, and invasion assay were used to detect the cell growth and invasive ability of TNBC cells after upregulation or downregulation of miR-205 expression. Luciferase reporter assay was used to confirm the potential target directly influenced by miR-205. Our results showed that miR-205 abnormal expression may be involved and associated with the biological traits of TNBC. Ectopic expression of miR-205 not only inhibited cell growth, but also suppressed migration and invasion of mesenchymal-like TNBC cells. In addition, we found that overexpression of miR-205 significantly suppressed HMGB1 by binding its 3′-untranslated region, and that miR-205 was inversely correlated with the expression of HMGB1 and RAGE in cell lines and clinical samples. Our study illustrated that miR-205 was a tumor suppressor in TNBC, which attenuated the viability and the acquisition of the epithelial-to-mesenchymal transition phenotype TNBC cells at least partially exerted through targeting of HMGB1–RAGE signaling pathway.

Background Cytokines are crucial factors in the non-cytolytic antiviral process to inhibit HBV gene expression and replication. Interleukin (IL)-21 has been suggested to play an important role in HBV infection, but it remains unknown whether IL-21 can inhibit HBV replication or how it inhibits HBV replication.Methods In this study, we investigated the influence of IL-21 on HBV replication based on human hepatoma Huh7.93 cells co-cultured with human peripheral blood mononuclear cells (PBMCs) and the possible correlation among IL-21, interferon-?, tumour necrosis factor-a and IL-10.Results We demonstrated that the decrease of IL-21 expression and the increase of IL-10 expression in PBMCs could promote HBV replication in vitro. We further revealed that IL-21 is not only able to effectively suppress HBV replication directly but also reduce HBV replication by inhibition of IL-10 secretion.Conclusions Our results provide important evidence for the non-cytolytic antiviral mechanism mediated by cytokines and their interactions in chronic hepatitis B.

A bacterium capable of simultaneous heterotrophic nitrification and aerobic denitrification at high concentrations of ammonia-nitrogen was screened and identified and the denitrification property was investigated in this paper. The strain was isolated from aeration tank of wastewater disposed by activated sludge and analyzed and identified by 16S rDNA. The effects of different carbon sources and carbon and nitrogen mass ratios on denitrification rate were studied. The changes of various forms of ammonia-nitrogens during the simultaneous heterotrophic nitrification and aerobic denitrification process were characterized. A strain capable of simultaneous heterotrophic nitrification and aerobic denitrification at 600 mg/L nitrogen concentration has been isolated and screened. Comparison of its 16S rDNA sequence showed 100% similarity to Bacillus licheniformis strain Lr124/6. The strain was named as Bacillus sp. A22. The optimal conditions for degradation of ammonia-nitrogen by Bacillus sp. A22 were trisodium citrate as carbon source and carbon and nitrogen mass ratios of 10. The denitrification rate was 98.2% after 96 h of culture under the optimal conditions and there was hardly any intermediates accumulation in the denitrification process. It has practical applications that the denitrification can be performed efficiently at high concentrations of ammonia-nitrogen by method of simultaneous heterotrophic nitrification and aerobic denitrification by Bacillus sp. A22 in nitrogen purification treatment of wastewater with high concentrations of ammonia-nitrogen.

The simultaneously co-production of Poly-β-hydroxybutyrate (PHB) and ectoine in a process (PHB/Ect co-production) and co-products extraction have great significant for reducing the manufacture cost and promoting industrialization of PHB and ectoine. The pure aqueous extraction method based on osmotic downshock was used for the extraction of PHB/Ect co-products by H. salina. The effects of osmotic pressure, extraction temperature and extraction time on the extraction rate of PHB were investigated. The ectoine was extracted and purified by the techniques of hollow fiber and ion exchange. The optimal conditions for PHB extraction were osmotic downshock in pure water, extraction temperature at 60 °C and extraction for 4 h. The extraction rate of PHB was 87.5%. The extraction rate of ectoine was 84.2%.

Natural gas pipeline laying process will inevitably go through some of the earthquake-prone areas, these areas of soil subsidence, will cause the pipeline vacant, vacant section of the pipeline failure may cause pipeline rupture. Effects of suspended pipeline stress safety usually have two factors: suspended length and the buoyancy of water. In order to explore the sensitivity of these two factors on suspended pipeline stress, we do numerical simulation of XX suspended pipeline using the general stress analysis software CAESAR II. Research shows that suspended length of pipe is having a greater sensitivity on pipeline stress, and the buoyancy of water is relatively small. The results provide some reference for safety management and selection of pipeline.

The hot deformation behaviors of the nickel-base superalloy GH4169 have been studied by isothermal constant true strain rate compression testing at 950°C-1150°C, 0.01s-1-10s-1 and the height reduction 50%. The processing maps of GH4169 alloy have been constructed at different strains on the basis of testing data using a dynamic materials modeling. The maps exhibited two domains: the first at 950°C - 1100°C and strain rate higher than 0.1s-1, with a peak efficiency of power dissipation of 0.1, and the second at 950°C-1100°C and strain rate lower than 1s-1, with a peak efficiency of power dissipation of 0.4 and the strain rate of 0.01s-1. On the basis of microstructure observations, the first exhibits adiabatic shear bands, which called instability domain, the second represents fine recrystallized grain structures, which called stability domain. The optimal hot-working parameters are at 1050°C, 0.01s-1.

Al-22Si-5Fe-4Mn-3Cu-1Mg alloy billet was prepared by spray forming processing, and the morphology and microstructure development of the over-spray powder were investigated in this paper. The results show that the diameter of the most powder was about 38um. With the decreasing of the powder size, its shape became more round and surface more smooth. Heterogeneous nucleation was the main nucleation way and the microstructures were dendrite grains for the most of over-spray powder. The formation mechanisms of the different microstructures were investigated through comparison with the microstructure of the spray formed ingot.

In order to understand the micro-interfacial relationship between environmental copper ions and loosely bound extracellular polymeric substances (LB-EPS), a fluorescence titration of LB-EPS from the Hongfeng lake sediment by Cu (Ⅱ) was studied. Results showed that Cu (Ⅱ) could debase the fluorescence intensity (FI) of LB-EPS. Titration of LB-EPS by Cu (Ⅱ) at pH values of 4.0, 6.0, 7.0 and 9.0 demonstrated an obvious variety of wavelength spectra. The FI of LB-EPS reacting with Cu (Ⅱ) (2.5×10-4M), with the increase of pH values, decreased, which was attributed to more conjunct capacity of the fluorophore with Cu (Ⅱ) in alkaline conditions. At low or middle pH, the quenching of LB-EPS by Cu (Ⅱ) was attributed to the complex quenching triggered by ligand processes; and in the high pH the cause of quenching was not only linked to complex quenching, but also related to collision quenching.

In order to study the Princess Line in women’s suits, based on the body type of young female in Zhejiang province, this research used 3 pieces pattern and 4 pieces pattern as templates. According to different modeling Princess Lines, the researchers made patterns and sample suits. Combining with subjective experiment by mean of trying suits on, the researchers used Fuzzy Comprehensive Evaluation of Fuzzy Mathematics to analyse the data. Compared with the 3 pieces pattern, the results showed that the suits of four pieces pattern has better three-dimensional shape, and it’s more fashionable and has better appearance. Both of the diverting amount of breast dart and the horizontal distance from BP to Princess Line are important keys to cloths appearance. Further more, for 4 pieces samples, when diverting amount of the dart at breast is 1/2, it can show best pleasant curve of the female. Considering of the trend of fashion, we also concluded that for four pieces of samples and the three pieces ones when the horizontal distance from BP to Princess Line is 3.5mm and 5.5mm respectively, Princess Line of the two types of suits will show more beautiful appearance.

Abstract—The present study was designed to test whether tramadol is effective in the control of neuropathic pain in rats. Chronic constriction injury (CCI) of the sciatic nerve was induced over the left hind limb in male Sprague‐Dawley rats. Identical surgery was performed on the opposite side except that the sciatic nerve was not ligated (sham surgery). Paw withdrawal latency (PWL) to heat was tested for each hind paw 1 day before surgery and on the 4th day after surgery to ensure the development of thermal hyperalgesia. In the acute treatment groups, saline or tramadol was administered subcutaneously at doses of 10, 20 or 30 mg/kg, and PWLs were measured 30, 60, 90, 120, 150 and 180 min after treatment. In the semi‐chronic treatment groups, continuous systemic administration of tramadol 40 mg/kg/day or saline for 7 days was provided at a uniform rate via osmotic mini pumps. Tramadol reversed PWL in a dose‐dependent manner in the acute treatment groups. PWLs were significantly reversed at 2 days after tramadol infusion, and this effect was sustained throughout the remainder of the treatment period in comparison with the saline group. Tramadol also resulted in a decreased sensitivity to thermal stimulus on the sham limb both in acute and semi‐chronic administration. We conclude that both acute and semi‐chronic tramadol treatment relieves thermal hyperalgesia effectively in rats with CCI of the sciatic nerve. This indicates that tramadol shows promise as a potential treatment for relief of neuropathic pain in humans.

The proposed adaptive ship steering autopilot is based on the internal model control method, which is characterized by a model‐based design approach that provides clear connections between the structure of the controller and that of the ship model. Specifically, the controller parameters depends explicitly on the ship model parameters and on a design parameter that specifies the closed‐loop system response speed. Once the ship model parameters are estimated on‐line, the controller parameters are adjusted accordingly to adapt to different operating conditions. A key feature of the proposed approach being that the rudder limit and rudder rate limit are directly taken into the adaptation design consideration. Specifically, a reference conditioning technique that modifies the reference input in such a way that the rudder command is always equal to the actual rudder input into the plant. This allows the controller to exert its full power without attempting to take on values beyond the bounds imposed by the rudder limit and rudder rate limit. Consequently, under different operating conditions, rapid course‐changing manoeuvres are achievable without introducing possible instability problem caused by the controller integrator wind‐up. Copyright © 2000 John Wiley & Sons, Ltd.

Artificial cells containing leucine dehydrogenase (EC 1.4.1.9), alcohol dehydrogenase (EC 1.1.1.1; or glucose dehydrogenase, EC 1.1.1.47; or lactic dehydrogenase, EC 1.1.1.27; or malic dehydrogenase, EC 1.1.1.37), urease (EC 3.5.1.5) and dextran-NAD+ were prepared. Ammonia or urea could be converted into L-leucine, L-valine and L-isoleucine using artificial cells with four different multienzyme systems.

A multienzyme system consisting of leucine dehydrogenase (EC 1.4.1.9), L-lactic dehydrogenase (EC 1.1.1.27), urease (EC 3.5.1.5), and dextran-NAD+was microencapsulated within artificial cells. This system could convert ammonia and urea into essential amino acids,L-leucine,L-valine, andL-isoleucine.L-lactate acted as a cosubstrate for the regeneration of dextran-NADH. Greater concentrations of L-lactate favored the higher conversion ratios. The effects of ammonium salts and urea on reaction rate were also studied. The relative reaction rates in ammonium salts solutions were 44.6–78.8% of those in urea solutions. More than 90% of the original activity was retained when artificial cells were kept at 4°C for 6 wk.

The objective of this paper is to explore a new comfort evaluation method, which is suitable for studying the comfort of casualty transported by a military ambulance. The paper applies existing vibration evaluation methods to quantitatively obtain comfort of non-ambulatory casualty, stimulates the patients with different vibrational conditions, and analyses the annoyance rates with psychophysics knowledge as well as the ratio of war to disaster injuries and susceptibility of the wounded. The road test proves that this new method is feasible for vibrational comfort evaluation of non-ambulatory casualty and gains quantitative advantages over the traditional methods....

trans-4,5-Disubstituted-γ-butyrolactones are found to adopt different conformations by NMR spectroscopy; their optical rotation signs are found to depend on the conformations they assume.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

A 32‐year‐old man who suffered from complex regional pain syndrome type I (CRPS I) of the right upper limb after surgical release of carpal tunnel syndrome of the right hand is the subject of this case report. Symptoms and signs over the right hand were alleviated under rehabilitation and conventional pharmacological management, but severe painful swelling of the right wrist persisted. Axillary brachial plexus block (BPB) with patient controlled analgesia (PCA) was performed on the 32ndpostoperative day, which soon resulted in significant reduction of pain with gradual improvement of function of the right wrist. Conclude that axillary BPB with PCA may provide patients with CRPS I of the upper limb a feasible and effective treatment.